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IntroductionIn recent years, many studies have been published on new diagnostic possibilities and management approaches in cohorts of patients suspected to have a disorder/difference of sex development (DSD).1–13 Based on these studies, it has become clear that services and institutions still differ in the composition antabuse online of the multidisciplinary teams that provide care for patients who have a DSD.11 14 Several projects have now worked to resolve this variability in care. The European Cooperation in Science and antabuse online Technology (EU COST) action BM1303 ‘A systematic elucidation of differences of sex development’ has been a platform to achieve European agreement on harmonisation of clinical management and laboratory practices.15–17 Another such initiative involved an update of the 2006 DSD consensus document by an international group of professionals and patient representatives.18 These initiatives have highlighted how cultural and financial aspects and the availability of resources differ significantly between countries and societies, a situation that hampers supranational agreement on common diagnostic protocols. As only a few national guidelines have been published in international journals, comparison of these guidelines is difficult even though such a comparison is necessary to capture the differences and initiate actions to overcome them.

Nonetheless, four DSD (expert) centres located in the Netherlands and Flanders (the Dutch-speaking Northern part of Belgium) have collaborated to produce a detailed guideline on diagnostics in DSD.19 This shows antabuse online that a supranational guideline can be a reasonable approach for countries with similarly structured healthcare systems and similar resources. Within the guideline there is agreement that optimisation of expertise and care can be achieved through centralisation, for example, by limiting analysis of next-generation sequencing (NGS)-based diagnostic panels to only a few centres and by centralising pathological review of gonadal tissues. International networks such as the European Reference Network for rare endocrine conditions (EndoERN), in which DSD is embedded, may facilitate the expansion of this kind of collaboration across Europe.This paper highlights key discussion points in the Dutch-Flemish guideline that have been insufficiently addressed in the literature thus far because they reflect evolving technologies antabuse online or less visible stakeholders.

For example, prenatal observation of an atypical aspect of the genitalia indicating a possible DSD is becoming increasingly common, and we discuss appropriate counselling and a diagnostic approach for these cases, including the option of using NGS-based genetic testing. So far, little attention has been paid to this process.20 21 Furthermore, informing patients and/or their parents about atypical sex development and why this may warrant referral to a specialised team may be challenging, especially for professionals with limited experience in DSD.22 23 Therefore, a antabuse online section of the Dutch-Flemish guideline was written for these healthcare providers. Moreover, this enables DSD specialists to refer to the guideline when advising a referral.

Transition from the prenatal to the postnatal team and from the paediatric to the antabuse online adult team requires optimal communication between the specialists involved. Application of NGS-based techniques may lead to a higher diagnostic yield, providing a molecular genetic diagnosis in previously unsolved cases.16 We address the timing of this testing and the problems associated with this technique such as the interpretation of variants of unknown clinical significance (VUS). Similarly, histopathological interpretation and classification of removed gonadal tissue is challenging and would benefit from international collaboration and centralisation of expertise.MethodsFor the guideline revision, an interdisciplinary multicentre group was formed with all members responsible for updating the literature for a antabuse online specific part of the guideline.

Literature search in PubMed was not systematic, but rather intended to be broad in order to cover all areas and follow expert opinions. This approach is more in line antabuse online with the Clinical Practice Advisory Document method described by Burke et al24 for guidelines involving genetic practice because it is often troublesome to substantiate such guidelines with sufficient evidence due to the rapid changes in testing methods, for example, gene panels. All input provided by the group was synthesised by the chairperson (YvB), who also reviewed abstracts of papers on DSD published between 2010 and September 2017 for the guideline and up to October 2019 for this paper.

Abstracts had antabuse online to be written in English and were identified using a broad range of Medical Subject Headings terms (eg, DSD, genetic, review, diagnosis, diagnostics, 46,XX DSD, 46,XY DSD, guideline, multidisciplinary care). Next, potentially relevant papers on diagnostic procedures in DSD were selected. Case reports were excluded, as were articles that were not antabuse online open access or retrievable through institutional access.

Based on this, a draft guideline was produced that was in line with the international principles of good diagnostic care in DSD. This draft antabuse online was discussed by the writing committee and, after having obtained agreement on remaining points of discussion, revised into a final draft. This version was sent to a broad group of professionals from academic centres and DSD teams whose members had volunteered to review the draft guideline.

After receiving antabuse online and incorporating their input, the final version was presented to the paediatric and genetic associations for approval. After approval by the members of the paediatric (NVK), clinical genetic (VKGN) and genetic laboratory (VKGL) associations, the guideline was published on their respective websites.19 Although Turner syndrome and Klinefelter syndrome are considered to be part of the DSD spectrum, they are not extensively discussed in this diagnostic guideline as guidelines dedicated to these syndromes already exist.25 26 However, some individuals with Turner syndrome or Klinefelter syndrome may present with ambiguous or atypical genitalia and may therefore initially follow the DSD diagnostic process.Guideline highlightsPrenatal settingPresentationThe most frequent prenatal presentation of a DSD condition is atypical genitalia found on prenatal ultrasound as an isolated finding or in combination with other structural anomalies. This usually occurs after the 20-week routine medical ultrasound for screening of congenital anomalies, but may also occur earlier, for example, when a commercial ultrasound is performed at the request of the parents.Another way DSD can be diagnosed before birth is when invasive prenatal genetic testing carried out for a different antabuse online reason, for example, due to suspicion of other structural anomalies, reveals a discrepancy between the genotypic sex and the phenotypic sex seen by ultrasound.

In certified laboratories, the possibility of a sample switch is extremely low but should be ruled out immediately. More often, the discrepancy will be due to sex-chromosome mosaicism or a true form of DSD.A situation now occurring with increasing frequency is a discrepancy between the genotypic sex revealed by non-invasive prenatal testing (NIPT), which is now available antabuse online to high-risk pregnant women in the Netherlands and to all pregnant women in Belgium, and later ultrasound findings. NIPT screens for CNVs in the fetus.

However, depending on legal restrictions and/or ethical considerations, the X and Y chromosomes are not antabuse online always included in NIPT analysis and reports. If the X and Y chromosomes are included, it is important to realise that the presence of a Y-chromosome does not necessarily imply male fetal development. At the time that NIPT is performed (usually 11–13 weeks), genital development cannot be reliably appreciated by ultrasound, so any discrepancy or atypical aspect of the genitalia will only be noticed later in pregnancy and should prompt further evaluation.Counselling and diagnosticsIf a DSD antabuse online is suspected, first-line sonographers and obstetricians should refer the couple to their colleague prenatal specialists working with or in a DSD team.

After confirming an atypical genital on ultrasound, the specialist team should offer the couple a referral for genetic counselling to discuss the possibility of performing invasive prenatal testing (usually an amniocentesis) to identify an underlying cause that fits the ultrasound findings.22 23 To enable the parents to make a well-informed decision, prenatal counselling should, in our opinion, include. Information on the ultrasound findings antabuse online and the limitations of this technique. The procedure(s) that can be followed, including the risks associated with an amniocentesis.

And the type of information genetic testing can and cannot provide antabuse online. Knowing which information has been provided and what words have been used by the prenatal specialist is very helpful for those involved in postnatal care.It is important that parents understand that the biological sex of a baby is determined by a complex interplay of chromosomes, genes and hormones, and thus that assessment of the presence or absence of a Y-chromosome alone is insufficient to assign the sex of their unborn child or, as in any unborn child, say anything about the child’s future gender identity.Expecting parents can be counselled by the clinical geneticist and the psychologist from the DSD team, although other DSD specialists can also be involved. The clinical geneticist should be experienced in prenatal counselling and well informed about the antabuse online diagnostic possibilities given the limited time span in which test results need to be available to allow parents to make a well-informed decision about whether or not to continue the pregnancy.

Termination of pregnancy can be considered, for instance, antabuse online in a syndromic form of DSD with multiple malformations, but when the DSD occurs as an apparently isolated condition, expecting parents may also consider termination of pregnancy, which, although considered controversial by some, is legal in Belgium and the Netherlands. The psychologist of the DSD team can support parents during and after pregnancy and help them cope with feelings of uncertainty and eventual considerations of a termination of pregnancy, as well as with practical issues, for example, how to inform others. The stress of not knowing exactly what the antabuse online child’s genitalia will look like and uncertainty about the diagnosis, treatment and prognosis cannot be avoided completely.

Parents are informed that if the postnatal phenotype is different from what was prenatally expected, the advice given about diagnostic testing can be adjusted accordingly, for example, if a hypospadias is milder than was expected based on prenatal ultrasound images. In our experience, parents appreciate having already spoken to some members of the DSD team during antabuse online pregnancy and having a contact person before birth.After expert prenatal counselling, a significant number of pregnant couples decline prenatal testing (personal experience IALG, MK, ABD, YvB, MC and HC-vdG). At birth, umbilical cord blood is a good source for (molecular) karyotyping and storage of DNA and can be obtained by the obstetrician, midwife or neonatologist.

The terminology used in communication with parents should be carefully chosen,22 23 and midwives and staff of neonatal and delivery units should be clearly instructed to use gender-neutral and non-stigmatising vocabulary (eg, ‘your baby’) as long as sex assignment is pending.An algorithm for diagnostic evaluation of a suspected DSD in the antabuse online prenatal situation is proposed in figure 1. When couples opt for invasive prenatal diagnosis, the genetic analysis usually involves an (SNP)-array. It was recently estimated that >30% of individuals who have a DSD have additional structural anomalies, with cardiac and neurological anomalies and fetal growth restriction being particularly common.27 28 If additional anomalies are seen, the geneticist can consider specific gene defects that antabuse online may underlie a known genetic syndrome or carry out NGS.

NGS-based techniques have also now made their appearance in prenatal diagnosis of congenital anomalies.29 30 Panels using these techniques can be specific for genes involved in DSD, or be larger panels covering multiple congenital anomalies, and are usually employed with trio-analysis to compare variants identified in the child with the parents’ genetics.29–31 Finding a genetic cause before delivery can help reduce parental stress in the neonatal period and speed up decisions regarding gender assignment. In such cases there is no tight time limit, and we propose completing the analysis well before the expected delivery.Disorders/differences of sex development (DSD) in antabuse online the prenatal setting. A diagnostic algorithm.

*SOX9. Upstream anomalies and balanced translocations at promotor sites!. Conventional karyotyping can be useful.

NGS, next-generation sequencing." data-icon-position data-hide-link-title="0">Figure 1 Disorders/differences of sex development (DSD) in the prenatal setting. A diagnostic algorithm. *SOX9.

Upstream anomalies and balanced translocations at promotor sites!. Conventional karyotyping can be useful. NGS, next-generation sequencing.First contact by a professional less experienced in DSDWhereas most current guidelines start from the point when an individual has been referred to the DSD team,1 15 the Dutch-Flemish guideline dedicates a chapter to healthcare professionals less experienced in DSD as they are often the first to suspect or identify such a condition.

Apart from the paper of Indyk,7 little guidance is available for these professionals about how to act in such a situation. The chapter in the Dutch-Flemish guideline summarises the various clinical presentations that a DSD can have and provides information on how to communicate with parents and/or patients about the findings of the physical examination, the first-line investigations and the need for prompt referral to a specialised centre for further evaluation. Clinical examples are offered to illustrate some of these recurring situations.

