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Although several studies have explored the molecular landscape of metastatic melanoma, the genetic determinants of therapy resistance are still largely unknown. Here, we aimed to determine the contribution of whole-exome sequencing and circulating free DNA (cfDNA) analysis in predicting response to therapy in a consecutive real-world cohort of 36 patients, undergoing fresh tissue biopsy and followed during treatment. Although the underpowered sample size limited statistical analysis, samples from non-responders had higher copy number variations and mutations in melanoma driver genes compared to responders in the BRAF V600+ subset. In the BRAF V600− subset, Tumor Mutational Burden (TMB) was twice that in responders vs. non-responders. Genomic layout revealed commonly known and novel potential intrinsic/acquired resistance driver gene variants. Among these, RAC1, FBXW7, GNAQ mutations, and BRAF/PTEN amplification/deletion were present in 42% and 67% of patients, respectively. Both Loss of Heterozygosity (LOH) load and tumor ploidy were inversely associated with TMB. In immunotherapy-treated patients, samples from responders showed higher TMB and lower LOH and were more frequently diploid compared to non-responders. Secondary germline testing and cfDNA analysis proved their efficacy in finding germline predisposing variants carriers (8.3%) and following dynamic changes during treatment as a surrogate of tissue biopsy, respectively.

O artigo científico possui a finalidade de analisar suscintamente o teletrabalho, regulamentado pela Lei nº 13.467/2017 – Reforma Trabalhista – dando destaque a algumas peculiaridades. Busca também definir o que é Dano existencial e o direito a desconexão, como ocorrem e suas decorrências dessa nova forma de prestação de trabalho. Por fim, avalia o inciso III no artigo 62 da Consolidação das Leis do Trabalho, incluído pela Reforma, que exclui o teletrabalhador do controle da jornada de trabalho, na tentativa de considerá-lo inconstitucional à medida que entra em choque com o inciso XIII do artigo 7° da Carta Maior., telework; Right to disconnect; Journey Control; Labor Reform; Unconstitutionality

Pancreatic ductal adenocarcinoma (PDAC) is a component of familial melanoma due to germline pathogenic variants (GPVs) inWe analyzed 189 cancer predisposition genes using parametric rare-variant association (RVA) tests and nonparametric permutation tests to identify gene-level associations in PDAC for patients with (In RVA tests,These results suggest that variants in other genes likely play a role in PDAC in all patients and that PDAC in

ATM germline pathogenic variants were recently found enriched in high-risk melanoma patients. However, ATM loss of heterozygosity (LOH) has never been investigated in melanoma and, therefore, a causal association with melanoma development has not been established yet. The purpose of this study was to functionally characterize 13 germline ATM variants found in high-risk melanoma patients—and classified by in silico tools as pathogenic, uncertain significance, or benign—using multiple assays evaluating ATM/pATM expression and/or LOH in melanoma tissues and cell lines. We assessed ATM status by Immunohistochemistry (IHC), Western Blot, Whole-Exome Sequencing/Copy Number Variation analysis, and RNA sequencing, supported by Sanger sequencing and microsatellite analyses. For most variants, IHC results matched those obtained with in silico classification and LOH analysis. Two pathogenic variants (p.Ser1135_Lys1192del and p.Ser1993ArgfsTer23) showed LOH and complete loss of ATM activation in melanoma. Two variants of unknown significance (p.Asn358Ile and p.Asn796His) showed reduced expression and LOH, suggestive of a deleterious effect. This study, showing a classic two-hit scenario in a well-known tumor suppressor gene, supports the inclusion of melanoma in the ATM-related cancer spectrum.

Multigene germline panel testing is recommended for Pancreatic Cancer (PC) patients; however, for non-BRCA1/2 genes, the clinical utility is unclear. A comprehensive multi-gene assessment in unselected Italian PC patients is missing. We evaluated the prevalence and impact of Pathogenic Variants (PV) in 51 PC susceptibility genes in a real-world series of 422 Italian PC patients unselected for Family History (FH), compared the clinical characteristics and conducted survival analyses. 17% of patients had PVs (70/422), mainly in BRCA1/2 (4.5%, all 50 y), ATM (2.1%). PV carriers were younger (64 vs. 67; p = 0.02) and had more frequent personal/FH of PC, melanoma and breast/ovarian cancer (all p < 0.05). The Overall Survival (OS) was longer in patients carrying PVs (HR 0.78; p = 0.090), comprising ATM carriers (HR 0.33; p = 0.054). In the oxaliplatin-treated subset, PV carriers showed better control of the disease, although this was not statistically significant (67% vs. 56%). CDKN2A, BRCA2 and ATM were the most frequently altered genes. ATM PVs were positively associated with OS in 41% of PV carriers, 60% of whom carried CDKN2A,BRCA2 or ATM PVs, had negative FH and would have been missed by traditional referral. Thus, CDKN2A and ATM should be added to BRCA1/2 testing regardless of FH.

