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People with dementia and their care partners report a lack of support, treatment, and information, fragmented services, and a lack of inclusion in decisions about their care. Care planning may address these issues; however, there is scarce literature on the process or benefits of care planning for people with dementia. This review describes the literature on care planning for community-dwelling people with dementia and their care partners. A systematic scoping methodology was followed to identify the research questions, identify relevant documents, select relevant documents, chart the data, and collate, summarise, and report the results. 31 full-text documents published between 2010 and May 2020 were identified and reviewed. Seven were guidelines, seven were expert opinion pieces, 11 were intervention studies, and six were descriptive studies. The topics and process of care planning varied depending on the service context (e.g., memory clinic, home care, and primary care). Care planning was presented as a component of case management in 15 papers. Six of the 11 intervention studies reported positive outcomes, one showed no improvement, and one did not evaluate outcomes for people with dementia or their care partners. Of the six with positive outcomes, four evaluated care planning in the context of care management. There is limited evidence that care planning alone improves outcomes for people with dementia and their care partners. It is unclear whether it may have benefits when combined with care management.

Attacks of hereditary angioedema are attributed to excessive plasma kallikrein (PKa) activity, which cleaves high-molecular-weight kininogen to generate the proinflammatory hormone bradykinin.We evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KVD900, an orally administered inhibitor of PKa in healthy adults.KVD900 was administered in 2 clinical studies. In the first study, healthy adult men received single ascending doses (5-600 mg) of KVD900 capsule or placebo, single 100 mg doses of KVD900 tablet and KVD900 capsule (crossover), and single 600 mg doses of KVD900 (6 × 100 mg tablets) under fed and fasting conditions (crossover). In a second study, 3 cohorts of healthy adults were provided 600 mg of KVD900 tablets at 8-, 4-, and 2-hour intervals.Overall, 98 healthy participants received KVD900. All adverse events (AEs) were mild, except for a single moderate AE (headache). Exposure to KVD900 was proportional to dose. The PK parameters for KVD900 600 mg in tablet form under fasted conditions were mean (coefficient of variation) maximum plasma concentration of 6460 (22.0) ng/mL, mean (coefficient of variation) area under the curve (AUCThese phase 1 studies evaluated the PK/PD profile of KVD900, showing that KVD900 rapidly achieves near-complete PKa inhibition and is generally safe and well tolerated.NCT04349800.

Engaging end user groups with machine learning (ML) models can help align the design of predictive systems with people's needs and expectations. We present a co-design study investigating the benefits and challenges of using computational notebooks to inform ML models with end user groups. We used a computational notebook to engage young adults, carers, and clinicians with an example ML model that predicted health risk in diabetes care. Through co-design workshops and retrospective interviews, we found that participants particularly valued using the interactive data visualisations of the computational notebook to scaffold multidisciplinary learning, anticipate benefits and harms of the example ML model, and create fictional feature importance plots to highlight care needs. Participants also reported challenges, from running code cells to managing information asymmetries and power imbalances. We discuss the potential of leveraging computational notebooks as interactive co-design tools to meet end user needs early in ML model lifecycles.

Hereditary angioedema (HAE) is a rare genetic disease that leads to recurrent episodes of swelling and pain caused by uncontrolled plasma kallikrein (PKa) activity. Current guidelines recommend ready availability of on-demand HAE treatments that can be administered early upon attack onset. This report describes the pharmacological and pharmacodynamic properties of the novel oral small-molecule PKa inhibitor KVD900 as a potential on-demand treatment for HAE.Pharmacological properties of KVD900 on PKa and closely related serine proteases were characterized using kinetic fluorogenic substrate activity assays. Effects of KVD900 on PKa activity and kallikrein kinin system activation in whole plasma were measured in the presence of dextran sulphate (DXS)-stimulation using a fluorogenic substrate and capillary immunoassays to quantify high molecular weight kininogen (HK), plasma prekallikrein and Factor XII cleavage. Pharmacodynamic effects of orally administered KVD900 were characterized in plasma samples from six healthy controls in a first in human phase 1 clinical trial and from 12 participants with HAE in a phase 2 clinical trial.KVD900 is a selective, competitive and reversible inhibitor of human PKa enzyme with a KKVD900 is a fast-acting oral PKa inhibitor that rapidly inhibits PKa activity, kallikrein kinin system activation and HK cleavage in plasma. On-demand administration of KVD900 may provide an opportunity to halt the generation of bradykinin and reverse HAE attacks.

