Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

ABSTRACT: Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.

Cohort scheduling of freshman exercise physiology majors improves social integration and perceptions of faculty but not academic performance.

Cohort scheduling intentionally places students in the same sections of several classes (e.g., biology, algebra, and writing) with a consistent peer group and is typically done for small groups (<30 students) to enable better interaction among students. The goal of this study was to compare cohort scheduling to traditional scheduling methods among freshmen in a physiology-related program. Outcomes included retention to the university and major, semester grades, and institutional integration and perceived group cohesion. Incoming freshmen (n = 209) were randomized into control (n = 43; scheduled with traditional methods) and intervention (n = 166; coenrolled in first-year seminar course, biology, and medical terminology) groups. Outcomes were collected via surveys or requested from the university registrar. There was no significant difference in the likelihood of retention to the university or major and no differences between groups in pass/fail rates for the first-year seminar or biology courses. At the end of the semester, there were no differences between groups in Perceived Cohesion for Small Groups (P = 0.102) or the Institutional Integration Scale (P = 0.357). However, the intervention group scored higher on the Institutional Integration Scale's subscales related to social integration and faculty. Cohort scheduling did not impact retention to the university or major but improved secondary outcomes related to retention, specifically social integration and student perceptions of faculty.NEW & NOTEWORTHY Compared with traditional scheduling methods, cohort scheduling freshman in physiology programs does not improve retention but improves students' social integration and perceptions of faculty.

Peer-supported physical activity intervention for academic probation freshmen in a physiology-related major: a feasibility study.

To retain students on academic probation, physiology and physiology-related programs may offer a variety of academic support initiatives. This pilot research study examined the feasibility and perceptions of implementing a success coach-led physical activity (PA) program for freshmen on academic probation in a physiology-related program. Freshman on academic probation [grade point average (GPA) <2.0] worked with a success coach on academic success strategies and PA. Freshmen completed validated surveys (Academic Self-Efficacy, Self-Efficacy of Regulated Learning, Institutional Integration Scale) before and after intervention and semistructured interviews after intervention. Retention rate was determined at longitudinal follow-up in Fall 2022. Six freshmen participated. Average GPA did not improve between Fall 2021 (1.561 ± 0.285) and Spring 2022 (1.606 ± 0.832) (P = 0.89). All felt that the program improved their study skills, but fewer (40%) felt that their grades improved. Most had positive perceptions of the PA program, including self-reported improvements in health/fitness (60%), mood/mental well-being (100%), and stress management (80%). Although most improved attention when studying (80%), this did not translate to improved academic performance (40%). For the Institutional Integration Scales, only the scale for "Faculty Concern for Student Development and Teaching" improved by the end of the semester (pre: 37 ± 7.6, post: 19 ± 3.4, P < 0.001). Retention rate of participants (83%) was higher than the university's overall retention rate for students on academic probation (37%). By fostering social integration, improving mood and mental well-being, and increasing university retention rates this pilot project confirmed the feasibility of using upperclassmen as success coaches for a physical activity intervention for academic probation freshmen.NEW & NOTEWORTHY Using upperclassmen as success coaches for a physical activity intervention for academic probation freshmen fostered social integration, improved mood and mental well-being, and increased university retention rates.

Experimental evidence on a "light-touch" personalized email intervention in an online, undergraduate physiology course.

In large physiology classes, there is a demand for low-effort, or "light touch," strategies that faculty can use to connect with students and promote increased academic performance and student engagement. The purpose of this study was to compare personalized versus standardized emails following unit quizzes on student perceptions of faculty engagement, participation in academic resources, and academic performance in a junior-level, online physiology course. Students completed the online unit quiz and received a subsequent feedback email from the course director. Students were randomized into the Control (n = 101) or the Experimental (n = 104) group for general or personalized performance feedback emails, respectively. Students completed start and end of semester surveys capturing demographics, course expectations, self-reported use of resources, and impressions of the faculty. Final exam and course grades were collected. Perceptions of faculty were similar between groups, and receiving professor feedback after quizzes did not make the Experimental group more likely to use any of the available academic support services. There was no difference in final exam grades (Control: 73.9 ± 14.1%; Experimental: 73.4 ± 15.3%) or final course grades between groups (Control: 79.2 ± 13.1%; Experimental: 78.7 ± 13.3; P > 0.05). Personalized performance feedback from light-touch emails did not improve student perceptions of faculty engagement, self-reported participation in academic resources, or academic performance compared with a standardized email in a junior-level, online physiology course. Overall, this study does not support the use of personalized emails regarding quiz performance in an online physiology course.NEW & NOTEWORTHY Personalized performance feedback from light-touch emails did not improve student perceptions of faculty engagement, self-reported participation in academic resources, or academic performance compared with a standardized email in a junior-level, online physiology course.

