Assessing Life-Space in a Population with Serious Mental Illness

BACKGROUND AND OBJECTIVE: The Life-Space Assessment (LSA) is a validated tool that quantitatively measures mobility patterns in community dwelling older adults. Decreased life-space in this population is generally a strong indicator of limited physical function. However in a population with serious mental illness (SMI), decreased life-space may be an indicator of other impairments and barriers pertaining to mental, physical and psychosocial health. Measuring life-space in this population offers a novel opportunity that could address these underlying associations. Specific interventions could target ways to improve mobility once the associations are examined. METHODS: A secondary analysis from the ACHIEVE trial was conducted. The trial was a successful behavioural weight-loss intervention that focused on promoting physical activity and healthy eating for persons with SMI. Life-space measurements were measured at baseline, 6-month and 18-month follow-up visits. Four different sub-scales measured life-space: the composite sub-scale, a daily sub-scale and a daily sub-scale for days when a person visited a psychiatric rehabilitation program (PRP) or did not. Measures pertaining to mental, physical and psychosocial health were assessed for their relationship on life-space at baseline and over follow-up. RESULTS: For 198 participants at baseline the mean age was 45.5 (SD=11.0), over 55% had schizophrenia or a schizoaffective disorder, 22% had bipolar disorder, 14% had major depressive disorder, and about 63% of the whole population presented with depressive symptoms based on the CES-D cut-off of 16 points or more. Positive affect was associated with an increase in all four of the LSA sub-scales at baseline while somatic symptoms were associated with a decrease in the daily sub-scale. Over time, decreasing life-space was associated with depressed affect and fewer activities with neighbors for days in which participants did not go to the PRP, but not for days in which they did. A decreasing life-space composite score and daily score were associated with problems surrounding interpersonal relationships and less social cohesion, respectively. CONCLUSION: The findings of this study suggests that life-space can be used to assess mobility patterns for persons with SMI and that this dimension of health can provide insight into a previously undocumented measure of health. The associations were more pronounced on days that individuals did not visit the PRP, indicating that social isolation could be associated with reduced mobility. The association between decreasing life-space and worse health outcomes that have been established in community dwelling older adults were also observed in this population. Promoting social engagement could increase mobility as well as subsequent health in this population

Rotational Grazing Increases Wool and Lamb Production from Phalaris-Subterranean Clover Pastures in South Eastern Australia

Wool and lamb production from different grazing systems was compared in a Mediterranean environment near Hamilton in southeastern Australia. The grazing systems were based on combinations of fertiliser inputs and grazing methods that could promote the growth and persistence of phalaris (Phalaris aquatica) and increase animal production compared to ‘typical’ unimproved pastures. In the first 2 years of this experiment, the most productive systems more than doubled ewe stocking rate and wool production, and more than trebled lamb production per hectare, compared to ‘typical’ unimproved pasture, low fertility, set-stocked systems. The change to a well fertilised phalaris/subterranean clover (Trifolium subterraneum) pasture system accounted for 50-80% of these gains in productivity per hectare, with additional benefits from applying extra phosphorus (P) fertiliser and rotational grazing. These results show the potential for producers to adopt simple changes in management practices that can significantly increase wool and lamb production in southeastern Australia

A Recombinant Blood-Stage Malaria Vaccine Reduces Plasmodium falciparum Density and Exerts Selective Pressure on Parasite Populations in a Phase 1-2b Trial in Papua New Guinea

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic type

Molecular Identification of a Malaria Merozoite Surface Sheddase

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface “sheddase,” but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite

The Partisan Republic: Democracy. Exclusion, the the Fall of the Founders\u27 Constitution, 1780s-1830s

This article is a forum on Gerald Leonard and Saul Cornell\u27s The Partisan Republic: Democracy. Exclusion, and the Fall of the Founders\u27 Constitution, 1780s-1830s (Cambridge University Press, 2019). ISBN 978-1-107-02416-8 Roundtable Contents: Introduction by Matthew Crow, Hobart and William Smith Colleges Review by Katlyn Marie Carter, University of Notre Dame Review by Graham G. Dodds, Concordia University, Montreal, Canada Review by Jessica K. Lowe, University of Virginia School of Law Review by Stephen J. Rockwell, St. Joseph\u27s University Author\u27s Response by Saul Cornell, Fordham University Author\u27s Response by Gerald Leonard, Boston Universit

Crystal Structure of Plasmodium knowlesi Apical Membrane Antigen 1 and Its Complex with an Invasion-Inhibitory Monoclonal Antibody