BACKGROUND Delirium, an acute confusional state highlighted by inattention, has been demonstrated to occur in 10 to 50% of COVID-19 patients. Recognizing delirium as a possible presenting symptom of COVID-19 by using information in Electronic Health Record (EHR) data may lead to earlier treatment of the underlying viral infection and improve outcomes in clinical and healthcare systems cost per patient. OBJECTIVE The specific aim of this research was to investigate the use of i2b2 as a tool to identify delirium as a presenting symptom during COVID-19. METHODS We used i2b2 to identify our sample. We included all COVID-19 positive adults (18 years and older) who presented to the emergency department and were subsequently admitted to our academic health system in central Florida between April 1, 2020, and April 1, 2022. The obtained data was used to produce descriptive statistics, including frequencies and percentages. We examined the data by individual diagnoses, as well as within time intervals corresponding to the national peaks of the alpha (3/27/2021 – 6/12/2021), delta (7/3/2021 – 9/30/2021), and omicron (12/1/2021 – 4/1/2022) variants. We identified delirium or encephalopathy by using the following ICD-10 codes: R41.0, R41.82, R41.9, F05, F44.89 for delirium and G92, G92.8, G92.9, G93.40, G93.41, F93.49 for encephalopathy. RESULTS A total of 4828 patients were hospitalized with COVID-19 through the ED during the study period. Slightly less than one-third of COVID-19 patients were diagnosed with a co-occurring neurocognitive disorder, (i.e., delirium or encephalopathy, n = 1,437; 29.8%). Among patients with both COVID-19 and a neurocognitive disorder, 56.9% were 65 years or older, a significantly higher proportion than those with no neurocognitive disorder. There was also a significantly higher proportion of male patients in this group, compared to those with no neurocognitive disorder. Just under a third of patients with both COVID-19 and a neurocognitive disorder expired during their hospital stay, which is a significantly higher proportion than among those with COVID-19 and no neurocognitive disorder. The length of stay in this group was also substantially higher (20.8 days). Statistically significant differences in outcomes were identified across types of neurocognitive disorders and at different COVID-19 variant peaks. CONCLUSIONS Identifying delirium as a presenting sign of COVID-19 may be beneficial to better develop care plans for patients and resource planning for hospitals. Knowing that delirium increases the staffing, nursing care needs, hospital resources used, and the length of stay as shown, identifying delirium early may benefit hospital administration when planning for newly anticipated COVID-19 surges. A robust and accessible data repository, such as the one used in this study, can provide invaluable support to clinicians and clinical administrators in such resource reallocation and clinical decision-making.

BACKGROUND: Increased weight-related stigma during the COVID-19 pandemic has amplified the need to minimise the impacts on mental wellbeing. We investigated the relationship between the perceived changes in the representation of obesity in the media and mental wellbeing during the pandemic in a sample of people with obesity across 10 European countries. We also investigated the potential moderating effect of loneliness. METHODS: Between September to December 2020 during the COVID-19 pandemic, participants reported data on demographics, mental wellbeing (measured by World Health Organisation Five Wellbeing Index and Patient Health Questionaire-4), loneliness (measured by De Jong Gierveld short scale), and perceived change in the representation of obesity in media (measured by a study-specific question) using the online, cross-sectional EURopean Obesity PatiEnt pANdemic Survey (EUROPEANS). Data were analysed using linear mixed-effects models, controlling for age, gender, body mass index, and shielding status, with random incept for country. RESULTS: The survey was completed by 2882 respondents. Most identified as female (56%) and reported their ethnicity as White or White-mix (92%). The total sample had a mean age of 41 years and a BMI of 35.4 kg/m2. During the peak of the pandemic, compared to pre-pandemic, perceiving more negative representation of people with obesity on social media was associated with worse psychological distress, depression, and wellbeing. Perceiving more positive representation, compared to no change in representation, of people with obesity on television was associated with greater wellbeing, yet also higher psychological distress and anxiety. Loneliness, as a moderator, explained ≤0.3% of the variance in outcomes in any of the models. CONCLUSIONS: Perceiving negative representation of obesity on social media was associated with poorer mental wellbeing outcomes during the pandemic; positive representation on television was associated with both positive and negative mental wellbeing outcomes. We encourage greater media accountability when representing people with obesity., The EUROPEANS study was funded by the European Association for the Study of Obesity (EASO) and the European Coalition for People with obesity (EPCO). RAJ and ALA are supported by the Medical Research Council (MRC) (Grant MC_UU_00006/6). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.

Increased weight-related stigma during the COVID-19 pandemic has amplified the need to minimise the impacts on mental wellbeing. We investigated the relationship between the perceived changes in the representation of obesity in the media and mental wellbeing during the pandemic in a sample of people with obesity across 10 European countries. We also investigated the potential moderating effect of loneliness.Between September to December 2020 during the COVID-19 pandemic, participants reported data on demographics, mental wellbeing (measured by World Health Organisation Five Wellbeing Index and Patient Health Questionaire-4), loneliness (measured by De Jong Gierveld short scale), and perceived change in the representation of obesity in media (measured by a study-specific question) using the online, cross-sectional EURopean Obesity PatiEnt pANdemic Survey (EUROPEANS). Data were analysed using linear mixed-effects models, controlling for age, gender, body mass index, and shielding status, with random incept for country.The survey was completed by 2882 respondents. Most identified as female (56%) and reported their ethnicity as White or White-mix (92%). The total sample had a mean age of 41 years and a BMI of 35.4 kg/mPerceiving negative representation of obesity on social media was associated with poorer mental wellbeing outcomes during the pandemic; positive representation on television was associated with both positive and negative mental wellbeing outcomes. We encourage greater media accountability when representing people with obesity.

