Search

Additional file 1: List of measures used for establishing construct validity of ASCOT-Proxy and ASCOT-Carer.

Additional file 2: Statistical analysis

Immunoglobulin G (IgG) autoantibodies reactive to fetal brain proteins in mothers of children with ASD have been described by several groups. To understand their pathologic significance, we developed a mouse model of maternal autoantibody related ASD (MAR-ASD) utilizing the peptide epitopes from human autoantibody reactivity patterns. Male and female offspring prenatally exposed to the salient maternal autoantibodies displayed robust deficits in social interactions and increased repetitive self-grooming behaviors as juveniles and adults. In the present study, neuroanatomical differences in adult MAR-ASD and control offspring were assessed via high-resolution ex vivo magnetic resonance imaging (MRI) at 6 months of age. Of interest, MAR-ASD mice displayed significantly larger total brain volume and of the 159 regions examined, 31 were found to differ significantly in absolute volume (mm3) at an FDR of

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus

Background: Calorie restriction (CR) retards aging and increases longevity in many animal models. However, it is unclear whether CR can be implemented in humans without adverse effects on body composition.Objective: We evaluated the effect of a 2-y CR regimen on body composition including the influence of sex and body mass index (BMI; in kg/m2) among participants enrolled in CALERIE-2 (Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy), a multicenter, randomized controlled trial.Design: Participants were 218 nonobese (BMI: 21.9-28.0) adults aged 21-51 y who were randomly assigned to 25% CR (CR, n = 143) or ad libitum control (AL, n = 75) in a 2:1 ratio. Measures at baseline and 12 and 24 mo included body weight, waist circumference, fat mass (FM), fat-free mass (FFM), and appendicular mass by dual-energy X-ray absorptiometry; activity-related energy expenditure (AREE) by doubly labeled water; and dietary protein intake by self-report. Values are expressed as means ± SDs.Results: The CR group achieved 11.9% ± 0.7% CR over 2-y and had significant decreases in weight (-7.6 ± 0.3 compared with 0.4 ± 0.5 kg), waist circumference (-6.2 ± 0.4 compared with 0.9 ± 0.5 cm), FM (-5.4 ± 0.3 compared with 0.5 ± 0.4 kg), and FFM (-2.0 ± 0.2 compared with -0.0 ± 0.2 kg) at 24 mo relative to the AL group (all between-group P < 0.001). Moreover, FFM as a percentage of body weight at 24 mo was higher, and percentage of FM was lower in the CR group than in the AL. AREE, but not protein intake, predicted preservation of FFM during CR (P < 0.01). Men in the CR group lost significantly more trunk fat (P = 0.03) and FFM expressed as a percentage of weight loss (P < 0.001) than women in the CR group.Conclusions: Two years of CR had broadly favorable effects on both whole-body and regional adiposity that could facilitate health span in humans. The decrements in FFM were commensurate with the reduced body mass; although men in the CR group lost more FFM than the women did, the percentage of FFM in the men in the CR group was higher than at baseline. CALERIE was registered at clinicaltrials.gov as NCT00427193.

Additional file 1: Table 1. Results from the iterative Rasch analyses from the current study in 1211 participants. Table 2. Fit Indices for Each Item in 1211 participants.

Additional file 1: Supplemental Table 1. Correlation (Spearman Rho) between each air pollutant. Supplemental Table 2. Correlation (Spearman Rho) between each measured immune marker. Supplemental Table 3. Linear Regression Models: ln (Immune Marker) ~ Air Pollutant + Covariates, among ASD w/ ID + GP analytic dataset. Supplemental Table 4. Linear Regression Models: ln (Immune Marker) ~ Air Pollutant + Covariates, among ASD wo/ ID + GP analytic dataset. Supplemental Table 5. Linear Regression Models: ln (Immune Marker) ~ Air Pollutant + Covariates, among ID w/o ASD + GP analytic dataset. Supplemental Table 6. Natural Effects Mediation Modeling to assess whether immune marker mediates association between air pollutant and ASD w/ ID (relative to GP). Supplemental Table 7. Natural Effects Mediation Modeling to assess whether immune marker mediates association between air pollutant and ASD w/o ID (relative to GP). Supplemental Table 8. Natural Effects Mediation Modeling to assess whether immune marker mediates association between air pollutant and ID w/o (relative to GP).

