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This study focuses on the recent evolution of a shallow-water dunefield system off La Pelosa Beach, located in the wind-dominated, microtidal, asymmetrical Asinelli Strait (Stintino, NW Sardinia, Italy). The system comprises four zones defined by a gradual decrease in current strength from the strait centre to more distal parts that form different bedforms. The strait centre (Zone A) is a substrate-carved channel passing downcurrent to a vast sandy shoal characterized by a subaqueous dunefield (Zone B) that is surrounded by a sandwave–ripple carpet (Zone C). The strait margin (Zone D) is dominated by a sandy cusp, the so-called La Pelosa Beach system. The extensive seagrass meadow located on the SE side of the strait-end zone feeds the system with bioclastic-rich sands. This carbonate sedimentary load is ensured by natural seagrass meadow retreats that are possibly boosted by human impact. The sediment transport is modulated by the interaction between two opposite currents triggered by the east-incoming Greco/Levante and NW-incoming Mistral winds. These currents experience a great variability due to multi-annual fluctuations (4–6 years) of the prevailing wind activities. Such cyclicity is responsible for periodic dune migration and and transport from La Pelosa Beach out of the system below the active part of the submerged beach (depth of closure). Bedform formations (ripples, dunes and sandwaves) and migrations within the strait are the result of complex physical processes observed in modern environments but rarely described in rock formations. The presented conceptual model can be used to recognize sediment ‘spillover’ processes on other modern, microtidal, wind-dominated straits, as well as proposing the main criteria for recognizing this strait sedimentary succession in the geological record.

We draw on social categorization theory to explain how entrepreneurial teams focused on research and development (R&D) are configured to deliver successful new venture performance. Research on entrepreneurial teams tends to aggregate individuals to the team level, which helps distill the effects of complementarities among social categories of team members. Specifically, we examine how scientists and managers apply their unique profiles (i.e., accumulated skills and expertise) to execute their respective roles within entrepreneurial teams engaged in commercial scientific discovery. In line with the entrepreneurial team literature, we distinguish between “focused” and “diversified” social categorizations of principal scientists and managers. As such, we differentiate between individuals’ deep knowledge of a discipline and a background in two professional areas with relative expertise in each, likened to the “jack-of-all-trades”. We analyze how team profile-to-role configurations might result in different new venture outcomes being R&D performance and commercial performance. To examine our models, we use multi-source, longitudinal, secondary data drawn from 153 government-funded research-intensive ventures associated with the National Cancer Institute in the United States (U.S.). Our results reveal differential effects for R&D performance and commercial performance. We find that teams aiming to enhance their R&D performance should seek diversified principal scientists, whereas teams seeking commercial gains should appoint diversified managers. By the same token, diversified team members may bypass their own shortcomings and complement their strengths by attracting team members with focused social categorizations.

Resume Il s’agit d’une proposition de penser l’epistemologie comme une epistemologie aux frontieres en reponse au travail de Mattieu Arminjon sur le developpement d’une psychanalyse experimentale.

INTRODUCTION: Roughly one-third of sexual minority adolescents (SMA) report at least one lifetime suicide attempt. Supportive connections are protective for ideation, yet little is known about this association with SMA—especially longitudinally. METHODS: Five-step logistic regressions examined the associations of bullying, SMA, and ideation, and also how connectedness mediates this from age 9 and 15 (Fragile Families and Child Wellbeing Study; N = 3,023 adolescents). RESULTS: At age 9, SMA reported higher levels of daily bullying compared with heterosexual peers (26% versus 14%), and at age 15, SMA reported daily (7%) and weekly (20%) bullying. SMA (32%) reported ideation compared with their heterosexual peers (13%) at age 15. Parental and school connectedness protected adolescents regardless of sexual orientation for SI, but parental attachment buffered the effect of SMA ideation more than school connectedness. CONCLUSION: Impressing upon schools to be mindful of bullying on their campuses, especially of SMA, is crucial for suicide prevention as we found heterosexual students connected to their school were protected from ideation, yet this was not found for SMA. Strong parent–child bonds can mediate the effects of bullying while at school, speaking to the importance of having at least one trusted adult in an adolescent’s life.

Using data on firm entries into the U.S. market for four product categories, we examine: (1) the complementary impact of marketing and R&D capabilities on firms’ market entry strategies, (i.e., entry timing, product innovativeness, and product line breadth); (2) the extent that entry timing mediates the relationship between marketing-R&D capability complementarity, product line breadth and product innovativeness; and, (3) the effects of the three market entry strategies on firms’ survival in the product categories. We provide three important contributions. First, we clarify the role of entry timing in influencing other market entry imperatives. Second, by providing evidence that both entry timing and product line breadth determine survival duration, we propose that the ‘optimal’ entry time varies along an entry-timing continuum. Third, we provide a more holistic examination of market entry considerations, which reveals the indirect relationship between marketing and R&D capability complementarity and survival through mediated paths.