Aim In a series of pre-registered online studies, we aimed to elucidate the magnitude of the effect of general sustainability labels on U.K. consumers’ food choices. Methods Four labels were displayed: ‘Sustainably sourced’, ‘Locally sourced’, ‘Environmentally friendly’, and ‘Low greenhouse gas emissions’. To ensure reliable results, contingency valuation elicitation was used alongside a novel analytical approach to provide a triangulation of evidence: Multilevel-modelling compared each label vs. no-label; Poisson-modelling compared label vs. label. Socioeconomic status, environmental awareness, health motivations, and nationalism/patriotism were included in our predictive models. Results Exp.1 Multilevel-modelling (N = 140) showed labelled products were chosen 344% more than non-labelled and consumers were willing-to-pay ∼£0.11 more, although no difference between label types was found. Poisson-modelling (N = 735) showed consumers chose Sustainably sourced and Locally sourced labels ∼20% more often but were willing-to-pay ∼£0.03 more only for Locally sourced products. Exp.2 was a direct replication. Multilevel-modelling (N = 149) showed virtually identical results (labels chosen 344% more, willingness-to-pay ∼£0.10 more), as did Poisson-modelling (N = 931) with Sustainably sourced and Locally sourced chosen ∼20% more and willingness-to-pay ∼£0.04 more for Locally sourced products. Environmental concern (specifically the ‘propensity to act’) was the only consistent predictor of preference for labelled vs. non-labelled products. Conclusions Findings suggest front-of-pack ‘green labels’ may yield substantive increases in consumer choice alongside relatively modest increases in willingness-to-pay for environmentally-sustainable foods. Specifically, references to ‘sustainable’ or ‘local’ sourcing may have the largest impact.

STUDY QUESTION What is the relationship between specific quality of life domains and depression, anxiety and stress in the endometriosis population? SUMMARY ANSWER Psychosocial domains of quality of life, such as a perception of social support and self-image, are more strongly associated with depression, anxiety and stress than pain and medical factors. WHAT IS KNOWN ALREADY Prior research indicates a high prevalence of anxiety and depression in individuals with endometriosis. Pain is thought to be critical in the development of psychological distress, however prior research has investigated this association without consideration of psychosocial quality of life domains such as social functioning, perceived social support and self-image. STUDY DESIGN, SIZE, DURATION This study is a cross-sectional analysis of baseline data collected in a longitudinal study exploring psychological distress in endometriosis (n = 584). PARTICIPANTS/MATERIALS, SETTING, METHODS Individuals living with endometriosis participated in this study and were recruited via online platforms of community organizations and support groups. Demographic and medical information concerning endometriosis treatment and diagnosis was self-reported. Psychological distress and quality of life was measured using the Depression, Anxiety and Stress Scale (DASS-21), Endometriosis Health Profile-30 (EHP-30) and the Short Form Survey (SF-36v2). A series of linear regression analyses explored the relationship between specific quality of life domains and the primary outcomes of depression, anxiety and stress. MAIN RESULTS AND THE ROLE OF CHANCE Approximately half of the participants in this sample reported moderate to severe anxiety, depression and stress. Quality of life domains, particularly perceived social support, social functioning and self-image, were more strongly associated with psychological distress than medical or demographic factors. Pain was associated with anxiety, but not depression or stress. A greater number of endometriosis symptoms was only associated with depression. LIMITATIONS, REASONS FOR CAUTION These data are cross-sectional and, therefore, causality cannot be inferred from this analysis. Information about endometriosis diagnosis and treatment was self-reported, and not verified against medical records. WIDER IMPLICATIONS OF THE FINDINGS This study indicates that psychosocial factors may be more salient factors underlying depression, anxiety and stress in the endometriosis population than pain and medical factors. There is a need for interventions that target psychological distress in this population with a focus on the broader impact of endometriosis beyond pain and physical symptomatology. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Research Training Program (RTP) Scholarship awarded to C.S.M. by Macquarie University. The remaining authors have nothing to declare. TRIAL REGISTRATION NUMBER ACTRN12619001508167.

Design and rationale: Obesity results from energy intake exceeding energy expenditure (EE) over a prolonged period. Many anti-obesity drugs are designed to decrease energy intake. However, their potential impact on EE is not well documented. We designed a placebo-controlled, double-blind, randomized cross-over study to determine the acute effects of several FDA-approved anti-obesity drugs on basal metabolic rate (BMR) under well-controlled conditions. Protocol and inclusion criteria: This ongoing study is limited to healthy males of all ethnicities aged 18–35 years with a BMI of 18.5 to 25.0 kg/m2. Following an overnight stay in the Metabolic Clinical Research Unit, fasting subjects were measured from 8:00am to 12:00pm in a whole-room indirect calorimeter, which was maintained at a thermoneutral temperature (26.7±0.9°C) to prevent non-shivering thermogenesis. The six treatments include placebo, caffeine as the positive control (300 mg), phentermine (37.5 mg), topiramate (200 mg), Qsymia (phentermine 15 mg / topiramate 92 mg), and naltrexone (100 mg), with a 1-week outpatient washout period after each treatment. Drug-naïve subjects received a single dose of each drug to minimize potential metabolic adaptations that may occur with weight-loss or chronic use. The prespecified primary outcome was a ≥5% increase in BMR vs. placebo for each drug. This difference can be detected for 16 subjects with 0.83 power at α=0.05 allowing for ≤25% dropout. Secondary outcomes include respiratory quotient (RQ), heart rate (HR), mean arterial pressure (MAP), and self-reported hunger. Preliminary data: To date, 7 subjects were recruited and 6 have completed the study (26.1±4.3 years, BMI 23.1±1.4 kg/m2, body fat percentage 18.4±4.1%). Interim analysis using paired t-tests shows, compared to placebo, caffeine trended towards increasing EE (1.17±0.07 vs. 1.27±0.12 kcal/min; p=0.07) and increased MAP by 5.5±4.2% (88±2 vs. 93±4; p Summary and future directions: Anti-obesity drugs may increase energy expenditure by upregulating sympathetic nervous system activity. Combined with appetite suppression, the impact on energy balance can lead to weight loss. We aim to complete our study to determine whether these drugs can acutely increase EE with minimal cardiovascular side-effects and compare our findings with long-term interventions.

