Creative Approaches to the Inclusion of Medical Students With Disabilities

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156200/2/aet210425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156200/1/aet210425_am.pd

Minimal immersions of closed surfaces in hyperbolic three-manifolds

We study minimal immersions of closed surfaces (of genus $g \ge 2$) in hyperbolic 3-manifolds, with prescribed data $(\sigma, t\alpha)$, where $\sigma$ is a conformal structure on a topological surface $S$, and $\alpha dz^2$ is a holomorphic quadratic differential on the surface $(S,\sigma)$. We show that, for each $t \in (0,\tau_0)$ for some $\tau_0 > 0$, depending only on $(\sigma, \alpha)$, there are at least two minimal immersions of closed surface of prescribed second fundamental form $Re(t\alpha)$ in the conformal structure $\sigma$. Moreover, for $t$ sufficiently large, there exists no such minimal immersion. Asymptotically, as $t \to 0$, the principal curvatures of one minimal immersion tend to zero, while the intrinsic curvatures of the other blow up in magnitude.Comment: 16 page

Epigenetic age acceleration in the emerging burden of cardiometabolic diseases among migrant and non-migrant African populations:the population based cross-sectional RODAM study

BACKGROUND: African populations are experiencing health transitions due to rapid urbanization and international migration. However, the role of biological aging in this emerging burden of cardiometabolic diseases (CMD) among migrant and non-migrant Africans is unknown. We aimed to examine differences in epigenetic age acceleration (EAA) as measured by four clocks (Horvath, Hannum, PhenoAge and GrimAge) and their associations with cardiometabolic factors among migrant Ghanaians in Europe and non-migrant Ghanaians. METHODS: Genome-wide DNA methylation (DNAm) data of 712 Ghanaians from cross-sectional RODAM study were used to quantify EAA. We assessed correlation of DNAmAge measures with chronological age, and then performed linear regressions to determine associations of body mass index (BMI), fasting blood glucose (FBG), blood pressure, alcohol consumption, smoking, physical activity, and one-carbon metabolism nutrients with EAA among migrant and non-migrants. We replicated our findings among 172 rural-urban sibling pairs from India migration study and among 120 native South Africans from PURE-SA-NW study. FINDINGS: We found that Ghanaian migrants have lower EAA than non-migrants. Within migrants, higher FBG was positively associated with EAA measures. Within non-migrants, higher BMI, and Vitamin B9 (folate) intake were negatively associated with EAA measures. Our findings on FBG, BMI and folate were replicated in the independent cohorts. INTERPRETATION: Our study shows that migration is negatively associated with EAA among Ghanaians. Moreover, cardiometabolic factors are differentially associated with EAA within migrant and non-migrant subgroups. Our results call for context-based interventions for CMD among transitioning populations that account for effects of biological aging. FUNDING: European Commission

New Modeling Approaches Using Detailed Kinetics for Advanced Engines

Ignition timing and control, as well as predictability of engine emissions, are critical factors in advanced-engine system design. The use of detailed chemical kinetics is key to simulating ignition performance and to predicting emissions. This paper describes a collaborative and systematic effort that is underway to enable computationally efficient use of accurate kinetics in engine simulation. The collaboration is focused on building a database of chemical information and on developing a complementary set of software tools that provide efficient engine-simulation capabilities. The goal is predictive simulations that capture the detailed behavior of complex fuels, such as gasoline and diesel, under homogeneous charge compression ignition (HCCI) and related operating conditions. Since directly accounting for all of the hundreds of constituent molecules in a fuel during simulation of real-fuel combustion is intractable, we employ a “model-fuel” or surrogate-fuel approach instead. Mixtures of model-fuel molecules can be determined to adequately represent important real-fuel properties and engine-combustion characteristics. In this work, model fuel compositions are determined by matching a mixture behavior to that of the real fuel, focusing on distillation-curve characteristics, net-heating value, hydrogen-to-carbon ratio, and octane/cetane numbers. This surrogate-definition process requires detailed chemical-kinetics mechanisms for a variety of model-fuel compounds. To build such a database of model-fuel component mechanisms, we have used a combination of automatic mechanism-generation and manual mechanism-development approaches. These methods adhere to a systematic set of class-based rules in determining elementary reaction rates, as well as thermodynamic and transport properties of species. In addition, a comprehensive validation study of the mechanisms, using a wide variety of both fundamental and engine experiments, has allowed refinement of these rules and improvement of both the mechanisms’ predictions and their consistency across components. Even though model fuels have a small number of components, their detailed mechanisms contain large numbers of species (>1000) and reactions (>10000). Systematic mechanism reduction is therefore required for many engineering applications. To this end, we have also developed a package of automated mechanism-reduction techniques. In addition, we have advanced the solution algorithms used in the kinetics simulations and developed a multi-zone engine model that provides good predictions of ignition behavior and emissions. We report on selected results of this systematic approach to using detailed kinetics in engineering simulation, as well as the challenges encountered

Health promotion interventions for community-dwelling older people with mild or pre-frailty : a systematic review and meta-analysis

BACKGROUND: Mild or pre-frailty is common and associated with increased risks of hospitalisation, functional decline, moves to long-term care, and death. Little is known about the effectiveness of health promotion in reducing these risks. This systematic review aimed to synthesise randomised controlled trials (RCTs) evaluating home and community-based health promotion interventions for older people with mild/pre-frailty. METHODS: We searched 20 bibliographic databases and 3 trials registers (January 1990 - May 2016) using mild/pre-frailty and associated terms. We included randomised controlled and crossover trials of health promotion interventions for community-dwelling older people (65+ years) with mild/pre-frailty and excluded studies focussing on populations in hospital, long term care facilities or with a specific condition. Risk of bias was assessed by two reviewers using the Cochrane Risk of Bias tool. We pooled study results using standardised mean differences (SMD) where possible and used narrative synthesis where insufficient outcome data were available. RESULTS: We included 10 articles reporting on seven trials (total n = 506 participants) and included five trials in a meta-analysis. Studies were predominantly small, of limited quality and six studies tested group exercise alone. One study additionally investigated a nutrition and exercise intervention and one evaluated telemonitoring. Interventions of exercise in groups showed mixed effects on functioning (no effects on self-reported functioning SMD 0.19 (95% CI -0.57 to 0.95) n = 3 studies; positive effects on performance-based functioning SMD 0.37 (95% CI 0.07 to 0.68) n = 3 studies). No studies assessed moves to long-term care or hospitalisations. CONCLUSIONS: Currently the evidence base is of insufficient size, quality and breadth to recommend specific health promotion interventions for older people with mild or pre- frailty. High quality studies of rigorously developed interventions are needed

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations