Clawback Provisions in Real Estate Investment Trusts

Using a sample of 195 unique real estate investment trusts (REITs), we examine factors related to the adoption of clawback provisions within managerial compensation contracts. In general, we find strong and consistent empirical evidence that clawback provision are directly related to firm size, complexity, leverage, growth options, monitoring incentives, and CEO performance incentives. We also find that clawbacks are associated with enhanced market and accounting performance, with stronger performance relations observed for adoption decisions tied directly to regulatory mandates. In sum, we conclude compensation clawback provisions represent a value-relevant, strategic governance mechanism for REITs

Characterisation of multiple regulatory domains spanning the major transcriptional start site of the FUS gene, a candidate gene for motor neurone disease

Fused-In-Sarcoma (FUS) is a candidate gene for neurological disorders including motor neurone disease and Parkinson’s disease in addition to various types of cancer. Recently it has been reported that over expression of FUS causes motor neurone disease in mouse models hence mutations leading to changes in gene expression may contribute to the development of neurodegenerative disease. Genome evolutionary conservation was used to predict important cis-acting DNA regulators of the FUS gene promoter that direct transcription. The putative regulators identified were analysed in reporter gene assays in cells and in chick embryos. Our analysis indicated in addition to regulatory domains 5’ of the transcriptional start site an important regulatory domain resides in intron 1 of the gene itself. This intronic domain functioned both in cell lines and in vivo in the neural tube of the chick embryo including developing motor neurones. Our data suggests the interaction of multiple domains including intronic domains are involved in expression of FUS. A better understanding of the regulation of expression of FUS may give insight into how its stimulus inducible expression may be associated with neurological disorders

End-to-end Molecular Communication Channels in Cell Metabolism: an Information Theoretic Study

The opportunity to control and fine-tune the behavior of biological cells is a fascinating possibility for many diverse disciplines, ranging from medicine and ecology, to chemical industry and space exploration. While synthetic biology is providing novel tools to reprogram cell behavior from their genetic code, many challenges need to be solved before it can become a true engineering discipline, such as reliability, safety assurance, reproducibility and stability. This paper aims to understand the limits in the controllability of the behavior of a natural (non-engineered) biological cell. In particular, the focus is on cell metabolism, and its natural regulation mechanisms, and their ability to react and change according to the chemical characteristics of the external environment. To understand the aforementioned limits of this ability, molecular communication is used to abstract biological cells into a series of channels that propagate information on the chemical composition of the extracellular environment to the cell’s behavior in terms of uptake and consumption of chemical compounds, and growth rate. This provides an information-theoretic framework to analyze the upper bound limit to the capacity of these channels to propagate information, which is based on a well-known and computationally efficient metabolic simulation technique. A numerical study is performed on two human gut microbes, where the upper bound is estimated for different environmental compounds, showing there is a potential for future practical applications