It has been estimated that autism spectrum disorder (ASD) now affects 1 in 59 children in the United States. Although the cause(s) of ASD remain largely unknown, it is becoming increasingly apparent that ASD can no longer be defined simply as a behavioral disorder, but is in effect a rather complex and highly heterogeneous biological disorder. Up until recently the brain was thought to be "immune privileged." However, it is now known that the immune system plays critical roles in the development and functioning of the brain throughout life. Recent evidence from multiple investigators has illustrated the deleterious role that dysregulation of the maternal immune system during gestation can play in the manifestation of changes in neurodevelopment, resulting in the development of neurobehavioral disorders such as ASD. One potential etiologic pathway through which the maternal immune system can interfere with neurodevelopment is through maternal autoantibodies that recognize proteins in the developing fetal brain. This mechanism of pathogenesis is now thought to lead to a subphenotype of ASD that has been termed maternal autoantibody related (MAR) ASD. This review provides an overview of the current research implicating the presence of brain-reactive maternal autoantibodies as a risk factor for MAR ASD.

Figure S1. Significance levels of each confounding factor across the entire set of maternal and neonatal immune mediators. Figure S2. Linkage disequilibrium regional genomic plots. Figure S3. Maternal and fetal SNPs (P

Background Task-specific training may be a suitable intervention to address mobility limitations in people with Huntington disease (HD). Objective The aim of this study was to assess the feasibility and safety of goal-directed, task-specific mobility training for individuals with mid-stage HD. Design This study was a randomized, blinded, feasibility trial; participants were randomly assigned to control (usual care) and intervention groups. Setting This multisite study was conducted in 6 sites in the United Kingdom. Patients Thirty individuals with mid-stage HD (13 men, 17 women; mean age=57.0 years, SD=10.1) were enrolled and randomly assigned to study groups. Intervention Task-specific training was conducted by physical therapists in participants' homes, focusing on walking, sit-to-stand transfers, and standing, twice a week for 8 weeks. Goal attainment scaling was used to individualize the intervention and monitor achievement of personal goals. Measurements Adherence and adverse events were recorded. Adjusted between-group comparisons on standardized outcome measures were conducted at 8 and 16 weeks to determine effect sizes. Results Loss to follow-up was minimal (n=2); adherence in the intervention group was excellent (96.9%). Ninety-two percent of goals were achieved at the end of the intervention; 46% of the participants achieved much better than expected outcomes. Effect sizes on all measures were small. Limitations Measurements of walking endurance were lacking. Conclusions The safety of and excellent adherence to a home-based, task-specific training program, in which most participants exceeded goal expectations, are encouraging given the range of motivational, behavioral, and mobility issues in people with HD. The design of the intervention in terms of frequency (dose), intensity (aerobic versus anaerobic), and specificity (focused training on individual tasks) may not have been sufficient to elicit any systematic effects. Thus, a larger-scale trial of this specific intervention does not seem warranted.

Pre- and Post-Intralipid Respiratory Quotient Values. A. Average RQ values measured during the Pre-Intralipid/Baseline phase of the test visit and post-Intralipid RQ values. #Denotes significant difference in LG group Pre-Intralipid/Baseline measure with respect to the LS group. &Denotes significant difference in LG group Pre-Intralipid/Baseline measure with respect to the OS group. *Denotes significant difference within group, Post-Intralipid measure with respect to the average Pre-Intralipid/Baseline measure. B. RQ measured under fasting conditions, with (CHO Diet) or without (Ad Lib Diet) high carbohydrate dietary intake, ±Glucose, and following Intralipid infusion. *Denotes significant difference within group, Post-Intralipid measure with respect to the average Pre-Intralipid measure. $Denotes significant difference in Post-Intralipid measure with respect to the Ad Lib Diet measure. #Denotes significant difference in Pre-Intralipid measure with respect to the Ad Lib Diet measure. C. Comparison of fasting RQ values (“Between Day”) and RQ values obtained during the saline or glucose infusion phase of the test visit (“Within Day”) to post-Intralipid RQ values. *Denotes significant difference within group, Post-Intralipid measure with respect to the Pre-Intralipid/Baseline measure. Note: For all symbols: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. (DOCX 667 kb)

Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.

The papers in this issue address, or illustrate, the relation between symbolic and numeric approaches to text and speech processing. This is currently an exciting and productive area of research and development in natural language processing research. This introduction summarizes the background, lists important questions to be addressed, indicates how the papers relate to these, and draws out major lessons to be learnt from this state–of–the–art collection.