Introdução: A Transposição dos Grandes Vasos é uma cardiopatia cianótica rara considerada a décima causa mais comum de defeito cardíaco congênito. O objetivo do presente artigo foi analisar a literatura acerca dos principais aspectos cirúrgicos e clínicos relacionados com a Transposição dos Grandes Vasos. Metodologia: Tratou-se de uma revisão da literatura de trabalhos pesquisados nas bases de dados MEDLINE/PubMED, SciELO e Google Acadêmico. Resultados e Discussão: Na transposição de grandes vasos tem-se a formação de uma circulação paralela incapaz de suprir as necessidades de oxigênio do corpo, sendo necessária uma cirurgia emergencial para correção. A Técnica de Jatene consiste na correção anatômica da transposição de grandes vasos, sendo que a operação ideal deve ser realizada a nível arterial. Todavia, o grande empecilho da cirurgia está na transferência das artérias coronárias. Conclusão: Conclui-se que a técnica de Jatene, mesmo descrita em 1976, ainda apresenta ótimos resultados na correção dessa anomalia cianótica.

The purpose of this first Special Issue is to provide a glance at the molecular advances in cancer genetics to untangle the complexity of tumorigenesis [...]

Forages are one of the most cultivated crops in the world. However nutritional deficiency is common, specifically in N, P and Ca in many forages growing regions. Silicon (Si) can attenuate the stress caused by nutritional deficiency, but studies on the effects of Si supply on in forages plants are still scarce. This research was carried out to evaluate whether the Si supply can mitigate the effects of N, P and Ca deficiencies of two forages and the physiological and nutritional mechanisms involved. Two experiments were carried out with two forage species (Urochloa brizantha cv. Marandu and Megathyrsus maximum cv. Massai). Was used nutrient solution under balanced nutrition conditions and nutritional stress due to the lack of N, P and Ca combined with the -Si and +Si. The deficiencies of N, P and Ca in both forages cultivation caused damage to physiological and nutritional variables, hence decreasing the plant dry matter. However, in both species forages the addition of Si to the nutrient solution decreased the extravasation of cellular electrolytes and increased the content of phenolic compounds, the green color index, the quantum efficiency of photosystem II, the efficiencies of use of N, P and Ca and the production of shoot dry mass. The beneficial effects of Si were evidenced in stressed and non-stressed plants. The research emphasized the advantage of using Si for the growth of U. brizantha and M. maximum under N, P and Ca deficiency, contributing to their sustainable cultivation.

Genomic studies have identified some of the most relevant genetic players in Neuroendocrine Neoplasm (NEN) tumorigenesis. However, we are still far from being able to draw a model that encompasses their heterogeneity, elucidates the different biological effects consequent to the identified molecular events, or incorporates extensive knowledge of molecular biomarkers and therapeutic targets. Here, we reviewed recent insights in NEN tumorigenesis from selected basic research studies on animal models, highlighting novel players in the intergenic cooperation and peculiar mechanisms including splicing dysregulation, chromatin stability, or cell dedifferentiation. Furthermore, models of tumorigenesis based on composite interactions other than a linear progression of events are proposed, exemplified by the involvement in NEN tumorigenesis of genes regulating complex functions, such as MEN1 or DAXX. Although limited by interspecies differences, animal models have proved helpful for the more in-depth study of every facet of tumorigenesis, showing that the identification of driver mutations is only one of the many necessary steps and that other mechanisms are worth investigating.

