A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.

Speciation within the Anopheles gambiae complex: high-throughput whole genome sequencing reveals evidence of a putative new cryptic taxon in 'far-west' Africa.

The two main Afrotropical malaria vectors - Anopheles coluzzii and An. gambiae - are genetically distinct and reproductively isolated across West Africa. However, populations at the western extreme of their range are assigned as "intermediate" between the two species by whole genome sequence (WGS) data, and as hybrid forms by conventional molecular diagnostics. By exploiting WGS data from 1,190 specimens collected across west Africa via the Anopheles gambiae 1000 Genomes network, we identify a novel putative taxon in the far-west (provisionally named Bissau molecular form), which did not arise by admixture but rather originated at the same time as the split between An. coluzzii and An. gambiae. Intriguingly, these populations lack insecticide resistance mechanisms commonly observed in the two main species. These findings lead to a change of perspective on malaria vector species in the far-west region with potential for epidemiological implications, and a new challenge for genetic-based mosquito control approaches.

A multi-lesional analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: a single-centre analysis.

AIM: To conduct a multi-lesional computed tomography (CT) analysis of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) patients to determine volumetric changes in lesions over 5 years. MATERIALS AND METHODS: A retrospective case-note review was undertaken to identify 16 patients with histological and radiological features of DIPNECH between 2012-2021. Area and volume were calculated for 17 sets of lesions identified on high-resolution CT. Clinical data were extracted from electronic patient records, which included demographic data, outpatient clinic letters, histology reports, and imaging reports. RESULTS: One hundred and twenty-eight lesions were identified in 16 patients (one male, 15 female) and followed-up annually over a median 1,985 days (range 1,450-2,290). At year 1 follow-up, lesion area ranged from 1-48 mm2, and lesion volume ranged from 8-18,380 mm3; lesion area ranged from 1-45mm2 and lesion volume ranged from 11-17,800 mm3 and year 5. Half (8/16) of the patients had concomitant typical carcinoid tumours and one patient had an atypical carcinoid tumour. No statistically significant correlation (p<0.05) was found between lesion cross-sectional area or volume and duration of follow-up (years and days). No metastatic spread was observed at the time of analysis. CONCLUSIONS: No significant increase was observed in the size of over 100 lesions in patients with DIPNECH over a 5-year period and no metastasis occurred during the study period affirming the relatively indolent course of the disease.

Mapping the Theoretical Domain Framework to the Consolidated Framework for Implementation Research: do multiple frameworks add value?

BACKGROUND: Implementation researchers often combine the Theoretical Domain Framework (TDF) and Consolidated Framework for Implementation Research (CFIR) in their studies. However there is some debate on the merits of using multiple frameworks-whether they contribute to results or provide superfluous analysis. Our recent research combined the TDF and CFIR to identify determinants to widespread incorporation of patient held medication lists (PHML) in healthcare practice. The aim of this report is to provide guidance on the use of the TDF and CFIR; by assessing the degree of overlap between the two frameworks in their application to interviews about PHML. METHODS: Semi-structured telephone interviews were conducted with healthcare professionals (HCPs) and non HCPs (people taking multiple medicines and caregivers).Interview data were transcribed and analysed using the TDF and CFIR. Within paired domains substantial intersection/overlap across constructs and domains within the two frameworks was classified as > 75% of coding references, consistent intersection/overlap was defined as > 50% and ≤ 75%, average intersection/overlap was defined as ≤ 50% and > 25% and non-substantial intersection/overlap was classified as ≤ 25% of coding references. RESULTS: Interview data were collected from 39 participants - 21 HCPs and 18 non HCPs. Mapping of TDF domains to CFIR domains/constructs identified key determinants in six TDF domains: Environmental context & resources, Beliefs about capabilities, Beliefs about consequences, Social influences, Behavioural regulation and Social/professional role & identity; and five CFIR domains: Intervention Characteristics, Outer Setting, Inner Setting, Characteristics of Individual and Process. A pattern of substantial intersection/overlap in coding emerged with broad TDF domains such as Environmental context & resources often linked to well-defined CFIR domains and constructs (e.g. design quality & packaging within Intervention Characteristics). Broad CFIR constructs such as knowledge & beliefs about intervention within Characteristics of Individuals also linked to more descriptive TDF domains like Beliefs about capabilities. In addition there was some unexpected non-substantial intersection/overlap in coding with the TDF domain Social influences less frequently linked to the CFIR Inner Setting domain and constructs such as networks and communications. CONCLUSIONS: Identifying intersections/overlaps in coding between CFIR and TDF can assist interpretation of findings in implementation research. The strengths of each framework were exploited in a reciprocal process which provided more information to broad/poorly defined domains and enabled identification of implementation determinants and innovation determinants.