The selection of herd bulls is important in determining profitability of commercial ranchers and cow-calf operators as well as purebred producers. In this research, the key attributes of bulls – based on visual, performance, and ultrasound data – are valued using a traditional hedonic pricing model. The data are collected from the annual bull test trial and sale at Southern Illinois University Carbondale. The results suggest that buyers at the SIUC Beef Evaluation Station are willing to pay more for bull characteristics associated with calving ease and weaning weights. For instance bulls with a combination of both lower birth weight Expected Progeny Differences (EPDs) and high yearling weight EPDs than average can command premiums of over $1,150 per head or 67 percent above the average sale price. Farm managers can use this information in the selection of herd bulls while purebred operators can attempt to select for the most valuable traits.

Given the present state of work in natural language processing, this address argues first, that advance in both science and applications requires a revival of concern about what language is about, broadly speaking the world; and second, that an attack on the summarising task, which is made ever more important by the growth of electronic text resources and requires an understanding of the role of large-scale discourse structure in marking important text content, is a good way forward., Comment: Presidential Address, 1994, Association for Computational Linguistics

We report here the summary statistics for the first large scale maternal and fetal genetic study of maternal mid-pregnancy and neonatal levels of 22 and 42 soluble immune mediators, respectively. We aimed to utilize genetic data to assess the role of maternal genetics in the maternal immune system during pregnancy, the role of fetal genetics in infant immune system at birth, influence of maternal genetics on infant immune status, and the role of fetal genetics on maternal immune status during pregnancy. We performed an ancestry-combined GW SNP-based heritability analyses and GW association studies of 64 immune mediators in both mothers and neonates. Table1.csv.gz Summary statistics for each maternal cytokine and chemokine GWAS with maternal genetics. Table2.csv.gz Summary statistics for each neonatal cytokine and chemokine GWAS with fetal genetics. Table3.csv.gz Summary statistics for each neonatal cytokine and chemokine GWAS with maternal genetics. Table4.csv.gz. Summary statistics for each maternal cytokine and chemokine GWAS with fetal genetics.

Supplemental methods. Neonatal filter extraction and validity of the multiplex assay for maternal and neonatal immune mediators. (PDF 42 kb)

Supplemental methods. Neonatal filter extraction and validity of the multiplex assay for maternal and neonatal immune mediators. (PDF 42 kb)

usc Aim: To determine the serum bile acid (BA) response to 75-g oral glucose in individuals without diabetes, and whether this is attenuated in patients with ‘early’ type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group. Methods: Forty newly diagnosed, treatment-naïve Han Chinese T2D subjects and 40 age-, gender-, and body mass index-matched controls without T2D ingested a 75-g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor-19 (FGF-19), total glucagon-like peptide-1 (GLP-1), and insulin, were measured before and 2 hours after oral glucose. Results: Fasting total BA levels were higher in T2D than control subjects (P

Context Premenopausal women are at a lower risk of type 2 diabetes (T2D) compared to men, but the underlying mechanism(s) remain elusive. The secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), from the small intestine is a major determinant of glucose homeostasis and may be influenced by sex. Objectives This study compared blood glucose and plasma insulin and incretin responses to intraduodenal glucose infusions in healthy young males and females. Design In Study 1, 9 women and 20 men received an intraduodenal glucose infusion at 2 kcal/min for 60 minutes. In Study 2, 10 women and 26 men received an intraduodenal glucose at 3 kcal/min for 60 minutes. Venous blood was sampled every 15 minutes for measurements of blood glucose and plasma insulin, GLP-1 and GIP. Results In response to intraduodenal glucose at 2 kcal/min, the incremental area under the curve between t = 0-60 minutes (iAUC0-60min) for blood glucose and plasma GIP did not differ between the 2 groups. However, iAUC0-60min for plasma GLP-1 (P = 0.016) and insulin (P = 0.011) were ∼2-fold higher in women than men. In response to intraduodenal glucose at 3 kcal/min, iAUC0-60min for blood glucose, plasma GIP, and insulin did not differ between women and men, but GLP-1 iAUC0-60min was 2.5-fold higher in women (P = 0.012). Conclusion Healthy young women exhibit comparable GIP but a markedly greater GLP-1 response to intraduodenal glucose than men. This disparity warrants further investigations to delineate the underlying mechanisms and may be of relevance to the reduced risk of diabetes in premenopausal women when compared to men.