The medical issues in DSD can be very challenging, and the social and psychological impact is high. For neonates with ambiguous genitalia, sex assignment is an urgent and crucial issue, and it is mandatory that parents are informed that it is possible to postpone registration of their child’s sex. In cases where sex assignment has already taken place, the message that the development of the gonads or genitalia is still atypical is complicated and distressing for patients and parents or carers.

A list of contact details for DSD centres and patient organisations in the Netherlands and Flanders is attached to the Dutch-Flemish guideline. Publishing such a list, either in guidelines or online, can help healthcare professionals find the nearest centres for consultations and provide patients and patient organisations with an overview of the centres where expertise is available.Timing and place of genetic testing using NGS-based gene panelsThe diagnostic workup that is proposed for 46,XX and 46,XY DSD is shown in figures 2 and 3, respectively. Even with the rapidly expanding molecular possibilities, a (family) history and a physical examination remain the essential first steps in the diagnostic process.

Biochemical and hormonal screening aim at investigating serum electrolytes, renal function and the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. Ultrasound screening of kidneys and internal genitalia, as well as establishing genotypic sex, should be accomplished within 48 hours and complete the baseline diagnostic work-up of a child born with ambiguous genitalia.1 16 32 3346,XX disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm.

NGS, next-generation sequencing. CAH, Congenital adrenal hyperplasia. AMH, Anti-Müllerian Hormone." data-icon-position data-hide-link-title="0">Figure 2 46,XX disorders/differences of sex development (DSD) in the postnatal setting.

A diagnostic algorithm. NGS, next-generation sequencing. CAH, Congenital adrenal hyperplasia.

AMH, Anti-Müllerian Hormone.46,XY disorders/differences of sex development (DSD) in the postnatal setting. A diagnostic algorithm. * SOX9.

Upstream anomalies and balanced translocations at promotor sites!. Conventional karyotyping can be useful. NGS, next-generation sequencing." data-icon-position data-hide-link-title="0">Figure 3 46,XY disorders/differences of sex development (DSD) in the postnatal setting.

A diagnostic algorithm. *SOX9. Upstream anomalies and balanced translocations at promotor sites!.

Conventional karyotyping can be useful. NGS, next-generation sequencing.Very recently, a European position paper has been published focusing on the genetic workup of DSD.16 It highlights the limitations and drawbacks of NGS-based tests, which include the chance of missing subtle structural variants such as CNVs and mosaicism and the fact that NGS cannot detect methylation defects or other epigenetic changes.16 28 31 Targeted DNA analysis is preferred in cases where hormonal investigations suggest a block in steroidogenesis (eg, 11-β-hydroxylase deficiency, 21-hydroxylase deficiency), or in the context of a specific clinical constellation such as the often coincidental finding of Müllerian structures in a boy with normal external genitalia or cryptorchidism, that is, persistent Müllerian duct syndrome.33 34 Alternative tests should also be considered depending on the available information. Sometimes, a simple mouth swab for FISH analysis can detect mosaic XY/X in a male with hypospadias or asymmetric gonadal development or in a female with little or no Turner syndrome stigmata and a normal male molecular karyotyping profile or peripheral blood karyotype.

Such targeted testing avoids incidental findings and is cheaper and faster than analysis of a large NGS-based panel, although the cost difference is rapidly declining.However, due to the genetic and phenotypic heterogeneity of DSD conditions, the most cost-effective next steps in the majority of cases are whole exome sequencing followed by panel analysis of genes involved in genital development and function or trio-analysis of a large gene panel (such as a Mendeliome).16 35–38 Pretest genetic counselling involves discussing what kind of information will be reported to patients or parents and the chance of detecting VUS, and the small risk of incidental findings when analysing a DSD panel should be mentioned. Laboratories also differ in what class of variants they report.39 In our experience, the fear of incidental findings is a major reason why some parents refrain from genetic testing.Timing of the DSD gene panel analysis is also important. While some patients or parents prefer that all diagnostic procedures be performed as soon as possible, others need time to reflect on the complex information related to more extensive genetic testing and on its possible consequences.

If parents or patients do not consent to panel-based genetic testing, analysis of specific genes, such as WT1, should be considered when appropriate in view of the clinical consequences if a mutation is present (eg, clinical surveillance of renal function and screening for Wilms’ tumour in the case of WT1 mutations). Genes that are more frequently involved in DSD (eg, SRY, NR5A1) and that match the specific clinical and hormonal features in a given patient could also be considered for sequencing. Targeted gene analysis may also be preferred in centres located in countries that do not have the resources or technical requirements to perform NGS panel-based genetic testing.

Alternatively, participation by these centres in international collaborative networks may allow them to outsource the molecular genetic workup abroad.Gene panels differ between centres and are regularly updated based on scientific progress. A comparison of DSD gene panels used in recent studies can be found at https://www.nature.com/articles/s41574-018-0010-8%23Sec46.15 The panels currently used at the coauthors’ institutions can be found on their respective websites. Given the pace of change, it is important to regularly consider repeating analysis in patients with an unexplained DSD, for example, when they transition into adult care or when they move from one centre to another.

This also applies to patients in whom a clinical diagnosis has never been genetically confirmed. Confusion may arise when the diagnosis cannot be confirmed or when a mutation is identified in a different gene, for example, NR5A1 in someone with a clinical diagnosis of CAIS that has other consequences for relatives. Hence, new genetic counselling should always accompany new diagnostic endeavours.Class 3 variants and histopathological examinationsThe rapidly evolving diagnostic possibilities raise new questions.

What do laboratories report?. How should we deal with the frequent findings of mainly unique VUS or class 3 variants (ACMG recommendation) in the many different DSD-related genes in the diagnostic setting?. Reporting VUS can be a source of uncertainty for parents, but not reporting these variants precludes further investigations to determine their possible pathogenicity.

It can also be difficult to prove variant pathogenicity, both on gene-level and variant-level.39 Moreover, given the gonad-specific expression of some genes and the variable phenotypic spectrum and reduced penetrance, segregation analysis is not always informative. A class 3 variant that does not fit the clinical presentation may be unrelated to the observed phenotype, but it could also represent a newly emerging phenotype. This was recently demonstrated by the identification of the NR5A1 mutation, R92W, in individuals with 46,XX testicular and ovotesticular DSD.40 This gene had previously been associated with 46,XY DSD.

In diagnostic laboratories, there is usually no capacity or expertise to conduct large-scale functional studies to determine pathogenicity of these unique class 3 VUS in the different genes involved in DSD. Functional validation of variants identified in novel genes may be more attractive in a research context. However, for individual families with VUS in well-established DSD genes such as AR or HSD17B3, functional analysis may provide a confirmed diagnosis that implies for relatives the option of undergoing their own DNA analysis and estimating the genetic risk of their own future offspring.

This makes genetic follow-up important in these cases and demonstrates the usefulness of international databases and networks and the centralisation of functional studies of genetic variants in order to reduce costs and maximise expertise.The same is true for histopathological description, germ-cell tumour risk assessment in specific forms of DSD and classification of gonadal samples. Germ-cell tumour risk is related to the type of DSD (among other factors), but it is impossible to make risk estimates in individual cases.41–44 Gonadectomy may be indicated in cases with high-risk dysgenetic abdominal gonads that cannot be brought into a stable superficial (ie, inguinal, labioscrotal) position that allows clinical or radiological surveillance, or to avoid virilisation due to 5-alpha reductase deficiency in a 46,XY girl with a stable female gender identity.45 Pathological examination of DSD gonads requires specific expertise. For example, the differentiation between benign germ cell abnormalities, such as delayed maturation and (pre)malignant development of germ cells, is crucial for clinical management but can be very troublesome.46 Centralised pathological examination of gonadal biopsy and gonadectomy samples in one centre, or a restricted number of centres, on a national scale can help to overcome the problem of non-uniform classification and has proven feasible in the Netherlands and Belgium.

We therefore believe that uniform assessment and classification of gonadal differentiation patterns should also be addressed in guidelines on DSD management.International databases of gonadal tissues are crucial for learning more about the risk of malignancy in different forms of DSD, but they are only reliable if uniform criteria for histological classification are strictly applied.46 These criteria could be incorporated in many existing networks such as the I-DSD consortium, the Disorders of Sex Development Translational Research Network, the European Reference Network on Urogenital Diseases (eUROGEN), the EndoERN and COST actions.15–17 47Communication at the transition from paediatric to adult carePaediatric and adult teams need to collaborate closely to facilitate a well-organised transition from paediatric to adult specialist care.15 48–50 Both teams need to exchange information optimally and should consider transition as a longitudinal process rather than a fixed moment in time. Age-appropriate information is key at all ages, and an overview of topics to be discussed at each stage is described by Cools et al.15 Table 1 shows an example of how transition can be organised.View this table:Table 1 Example of transition table as used in the DSD clinic of the Erasmus Medical CenterPsychological support and the continued provision of information remains important for individuals with a DSD at all ages.15 22 In addition to the information given by the DSD team members, families and patients can benefit from resources such as support groups and information available on the internet.47 Information available online should be checked for accuracy and completeness when referring patients and parents to internet sites.Recommendations for future actionsMost guidelines and articles on the diagnosis and management of DSD are aimed at specialists and are only published in specialist journals or on websites for endocrinologists, urologists or geneticists. Yet there is a need for guidelines directed towards first-line and second-line healthcare workers that summarise the recommendations about the first crucial steps in the management of DSD.

These should be published in widely available general medical journals and online, along with a national list of DSD centres. Furthermore, DSD (expert) centres should provide continuous education to all those who may be involved in the identification of individuals with a DSD in order to enable these healthcare professionals to recognise atypical genitalia, to promptly refer individuals who have a DSD and to inform the patient and parents about this and subsequent diagnostic procedures.As DSD continues to be a rare condition, it will take time to evaluate the effects of having such a guideline on the preparedness of first-line and second-line healthcare workers to recognise DSD conditions. One way to evaluate this might be the development and use of questionnaires asking patients, carers and families and referring physicians how satisfied they were with the initial medical consultation and referral and what could be improved.

A helpful addition to existing international databases that collect information on genetic variations would be a list of centres that offer suitable functional studies for certain genes, ideally covering the most frequently mutated genes (at minimum).Patient organisations can also play an important role in informing patients about newly available diagnostic or therapeutic strategies and options, and their influence and specific role has now been recognised and discussed in several publications.17 47 However, it should be kept in mind that these organisations do not represent all patients, as a substantial number of patients and parents are not member of such an organisation.Professionals have to provide optimal medical care based on well-established evidence, or at least on broad consensus. Yet not everything can be regulated by recommendations and guidelines. Options, ideas and wishes should be openly discussed between professionals, patients and families within their confidential relationship.

