Neglected Issues in Research on In-Home Services in Child Welfare: Final Report

This study considers several previously unexamined issues that affect the delivery and outcomes of intensive, in-home services for families of abused and neglected children. In this report, we present new, empirical data on parents\u27 and other primary caretakers\u27 readiness for change, their alliances (working relationships) with in-home services caseworkers, and the nature and extent of their substance use. we look at these issues--and at caretakers\u27 tendencies to give socially desirable responses--in relation to change over time in caretaker and family functioning, housing and economic conditions, social support, child well-being, the recurrence of child maltreatment, and out-of-home placement. Conducted as a supplement to a large evaluation of in-home services in child welfare (the Evaluation of Family Preservation and Reunification Services), our study includes 353 families who were referred for intensive family preservation services in Philadelphia county between March 1997 and June 1999. All of these families were the subject of at least one substantiated report of child abuse or neglect prior to referral. For purposes of the Evaluation of Family Preservation and Reunification Services (EFPRS), the families were randomly assigned to intensive, in-home family preservation services (FPS) or less intensive Services to Children in their Own Homes (SCOH). Longitudinal data were gathered by Westat, Inc. via interviews with primary caretakers and FPS/SCOH caseworkers, self-administered surveys of caseworkers and intake workers, and administrative databases. Interviews with caretakers were conducted at three points in time: within a few weeks of random assignment (Time 1), at approximately four months (Time 2), and at one year after random assignment (Time 3). Most of the primary caretakers in the study are African-American (81%) women (95%) who were unmarried (90%) and unemployed (83%). At the time of referral, their average age was 32 (the range is 19 to 78) and they had 3.4 children on average. More than half (53%) of the caretakers were the only adult in their household. Approximately 70% were receiving TANF at referral; hence, most had annual household incomes under $l0,000. At least 20% had difficulty buying food for their families and paying rent. Nearly 40% reported difficulty paying electric and heating bills and buying clothes for their children. FPS and SCOH caseworkers were predominately women (70%) and two-thirds were African-American. Almost half had some graduate-level education. On average, the caseworkers had 9 years of social work experience and 6 years of experience in child welfare. Unanticipated delays in the assignment of FPS and SCOH caseworkers to cases in the study affected service delivery and data collection. We encountered more problems than expected with missing data, particularly from caseworkers and on alliances

Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease s attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment

Human Vault Nanoparticle Targeted Delivery of Antiretroviral Drugs to Inhibit Human Immunodeficiency Virus Type 1 Infection.

"Vaults" are ubiquitously expressed endogenous ribonucleoprotein nanoparticles with potential utility for targeted drug delivery. Here, we show that recombinant human vault nanoparticles are readily engulfed by certain key human peripheral blood mononuclear cells (PBMC), predominately dendritic cells, monocytes/macrophages, and activated T cells. As these cell types are the primary targets for human immunodeficiency virus type 1 (HIV-1) infection, we examined the utility of recombinant human vaults for targeted delivery of antiretroviral drugs. We chemically modified three different antiretroviral drugs, zidovudine, tenofovir, and elvitegravir, for direct conjugation to vaults. Tested in infection assays, drug-conjugated vaults inhibited HIV-1 infection of PBMC with equivalent activity to free drugs, indicating vault delivery and drug release in the cytoplasm of HIV-1-susceptible cells. The ability to deliver functional drugs via vault nanoparticle conjugates suggests their potential utility for targeted drug delivery against HIV-1

Osteopathology and insect traces in the Australopithecus africanus skeleton StW 431

We present the first application of high-resolution micro computed tomography in an analysis of both the internal and external morphology of the lumbar region of StW 431 – a hominin skeleton recovered from Member 4 infill of the Sterkfontein Caves (South Africa) in 1987. The lumbar vertebrae of the individual present a number of proliferative and erosive bony processes, which were investigated in this study. Investigations suggest a complex history of taphonomic alteration to pre-existing spinal degenerative joint disease (SDJD) as well as post-mortem modification by an unknown insect. This study is in agreement with previous pathological diagnoses of SDJD which affected StW 431 and is the first time insect traces on this hominin are described. The results of this analysis attest to the complex series of post-mortem processes affecting the Sterkfontein site and its fossil assemblages

Transmission spectroscopy of the lowest-density gas giant: metals and a potential extended outflow in HAT-P-67b