A decade of Clostridioides difficile infection: a constant challenge to maintain the status quo.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated (HA) diarrhoea. We retrospectively investigated data from a comprehensive, multidisciplinary C. difficile surveillance programme focusing on hospitalized patients in a tertiary Irish hospital over 10 years. METHODS: Data from 2012 to 2021 were extracted from a centralized database, including patient demographics, admission, case and outbreak details, ribotypes (RTs), and (since 2016) antimicrobial exposures and CDI treatments. Counts of CDI by origin of infection were explored using ꭓ2 analyses, Poisson regression was used to investigate trends in rates of CDI and possible risk factors. Time to recurrent CDI was examined by a Cox proportional hazards regression. RESULTS: Over 10 years, 954 CDI patients had a 9% recurrent CDI rate. CDI testing requests occurred in only 22% of patients. Most CDIs were HA (82.2%) and affected females (odds ratio: 2.3, P<0.01). Fidaxomicin significantly reduced the hazard ratio of time to recurrent CDI. No trends in HA-CDI incidence were observed despite key time-point events and increasing hospital activity. In 2021, community-associated (CA)-CDI increased. RTs did not differ for HA versus CA for the most common RTs (014, 078, 005 and 015). Average length-of-stay differed significantly between HA (67.1 days) and CA (14.6 days) CDI. CONCLUSION: HA-CDI rates remained unchanged despite key events and increased hospital activity, whereas by 2021, CA-CDI was at its highest in a decade. The convergence of CA and HA RTs, and the proportion of CA-CDI, question the relevance of current case definitions when increasingly patients receive hospital care without an overnight hospital stay.

Validity of total body water measured by multi-frequency bioelectrical impedance devices in a multi-ethnic sample.

BACKGROUND & AIMS: Total body water (TBW) is the largest component of fat free mass and therefore is commonly used in multi-compartment body composition models and as a stand-alone method to assess body composition. Previous literature has not validated bioelectrical impedance spectroscopy device estimates of TBW in racial and ethnic minority populations; previous studies have focused on bioelectrical impedance analysis devices that rely on proprietary algorithms and participant characteristics for accuracy. The purpose of this study was to assess the validity of two bioelectrical impedance spectroscopy devices for measures of TBW compared to a deuterium dilution criterion in a multi-ethnic sample. METHODS: 109 individuals (55% female, Age: 26.6 ± 6.9 yrs, BMI: 25.3 ± 4.0 kg/m2) identifying as Asian, African American/Black, Caucasian/White, Hispanic, and Multi-racial were enrolled. After a 12 h fast, participants provided a saliva sample for the criterion baseline TBW measure and completed two bioelectrical impedance device (BIS, IB) measurements of TBW. Participants then ingested deuterium oxide (D2O). After an equilibration period, participants provided a second saliva sample for analysis of TBW. RESULTS: For the total multi-ethnic sample, BIS estimates demonstrated good to fairly good agreement (Total error [TE] = 2.56 L, R2 = 0.951) and IB estimates were excellent to very good (TE = 1.95 L, R2 = 0.975). Validity results did not vary meaningfully between race and ethnicity. CONCLUSIONS: The results suggest the BIS and IB devices evaluated can produce valid TBW estimates compared to D2O in a multi-ethnic sample. TBW estimates from the IB may have better agreement with D2O compared to the BIS when using the default settings.

Cooperation of chromatin remodeling SWI/SNF complex and pioneer factor AP-1 shapes 3D enhancer landscapes.

