The coral reefs of the Pitcairn Islands are in one of the most remote areas of the Pacific Ocean, and yet they are exposed to the impacts of anthropogenic climate change. The Pitcairn Islands Marine Protected Area was designated in 2016 and is one of the largest in the world, but the marine environment around these highly isolated islands remains poorly documented. Evidence collated here indicates that while the Pitcairn Islands' reefs have thus far been relatively sheltered from the effect of warming sea temperatures, there is substantial risk of future coral decalcification due to ocean acidification. The projected acceleration in the rate of sea level rise, and the reefs' exposure to risks from distant ocean swells and cold-water intrusions, add further uncertainty as to whether these islands and their reefs will continue to adapt and persist into the future. Coordinated action within the context of the Pitcairn Islands Marine Protected Area can help enhance the resilience of the reefs in the Pitcairn Islands. Options include management of other human pressures, control of invasive species and active reef interventions. More research, however, is needed in order to better assess what are the most appropriate and feasible options to protect these reefs.

Epidemic intelligence activities are undertaken by the WHO Regional Office for Africa to support member states in early detection and response to outbreaks to prevent the international spread of diseases. We reviewed epidemic intelligence activities conducted by the organisation from 2017 to 2020, processes used, key results and how lessons learned can be used to strengthen preparedness, early detection and rapid response to outbreaks that may constitute a public health event of international concern. A total of 415 outbreaks were detected and notified to WHO, using both indicator-based and event-based surveillance. Media monitoring contributed to the initial detection of a quarter of all events reported. The most frequent outbreaks detected were vaccine-preventable diseases, followed by food-and-water-borne diseases, vector-borne diseases and viral haemorrhagic fevers. Rapid risk assessments generated evidence and provided the basis for WHO to trigger operational processes to provide rapid support to member states to respond to outbreaks with a potential for international spread. This is crucial in assisting member states in their obligations under the International Health Regulations (IHR) (2005). Member states in the region require scaled-up support, particularly in preventing recurrent outbreaks of infectious diseases and enhancing their event-based surveillance capacities with automated tools and processes.

We provide a new way of deriving a number of dynamic unobserved factors from a set of variables. We show how standard principal components may be expressed in state space form and estimated using the Kalman filter. To illustrate our procedure, we perform two exercises. First, we use it to estimate a measure of the current account imbalances among northern and southern euro area countries that developed during the period leading up to the outbreak of the euro area crisis, before looking at adjustment in the post-crisis period. Second, we show how these dynamic factors can improve forecasting of the euro exchange rate.

Animal-derived dietary protein ingestion and physical activity stimulate myofibrillar protein synthesis rates in older adults. We determined whether a non-animal-derived diet can support daily myofibrillar protein synthesis rates to the same extent as an omnivorous diet. Nineteen healthy older adults (aged 66 (sem 1) years; BMI 24 (sem 1) kg/m2; twelve males, seven females) participated in a randomised, parallel-group, controlled trial during which they consumed a 3-d isoenergetic high-protein (1·8 g/kg body mass per d) diet, where the protein was provided from predominantly (71 %) animal (OMNI; n 9; six males, three females) or exclusively vegan (VEG; n 10; six males, four females; mycoprotein providing 57 % of daily protein intake) sources. During the dietary control period, participants conducted a daily bout of unilateral resistance-type leg extension exercise. Before the dietary control period, participants ingested 400 ml of deuterated water, with 50-ml doses consumed daily thereafter. Saliva samples were collected throughout to determine body water 2H enrichments, and muscle samples were collected from rested and exercised muscle to determine daily myofibrillar protein synthesis rates. Deuterated water dosing resulted in body water 2H enrichments of approximately 0·78 (sem 0·03) %. Daily myofibrillar protein synthesis rates were 13 (sem 8) (P = 0·169) and 12 (sem 4) % (P = 0·016) greater in the exercised compared with rested leg (1·59 (sem 0·12) v. 1·77 (sem 0·12) and 1·76 (sem 0·14) v. 1·93 (sem 0·12) %/d) in OMNI and VEG groups, respectively. Daily myofibrillar protein synthesis rates did not differ between OMNI and VEG in either rested or exercised muscle (P > 0·05). Over the course of a 3-d intervention, omnivorous- or vegan-derived dietary protein sources can support equivalent rested and exercised daily myofibrillar protein synthesis rates in healthy older adults consuming a high-protein diet.

The Cal-DSH Diversion Guidelines provide 10 general guidelines that jurisdictions should consider when developing diversion programs for individuals with a serious mental illness (SMI) who become involved in the criminal justice system. Screening for SMI in a jail setting is reviewed. In addition, important treatment interventions for SMI and substance use disorders are highlighted with the need to address criminogenic risk factors highlighted.