Perceptions of academic preparedness of first-gen freshmen in a physiology major inform recommendations for program-level academic development initiatives.

Many factors contribute to students' academic success, and some, including first-generation (FG) college student status and academic preparation, are especially relevant in physiology programs. The purpose of this qualitative study was to examine FG college students' perceptions of academic preparedness and intended success strategies with the goal of informing program-level strategies to support FG students in similar undergraduate physiology-related programs. FG freshmen completed short surveys and reflections at the start and end of the semester. Qualitative responses from written reflections were compiled, and content was analyzed. Students were high achievers in high school; 98% expected As and Bs in college, but only 53% had achieved this by the end of the first semester. At the start of the semester, FG students reported feeling prepared academically but were hoping to improve their academic readiness skills, and academic success plans focused on organizational strategies. At the end of the semester, some thought they were as prepared as they expected, but most found they were not as academically prepared for college as they had expected. Several minor themes were identified as areas to address with future cohorts. This study proposes several potential avenues by which to support FG freshmen's academic success in similar physiology programs, including early identification of at-risk students, setting realistic expectations, educating students early and often about evidence-based strategies, and developing academic recovery strategies as needed.NEW & NOTEWORTHY A qualitative investigation of first-generation (FG) college freshmen's perceptions of academic preparedness and intended success strategies informs the development of potential avenues by which to support FG freshmen in physiology programs.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

HIV infection and anaemia do not affect HbA1c for the detection of diabetes in black South Africans: Evidence from the Durban Diabetes Study.

OBJECTIVE: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS: In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: ß  = -3.4 mmol/mol or -0.31%, p < 0.001 [macrocytic anaemia] to ß = 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART-treated HIV (2.9% vs. 1.2%, p = 0.08). CONCLUSIONS: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub-Saharan African populations.

Differences in joint power distribution in high and low lactate threshold cyclists.

PURPOSE: The biomechanical differences between cyclists with a high compared with a low blood lactate threshold (HLT; 80% VO2max vs LLT, 70% VO2max) have yet to be completely described. We hypothesize that HLT cyclists reduce the stress placed on the knee extensor muscles by increasing the relative contribution from the hip joint during high-intensity cycling. METHOD: Sixteen well-trained endurance athletes, with equally high VO2max while cycling and running completed submaximal tests during incremental exercise to identify lactate threshold ([Formula: see text]) while running and cycling. Subjects were separated into two groups based on % VO2max at LT during cycling (high; HLT: 80.2 ± 2.1% VO2max; n = 8) and (LLT: 70.3 ± 2.9% VO2max; n = 8; p < 0.01). Absolute and relative joint specific powers were calculated from kinematic and pedal forces using inverse dynamics while cycling at intensities ranging from 60-90% VO2max for between group comparisons. RESULT: There was no difference between HLT and LLT in [Formula: see text] (p > 0.05) while running. While cycling in LLT, knee joint absolute power increased with work rate (p < 0.05); however, in HLT no changes in knee joint absolute power occurred with increased work rate (p > 0.05). The HLT generated significantly greater relative hip power compared with the LLT group at 90% VO2max (p < 0.05). CONCLUSION: These data suggest that HLT cyclists exhibit a greater relative hip contribution to power output during cycling at 90% VO2max. These observations support the theory that lactate production during cycling can be reduced by spreading the work rate between various muscle groups.

Developmental bias in the evolution of phalanges.