The mechanism controlling the dynamic targeting of SWI/SNF has long been postulated to be coordinated by transcription factors (TFs), yet demonstrating a specific TF influence has proven difficult. Here we take a multi-omics approach to interrogate transient SWI/SNF interactors, chromatin targeting and the resulting three-dimensional epigenetic landscape. We utilize the labeling technique TurboID to map the SWI/SNF interactome and identify the activator protein-1 (AP-1) family members as critical interacting partners for SWI/SNF complexes. CUT&RUN profiling demonstrates SWI/SNF targeting enrichment at AP-1 bound loci, as well as SWI/SNF-AP-1 cooperation in chromatin targeting. HiChIP reveals AP-1-SWI/SNF-dependent restructuring of the three-dimensional promoter-enhancer architecture and generation of enhancer hubs. Through interrogation of the SWI/SNF-AP-1 interaction, we demonstrate an SWI/SNF dependency on AP-1-mediated chromatin localization. We propose that pioneer factors, such as AP-1, bind and target SWI/SNF to inactive chromatin, where it restructures the genomic landscape into an active state through epigenetic rewiring spanning multiple dimensions.

Partner bereavement when parenting dependent children: What factors influence adjustment?

Little is known about those who are widowed while raising dependent children. This study aimed to explore the factors which influence adjustment to partner death. Seven fathers and five mothers were interviewed, and constructivist grounded theory was used. Three interrelated themes were identified: Interpersonal influences, Intrapersonal influences, and Contextual influences. Dependent children meant sole responsibility and increased demands, yet ultimately provided widowed parents a purpose. Participants highlighted the need for increased awareness of young widowhood at a systemic and cultural level, to improve communication around death and young widowhood. Implications included social, financial and therapeutic interventions.

Antipsychotic prescribing in GMS paediatric and young adult population in Ireland 2005-2015: repeated cross-sectional study.

OBJECTIVES: To examine the rates of antipsychotic prescribing in the Irish paediatric and young adult population enrolled in the Irish General Medical Services Scheme pharmacy claims database from the Health Service Executive Primary Care Reimbursement Services database, with a focus on age and sex differences. To examine concomitant prescribing of certain other related medicines in this population. METHODS: Data were obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive (HSE) - Primary Care Reimbursement Services (PCRS). Participants included children aged <16 years and youth aged 16-24 years availing of medicines under the HSE-PCRS GMS scheme between January 2005 and December 2015. Outcome measures included prescribing rates of antipsychotics from 2005 to 2015, differences in prescribing rates between different ages and sexes, and percentage of concomitant prescriptions for antidepressants, psychostimulants, anxiolytics and hypnosedatives. RESULTS: Overall the trend in prescribing rates of antipsychotic medications was stable at 3.94/1000 in 2005 compared with 3.97/1000 in 2015 for children <16 years, and 48.37/1000 eligible population in 2005 compared to 39.64/1000 in 2015 for those aged 16-24. There was a significant decrease in prescribing rates for males in the 16-24 age group. CONCLUSIONS: While rates of antipsychotic prescribing have decreased or remained stable over the timeframe of the study, we did find a significant proportion of this population were prescribed antipsychotics. This study also shows that co-prescribing of antidepressants increased and highlights the need for guidelines for antipsychotic prescribing in children and youth in terms of clinical indication, monitoring, co-prescribing and treatment duration.

A scoping review protocol of the rehabilitation needs of people with brain tumours.

Background: Every year 480 people are diagnosed with a primary brain tumour in Ireland. Brain tumours can vary in type, location, treatment, and progression but neurological impairments are a consistent feature. Such neurological disability creates significant symptom burden that can seriously impact peoples' functional ability and quality of life. Rehabilitation can improve functional prognosis (motor and cognitive) and quality of life in people with brain tumours. However, research and experience consistently show that people with brain tumours can have difficulties accessing rehabilitation services. Our scoping review will investigate the research evidence concerning the rehabilitation needs of people with brain tumours. Methods: The scoping review will be conducted in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) reporting guidelines. Relevant databases (PubMed, Embase, CINAHL+, PsychINFO, PEDro) and grey literature sources will be searched. Publications relating to international rehabilitation practices will be included. A data extraction table will be created to facilitate narrative synthesis of the results. Conclusions: This scoping review will examine the scope of the literature on the rehabilitation needs of people with brain tumours. The findings will inform a research project entitled "Surgery, radiotherapy, chemotherapy, but now what? Exploring the rehabilitation needs of people with brain tumours in Ireland". An article reporting the results of the scoping review will be submitted to a scientific journal and presented at relevant national and international conferences.

