Interaction style of mothers of young children with Williams syndrome and relations with child expressive vocabulary.

Children of a given age vary widely in their expressive vocabulary abilities. One factor that is related to child expressive vocabulary ability is the style in which the mother interacts with her child. Studies that have considered this relation for either typically-developing (TD) children or children with developmental or intellectual disability (DD/ID) (e.g., autism spectrum disorder, fragile X syndrome) have shown that children whose mothers have a more sensitive/responsive interaction style have significantly larger expressive vocabularies than do children whose parents have a less sensitive/responsive style (e.g., Baker et al., 2010; Belsky et al., 2007; Brady et al., 2014; NICHD Early Child Care Research Network, 2003). In this dissertation, I provide the first examination of relations between child expressive vocabulary, child chronological age (CA), child nonverbal reasoning IQ, estimated annual family income, and maternal interaction style for young children with Williams syndrome (WS). The hypothesis of the study was that child expressive vocabulary ability relative to TD peers would be predicted by maternal interaction style beyond the effect of child nonverbal reasoning ability relative to TD peers. Participants were 75 children (35 girls, 40 boys) with classic WS deletions aged 4.01 – 8.39 years. Median estimated family income was $120,000 (IQR:$70,000 - $200,000). Children completed the Differential Ability Scales-II (DAS-II; mean Nonverbal Reasoning Cluster standard score (SS): 79.4, SD: 14.8) and the Expressive Vocabulary Test-2 (EVT-2; mean SS: 81.6, SD: 16.5). In addition, each mother-child dyad participated in a 30-minute play session with developmentally appropriate toys. Play sessions were videotaped. The mothers’ behavior during the play sessions was coded from the video-recordings using three scales from the NICHD Early Child Care Research Network: Supportive Presence, Respect for Child Autonomy, and Hostility (reversed). A 7-point Likert scale was used for each scale, with higher scores indicating more responsive maternal interaction. As in previous studies (e.g., Belsky et al., 2007; Downer & Pianta, 2006; NICHD Early Child Care Research Network, 2003), a composite of these ratings was used to evaluate maternal interaction style. The median maternal interaction style composite score was 16.0 (range: 10.5 – 21.0). To examine relations between child expressive vocabulary, child CA, child nonverbal reasoning SS, estimated annual family income, and maternal interaction style composite bivariate nonparametric correlations were computed. The maternal interaction style composite was moderately positively correlated with EVT-2 SS (rs = .42, p \u3c .001) and DAS-II Nonverbal Reasoning Cluster SS (rs = .42, p \u3c .001). EVT-2 SS was strongly positively correlated with DAS-II Nonverbal Reasoning Cluster SS (rs = .62, p\u3c .001). Estimated annual family income and child CA were not significantly correlated with any of the study variables (Mdn p-values = .849 and .382, respectively). To test the study hypothesis, sequential-model multiple regression analysis was performed. Model 1 was comprised of child CA, estimated annual family income, and DAS-II Nonverbal Reasoning Cluster SS. Maternal interaction style composite was added in Model 2. Model 2 provided a significantly better fit to the data than did Model 1, accounting for 43.4% of the variance in EVT-2 SS. Child CA and estimated family income were not significant predictors of child EVT-2 SS (ps\u3e .5). Maternal interaction style composite and DAS-II Nonverbal Reasoning Cluster SS were significant predictors of child EVT-2 SS (p = .02 and p \u3c .001, respectively). These results support the hypothesis that maternal interaction style significantly predicts child expressive vocabulary SS in children with Williams syndrome aged 4– 8 years even after taking into account the effects of nonverbal reasoning SS, estimated annual family income, and child CA. Implications for clinical interventions to facilitate more positive parent-child interactions are discussed

Practice Issues for Evaluation and Management of the Suicidal Left Ventricular Assist Device Patient

There is a high prevalence of depression among left ventricular assist device patients, who present with an increased risk of suicidality given access to means via the device either with nonadherence or disconnection. Suicidality via device nonadherence/disconnection is an underresearched clinical issue, as paradoxically this life-saving procedure can also provide a method of lethal means to patients with significant mental health concerns. A case study is used to highlight the course of an attempted suicide by ventricular assistive device nonadherence. Clinical implications and recommendations for practice include a thorough psychological evaluation presurgery, monitoring quality of life and coping styles before and after placement, psychological testing, outlining specific suicide protocols, psychiatric care considerations for patients with highly specialized medical devices, and related ethical concerns

Insurance-Based Differences in Time to Diagnostic Follow-up after Positive Screening Mammography

Insurance may lengthen or inhibit time to follow-up after positive screening mammography. We assessed the association between insurance status and time to initial diagnostic follow-up after a positive screening mammogram