Malocclusion is an alteration of the normal relationships between skeletal, muscle and dental structures that can lead to impaired functionality as well as aesthetic alteration of the stomatognathic system. Functional alteration can affect various aspects, ranging from chewing ability to respiratory disorders. Paediatricians and dentists are called to prevent and diagnose these conditions as early as possible in order to preserve the patient's health. The purpose of this research is to study the incidence of malocclusion and its relationship with Obstructive Sleep Apnea Syndrome (OSAS) in a young population. Also, the role of paediatricians and dentists in prevention and early diagnosis of this condition was evaluated METHODS: An anonymous survey was given through Google form to 300 Italian children (139 males and 161 females) from different private dental practices in Italy. No personal information that identifies the individuals was collected, and the data was analysed in aggregate form only. All data was collected and statistically analysed.The data highlight the patients' good attitude towards dental check-ups, which help to intercept malocclusions. Unlike the past, the knowledge of the importance of oral health and dental occlusion is high among young patients, parents and paediatricians. This study underlines the role of paediatricians as key players in the prevention of dental health problems.

Intratumoral heterogeneity is caused by genomic instability and phenotypic plasticity, but how these features co-evolve remains unclear. SOX10 is a neural crest stem cell (NCSC) specifier and candidate mediator of phenotypic plasticity in cancer. We investigated its relevance in breast cancer by immunophenotyping 21 normal breast and 1860 tumour samples. Nuclear SOX10 was detected in normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In tumours, nuclear SOX10 was almost exclusive to TNBC, and predicted poorer outcome amongst cross-sectional (p = 0.0015, hazard ratio 2.02, n = 224) and metaplastic (p = 0.04, n = 66) cases. To understand SOX10’s influence over the transcriptome during the transition from normal to malignant states, we performed a systems-level analysis of co-expression data, de-noising the networks with an eigen-decomposition method. This identified a core module in SOX10’s normal mammary epithelial network that becomes rewired to NCSC genes in TNBC. Crucially, this reprogramming was proportional to genome-wide promoter methylation loss, particularly at lineage-specifying CpG-island shores. We propose that the progressive, genome-wide methylation loss in TNBC simulates more primitive epigenome architecture, making cells vulnerable to SOX10-driven reprogramming. This study demonstrates potential utility for SOX10 as a prognostic biomarker in TNBC and provides new insights about developmental phenotypic mimicry—a major contributor to intratumoral heterogeneity.

Conventional and chemometric spectrophotometric techniques were compared for their analytical performance in determining a tri-component pharmaceutical mixture containing altizide, potassium canrenoate, and rescinnamine. These components were characterized by a notable spectral overlap, thus making their quantitative determination particularly difficult. The determination of altizide and canrenoate was performed using the technique of different order-derivative spectrophotometry, while rescinnamine was determined by fluorometry with activation and fluorescence maxima respectively at 325 and 427 nm thanks to a total absence of interference from the other two components. The analysis of the mixture was carried out by applying multivariate calibration methods, including principal component (PCR) and partial least squares (PLS) regression approaches. The calibration sample set was defined by a simplex-lattice experimental design to cover the experimental domain distributed over five concentration levels. The prediction accuracy of the defined methods was evaluated through external validation on new unknown samples and commercial pharmaceuticals. Significant advantages were found in the prediction of all the analytes when using the chemometric methods, which proved to be simpler, faster, and showing better statistical results with accuracy values between 96.12 and 103.36% and relative standard errors lower than 1.7%.

Big data technologies and analytics enable new digital services and are often associated with superior performance. However, firms investing in big data often fail to attain those advantages. To answer the questions of how and when big data pay off, marketing scholars need new theoretical approaches and empirical tools that account for the digitized world. Building on affordance theory, the authors develop a novel, conceptually rigorous, and practice-oriented framework of the impact of big data investments on service innovation and performance. Affordances represent action possibilities, namely what individuals or organizations with certain goals and capabilities can do with a technology. The authors conceptualize and operationalize three important big data marketing affordances: customer behavior pattern spotting, real-time market responsiveness, and data-driven market ambidexterity. The empirical analysis establishes construct validity and offers a preliminary nomological test of direct, indirect, and conditional effects of big data marketing affordances on perceived big data performance.

Congenital analbuminaemia (OMIM # 616,000) is a rare autosomal recessive disorder, characterized by the near-complete absence, or very low levels, of serum albumin. The clinical diagnosis is usuall...

