Associations of antenatal maternal psychological distress with infant birth and development outcomes: Results from a South African birth cohort.

BACKGROUND: Antenatal maternal psychological distress is common in low and middle-income countries (LMIC), but there is a dearth of research on its effect on birth and developmental outcomes in these settings, particularly in Sub-Saharan Africa. This study set out to identify risk factors for antenatal maternal psychological distress and determine whether antenatal maternal psychological distress was associated with infant birth and developmental outcomes, using data from the Drakenstein Child Health Study (DCHS), a birth cohort study in South Africa. METHODS: Pregnant women were enrolled in the DCHS from primary care antenatal clinics. Antenatal maternal psychological distress was measured using the Self-Reporting Questionnaire 20-item (SRQ-20). A range of psychosocial measures, including maternal childhood trauma, depression, and posttraumatic stress disorder (PTSD) were administered. Birth outcomes, including premature birth, weight-for-age z-score and head circumference-for-age z-score, were measured using revised Fenton growth charts. The Bayley III Scales of Infant and Toddler Development was administered at 6 months of age to assess infant development outcomes, including cognitive, language, and motor domains in a subset of n=231. Associations of maternal antenatal psychological distress with psychosocial measures, and with infant birth and developmental outcomes were examined using linear regression models. RESULTS: 961 women were included in this analysis, with 197 (21%) reporting scores indicating the presence of psychological distress. Antenatal psychological distress was associated with maternal childhood trauma, antenatal depression, and PTSD, and inversely associated with partner support. No association was observed between antenatal maternal psychological distress and preterm birth or early developmental outcomes, but antenatal maternal psychological distress was associated with a smaller head circumference at birth (coefficient=-0.30, 95% CI: -0.49; -0.10). CONCLUSION: Antenatal maternal psychological distress is common in LMIC settings and was found to be associated with key psychosocial measures during pregnancy, as well as with adverse birth outcomes, in our study population. These associations highlight the potential value of screening for antenatal maternal psychological distress as well as of developing targeted interventions.

Highly Resolved Measurements of a Developing Strong Collisional Plasma Shock.

The structure of a strong collisional shock front forming in a plasma is directly probed for the first time in laser-driven gas-jet experiments. Thomson scattering of a 526.5 nm probe beam was used to diagnose temperature and ion velocity distribution in a strong shock (M∼11) propagating through a low-density (ρ∼0.01 mg/cc) plasma composed of hydrogen. A forward-streaming population of ions traveling in excess of the shock velocity was observed to heat and slow down on an unmoving, unshocked population of cold protons, until ultimately the populations merge and begin to thermalize. Instabilities are observed during the merging, indicating a uniquely plasma-phase process in shock front formation.

Iridescence-free and narrowband perfect light absorption in critically coupled metal high-index dielectric cavities.

Perfect light absorption in the visible and near-infrared (NIR) was demonstrated using metamaterials, plasmonic nanostructures, and thin films. Thin film absorbers offer a simple and low-cost design as they can be produced on large areas and without lithography. Light is strongly absorbed in thin film metal-dielectric-metal (MDM) cavities at their resonance frequencies. However, a major drawback of MDM absorbers is their strong resonance iridescence, i.e., angle dependence. Here, we solve the iridescence problem by achieving angle-insensitive narrowband perfect and near-perfect light absorption. In particular, we show analytically that using a high-index dielectric in MDM cavities is sufficient to achieve angle-insensitive cavity resonance. We demonstrate experimentally angle-insensitive perfect and near-perfect absorbers in the NIR and visible regimes up to ±60°. By overcoming the iridescence problem, we open the door for practical applications of MDM absorbers at optical frequencies.

Low Fuel Convergence Path to Direct-Drive Fusion Ignition.

A new class of inertial fusion capsules is presented that combines multishell targets with laser direct drive at low intensity (2.8×10^{14} W/cm^{2}) to achieve robust ignition. The targets consist of three concentric, heavy, metal shells, enclosing a volume of tens of µg of liquid deuterium-tritium fuel. Ignition is designed to occur well "upstream" from stagnation, with minimal pusher deceleration to mitigate interface Rayleigh-Taylor growth. Laser intensities below thresholds for laser plasma instability and cross beam energy transfer facilitate high hydrodynamic efficiency (∼10%).

Ion thermal decoupling and species separation in shock-driven implosions.