Evolutionary theory has long argued that the entrenched rules of development constrain the range of variations in a given form, but few empirical examples are known. Here we provide evidence for a very deeply conserved skeletal module constraining the morphology of the phalanges within a digit. We measured the sizes of phalanges within populations of two bird species and found that successive phalanges within a digit exhibit predictable relative proportions, whether those phalanges are nearly equal in size or exhibit a more striking gradient in size from large to small. Experimental perturbations during early stages of digit formation demonstrate that the sizes of the phalanges within a digit are regulated as a system rather than individually. However, the sizes of the phalanges are independent of the metatarsals. Temporal studies indicate that the relative sizes of the phalanges are established at the time of initial cell condensation. Measurements of phalanges across species from six major taxonomic lineages showed that the same predictable range of variants is conserved across vast taxonomic diversity and evolutionary time, starting with the very origins of tetrapods. Although in general phalangeal variations fall within a range of nearly equal-sized phalanges to those following a steep large-to-small gradient, a novel derived condition of excessive elongation of the distal-most phalanges has evolved convergently in multiple lineages, for example under selection for grasping rather than walking or swimming. Even in the context of this exception, phalangeal variations observed in nature are a small subset of potential morphospace.

Are Wearable Photoplethysmogram-Based Heart Rate Variability Measures Equivalent to Electrocardiogram? A Simulation Study.

BACKGROUND: Traditional electrocardiography (ECG)-derived heart rate variability (HRV) and photoplethysmography (PPG)-derived "HRV" (termed PRV) have been reported interchangeably. Any potential dissociation between HRV and PRV could be due to the variability in pulse arrival time (PAT; time between heartbeat and peripheral pulse). OBJECTIVE: This study examined if PRV is equivalent to ECG-derived HRV and if PRV's innate error makes it a high-quality measurement separate from HRV. METHODS: ECG data from 1084 subjects were obtained from the PhysioNet Autonomic Aging dataset, and individual PAT dispersions for both the wrist (n = 42) and finger (n = 49) were derived from Mol et al. (Exp Gerontol. 2020; 135: 110938). A Bayesian simulation was constructed whereby the individual arrival times of the PPG wave were calculated by placing a Gaussian prior on the individual QRS-wave timings of each ECG series. The standard deviation (σ) of the prior corresponds to the PAT dispersion from Mol et al. This was simulated 10,000 times for each PAT σ. The root mean square of successive differences (RMSSD) and standard deviation of N-N intervals (SDNN) were calculated for both HRV and PRV. The Region of Practical Equivalence bounds (ROPE) were set a priori at ± 0.2% of true HRV. The highest density interval (HDI) width, encompassing 95% of the posterior distribution, was calculated for each PAT σ. RESULTS: The lowest PAT σ (2.0 SD) corresponded to 88.4% within ROPE for SDNN and 21.4% for RMSSD. As the σ of PAT increases, the equivalence of PRV and HRV decreases for both SDNN and RMSSD. The HDI interval width increases with increasing PAT σ, with the HDI width increasing at a higher rate for RMSSD than SDNN. CONCLUSIONS: For individuals with greater PAT variability, PRV is not a surrogate for HRV. When considering PRV as a unique biometric measure, SDNN may have more favorable measurement properties than RMSSD, though both exhibit a non-uniform measurement error.

Arch Stiffness Does Not Determine Running Economy in Recreational Runners.

The primary purpose of this study was to determine the relationship between foot length, arch stiffness, and running economy in recreational runner at low running velocities. Sixteen trained endurance (age 20.5 ± 0.4 yrs, height 172 ± 1.8 cm, and mass 68.53 ± 2.40 kg) athletes had their foot anthropometrics and running economy measured. Foot anthropometrics including Foot Length (FL), Arch Stiffness Index (ASI), and Achilles Tendon Moment Arm Length (ATML) were assessed. Subjects then completed a maximal oxygen consumption (VO2max) test and running economy (RE) assessment. RE was measured as the oxygen consumption during running at velocities of 9.9 km/h and 11.9 km/h at a 1% grade. Data is reported as Mean ± SE, and the relationship between foot anthropometrics and running economy was assessed with linear regression (α = 0.05). Results: Absolute and relative VO2max values were 3.68 ± 0.19 L/min and 52.96 ± 1.51 mL/kg/min. ASI was 1513 ± 174.27 A.U. with a standing foot length of 25.41 ± 0.4 cm. Subject oxygen consumption at 9.9 km/h and 11.9 km/h was 34.9 ± 0.80 mL/kg/min and 41.02 ± 0.82 mL/kg/min, respectively. There was no correlation between ASI, FL, AHI, and RE (p > 0.05). Arch stiffness and Achilles tendon moment arm do not determine running economy. Therefore, running economy may be impacted by other physiological and biomechanical factors at low running velocities.