This will enable highly individualised holistic care tailored to the patient’s needs and expectations. Once they are well-informed of all available options, parents and/or patients can choose what they consider the optimal care for their children or themselves.15 16ConclusionThe Dutch-Flemish guideline uniquely addresses some topics that are under-represented in the literature, thus adding some key aspects to those addressed in recent consensus papers and guidelines.15–17 33 47As more children with a DSD are now being identified prenatally, and the literature on prenatal diagnosis of DSD remains scarce,20 21 we propose a prenatal diagnostic algorithm and emphasise the importance of having a prenatal specialist involved in or collaborating with DSD (expert) centres.We also stress that good communication between all involved parties is essential. Professionals should be well informed about protocols and communication.

Collaboration between centres is necessary to optimise aspects of care such as uniform interpretation of gonadal pathology and functional testing of class 3 variants found by genetic testing. Guidelines can provide a framework within which individualised patient care should be discussed with all stakeholders.AcknowledgmentsThe authors would like to thank the colleagues of the DSD teams for their input in and critical reading of the Dutch-Flemish guideline. Amsterdam University Center (AMC and VU), Maastricht University Medical Center, Erasmus Medical Center Rotterdam, Radboud University Medical Center Nijmegen, University Medical Center Groningen, University Medical Center Utrecht, Ghent University Hospital.

The authors would like to thank Kate McIntyre for editing the revised manuscript and Tom de Vries Lentsch for providing the figures as a PDF. Three of the authors of this publication are members of the European Reference Network for rare endocrine diseases—Project ID 739543.IntroductionEndometrial cancer is the most common gynaecological malignancy in the developed world.1 Its incidence has risen over the last two decades as a consequence of the ageing population, fewer hysterectomies for benign disease and the obesity epidemic. In the USA, it is estimated that women have a 1 in 35 lifetime risk of endometrial cancer, and in contrast to cancers of most other sites, cancer-specific mortality has risen by approximately 2% every year since 2008 related to the rapidly rising incidence.2Endometrial cancer has traditionally been classified into type I and type II based on morphology.3 The more common subtype, type I, is mostly comprised of endometrioid tumours and is oestrogen-driven, arises from a hyperplastic endometrium, presents at an early stage and has an excellent 5 year survival rate.4 By contrast, type II includes non-endometrioid tumours, specifically serous, carcinosarcoma and clear cell subtypes, which are biologically aggressive tumours with a poor prognosis that are often diagnosed at an advanced stage.5 Recent efforts have focused on a molecular classification system for more accurate categorisation of endometrial tumours into four groups with distinct prognostic profiles.6 7The majority of endometrial cancers arise through the interplay of familial, genetic and lifestyle factors.

Two inherited cancer predisposition syndromes, Lynch syndrome and the much rarer Cowden syndrome, substantially increase the lifetime risk of endometrial cancer, but these only account for around 3–5% of cases.8–10 Having first or second degree relative(s) with endometrial or colorectal cancer increases endometrial cancer risk, although a large European twin study failed to demonstrate a strong heritable link.11 The authors failed to show that there was greater concordance in monozygotic than dizygotic twins, but the study was based on relatively small numbers of endometrial cancers. Lu and colleagues reported an association between common single nucleotide polymorphisms (SNPs) and endometrial cancer risk, revealing the potential role of SNPs in explaining part of the risk in both the familial and general populations.12 Thus far, many SNPs have been reported to modify susceptibility to endometrial cancer. However, much of this work predated genome wide association studies and is of variable quality.

Understanding genetic predisposition to endometrial cancer could facilitate personalised risk assessment with a view to targeted prevention and screening interventions.13 This emerged as the most important unanswered research question in endometrial cancer according to patients, carers and healthcare professionals in our recently completed James Lind Womb Cancer Alliance Priority Setting Partnership.14 It would be particularly useful for non-endometrioid endometrial cancers, for which advancing age is so far the only predictor.15We therefore conducted a comprehensive systematic review of the literature to provide an overview of the relationship between SNPs and endometrial cancer risk. We compiled a list of the most robust endometrial cancer-associated SNPs. We assessed the applicability of this panel of SNPs with a theoretical polygenic risk score (PRS) calculation.

We also critically appraised the meta-analyses investigating the most frequently reported SNPs in MDM2. Finally, we described all SNPs reported within genes and pathways that are likely involved in endometrial carcinogenesis and metastasis.MethodsOur systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) collaboration 2009 recommendations. The registered protocol is available through PROSPERO (CRD42018091907).16Search strategyWe searched Embase, MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases via the Healthcare Databases Advanced Search (HDAS) platform, from 2007 to 2018, to identify studies reporting associations between polymorphisms and endometrial cancer risk.

Key words including MeSH (Medical Subject Heading) terms and free-text words were searched in both titles and abstracts. The following terms were used. €œendomet*”,“uter*”, “womb”, “cancer(s)”, “neoplasm(s)”, “endometrium tumour”, “carcinoma”, “adenosarcoma”, “clear cell carcinoma”, “carcinosarcoma”, “SNP”, “single nucleotide polymorphism”, “GWAS”, and “genome-wide association study/ies”.

No other restrictions were applied. The search was repeated with time restrictions between 2018 and June 2019 to capture any recent publications.Eligibility criteriaStudies were selected for full-text evaluation if they were primary articles investigating a relationship between endometrial cancer and SNPs. Study outcome was either the increased or decreased risk of endometrial cancer relative to controls reported as an odds ratio (OR) with corresponding 95% confidence intervals (95% CIs).Study selectionThree independent reviewers screened all articles uploaded to a screening spreadsheet developed by Helena VonVille.17 Disagreements were resolved by discussion.

Chronbach’s α score was calculated between reviewers and indicated high consistency at 0.92. Case–control, prospective and retrospective studies, genome-wide association studies (GWAS), and both discovery and validation studies were selected for full-text evaluation. Non-English articles, editorials, conference abstracts and proceedings, letters and correspondence, case reports and review articles were excluded.Candidate-gene studies with at least 100 women and GWAS with at least 1000 women in the case arm were selected to ensure reliability of the results, as explained by Spencer et al.18 To construct a panel of up to 30 SNPs with the strongest evidence of association, those with the strongest p values were selected.

For the purpose of an SNP panel, articles utilising broad European or multi-ethnic cohorts were selected. Where overlapping populations were identified, the most comprehensive study was included.Data extraction and synthesisFor each study, the following data were extracted. SNP ID, nearby gene(s)/chromosome location, OR (95% CI), p value, minor or effect allele frequency (MAF/EAF), EA (effect allele) and OA (other allele), adjustment, ethnicity and ancestry, number of cases and controls, endometrial cancer type, and study type including discovery or validation study and meta-analysis.

For risk estimates, a preference towards most adjusted results was applied. For candidate-gene studies, a standard p value of<0.05 was applied and for GWAS a p value of <5×10-8, indicating genome-wide significance, was accepted as statistically significant. However, due to the limited number of SNPs with p values reaching genome-wide significance, this threshold was then lowered to <1×10-5, allowing for marginally significant SNPs to be included.

As shown by Mavaddat et al, for breast cancer, SNPs that fall below genome-wide significance may still be useful for generating a PRS and improving the models.19We estimated the potential value of a PRS based on the most significant SNPs by comparing the predicted risk for a woman with a risk score in the top 1% of the distribution to the mean predicted risk. Per-allele ORs and MAFs were taken from the publications and standard errors (SEs) for the lnORs were derived from published 95% CIs. The PRS was assumed to have a Normal distribution, with mean 2∑βipI and SE, σ, equal to √2∑βi2pI(1−pi), according to the binomial distribution, where the summation is over all SNPs in the risk score.

Hence the relative risk (RR) comparing the top 1% of the distribution to the mean is given by exp(Z0.01σ), where Z is the inverse of the standard normal cumulative distribution.ResultsThe flow chart of study selection is illustrated in figure 1. In total, 453 text articles were evaluated and, of those, 149 articles met our inclusion criteria. One study was excluded from table 1, for having an Asian-only population, as this would make it harder to compare with the rest of the results which were all either multi-ethnic or Caucasian cohorts, as stated in our inclusion criteria for the SNP panel.20 Any SNPs without 95% CIs were also excluded from any downstream analysis.

Additionally, SNPs in linkage disequilibrium (r2 >0.2) with each other were examined, and of those in linkage disequilibrium, the SNP with strongest association was reported. Per allele ORs were used unless stated otherwise.View this table:Table 1 List of top SNPs most likely to contribute to endometrial cancer risk identified through systematic review of recent literature21–25Study selection flow diagram. *Reasons.

Irrelevant articles, articles focusing on other conditions, non-GWAS/candidate-gene study related articles, technical and duplicate articles. GWAS, genome-wide association study. Adapted from.

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The PRISMA Statement.

PLoS Med 6(6). E1000097. Doi:10.1371/journal.pmed1000097." data-icon-position data-hide-link-title="0">Figure 1 Study selection flow diagram.

*Reasons. Irrelevant articles, articles focusing on other conditions, non-GWAS/candidate-gene study related articles, technical and duplicate articles. GWAS, genome-wide association study.

Adapted from. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

The PRISMA Statement. PLoS Med 6(6). E1000097.

Doi:10.1371/journal.pmed1000097.Top SNPs associated with endometrial cancer riskFollowing careful interpretation of the data, 24 independent SNPs with the lowest p values that showed the strongest association with endometrial cancer were obtained (table 1).21–25 These SNPs are located in or around genes coding for transcription factors, cell growth and apoptosis regulators, and enzymes involved in the steroidogenesis pathway. All the SNPs presented here were reported on the basis of a GWAS or in one case, an exome-wide association study, and hence no SNPs from candidate-gene studies made it to the list. This is partly due to the nature of larger GWAS providing more comprehensive and powered results as opposed to candidate gene studies.

Additionally, a vast majority of SNPs reported by candidate-gene studies were later refuted by large-scale GWAS such as in the case of TERT and MDM2 variants.26 27 The exception to this is the CYP19 gene, where candidate-gene studies reported an association between variants in this gene with endometrial cancer in both Asian and broad European populations, and this association was more recently confirmed by large-scale GWAS.21 28–30 Moreover, a recent article authored by O’Mara and colleagues reviewed the GWAS that identified most of the currently known SNPs associated with endometrial cancer.31Most of the studies represented in table 1 are GWAS and the majority of these involved broad European populations. Those having a multi-ethnic cohort also consisted primarily of broad European populations. Only four of the variants in table 1 are located in coding regions of a gene, or in regulatory flanking regions around the gene.

Thus, most of these variants would not be expected to cause any functional effects on the gene or the resulting protein. An eQTL search using GTEx Portal showed that some of the SNPs are significantly associated (p<0.05) with modified transcription levels of the respective genes in various tissues such as prostate (rs11263761), thyroid (rs9668337), pituitary (rs2747716), breast mammary (rs882380) and testicular (rs2498794) tissue, as summarised in table 2.View this table:Table 2 List of eQTL hits for the selected panel of SNPsThe only variant for which there was an indication of a specific association with non-endometrioid endometrial cancer was rs148261157 near the BCL11A gene. The A allele of this SNP had a moderately higher association in the non-endometrioid arm (OR 1.64, 95% CI 1.32 to 2.04.

