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Recently, covariance analysis has found significant use in the field of chemical reaction dynamics. When coupled with data from product time-of-flight mass spectrometry and/or multi-mass velocity-map imaging, it allows us to uncover correlations between two or more ions formed from the same parent molecule. While the approach has parallels with coincidence measurements, covariance analysis allows experiments to be performed at much higher count rates than traditional coincidence methods. We report results from electron-molecule crossed-beam experiments, in which covariance analysis is used to elucidate the dissociation dynamics of multiply-charged ions formed by electron ionisation over the energy range from 50 to 300 eV. The approach is able to isolate signal contributions from multiply charged ions even against a very large 'background' of signal arising from dissociation of singly-charged parent ions. Covariance between the product time-of-flight spectra identifies pairs of fragments arising from the same parent ions, while covariances between the velocity-map images ('recoil-frame covariances') reveal the relative velocity distributions of the ion pairs. We show that recoil-frame covariance analysis can be used to distinguish between multiple plausible dissociation mechanisms, including multi-step processes, and that the approach becomes particularly powerful when investigating the fragmentation dynamics of larger molecules with a higher number of possible fragmentation pathways.

Refereed/Peer-reviewed Background: Women prisoners are a growing portion of the prison population. Health and social outcomes of their children have been studied and found to be poor, but little is known about child protection outcomes. Objectives: Ascertain child protection system contact of children exposed to maternal incarceration. Participants and setting: All children born between 1985 and 2011 exposed to the incarceration of their mothers in a Western Australian correctional facility and a matched comparison group. Methods: A matched cohort study using linked administrative data on 2637 mothers entering prison between 1985 and 2015 and their 6680 children. We estimated hazard ratios (HRs) and incidence rate ratios (IRRs) of child protection service (CPS) contact post maternal incarceration (four concern levels), comparing rates for children exposed to maternal incarceration with a matched non-exposed group, adjusting for maternal and child factors. Findings: Exposure to maternal incarceration increased risk of CPS contact. Unadjusted HRs exposed vs unexposed children were 7.06 (95%CI = 6.49–7.69) for substantiated child maltreatment and 12.89 (95%CI = 11.42–14.55) for out-of-home care (OOHC). Unadjusted IRRs were 6.04 (95%CI = 5.57–6.55) for number of substantiations and 12.47 (95%CI = 10.65–14.59) for number of removals to OOHC. HRs and IRRs were only slightly attenuated in adjusted models. Conclusions: Maternal incarceration is a warning flag for a child at high risk of serious child protection concerns. Family-friendly rehabilitative women's prisons, incorporating support for more nurturing mother-child relationships could provide a placed-based public health opportunity for disrupting distressing life trajectories and intergenerational pathways of disadvantage of these vulnerable children and their mothers. This population should be a priority for trauma-informed family support services.

Refereed/Peer-reviewed Background: Exposure to family and domestic violence (FDV) in childhood can have a detrimental effect on children's health and social outcomes. However, research on the school outcomes of children exposed to FDV is scant. Objectives: To investigate the impact of FDV exposure on school attendance and suspension in Aboriginal and non-Aboriginal children. Methods: A population-based retrospective cohort study of school children, in grade 1 to 10, born from 1993 to 2006 in Western Australia (n = 26,743) using linked administrative data. Multivariate logistic regression analysis was used to calculate odds ratios and 95% confidence intervals to determine the association with school attendance and suspension outcomes for children exposed to FDV compared to non-exposed children. Results: Compared to non-exposed children, children exposed to FDV have an increase of poor school attendance: Aboriginal children adjusted odds ratio (aOR) = 1.91, 95% confidence interval (CI): 1.75–2.07, non-Aboriginal children aOR = 2.42, 95%CI: 2.12–2.75. FDV-exposed children also have an increased risk of school suspension: Aboriginal children aOR = 1.60, 95%CI: 1.47–1.74, non-Aboriginal children aOR = 2.68, 95%CI: 2.35–3.05, compared to non-exposed counterparts. Conclusion: Exposure to FDV is associated with an increased odds of poor school attendance and school suspension. Evidence-based and innovative strategies are needed to support children who are exposed to FDV. This involves responding in ways that does not cause further trauma to children; a restorative and trauma-informed approach is vital.

Tubulinopathies are a group of conditions caused by variants in 6 tubulin genes that present with a spectrum of brain malformations. One of these conditions is TUBB2A-related tubulinopathy. Currently, there are 9 reported individuals with pathogenic variants within the TUBB2A gene, with common manifestations including, but not limited to, global developmental delay, seizures, cortical dysplasia, and dysmorphic corpus callosum. We report 3 patients identified by exome and genome sequencing to have a novel, pathogenic, missense variant in TUBB2A (p.Gly98Arg). They presented similarly with intellectual disability, hypotonia, and global developmental delay and varied with respect to the type of cortical brain malformation, seizure history, diagnosis of autism spectrum disorder, and other features. This case series expands the natural history of TUBB2A-related tubulinopathy while describing the presentation of a novel, pathogenic, missense variant in 3 patients.