An Analysis of Implicit Bias in Medical Education

Background: The Implicit Association Test (IAT) is a well-researched method of identifying an individual\u27s implicit bias. Occurring outside of conscious awareness, implicit bias manifests itself in the form of nonverbal thoughts, behaviors and actions that influence an individual and that are suggestive of unequal treatment. In the undergraduate medical education curriculum, the IAT is commonly used to assess the medical students\u27 personal bias. Studies from the American Association of Medical Colleges (AAMC) have shown that bias is ranked highly as one of the least addressed educational goals in medical education and training. The medical literature suggests that implicit bias affects how clinical faculty make patient care decisions, and that this in turn affects medical student education. Data collected from our medical school\u27s first year curriculum suggest that there are missed opportunities to explore the effects of bias on health outcomes. Objective: The purpose of this study was to analyze comments in reflection papers submitted by students enrolled in the required Determinants of Health (DoH) course during the Fall 2014- Spring 2015 curriculum at the University of Massachusetts Medical School (UMMS). The DoH course assignment asked students to select a reading, experience in taking the IAT or class discussion, and comment on how the material led to new insight about the potential effect of biases or stereotyping on future clinical decisions. The themes from this analysis provided context for relevant areas for further exploration of the impact of implicit bias in medical education. Method: 125 first-year medical students (48% female, 52% male; mean age 25 years; 95% from Massachusetts, 9% identified as under-represented ethnic/racial minorities) in the entering class of 2014 submitted written reflections following attendance and discussion-based learning in the DoH course. Grounded theory methodology was used for the qualitative analysis of the comments. Papers were de-identified, read, and codes were constructed according to emerging themes (descriptive, diagnostic, and prescriptive) found. The codebook development focused on bias, systemic/institutional bias, individual bias, awareness and health disparities . Student commentary was coded for themes and tallied for total amount of discussion for each theme. Inter-rater reliability was calculated for 20% of the sample using Cohen\u27s kappa. Results: The following themes emerged: 1) an understanding of the IAT and the results of the IAT; 2) a definition of bias; 3) a suggestion of source of bias; 4) factors informing bias; and 5) action items to combat the effects of implicit bias on future physicians. Ninety-five of 125 students\u27 comments (76%) mapped to descriptive themes associated with bias; 27% (n=26/95) of comments suggested all individuals have bias; 57% (n=55) of comments suggested potential sources of bias, ranging from cultural and community upbringings to societal media; 83% (n=79) of comments focused on the negative effect implicit bias can have on decision-making in patient care; and nearly 96% (n=91) of comments felt that acknowledging their own implicit bias would benefit their interactions with patients in their future medical careers. Additionally, 58% (n=73/125) of students\u27 comments noted that making a conscious effort to self-reflect and address bias would improve decision-making, and 32% (n=40) of comments noted it was a physician\u27s responsibility to dismantle the bias found in the healthcare system (15 comments suggested this happen through avenues such as advocacy and legislation). Seventy students\u27 comments (56%) mapped to comments discussing the lAT. Forty-three percent (n=30) comments noted students surprised by their results and 29% (n=20) of comments suggested that the student was not surprised. While 75 students (60%) did not comment on their reaction, the IAT sparked self-reflection of implicit bias and its origin in 68 of these students, and 16% (n=20) of comments found the IAT to be a valuable tool in identifying implicit bias. With regard to the current climate ofhealthcare, 40 responding students (32%) identified racism or racial bias existing within the medical field, noting potential sources of racism including lack of trust in physicians from historical events such as the Tuskegee Syphilis Experiment and societal inequalities as a whole. Additionally, 29 students\u27 comments (23%) mentioned systemic/institutional bias as potentially having an impact on individual bias and vice versa. Conclusions: The use of the IAT in the medical education curriculum is informative and the medical student response to it is impactful. Medical students gain insight into the importance of understanding personal implicit bias and the effect it may have on clinical decision-making through courses such as Determinants of Health. Students have the ability and the desire to identify and self-reflect on the development of behaviors and skills that will facilitate improved decision-making in the care of patients, and improved patient interactions. This analysis also points to the significance of further exploration of faculty involvement in these topics to further engage medical students throughout their undergraduate medical training. As over 93% of the first-year medical school courses did not utilize race identifiers and non-medical factors in clinical vignettes, this is another opportunity to apply real-life scenarios to the educational curriculum

Pre-clinical medical student reflections on implicit bias: Implications for learning and teaching

CONTEXT: Implicit bias affects health professionals\u27 clinical decision-making; nevertheless, published reports of medical education curricula exploring this concept have been limited. This research documents a recent approach to teaching implicit bias. METHODS: Medical students matriculating during 2014 and 2015 participated in a determinants of health course including instruction about implicit bias. Each submitted a reflective essay discussing implicit bias, the experience of taking the Implicit Association Test (IAT), and other course content. Using grounded theory methodology, student essays that discussed reactions to the IAT were analyzed for content themes based on specific statements mapping to each theme. Twenty-five percent of essays underwent a second review to calculate agreement between raters regarding identification of statements mapping to themes. OUTCOME: Of 250 essays, three-quarters discussed students\u27 results on the IAT. Theme comments related to: a) experience taking the IAT, b) bias in medicine, and c) prescriptive comments. Most of the comments (84%) related to students\u27 acknowledging the importance of recognizing implicit bias. More than one-half (60%) noted that bias affects clinical decision-making, and one-fifth (19%) stated that they believe it is the physician\u27s responsibility to advocate for dismantling bias. CONCLUSIONS: Through taking the IAT and developing an understanding of implicit bias, medical students can gain insight into the effect it may have on clinical decision-making. Having pre-clinical medical students explore implicit bias through the IAT can lay a foundation for discussing this very human tendency