P=9.6×10-6) compared with the endometrioid arm (OR 1.25, 95% CI 1.14 to 1.38. P=4.7×10-6).21Oestrogen receptors α and β encoded by ESR1 and ESR2, respectively, have been extensively studied due to the assumed role of oestrogens in the development of endometrial cancer. O’Mara et al reported a lead SNP (rs79575945) in the ESR1 region that was associated with endometrial cancer (p=1.86×10-5).24 However, this SNP did not reach genome-wide significance in a more recent larger GWAS.21 No statistically significant associations have been reported between endometrial cancer and SNPs in the ESR2 gene region.AKT is an oncogene linked to endometrial carcinogenesis.

It is involved in the PI3K/AKT/mTOR pro-proliferative signalling pathway to inactivate apoptosis and allow cell survival. The A allele of rs2494737 and G allele of rs2498796 were reported to be associated with increased and decreased risk of endometrial cancer in 2016, respectively.22 30 However, this association was not replicated in a larger GWAS in 2018.21 Nevertheless, given the previous strong indications, and biological basis that could explain endometrial carcinogenesis, we decided to include an AKT1 variant (rs2498794) in our results.PTEN is a multi-functional tumour suppressor gene that regulates the AKT/PKB signalling pathway and is commonly mutated in many cancers including endometrial cancer.32 Loss-of-function germline mutations in PTEN are responsible for Cowden syndrome, which exerts a lifetime risk of endometrial cancer of up to 28%.9 Lacey and colleagues studied SNPs in the PTEN gene region. However, none showed significant differences in frequency between 447 endometrial cancer cases and 439 controls of European ancestry.33KRAS mutations are known to be present in endometrial cancer.

These can be activated by high levels of KLF5 (transcriptional activator). Three SNPs have been identified in or around KLF5 that are associated with endometrial cancer. The G allele of rs11841589 (OR 1.15, 95% CI 1.11 to 1.21.

P=4.83×10-11), the A allele of rs9600103 (OR 1.23, 95% CI 1.16 to 1.30. P=3.76×10-12) and C allele of rs7981863 (OR 1.16, 95% CI 1.12 to 1.20. P=2.70×10-17) have all been found to be associated with an increased likelihood of endometrial cancer in large European cohorts.21 30 34 It is worth noting that these SNPs are not independent, and hence they quite possibly tag the same causal variant.The MYC family of proto-oncogenes encode transcription factors that regulate cell proliferation, which can contribute to cancer development if dysregulated.

The recent GWAS by O’Mara et al reported three SNPs within the MYC region that reached genome-wide significance with conditional p values reaching at least 5×10–8.35To test the utility of these SNPs as predictive markers, we devised a theoretical PRS calculation using the log ORs and EAFs per SNP from the published data. The results were very encouraging with an RR of 3.16 for the top 1% versus the mean, using all the top SNPs presented in table 1 and 2.09 when using only the SNPs that reached genome-wide significance (including AKT1).Controversy surrounding MDM2 variant SNP309MDM2 negatively regulates tumour suppressor gene TP53, and as such, has been extensively studied in relation to its potential role in predisposition to endometrial cancer. Our search identified six original studies of the association between MDM2 SNP rs2279744 (also referred to as SNP309) and endometrial cancer, all of which found a statistically significant increased risk per copy of the G allele.

Two more original studies were identified through our full-text evaluation. However, these were not included here as they did not meet our inclusion criteria—one due to small sample size, the other due to studying rs2279744 status dependent on another SNP.36 37 Even so, the two studies were described in multiple meta-analyses that are listed in table 3. Different permutations of these eight original studies appear in at least eight published meta-analyses.

However, even the largest meta-analysis contained <2000 cases (table 3)38View this table:Table 3 Characteristics of studies that examined MDM2 SNP rs2279744In comparison, a GWAS including nearly 13 000 cases found no evidence of an association with OR and corresponding 95% CI of 1.00 (0.97 to 1.03) and a p value of 0.93 (personal communication).21 Nevertheless, we cannot completely rule out a role for MDM2 variants in endometrial cancer predisposition as the candidate-gene studies reported larger effects in Asians, whereas the GWAS primarily contained participants of European ancestry. There is also some suggestion that the SNP309 variant is in linkage disequilibrium with another variant, SNP285, which confers an opposite effect.It is worth noting that the SNP285C/SNP309G haplotype frequency was observed in up to 8% of Europeans, thus requiring correction for the confounding effect of SNP285C in European studies.39 However, aside from one study conducted by Knappskog et al, no other study including the meta-analyses corrected for the confounding effect of SNP285.40 Among the studies presented in table 3, Knappskog et al (2012) reported that after correcting for SNP285, the OR for association of this haplotype with endometrial cancer was much lower, though still significant. Unfortunately, the meta-analyses which synthesised Knappskog et al (2012), as part of their analysis, did not correct for SNP285C in the European-based studies they included.38 41 42 It is also concerning that two meta-analyses using the same primary articles failed to report the same result, in two instances.38 42–44DiscussionThis article represents the most comprehensive systematic review to date, regarding critical appraisal of the available evidence of common low-penetrance variants implicated in predisposition to endometrial cancer.

We have identified the most robust SNPs in the context of endometrial cancer risk. Of those, only 19 were significant at genome-wide level and a further five were considered marginally significant. The largest GWAS conducted in this field was the discovery- and meta-GWAS by O’Mara et al, which utilised 12 096 cases and 108 979 controls.21 Despite the inclusion of all published GWAS and around 5000 newly genotyped cases, the total number did not reach anywhere near what is currently available for other common cancers such as breast cancer.

For instance, BCAC (Breast Cancer Association Consortium) stands at well over 200 000 individuals with more than half being cases, and resulted in identification of ~170 SNPs in relation to breast cancer.19 45 A total of 313 SNPs including imputations were then used to derive a PRS for breast cancer.19 Therefore, further efforts should be directed to recruit more patients, with deep phenotypic clinical data to allow for relevant adjustments and subgroup analyses to be conducted for better precision.A recent pre-print study by Zhang and colleagues examined the polygenicity and potential for SNP-based risk prediction for 14 common cancers, including endometrial cancer, using available summary-level data from European-ancestry datasets.46 They estimated that there are just over 1000 independent endometrial cancer susceptibility SNPs, and that a PRS comprising all such SNPs would have an area under the receiver-operator curve of 0.64, similar to that predicted for ovarian cancer, but lower than that for the other cancers in the study. The modelling in the paper suggests that an endometrial cancer GWAS double the size of the current largest study would be able to identify susceptibility SNPs together explaining 40% of the genetic variance, but that in order to explain 75% of the genetic variance it would be necessary to have a GWAS comprising close to 150 000 cases and controls, far in excess of what is currently feasible.We found that the literature consists mainly of candidate-gene studies with small sample sizes, meta-analyses reporting conflicting results despite using the same set of primary articles, and multiple reports of significant SNPs that have not been validated by any larger GWAS. The candidate-gene studies were indeed the most useful and cheaper technique available until the mid to late 2000s.

However, a lack of reproducibility (particularly due to population stratification and reporting bias), uncertainty of reported associations, and considerably high false discovery rates make these studies much less appropriate in the post-GWAS era. Unlike the candidate-gene approach, GWAS do not require prior knowledge, selection of genes or SNPs, and provide vast amounts of data. Furthermore, both the genotyping process and data analysis phases have become cheaper, the latter particularly due to faster and open-access pre-phasing and imputation tools being made available.It is clear from table 1 that some SNPs were reported with wide 95% CI, which can be directly attributed to small sample sizes particularly when restricting the cases to non-endometrioid histology only, low EAF or poor imputation quality.

Thus, these should be interpreted with caution. Additionally, most of the SNPs reported by candidate-gene studies were not detected by the largest GWAS to date conducted by O’Mara et al.21 However, this does not necessarily mean that the possibility of those SNPs being relevant should be completely dismissed. Moreover, meta-analyses were attempted for other variants.

However, these showed no statistically significant association and many presented with high heterogeneity between the respective studies (data not shown). Furthermore, as many studies utilised the same set of cases and/or controls, conducting a meta-analysis was not possible for a good number of SNPs. It is therefore unequivocal that the literature is crowded with numerous small candidate-gene studies and conflicting data.

This makes it particularly hard to detect novel SNPs and conduct meaningful meta-analyses.We found convincing evidence for 19 variants that indicated the strongest association with endometrial cancer, as shown in table 1. The associations between endometrial cancer and variants in or around HNF1B, CYP19A1, SOX4, MYC, KLF and EIF2AK found in earlier GWAS were then replicated in the latest and largest GWAS. These SNPs showed promising potential in a theoretical PRS we devised based on published data.

Using all 24 or genome-wide significant SNPs only, women with a PRS in the top 1% of the distribution would be predicted to have a risk of endometrial cancer 3.16 and 2.09 times higher than the mean risk, respectively.However, the importance of these variants and relevance of the proximate genes in a functional or biological context is challenging to evaluate. Long distance promoter regulation by enhancers may disguise the genuine target gene. In addition, enhancers often do not loop to the nearest gene, further complicating the relevance of nearby gene(s) to a GWAS hit.

In order to elucidate biologically relevant candidate target genes in endometrial cancer, O’Mara et al looked into promoter-associated chromatin looping using a modern HiChIP approach.47 The authors utilised normal and tumoural endometrial cell lines for this analysis which showed significant enrichment for endometrial cancer heritability, with 103 candidate target genes identified across the 13 risk loci identified by the largest ECAC GWAS. Notable genes identified here were CDKN2A and WT1, and their antisense counterparts. The former was reported to be nearby of rs1679014 and the latter of rs10835920, as shown in table 1.

Moreover, of the 36 candidate target genes, 17 were found to be downregulated while 19 were upregulated in endometrial tumours.The authors also investigated overlap between the 13 endometrial cancer risk loci and top eQTL variants for each target gene.47 In whole blood, of the two particular lead SNPs, rs8822380 at 17q21.32 was a top eQTL for SNX11 and HOXB2, whereas rs937213 at 15q15.1 was a top eQTL for SRP14. In endometrial tumour, rs7579014 at 2p16.1 was found to be a top eQTL for BCL11A. This is particularly interesting because BCL11A was the only nearby/candidate gene that had a GWAS association reported in both endometrioid and non-endometrioid subtypes.

The study looked at protein–protein interactions between endometrial cancer drivers and candidate target gene products. Significant interactions were observed with TP53 (most significant), AKT, PTEN, ESR1 and KRAS, among others. Finally, when 103 target candidate genes and 387 proteins were combined together, 462 pathways were found to be significantly enriched.

Many of these are related to gene regulation, cancer, obesity, insulinaemia and oestrogen exposure. This study clearly showed a potential biological relevance for some of the SNPs reported by ECAC GWAS in 2018.Most of the larger included studies used cohorts primarily composed of women of broad European descent. Hence, there are negligible data available for other ethnicities, particularly African women.

This is compounded by the lack of reference genotype data available for comparative analysis, making it harder for research to be conducted in ethnicities other than Europeans. This poses a problem for developing risk prediction models that are equally valuable and predictive across populations. Thus, our results also are of limited applicability to non-European populations.Furthermore, considering that non-endometrioid cases comprise a small proportion (~20%) of all endometrial cancer cases, much larger cohort sizes are needed to detect any genuine signals for non-endometrioid tumours.