Despite interest in exercise as a treatment for anxiety disorders the mechanism behind the anxiolytic effects of exercise is unclear. Two observations motivate the present work. First, engagement of attention control during increased working memory (WM) load can decrease anxiety. Second, exercise can improve attention control. Therefore, exercise could boost the anxiolytic effects of increased WM load via its strengthening of attention control. Anxiety was induced by threat of shock and was quantified with anxiety-potentiated startle (APS). Thirty-five healthy volunteers (19 male, age M = 26.11, SD = 5.52) participated in two types of activity, exercise (biking at 60-70% of heart rate reserve) and control-activity (biking at 10-20% of heart rate reserve). After each activity, participants completed a WM task (n-back) at low- and high-load during safe and threat. Results were not consistent with the hypothesis: exercise vs. control-activity increased APS in high-load (p = .03). However, this increased APS was not accompanied with threat-induced impairment in WM performance (p = .37). Facilitation of both task-relevant stimulus processing and task-irrelevant threat processing, concurrent with prevention of threat interference on cognition, suggests that exercise increases cognitive ability. Future studies should explore how exercise affects the interplay of cognition and anxiety in patients with anxiety disorders.

Background Research supports the anxiolytic effect of exercise, but the mechanism underlying this effect is unclear. This study examines the influence of exercise in healthy controls on two distinct defensive states implicated in anxiety disorders: fear, a phasic response to a predictable threat, and anxiety, a sustained response to an unpredictable threat. Methods Thirty-four healthy volunteers (17 male, age M = 26.18, SD = 5.6) participated in sessions of exercise (biking at 60-70% of heart rate reserve) and control (biking at 10-20% of heart rate reserve) activity for 30 min, separated by 1 week. Threat responses were measured by eyeblink startle and assessed with the "Neutral-Predictable-Unpredictable threat test," which includes a neutral (N) and two threat conditions, one with predictable (P) and one with unpredictable (U) shock. Results Results show that exercise versus control activity reduces startle potentiation during unpredictable threat (P = .031), but has no effect on startle potentiation during predictable threat (P = .609). Conclusions These results suggest that exercise reduces defensive response to unpredictable, but not predictable, threat, a dissociation that may help inform clinical indications for this behavioral intervention, as well as provide clues to its underlying neurobehavioral mechanisms.

To develop a safe and noninvasive in vivo assay of hepatic propionate oxidative capacity. A modified 1-13C-propionate breath test was administered to 57 methylmalonic acidemia (MMA) subjects, including 19 transplant recipients, and 16 healthy volunteers. Isotopomer enrichment (13CO2/12CO2) was measured in exhaled breath after an enteral bolus of sodium-1-13C-propionate, and normalized for CO2 production. 1-13C-propionate oxidation was then correlated with clinical, laboratory, and imaging parameters collected via a dedicated natural history protocol. Lower propionate oxidation was observed in patients with the severe mut0 and cblB subtypes of MMA, but was near normal in those with the cblA and mut− forms of the disorder. Liver transplant recipients demonstrated complete restoration of 1-13C-propionate oxidation to control levels. 1-13C-propionate oxidation correlated with cognitive test result, growth indices, bone mineral density, renal function, and serum biomarkers. Test repeatability was robust in controls and in MMA subjects (mean coefficient of variation 6.9% and 12.8%, respectively), despite widely variable serum methylmalonic acid concentrations in the patients. Propionate oxidative capacity, as measured with 1-13C-propionate breath testing, predicts disease severity and clinical outcomes, and could be used to assess the therapeutic effects of liver-targeted genomic therapies for MMA and related disorders of propionate metabolism. This clinical study is registered in www.clinicaltrials.gov with the ID: NCT00078078. Study URL: http://clinicaltrials.gov/ct2/show/NCT00078078