Normative isometric plantarflexion strength values for professional level, male rugby union athletes.

OBJECTIVES: The primary aim was to establish normative values of isometric plantarflexor muscle strength in professional male rugby union players and compare forwards with backs. The secondary aims were to examine how individual playing position or age influences isometric plantarflexor strength. DESIGN: Cross-sectional. SETTING: Testing at professional rugby clubs. PARTICIPANTS: 355 players (201 forwards and 154 backs) from 9 clubs in the English Premiership club competition. MAIN OUTCOME MEASURES: Maximal unilateral isometric plantarflexion strength was measured, using a Fysiometer C-Station, in a seated position with a flexed knee and in maximal available dorsiflexion. Values are reported normalised to body mass and specific to playing position. RESULTS: Mean combined limb isometric plantarflexion strength for the group was 193.1 kg (SD 32) or 1.86 xBW. (SD 0.31). Forwards were significantly weaker than backs (forwards = 1.75xBW (SD 0.26), backs = 2.00xBW (SD 0.28) (p=<0.0001)). Age category revealed no influence on plantarflexor strength. CONCLUSION: This study presents normative isometric plantarflexion strength values for professional male rugby union players. Forwards are typically relatively weaker than backs.

The relationship between isometric force-time curve characteristics and club head speed in recreational golfers.

The primary purpose of the present investigation was to examine the relationships between club head speed, isometric midthigh pull performance, and vertical jump performance in a cohort of recreational golfers. Twelve recreational golfers (age, 20.4 ± 1.0 years; weight, 77.0 ± 9.8 kg; height, 177.8 ± 6.3 cm; body fat, 17.1 ± 7.6%; handicap, 14.5 ± 7.3; experience, 8.9 ± 3.6 years) completed 3 testing sessions: (a) familiarization session and body composition measurements; (b) measurement of force-time curves in the isometric midthigh pull, countermovement, and static vertical jump (SJ); and (c) measurement of club head speed. During sessions 1 and 2, subjects performed 5 countermovement jumps, 5 SJ, and 2 isometric midthigh pulls. Isometric peak force was measured at 30, 50, 90, 100, 200, and 250 milliseconds. Rate of force development was measured among 0-30, 0-50, 0-90, 0-100, 0-200, and 0-250 milliseconds. Peak rate of force development was determined as the highest value in a 10-millisecond sampling windows. During session 3, subjects performed 10 maximal golf swings with a driver to measure club head speed; peak and average club head speed were analyzed across the 10 swings. Golf handicap was moderately correlated with average (r = -0.52, p = 0.04) and maximal club head speed (r = -0.45, p = 0.07). Force at 150 milliseconds during the isomeric midthigh pull test was moderately correlated with average (r = 0.46, p = 0.07) and maximal club head speed (r = 0.47, p = 0.06). Moderate correlations were also found between the rate of force development from 0 to 150 milliseconds and average (r = 0.38, p = 0.11) and maximal club head speed (r = 0.36, p = 0.12). The present findings suggest that the ability to exhibit high ground reaction forces in time frames <200 milliseconds are related to high club head speeds.

Femoral Artery Closure Devices vs Manual Compression During Cardiac Catheterization and Percutaneous Coronary Intervention.