Metabolic Synergy between Human Symbionts \u3ci\u3eBacteroides\u3c/i\u3e and \u3ci\u3eMethanobrevibacter\u3c/i\u3e

ABSTRACT Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing techniques to analyze growth under a range of conditions representing the nutrient environment of the host. We verify that B. thetaiotaomicron fermentation products are sufficient for M. smithii growth and that accumulation of fermentation products alters secretion of metabolites by B. thetaiotaomicron to benefit M. smithii. Studies suggest that B. thetaiotaomicron metabolic efficiency is greater in the absence of fermentation products or in the presence of M. smithii. Under certain conditions, B. thetaiotaomicron and M. smithii form interspecies granules consistent with behavior observed for syntrophic partnerships between microbes in soil or sediment enrichments and anaerobic digesters. Furthermore, when vitamin B12, hematin, and hydrogen gas are abundant, coculture growth is greater than the sum of growth observed for monocultures, suggesting that both organisms benefit from a synergistic mutual metabolic relationship. IMPORTANCE The human gut functions through a complex system of interactions between the host human tissue and the microbes which inhabit it. These diverse interactions are difficult to model or examine under controlled laboratory conditions. We studied the interactions between two dominant human gut microbes, B. thetaiotaomicron and M. smithii, using a seven-component culturing approach that allows the systematic examination of the metabolic complexity of this binary microbial system. By combining high-throughput methods with machine learning techniques, we were able to investigate the interactions between two dominant genera of the gut microbiome in a wide variety of environmental conditions. Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase

Detection of Prion Protein in Urine-Derived Injectable Fertility Products by a Targeted Proteomic Approach

BACKGROUND: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG). METHODOLOGY/PRINCIPAL FINDINGS: Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products. CONCLUSIONS/SIGNIFICANCE: The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products

Procedural and physical interventions for vaccine injections systematic review of randomized controlled trials and quasi-randomized controlled trials

Background: This systematic review evaluated the effectiveness of physical and procedural interventions for reducing pain and related outcomes during vaccination. Design/Methods: Databases were searched using a broad search strategy to identify relevant randomized and quasi-randomized controlled trials. Data were extracted according to procedure phase (preprocedure, acute, recovery, and combinations of these) and pooled using established methods. Results: A total of 31 studies were included. Acute infant distress was diminished during intramuscular injection without aspiration (n=313): standardized mean difference (SMD) -0.82 (95% confidence interval [CI]: -1.18, -0.46). Injecting the most painful vaccine last during vaccinations reduced acute infant distress (n=196): SMD -0.69 (95%CI: -0.98, -0.4). Simultaneous injections reduced acute infant distress compared with sequential injections (n=172): SMD -0.56 (95%CI: -0.87, -0.25). There was no benefit of simultaneous injections in children. Less infant distress during the acute and recovery phases combined occurred with vastus lateralis (vs. deltoid) injections (n=185): SMD -0.70 (95%CI: -1.00, -0.41). Skin-to-skin contact in neonates (n=736) reduced acute distress: SMD -0.65 (95% CI: -1.05, -0.25). Holding infants reduced acute distress after removal of the data from 1 methodologically diverse study (n=107): SMD -1.25 (95% CI: -2.05, -0.46). Holding after vaccination (n=417) reduced infant distress during the acute and recovery phases combined: SMD -0.65 (95% CI: -1.08, -0.22). Self-reported fear was reduced for children positioned upright (n=107): SMD -0.39 (95% CI: -0.77, -0.01). Non-nutritive sucking (n=186) reduced acute distress in infants: SMD -1.88 (95% CI: -2.57, -1.18). Manual tactile stimulation did not reduce pain across the lifespan. An external vibrating device and cold reduced pain in children (n=145): SMD -1.23 (95% CI: -1.58, -0.87). There was no benefit of warming the vaccine in adults. Muscle tension was beneficial in selected indices of fainting in adolescents and adults. Conclusions: Interventions with evidence of benefit in select populations include: no aspiration, injecting most painful vaccine last, simultaneous injections, vastus lateralis injection, positioning interventions, non-nutritive sucking, external vibrating device with cold, and muscle tension