Most of the evaluated studies looked at either overall/mixed endometrial cancer subtypes or endometrioid histology, and those that looked at variant associations with non-endometrioid histology were unlikely to have enough power to detect any signal with statistical significance. This is particularly concerning because non-endometrioid subtypes are biologically aggressive tumours with a much poorer prognosis that contribute disproportionately to mortality from endometrial cancer. It is particularly important that attempts to improve early detection and prevention of endometrial cancer focus primarily on improving outcomes from these subtypes.

It is also worth noting that, despite the current shift towards a molecular classification of endometrial cancer, most studies used the overarching classical Bokhman’s classification system, type I versus type II, or no histological classification system at all. Therefore, it is important to create and follow a standardised and comprehensive classification system for reporting tumour subtypes for future studies.This study compiled and presented available information for an extensively studied, yet unproven in large datasets, SNP309 variant in MDM2. Currently, there is no convincing evidence for an association between this variant and endometrial cancer risk.

Additionally, of all the studies, only one accounted for the opposing effect of a nearby variant SNP285 in their analyses. Thus, we conclude that until confirmed by a sufficiently large GWAS, this variant should not be considered significant in influencing the risk of endometrial cancer and therefore not included in a PRS. This is also true for the majority of the SNPs reported in candidate-gene studies, as the numbers fall far short of being able to detect genuine signals.This systematic review presents the most up-to-date evidence for endometrial cancer susceptibility variants, emphasising the need for further large-scale studies to identify more variants of importance, and validation of these associations.

Until data from larger and more diverse cohorts are available, the top 24 SNPs presented here are the most robust common genetic variants that affect endometrial cancer risk. The multiplicative effects of these SNPs could be used in a PRS to allow personalised risk prediction models to be developed for targeted screening and prevention interventions for women at greatest risk of endometrial cancer..

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About Health Catalyst Health Catalyst is a leading provider of data and analytics technology and services to healthcare organizations and is committed to being the catalyst for massive, measurable, data-informed healthcare improvement. Its customers leverage the cloud-based data platform—powered by data from more than 100 million patient records and encompassing trillions of facts—as well as its analytics software and professional services expertise to why don t doctors prescribe antabuse make data-informed decisions and realize measurable clinical, financial, and operational improvements. Health Catalyst envisions a future in which all healthcare decisions are data informed. Forward Looking Statements This press release may contain forward-looking statements, why don t doctors prescribe antabuse including, among others, statements regarding the timing, size and completion of the public offering. These forward-looking statements are based upon the current expectations and beliefs of the Company’s management as of the date of this release, and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements.

The reader why don t doctors prescribe antabuse is cautioned not to rely on the forward-looking statements contained in this press release. Additional information on potential factors that could affect the Company’s results and other risks and uncertainties are detailed in its Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q and filed with the SEC and available at www.sec.gov. All forward-looking statements in this why don t doctors prescribe antabuse press release are based on information available to the Company as of the date hereof, and the Company disclaims any obligation to update these forward-looking statements. Contact. Health Catalyst Investor Relations Contact:Adam BrownSenior Vice President, Investor Relations and FP&A+1 (855) 309-6800ir@healthcatalyst.com Health Catalyst Media Contact:Amanda HundtVice President, Corporate Communicationsamanda.hundt@healthcatalyst.com+1 (575) 491-0974.

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Inspectors observed buy antabuse with prescription the same hazards during a second inspection two days later, prompting the third inspection on Oct. 31. After the three inspections, OSHA proposed total penalties of $244,397 and cited the companies collectively for four willful and 35 serious violations, including exposing workers to falls greater than 6 feet and not providing personal protective equipment. The companies, citations and proposed penalties are buy antabuse with prescription. Company Name Address City State Citations Proposed Penalty Claudio DeSousa, operating as Lifetime Contractor Corp.

7132 South St. Philadelphia PA buy antabuse with prescription 2 willful 14 serious $107,279 Lezinho Sousa, operating as Lifetime Contractor Corp. 3304 Cooper Ave. Pennsauken NJ 2 willful buy antabuse with prescription 9 serious $87,381 WSJ Construction 1302 Monroe Ave. Asbury Park NJ 3 serious $16,383 Gustavo Quintomillno, operating as Lifetime Contractor Corp.

120 Elm Street, Beverly NJ 4 serious $12,874 LWJ Construction LLC 85 Lippincott Ave. Long Branch NJ 3 serious $12,288 RMM Contractor LLC 274 buy antabuse with prescription Morris Ave. Long Branch NJ 2 serious $8,192 “A fall can permanently alter or end a worker’s life in a matter of seconds,” said OSHA Area Director Paula Dixon-Roderick in Marlton, New Jersey. €œContractors and subcontractors in the construction industry have a legal obligation to comply with the law and ensure their workers end their shifts safely. When employers fail to follow requirements, OSHA will hold them responsible to the fullest extent of the law.” OSHA encourages employers to use its Stop Falls online resources, including detailed information on fall protection standards buy antabuse with prescription in English and Spanish.

The site offers fact sheets, posters and videos that illustrate various fall hazards and appropriate preventive measures. The companies have 15 business days from receipt of their citations and penalties to comply, request an informal conference with OSHA’s area director, or contest the findings before the independent Occupational Safety and Health Review Commission. Under the Occupational Safety and Health Act of 1970, employers are responsible buy antabuse with prescription for providing safe and healthful workplaces for their employees. OSHA’s role is to help ensure these conditions for America’s working men and women by setting and enforcing standards, and providing training, education and assistance. Learn more about OSHA.MINNEAPOLIS – A Minnesota lawn care and snow removal company took advantage of more than 70 temporary foreign workers – charging them higher rent than allowed, requiring them to pay for their international transportation and demanding payment to keep their jobs – all in buy antabuse with prescription violation of the federal H-2B Visa program.

The program helps supply employers with temporary foreign workers when sufficient numbers of U.S. Workers are not available.A U.S. Department of Labor investigation of Valdes Lawn Care and Snow Removal LLC in Lake Elmo buy antabuse with prescription has led to the recovery of $118,950 in back wages and $38,688 in liquidated damages for 72 employees for violations of H-2B prevailing wage rate requirements and for violations of the overtime and record keeping provisions of the Fair Labor Standards Act. The company will also pay $127,561 in civil money penalties, and be debarred from eligibility to participate in the H-2B program for three years. The payments and the debarment are part of a consent judgment entered by an administrative law judge in Pittsburgh.

€œEmployers who exploit temporary buy antabuse with prescription workers hurt both foreign and U.S. Workers,” said Wage and Hour Division Assistant District Director Kristin Tout in Minneapolis. €œThe Wage and Hour Division is committed to ensuring that all workers receive their hard-earned wages, and that employers using the H-2B visa program abide by all program requirements. Our enforcement protects workers and levels the playing field for employers who play by the rules.” The division determined Valdes violated the buy antabuse with prescription H-2B Visa program when it. Failed to disclose that housing was available at a cost and then profited off workers by charging monthly rent fees that were higher than the cost to Valdes.

Demanded guest workers each pay them up to $800 buy antabuse with prescription as a condition of employment. Failed to reimburse guest workers for travel expenses from and to their home countries, as required. Failed to offer guest workers at least 35 hours per workweek during the first months of the work season as required. Employed at least four temporary foreign workers hired for landscaping and snow removal work buy antabuse with prescription to perform construction work. Misrepresented the need for workers.

For a four-month period, the employer had little to no work available. Failed to provide workers with a copy of the job order outlining the terms buy antabuse with prescription and conditions of employment. Failed to post the mandatory Employee Rights Under the H-2B Program poster. Additionally, the company violated FLSA minimum wage and overtime requirements when it. Failed to pay overtime after 40 hours in a work week and instead paid overtime only after 80 hours worked in buy antabuse with prescription a two-week pay period.

Failed to pay guest workers overtime at the required rates. Paid nine U.S buy antabuse with prescription. Workers flat salaries regardless of the number of hours that they worked, failing to pay overtime when they worked more than 40 hours in a workweek. Failed to keep records of the number of hours employees actually worked by salaried workers, and by H-2B workers who performed construction and laborer work at the employer’s home. For more information about the H-2B Program, the FLSA and other laws enforced by the Wage and Hour Division, contact the division’s toll-free helpline at 866-4US-WAGE (487-9243).

Learn more about the Wage and Hour Division, including a search tool to use if you think you may be owed back wages collected by the division. COURT NO. Administrator, Wage and Hour Division, U.S. Department of Labor V. Valdes Lawn Care and Snow Removal LLC, 2020-TNE-00034.

MARLTON, NJ – Six contractors constructing luxury single-family homes at the future site of Hawthorne Estates in Medford put workers at risk of http://www.ec-sud-illkirch-graffenstaden.site.ac-strasbourg.fr/?p=4897 serious or fatal injuries by failing to comply with federal requirements to prevent falls, the leading cause of death in the construction industry.After multiple on-site investigations, the U.S antabuse online. Department of Labor’s Occupational Safety and Health Administration cited the companies for exposing workers to falls and other dangerous safety hazards while erecting walls and sheathing roofs. OSHA initiated three of the inspections as part of its Regional Emphasis Program on antabuse online Falls in Construction.

During the first on Oct. 20, 2020, the compliance officer observed workers exposed to falls and other hazards. Inspectors observed the same antabuse online hazards during a second inspection two days later, prompting the third inspection on Oct.

31. After the three inspections, OSHA proposed total penalties of $244,397 and cited the companies collectively for four willful and 35 serious violations, including exposing workers to falls greater than 6 feet and not providing personal protective equipment. The companies, citations antabuse online and proposed penalties are.

Company Name Address City State Citations Proposed Penalty Claudio DeSousa, operating as Lifetime Contractor Corp. 7132 South St. Philadelphia PA 2 willful 14 serious $107,279 Lezinho Sousa, operating antabuse online as Lifetime Contractor Corp.

3304 Cooper Ave. Pennsauken NJ 2 willful 9 antabuse online serious $87,381 WSJ Construction 1302 Monroe Ave. Asbury Park NJ 3 serious $16,383 Gustavo Quintomillno, operating as Lifetime Contractor Corp.

120 Elm Street, Beverly NJ 4 serious $12,874 LWJ Construction LLC 85 Lippincott Ave. Long Branch NJ 3 serious $12,288 RMM Contractor LLC antabuse online 274 Morris Ave. Long Branch NJ 2 serious $8,192 “A fall can permanently alter or end a worker’s life in a matter of seconds,” said OSHA Area Director Paula Dixon-Roderick in Marlton, New Jersey.

€œContractors and subcontractors in the construction industry have a legal obligation to comply with the law and ensure their workers end their shifts safely. When employers fail to follow requirements, OSHA will hold them responsible to the fullest extent of the law.” OSHA encourages employers to use its Stop Falls online resources, including antabuse online detailed information on fall protection standards in English and Spanish. The site offers fact sheets, posters and videos that illustrate various fall hazards and appropriate preventive measures.