A double-blind randomised crossover trial of low-dose flumazenil for benzodiazepine withdrawal: A proof of concept.

INTRODUCTION: Benzodiazepines (BZD) are a class of anxiolytics with varying uses, which primarily act on the GABAA receptor resulting in hyperpolarisation. BZDs are often a difficult drug class to cease once neuroadaptation has occurred; recommendations usually involve gradual dose reductions at variable rates. A growing body of evidence has suggested that low-dose flumazenil, a GABAA receptor antagonist, may be a useful agent to allow for rapid detoxification. AIM: To collect pilot data on the safety and efficacy of low-dose subcutaneous flumazenil to reduce BZD use, withdrawal symptoms, and craving in participants taking above and below the therapeutic maximum diazepam equivalent of 30 mg to inform on sample size for future trials. METHOD: In a randomised double-blinded crossover study design, participants received low-dose flumazenil first (4 mg/24 h for approximately eight days) or placebo first. Groups were divided into those taking < 30 mg diazepam equivalent and ≥ 30 mg diazepam equivalent at baseline. Main outcome measures were percentage reduction in daily diazepam use, withdrawal symptoms, and craving scores from baseline, difference in diazepam use across the placebo first group, and flumazenil related adverse events. RESULTS: Twenty-eight participants were recruited and randomised to flumazenil first (n = 14) and placebo first (n = 14). In participants taking ≥ 30 mg diazepam equivalent at baseline (n = 15), flumazenil significantly reduced diazepam use by 30.5% (p = 0.024) compared to placebo. CONCLUSION: Low-dose flumazenil may aid in BZD detoxification in participants taking daily diazepam equivalent doses greater than or equal to the therapeutic maximum (≥30 mg) by reducing the need for diazepam.

Evaluating suitability of saliva to measure steroid concentrations in grey seal pups.

Measurement of steroids in wild pinnipeds can facilitate assessment of breeding, nutritional and stress status, and is useful in understanding behavioral responses. Even in young animals, sex steroids may be important in behavioral interactions and immune modulation. Use of saliva can avoid the large fluctuations seen in some steroids in plasma, and can negate the need for venipuncture, making it a potentially useful matrix in the wildlife. However, its utility in estimating steroid levels in wild young pinnipeds has not been evaluated. Here, we investigated the suitability of saliva for steroid hormone analysis in wild grey seal pups during their suckling and post-weaning fast periods. We collected saliva (n = 38) and plasma (n = 71) samples during the breeding season on the Isle of May, Scotland, 2012. We investigated success of sample collection, ease of preparation, accuracy and precision of analysis, and, where possible, comparability of measurements (n = 27) from saliva and plasma. Plasma sampling was rapid, whereas sampling saliva took up to five times longer. Analytical performance criteria (parallelism, accuracy, and precision (intra and inter assay co-efficient of variation (% CV)) of commercial ELISA kits to measure estradiol, testosterone and cortisol in both matrices were assessed. Estradiol and cortisol assays performed well and can be used in plasma and saliva. However, we could not confidently validate testosterone for either matrix. Saliva estradiol correlated with levels in plasma. Saliva sample preparation was faster and simpler than plasma preparation because it did not require extraction. However, given the additional time taken to obtain saliva in the wild, the possibility of blood contamination from oral damage and the lower success rate in obtaining sufficient sample for analysis, we recommend that this matrix only be used as an alternative to plasma sampling measurement in pinnipeds when animals are anaesthetized, tolerate mouth swabbing, or have been trained to accept saliva sampling in captivity.

Modeling Noise-Related Timbre Semantic Categories of Orchestral Instrument Sounds With Audio Features, Pitch Register, and Instrument Family.