Extremely low-density exoplanets are tantalizing targets for atmospheric characterization because of their promisingly large signals in transmission spectroscopy. We present the first analysis of the atmosphere of the lowest-density gas giant currently known, HAT-P-67 b. This inflated Saturn-mass exoplanet sits at the boundary between hot and ultrahot gas giants, where thermal dissociation of molecules begins to dominate atmospheric composition. We observed a transit of HAT-P-67 b at high spectral resolution with CARMENES and searched for atomic and molecular species using cross-correlation and likelihood mapping. Furthermore, we explored potential atmospheric escape by targeting H$\alpha$ and the metastable helium line. We detect Ca II and Na I with significances of 13.2$\sigma$ and 4.6$\sigma$, respectively. Unlike in several ultrahot Jupiters, we do not measure a day-to-night wind. The large line depths of Ca II suggest that the upper atmosphere may be more ionized than models predict. We detect strong variability in H$\alpha$ and the helium triplet during the observations. These signals suggest the possible presence of an extended planetary outflow that causes an early ingress and late egress. In the averaged transmission spectrum, we measure redshifted absorption at the $\sim 3.8\%$ and $\sim 4.5\%$ level in the H$\alpha$ and He I triplet lines, respectively. From an isothermal Parker wind model, we derive a mass loss rate of $\dot{M} \sim 10^{13}~\rm{g/s}$ and an outflow temperature of $T \sim 9900~\rm{K}$. However, due to the lack of a longer out-of-transit baseline in our data, additional observations are needed to rule out stellar variability as the source of the H$\alpha$ and He signals.Comment: The Astronomical Journal, in press. 17 pages, 9 figure

Changes in Muscle Metabolism are Associated with Phenotypic Variability in Golden Retriever Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is an X-chromosome-linked disorder and the most common monogenic disease in people. Affected boys are diagnosed at a young age, become non-ambulatory by their early teens, and succumb to cardiorespiratory failure by their thirties. Despite being a monogenic condition resulting from mutations in the DMD gene, affected boys have noteworthy phenotypic variability. Efforts have identified genetic modifiers that could modify disease progression and be pharmacologic targets. Dogs affected with golden retriever muscular dystrophy (GRMD) have absent dystrophin and demonstrate phenotypic variability at the functional, histopathological, and molecular level. Our laboratory is particularly interested in muscle metabolism changes in dystrophin-deficient muscle. We identified several metabolic alterations, including myofiber type switching from fast (type II) to slow (type I), reduced glycolytic enzyme expression, reduced and morphologically abnormal mitochondria, and differential AMP-kinase phosphorylation (activation) between hypertrophied and wasted muscle. We hypothesize that muscle metabolism changes are, in part, responsible for phenotypic variability in GRMD. Pharmacological therapies aimed at modulating muscle metabolism can be tested in GRMD dogs for efficacy

Searching For Dark Matter with Plasma Haloscopes

We summarise the recent progress of the Axion Longitudinal Plasma HAloscope (ALPHA) Consortium, a new experimental collaboration to build a plasma haloscope to search for axions and dark photons. The plasma haloscope is a novel method for the detection of the resonant conversion of light dark matter to photons. ALPHA will be sensitive to QCD axions over almost a decade of parameter space, potentially discovering dark matter and resolving the Strong CP problem. Unlike traditional cavity haloscopes, which are generally limited in volume by the Compton wavelength of the dark matter, plasma haloscopes use a wire metamaterial to create a tuneable artificial plasma frequency, decoupling the wavelength of light from the Compton wavelength and allowing for much stronger signals. We develop the theoretical foundations of plasma haloscopes and discuss recent experimental progress. Finally, we outline a baseline design for ALPHA and show that a full-scale experiment could discover QCD axions over almost a decade of parameter space.Comment: Endorsers: Jens Dilling, Michael Febbraro, Stefan Knirck, and Claire Marvinney. 26 pages, 17 figures, version accepted in Physical Review

Prenatal maternal antidepressants, anxiety, and depression and offspring DNA methylation: epigenome-wide associations at birth and persistence into early childhood

Background Maternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA. Methods A discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts. Results In Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, − 10.4, − 4.1; P = 1.03 × 10−8) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = − 2.5%; 95% CI − 4.2, − 0.7; P = 0.006). In Project Viva, the association persisted in early (β = − 6.2%; 95% CI − 10.7, − 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate. Conclusions The ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation

Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood

Severe obesity is a rapidly growing global health threat. Although often attributed to unhealthy lifestyle choices or environmental factors, obesity is known to be heritable and highly polygenic; the majority of inherited susceptibility is related to the cumulative effect of many common DNA variants. Here we derive and validate a new polygenic predictor comprised of 2.1 million common variants to quantify this susceptibility and test this predictor in more than 300,000 individuals ranging from middle age to birth. Among middle-aged adults, we observe a 13-kg gradient in weight and a 25-fold gradient in risk of severe obesity across polygenic score deciles. In a longitudinal birth cohort, we note minimal differences in birthweight across score deciles, but a significant gradient emerged in early childhood and reached 12 kg by 18 years of age. This new approach to quantify inherited susceptibility to obesity affords new opportunities for clinical prevention and mechanistic assessment. © 2019 Author(s)National Human Genome Research Institute (1K08HG0101)Wellcome Trust (202802/Z/16/Z)University of Bristol NIHR Biomedical Research Centre (S- BRC-1215-20011)National Human Genome Research Institute (HG008895)National Heart, Lung, and Blood Institute (NHLBI) HHSN268201300025CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300026CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300027CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300028CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268201300029CNational Heart, Lung, and Blood Institute (NHLBI) HHSN268200900041CNational Institute on Aging (AG0005)NHLBI (AG0005)National Human Genome Research Institute (U01-HG004729)National Human Genome Research Institute (U01-HG04424)National Human Genome Research Institute (U01-HG004446)Wellcome (102215/2/13/2