The companies have 15 business days from receipt of their citations and penalties to comply, request an informal conference with OSHA’s area director, or contest the findings before the independent Occupational Safety and Health Review Commission. Under the Occupational Safety and Health Act of 1970, employers are responsible for providing antabuse online safe and healthful workplaces for their employees. OSHA’s role is to help ensure these conditions for America’s working men and women by setting and enforcing standards, and providing training, education and assistance.

Learn more about OSHA.MINNEAPOLIS – A Minnesota lawn care and snow removal company took advantage of more than 70 temporary foreign workers – charging them higher rent than allowed, requiring them to pay for their international transportation antabuse online and demanding payment to keep their jobs – all in violation of the federal H-2B Visa program. The program helps supply employers with temporary foreign workers when sufficient numbers of U.S. Workers are not available.A U.S.

Department of Labor investigation of Valdes Lawn Care and Snow Removal antabuse online LLC in Lake Elmo has led to the recovery of $118,950 in back wages and $38,688 in liquidated damages for 72 employees for violations of H-2B prevailing wage rate requirements and for violations of the overtime and record keeping find out this here provisions of the Fair Labor Standards Act. The company will also pay $127,561 in civil money penalties, and be debarred from eligibility to participate in the H-2B program for three years. The payments and the debarment are part of a consent judgment entered by an administrative law judge in Pittsburgh.

€œEmployers who exploit temporary workers hurt antabuse online both foreign and U.S. Workers,” said Wage and Hour Division Assistant District Director Kristin Tout in Minneapolis. €œThe Wage and Hour Division is committed to ensuring that all workers receive their hard-earned wages, and that employers using the H-2B visa program abide by all program requirements.

Our enforcement protects workers and levels the playing field for employers who play by the rules.” antabuse online The division determined Valdes violated the H-2B Visa program when it. Failed to disclose that housing was available at a cost and then profited off workers by charging monthly rent fees that were higher than the cost to Valdes. Demanded antabuse online guest workers each pay them up to $800 as a condition of employment.

Failed to reimburse guest workers for travel expenses from and to their home countries, as required. Failed to offer guest workers at least 35 hours per workweek during the first months of the work season as required. Employed at least four temporary foreign workers hired for landscaping antabuse online and snow removal work to perform construction work.

Misrepresented the need for workers. For a four-month period, the employer had little to no work available. Failed to antabuse online provide workers with a copy of the job order outlining the terms and conditions of employment.

Failed to post the mandatory Employee Rights Under the H-2B Program poster. Additionally, the company violated FLSA minimum wage and overtime requirements when it. Failed to pay overtime after 40 hours in a work week and instead paid overtime only after 80 hours worked in a two-week pay period.

Failed to pay guest workers overtime at the required rates. Paid nine U.S. Workers flat salaries regardless of the number of hours that they worked, failing to pay overtime when they worked more than 40 hours in a workweek.

Failed to keep records of the number of hours employees actually worked by salaried workers, and by H-2B workers who performed construction and laborer work at the employer’s home. For more information about the H-2B Program, the FLSA and other laws enforced by the Wage and Hour Division, contact the division’s toll-free helpline at 866-4US-WAGE (487-9243). Learn more about the Wage and Hour Division, including a search tool to use if you think you may be owed back wages collected by the division.

COURT NO. Administrator, Wage and Hour Division, U.S. Department of Labor V.

Valdes Lawn Care and Snow Removal LLC, 2020-TNE-00034.

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FOR IMMEDIATE RELEASEJune 9 low price antabuse Today, the Health Resources and Services Administration (HRSA), announced $22 million in awards to 56 recipients as Get More Information part of the Behavioral Health Workforce and Education Training (BHWET) Program for Professionals. Thanks to the American Rescue Plan, this brings the total BHWET awards to $66 million for 168 organizations."Collaborating with community-based partners such as public health organizations, hospitals, and schools presents an opportunity to reduce disparities in access to behavioral health services," said Acting HRSA Administrator Diana Espinosa. "Through these experiential training opportunities, members of the behavioral health workforce will get on-the-ground training in the communities and with the populations they will serve."Recipient organizations will train graduate level students of social work, psychology, and other behavioral and mental health disciplines to work with vulnerable populations, particularly children, adolescents and transitional-aged youth at risk low price antabuse for behavioral health disorders. Through placements at health centers and other community-based settings, trainees will gain experience working in the underserved communities where behavioral health services are most urgently needed.For a complete list of fiscal year 2021 BHWET-Professionals recipients, visit.

Https://bhw.hrsa.gov/funding/behavioral-health-workforce-education-training-fy2021-awardsLearn more about HRSA Behavioral Health Workforce Development Programs.Learn more about HRSA’s funding opportunities.ELK CITY — One student throws his classmates’ pencil box on the floor in anger. Another bites her own arm out low price antabuse of frustration. Others run screaming from their classrooms. Some Elk City Elementary School students are celebrating as summer break approaches.

Others are dreading the end of the school year, low price antabuse acting out in fear of what the next three months could bring. School counselor Kim Hamm worries about students who won’t have enough to eat this summer. And those without air conditioning or running water. She wonders how many will be left alone while their low price antabuse caretakers are working two or three jobs.

And who will spend their days anticipating the next attack from an abusive family member. Hamm has spent most of May helping students low price antabuse ages 4 to 9 identify and cope with their feelings, which can be triggered by instability at home. “They know that, here, they’re safe and we’re not going to hurt them,” Hamm said. €œAnd a lot of our kids, unfortunately, don’t go home to that every day.” About 100 miles west of Oklahoma City on Interstate 40, Elk City is home to nearly 12,000 residents whose financial stability ebbs and flows with the volatile oil and gas industry.

The nearby North Fork Correctional Facility brought some families to town to be close to a loved low price antabuse one. And students face rates of poverty, special needs and suicide higher than the state average. Kim Hamm, an Elk City Elementary School counselor, talks to a pre-kindergarten student who is playing with sensory toys purchased with Project AWARE funds in her office. Hamm said disadvantaged, abused and neglected students’ behavior deteriorates toward the end of the school year because they’re afraid or stressed about spending months away from school, which provides safety low price antabuse when life at home is turbulent.

(Courtesy photo) In her six years as a school counselor, Hamm has learned to anticipate these needs, making more time towards the end of the school year to meet with students one-on-one. But she doesn’t always have the bandwidth. School counselors’ duties range from helping develop individualized learning plans for students with special needs to low price antabuse proctoring the third-grade reading test. They enroll students in classes and ensure they meet state math and science requirements.

They provide college and career advice and help them find and apply for scholarships. They wrangle students during morning drop-off and afternoon low price antabuse pick-up, run school-sponsored food and clothes pantries and teach breathing techniques to those with test anxiety. Low pay and increasing obligations have left Oklahoma with a teacher shortage, which means counselors like Hamm are taking on more work leaving less time for struggling students. Counselors refer the most troubled kids to community mental health counselors low price antabuse.

But they are also in short supply especially in rural areas like Elk City where the ratio of mental healthcare providers to residents is 1 to 150,000. Without adequate local resources, the responsibility of students’ mental health care is falling to school counselors who are outnumbered and overwhelmed. A federal program is increasing support for students in six rural school districts in what the state mental health and education departments call “mental health deserts.” But schools are finding it difficult to hire qualified caregivers and low price antabuse alcoholism treatment restrictions have halted programs and limited in-person treatment. Students are seen leaving Elk City Elementary School at the end of the school day.

School counselor Kim Hamm said for some students school is a safe place and leaving is not a happy but fearful time of day for students who don’t have enough to eat or are abused by family members at home. (Whitney Bryen/Oklahoma Watch) A Response Inspired By Sandy Hook Since low price antabuse 2018, the State Department of Education has received two U.S. Department of Health and Human Services grants totaling $18 million. Oklahoma’s Project AWARE, short for Advancing Wellness and Resiliency in Education, is in its third year of the five-year grant at Woodward, Elk City and Weatherford Public Schools and its first year at Ada, Atoka and Checotah Public Schools.

Subscribe to low price antabuse Jennifer Palmer's Education Watch newsletter Processing… Success!. You're on the list. Whoops! low price antabuse. There was an error and we couldn't process your subscription.

Please reload the page and try again. The districts were chosen by the state department for their lack of treatment providers and high-risk student populations low price antabuse. Oklahoma students are some of the most traumatized in the nation, according to several national health rankings including a recent survey conducted by a group based at Johns Hopkins University. But kids in these rural districts were more likely to have access to firearms, live in poverty, have an incarcerated parent, use drugs, experience depression and die by suicide, according to the state’s grant application.

These students low price antabuse are more susceptible to mental illness. And without treatment, they can face even more dangerous obstacles as they age, often leading to their own violent encounters, substance abuse or incarceration. Subscribe to our First Watch newsletter Processing… Success!. You're low price antabuse on the list.

Whoops!. There was an error and we couldn't process your subscription. Please reload the page low price antabuse and try again. In one of the country’s deadliest school shootings, a 20-year-old killed six adults and 20 students at Sandy Hook Elementary School in 2012.

Since then, the Substance Abuse and Mental Health Services Administration has sent millions to schools nationwide with high-risk low price antabuse students to prevent violence perpetrated by young people. This story was reported in partnership with the Solutions Journalism Network. For more information, go to solutionsjournalism.org. In their first year of the grant, Atoka, Ada and Checotah schools in Eastern Oklahoma spent low price antabuse most of the year assessing student needs and training staff.

At Elk City, Weatherford and Woodward schools in Western Oklahoma, Project AWARE forged ahead despite changes to programs that were derailed by the antabuse. Community events aim to reduce stigma around mental health challenges and treatment and teach parents and students about healthy habits like the importance of sleep and recommendations for social media use. Elk City paused events in the spring of 2020 while Weatherford took its online and saw a spike low price antabuse in participation. Fifth through 12th grade students at all six districts completed mental health assessments, which helps educators identify students who are distracted, unhappy, scared, lonely or are prone to acting out.

Community mental health counselors had started to meet with troubled students in some of the Western Oklahoma schools. Parents have to agree to therapy but bringing professionals into the schools reduces barriers for families who lack transportation or who feel embarrassed visiting a local treatment facility low price antabuse. Many of these services were paused due to alcoholism treatment. Some Project AWARE schools started group therapy sessions led by licensed mental health professionals for students low price antabuse with chronic stress often triggered by traumatic experiences like an absent or abusive parent.

The grant also trained educators at all six districts in a classroom program that teaches conflict resolution and empathy. Liz Henthorn, a kindergarten teacher at Elk City Elementary School, listens as her students rate how they’re feeling at the end of the day. Henthorn checks in with her students twice a day through a program known as Circles that she low price antabuse says teaches students coping skills and empathy. (Whitney Bryen/Oklahoma Watch) Just before the bell rang on a Monday afternoon, kindergarteners sat in a circle on a rug at the front of Liz Henthorn’s classroom at Elk City Elementary School.

One-by-one the students rated how they’re feeling as they prepared to go home. They describe low price antabuse their feelings as green, yellow or red if they’re having a difficult day and their peers offer comfort and advice. One student said he was feeling sad because his dog ran away that morning. Another student was feeling red because she had a bad dream.