Audio features such as inharmonicity, noisiness, and spectral roll-off have been identified as correlates of "noisy" sounds. However, such features are likely involved in the experience of multiple semantic timbre categories of varied meaning and valence. This paper examines the relationships of stimulus properties and audio features with the semantic timbre categories raspy/grainy/rough, harsh/noisy, and airy/breathy. Participants (n = 153) rated a random subset of 52 stimuli from a set of 156 approximately 2-s orchestral instrument sounds representing varied instrument families (woodwinds, brass, strings, percussion), registers (octaves 2 through 6, where middle C is in octave 4), and both traditional and extended playing techniques (e.g., flutter-tonguing, bowing at the bridge). Stimuli were rated on the three semantic categories of interest, as well as on perceived playing exertion and emotional valence. Correlational analyses demonstrated a strong negative relationship between positive valence and perceived physical exertion. Exploratory linear mixed models revealed significant effects of extended technique and pitch register on valence, the perception of physical exertion, raspy/grainy/rough, and harsh/noisy. Instrument family was significantly related to ratings of airy/breathy. With an updated version of the Timbre Toolbox (R-2021 A), we used 44 summary audio features, extracted from the stimuli using spectral and harmonic representations, as input for various models built to predict mean semantic ratings for each sound on the three semantic categories, on perceived exertion, and on valence. Random Forest models predicting semantic ratings from audio features outperformed Partial Least-Squares Regression models, consistent with previous results suggesting that non-linear methods are advantageous in timbre semantic predictions using audio features. Relative Variable Importance measures from the models among the three semantic categories demonstrate that although these related semantic categories are associated in part with overlapping features, they can be differentiated through individual patterns of audio feature relationships.

The validation of contemporary body composition methods in various races and ethnicities.

Few investigations have evaluated the validity of current body composition technology among racially and ethnically diverse populations. This study assessed the validity of common body composition methods in a multi-ethnic sample stratified by race and ethnicity. One hundred and ten individuals (55 % female, age: 26·5 (sd 6·9) years) identifying as Asian, African American/Black, Caucasian/White, Hispanic, Multi-racial and Native American were enrolled. Seven body composition models (dual-energy X-ray absorptiometry (DXA), air displacement plethysmography (ADP), two bioelectrical impedance devices (BIS, IB) and three multi-compartment models) were evaluated against a four-compartment criterion model by assessing total error (TE) and standard error of the estimate. For the total sample, measures of % fat and fat-free mass (FFM) from multi-compartment models were all excellent to ideal (% fat: TE = 0·94-2·37 %; FFM: TE = 0·72-1·78 kg) compared with the criterion. % fat measures were very good to excellent for DXA, ADP and IB (TE = 2·52-2·89 %) and fairly good for BIS (TE = 4·12 %). For FFM, single device estimates were good (BIS; TE = 3·12 kg) to ideal (DXA, ADP, IB; TE = 1·21-2·15 kg). Results did not vary meaningfully between each race and ethnicity, except BIS was not valid for African American/Black, Caucasian/White and Multi-racial participants for % fat (TE = 4·3-4·9 %). The multi-compartment models evaluated can be utilised in a multi-ethnic sample and in each individual race and ethnicity to obtain highly valid results for % fat and FFM. Estimates from DXA, ADP and IB were also valid. The BIS may demonstrate greater TE for all racial and ethnic cohorts and results should be interpreted cautiously.

Contexts and mechanisms relevant to General Practitioner (GP) based interventions to reduce adverse drug events (ADE) in community dwelling older adults: a rapid realist review.

Background: Older adults in Ireland are at increased risk of adverse drug events (ADE) due, in part, to increasing rates of polypharmacy. Interventions to reduce ADE in community dwelling older adults (CDOA) have had limited success, therefore, new approaches are required.A realist review uses a different lens to examine why and how interventions were supposed to work rather than if, they worked. A rapid realist review (RRR) is a more focused and accelerated version.The aim of this RRR is to identify and examine the contexts and mechanisms that play a role in the outcomes relevant to reducing ADE in CDOA in the GP setting that could inform the development of interventions in Ireland. Methods: Six candidate theories (CT) were developed, based on knowledge of the field and recent literature, in relation to how interventions are expected to work. These formed the search strategy. Eighty full texts from 633 abstracts were reviewed, of which 27 were included. Snowballing added a further five articles, relevant policy documents increased the total number to 45. Data were extracted relevant to the theories under iteratively developed sub-themes using NVivo software. Results: Of the six theories, three theories, relating to GP engagement in interventions, relevance of health policy documents for older adults, and shared decision-making, provided data to guide future interventions to reduce ADEs for CDOA in an Irish setting. There was insufficient data for two theories, a third was rejected as existing barriers in the Irish setting made it impractical to use. Conclusions: To improve the success of Irish GP based interventions to reduce ADEs for CDOA, interventions must be relevant and easily applied in practice, supported by national policy and be adequately resourced. Future research is required to test our theories within a newly developed intervention.

