The gut microbiome is impacted by certain types of dietary fibre. However, the type, duration, and dose needed to elicit gut microbial changes, and whether these changes also influence microbial metabolites, remains unclear. This study investigated the effects of supplementing healthy participants with two types of non-digestible carbohydrates (resistant starch (RS) and polydextrose (PD)), on the stool microbiota and microbial metabolite concentrations in plasma, stool, and urine, as secondary outcomes in the Dietary Intervention Stem Cells and Colorectal Cancer (DISC) Study.

The DISC Study was a double-blind, randomised controlled trial that supplemented healthy participants with RS and/or PD or placebo for 50 days in a 2*2 factorial design. DNA was extracted from stool samples collected pre- and post-intervention, and V4 16S rRNA gene sequencing was used to profile the gut microbiota. Metabolite concentrations were measured in stool, plasma, and urine by high-performance liquid chromatography.

A total of 58 participants with paired samples available were included. After 50 days, no effects of RS or PD were detected on composition of the gut microbiota diversity (alpha- and beta-diversity), on genus relative abundance, or on metabolite concentrations. However, Drichlet’s multinomial mixture clustering-based approach suggests that some participants changed microbial enterotype post-intervention.

The gut microbiome and faecal, plasma, and urinary microbial metabolites were stable in response to a 50-day fibre intervention in middle aged adults. Larger and longer studies, including those which explore the effects of specific fibre sub-types, may be required to determine the relationships between fibre intake, the gut microbiome, and host-health.

We investigate structural features and processes associated with the onset of systemic conflict using an approach which integrates complex systems theory with network modeling and analysis. We present a signed network model of cooperation and conflict dynamics in the context of international relations between states. The model evolves ties between nodes under the influence of a structural balance force and a dyad-specific force. Model simulations exhibit a sharp bifurcation from peace to systemic war as structural balance pressures increase, a bistable regime in which both peace and war stable equilibria exist, and a hysteretic reverse bifurcation from war to peace. We show how the analytical expression we derive for the peace-to-war bifurcation condition implies that polarized network structure increases susceptibility to systemic war. We develop a framework for identifying patterns of relationship perturbations that are most destabilizing and apply it to the network of European great powers before World War I. We also show that the model exhibits critical slowing down, in which perturbations to the peace equilibrium take longer to decay as the system draws closer to the bifurcation. We discuss how our results relate to international relations theories on the causes and catalysts of systemic war.

Five international consensus statements on concussion in sports have been published. This commentary argues that there is a strong need for a new approach to them that foregrounds public health expertise and patient-centered guidance. Doing so will help players, parents and practitioners keep perspective about these potentially life-altering injuries especially when they recur.

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.

Medical care is predicated on ‘do no harm’, yet the urgency to find drugs and vaccines to treat or prevent COVID-19 has led to an extraordinary effort to develop and test new therapies. Whilst this is an essential cornerstone of a united global response to the COVID-19 pandemic, the absolute requirements for meticulous efficacy and safety data remain. This is especially pertinent to the needs of pregnant women; a group traditionally poorly represented in drug trials, yet a group at heightened risk of unintended adverse materno-fetal consequences due to the unique physiology of pregnancy and the life course implications of fetal or neonatal drug exposure. However, due to the complexities of drug trial participation when pregnant (be they vaccines or therapeutics for acute disease), many clinical drug trials will exclude them. Clinicians must determine the best course of drug treatment with a dearth of evidence from either clinical or preclinical studies, where at least in the short term they may be more focused on the outcome of the mother than of her offspring.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

OBJECTIVES/SPECIFIC AIMS: N/A. METHODS/STUDY POPULATION: Over a million people gained insurance in Los Angeles (LA) County under the Affordable Care Act (ACA). The vast majority gained Medicaid—government sponsored insurance with low-cost sharing. LA County also made significant investments in the safety net including a program called MyHealthLA, which provides primary and tertiary care for the residually uninsured including poor undocumented individuals at specific sites. Despite this insurance expansion, approximately 3 quarters of a million people in the county remain uninsured. Regardless of insurance status, nearly a quarter of LA County residents reported having difficulty obtaining needed medical care, and among those making less than the poverty level, 43% had difficulties. There is still much to understand about barriers to obtaining insurance and accessing healthcare in Los Angeles in the post-ACA era. Our primary objective was to understand how safety net patients are obtaining, maintaining and using their insurance after the ACA. Specifically we hope to understand the barriers and drivers of these three processes. RESULTS/ANTICIPATED RESULTS: We conducted a qualitative study of 34 safety net patients with 3 different insurance types in LA County. We conducted in-person interviews with adult patients (ages 18–64 years), who had either MediCal, MyHealthLA, or were unsinsured. Our interview guide was based on existing literature, a previous qualitative study conducted in Massachusetts and input from experts in the field. We pilot tested our interviews in English and Spanish and then recruited our participants from 3 sites: LAC+USC (a publically funded county hospital), The Wellness Center (a resource center for safety net patients), and White Memorial Medical Center (a private safety net hospital). We approached patients in the ED and urgent care waiting rooms and obtained informed consent for this IRB approved study. We excluded patients who were non-English and non-Spanish speaking or too ill to interview. We recorded interviews, which were then transcribed and translated into English by a contracted agency. We analyzed our interviews using a framework approach, which included a set of a priori codes from the literature as well as emerging codes from patient responses. We will check a sample of our transcripts for coding consistency (aiming for an inter-rater reliability of >80%). DISCUSSION/SIGNIFICANCE OF IMPACT: We recruited a diverse group of patients that were demographically representative of those who gained insurance under the ACA (childless adults making less than 138% of the Federal Poverty Level). Our preliminary results (based on 17 transcripts), suggest that patients, regardless of insurance type have difficulty accessing primary care. We identified seven domains under the broader theme of barriers to accessing primary care: finding a primary care clinic or physician (PCP), getting timely appointments, geography and transportation, continuity of care, using the Emergency Department (ED) or urgent care as a PCP, switching PCPs or clinics, and cost or coverage.