Interfacial inversion symmetry breaking gives rise to electronic properties that differ substantially from those of the bulk constituent materials. Here, we report on the realization of an artificial ferromagnetic quasi-two-dimensional electron gas (q2DEG) at the (111) interfaces between LaAlO3, EuTiO3, and SrTiO3characterized by a reconstruction of the bulk quasioctahedral crystal field into a trigonal one. The q2DEG is created through a transfer of electrons to the EuTiO3layers at the interface with LaAlO3, extending into the first layers of SrTiO3, as shown by an electron-energy-loss spectroscopy map of the titanium valence with atomic column resolution. Interestingly, polarized X-ray absorption spectroscopy shows that the Eu-4f and the Ti-3d magnetic moments order ferromagnetically and exhibit the same magnetic field dependence at low temperature. In addition, the q2DEG presents a sizable in-plane orbital moment even at low magnetic field (0.1 T) possibly related to Ti-3d electrons occupying bands with the main a1gorbital character. The results show an intriguing interplay between ferromagnetism, spin-orbit coupling, and trigonal crystal field splitting in the (111) LaAlO3/EuTiO3/SrTiO3q2DEG.

Background: Sporotrichosis occurs through contact with contaminated soil and plant. However, the incidence of sporotrichosis as a zoonotic epidemic has increased, particularly in Rio de Janeiro. Aim: In this work, we decided to evaluate some T-cell phenotypes involved in the immune response. Materials & methods: We used flow cytometry to quantify TCD4+ and TCD8+ and Treg from immunocompetent and immunosuppressed mice infected with Sporothrix species with different levels of virulence and pathogenicity. Results: It was demonstrated the predominance of TCD4+ over the TCD8+ cells in both groups, inoculated with all the species, and percentages of Treg observed in infected immunocompetent mice. Conclusion: This regulatory phenotype can be associated with a protective immunity in the initial periods of infection.

Parent Management Training-Oregon (PMTO) model has demonstrated significantly improvements in parental functioning and child’s social skills and socio-emotional well-being among families whose children were placed in foster care. Yet, there is a dearth of studies examining for whom PMTO works the best. The aim of this study was to examine the potential familial typologies in relation to parental and children’s functioning and how these typologies change after participating in PMTO. The sample consisted of 918 children in foster care and their biological parents recruited in September 2012-2014 in a Midwestern state and randomized to in-home PMTO (n = 461) or services as usual (SAU) (n = 457). Latent profile transition analysis examines how participation in PMTO influences changes in children’s behavior and their biological parent’s functioning over time while placed in out-of-home care. PMTO families reporting high parental functioning and children’s social-emotional outcomes were more likely to move to a higher functioning class (OR = 0.22, p = 0.01) than SAU families all characteristics equal. Yet, when families experienced poor parental functioning of all four types, PMTO was not helpful in improving parent’s functioning and children’s problem behaviors (OR = 4.41, p = 0.01). This study provides empirical support for child welfare agencies to sustain the PMTO program to improve children’s emotional and behavioral health.

Objective To examine how the associations of specific religious affiliations with recent suicidal ideation vary by sexual orientation among young adults. Method This project was a cross-sectional secondary analysis of data from the 2006 and 2011 surveys of the National Research Consortium of Counseling Centers in Higher Education. The analytic sample was restricted to persons between the ages of 18-29 (n = 40,150). Multiple logistic regression analyses were used to examine associations of religious affiliations with recent suicidal ideation between heterosexual and sexual minority (e.g., gay, lesbian, bisexual, questioning) young adults. Results Approximately 6.7% of the sample self-identified as sexual minority. Compared to heterosexuals, sexual minorities were more likely to report recent suicidal ideation (aOR = 4.52, 95% CI = 3.97-5.16). Among heterosexuals, Unspecified Christian and Catholic denominations were associated with 24% and 37% reduced odds of recent suicidal ideation compared to agnostic/atheist heterosexuals. However, among sexual minorities, Unspecified Christian and Catholic denominations were associated with 68% and 77% increased odds of recent suicidal ideation compared to agnostic/atheist sexual minorities. Unspecified Christian and Catholic sexual minorities had 184% and 198% increased odds of recent suicidal ideation compared to Unitarian/Universalist sexual minorities. Conclusions Although protective for heterosexuals, religious affiliation may not be globally protective against suicidal ideation among sexual minorities.