Changes in Bone Mineral Density Following Conventional Oral Phosphonate Treatment of Hypophosphatemic Osteomalacia: A Non-Randomized Controlled Study.

PURPOSE: There are limited clinical studies aimed at solving the problem of the efficiency of conventional treatment with oral phosphate and calcitriol in adults with hypophosphatemic osteomalacia (HO). In addition, there still had no good non-hazardous markers to evaluate the severity of bone loss of osteomalacia before and after treatment. Therefore, the purpose of this study was to assess the efficacy of conventional treatment with a self-blended phosphate supplementation and calcitriol on patients with HO and whether bone mineral density (BMD) can be helpful for monitoring the efficacy. PATIENTS AND METHODS: A total of 21 HO patients and 105 healthy controls were enrolled. All patients were tested for serum biomarkers and BMD of the lumbar spine (L1-L4), femoral neck, and total left hip. After three years of treatment, 11 of 21 HO patients were recalled for BMD measurement. According to the administration of drugs, HO patients with calcium and calcitriol were divided into three phosphate treatment groups: patients in group A (n = 3) received continuous phosphate supplementation, patients in group B (n = 5) received intermittent phosphate supplementation and patients in group C (n = 3) received no phosphate supplementation. RESULTS: The diagnoses of 21 HO patients were 5 cases of hereditary hypophosphatemic rickets, 4 cases of Fanconi syndrome with the features of renal tubular acidosis and vitamin D deficiency, and 12 cases of hereditary vitamin D abnormality. The average initial serum phosphorus level of the patient group was approximately 50% lower than that of the control group. Lower BMD was significantly observed in the HO group than the control group at the lumbar spine and total hip. Continuous treatment with the phosphate supplement could increase BMD in the lumbar spine and total hip by 33.4-52.3% and in the femoral neck increased by 43.2-79.3% compared with baseline, and the effect appears to be continued once treatment is discontinued. CONCLUSION: These findings suggest that conventional therapy can improve bone mineral defects in patients with HO, especially in the femoral neck. Detection of BMD in HO patients is a good tool to assess the extent of bone defects and the therapeutic effect. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-16010095. Registered 7 December 2016. Retrospectively registered.

A pose-independent method for accurate and precise body composition from 3D optical scans.

OBJECTIVE: The aim of this study was to investigate whether digitally re-posing three-dimensional optical (3DO) whole-body scans to a standardized pose would improve body composition accuracy and precision regardless of the initial pose. METHODS: Healthy adults (n = 540), stratified by sex, BMI, and age, completed whole-body 3DO and dual-energy X-ray absorptiometry (DXA) scans in the Shape Up! Adults study. The 3DO mesh vertices were represented with standardized templates and a low-dimensional space by principal component analysis (stratified by sex). The total sample was split into a training (80%) and test (20%) set for both males and females. Stepwise linear regression was used to build prediction models for body composition and anthropometry outputs using 3DO principal components (PCs). RESULTS: The analysis included 472 participants after exclusions. After re-posing, three PCs described 95% of the shape variance in the male and female training sets. 3DO body composition accuracy compared with DXA was as follows: fat mass R2 = 0.91 male, 0.94 female; fat-free mass R2 = 0.95 male, 0.92 female; visceral fat mass R2 = 0.77 male, 0.79 female. CONCLUSIONS: Re-posed 3DO body shape PCs produced more accurate and precise body composition models that may be used in clinical or nonclinical settings when DXA is unavailable or when frequent ionizing radiation exposure is unwanted.

Shock Ignition Laser-Plasma Interactions in Ignition-Scale Plasmas.