Close double neutron stars (DNSs) have been observed as Galactic radio pulsars, while their mergers have been detected as gamma-ray bursts and gravitational wave sources. They are believed to have experienced at least one common envelope episode (CEE) during their evolution prior to DNS formation. In the last decades, there have been numerous efforts to understand the details of the common envelope (CE) phase, but its computational modelling remains challenging. We present and discuss the properties of the donor and the binary at the onset of the Roche lobe overflow (RLOF) leading to these CEEs as predicted by rapid binary population synthesis models. These properties can be used as initial conditions for detailed simulations of the CE phase. There are three distinctive populations, classified by the evolutionary stage of the donor at the moment of the onset of the RLOF: giant donors with fully convective envelopes, cool donors with partially convective envelopes, and hot donors with radiative envelopes. We also estimate that, for standard assumptions, tides would not circularise a large fraction of these systems by the onset of RLOF. This makes the study and understanding of eccentric mass-transferring systems relevant for DNS populations.

We analysed thirty-five 400-m2 plots encompassing forest, savanna and intermediate vegetation types in an ecotonal area in Ghana, West Africa. Across all plots, fire frequency was over a period of 15 years relatively uniform (once in 2–4 years). Although woodlands were dominated by species typically associated with savanna-type formations, and with forest formations dominated by species usually associated with closed canopies, these associations were non-obligatory and with a discrete non-specialized species grouping also identified. Across all plots, crown area index, stem basal area and above-ground biomass were positively associated with higher soil exchangeable potassium and silt contents: this supporting recent suggestions of interplays between potassium and soil water storage potential as a significant influence on tropical vegetation structure. We also found an average NDVI cover increase of ~0.15% year−1 (1984–2011) with plots dominated by non-specialized species increasing more than those dominated by either forest- or savanna-affiliated species. Our results challenge the traditional view of a simple forest vs. savanna dichotomy controlled by fire, and with our newly identified third non-specialized species grouping also potentially important in understanding ecotonal responses to climate change.

To investigate the extent of suspected hybridization between the brolga Antigone rubicunda and the Australian sarus crane Antigone antigone gillae, first noted in the 1970s, we analysed the genetic diversity of 389 feathers collected from breeding and flocking areas in north Queensland, Australia. We compared these with 15 samples from birds of known identity, or that were phenotypically typical. Bayesian clustering based on 10 microsatellite loci identified nine admixed birds, confirming that Australian cranes hybridize in the wild. Four of these were backcrosses, also confirming that wild Australian crane hybrids are fertile. Genetic analyses identified 10 times more hybrids than our accompanying visual field observations. Our analyses also provide the first definitive evidence that both brolgas and sarus cranes migrate between the Gulf Plains, the principal breeding area for sarus cranes, and major non-breeding locations on the Atherton Tablelands. We suggest that genetic analysis of shed feathers could potentially offer a cost-effective means to provide ongoing monitoring of this migration. The first observations of hybrids coincided with significantly increased opportunities for interaction between the two species when foraging on agricultural crops, which have developed significantly in the Atherton Tablelands flocking area since the 1960s. As the sarus crane is declining in much of its Asian range, challenges to the genetic integrity of the Australian sarus crane populations have international conservation significance.