Anomalous reduction of the fusion yields by 50% and anomalous scaling of the burn-averaged ion temperatures with the ion-species fraction has been observed for the first time in D^{3}He-filled shock-driven inertial confinement fusion implosions. Two ion kinetic mechanisms are used to explain the anomalous observations: thermal decoupling of the D and ^{3}He populations and diffusive species separation. The observed insensitivity of ion temperature to a varying deuterium fraction is shown to be a signature of ion thermal decoupling in shock-heated plasmas. The burn-averaged deuterium fraction calculated from the experimental data demonstrates a reduction in the average core deuterium density, as predicted by simulations that use a diffusion model. Accounting for each of these effects in simulations reproduces the observed yield trends.

Exploration of the transition from the hydrodynamiclike to the strongly kinetic regime in shock-driven implosions.

Clear evidence of the transition from hydrodynamiclike to strongly kinetic shock-driven implosions is, for the first time, revealed and quantitatively assessed. Implosions with a range of initial equimolar D3He gas densities show that as the density is decreased, hydrodynamic simulations strongly diverge from and increasingly overpredict the observed nuclear yields, from a factor of ∼2 at 3.1 mg/cm3 to a factor of 100 at 0.14 mg/cm3. (The corresponding Knudsen number, the ratio of ion mean-free path to minimum shell radius, varied from 0.3 to 9; similarly, the ratio of fusion burn duration to ion diffusion time, another figure of merit of kinetic effects, varied from 0.3 to 14.) This result is shown to be unrelated to the effects of hydrodynamic mix. As a first step to garner insight into this transition, a reduced ion kinetic (RIK) model that includes gradient-diffusion and loss-term approximations to several transport processes was implemented within the framework of a one-dimensional radiation-transport code. After empirical calibration, the RIK simulations reproduce the observed yield trends, largely as a result of ion diffusion and the depletion of the reacting tail ions.

Prenatal alcohol exposure and white matter microstructural changes across the first 6-7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort.

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2-3 (N = 121 scans: 27 PAE; 94 controls) and 6-7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks' gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2-3 years of age, followed by a more tapered trajectory for the period from 2-3 to 6-7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Design of multi neutron-to-gamma converter array for measuring time resolved ion temperature of inertial confinement fusion implosions.

The ion temperature varying during inertial confinement fusion implosions changes the amount of Doppler broadening of the fusion products, creating subtle changes in the fusion neutron pulse as it moves away from the implosion. A diagnostic design to try to measure these subtle effects is introduced-leveraging the fast time resolution of gas Cherenkov detectors along with a multi-puck array that converts a small amount of the neutron pulse into gamma-rays, one can measure multiple snapshots of the neutron pulse at intermediate distances. Precise measurements of the propagating neutron pulse, specifically the variation in the peak location and the skew, could be used to infer time-evolved ion temperature evolved during peak compression.

Diagnostic signature of the compressibility of the inertial-confinement-fusion pusher.

Carbon shell areal density measurements from many types of inertial confinement fusion implosions at the National Ignition Facility (NIF) demonstrate that the final state of the outside portion of the shell is set primarily by capsule coast time, the coasting period between main laser shut off and peak fusion output. However, the fuel areal density does not correlate with the increasing carbon compression. While two-dimensional (2D) radiation-hydrodynamic simulations successfully capture the carbon compression, energy must be added to the simulated fuel-ice layer to reproduce fuel areal density measurements. The data presented demonstrates that the degradation mechanisms that reduce the compressibility of the fuel do not reduce the compressibility of the ablator.

Medicine-use evaluation of doxazosin prescribing to inform formulary recommendations.

BACKGROUND: It is estimated that >50% of all medicines are inappropriately prescribed, dispensed or sold. In 2018, the Western Cape Government Health (WCGH) Provincial Pharmacy and Therapeutics Committee (PPTC) endorsed an investigation of doxazosin use in provincial public sector healthcare facilities using a medicine-use evaluation (MUE). This was based on potential inappropriate prescribing, high usage and high costs associated with doxazosin. OBJECTIVES: To determine whether doxazosin was being prescribed in accordance with recommendations from standard treatment guidelines and essential medicines lists for hospital and primary healthcare level, as well as from the WCGH provincial code list. METHODS: The study design consisted of a retrospective multicentre prescription review. The study population included all adult outpatients who were prescribed doxazosin, which was to be dispensed by the WCGH Chronic Dispensing Unit. Criteria for evaluation included indications for doxazosin administration and total daily dose prescribed. RESULTS: The study sample comprised 171 patients. The main indication for doxazosin administration was as a fourth-line agent for the treatment of hypertension (82%). The remaining indications were not guideline approved (18%). The total daily doses identified were 4 mg (62%), followed by 8 mg (36%) and 2 mg (2%). All of these were approved dosages as per guideline recommendations. CONCLUSIONS: MUEs are an untapped resource for medication-use monitoring and practice improvement. MUEs offer a distinct, cost-effective approach to improve medicine use in all settings. This MUE revealed a relatively minor concern with doxazosin prescribing. MUEs can be beneficial to inform formulary changes and re-evaluate medication-use restrictions.