ObjectiveCold exposure increases energy expenditure (EE) and could have a role in combating obesity. To understand this potential, we determined the capacity for cold-induced thermogenesis (CIT), the EE increase above the basal metabolic rate at the individualized coldest tolerable temperature before overt shivering.DesignDuring a 13-day inpatient protocol, we quantitated the EE of 12 lean men and 9 men with obesity at various randomly ordered ambient temperatures in a room calorimeter. Subjects underwent brown fat imaging after exposure to their coldest tolerable temperature.ResultsCIT capacity was 300 ± 218 kcal/d (mean ± SD) or 17 ± 11% in lean men and 125 ± 146 kcal/d or 6 ± 7% in men with obesity (P = 0.01). The temperature below which EE increased, lower critical temperature (Tlc), was warmer in lean men than men with obesity (22.9 ± 1.2 vs 21.1 ± 1.7°C, P = 0.03), but both had similar skin temperature (Tskin) changes and coldest tolerable temperatures. Whereas lean subjects had higher brown fat activity, skeletal muscle activity increased synchronously with CIT beginning at the Tlc in both groups, indicating that muscle is recruited for CIT in parallel with brown fat, not sequentially after nonshivering thermogenesis is maximal.ConclusionsDespite greater insulation from fat, men with obesity had a narrower range of tolerable cool temperatures available for increasing EE and less capacity for CIT than lean men, likely as a result of greater basal heat production and similar perception to Tskin cooling. Further study of the reduced CIT capacity in men with obesity may inform treatment opportunities for obesity.

This report examines how well the processes and timeline for generating ready forces from the Army reserve component (RC) units align with a need for rapid deployment to a future major conflict overseas. The report focuses on how the dynamics of the mobilization process for Army RC units can, or should, affect decisionmaking about force mix, as well as how policy and resourcing decisions can either enhance or inhibit mobilization.

β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [18F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUVmean] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.

Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m2; 8 obese, BMI 34.8 ± 3.3 kg/m2] after 5 h of tolerable cold exposure, we measured BAT volume and activity by 18F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1–71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT—cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal—with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots in the upper torso. These nonsubcutaneous fat depots amounted to 1.5% of total body mass (4.3% of total fat mass), and up to 90% of each depot could be activated BAT. The amount and activity of BAT was significantly influenced by region of interest selection methods, PET threshold criteria, and PET resolutions. The present study suggests that active BAT can be found in specific adipose depots in adult humans, but less than one-half of the fat in these depots is stimulated by acute cold exposure, demonstrating a previously underappreciated thermogenic potential.

We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and high signal-to-noise ratio in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially-resolved spectroscopy for thousands of nearby galaxies (median redshift of z = 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between redshifts z = 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGN and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5-meter Sloan Foundation Telescope at Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5-meter du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in July 2016., Published in Astronomical Journal

Discusses the results of a new approach to develop an improved crosswalk between Army military occupational specialties (MOSs) and civilian occupations, highlighting ten of the Army's most populous combat and noncombat MOSs.

This report documents one of the primary tasks of a research project titled Facilitating AC-to-RC and AC-to-Civilian Transitions. The overall purpose of the project was to assess the level and importance of the knowledge, skills, and abilities needed to perform in Army military occupational specialties (MOSs) to develop improved crosswalks between military and civilian occupations and to make other recommendations to improve the transition process for soldiers leaving the Regular Army. In this report, we discuss the results of occupation surveys administered to soldiers in ten of the most populous Army MOSs, including the knowledge, skills, and abilities rated most important by soldiers in those MOSs, the best-matching civilian occupations, and comparisons with other military-civilian occupation crosswalks.

Three experiments tested the effects of feeding CaO as part of the TMR or as CaO-treated corn stover (CS) on growth performance, carcass characteristics, and ruminal metabolism of cattle. In Exp. 1, steers (n = 162) were fed 1 of 3 diets containing 20% CS and 40% modified wet distillers grains with solubles: untreated CS (UCS), treated CS with 5% CaO (DM basis; TCS), and dietary inclusion of 1% CaO (DM basis; DC). Feeding DC or TCS decreased (P < 0.05) DMI, final BW, HCW, and back fat compared with feeding UCS. Feeding TCS decreased (P < 0.05) ADG compared with feeding UCS. In Exp. 2, heifers (n = 138) were fed 1 of 3 diets: UCS, TCS, and 40% corn silage (DM basis; SIL). Feeding TCS decreased (P ≤ 0.05) DMI, and final BW, and back fat compared with feeding UCS and SIL. Heifers fed UCS had similar (P ≤ 0.05) ADG, DMI, and marbling score as heifers fed SIL; however, final BW and G:F were decreased (P ≤ 0.05). In Exp. 3, steers (n = 5) were fed in a 5 × 5 Latin square; diets were UCS, TCS, DC, SIL, and a control of 50% cracked corn. Feeding TCS tended to decrease (P = 0.06) ruminal pH when compared with UCS. Steers fed UCS had the least (P ≤ 0.05) DM digestibility and steers fed the control had the greatest. Treating CS with CaO effectively increased digestibility; however, it did not improve cattle performance. Feeding cattle untreated, ensiled CS resulted in ADG and G:F comparable to feeding corn silage.