Emerging evidence indicates that the built environment influences early child development. Access to, and the quality of, built environment features vary with the socioeconomic status (SES) of neighbourhoods. It has not yet been established whether the association between built environment features and early child development varies by neighbourhood SES. We sought to identify built environment features associated with neighbourhood-level variations in the early child development domains of physical health and wellbeing, social competence, and emotional maturity, and how these associations differ among high and low SES neighbourhoods where child development patterns follow expected outcomes ("on-diagonal" neighbourhoods) and where child development patterns differ from expected outcomes ("off-diagonal" neighbourhoods). This cross-sectional study analysed data from the Australian Early Development Census (AEDC) for children residing in 3839 neighbourhoods in the Perth and Peel metropolitan areas of Western Australia. Children's AEDC scores were aggregated at the area-level and merged with Geographic Information Systems derived measures of neighbourhood residential density, parks, walkability, community facilities and public transport. Multivariate logistic regressions modelled the odds of low and high SES neighbourhoods having a higher proportion of children developmentally "on-track" (scores in the 26th to 100th percentile of the AEDC) or "not on-track" (scores in the bottom 25th percentile of the AEDC) for each built environment feature. In high SES neighbourhoods, better development across all three domains was associated with greater residential density and improved access to parks, public transport, learning, childcare and health services. Conversely, in low SES neighbourhoods, greater residential density was associated with better physical, but poorer social and emotional development; increased traffic and street connectivity were associated with poorer physical and emotional development; shorter distances to parks, learning, childcare and health services were associated with poorer physical and emotional development; and more services and public transport stops were associated with poorer emotional development. The mixed findings in low SES neighbourhoods suggest that positive associations with built environment features seen in one domain of early child development may be negative in other domains. The reasons for the mixed findings in low SES neighbourhoods are likely multifactorial and may include parental neighbourhood perceptions, as well as quality and usage of built environment features. These findings can be used to inform state and local governments to establish child-friendly town planning and urban design features. Further research is needed to confirm the interplay between SES, early child development, the built environment and other unmeasured factors to better inform public health policy.

A major goal of the current personalized medicine era is to utilize pharmacogenetics (PGx) in order to influence how medications and therapies are prescribed by providers. However, disparities for prescribing medications between adults and children exist. Research has shown that children are not just small adults and there are different challenges for pediatric providers in regards to ordering and interpreting PGx tests. The goal of this study was to obtain an initial understanding of current pharmacogenetic testing by pediatric providers, as well as determine perceived barriers.We distributed an online survey to pediatric providers at six different institutions across the U.S.Of the 252 respondents who completed the survey, 24 percent reported previously ordering PGx tests, however, over 90 percent of respondents reported they would feel more comfortable ordering and interpreting results with the assistance of a pharmacist, geneticist, genetic counselor or PGx expert. Additionally, participants identified specific barriers towards the utilization of PGx testing, as well as suggested solutions to overcome these barriers, including increasing provider education regarding testing, collaboration through a multidisciplinary team approach and established PGx programs.As the pharmacogenetic field continues to demonstrate clinical utility in the pediatric population, it will be important to continuously identify and address barriers that exist for providers to allow for more successful implementation of PGx in the pediatric setting, as well as enhance patient care.

Conscience clauses are laws that allow healthcare providers to refuse to participate in legal medical services based on moral or ethical objections. Genetic counselors encounter a variety of ethical and moral issues, including counseling about abortions. Currently, three states (Oklahoma, Nebraska, and Virginia) have genetic counseling conscience clause laws that allow genetic counselors to refuse to counsel about abortions. Conscience clause laws applying to physicians and pharmacists have been studied; however, they have not been studied in genetic counseling to date. We conducted an exploratory study assessing conscience clause awareness, attitudes, perceived obligations if utilizing a conscience clause, and alignment with the National Society of Genetic Counseling (NSGC) Code of Ethics. Genetic counselors (n = 274) currently practicing in the United States completed an online survey recruited through the NSGC listserv. The majority of participants were not aware that conscience clauses exist for genetic counseling (90%). There was uncertainty about whether genetic counselors had the right to utilize a conscience clause in practice (24% said yes, 31% said no, and 45% were unsure/needed more information). The majority reported an obligation to refer a patient if implementing a conscience clause (90%), although there were discrepancies among what constitutes an appropriate referral. When asked about the interaction between conscience clauses and the NSGC Code of Ethics, 45% believe they are separate and one does not supersede the other, 31% felt the Code of Ethics supersedes, 8% felt conscience clauses supersede, and 16% were unsure. Our study shows overall uncertainty with how conscience clause laws may be applied in clinical practice. Further clarity and education, especially in states where these laws exist, is critical to navigate the interaction between conscience clause laws and genetic counseling practice.