Acoustic Diagnostics is an Italian Space Agency (ASI) biomedical experiment exploiting the diagnostic potential of otoacoustic emissions (OAEs) to monitor the astronauts’ hearing health on board the International Space Station (ISS). It is being performed (July 2019–April 2020) on the ISS, in the framework of the BEYOND mission, sponsored by European Space Agency (ESA). A dedicated instrument for measuring distortion product OAE (DPOAE) in a noisy environment was designed by University of Rome Tor Vergata and INAIL. Aerospace Logistics Technology Engineering Company (ALTEC) took care of the payload development, mechanical, thermal and electromagnetic tests, verification, and acceptance. Two astronauts were subjected, before leaving for their mission on the ISS, to the DPOAE test, along with a full set of audiological tests (Baseline Data Collection, BDC), especially designed at University of Roma La Sapienza and Campus Bio-Medico. An identical DPOAE apparatus was used five times on board the ISS to test the two astronauts. Finally, a post-flight BDC was performed, few days after return to Earth. Preliminary analysis demonstrated that the payload was able to record DPOAEs on board the ISS with very low instrumental noise level, despite the high noise level of the ISS environment. ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country, provides access to the ISS as a laboratory in space. The utilization support services are provided, thanks to a contract, awarded by ASI, to ARGOTEC/Telespazio (UTISS Team).

SRJ 2019 Q1; Contexte La multiplicité actuelle des méthodes de recherche dans le champ de la clinique référée à la psychanalyse court le risque d’un positionnement qui prône la superposition des modèles en abolissant les antagonismes pour mieux valoriser les complémentarités, donnant parfois l’illusion d’une profusion méthodologique dépliant le champ des possibles. Objectif Cet article se propose de revenir sur les soubassements épistémologiques de ces modèles qui remet invariablement sur le chantier l’adéquation des critères de scientificité retenus, dans le but de se déprendre d’un rabattement syncrétique qui participerait sinon à l’appauvrissement de cette hétérogénéité structurante. Par ailleurs, loin de nous défier a priori des principes méthodologiques issus du modèle expérimental, qui tendent à s’imposer actuellement dans le champ des sciences humaines et sociales, cet article vise néanmoins à se départir du risque hégémonique, ou tout au moins d’une homogénéisation croissante et impérieuse liée à la standardisation de la publication scientifique, en examinant les voies de passage qui permettrait un dialogue fécond aux frontières de la psychanalyse. Méthode L’article questionne les soubassements épistémologiques, d’une part, de deux méthodologies régulièrement rencontrées dans le champ clinique — la méthode du cas unique et la méthode hypothético-déductive — puis, d’autre part, de modèles issus historiquement de l’anthropologie et de la sociologie — modèle de la théorisation ancrée et modèle de la traduction élargie —, qui partagent avec notre approche le souci de la défense et de la valorisation de la recherche qualitative. Résultats La mise en tension de ces différents modèles est mise au service du dégagement des apports et des limites susceptibles d’éclairer les enjeux épistémologiques spécifiques, les choix d’opérationnalisation méthodologique et les choix d’exposition des résultats des recherches cliniques se référant à la psychanalyse. L’article soutient l’intérêt, pour la psychanalyse, de trouver une opportunité de structuration de ses travaux autour du maintien d’un homomorphisme entre processus psychanalytique et processus de recherche. Ces considérations nous amènent à faire porter l’attention sur les conditions de possibilité requises pour inscrire la processualité ainsi que l’exigence de maintien d’un écart théorico-clinique au cœur de la méthode de recherche clinique. Dans cette voie, l’article pose les prémisses d’une modélisation d’une méthode de recherche hypothétique et processuelle fondée sur la prise en compte de l’appréhension complexe et nécessairement asymptotique de l’inconscient. Dans cette perspective, le temps de l’écriture de la recherche revêt une double fonction : il redouble, d’une part, les effets de processualité et d’après-coup du dispositif de recherche ; il aménage, d’autre part, à travers le choix d’exposition méthodologique des résultats, des conditions communes de débats promptes à situer les différentes partitions du dialogue à plusieurs au sein d’un champ de controverse. Conclusion Cet article propose une première étape de formalisation d’une « méthode de recherche hypothétique et processuelle » susceptible d’offrir une narration qui intègre tout à la fois les contraintes inhérentes à la dynamique de production singulière de la connaissance dans le champ clinique référé à la psychanalyse et celles inhérentes à la possibilité d’un débat scientifique élargi. The current multiplicity of research methods in the field of clinical psychoanalysis runs the risk of advocating the superposition of models by abolishing antagonisms to better accentuate complementarities, sometimes giving the illusion of a methodological profusion expanding the field of possibilities. Goal This article proposes to return to the epistemological foundations of these models, which invariably questions the adequacy of the selected scientific criteria. It aims to get rid of a syncretic drawdown that would otherwise contribute to the impoverishment of this structuring heterogeneity. The methodological principles derived from the experimental model are now becoming established in the field of human and social sciences. Far from challenging this model, this article nevertheless aims to question this hegemonic risk, or at least an increasing and imperative homogenization linked to the standardization of scientific publication, by examining the passageways that would allow a fruitful dialogue at the borders of psychoanalysis. Method The article questions the epistemological foundations, first, of two methodologies regularly encountered in the clinical field — the single case method and the hypothetical-deductive method — and then, of models historically derived from anthropology and sociology — grounded theory model and extended translation model. The latter share with our approach the concern for the defense and enhancement of qualitative research. Results The tension between these different models is used to identify the contributions and limits likely to shed light on the specific epistemological issues, the choices of methodological operationalization, and the choices of exposure of clinical research results related to psychoanalysis. The article encourages psychoanalysts to find opportunities to structure their work around the maintenance of a homomorphism between psychoanalytic and research processes. These considerations lead us to focus attention on the conditions required to inscribe processuality and the maintenance of a theoretical-clinical gap at the heart of the clinical research method. In this way, the paper lays the foundations for a modeling of a hypothetical and process-oriented research method. This method is based on taking the complex and necessarily asymptotic apprehension of the unconscious into account. From this perspective, the writing phase has a dual function: on the one hand, it doubles the effects of processuality and of the “après-coup” of research; on the other hand, the choice of methodological exposure of the results must propose common conditions for debate within a controversial field. Conclusion This article proposes a first step in the formalization of a “hypothetical and processual research method.” This method is likely to offer a narrative that integrates both the constraints related to the dynamics of the singular production of knowledge in psychoanalysis's clinical field and the constraints promoting a broader scientific debate.

BackgroundCoronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm.MethodsIn this study, we report that severe acutely infected patients have high levels of both type-1 and type-2 cytokines.ResultsOur results show abnormal cytokine levels upon T-cell stimulation, in a nonpolarized profile. Furthermore, our findings indicate that this hyperactive cytokine response is associated with a significantly increased frequency of late-differentiated T cells with particular phenotype of effector exhausted/senescent CD28−CD57+ cells. Of note, we demonstrated for the first time an increased frequency of CD3+CD4+CD28−CD57+ T cells with expression of programmed death 1, one of the hallmarks of T-cell exhaustion.ConclusionsThese findings reveal that COVID-19 is associated with acute immunodeficiency, especially within the CD4+ T-cell compartment, and points to possible mechanisms of loss of clonal repertoire and susceptibility to viral relapse and reinfection events.

Big data technologies and analytics enable new digital services and are often associated with superior performance. However, firms investing in big data often fail to attain those advantages. To answer the questions of how and when big data pay off, marketing scholars need new theoretical approaches and empirical tools that account for the digitized world. Building on affordance theory, the authors develop a novel, conceptually rigorous, and practice-oriented framework of the impact of big data investments on service innovation and performance. Affordances representaction possibilities, namely what individuals or organizations with certain goals and capabilities can do with a technology. The authors conceptualize and operationalize three important big data marketing affordances: customer behavior pattern spotting, real-time market responsiveness, and data-driven market ambidexterity. The empirical analysis establishes construct validity and offers a preliminary nomological test of direct, indirect, and conditional effects of big data marketing affordances on perceived big data performance.

Resume Objectifs L’adolescence est une periode de profonds remaniements corporels et psychiques, venant ebranler autant le rapport a soi qu’aux autres. Si les changements corporels erratiques annoncent de nombreux benefices, ils suscitent aussi bien des angoisses, liees a la fragilite de l’image du corps et du sentiment d’identite. Face au vacillement des reperes narcissiques et objectaux l’adolescent peut chercher dans la quete de contemplation dans le miroir un moyen de se rassurer. L’objectif est de proposer une reflexion sur le signe du miroir et ses fonctions a l’adolescence, tout aussi bien symptome courant et transitoire que signe pathologique quand il temoigne d’une desorganisation identitaire. Methode La methode est celle de l’analyse de cas, celle de deux adolescentes chez qui le signe du miroir constitue un symptome preoccupant. La mise en perspective de ces deux situations cliniques soutient l’idee d’un continuum entre normal et pathologique. Resultats Si le signe du miroir peut etre le symptome d’une desorganisation psychotique grave, il peut tout aussi bien constituer un recours narcissique trophique dans les aleas du processus adolescent. Discussion Le signifiant « signe » recouvre bien des realites psychiques, non reductibles aux manifestations symptomatiques que l’on aurait trop vite fait de mettre au compte d’un trouble schizophrenique. Derriere un symptome se decouvrent des significations, engageant, dans des modalites et des proportions propres a chacun, la qualite des ressources narcissiques. Conclusion La contemplation interrogative de son image dans le miroir associee au sentiment de depersonnalisation, peut-etre trop rapidement mise au compte d’un trouble schizophrenique. La mise en perspective de deux cas cliniques d’adolescentes presentant un signe du miroir, permet de resituer ce symptome dans sa fonction dynamique. Trophique chez Isis en ce qu’il constitue un recours narcissique salvateur, temoin d’un effondrement narcissique majeur chez Flore, luttant contre une desorganisation identitaire majeure.