Funder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; doi: http://dx.doi.org/10.13039/501100002322, Funder: Radiumhemmets Forskningsfonder; doi: http://dx.doi.org/10.13039/501100007232, Funder: Swedish Cancer Society, Funder: Lunds Universitet Paulsson Trust, Funder: CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Funder: European Regional Development Fund; doi: http://dx.doi.org/10.13039/501100008530, Funder: Diagnoptics, Funder: CERCA Programme Generalitat de Catalunya, Funder: Esther Koplowitz Center, Barcelona, Spain, Funder: Comision Honoraria de Lucha Contra el Cancer, CSIC, Fundacion Manuel Perez, Montevideo, Uruguay, BACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

Introdução: A Transposição dos Grandes Vasos é uma cardiopatia cianótica rara considerada a décima causa mais comum de defeito cardíaco congênito. O objetivo do presente artigo foi analisar a literatura acerca dos principais aspectos cirúrgicos e clínicos relacionados com a Transposição dos Grandes Vasos. Metodologia: Tratou-se de uma revisão da literatura de trabalhos pesquisados nas bases de dados MEDLINE/PubMED, SciELO e Google Acadêmico. Resultados e Discussão: Na transposição de grandes vasos tem-se a formação de uma circulação paralela incapaz de suprir as necessidades de oxigênio do corpo, sendo necessária uma cirurgia emergencial para correção. A Técnica de Jatene consiste na correção anatômica da transposição de grandes vasos, sendo que a operação ideal deve ser realizada a nível arterial. Todavia, o grande empecilho da cirurgia está na transferência das artérias coronárias. Conclusão: Conclui-se que a técnica de Jatene, mesmo descrita em 1976, ainda apresenta ótimos resultados na correção dessa anomalia cianótica.

The BRCA1/2 germline and/or somatic pathogenic variants (PVs) are key players in the hereditary predisposition and therapeutic response for breast, ovarian and, more recently, pancreatic and prostate cancers. Aberrations in other genes involved in homologous recombination and DNA damage response (DDR) pathways are being investigated as promising targets in ongoing clinical trials. However, DDR genes are not routinely tested worldwide. Due to heterogeneity in cohort selection and dissimilar sequencing approaches across studies, neither the burden of PVs in DDR genes nor the prevalence of PVs in genes in common among pancreatic and prostate cancer can be easily quantified. We aim to contextualize these genes, altered in both pancreatic and prostate cancers, in the DDR process, to summarize their hereditary and somatic burden in different studies and harness their deficiency for cancer treatments in the context of currently ongoing clinical trials. We conclude that the inclusion of DDR genes, other than BRCA1/2, shared by both cancers considerably increases the detection rate of potentially actionable variants, which are triplicated in pancreatic and almost doubled in prostate cancer. Thus, DDR alterations are suitable targets for drug development and to improve the outcome in both pancreatic and prostate cancer patients. Importantly, this will increase the detection of germline pathogenic variants, thereby patient referral to genetic counseling.

Background Mental illness is common amongst refugees and can differ depending on cultural background, experiences, and access to care. Given significant risk factors including high rates of exposure to sexual violence and different barriers to seeking adequate health care, refugee mothers are uniquely at risk. Methods In 2012–2013, surveys were administered to a convenience sample of Somali and systematic random sample of Iraqi refugee mothers to identify differences in mental health between the populations. The Hopkins Symptom Checklist (HSCL-25) identified respondents with major depression and emotional distress. We used multivariable logistic regression to compare these populations and identify variables associated with mental illness. Results 198 Somali and 219 Iraqi women were included. Most Iraqis (60.27%) had not seen a mental health provider while most Somalis (62.63%) had. On average, Iraqis scored 0.34 points higher (worse) on the HSCL-25 compared to Somalis (95% CI, 0.22–0.46; P < 0.001). Iraqis were more likely to have major depression (OR = 2.62, 95% CI 1.50–4.57, P = 0.001). On multivariable analysis accounting for the country of origin, those who saw a mental health provider were less likely to have major depression or emotional distress (OR 0.42, 95% CI 0.22–0.82, P = 0.011; OR 0.43, 95% CI 0.22–0.85, P = 0.015, respectively). Discussion Iraqi refugee mothers were more likely to have depression compared to Somalis. Refugee mothers who saw a mental health provider were less likely to have depression or emotional distress. These results suggest the cultural background and access to health services among refugee mothers’ impact on mental health.