The objectives of this study were to determine the effects of feeding dried corn distillers grains (DDGS) or modified wet corn distillers grains (MDGS) with or without CaO treatment to feedlot steers on 1) growth performance and carcass characteristics and 2) diet digestibility, pattern of intake, and meal distribution. In Exp. 1, steers (n = 139; average initial BW = 336 ± 75 kg) were used in a randomized complete block design. Treatments were arranged in a 2 × 2 factorial design, and pens were randomly allotted to 1 of the 4 dietary treatments (DM basis): 1) 50% DDGS untreated, 2) 48.8% DDGS treated with 1.2% CaO, 3) 50% MDGS untreated, or 4) 48.8% MDGS treated with 1.2% CaO. The remainder of the diet was corn husklage, dry rolled corn, and vitamin and mineral supplement. In Exp. 2, fistulated steers (n = 8; average initial BW = 540 ± 250 kg) were used in a replicated 4 × 4 Latin square design with the same dietary treatments as in Exp. 1. There was no interaction (P ≥ 0.14) between distillers grains plus solubles (DGS) and CaO inclusion for DMI, ADG, final BW, or USDA yield and quality grades. However, steers fed CaO-treated DGS had decreased (P < 0.01) DMI, regardless of DGS type. Because CaO treatment decreased DMI without affecting (P = 0.66) ADG, steers fed CaO-treated DGS had increased (P < 0.01) G:F compared to steers not fed CaO. The variation in DMI found in this experiment could be explained by differences in meal size and distribution. Steers fed CaO-treated DGS ate a similar (P = 0.36) number of meals but ate smaller (P < 0.01) meals. No effects (P ≥ 0.55) of CaO treatment or its interaction with DGS type were found for apparent total tract DM or NDF digestibility. However, steers fed MDGS had increased (P < 0.01) NDF digestibility compared to steers fed DDGS. In conclusion, CaO treatment of DGS improved feed efficiency when DGS-based diets were fed but did not improve digestibility.

Central nervous system (CNS) germ cell tumors (GCTs) are separated into germinomas and nongerminomatous germ cell tumors (NGGCTs). The latter group includes teratoma (mature and immature), teratoma with malignant transformation, yolk sac tumor, embryonal carcinoma, choriocarcinoma, and mixed GCTs. CNS GCTs can be classified based on their histologic appearance and immunohistochemical profiles with histologic subtype being the best predictor of outcome. Germinomas respond exceptionally well to chemotherapy and irradiation and have been shown to have survival rates in excess of 90 %. In contrast, NGGCTs are more resistant to therapy and require more intensive chemotherapy, as well as higher doses of irradiation. There is little information on the histogenesis and molecular genetics of CNS GCTs. Fluorescent in situ hybridization (FISH) studies have shown a gain of X chromosome in a majority of GCTs. Other studies have shown that 12p abnormalities (gains and isochromosome 12p) are common, especially in germinomas. Gene expression analysis studies show overexpression of self-renewing pluripotency genes and genes responsible for tumor growth and differentiation in various tumors with no significant differences in gene expression between CNS GCTs of similar histology arising at different sites and different ages within the pediatric age group. Differences in microRNA expression have been demonstrated between histologic subtypes of CNS GCTs, and their potential use as a biomarker in the serum and cerebrospinal fluid is being explored. KIT mutations are the most commonly found abnormality on whole genome sequencing, predominantly in germinomas, followed by genes involved in the MAPK signaling pathway, suggesting a role for KIT inhibitors in the management of these tumors.

Central pulse pressure can be non-invasively derived using the radial artery tonometric methods. Knowledge of central pressure profiles has predicted cardiovascular morbidity and mortality in several populations of patients, particularly those with known coronary artery disease and those receiving dialysis. Few data exist characterizing central pressure profiles in patients with mild-moderate chronic kidney disease who are not on dialysis. We measured central pulse pressure cross-sectionally in 2531 participants in the Chronic Renal Insufficiency Cohort study to determine correlates of the magnitude of central pulse pressure in the setting of chronic kidney disease. Tertiles of central pulse pressure (CPP) were < 36 mmHg, 36–51 mmHg and > 51 mmHg with an overall mean (± S.D.) of 46 ± 19 mmHg. Multivariable regression identified the following independent correlates of central pulse pressure: age, gender, diabetes mellitus, heart rate (negatively correlated), glycosylated hemoglobin, hemoglobin, glucose and PTH concentrations. Additional adjustment for brachial mean arterial pressure and brachial pulse pressure showed associations for age, gender, diabetes, weight and heart rate. Discrete intervals of brachial pulse pressure stratification showed substantial overlap within the associated central pulse pressure values. The large size of this unique chronic kidney disease cohort provides an ideal situation to study the role of brachial and central pressure measurements in kidney disease progression and cardiovascular disease incidence.

Understanding the current status of the discovery and development of anti-Helicobacter therapies requires an overview of the searches for therapeutic targets performed to date. A summary is given of the very substantial body of work conducted in the quest to find Helicobacter pylori genes that could be suitable candidates for therapeutic intervention. The products of most of these genes perform metabolic functions, and others have roles in growth, cell motility and colonization. The genes identified as potential targets have been organized into three categories according to their degree of characterization. A short description and evaluation is provided of the main candidates in each category. Investigations of potential therapeutic targets have generated a wealth of information about the physiology and genetics of H. pylori, and its interactions with the host, but have yielded little by way of new therapies.