We use a subignition scale laser, the 30 kJ Omega, and a novel shallow-cone target to study laser-plasma interactions at the ablation-plasma density scale lengths and laser intensities anticipated for direct drive shock-ignition implosions at National Ignition Facility scale. Our results show that, under these conditions, the dominant instability is convective stimulated Raman scatter with experimental evidence of two plasmon decay (TPD) only when the density scale length is reduced. Particle-in-cell simulations indicate this is due to TPD being shifted to lower densities, removing the experimental back-scatter signature and reducing the hot-electron temperature. The experimental laser energy-coupling to hot electrons was found to be 1%-2.5%, with electron temperatures between 35 and 45 keV. Radiation-hydrodynamics simulations employing these hot-electron characteristics indicate that they should not preheat the fuel in MJ-scale shock ignition experiments.

Brine-driven destruction of clay minerals in Gale crater, Mars.

Mars' sedimentary rock record preserves information on geological (and potential astrobiological) processes that occurred on the planet billions of years ago. The Curiosity rover is exploring the lower reaches of Mount Sharp, in Gale crater on Mars. A traverse from Vera Rubin ridge to Glen Torridon has allowed Curiosity to examine a lateral transect of rock strata laid down in a martian lake ~3.5 billion years ago. We report spatial differences in the mineralogy of time-equivalent sedimentary rocks <400 meters apart. These differences indicate localized infiltration of silica-poor brines, generated during deposition of overlying magnesium sulfate-bearing strata. We propose that destabilization of silicate minerals driven by silica-poor brines (rarely observed on Earth) was widespread on ancient Mars, because sulfate deposits are globally distributed.

Stability of hippocampal subfield volumes after trauma and relationship to development of PTSD symptoms.

BACKGROUND: The hippocampus plays a central role in post-traumatic stress disorder (PTSD) pathogenesis, and the majority of neuroimaging research on PTSD has studied the hippocampus in its entirety. Although extensive literature demonstrates changes in hippocampal volume are associated with PTSD, fewer studies have probed the relationship between symptoms and the hippocampus' functionally and structurally distinct subfields. We utilized data from a longitudinal study examining post-trauma outcomes to determine whether hippocampal subfield volumes change post-trauma and whether specific subfields are significantly associated with, or prospectively related to, PTSD symptom severity. As a secondary aim, we leveraged our unique study design sample to also investigate reliability of hippocampal subfield volumes using both cross-sectional and longitudinal pipelines available in FreeSurfer v6.0. METHODS: Two-hundred and fifteen traumatically injured individuals were recruited from an urban Emergency Department. Two-weeks post-injury, participants underwent two consecutive days of neuroimaging (time 1: T1, and time 2: T2) with magnetic resonance imaging (MRI) and completed self-report assessments. Six-months later (time 3: T3), participants underwent an additional scan and were administered a structured interview assessing PTSD symptoms. First, we calculated reliability of hippocampal measurements at T1 and T2 (automatically segmented with FreeSurfer v6.0). We then examined the prospective (T1 subfields) and cross-sectional (T3 subfields) relationship between volumes and PTSD. Finally, we tested whether change in subfield volumes between T1 and T3 explained PTSD symptom variability. RESULTS: After controlling for sex, age, and total brain volume, none of the subfield volumes (T1) were prospectively related to T3 PTSD symptoms nor were subfield volumes (T3) associated with current PTSD symptoms (T3). Tl - T2 reliability of all hippocampal subfields ranged from good to excellent (intraclass correlation coefficient (ICC) values > 0.83), with poorer reliability in the hippocampal fissure. CONCLUSION: Our study was a novel examination of the prospective relationship between hippocampal subfield volumes in relation to PTSD in a large trauma-exposed urban sample. There was no significant relationship between subfield volumes and PTSD symptoms, however, we confirmed FreeSurfer v6.0 hippocampal subfield segmentation is reliable when applied to a traumatically-injured sample, using both cross-sectional and longitudinal analysis pipelines. Although hippocampal subfield volumes may be an important marker of individual variability in PTSD, findings are likely conditional on the timing of the measurements (e.g. acute or chronic post-trauma periods) and analysis strategy (e.g. cross-sectional or prospective).