The protracted conflict in Yemen-a civil war fought by proxies of Iran on one side and Saudi Arabia and the United States on the other-has ravaged the health care sector and facilitated the worst cholera outbreak on record, with more than 1 2 million people infected 2 Public health experts believe that destruction of infrastructure vital for health care delivery, such as the nation's largest seaport-an important gateway for the delivery of medical supplies and water, sanitation, and hygiene infrastructure-as well as security concerns related to ongoing violence, allowed this vaccinepreventable disease to rapidly propagate through the affected population The war, which started in 2011 as an outgrowth of the Arab Spring, marked a reversal of this trajectory 3 Perhaps most detrimental to public health in Syria are deliberate attacks on health care workers and facilities, which have been well documented since 2011 and are unprecedented in terms of scale 4 The United Nations and nongovernmental advocacy groups have documented and spoken out about the direct targeting of medical personnel, which amounts to war crimes under international law 4 Not only have these attacks limited the number of health care workers willing or able to address the health care needs ofthe besieged population, but they have created a powerful deterrent, preventing civilians from seeking care for fear of being caught in an assault- which is, perhaps, the intended goal The First Gulf War, along with crippling sanctions imposed by the United States, negatively affected Iraq's health care infrastructure, an effect that intensified during and after the 2003 US invasion 5 According to interviews with Iraqi refugee doctors, the war resulted in a substantial decline in health care services 5 In fact, four vaccinepreventable disease outbreaks- measles in 2009, mumps in 2004 and 2016, and rubella in 2004- occurred in the postinvasion period 6 Outbreaks such as these remind us that the lingering effects of conflict can last years or even decades after the declared war ends

Submitted by Fabiano Jucá (fjuca@unicentro.br) on 2021-06-16T12:02:18Z No. of bitstreams: 1 dissertação WILLIAM BRUNO CORREA.pdf: 2339100 bytes, checksum: d09486762818139921cb9ed0ce12518f (MD5) Made available in DSpace on 2021-06-16T12:02:18Z (GMT). No. of bitstreams: 1 dissertação WILLIAM BRUNO CORREA.pdf: 2339100 bytes, checksum: d09486762818139921cb9ed0ce12518f (MD5) Previous issue date: 2020-04-30 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES This thesis analyzes the marginalized pornochanchanda movie genre, a genre of cinema in the Brazilian context of the 1970s. It seeks to understand how body representations can be a mirror of Brazilian society of that period, in which the population lived under a military regime, and in which artistic production suffered various kinds of censorship. I analyse two pornochanchadas: “A Super Fêmea”, and “Guerra Conjugal”. I discuss the theme from an approach that merges cinema and cultural history, in order to identify and discuss cinematographic perceptions of the time about the masculine, the feminine, the homosexual, the obese, the black, the poor, the rich, in short, all the perceptions that pornochanchada can produce and its senses. Esta dissertação analisa as marginalizadas pornochanchandas, gênero famoso no cinema brasileiro da década de 1970. Busca compreender como as representações corporais podem ser um espelho da sociedade brasileira daquela década, período em que a população vivia sob o regime militar, e no qual manifestações artísticas sofriam com a censura, e onde o cinema era alvo de reprimendas que comprometiam o conteúdo final. Neste trabalho são analisadas duas pornochanchadas, A Super Fêmea e Guerra Conjugal. Discuto o tema a partir de uma abordagem que aproxima cinema e história cultural, com vistas a identificar e discutir percepções cinematográficas da época sobre o masculino, o feminino, o homossexual, o obeso, o negro, o pobre, o rico, enfim, todas as percepções que a pornochanchada pode produzir e seus sentidos.