This joint report from the American Educational Research Association (AERA) and the Spencer Foundation explores the impact of the COVID-19 pandemic on early career scholars and doctoral students in education research. The report presents findings and recommendations based on a focus group study held in May and June of 2020. The purpose of the study was to listen to and learn from the experiences of education researchers. The study included separate groups of scholars of color, women of color, and doctoral students of color, given that the COVID-19 crisis was highly racialized and having a disproportionate impact on communities of color. The aim of the report is to provide information that higher education institutions, agencies funding research, professional associations, and other research organizations can use to support the next generation of researchers and help buffer or contain adverse impacts to them. The report offers seven recommendations that could help to foster institutional and organizational responses to COVID-19 that are equitable and enriching. It is part of an ongoing initiative by AERA and Spencer to survey and assess the pressing needs of early career scholars and doctoral students at this pernicious time of a national pandemic.

While traditional components of genetic counseling sessions are well recognized, less is known about insurance and financial discussions. This study sought to examine "genesurance counseling" which we defined as: that portion of a genetic counseling session, whether intentional or non-intentional, that is devoted to the topic of costs and insurance/third party coverage (particularly for genetic testing). Our objective was to assess genetic counselors' practices and perspective related to genesurance counseling. A survey link was sent by e-mail to members of the National Society of Genetic Counselors (approximately 3100 NSGC members). A total of 571 genetic counselors participated in the survey of which 550 identified as clinical genetic counselors. Survey data were used to investigate differences between specialties, impact on patient rapport, changes in practice dynamics, and devotion of clinic time. Overwhelmingly, 99% of participants acknowledged conducting genesurance counseling, 87% believed it to be part of their job description, and 85% viewed it as an important aspect of genetic counseling. On average, respondents estimated they devoted 10% of their session, or 6 min, to genesurance counseling. Of the surveyed participants, 95% reported genesurance counseling as having some form of influence in a patient's decision regarding genetic testing, and 74% stated that genesurance counseling concerns change the practice and dynamic of their clinic. "Genesurance counseling" is not a topic which has been studied to date. Our study highlights the changes in genetic counselors' roles and responsibilities regarding insurance and financial counseling.

Uncertainty is a challenging aspect of caring for children with Duchenne/Becker muscular dystrophies (DBMD). Although uncertainty is often perceived as a state to be avoided, hope may influence caregivers' perceptions of uncertainty as opportunity. The goal of this cross-sectional quantitative study was to pilot a novel measure of state-based hope, and test relationships among uncertainty, hope, spirituality, and coping efficacy in mothers of children with DBMD. Mothers (n = 202) were recruited through DuchenneConnect, Parent Project Muscular Dystrophy, and Cincinnati's Children Hospital. A one-component solution for the novel Parent Hope Scale explained 44.3% of the variance, and the measure showed high internal consistency. Higher hope (P < 0.001), further disease progression (P = 0.042), and older mother's age (P = 0.001) were significantly associated with lower perceptions of uncertainty. Mothers reporting less hope (P < 0.001), higher perceptions of uncertainty (P < 0.001), and less spirituality (P = 0.001) reported lower coping efficacy. As such, hope appears to be a key variable in shaping uncertainty appraisals and facilitating coping efficacy. While further research is needed, counseling aimed at bolstering hope, particularly among less-hopeful mothers, and interventions to reappraise uncertainty, may be helpful in promoting coping efficacy.

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.

Personalized medicine and patient engagement have become common buzzwords in the context of health care reform. Independently both concepts have showed some promise in impacting health outcomes, but when synergistically applied, they have more power, as both are critical pieces of personalized health care (PHC). PHC is a health care model that embraces the need for patient engagement along with personalized medicine technologies to make the health care process more personalized, patient-driven, and proactive. Primary care presents an ideal setting for the application of PHC through the use of patient engagement techniques such as patient portals, patient-generated health data, and self-management programs, with the goal of supporting a preventative proactive health care approach.

Patients with abdominal pain and bloody diarrhea often present in the acute setting to the emergency department for evaluation. After the appropriate clinical assessment, cross-sectional imaging is often utilized to evaluate for the severity of the disease. Although a wide spectrum of findings may be seen, diffuse colonic mural thickening, consistent with pancolitis, is most common. We report an Escherichia coli 0157:H7-related pancolitis in a patient with spinach intake linked to the recent outbreak.

Contains fulltext : 107772.pdf (Publisher’s version ) (Open Access) In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression.

Tyrosine kinases, like the ErbB and Src families, can mediate potent oncogenic growth and are successful therapeutic targets of human cancers. However, many cancer cells overcome or successfully modulate these downstream signaling cascades in the absence of growth factor or kinase over-expression. We have previously identified a cellular phosphatase, PTPN13 that significantly modulates mitogenic signaling and can function as tumor suppressors. Decreased PTPN13 expression enhances ErbB2-mediated MAP Kinase activation, and is also associated with decreased survival in breast cancer. Here we show that PTPN13 regulates a signaling complex consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation, proximity ligation assay and immunofluoroscence studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further potentiates these changes. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in cancers harboring ErbB2-activating mutations and decreased PTPN13 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-143. doi:1538-7445.AM2012-LB-143