Aim: To evaluate the effect of gastric distension, induced using a gastric ‘barostat’, on the secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the presence and absence of small intestinal nutrients in healthy individuals. Materials and Methods: Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m2) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. Results: Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP-1 with or without gastric distension (P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension (P = 1.00 for saline infusion and P = .99 for glucose infusion). Conclusions: Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans. Refereed/Peer-reviewed

Cholecystectomy has been reported to be associated with increased risk of diabetes in cross-sectional studies. In the current study, we performed both cross-sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community-dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow-up visit were calculated to define glycaemic control as stable (−10% ≤ Δ

Refereed/Peer-reviewed Aims: The aim of this study was to evaluate the comparative effects of low-carbohydrate (LC), full-strength (FS), and low-alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health. Methods: Eight subjects (four male, four female; age: 20.4 +/- 0.4 years; BMI 22.7 +/- 0.4 kg/m(2)) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc-calcium phytate, in random order. Results: There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 +/- 13.5 min vs LC: 79.5 +/- 12.9 min vs LA: 74.6 +/- 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = -0.87, P < .01) and a trend for inverse relationships after LC (r = -0.67, P = .07) and FS (r = -0.69, P = .06). The AUC 0-180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0). Conclusion: In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response.

In 1947, in Everson v. Board of Education, the United States Supreme Court held for the first time that the Establishment Clause of the First Amendment was applicable to the states through the Fourteenth Amendment. The Establishment Clause states: “Congress shall make no law respecting an establishment of religion” and governs the institutional relationships between the churches and the state in the United States. With Everson began a controversial and long-running debate: what exactly does the Establishment Clause mean and what kinds of relationship between church and state are forbidden under its terms? As arbiter of the Constitution, the task of interpreting the Clause and its meaning in the modern United States fell to the Supreme Court. This thesis investigates the Court’s interpretation of the Establishment Clause between Everson in 1947 and Agostini v. Felton in 1997, when the Court overruled itself for the first time in this area of constitutional law.\ud This thesis focuses on the Court’s decisions in the area of schools and education policy, such cases accounting for a majority of the Court’s Establishment Clause jurisprudence. It considers school aid and the provision of government benefits to religious schools and their students, school prayer and other school-sponsored religious exercises on public school grounds, and equal access, the question of voluntary student-initiated religious activities on public school premises. In seeking to investigate the Court’s decisions, three main influences are considered: the opinions of the Court, the Justices’ private discussions and the alignment of Justices in each case, and the social and political context against which the cases arose and were decided. This thesis takes an historical approach to analysing these events and investigates influences on the Court beyond those of legal origin. In taking this approach, the thesis addresses how and why the Court made its decisions and rulings, the consequences of those rulings for the meaning of the Establishment Clause, and the effect of both on the relationship between the institutions of the churches and the state in the modern United States.

Previous studies of British bloodsports have tended to focus solely on elite participants, examining how themes of class and ethnicity have affected the ways in which they visualised and conducted their chosen sports. This thesis takes a slightly different approach, choosing to chart the use of rituals within the cultures of a widely divergent set of blood sports communities across a period of one-hundred and fourteen years. During that time, both the social and the environmental landscapes evolved a good deal which duly shaped how many of these communities chose to represent themselves. However, the one constant was the theme of authority which these different communities were chasing. Across these different cultures, authority was a key part of sporting ritual, designed both to promote the community as a whole and the reputation of the personal protagonist. Whether it was enacted through the mechanisms of gender, class, culture or morality, appearing powerful and in control was what all blood sports enthusiasts desired, whatever their social background. Authority bound these communities together as well as exalting individuals, making them feel protected and accepted in an oft-changing world. Despite the different social demographics, moral standards and geographies over which they indulged in their sports, these feelings of community and authority was what drove them all and continued to inspire their love for the thrill of the chase.

Children's playgrounds are a ubiquitous feature of British towns and cities. And yet the politics and values that have informed their creation, purpose and form have rarely been historicised by scholars, professionals or the wider public. To address this, Swings and Roundabouts answers two broad questions. Firstly, why do children's playgrounds exist and, secondly, why do they look the way they do? Focusing on dedicated public spaces for play, the study examines the individuals and organisations that promoted and created such places, explores the changing social, political and environmental assumptions that informed such work, and reveals how play spaces and the wider urban environment changed as a result. Grounded in the fields of environmental history and critical geography, the thesis uncovers the changing eco-cultural values that helped to establish the principle of the playground and in turn shaped its material form. To do so, it draws on the archival materials of social reformers and parks superintendents, equipment manufacturers and architects, from the nineteenth and twentieth centuries. It finds that the ideal playground has long represented a site where changing conceptions of nature, health, childhood, commerce and technology have all been played out, with a corresponding impact on the built form of towns and cities across Britain. As such, Swings and Roundabouts plots the erratic evolution of the playground in public parks, housing estates and other spaces in the urban environment, charting its journey from marginal obscurity to popular ubiquity and the subsequent challenges to its status as a site of health, nature and safety. In doing so, this study sheds light on a previously unacknowledged influence on the urban environment and points to the enduring power of historical values in shaping the public places where we live and play. As a result, it provides vital contextual information for scholars and policymakers seeking to imagine and create more equitable opportunities for the child in the city.