It is impossible to read newspapers or plastics trade magazines without seeing articles about companies investing in Asia to benefit from the tremendous growth in China or the potential of India. There is no doubt that both these regions represent opportunities for western companies, but it is easy to be seduced by the statistics and a thorough assessment of the opportunity and the risks is needed. For every success story there are three or four instances where things did not go as anticipated. In the second of his articles on issues arising from globalization, Stephen Duckworth of Euro-Asia Connect highlights some of the issues that he believes need to be considered as part of an entry strategy to Asian markets.

Human cathepsin D (hCatD) is an aspartic peptidase with a low pH optimum. X-ray crystal structures have been solved for an active, low pH (pH 5.1) form (CatD(lo)) [Baldwin, E. T., Bhat, T. N., Gulnik, S., Hosur, M. V., Sowder, R. C., Cachau, R. E., Collins, J., Silva, A. M., and Erickson, J. W. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6796-6800] and an inactive, high pH (pH 7.5) form (CatD(hi)) [Lee, A. Y., Gulnik, S. V., and Erickson, J. W. (1998) Nat. Struct. Biol. 5, 866-871]. It has been suggested that ionizable switches involving the carboxylate side chains of E5, E180, and D187 may mediate the reversible interconversion between CatD(hi) and CatD(lo) and that Y10 stabilizes CatD(hi) [Lee, A. Y., Gulnik, S. V., and Erickson, J. W. (1998) Nat. Struct. Biol. 5, 866-871]. To test these hypotheses, we generated single point mutants in "short" recombinant human pseudocathepsin D (srCatD), a model kinetically similar to hCatD [Beyer, B. M., and Dunn, B. M. (1996) J. Biol. Chem. 271, 15590-15596]. E180Q, Y10F, and D187N exhibit significantly higher kcat/Km values (2-, 3-, and 6-fold, respectively) at pH 3.7 and 4.75 compared to srCatD, indicating that these residues are important in stabilizing the CatD(hi). E5Q exhibits a 2-fold lower kcat/Km compared to srCatD at both pH values, indicating the importance of E5 in stabilizing the CatD(lo). Accordingly, full time-course "pH-jump" (pH 5.5-4.75) studies of substrate hydrolysis indicate that E180Q, D187N, and Y10F have shorter kinetic lag phases that represent the change from CatD(hi) to CatD(lo) compared to srCatD and E5Q. Intrinsic tryptophan fluorescence reveals that the variants have a native-like structure over the pH range of our assays. The results indicate that E180 and D187 participate as an electrostatic switch that initiates the conformational change of CatD(lo) to CatD(hi) and Y10 stabilizes CatD(hi) by hydrogen bonding to the catalytic Asp 33. E5 appears to play a less significant role as an ionic switch that stabilizes CatD(lo).

Whether we like it or not, the plastics industry is now a truly global phenomena. Many companies in North America and Europe are looking to either manufacture in China or take advantage of rapidly expanding domestic markets in Asia. Likewise many Chinese and other Asian companies are keen to find new markets for their products around the world. In a series of two articles addressing both sides of this globalization movement, Stephen Duckworth of Euro-Asia Connect reviews some of the issues that plastics companies need to address if they want to be successful in unfamiliar markets. In this issue, he argues that Asian companies need to consider a great deal more than price if they want to be successful exporters.

Postmortem brain studies have shown deficits in the cortical gamma-aminobutyric acid (GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme (glutamic acid decarboxylase (GAD67) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD67, were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia (COS) (n=72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 5' upstream region of GAD1 showed a positive pairwise association with illness in these families (P=0.022-0.057). Significant transmission distortion of 4-SNP haplotypes was also observed (P=0.003-0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD67 may be a common risk factor for schizophrenia.

In subsurface excavations, auxiliary ventilation systems are an important and integrated component of the overall ventilation scheme. Without adequate auxiliary ventilation, it is impossible to provide sufficient air to working faces, regardless of the quantity or quality of air in the main airways. Extended development headings are typically ventilated using fan and duct systems, which either force or exhaust air through the duct. The optimum design of such systems can be complex, depending on factors such as duct resistance, leakage and diameter, fan selection and spacing, and shock losses. This paper describes the development and application of a comprehensive design process for auxiliary ventilation systems. Included is a summary of published theory and literature, a description of software development, information and results from detailed field measurements, and a description of the application of the software to the design of an actual extended auxiliary fan and duct system.

ObjectivesTo determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD).DesignProspective observational study.SettingChronic Renal Insufficiency Cohort Cognitive Study.ParticipantsIndividuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N=821; mean age 64.9, 50.6% male, 48.6% white).MeasurementsLevels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean).ResultsAfter multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P&nbsp