Internal gravity wave energy contributes significantly to the energy budget of the oceans, affecting mixing and the thermohaline circulation. Hence it is important to determine the internal wave energy flux $\boldsymbol{J}=p\,\boldsymbol{v}$, where $p$ is the pressure perturbation field and $\boldsymbol{v}$ is the velocity perturbation field. However, the pressure perturbation field is not directly accessible in laboratory or field observations. Previously, a Green’s function based method was developed to calculate the instantaneous energy flux field from a measured density perturbation field $\unicode[STIX]{x1D70C}(x,z,t)$, given a constant buoyancy frequency $N$. Here we present methods for computing the instantaneous energy flux $\boldsymbol{J}(x,z,t)$ for an internal wave field with vertically varying background $N(z)$, as in the oceans where $N(z)$ typically decreases by two orders of magnitude from the pycnocline to the deep ocean. Analytic methods are presented for computing $\boldsymbol{J}(x,z,t)$ from a density perturbation field for $N(z)$ varying linearly with $z$ and for $N^{2}(z)$ varying as $\tanh (z)$. To generalize this approach to arbitrary $N(z)$, we present a computational method for obtaining $\boldsymbol{J}(x,z,t)$. The results for $\boldsymbol{J}(x,z,t)$ for the different cases agree well with results from direct numerical simulations of the Navier–Stokes equations. Our computational method can be applied to any density perturbation data using the MATLAB graphical user interface ‘EnergyFlux’.

The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis as well as transcriptome data across 763 primary tumors. Characterization of CD271+ and CD271- cells by RNA sequencing revealed that these two subpopulations are molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling is upregulated in the CD271+ population and inhibiting this pathway reduced CD271 levels, stem/progenitor cell proliferation and cell survival as well as cell migration in vitro. Importantly, the MEK inhibitor selumetinib extends survival and reduces CD271 levels in vivo. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells.

OBJECTIVES/SPECIFIC AIMS: (1) Characterize the prevalence and initial pharmacological management of chronic pain syndromes during pregnancy in a women’s mental health program. (2) Describe the severity and qualitative characteristics of chronic pain during pregnancy and the acute postpartum period. (3) Compare obstetrical and neonatal outcomes between pregnant women with and without chronic pain syndromes. METHODS/STUDY POPULATION: A chart review was conducted to identify all pregnant women who presented for an initial evaluation to the Women’s Mental Health Program (WMHP) at the University of Arkansas for Medical Sciences from July 2013 to June 2016. We excluded respondents <18 years of age or who did not consent to having their information used for research purposes. Demographic information, past and current medical histories, and medication history were obtained from written and electronic medical records. Chronic pain complaints and medication history are presented as counts and percentages. In an ongoing prospective, longitudinal study of pregnant women with chronic pain, women are enrolled before 20 weeks gestation and followed throughout pregnancy and the first 3 months postpartum. Study visits occur at 4-week intervals; and pain characteristics, analgesic exposures, other medications, and depressive measures are collected. Obstetrical and neonatal outcomes are obtained following delivery. Subjects will be compared based on pain types (ie, neuropathic pain, non-neuropathic pain, and controls) and treatment exposures (eg, +/− opioids). Primary outcome measures include visual analog scale (VAS). Secondary outcome measures include other pain and depression assessments. Data will be analyzed using SAS 9.4. A p-value of<0.05 was considered statistically significant. RESULTS/ANTICIPATED RESULTS: (1) Chronic pain conditions were reported by 28.2% (44/156) of the initial referrals to the WMHP. (2) 95.5% of respondents with chronic pain were taking at least 1 medication, and 59.5% were taking 2 or more medications. Mean number of medications used were 2.6±2.1.3. The most common medications reported were acetaminophen (43.2%), opioids (43.2%), and sedative/hypnotics (36.4%). Non-pharmacological therapy (eg, physical therapy and transcutaneous electrical nerve stimulation) was reported by 20.5% of respondents. (4) We anticipate that measures of pain severity will increase in pregnancy, peak in the third trimester, and decline in the postpartum period. (5) We foresee that the prospective results will confirm the chart review as indicated by a higher rate of medication exposures during pregnancy, including non-analgesic medications in the women with chronic pain syndromes. (6) We expect women with chronic pain syndromes to have a higher rate of obstetrical complications, specifically pre-term delivery and operative delivery. (7) Finally, we anticipate that chronic pain syndromes and management will result in a higher rate of neonatal complications, specifically neonatal intensive care unit admission, neonatal respiratory problems, and small for gestational age infants. DISCUSSION/SIGNIFICANCE OF IMPACT: Chronic pain syndromes are prevalent in more than one-quarter of pregnant women in our study with the majority of women using pharmacological agents to manage their condition. This prevalence is greater or equal to than other common obstetrical conditions, such as gestational diabetes or preterm delivery. The novel prospective data will be germane to the clinical care of pregnant women with chronic pain disorders. Clinical practice will be better informed by our data regarding the potential impact of chronic pain and its management on pregnancy course and perinatal outcomes. These data will provide the initial foundation for the development of treatment guidelines for the management of chronic pain syndromes during the perinatal period.