We read with interest the study by Rosenstock et al. (1), which demonstrates that in patients with type 2 diabetes managed on a basal-bolus insulin regimen, switching three prandial insulin injections for a long-acting glucagon-like peptide 1 receptor agonist (GLP-1RA), albiglutide, while maintaining the basal insulin, represents an effective strategy for optimizing glycemic control with reduced risks of hypoglycemia and weight gain along with increased convenience. In the cohort studied, baseline glycated hemoglobin levels were 7.8 ± 0.6% (albiglutide group) and 7.7 ± 0.6% (placebo group), indicating that in many participants, postprandial glycemic excursions were the dominant contributor of hyperglycemia. Achieving good glycemic control in those patients would, …

Aim: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM). Materials and methods: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink. Results: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001). Conclusions: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension. usc Refereed/Peer-reviewed

OBJECTIVES: Stress hyperglycemia occurs in critically ill patients and may be a risk factor for subsequent diabetes. The aims of this study were to determine incident diabetes and prevalent prediabetes in survivors of critical illness experiencing stress hyperglycemia and to explore underlying mechanisms. DESIGN: This was a prospective, single center, cohort study. At admission to ICU, hemoglobin A1c was measured in eligible patients. Participants returned at 3 and 12 months after ICU admission and underwent hemoglobin A1c testing and an oral glucose tolerance test. Blood was also collected for hormone concentrations, whereas gastric emptying was measured via an isotope breath test. β-cell function was modeled using standard techniques. SETTING: Tertiary-referral, mixed medical-surgical ICU. PATIENTS: Consecutively admitted patients who developed stress hyperglycemia and survived to hospital discharge were eligible. MEASUREMENTS AND MAIN RESULTS: Consent was obtained from 40 patients (mean age, 58 yr [SD, 10], hemoglobin A1c 36.8 mmol/mol [4.9 mmol/mol]) with 35 attending the 3-month and 26 the 12-month visits. At 3 months, 13 (37%) had diabetes and 15 (43%) had prediabetes. At 12 months, seven (27%) participants had diabetes, whereas 11 (42%) had prediabetes. Mean hemoglobin A1c increased from baseline during the study: +0.7 mmol/mol (-1.2 to 2.5 mmol/mol) at 3 months and +3.3 mmol/mol (0.98-5.59 mmol/mol) at 12 months (p = 0.02). Gastric emptying was not significantly different across groups at either 3 or 12 months. CONCLUSIONS: Diabetes and prediabetes occur frequently in survivors of ICU experiencing stress hyperglycemia. Based on the occurrence rate observed in this cohort, structured screening and intervention programs appear warranted. usc Refereed/Peer-reviewed

Allegations of voting on partisan or political lines has become a regular feature of discussions on the role of the U.S. judiciary. The result has been the framing of judges within the conventional political binary of liberalism and conservatism. This tendency has also extended to the scholarly analysis of historical judicial actors. However, this thesis argues that the application of such labels distorts and simplifies the complex role of judges, both past and present. It does so by investigating the role of fellow lower federal court judges, and cousins, Learned and Augustus Hand, in civil liberties cases in the early-to-mid twentieth century. Although both men have been popularly regarded as symbols of judicial independence, their contributions to law have typically been framed in political terms. This thesis examines the Hands through a judicial biography focused on civil liberties cases to reveal the ways in which their opinions and rulings reflected a complex philosophical methodology that transcended political labels. In turn, it exposes the limitations of the contemporary political binary as an accurate measure of judicial decision making.The thesis traces this approach through the Hands' formative years and the legal areas of political speech, obscenity, immigration, and criminal rights. It scrutinises landmark and highly contentious civil liberties cases, as well as lesser known and unstudied cases, to highlight how they reshaped law whilst maintaining judicial independence. Furthermore, it draws on new documents and letters to display how their relationship dynamic prompted differing views on the optimal approach to maintaining judicial restraint. In so doing, the thesis shows how the Hands were able to avoid political and personal inclinations to provide lasting contributions that continue to influence and shape current legal debates. With the Supreme Court under intensifying calls for reform, this thesis adds timely nuance to our historical understanding of the delicate relationship between politics and law.

Refereed/Peer-reviewed