Characterization of the Stanford Integrated Psychosocial Assessment for Transplant (SIPAT) in Lung Transplant Candidates

The SIPAT is a standardized measure for pre-transplant psychosocial evaluation. Previous SIPAT studies utilized a relatively small lung transplant sample and only included listed patients. This study characterized the SIPAT in 147 lung transplant candidates to better elucidate its utility. The average score corresponded to a minimally acceptable rating and nearly half of the patients had relative or absolute contraindications. Interstitial Lung Disease (ILD) patients scored more favorably than non-ILD patients (U = 7.69, p < .05). The Total (β = − .05, SE = .018, p < .01), Social Support Subscale (β = − .133, SE = .058, p < .05), and Psychosocial Stability and Psychopathology Subscale (β = − .103, SE = .040, p < .05) significantly predicted listing status. The SIPAT has a unique profile in lung transplant candidates and demonstrated utility for guiding transplant decisions. Future research should examine which lung transplant outcomes are significantly associated with SIPAT scores

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Canvass: A Crowd-Sourced, Natural-Product Screening Library for Exploring Biological Space

Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (−)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening

Development of a measure of model fidelity for mental health Crisis Resolution Teams

Background Crisis Resolution Teams (CRTs) provide short-term intensive home treatment to people experiencing mental health crisis. Trial evidence suggests CRTs can be effective at reducing hospital admissions and increasing satisfaction with acute care. When scaled up to national level however, CRT implementation and outcomes have been variable. We aimed to develop and test a fidelity scale to assess adherence to a model of best practice for CRTs, based on best available evidence. Methods A concept mapping process was used to develop a CRT fidelity scale. Participants (n = 68) from a range of stakeholder groups prioritised and grouped statements (n = 72) about important components of the CRT model, generated from a literature review, national survey and qualitative interviews. These data were analysed using Ariadne software and the resultant cluster solution informed item selection for a CRT fidelity scale. Operational criteria and scoring anchor points were developed for each item. The CORE CRT fidelity scale was then piloted in 75 CRTs in the UK to assess the range of scores achieved and feasibility for use in a 1-day fidelity review process. Trained reviewers (n = 16) rated CRT service fidelity in a vignette exercise to test the scale’s inter-rater reliability. Results There were high levels of agreement within and between stakeholder groups regarding the most important components of the CRT model. A 39-item measure of CRT model fidelity was developed. Piloting indicated that the scale was feasible for use to assess CRT model fidelity and had good face validity. The wide range of item scores and total scores across CRT services in the pilot demonstrate the measure can distinguish lower and higher fidelity services. Moderately good inter-rater reliability was found, with an estimated correlation between individual ratings of 0.65 (95% CI: 0.54 to 0.76). Conclusions The CORE CRT Fidelity Scale has been developed through a rigorous and systematic process. Promising initial testing indicates its value in assessing adherence to a model of CRT best practice and to support service improvement monitoring and planning. Further research is required to establish its psychometric properties and international applicability

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Lassa Fever in Post-Conflict Sierra Leone

Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF

What Role Does Substance Use Play in Intimate Partner Violence? A Narrative Analysis of In-Depth Interviews With Men in Substance Use Treatment and Their Current or Former Female Partner

Few studies have examined intimate partner violence (IPV) in relationships where one or both partners are in treatment for substance use, from the perspectives of both members of a couple. This study used thematic and narrative analysis of the accounts of 14 men recruited from substance use services and 14 women who were their current or former intimate partners. Separate researchers interviewed men and women from the same dyad pair. The psychopharmacological effects of substance use (including intoxication, craving, and withdrawal) were rarely the only explanation offered for IPV. Violence was reported to be primed and entangled with sexual jealousy, with perceptions of female impropriety and with women’s opposition to male authority. Both partners reported adversities and psychological vulnerabilities that they considered relevant to conflict and abuse. Male participants were more likely to describe IPV as uncharacteristic isolated events that arose from specific disputes—either aggravated by intoxication or withdrawal or about substance use and its resourcing—whereas women described enduring patterns of abusive behavior often linked to intoxication, craving, withdrawal, and to disputes linked to raising funds for substances. In relationships where both partners used substances, men described the need to protect their partners from addiction and from unscrupulous others while women described highly controlling behavior. In relationships where women were not dependent substance users, they reported the combined effects of psychological and financial abuse often linked to recurring patterns of substance use and relapse. These findings highlight the challenges faced by practitioners working with male perpetrators who use substances as well as the need of those working with women who have been abused to engage with the ways in which hesitance to leave male abusers can be complicated by shared drug dependency