Vitamin A and D intake in pregnancy, infant supplementation, and asthma development:the Norwegian Mother and Child Cohort

Background Western diets may provide excess vitamin A, which is potentially toxic and could adversely affect respiratory health and counteract benefits from vitamin D. Objective The aim of this study was to examine child asthma at age 7 y in relation to maternal intake of vitamins A and D during pregnancy, infant supplementation with these vitamins, and their potential interaction. Design We studied 61,676 school-age children (born during 2002–2007) from the Norwegian Mother and Child Cohort with data on maternal total (food and supplement) nutrient intake in pregnancy (food-frequency questionnaire validated against biomarkers) and infant supplement use at age 6 mo (n = 54,142 children). Linkage with the Norwegian Prescription Database enabled near-complete follow-up (end of second quarter in 2015) for dispensed medications to classify asthma. We used log-binomial regression to calculate adjusted RRs (aRRs) for asthma with 95% CIs. Results Asthma increased according to maternal intake of total vitamin A [retinol activity equivalents (RAEs)] in the highest (≥2031 RAEs/d) compared with the lowest (≤779 RAEs/d) quintile (aRR: 1.21; 95% CI: 1.05, 1.40) and decreased for total vitamin D in the highest (≥13.6 µg/d) compared with the lowest (≤3.5 µg/d) quintile (aRR: 0.81; 95% CI: 0.67, 0.97) during pregnancy. No association was observed for maternal intake in the highest quintiles of both nutrients (aRR: 0.99; 95% CI: 0.83, 1.18) and infant supplementation with vitamin D or cod liver oil. Conclusions Excess vitamin A (≥2.5 times the recommended intake) during pregnancy was associated with increased risk, whereas vitamin D intake close to recommendations was associated with a reduced risk of asthma in school-age children. No association for high intakes of both nutrients suggests antagonistic effects of vitamins A and D. This trial was registered at http://www.clinicaltrials.gov as NCT03197233. © 2018 American Society for Nutrition. This work is written by (a) US Government employee(s) and is in the public domain in the US

End-to-end Molecular Communication Channels in Cell Metabolism: an Information Theoretic Study

The opportunity to control and fine-tune the behavior of biological cells is a fascinating possibility for many diverse disciplines, ranging from medicine and ecology, to chemical industry and space exploration. While synthetic biology is providing novel tools to reprogram cell behavior from their genetic code, many challenges need to be solved before it can become a true engineering discipline, such as reliability, safety assurance, reproducibility and stability. This paper aims to understand the limits in the controllability of the behavior of a natural (non-engineered) biological cell. In particular, the focus is on cell metabolism, and its natural regulation mechanisms, and their ability to react and change according to the chemical characteristics of the external environment. To understand the aforementioned limits of this ability, molecular communication is used to abstract biological cells into a series of channels that propagate information on the chemical composition of the extracellular environment to the cell’s behavior in terms of uptake and consumption of chemical compounds, and growth rate. This provides an information-theoretic framework to analyze the upper bound limit to the capacity of these channels to propagate information, which is based on a well-known and computationally efficient metabolic simulation technique. A numerical study is performed on two human gut microbes, where the upper bound is estimated for different environmental compounds, showing there is a potential for future practical applications