Submitted by William Bruno Silva Araújo (wbrunu@gmail.com) on 2021-12-01T19:42:52Z No. of bitstreams: 1 Tese William Bruno.pdf: 798508 bytes, checksum: fde99e5507ae414ca1bf6ab62076493a (MD5) Approved for entry into archive by Laudicélia Martins Arantes (lm.arantes@unesp.br) on 2021-12-02T11:34:16Z (GMT) No. of bitstreams: 1 araujo_wbs_dr_jabo.pdf: 798508 bytes, checksum: fde99e5507ae414ca1bf6ab62076493a (MD5) Made available in DSpace on 2021-12-02T11:34:16Z (GMT). No. of bitstreams: 1 araujo_wbs_dr_jabo.pdf: 798508 bytes, checksum: fde99e5507ae414ca1bf6ab62076493a (MD5) Previous issue date: 2020-01-24 RESUMO - Em forrageiras tropicais é comum ocorrer deficiência de nitrogênio (N), fósforo (P) e cálcio (Ca). O Si pode ser uma opção para mitigar os efeitos dessas deficiências, mas os mecanismos de ação deste elemento benéfico ainda não são conhecidos para os genótipos Urochloa brizantha cultivar Marandu e Megathyrsus maximum cultivar Massai. Objetivou-se avaliar se o fornecimento de Si pode mitigar a deficiência destes nutrientes em dois genótipos de forrageiras tropicais, cultivadas em solução nutritiva equilibrada e com deficiências isoladas de N, P e Ca. Os tratamentos foram construídos de solução nutritiva equilibrada e deficiências isoladas N, P e Ca, na ausência e na presença de Si. O delineamento foi inteiramente casualizado, com oito tratamentos e seis repetições em fatorial 4 x 2. A fonte de Si foi o silicato de sódio estabilizado com sorbitol (94,2 g L-1 de Si e 60 g L-1 de Na). Os experimentos foram conduzidos em condições de casa de vegetação. Inicialmente com a semeadura em bandejas de poliestireno contendo substrato de vermiculita e fornecimento de água potável durante 20 dias. Depois desse período as plantas foram transplantadas para vasos de polietileno de 1,7 dm3 contendo areia lavada e passaram a receber solução nutritiva. Foi realizado corte de uniformização aos 45 após o transplantio. Aos 45 dias depois do corte de uniformização foram obtidos os parâmetros extravasamento de eletrólitos, índice de cor verde e rendimento quântico da fluorescência. Aos 55 dias após o corte de uniformização foram obtidas as variáveis comprimento das plantas e número de perfilhos e realizado novo corte. O material vegetal foi lavado e seco em estufa até atingir massa constante para a obtenção da massa seca da parte aérea por vaso. Determinou-se o teor de compostos fenólicos, o teor de Si e os teores de N, P e Ca. Obteve-se a eficiência de uso do N, P, e Ca. Em ambos os genótipos a adição de Si na solução nutritiva diminuiu o extravasamento de eletrólitos celular e incrementou o teor de compostos fenólicos, o índice de cor verde, o rendimento quântico da fluorescência, a eficiência de utilização de N, P e Ca e a produção de massa seca da parte aérea, em comparação com os tratamentos que não receberam Si. Esses resultados indicam que o Si mitiga os efeitos da deficiência de N, P e Ca nos genótipos estudados, pelo seu papel antioxidante, que reflete na melhoria da eficiência da fotossíntese e de uso de N, P e Ca induzindo aumento na produção de massa seca. O acréscimo de Si também teve efeito benéfico nas forrageiras sem estresse nutricional. ABSTRACT - In tropical forages, nitrogen (N), phosphorus (P) and calcium (Ca) deficiencies are common. Si can be an option to mitigate the effects of these deficiencies, but the mechanisms of action of this beneficial element are not yet known for the genotypes Urochloa brizantha cultivar Marandu and Megathyrsus maximum cultivar Massai. The objective of this study was to evaluate whether the supply of Si can mitigate the deficiency of these nutrients in two genotypes of tropical forages, cultivated in balanced nutrient solution and with isolated N, P and Ca deficiencies. The treatments consisted of a balanced nutrient solution and isolated N deficiencies, P and Ca, in the absence and presence of Si. The design was completely randomized, with eight treatments and six replications in a 4 x 2 factorial. The source of Si was sodium silicate stabilized with sorbitol (94.2 g L- 1 of Si and 60 g L-1 of Na). The experiments were carried out under greenhouse conditions. Initially with sowing in polystyrene trays containing vermiculite substrate and supply of drinking water for 20 days. After this period, the plants were transplanted to 1.7 dm3 polyethylene pots containing washed sand and began to receive a nutrient solution. A uniform cut was performed at 45 after transplanting. At 45 days after the standardization cut, the parameters of electrolyte leakage, green color index and fluorescence quantum yield were obtained. At 55 days after the standardization cut, the variables plant length and number of tillers were obtained and a new cut was performed. The plant material was washed and dried in an oven until reaching a constant mass to obtain the dry mass of the aerial part per pot. The content of phenolic compounds, the Si content and the N, P and Ca contents were determined. The efficiency of use of N, P, and Ca was obtained. In both genotypes the addition of Si to the nutrient solution decreased the extravasation of cellular electrolytes and increased the content of phenolic compounds, the green color index, the quantum yield of fluorescence, the efficiency of N, P and Ca utilization and the production of shoot dry mass, compared to the treatments that did not receive Si. These results indicate that Si mitigates the effects of N, P and Ca deficiency in the studied genotypes, due to its antioxidant role, which reflects in the improvement of photosynthesis efficiency and the use of N, P and Ca inducing increase in the production of dry mass. The addition of Si also had a beneficial effect on forages without nutritional stress.