Other students spoke up saying they could relate or that they’re low price antabuse sorry that happened. “We’re teaching kids to identify their feelings and giving suggestions to cope,” Henthorn said. €œAnd when we do it as a group the kids are learning about empathy and thinking about ways to help each other low price antabuse and that is just as important.” Liz Henthorn, a kindergarten teacher at Elk City Elementary School, listens as her students rate how they’re feeling at the end of the day. (Whitney Bryen/Oklahoma Watch) Teachers, counselors and administrators were trained to provide coping skills to students who face universal challenges like disagreements with classmates or stress about what to do after graduation.

But few are qualified to help more critical students, like those with mental illness or who have experienced trauma. Woodward Public Schools reported 82 homeless students low price antabuse during the 2017-18 school year – more than twice the state average. Nearly two-thirds of students at Woodward and Elk City Public Schools qualified for free and reduced lunches, compared to the state’s average of 50%. In Elk City, 140 of the district’s 2,110 students had a parent who was incarcerated.

And all three Western low price antabuse Oklahoma districts had higher than average suicide rates. Those districts rely on school counselors to support these students, though most lack the training. And the grant does not address the ratio of counselors to students, which is far above national recommendations. Districts also planned to low price antabuse increase referrals to community treatment centers facilitated by the grant.

Demand for mental health care spiked during the antabuse, further straining the area’s providers and leaving families with few options. Weatherford elementary students are seen eating lunch in the school’s cafeteria. (Whitney Bryen/Oklahoma Watch) The Complicated Search for Counselors low price antabuse School counselors can listen to students and offer coping techniques, but their ability to help is limited. Licensed counselors can provide therapy and diagnose students with mental illness.

Elk City, Woodward and Weatherford districts hoped to bring more licensed professional counselors into schools by hiring new staff and using Project AWARE funds to pay for training for current school low price antabuse counselors. Each district hired one licensed mental health provider who serves all students. The districts have been unable to hire any new school counselors and no existing counselors have been licensed. The state low price antabuse requires school counselors to have a master’s degree in a related field or two years of experience, and pass the state’s general education, professional teaching and school counseling exams.

Training for licensed professional counselors requires an additional 60 graduate-level college hours and 3,000 hours of supervised counseling. Counselors must also pass an exam before being licensed. Education costs are likely to total $21,000 to $33,000 depending on the school, according to low price antabuse the most recent state averages. And that doesn’t include fees for supervision or the licensing exam.

The grant will pay tuition costs for school counselors to get their license. Only two of low price antabuse 16 school counselors in Elk City, Weatherford and Woodward have taken the offer. School counselors said it is still an expensive and lengthy endeavour that results in more work without a boost in pay or a promotion. “I know that it would give me more in depth counseling training, but I think at this time in my life with small children it’s just probably not going low price antabuse to happen,” said Hamm, who has a 10-month-old and a 3-year-old.

€œIf I was going to make more as a school counselor with it then maybe I would, but I’m not going to so I’m just not going to spend a whole lot of time to get that.” For school counselors who do get their license, the job doesn’t change much. They often have the same paperwork, testing responsibilities and recess duty. But they’re also counseling the school’s most traumatized low price antabuse kids, a group that is growing following the antabuse. Oklahoma has 1,841 school counselors and nearly 695,000 students, according to State Department of Education reports.

The department does not track how many school counselors have their professional counseling license. The American School Counselor Association recommends low price antabuse a ratio of 1 school counselor to 250 students. Oklahoma mandates 1 school counselor per 450 middle and high school students. The state does not have a threshold for elementary schools.

Not every school low price antabuse has a dedicated counselor. Some have teams depending on student population, how schools prioritize funding and disperse tasks. The Association also recommends counselors spend at least 80% of their time working directly with or for individual students. Oklahoma Watch low price antabuse interviewed 10 counselors across the state.

Most said they spend the majority of their day doing clerical work. Depending on the time of year, about 20 to 50% of low price antabuse their time is spent with students. Elizabeth Moss, a seventh and eighth grade counselor at Woodward Middle School, said she is one of the fortunate ones because she spends about 50% of her time meeting with students one-on-one thanks to the help of her administration. Even with the group sessions she leads, Moss said she still hasn’t been able to meet the national recommendation.

€œA lot of what I deal with are the results of families who are in crisis, where there’s addiction, other issues that are related to poverty and the kids show up to school and there’s a lot of low price antabuse fallout from that,” Moss said. €œAnd so we have kids who are depressed. We’ve had kids who are suicidal. Anxieties are really high.” Lora Anderson, a school counselor at Ada Junior High low price antabuse School, talks to students about online enrollment and how to choose classes for next school year.

(Courtesy photo) Moss is one of two school counselors taking advantage of Project AWARE funding to get her professional counseling license. Her principal took over her ACT and pre-ACT testing, scheduling and enrollment duties allowing Moss to spend more time with students in crisis. “I would love to see even more taken off low price antabuse of the shoulders of counselors so that we could take care of our kids’ needs better,” Moss said. €œBut I truly feel blessed here that I am not overwhelmed, like so many counselors.” At Ada Junior High School, counselor Lora Anderson spends about 25% of her time working with troubled students.

Many school counselors go into the job to propel students’ academic success, not to provide therapy. Anderson does her best to help students but said she isn’t trained to help kids with acute needs. €œThat’s not what I want to do,” Anderson said after returning to her desk from lunch duty. €œI do so many different things to help students.

If I wanted to be a mental health counselor, I wouldn’t work in a school.” Michelle Taylor, President-Elect of the Oklahoma School Counselor Association and counselor at Adair High School, said the job has changed a lot since she started and counselors at smaller schools like hers are often overwhelmed juggling paperwork, test proctoring and counseling students. (Courtesy photo) Michelle Taylor, President-Elect of the Oklahoma School Counselor Association, said the organization doesn’t track how many school counselors have their license. But based on training she’s attended and led over the years, Taylor said it’s likely that about 1 in 5 school counselors goes on to become licensed. School counselors are serving dual roles whether they want to or not.

Like swim instructors at a pool, most school counselors see their role as building stronger swimmers. But as mental health challenges continue to grow, counselors also have to serve as lifeguards, diving into the deep end to rescue drowning kids. “Counselors in rural schools tend to be treading more water,” Taylor said. €œSome folks are so overwhelmed with the job they have, they don’t have the time or the motivation to seek out additional training.

It’s just not accessible for folks.” Taylor has been a school counselor for more than 20 years and has her professional counseling license. She currently works with students at Adair High School in northeast Oklahoma. She said the job has changed a lot since she started. Test requirements are constantly evolving.

College admissions and scholarship applications seem to get longer every year. And students want to talk more. Kids are more willing to open up about their issues, especially since mental health is talked about more openly since the antabuse, Taylor said. And school counselors have to be ready to listen and help.

“I think we should be the ones doing this work because we already know the students and they already know us so it’s quicker to get to that trust that can take a long time to develop,” Taylor said. €œThat’s when it becomes about priorities and we have to respond to what the students need first and then worry about everything else.” Elk City Middle School students took a mental health screening at the beginning of Lana Graham’s geography class in March. Graham said since the alcoholism antabuse began, her students seem more anxious and depressed than ever. (Whitney Bryen/Oklahoma Watch) Support our publicationEvery day we strive to produce journalism that matters — stories that strengthen accountability and transparency, provide value and resonate with readers like you.This work is essential to a better-informed community and a healthy democracy.

But it isn’t possible without your support. Donate now.

FOR IMMEDIATE RELEASEJune 9 Today, the Health Resources and Services Administration (HRSA), announced $22 million in antabuse online awards to 56 recipients as part of the Behavioral Health Workforce and Education Training (BHWET) Program for Professionals. Thanks to the American Rescue Plan, this brings the total BHWET awards to $66 million for 168 organizations."Collaborating with community-based partners such as public health organizations, hospitals, and schools presents an opportunity to reduce disparities in access to behavioral health services," said Acting HRSA Administrator Diana Espinosa. "Through these experiential training opportunities, members of the behavioral health workforce will get on-the-ground training in the communities and with the populations they will serve."Recipient organizations will train graduate level students of social work, psychology, and other behavioral and mental health disciplines to work antabuse online with vulnerable populations, particularly children, adolescents and transitional-aged youth at risk for behavioral health disorders. Through placements at health centers and other community-based settings, trainees will gain experience working in the underserved communities where behavioral health services are most urgently needed.For a complete list of fiscal year 2021 BHWET-Professionals recipients, visit.

Https://bhw.hrsa.gov/funding/behavioral-health-workforce-education-training-fy2021-awardsLearn more about HRSA Behavioral Health Workforce Development Programs.Learn more about HRSA’s funding opportunities.ELK CITY — One student throws his classmates’ pencil box on the floor in anger. Another bites her own antabuse online arm out of frustration. Others run screaming from their classrooms. Some Elk City Elementary School students are celebrating as summer break approaches.

Others are dreading the end of the antabuse online school year, acting out in fear of what the next three months could bring. School counselor Kim Hamm worries about students who won’t have enough to eat this summer. And those without air conditioning or running water. She wonders how many will be left alone while antabuse online their caretakers are working two or three jobs.

And who will spend their days anticipating the next attack from an abusive family member. Hamm has spent most of May helping students ages 4 to 9 identify and cope with their feelings, which can be triggered antabuse online by instability at home. “They know that, here, they’re safe and we’re not going to hurt them,” Hamm said. €œAnd a lot of our kids, unfortunately, don’t go home to that every day.” About 100 miles west of Oklahoma City on Interstate 40, Elk City is home to nearly 12,000 residents whose financial stability ebbs and flows with the volatile oil and gas industry.

The nearby North Fork Correctional Facility brought some families antabuse online to town to be close to a loved one. And students face rates of poverty, special needs and suicide higher than the state average. Kim Hamm, an Elk City Elementary School counselor, talks to a pre-kindergarten student who is playing with sensory toys purchased with Project AWARE funds in her office. Hamm said disadvantaged, abused and neglected students’ behavior deteriorates toward the end of the school year because they’re afraid or stressed about spending months away from school, which provides safety when life at home antabuse online is turbulent.

(Courtesy photo) In her six years as a school counselor, Hamm has learned to anticipate these needs, making more time towards the end of the school year to meet with students one-on-one. But she doesn’t always have the bandwidth. School counselors’ duties range from helping develop individualized learning plans for students with special needs to proctoring antabuse online the third-grade reading test. They enroll students in classes and ensure they meet state math and science requirements.

They provide college and career advice and help them find and apply for scholarships. They wrangle students during morning antabuse online drop-off and afternoon pick-up, run school-sponsored food and clothes pantries and teach breathing techniques to those with test anxiety. Low pay and increasing obligations have left Oklahoma with a teacher shortage, which means counselors like Hamm are taking on more work leaving less time for struggling students. Counselors refer the most antabuse online troubled kids to community mental health counselors.

But they are also in short supply especially in rural areas like Elk City where the ratio of mental healthcare providers to residents is 1 to 150,000. Without adequate local resources, the responsibility of students’ mental health care is falling to school counselors who are outnumbered and overwhelmed. A federal program is increasing support for students in six rural school districts in what the state mental health and education departments call antabuse online “mental health deserts.” But schools are finding it difficult to hire qualified caregivers and alcoholism treatment restrictions have halted programs and limited in-person treatment. Students are seen leaving Elk City Elementary School at the end of the school day.