Young adolescents’ endorsement of help-seeking and reported levels of connectedness are vital for culturally-tailored prevention initiatives. There is a dearth of information on how younger adolescents attending middle schools (ages 11–15) obtain help from trusted adults, especially among Hispanics. This is problematic as Hispanics, especially female high school students, have consistently reported higher rates of depression and suicidal behaviors for over 30 years. This pilot study included 72 young adolescents (86% Hispanic) in Central Texas. Surprisingly, although there were significant gender and age differences, no group strongly endorsed seeking help during times of distress. Yet, females were more likely to report that they would talk to a counselor or other adult at school when distressed compared to males. While no gender differences were found endorsing trusted adults as helpful, younger female adolescents held higher beliefs these individuals could help during times of distress. What is most pivotal is that this study suggests that changes in help seeking attitudes can occur from one grade to another. Therefore, early adolescence, instead of the more common period of high school, might be a critical time to offer upstream mental health prevention approaches.

Approximately 10-15% of breast cancers are associated with a strong family history of disease. Pathogenic variants in BRCA1, BRCA2 or other moderate to highly penetrant susceptibility genes (e.g. TP53, ATM, CHEK2, PALB2 and PTEN) account for a number of breast cancer families. However, for over 50% of families the underlying genetic contribution to their risk remains unknown (termed here as non-BRCA1/2). This has a profound impact for how individuals and their families are managed in the clinic. We applied whole genome sequencing (WGS) to determine whether somatic mutation analysis can reveal insight into the aetiology of familial breast cancer. The full repertoire of somatic mutations was evaluated in 26 BRCA1, 22 BRCA2 and 32 non-BRCA1/2 tumours; including SNPs, indels, copy number changes and structural rearrangements, and mutational signatures. Genomes were also analysed using the HRD Index and HRDetect, as predictors of homologous recombination deficiency. BRCA1, BRCA2 and non-BRCA1/2 tumours exhibited a different burden of mutations, a different spectrum of mutational signatures and different telomere length. Based on collective patterns of mutation signatures, tumours were classified as 'BRCA1-like', 'BRCA2-like' or 'non-BRCA1/2-like' with a 15% rate of tumour re-classification from their original clinical BRCA status. The results demonstrate the power of WGS to differentiate between BRCA1 and BRCA2 driven tumours; in the identification of double-pathogenic germline mutation carriers based on the resulting somatic mutation signature; and in the interpretation of BRCA unclassified variants. WGS of tumour genomes reveals fascinating insights into tumour aetiology and could compliment current genetic testing of breast cancer families. Citation Format: Simpson P, Nones K, Johnson J, Newell F, Patch A-M, Thorne H, Kazakoff S, De Luca X, Parsons M, Ferguson K, Reid L, McCart Reed A, Srihari S, Lakis V, Davidson A, Mukhopadhyay P, Holmes O, Xu Q, Wood S, Leonard C, Beasley J, Degasperi A, Nik-Zainal S, Ragan M, Spurdle A, Khanna KK, Lakhani S, Pearson J, Chenevix-Trench G, Waddell N. Using whole genome sequencing and somatic mutation signatures to unravel insight into familial breast cancer aetiology [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-10-01.

Objective: Suicide is the second leading cause of death among emerging adults, yet little is known regarding their online help-seeking. Participants: The National Research Consortium of Counseling Centers in Higher Education's dataset (N=26,292). Methods: Students across the United States were recruited from 73 four-year institutions to participate during the 2010-2011 school year. Results: Observed the effectiveness of online and traditional help-seeking stratified by recent suicidal ideation related to their most distressful period in the past year. Females and younger students endorsed both types of help-seeking, yet those with recent ideation were less likely to disclose any help-seeking. Among those reporting recent ideation, only females reported that traditional supports were more than moderately helpful. Regardless of whether students endorsed ideation, students who were younger, engaged in risky behaviors and identified as females reported that online resources were more than moderately helpful. Conclusions: Online resources could potentially bridge barriers to traditional help-seeking for those reluctant to seek out care, yet traditional resources were reported to be the most effective among this sample.