Astrophysics Telescope for Large Area Spectroscopy Probe is a concept for a National Aeronautics and Space Administration probe-class space mission that will achieve ground-breaking science in the fields of galaxy evolution, cosmology, Milky Way, and the Solar System. It is the follow-up space mission to Wide Field Infrared Survey Telescope (WFIRST), boosting its scientific return by obtaining deep 1–4 μm slit spectroscopy for ∼70% of all galaxies imaged by the ∼2 000 deg2 WFIRST High Latitude Survey at z > 0.5. Astrophysics Telescope for Large Area Spectroscopy will measure accurate and precise redshifts for ∼200 M galaxies out to z < 7, and deliver spectra that enable a wide range of diagnostic studies of the physical properties of galaxies over most of cosmic history. Astrophysics Telescope for Large Area Spectroscopy Probe and WFIRST together will produce a 3D map of the Universe over 2 000 deg2, the definitive data sets for studying galaxy evolution, probing dark matter, dark energy and modifications of General Relativity, and quantifying the 3D structure and stellar content of the Milky Way. Astrophysics Telescope for Large Area Spectroscopy Probe science spans four broad categories: (1) Revolutionising galaxy evolution studies by tracing the relation between galaxies and dark matter from galaxy groups to cosmic voids and filaments, from the epoch of reionisation through the peak era of galaxy assembly; (2) Opening a new window into the dark Universe by weighing the dark matter filaments using 3D weak lensing with spectroscopic redshifts, and obtaining definitive measurements of dark energy and modification of General Relativity using galaxy clustering; (3) Probing the Milky Way’s dust-enshrouded regions, reaching the far side of our Galaxy; and (4) Exploring the formation history of the outer Solar System by characterising Kuiper Belt Objects. Astrophysics Telescope for Large Area Spectroscopy Probe is a 1.5 m telescope with a field of view of 0.4 deg2, and uses digital micro-mirror devices as slit selectors. It has a spectroscopic resolution of R = 1 000, and a wavelength range of 1–4 μm. The lack of slit spectroscopy from space over a wide field of view is the obvious gap in current and planned future space missions; Astrophysics Telescope for Large Area Spectroscopy fills this big gap with an unprecedented spectroscopic capability based on digital micro-mirror devices (with an estimated spectroscopic multiplex factor greater than 5 000). Astrophysics Telescope for Large Area Spectroscopy is designed to fit within the National Aeronautics and Space Administration probe-class space mission cost envelope; it has a single instrument, a telescope aperture that allows for a lighter launch vehicle, and mature technology (we have identified a path for digital micro-mirror devices to reach Technology Readiness Level 6 within 2 yr). Astrophysics Telescope for Large Area Spectroscopy Probe will lead to transformative science over the entire range of astrophysics: from galaxy evolution to the dark Universe, from Solar System objects to the dusty regions of the Milky Way.

Differential tree seedling recruitment across forest-savanna ecotones is poorly understood, but hypothesized to be influenced by vegetation cover and associated factors. In a 3-y-long field transplant experiment in the forest-savanna ecotone of Ghana, we assessed performance and root allocation of 864 seedlings for two forest (Khaya ivorensis and Terminalia superba) and two savanna (Khaya senegalensis and Terminalia macroptera) species in savanna woodland, closed-woodland and forest. Herbaceous vegetation biomass was significantly higher in savanna woodland (1.0 ± 0.4 kg m−2 vs 0.2 ± 0.1 kg m−2 in forest) and hence expected fire intensities, while some soil properties were improved in forest. Regardless, seedling survival declined significantly in the first-year dry-season for all species with huge declines for the forest species (50% vs 6% for Khaya and 16% vs 2% for Terminalia) by year 2. After 3 y, only savanna species survived in savanna woodland. However, best performance for savanna Khaya was in forest, but in savanna woodland for savanna Terminalia which also had the highest biomass fraction (0.8 ± 0.1 g g−1 vs 0.6 ± 0.1 g g−1 and 0.4 ± 0.1 g g−1) and starch concentration (27% ± 10% vs 15% ± 7% and 10% ± 4%) in roots relative to savanna and forest Khaya respectively. Our results demonstrate that tree cover variation has species-specific effects on tree seedling recruitment which is related to root storage functions.

OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common primary tumor type in the central nervous system across all age groups; affected adults have a life expectancy of just 14 months. As glioma cells invade the surrounding normal parenchyma they remodel the composition and ultrastructure of the surrounding extracellular matrix (ECM), suggesting that the native (i.e., “normal”) microenvironment is not ideal for their survival and proliferation. Recent reports describe suppressive and/or lethal effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic tissue resection in humans have never been reported to facilitate cancer recurrence. The objective of the present research is to evaluate mammalian ECM as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM hydrogels from porcine dermis, small intestine, and urinary bladder were produced as described previously. Primary glioma cells were graciously supplied by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through ATCC. Cells were plated onto tissue culture plastic at ~60% confluence and allowed to attach for 24 hours before treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing lyophilized, comminuted ECM with 0.9% saline for 24 hours then filtering the resulting mixture through a 10 kDa molecular weight cutoff column. All assays and kits were followed according to the manufacturer’s instructions. Cell viability was measured via MTT assay (Vybrant® MTT Cell Proliferation Assay, Invitrogen) and by live/dead staining (LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time lapse videos were created by taking images every 20 minutes for 18 hours (phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo work was conducted according to protocols approved by the University of Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS: ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder all decreased the viability of primary glioma cells in vitro, with urinary bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was sufficient to recapitulate this detrimental effect upon neoplastic cells in vitro and was used for the remainder of the experiments described herein. In a cell viability assay normalized to the media treatment, non-neoplastic CHME5 and N1E-115 cells scored 103% and 114% after 48 hours when treated with UBM-SSF and 2 primary high-grade glioma cell types scored 17% and 30.5% with UBM-SSF (n=2). Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of UBM-SSF for 18 hours while most primary glioma cells shriveled and died within this time. Darkfield time-lapse video of wells containing Nucview dye, fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In culture with primary astrocytes, high grade primary glioma cells, and U-87 MG glioma cells for 24 hours, UBM-SSF was found to significantly increase the population of primary astrocytes compared with media (p<0.05) while decreasing the 2 glioma cell types to approximately one-third as many cells as the media control (p<0.0001). A dose-response of temozolomide from 0 to 10,000 μM showed that when treating 2 non-neoplastic cell types (CHME5 and HFF) and 2 types of primary glioma cell there was no difference in survivability at any concentration. Contrasted to this, a dose-response of UBM-SSF from 350 to 7000 μg/mL showed that the non-neoplastic cells survived significantly better than the glioma cells at concentrations of 875 μg/mL and upward (p<0.05). In preliminary animal experiments, large primary glioma tumors in the flanks of athymic nude mice were resected and replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth if any compared with the dramatic recurrence seen in the Matrigel injection sites (n=2). In a separate survival study comparing PBS to UBM-SSF injections in the flank-resection model, all animals given PBS had to be sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ in 2005, the standard of care for patients with glioblastoma multiforme has not improved. These findings indicate that non-neoplastic ECM contains potent bioactive regulators capable of abrogating malignancy. Our in vitro data suggest these molecules appear to have no deleterious effect on non-neoplastic cells while specifically inducing apoptosis in glioma cells. Our in vivo data suggest that these molecules may be useful in delaying glioma recurrence, thus resulting in extended lifespan. Delivering soluble fractions of ECM to a tumor site may represent a novel approach to glioma therapy, sidestepping traditional cytotoxic therapies in favor of utilizing putative endogenous anti-tumor pathways.

The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.

A sizeable proportion of households is forced to share single long-lasting insecticide treated net (LLIN). However, the relationship between increasing numbers of people sharing a net and the risk for Plasmodium infection is unclear. This study revealed whether risk for Plasmodium falciparum infection is associated with the number of people sharing a LLIN in a holoendemic area of Kenya. Children ⩽5 years of age were tested for P. falciparum infection using polymerase chain reaction. Of 558 children surveyed, 293 (52.5%) tested positive for parasitaemia. Four hundred and fifty-eight (82.1%) reported sleeping under a LLIN. Of those, the number of people sharing a net with the sampled child ranged from 1 to 5 (median = 2). Children using a net alone or with one other person were at lower risk than non-users (OR = 0.29, 95% CI 0.10–0.82 and OR = 0.47, 95% CI 0.22–0.97, respectively). On the other hand, there was no significant difference between non-users and children sharing a net with two (OR = 0.88, 95% CI 0.44–1.77) or more other persons (OR = 0.75, 95% CI 0.32–1.72). LLINs are effective in protecting against Plasmodium infection in children when used alone or with one other person compared with not using them. Public health professionals should inform caretakers of the risks of too many people sharing a net.

This study determines the prevalence of inadequate micronutrient intakes consumed by long-term care (LTC) residents. This cross-sectional study was completed in thirty-two LTC homes in four Canadian provinces. Weighed and estimated food and beverage intake were collected over 3 non-consecutive days from 632 randomly selected residents. Nutrient intakes were adjusted for intra-individual variation and compared with the Dietary Reference Intakes. Proportion of participants, stratified by sex and use of modified (MTF) or regular texture foods, with intakes below the Estimated Average Requirement (EAR) or Adequate Intake (AI), were identified. Numbers of participants that met these adequacy values with use of micronutrient supplements was determined. Mean age of males (n 197) was 85·2 (sd 7·6) years and females (n 435) was 87·4 (sd 7·8) years. In all, 33 % consumed MTF; 78·2 % (males) and 76·1 % (females) took at least one micronutrient pill. Participants on a MTF had lower intake for some nutrients (males=4; females=8), but also consumed a few nutrients in larger amounts than regular texture consumers (males=4; females =1). More than 50 % of participants in both sexes and texture groups consumed inadequate amounts of folate, vitamins B6, Ca, Mg and Zn (males only), with >90 % consuming amounts below the EAR/AI for vitamin D, E, K, Mg (males only) and K. Vitamin D supplements resolved inadequate intakes for 50–70 % of participants. High proportions of LTC residents have intakes for nine of twenty nutrients examined below the EAR or AI. Strategies to improve intake specific to these nutrients are needed.