School counselor Kim Hamm said for some students school is a safe place and leaving is not a happy but fearful time of day for students who don’t have enough to eat or are abused by family members at home. (Whitney Bryen/Oklahoma Watch) A Response Inspired By antabuse online Sandy Hook Since 2018, the State Department of Education has received two U.S. Department of Health and Human Services grants totaling $18 million. Oklahoma’s Project AWARE, short for Advancing Wellness and Resiliency in Education, is in its third year of the five-year grant at Woodward, Elk City and Weatherford Public Schools and its first year at Ada, Atoka and Checotah Public Schools.

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Please reload the page and try again. The districts were chosen by the state department for their lack antabuse online of treatment providers and high-risk student populations. Oklahoma students are some of the most traumatized in the nation, according to several national health rankings including a recent survey conducted by a group based at Johns Hopkins University. But kids in these rural districts were more likely to have access to firearms, live in poverty, have an incarcerated parent, use drugs, experience depression and die by suicide, according to the state’s grant application.

These students antabuse online are more susceptible to mental illness. And without treatment, they can face even more dangerous obstacles as they age, often leading to their own violent encounters, substance abuse or incarceration. Subscribe to our First Watch newsletter Processing… Success!. You're on antabuse online the list.

Whoops!. There was an error and we couldn't process your subscription. Please reload antabuse online the page and try again. In one of the country’s deadliest school shootings, a 20-year-old killed six adults and 20 students at Sandy Hook Elementary School in 2012.

Since then, the Substance Abuse and Mental Health Services Administration has sent millions to schools nationwide with high-risk students to prevent violence perpetrated by young people antabuse online. This story was reported in partnership with the Solutions Journalism Network. For more information, go to solutionsjournalism.org. In their first year of the grant, Atoka, Ada and Checotah schools in Eastern Oklahoma antabuse online spent most of the year assessing student needs and training staff.

At Elk City, Weatherford and Woodward schools in Western Oklahoma, Project AWARE forged ahead despite changes to programs that were derailed by the antabuse. Community events aim to reduce stigma around mental health challenges and treatment and teach parents and students about healthy habits like the importance of sleep and recommendations for social media use. Elk City paused events in the spring of antabuse online 2020 while Weatherford took its online and saw a spike in participation. Fifth through 12th grade students at all six districts completed mental health assessments, which helps educators identify students who are distracted, unhappy, scared, lonely or are prone to acting out.

Community mental health counselors had started to meet with troubled students in some of the Western Oklahoma schools. Parents have to agree to therapy but bringing professionals into the schools reduces barriers for families who lack transportation or who feel embarrassed visiting a antabuse online local treatment facility. Many of these services were paused due to alcoholism treatment. Some Project AWARE schools started group therapy sessions led antabuse online by licensed mental health professionals for students with chronic stress often triggered by traumatic experiences like an absent or abusive parent.

The grant also trained educators at all six districts in a classroom program that teaches conflict resolution and empathy. Liz Henthorn, a kindergarten teacher at Elk City Elementary School, listens as her students rate how they’re feeling at the end of the day. Henthorn checks in with her students twice a day through a program known as Circles that she says teaches students coping skills antabuse online and empathy. (Whitney Bryen/Oklahoma Watch) Just before the bell rang on a Monday afternoon, kindergarteners sat in a circle on a rug at the front of Liz Henthorn’s classroom at Elk City Elementary School.

One-by-one the students rated how they’re feeling as they prepared to go home. They describe their feelings as green, yellow or red if they’re antabuse online having a difficult day and their peers offer comfort and advice. One student said he was feeling sad because his dog ran away that morning. Another student was feeling red because she had a bad dream.

Other students spoke up saying they could relate antabuse online or that they’re sorry that happened. “We’re teaching kids to identify their feelings and giving suggestions to cope,” Henthorn said. €œAnd when we do it as a group the kids are learning about empathy and thinking about ways to help each other and that is just as important.” Liz Henthorn, a kindergarten teacher at Elk City Elementary antabuse online School, listens as her students rate how they’re feeling at the end of the day. (Whitney Bryen/Oklahoma Watch) Teachers, counselors and administrators were trained to provide coping skills to students who face universal challenges like disagreements with classmates or stress about what to do after graduation.

But few are qualified to help more critical students, like those with mental illness or who have experienced trauma. Woodward Public Schools reported 82 homeless students during the 2017-18 school antabuse online year – more than twice the state average. Nearly two-thirds of students at Woodward and Elk City Public Schools qualified for free and reduced lunches, compared to the state’s average of 50%. In Elk City, 140 of the district’s 2,110 students had a parent who was incarcerated.

And all three Western Oklahoma districts had higher than average suicide antabuse online rates. Those districts rely on school counselors to support these students, though most lack the training. And the grant does not address the ratio of counselors to students, which is far above national recommendations. Districts also antabuse online planned to increase referrals to community treatment centers facilitated by the grant.

Demand for mental health care spiked during the antabuse, further straining the area’s providers and leaving families with few options. Weatherford elementary students are seen eating lunch in the school’s cafeteria. (Whitney Bryen/Oklahoma Watch) The Complicated Search for Counselors School counselors can listen to antabuse online students and offer coping techniques, but their ability to help is limited. Licensed counselors can provide therapy and diagnose students with mental illness.

Elk City, Woodward and Weatherford districts hoped to bring more licensed professional counselors into schools by hiring new staff and antabuse online using Project AWARE funds to pay for training for current school counselors. Each district hired one licensed mental health provider who serves all students. The districts have been unable to hire any new school counselors and no existing counselors have been licensed. The state requires school counselors to have a master’s antabuse online degree in a related field or two years of experience, and pass the state’s general education, professional teaching and school counseling exams.

Training for licensed professional counselors requires an additional 60 graduate-level college hours and 3,000 hours of supervised counseling. Counselors must also pass an exam before being licensed. Education costs are likely to total $21,000 to $33,000 depending on the school, according to the most recent antabuse online state averages. And that doesn’t include fees for supervision or the licensing exam.

The grant will pay tuition costs for school counselors to get their license. Only two of 16 school counselors in Elk antabuse online City, Weatherford and Woodward have taken the offer. School counselors said it is still an expensive and lengthy endeavour that results in more work without a boost in pay or a promotion. “I know that it would give me more in depth counseling training, but I think at this time in my antabuse online life with small children it’s just probably not going to happen,” said Hamm, who has a 10-month-old and a 3-year-old.

€œIf I was going to make more as a school counselor with it then maybe I would, but I’m not going to so I’m just not going to spend a whole lot of time to get that.” For school counselors who do get their license, the job doesn’t change much. They often have the same paperwork, testing responsibilities and recess duty. But they’re also counseling antabuse online the school’s most traumatized kids, a group that is growing following the antabuse. Oklahoma has 1,841 school counselors and nearly 695,000 students, according to State Department of Education reports.

The department does not track how many school counselors have their professional counseling license. The American antabuse online School Counselor Association recommends a ratio of 1 school counselor to 250 students. Oklahoma mandates 1 school counselor per 450 middle and high school students. The state does not have a threshold for elementary schools.

Not every school has a dedicated counselor antabuse online. Some have teams depending on student population, how schools prioritize funding and disperse tasks. The Association also recommends counselors spend at least 80% of their time working directly with or for individual students. Oklahoma Watch interviewed 10 counselors across antabuse online the state.

Most said they spend the majority of their day doing clerical work. Depending on the time of year, about antabuse online 20 to 50% of their time is spent with students. Elizabeth Moss, a seventh and eighth grade counselor at Woodward Middle School, said she is one of the fortunate ones because she spends about 50% of her time meeting with students one-on-one thanks to the help of her administration. Even with the group sessions she leads, Moss said she still hasn’t been able to meet the national recommendation.

€œA lot of what I deal with are the results of families antabuse online who are in crisis, where there’s addiction, other issues that are related to poverty and the kids show up to school and there’s a lot of fallout from that,” Moss said. €œAnd so we have kids who are depressed. We’ve had kids who are suicidal. Anxieties are really high.” Lora Anderson, a school counselor at Ada antabuse online Junior High School, talks to students about online enrollment and how to choose classes for next school year.

(Courtesy photo) Moss is one of two school counselors taking advantage of Project AWARE funding to get her professional counseling license. Her principal took over her ACT and pre-ACT testing, scheduling and enrollment duties allowing Moss to spend more time with students in crisis. “I would love to see antabuse online even more taken off of the shoulders of counselors so that we could take care of our kids’ needs better,” Moss said. €œBut I truly feel blessed here that I am not overwhelmed, like so many counselors.” At Ada Junior High School, counselor Lora Anderson spends about 25% of her time working with troubled students.

Many school counselors go into the job to propel students’ academic success, not to provide therapy antabuse online. Anderson does her best to help students but said she isn’t trained to help kids with acute needs. €œThat’s not what I want to do,” Anderson said after returning to her desk from lunch duty. €œI do so many different antabuse online things to help students.

If I wanted to be a mental health counselor, I wouldn’t work in a school.” Michelle Taylor, President-Elect of the Oklahoma School Counselor Association and counselor at Adair High School, said the job has changed a lot since she started and counselors at smaller schools like hers are often overwhelmed juggling paperwork, test proctoring and counseling students. (Courtesy photo) Michelle Taylor, President-Elect of the Oklahoma School Counselor Association, said the organization doesn’t track how many school counselors have their license. But based on training she’s attended and led over the years, Taylor said it’s likely that about 1 in 5 antabuse online school counselors goes on to become licensed. School counselors are serving dual roles whether they want to or not.

Like swim instructors at a pool, most school counselors see their role as building stronger swimmers. But as antabuse online mental health challenges continue to grow, counselors also have to serve as lifeguards, diving into the deep end to rescue drowning kids. “Counselors in rural schools tend to be treading more water,” Taylor said. €œSome folks are so overwhelmed with the job they have, they don’t have the time or the motivation to seek out additional training.

It’s just not accessible for folks.” Taylor has been a school counselor antabuse online for more than 20 years and has her professional counseling license. She currently works with students at Adair High School in northeast Oklahoma. She said the antabuse online job has changed a lot since she started. Test requirements are constantly evolving.

College admissions and scholarship applications seem to get longer every year. And students want antabuse online to talk more. Kids are more willing to open up about their issues, especially since mental health is talked about more openly since the antabuse, Taylor said. And school counselors have to be ready to listen and help.

“I think we should be the ones doing this work because we already know the students and they already know us so it’s quicker to get to that trust that can take a long time to develop,” Taylor said. €œThat’s when it becomes about priorities and we have to respond to what the students need first and then worry about everything else.” Elk City Middle School students took a mental health screening at the beginning of Lana Graham’s geography class in March. Graham said since the alcoholism antabuse began, her students seem more anxious and depressed than ever. (Whitney Bryen/Oklahoma Watch) Support our publicationEvery day we strive to produce journalism that matters — stories that strengthen accountability and transparency, provide value and resonate with readers like you.This work is essential to a better-informed community and a healthy democracy.

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