Purpose Bullying is a prominent public health concern that affects adolescents' mental and behavioral outcomes. Little is known about the effects of bullying victimization on adolescents' self-rated health. This study explores the relationship between bullying victimization and adolescents' self-rated health. Method Using the most recent wave (Year 15 follow-up, Wave 5) of the Fragile Families and Child Wellbeing Study (FFCWS), this study uses the responses from the now 15-year-old adolescents (n = 3444, 74%) and 3580 primary caregivers (77%). Multinomial logistic regression analysis was used to explore the relationship between bullying victimization and adolescents' self-rated health as well as the moderating role of gender. Subgroup analysis also explores the differential effects of relational victimization versus physical aggression on adolescents' self-rated health. Results Accounting for social contextual and controlling variables, bullying victimization was negatively associated with adolescents' self-rated health. Gender moderated the relationship between bullying victimization and self-rated health with the relationship significantly greater among male adolescents than girls. Subgroup analyses indicated the harmful linkage between bullying victimization and self-rated health only exist among those who experienced relational victimization but not those who experienced physical aggression. Conclusions Implications call for teachers, school mental health providers, school nurses and other school-based professionals to be aware of the gender disparity among adolescents experiencing bullying. In addition, practitioners need to be mindful of the differential effect of relational victimization versus physical aggression while working with adolescents experiencing bullying.

Acinetobacter baumannii is a multiple drug resistance opportunistic pathogen who has been responsible for severe outbreaks in nosocomial environment. A. baumannii possesses several mechanisms of antibiotic resistance that make it resistant to β-lactamics, mainly due to OXA-type carbapenemases expression, and others antibiotics. The blaKPC gene is an antibiotic resistance gene typical of K. pneumoniae and P. Aeruginosa. In 2009, blaKPC was found in A. baumannii isolates in Puerto Rico and later in Sao Luis, Brazil. The aim of this study is to screening the presence of blaKPC in nosocomial A. baumannii isolates from hospital environment monitoring. The study was approved by the Research Ethics Committee of the Universidade Estadual de Montes Claros under number 852.002/2014. Thirty-one DNA samples of Acinetobacter spp extensively drug resistant isolated from hospitalized patients in the southeast of Minas Gerais state – Brazil and kept at -20°C were used for PCR amplification of blaKPC gene detection. The expected amplicon size of 876 bp was visualized on 1.5% agarose gel stained with ethidium bromide and photographed. Twenty-eight DNA samples of Acinetobacter spp. tested negative to blaKPC gene and three isolates showed PCR expected amplicon of 876 bp. The presence of K. pneumoniae and Acinetobacter spp. in the same hospital environment could results in gene transfer between them. Also, the widespread and increasing uses of carbapenems could accelerate the spread of carbapenems-resistant strains by transferring resistance genes among the enterobacteriaceae and related microorganisms, impacting the public health system.

The Supplementary Nutrition Assistance Program (SNAP) Challenge encourages critical self-reflection and analysis of biases over seven consecutive days. Active learning methodologies are discussed compared to pre-formed lectures. Adaptive flexibility and empathy are salient skills for social workers that are emphasized in simulations. Students are challenged to only eat the average daily allowance for approved food options ($4.50/day) and chronical their observations. The Challenge improves students’ awareness of power and privilege with their future clients. This novel approach not only addresses the Council of Social Work’s Core Competencies but also trains new social workers to effectively deliver social services empathically.

Purpose: The current study examines differences between lesbian, gay, bisexual, and questioning (LGBQ) students and heterosexual students in terms of counseling and mental health services received (healthcare utilization), from whom students would seek help, and who contributed positively to students' ability to cope during a stressful period.Methods: An online survey was administered among 25,844 college students, enrolled in 76 schools (mean age = 25.52). The majority of participants was graduate students (42.81%) and reported their race/ethnicity as non-Hispanic White (70.49%).Results: Compared with their heterosexual counterparts, gay males and lesbian/gay and bisexual females reported receiving more counseling or mental health services, most notably from counselors, therapists, psychologists, and/or social workers. Bisexual males and LGBQ females were less likely to seek help from a parent or family member compared with heterosexual males and females, respectively. Racial/ethnic minority bisexual females were less likely to seek help from a friend or roommate than non-Hispanic White bisexual females. Compared with their heterosexual counterparts, gay and questioning males and LGBQ females were more likely to report that religion reduced their ability to cope.Conclusion: The current findings illuminate important differences by sexual orientation in terms of seeking and receiving mental health services. Although we found that lesbian/gay and bisexual college students were more likely to receive counseling and mental healthcare, we cannot ascertain whether they were satisfied with the services they received. The findings also suggest that certain groups of LGBQ students do not find support with their clergy and family, which may indicate a lack of understanding or acceptance of LGBQ issues.

BackgroundIntratumoural heterogeneity is a poor prognostic feature in triple-negative breast cancer (TNBC) and other high-grade malignancies. It is caused by genomic instability and phenotypic plasticity, but how these features co-evolve during tumour development remains unclear. SOX10 is a transcription factor, neural crest stem cell (NCSC) specifier and candidate mediator of cancer-associated phenotypic plasticity.MethodsUsing immunophenotyping, we investigated the expression of SOX10 in normal human breast tissue and breast cancer (n=21 cosmetic breast reduction and 1,860 tumour samples with clinical annotation). We then defined the context and evolution of its expression in TNBC compared to 21 other malignancies using systems-level transcriptomics.ResultsSOX10 was detected in nuclei of normal mammary luminal progenitor cells, the histogenic origin of most TNBCs. In breast cancer, nuclear SOX10 predicted poor outcome amongst cross-sectional (log-rank p=0.0015, hazard ratio 2.02, n=224) and metaplastic (log-rank p=0.04, n=66) TNBCs. Systems-level transcriptional network analysis identified a core module in SOX10’s normal mammary epithelial transcription program that is rewired to NCSC genes in TNBC. Reprogramming was proportional to DNA damage and genome-wide promoter hypomethylation, particularly at CpG island shores. Using a novel network analysis pipeline, we found that NCSC-like transcriptional reprogramming is also strongly associated with promoter hypomethylation in other SOX10+ malignancies: glioma and melanoma.ConclusionsWe propose that cancer-associated genome hypomethylation simulates the open chromatin landscape of more primitive cell states, and that on this relatively unrestricted background, SOX10 recreates its ancestral gene regulatory circuits by default. These findings provide new insights about the basis of intratumoural heterogeneity and resurrection of developmental phenotypes in cancer; and highlight the potential for therapeutics that limit chromatin remodelling.

Numerical simulations of gravitational planar liquid sheet flows, interacting with unconfined gaseous environments located on both sides of the liquid phase, are performed through Volume-of-Fluid (VOF) technique. The global unsteady dynamics of the non-parallel flow is analyzed by perturbing the initial steady configuration by means of a Gaussian bump in the transverse velocity component of relatively very small amplitude, thereby exciting sinuous modes. Thanks to the development of a theoretical linear one-dimensional model, more physical insights are gained on the flow system. It is found that surface tension plays a stabilizing role for the gravitational sheet, and for relatively high values of density ratio rr of gaseous-to-liquid phases it becomes unstable. An analogy is shown between the global unstable behavior exhibited by the liquid sheet as rr increases, and the shear-induced global instability found by Tammisola et al. [“Surface tension-induced global instability of planar jets and wakes”, J. Fluid Mech. 713, 632–658 (2012)] for planar jet and wake flows of two immiscible fluids in the presence of surface tension.

The heterogeneity of tumor infiltrating lymphocytes is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune cell subsets in brain metastasis tissues to test which immunosuppressive routes are involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on twenty formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and Iba1, and analyzed an average of 15000 cells per sample. We classified tumours as either high (>30%) or low (

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.

An investigation based on the application of spectral proper orthogonal decomposition (SPOD) of pressure measurements and Fourier analysis of velocity measurements is carried out to further elucidate the properties of separated flow behind a backward-facing ramp in uncontrolled and controlled conditions. Several flow control conditions are considered, varying the duty cycle and the frequency of an actuation system composed of 89 pulsed jets, issuing normally to the flow direction. The SPOD is applied to unsteady pressure measurements to characterize the main features of the flow and to extract the most energetically and dynamically relevant space-time coherent structures. Fourier analysis is applied to the velocity measurements and is complementary to the SPOD analysis. In uncontrolled conditions four major modes, together with their typical frequencies, have been identified and associated with (1) presence of large-scale longitudinal roll-up vortices which oscillate at the slanted ramp side edges, (2) flapping motion of the central recirculation region, (3) large-scale vortex emission from the shear layer at the slant edge, and (4) onset of high-frequency Kelvin-Helmholtz instability occurring in the shear layer near the slant edge. The control suppresses the recirculation mode and all associated mechanisms. As expected, the mode related to the lateral roll-up vortices persists. The modal analysis also shows that distinctive peaked bands emerge, which are ascribed to the presence of the control pulsed jets. Focusing on the SPOD mode associated with the actuation allows one to analyze the extension of the receptivity region of the flow to the action of control. Some peculiar aspects of SPOD field reconstruction are suggested by the specific physical characteristics of the flow.