The malaria parasite Plasmodiumknowlesi, previously associated only with infection of macaques, is now known to infect humans as well and has become a significant public health problem in Southeast Asia. This species should therefore be targeted in vaccine and therapeutic strategies against human malaria. Apical Membrane Antigen 1 (AMA1), which plays a role in Plasmodium merozoite invasion of the erythrocyte, is currently being pursued in human vaccine trials against P. falciparum. Recent vaccine trials in macaques using the P. knowlesi orthologue PkAMA1 have shown that it protects against infection by this parasite species and thus should be developed for human vaccination as well. Here, we present the crystal structure of Domains 1 and 2 of the PkAMA1 ectodomain, and of its complex with the invasion-inhibitory monoclonal antibody R31C2. The Domain 2 (D2) loop, which is displaced upon binding the Rhoptry Neck Protein 2 (RON2) receptor, makes significant contacts with the antibody. R31C2 inhibits binding of the Rhoptry Neck Protein 2 (RON2) receptor by steric blocking of the hydrophobic groove and by preventing the displacement of the D2 loop which is essential for exposing the complete binding site on AMA1. R31C2 recognizes a non-polymorphic epitope and should thus be cross-strain reactive. PkAMA1 is much less polymorphic than the P. falciparum and P. vivax orthologues. Unlike these two latter species, there are no polymorphic sites close to the RON2-binding site of PkAMA1, suggesting that P. knowlesi has not developed a mechanism of immune escape from the host’s humoral response to AMA1

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Purification of antibodies to O antigen of Salmonella Typhimurium from human serum by affinity chromatography

AbstractNontyphoidal Salmonellae (NTS) are a common cause of bacteraemia in children and HIV-infected adults in Sub-Saharan Africa. We have previously shown that antibodies play a key role in both bactericidal and cellular mechanisms of immunity to NTS, but found that high concentrations of antibody to Salmonella Typhimurium O antigen (OAg) in the serum of some HIV-infected African adults is associated with impaired killing of NTS. To further investigate the function of antibodies to the OAg of NTS, we developed a method to purify these antibodies from human serum by affinity chromatography. Purified Salmonella Typhimurium OAg was activated with adipic acid dihydrazide (ADH) via two different chemistries before linking to N-hydroxysuccinamide-Sepharose resin: one ADH molecule was introduced per OAg chain on its terminal 3-deoxy-D-manno-octulosonic acid sugar (OAg–ADH), or multiple ADH molecules were attached along the OAg chain after oxidation with sodium periodate (OAgoxADH). Both resulting columns worked well when tested with commercial polyclonal anti-O:4,5 antibodies from rabbit serum. Over 90% of the applied antibodies bound to the resin and 89% of these antibodies were then eluted as detected by ELISA. OAg–ADH was preferred as the method for OAg derivatisation as it does not modify the saccharide chain and can be applied to OAg from different bacteria. Both columns were able to bind OAg-specific antibodies in human serum, but antibody recovery was initially low. Different elution buffers were tested and different amounts of OAg–ADH were linked to the resin to improve the yield. Optimal recovery (51%) was obtained by loading 1mg of activated OAg per ml of resin and eluting with 0.1M glycine, 0.1M NaCl pH2.4. The column matrix could be regenerated following elution with no detectable loss in performance for over ten uses. This method offers the potential to purify antibodies to Salmonella OAg from polyclonal serum following vaccination or natural exposure to Salmonella and so investigate the functionality and diversity of the antibody response to OAg

Orbital decay in an accreting and eclipsing 13.7 minute orbital period binary with a luminous donor

We report the discovery of ZTF J0127+5258, a compact mass-transferring binary with an orbital period of 13.7 minutes. The system contains a white dwarf accretor, which likely originated as a post-common envelope carbon-oxygen (CO) white dwarf, and a warm donor ($T_{\rm eff,\,donor}= 16,400\pm1000\,\rm K$). The donor probably formed during a common envelope phase between the CO white dwarf and an evolving giant which left behind a helium star or helium white dwarf in a close orbit with the CO white dwarf. We measure gravitational wave-driven orbital inspiral with $\sim 35\sigma$ significance, which yields a joint constraint on the component masses and mass transfer rate. While the accretion disk in the system is dominated by ionized helium emission, the donor exhibits a mixture of hydrogen and helium absorption lines. Phase-resolved spectroscopy yields a donor radial-velocity semi-amplitude of $771\pm27\,\rm km\, s^{-1}$, and high-speed photometry reveals that the system is eclipsing. We detect a {\it Chandra} X-ray counterpart with $L_{X}\sim 3\times 10^{31}\,\rm erg\,s^{-1}$. Depending on the mass-transfer rate, the system will likely evolve into either a stably mass-transferring helium CV, merge to become an R Crb star, or explode as a Type Ia supernova in the next million years. We predict that the Laser Space Interferometer Antenna (LISA) will detect the source with a signal-to-noise ratio of $24\pm6$ after 4 years of observations. The system is the first \emph{LISA}-loud mass-transferring binary with an intrinsically luminous donor, a class of sources that provide the opportunity to leverage the synergy between optical and infrared time domain surveys, X-ray facilities, and gravitational-wave observatories to probe general relativity, accretion physics, and binary evolution.Comment: 13 pages, 7 figures, 2 tables, submitted to ApJ