We present a novel framework for finite element particle-in-cell methods based on the discretization of the underlying Hamiltonian structure of the Vlasov–Maxwell system. We derive a semi-discrete Poisson bracket, which retains the defining properties of a bracket, anti-symmetry and the Jacobi identity, as well as conservation of its Casimir invariants, implying that the semi-discrete system is still a Hamiltonian system. In order to obtain a fully discrete Poisson integrator, the semi-discrete bracket is used in conjunction with Hamiltonian splitting methods for integration in time. Techniques from finite element exterior calculus ensure conservation of the divergence of the magnetic field and Gauss’ law as well as stability of the field solver. The resulting methods are gauge invariant, feature exact charge conservation and show excellent long-time energy and momentum behaviour. Due to the generality of our framework, these conservation properties are guaranteed independently of a particular choice of the finite element basis, as long as the corresponding finite element spaces satisfy certain compatibility conditions.

Detailed, chronologically tightly constrained, lake-sediment-based geochemical and pollen records have enabled local changes in soil erosion, woodland cover and composition, and prehistoric farming impact to be reconstructed in considerable detail. The profile opens shortly after 7800 BC when tall canopy trees were well-established and presumably in equilibrium with their environment. A distinct perturbation that involved an increase in pine and birch, a decrease in oak and a minor opening-up of the woodland is regarded as the local expression of the 8.2 ka climate anomaly. Lack of response in the geochemical erosional indicators is interpreted as evidence for drier conditions. A short-lived, over-compensation in climate recovery followed the 8.2 ka event. Neolithic farming impact is clearly expressed in both the pollen and geochemical data. Both datasets indicate that Neolithic impact was concentrated in the early Neolithic (3715–3440 BC). In the interval 3000–2700 BC there appears to have been a break in farming activity. The pollen data suggest substantially increased farming impact (both arable and pastoral) in the Bronze Age, with maximum farming and woodland clearances taking place in the late Bronze Age (1155–935 BC). These developments are poorly expressed in the geochemical record, possibly due to within-lake changes.

Pathogenic animal trypanosomes affecting livestock have represented a major constraint to agricultural development in Africa for centuries, and their negative economic impact is increasing in South America and Asia. Chemotherapy and chemoprophylaxis represent the main means of control. However, research into new trypanocides has remained inadequate for decades, leading to a situation where the few compounds available are losing efficacy due to the emergence of drug-resistant parasites. In this review, we provide a comprehensive overview of the current options available for the treatment and prophylaxis of the animal trypanosomiases, with a special focus on the problem of resistance. The key issues surrounding the main economically important animal trypanosome species and the diseases they cause are also presented. As new investment becomes available to develop improved tools to control the animal trypanosomiases, we stress that efforts should be directed towards a better understanding of the biology of the relevant parasite species and strains, to identify new drug targets and interrogate resistance mechanisms.

Extremely low birth weight (ELBW; <1000 g) infants have been exposed to stressful intrauterine and early postnatal environments. Even greater early adversity has been experienced by ELBW survivors who were also born small for gestational age (SGA; <10th percentile for GA) compared to those born appropriate for GA (AGA). ELBW survivors, particularly those born SGA, face increased risk for internalizing problems compared to normal BW (NBW; ≥2500 g) controls. Internalizing problems are related to allelic variations in the promoter region of the serotonin transporter linked polymorphic region gene (5-HTTLPR). We followed the oldest longitudinal cohort of ELBW survivors to adulthood. Participants provided buccal cells and reported on internalizing problems, using the Young Adult Self-Report when they were in their mid-20s (ELBW/SGA, N = 28; ELBW/AGA, N = 60; NBW, N = 81) and mid-30s (ELBW/SGA, N = 27; ELBW/AGA, N = 58; NBW, N = 76). The findings indicate that ELBW/SGAs carrying the 5-HTTLPR short allele reported increased internalizing problems, particularly depression, during the third and fourth decades of life. This is the first known report on gene–environment interactions predicting psychopathology among ELBW survivors. Our findings elucidate putative neurobiological pathways that underlie risk for psychopathology.