The objectives of this study were to determine the effects of feeding dried corn distillers grains (DDGS) or modified wet corn distillers grains (MDGS) with or without CaO treatment to feedlot steers on 1) growth performance and carcass characteristics and 2) diet digestibility, pattern of intake, and meal distribution. In Exp. 1, steers (n = 139; average initial BW = 336 ± 75 kg) were used in a randomized complete block design. Treatments were arranged in a 2 × 2 factorial design, and pens were randomly allotted to 1 of the 4 dietary treatments (DM basis): 1) 50% DDGS untreated, 2) 48.8% DDGS treated with 1.2% CaO, 3) 50% MDGS untreated, or 4) 48.8% MDGS treated with 1.2% CaO. The remainder of the diet was corn husklage, dry rolled corn, and vitamin and mineral supplement. In Exp. 2, fistulated steers (n = 8; average initial BW = 540 ± 250 kg) were used in a replicated 4 × 4 Latin square design with the same dietary treatments as in Exp. 1. There was no interaction (P ≥ 0.14) between distillers grains plus solubles (DGS) and CaO inclusion for DMI, ADG, final BW, or USDA yield and quality grades. However, steers fed CaO-treated DGS had decreased (P0.01) DMI, regardless of DGS type. Because CaO treatment decreased DMI without affecting (P = 0.66) ADG, steers fed CaO-treated DGS had increased (P0.01) G:F compared to steers not fed CaO. The variation in DMI found in this experiment could be explained by differences in meal size and distribution. Steers fed CaO-treated DGS ate a similar (P = 0.36) number of meals but ate smaller (P0.01) meals. No effects (P ≥ 0.55) of CaO treatment or its interaction with DGS type were found for apparent total tract DM or NDF digestibility. However, steers fed MDGS had increased (P0.01) NDF digestibility compared to steers fed DDGS. In conclusion, CaO treatment of DGS improved feed efficiency when DGS-based diets were fed but did not improve digestibility.

BACKGROUND: Glutathione S-transferase (GST) enzymes are involved in detoxifying chemotherapy agents and clearing reactive oxygen species formed by radiation. In this study, we explored the relationship between the host GSTP1-105 polymorphism (rs1695), tumor GSTpi protein expression, and clinical outcomes in pediatric medulloblastoma. We hypothesized that the GSTP1-105 G-allele and increased tumor GSTpi expression would be associated with lower progression-free survival and fewer adverse events. METHODS: The study included 106 medulloblastoma/primitive neuroectodermal tumor (PNET) patients seen at Texas Children’s Cancer Center. Genotyping was performed using an Illumina HumanOmni1-Quad BeadChip and tumor GSTpi expression was assessed using immunohistochemistry. We used the Kaplan-Meier method for survival analyses and multivariable logistic regression for toxicity comparisons. RESULTS: Patients with a GSTP1-105 AG/GG genotype or who had received a higher dose of craniospinal radiation (median 36 Gy) had a greater risk of requiring hearing aids than their respective counterparts (OR 4.0, 95%CI 1.2 - 13.6, and OR 3.1, 95%CI 1.1 - 8.8, respectively). Additionally, there was a statistically significant interaction between the two variables. Compared with the lowest risk group (GSTP1-105 AA-lower dose radiation) patients with a GSTP1-105 AG/GG genotype who received a higher dose radiation were 8.4 times more likely to require hearing aids (95%CI 1.4 - 49.9, p-trend ¼ 0.005). When adjusted for age, gender, and amifostine use, the association remained. CONCLUSIONS: The GSTP1-105 G-allele is associated with permanent ototoxicity in pediatric medulloblastoma/PNET and strongly interacts with radiation dose. A possible mechanism for this finding is that the GSTP1-105 G-allele leads to reduced GSTpi free radical detoxification in the setting of multimodality therapy including cisplatin and radiation. Patients with this allele should be considered for clinical trials employing radiation dose modifications and more targeted cytoprotectant strategies than are currently being used with amifostine.

This paper describes the latest algorithm being developed by the Worcester Polytechnic Institute (WPI) Precision Personnel Location (PPL) project. Our goal is to produce a rapidly deployable, ad-hoc system that can achieve sub meter positioning accuracy in any type of emergency response scenario using available spectrum; specifically we wish to locate first responders in and around buildings. Previous work [1] has led to separate or loosely coupled approaches for fusing RF and inertial positioning data, as well as data from other sensors. The Inverse Synthetic Array Reconciliation Tomography (IS-ART) algorithm is a fusion of RF and inertial measurements that is fundamentally different from previous systems. Instead of fusing positioning results, we use the inertial displacements to coherently fuse successive RF captures. The benefits of this approach are twofold. First, the fusion depends only on relationships between inertial values spanning small time intervals, so that we do not accumulate large inertial drift errors. Second, the RF conditions at each point are expected to be very different because high multi-path environments are very sensitive to spatial perturbations. Since the multi-path signal components are changing rapidly with position we expect that only the direct path signals will be correlated between successive RF data captures taken from unique positions. In order for the direct path signals from different locations to be correlated these captures must be aligned for fusion with the inertial displacement data. The ISART algorithm performs this signal alignment and computes a metric based on this direct path correlation using the sample processing employed by the Singular Value Array Reconciliation Tomography (σART ) algorithm [2]; the ISART solution is the point where the metric is maximal.

The paper looks at the problem of ensuring the performance of real-time applications hosted on Galactica Net, a mesh-based distributed cache coherent shared memory multiprocessing system. A method for determining strict upper bounds on worst case latencies in wormhole routed networks of known or unknown communication patterns is presented. From this, a tool for determining upper bounds for shared memory update latencies is developed, and it is shown that the update latency of Galactica Net is deterministic. The analytical bounds are then compared with maximum latencies observed in simulations of GNet, with which they compare favorably. Finally, it is shown that the tool for determining update latency bounds is useful for comparing differing GNet system configurations in order to minimize update latency bounds.