The effect of technology assisted therapy for intellectually and visually impaired adults suffering from separation anxiety: Conquering the fear.

Persons with an intellectual disability (ID) are at risk of developing separation anxiety (SA) and, if left untreated, this can be a risk factor for the development of psychopathology. The effects of an intervention, namely technology assisted therapy for SA (TTSA), were examined on the SA, challenging behavior, psychosocial functioning, and quality of life (QOL) experienced by moderate to mild intellectually and visually disabled adults. This study aimed to determine whether TTSA reduces SA and challenging behavior in persons with ID and visual impairment, and if this results in increased psychosocial functioning and QOL. A pre-experimental within-group design with randomized multiple baselines and staggered intervention start-points was used (n = 6). The variables were monitored with standardized instruments. The frequencies of each participant's use of the technology and the frequency and intensity of their behavior were recorded over time. Results indicate that the SA and challenging behavior experienced by the participants decreased significantly and their psychosocial functioning and QOL increased significantly. The conclusions are that TTSA has the potential to be a valid intervention to address SA in adults with visual and moderate to mild IDs.

Improved inertial confinement fusion gamma reaction history 12C gamma-ray signal by direct subtraction.

The Gamma Reaction History (GRH) diagnostic located at the National Ignition Facility (NIF) measures time resolved gamma rays released from inertial confinement fusion experiments by converting the emitted gamma rays into Cherenkov light. Imploded capsules have a bright 4.4 MeV gamma ray from fusion neutrons inelastically scattering with carbon atoms in the remaining ablator. The strength of the 4.4 MeV gamma ray line is proportional to the capsule's carbon ablator areal density and can be used to understand the dynamics and energy budget of a carbon-based ablator capsule implosion. Historically, the GRH's four gas cells use the energy thresholding from the Cherenkov process to forward fit an estimation of the experiment's complete gamma ray spectrum by modeling the surrounding environment in order to estimate the 4.4 MeV neutron induced carbon gamma ray signal. However, the high number of variables, local minima, and uncertainties in detector sensitivities and relative timing had prevented the routine use of the forward fit to generate carbon areal density measurements. A new, more straightforward process of direct subtraction of deconvolved signals was developed to simplify the extraction of the carbon areal density. Beryllium capsules are used as a calibration to measure the capsule environment with no carbon signal. The proposed method is then used to appropriately subtract and isolate the carbon signal on shots with carbon ablators. The subtraction algorithm achieves good results across all major capsule campaigns, achieving similar results to the forward fit. This method is now routinely used to measure carbon areal density for NIF shots.

Health-Related Quality of Life Following Concussion in Collegiate Student-Athletes With and Without Concussion History.

The purpose of this study was to compare global and specific health-related quality of life (HRQOL) throughout concussion recovery between those with and without concussion history. Student-athletes diagnosed with concussion completed global (Short Form-12v2; SF-12) and specific (Hospital Anxiety and Depression Scale: HADS) HRQOL assessments at baseline, 24-48 h, asymptomatic, return-to-play, and 6-months post-injury. Baseline scores were compared to post-injury time points for SF-12 subscores (physical and mental; PCS-12, MCS-12) and HADS subscores (depression and anxiety; HADS-D, HADS-A). We conducted a 2 × 5 mixed model ANOVA for group (with and without concussion history) and time (four post-injury assessments compared to baseline). We did not observe interaction or main effects for group, except those with concussion history had worse HADS-D subscores than those without concussion history. PCS-12 subscores were worse at 24-48 h, asymptomatic, and return-to-play compared to baseline, but returned to baseline 6-months post-injury. MCS-12 subscores did not differ at any time points. HADS-D subscores worsened 24-48 h post-injury, but improved for additional assessments compared to baseline. HADS-A improved post-injury compared to baseline at asymptomatic, return-to-play, and 6-month assessments, but was similar to baseline 24-48 h post-injury. HRQOL physical aspects slightly worsened post-injury and restored to baseline after returning to play.

Cherenkov detector analysis for implosions with multiple nuclear reactions.

Nuclear reactions that produce γ rays occur in inertial fusion implosions and are commonly measured with Cherenkov detectors. Typically a detector is primarily sensitive to a single reaction, but in some implosions, multiple fusion reactions can occur and are combined in the data. We discuss an analysis technique using multiple thresholded detectors to reproduce the individual burn histories from reactions like DT and HT fusion, which is applicable to separated-reactant mix experiments. Requirements for this technique and resulting analysis uncertainties are quantified using synthetic data.

Diffusion-dominated mixing in moderate convergence implosions.