is missing (Short communication)

The contribution of recently established or candidate susceptibility genes to melanoma missing heritability has yet to be determined. Multigene panel testing could increase diagnostic yield and better define the role of candidate genes. We characterized 273 CDKN2A/ARF and CDK4-negative probands through a custom-designed targeted gene panel that included CDKN2A/ARF, CDK4, ACD, BAP1, MITF, POT1, TERF2IP, ATM, and PALB2. Co-segregation, loss of heterozygosity (LOH)/protein expression analysis, and splicing characterization were performed to improve variant classification. We identified 16 (5.9%) pathogenic and likely pathogenic variants in established high/medium penetrance cutaneous melanoma susceptibility genes (BAP1, POT1, ACD, MITF, and TERF2IP), including two novel variants in BAP1 and 4 in POT1. We also found four deleterious and five likely deleterious variants in ATM (3.3%). Thus, including potentially deleterious variants in ATM increased the diagnostic yield to about 9%. Inclusion of rare variants of uncertain significance would increase the overall detection yield to 14%. At least 10% of melanoma missing heritability may be explained through panel testing in our population. To our knowledge, this is the highest frequency of putative ATM deleterious variants reported in melanoma families, suggesting a possible role in melanoma susceptibility, which needs further investigation.

RESUMONa sociedade repleta de litígios, pressionada pela ineficiência dos órgãos judiciais, destacam-se técnicas alternativas para soluções desses conflitos, particularmente a arbitragem. O regramento próprio configura a autonomia da vontade que é a essência desse procedimento. Sob tal ângulo, este artigo examina sua aplicabilidade nos dissídios individuais e coletivos a cargo da Justiça do Trabalho. O objetivo é verificar a latitude da aplicação, orientado pelo método indutivo-prospectivo, examinando o estado da arte plasmado na jurisprudência e literatura, realçando sua importância na quadra atual de inibição de acesso à Justiça do trabalho pelo risco das penas pecuniárias previstas para o vencido.

Background Research around humanitarian crises, aid delivery, and the impact of these crises on health and well-being has expanded dramatically. Ethical issues around these topics have recently received more attention. We conducted a systematic literature review to synthesize the lessons learned regarding the ethics of research in humanitarian crises. Methods We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines to identify articles regarding the ethics of research in humanitarian contexts between January 1, 1997 and September 1, 2019. We analyzed the articles to extract key themes and develop an agenda for future research. Results We identified 52 articles that matched our inclusion criteria. We categorized the article data into five categories of analysis: 32 were expert statements, 18 were case studies, 11 contained original research, eight were literature reviews and three were book chapters. All included articles were published in English. Using a step-wise qualitative analysis, we identified 10 major themes that encompassed these concepts and points. These major themes were: ethics review process (21 articles, [40.38%]); community engagement (15 articles [28.85%]); the dual imperative, or necessity that research be both academically sound and policy driven, clinical trials in the humanitarian setting (13 articles for each, [25.0%)]; informed consent (10 articles [19.23%]); cultural considerations (6 articles, [11.54%]); risks to researchers (5 articles, [9.62%]); child participation (4 articles [7.69%]); and finally mental health, and data ownership (2 articles for each [3.85%]). Conclusions Interest in the ethics of studying humanitarian crises has been dramatically increasing in recent years. While key concepts within all research settings such as beneficence, justice and respect for persons are crucially relevant, there are considerations unique to the humanitarian context. The particular vulnerabilities of conflict-affected populations, the contextual challenges of working in humanitarian settings, and the need for ensuring strong community engagement at all levels make this area of research particularly challenging. Humanitarian crises are prevalent throughout the globe, and studying them with the utmost ethical forethought is critical to maintaining sound research principles and ethical standards.

Background: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved.Methods: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics.Results: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance.Conclusion: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.

Background: In the midst of a global refugee crisis, addressing mental health is critical for refugee health care delivery. Understanding efficacy of mental health interventions is more important t...