The Value of Instability: An Investigation of Intra-Subject Variability in Brain Activity Among Obese Adolescent Girls

BACKGROUND: The present study investigated the value of intra-subject variability (ISV) as a metric for revealing differences in cognition and brain activation associated with an obese versus lean body mass. METHODS: Ninety-six adolescents with a lean body mass (BMI %-ile = 5-85), and 92 adolescents with an obese body mass (BMI %-ile \u3e=95), performed two tasks (Stroop and Go/NoGo) challenging response inhibition skills. The standard deviations and averages of their reaction time and P300 electroencephalographic responses to task stimuli were computed across trials. RESULTS: During the Go/NoGo task, the reaction times of subjects with an obese body mass were more variable than those of their lean body mass peers. Accompanying the greater ISV in reaction times was a group difference in P300 amplitude ISV in the opposite direction across both tasks. The effect sizes associated with these group differences in ISV were marginally greater than the effect sizes for the comparisons of the group means. CONCLUSIONS: ISV may be superior to the mean as a tool for differentiating groups without significant cognitive impairment. The co-occurrence of reduced ISV in P300 amplitude and elevated ISV in reaction time may indicate a constraint among obese adolescent girls in the range of information processing strategies and neural networks that can compete to optimize response output. It remains to be determined if this decrement in neural plasticity has implications for their problem solving skills as well as their response to weight management interventions

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Title IX Sexual Assault Investigations in Public Institutions of Higher Education: Constitutional Due Process Implications of the Evidentiary Standard Set Forth in the Department of Education\u27s 2011 Dear Colleague Letter

This Article examines the constitutional due process impact of the vastly opposite and conflicting standards of review in Title IX sexual assault investigations. Thousands of unionized public employees are subject to the terms and conditions of a public university collective bargaining agreement, which requires a heightened standard of clear and convincing evidence to discipline employees. At the same timeperhaps unknowingly-the employee is also held to the strict federally mandated standard of a preponderance of the evidence, which has a lower standard of review. In short, under the same facts and within the same Title IX investigation, the employee is subject to two conflicting legal standards. The circumstances and facts revealed that many Title IX sexual assault investigations can lead to: employee discipline, suspension, termination or even a private right of action. With this valuable right at stake for unionized public university employees, the legal conflict surrounding standards of review has manifested as one of the nation\u27s most pressing social, political, and legal matters of this decade. By examining this constitutionally important case, I define and articulate the historical and legal origins of (1) collective bargaining rights in the public sector; (2) the origins of Title IX from its initial legislative embodiment to its present day form; and (3) the intersection of unionization and due process rights in Title IX sexual assault investigations which result in an unintended constitutional conflict that may challenge at the core the legal permissibility of the manner in which sexual assault investigations are conducted nationwide. At the outset, I use two major research strategies: (1) a qualitative analysis and nationwide data sample of numerous public sector university collective bargaining agreements; and (2) established legal precedent. Data has been collected from interviews, newspapers, legal precedent, case law and published reports. Undoubtedly, this Article challenges the constitutionality of the preponderance of the evidence standard. While public institutions and public employee unions grapple with this important issue at the grassroots level, the facts uncovered in this critical research reveals that, upon legal challenge to the U.S. Supreme Court, the now ubiquitous preponderance of the standard, ostensibly mandated by the U.S. Department of Education\u27s 2011 Dear Colleague Letter is, in fact, contrary to federal law and violates the Due Process Clause of the U.S. Constitution. This contention is not made lightly however. For what is at stake for public education institutions, Congress, the courts, labor unions and the like is of utmost legal importance. Yet, in view of the legal precedent revealed in this research, there can be only one reasonable conclusion when the evidence is considered in its totality; the April 2011 Dear Colleague Letter is not binding law. Rather, it is merely suggestive agency guidance cleverly held out to the public as binding law but, in actuality, lacks the necessary constitutional authority sufficient to withstand legal challenge