High-Z material mixed into the fuel degrades inertial fusion implosions and can prevent ignition. Mix is often assumed to be dominated by hydrodynamic instabilities, but we report Omega data, using shells with ∼150nm deuterated layers to gain unprecedented resolution, which give strong evidence that the dominant mix mechanism is diffusion for these moderate temperature (≲6 keV) and convergence (∼12) implosions. Small-scale instability-driven or turbulent mix is negligible.

First measurements of remaining shell areal density on the OMEGA laser using the Diagnostic for Areal Density (DAD).

A glass Cherenkov detector, called the Diagnostic for Areal Density (DAD), has been built and implemented at the OMEGA laser facility for measuring fusion gammas above 430 keV, from which remaining shell ⟨ρR⟩ abl can be determined. A proof-of-principle experiment is discussed, where signals from a surrogate gas Cherenkov detector are compared with reported values from the wedge range filter and charged particle spectrometer and found to correlate strongly. The design of the more compact port-based DAD diagnostic and results from the commissioning shots are then presented. Once absolutely calibrated, the DAD will be capable of reporting remaining shell ⟨ρR⟩ abl for plastic and glass capsules within minutes of a shot and with potentially higher precision than existing techniques.

A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes.

The protein product of the c-Cbl proto-oncogene is prominently tyrosine phosphorylated in response to insulin in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with endogenous c-Crk and Fyn. These results suggest a role for tyrosine-phosphorylated c-Cbl in 3T3-L1 adipocyte activation by insulin. A yeast two-hybrid cDNA library prepared from fully differentiated 3T3-L1 adipocytes was screened with full-length c-Cbl as the target protein in an attempt to identify adipose-specific signaling proteins that interact with c-Cbl and potentially are involved in its tyrosine phosphorylation in 3T3-L1 adipocytes. Here we describe the isolation and the characterization of a novel protein that we termed CAP for c-Cbl-associated protein. CAP contains a unique structure with three adjacent Src homology 3 (SH3) domains in the C terminus and a region showing significant sequence similarity with the peptide hormone sorbin. Both CAP mRNA and proteins are expressed predominately in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. CAP associates with c-Cbl in 3T3-L1 adipocytes independently of insulin stimulation in vivo and in vitro in an SH3-domain-mediated manner. Furthermore, we detected the association of CAP with the insulin receptor. Insulin stimulation resulted in the dissociation of CAP from the insulin receptor. Taken together, these data suggest that CAP represents a novel c-Cbl binding protein in 3T3-L1 adipocytes likely to participate in insulin signaling.

Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins.

Based on the prevalence of modular protein domains, such as Src homology domain 3 and 2 (SH3 and SH2), among important signaling molecules, we have sought to identify new SH3 domain-containing proteins. However, modest sequence similarity among these domains restricts the use of DNA-based methods for this purpose. To circumvent this limitation, we have developed a functional screen that permits the rapid cloning of modular domains based on their ligand-binding activity. Using operationally defined SH3 ligands from combinatorial peptide libraries, we screened a series of mouse and human cDNA expression libraries. We found that 69 of the 74 clones isolated encode at least one SH3 domain. These clones encode 18 different SH3-containing proteins, 10 of which have not been described previously. The isolation of entire repertoires of modular domain-containing proteins will prove invaluable in genome analysis and in bringing new targets into drug discovery programs.

Pool size of pluripotential hematopoietic stem cells increased in continuous bone marrow culture by Friend spleen focus-forming virus.

Continuous mouse bone marrow cultures were infected with Friend murine leukemia virus. Production of nonadherent (NA) and adherent cells, granulocyte-macrophage colony-forming unit(s) of progenitor cells (GM-CFUc), pluripotential hematopoietic stem cells (CFUs), the self-renewal potential (Rs) of CFUs, and generation of factor-dependent (FD) multipotential and committed permanent stem cell cloned lines were measured. Uninfected marrow cultures from C57BL/6J, C57BL/6JUt, B6.S, C3H/HeJ, (C57BL/6J x DBA/2J)F1, CD- 1 Swiss, or N:NIH(S) mice generated NA cells, GM-CFUc, and CFUs for 20-41 weeks; cultures infected with Rauscher or other helper viruses generated them for 35-45 weeks. GM-CFUc and CFUs production in SFFV-positive cultures persisted for over 65 weeks and exceeded control levels by twentyfold to fiftyfold. The Rs of CFUs in SFFV-positive cultures was not detectably increased above control cultures. Multipotential (erythroid-neutrophil-mast cell-basophil-eosinophil) permanent FD cell clones were derived from control and SFFV-positive cultures. Thus SFFV amplifies the stem cell pool in vitro without detectably increasing the Rs capacity of CFUs.