Background: Femoral arterial access remains widely used despite recent increase in radial access for cardiac catheterization and percutaneous coronary intervention (PCI). Various femoral artery closure devices have been developed and are commonly used to shorten vascular closure times, with variable rates of vascular complications observed in clinical trials. We sought to examine the rates of contemporary outcomes during diagnostic catheterization and PCI with the most common femoral artery closure devices. Methods: We identified patients who had undergone either diagnostic catheterization alone (n = 14,401) or PCI (n = 11,712) through femoral artery access in the Indiana University Health Multicenter Cardiac Cath registry. We compared outcomes according to closure type: manual compression, Angio-Seal, Perclose, or Mynx. Access complications and bleeding outcomes were measured according to National Cardiovascular Data â€‹Registry standard definitions. Results: The use of any vascular closure device as compared to manual femoral arterial access hold was associated with a significant reduction in vascular access complications and bleeding events in patients who underwent PCI. No significant difference in access-site complications was observed for diagnostic catheterization alone. Among closure devices, Perclose and Angio-Seal had a lower rate of hematoma than Mynx. Conclusions: The use of femoral artery access closure devices is associated with a reduction in vascular access complication rates as compared to manual femoral artery compression in patients who undergo PCI.

Self-functioning and perceived parenting: relations of parental empathy and love inconsistency with narcissism, depression, and self-esteem.

In Heinz Kohut's (1977, 1984) theory of the psychology of the self, good parenting provides a child with optimal frustration and just the right amount of loving empathic concern. In the present study, the authors examined the relations of perceived parental empathy and love inconsistency with measures of narcissism, self-esteem, and depression. In a sample of university undergraduates (N=232; 78 men, 153 women, and 1 nonresponder), perceived parental empathy predicted more adaptive self-functioning, whereas parental love inconsistency was related to psychological maladjustment. These results support the theoretical assumption that perceived parental empathy is associated with healthy self-development.

Cardiovascular responses to exercise when increasing skin temperature with narrowing of the core-to-skin temperature gradient.

The decline in stroke volume (SV) during exercise in the heat has been attributed to either an increase in cutaneous blood flow (CBF) that reduces venous return or an increase in heart rate (HR) that reduces cardiac filling time. However, the evidence supporting each mechanism arises under experimental conditions with different skin temperatures (Tsk; e.g., ≥38°C vs. ≤36°C, respectively). We systematically studied cardiovascular responses to progressively increased Tsk (32°C-39°C) with narrowing of the core-to-skin gradient during moderate intensity exercise. Eight men cycled at 63 ± 1% peak oxygen consumption for 20-30 min. Tsk was manipulated by having subjects wear a water-perfused suit that covered most of the body and maintained Tsk that was significantly different between trials and averaged 32.4 ± 0.2, 35.5 ± 0.1, 37.5 ± 0.1, and 39.5 ± 0.1°C, respectively. The graded heating of Tsk ultimately produced a graded elevation of esophageal temperature (Tes) at the end of exercise. Incrementally increasing Tsk resulted in a graded increase in HR and a graded decrease in SV. CBF reached a similar average plateau value in all trials when Tes was above ~38°C, independent of Tsk. Tsk had no apparent effect on forearm venous volume (FVV). In conclusion, the CBF and FVV responses suggest no further pooling of blood in the skin when Tsk is increased from 32.4°C to 39.5°C. The decrease in SV during moderate intensity exercise when heating the skin to high levels appears related to an increase in HR and not an increase in CBF. NEW & NOTEWORTHY This study systematically investigated the effect of increasing skin temperature (Tsk) to high levels on cardiovascular responses during moderate intensity exercise. We conclude that the declines in stroke volume were related to the increases in heart rate but not the changes in cutaneous blood flow (CBF) and forearm venous volume (FVV) during moderate intensity exercise when Tsk increased from ~32°C to ~39°C. High Tsk (≥38°C) did not further elevate CBF and FVV compared with lower Tsk during moderate intensity exercise.

Transcript annotation prioritization and screening system (TrAPSS) for mutation screening.

When searching for disease-causing mutations with polymerase chain reaction (PCR)-based methods, candidate genes are usually screened in their entirety, exon by exon. Genomic resources (i.e. www.ncbi.nih.gov, www.ensembl.org, and genome.ucsc.edu) largely support this paradigm for mutation screening by making it easy to view and access sequence data associated with genes in their genomic context. However, the administrative burden of conducting mutation screening in potentially hundreds of genes and thousands of exons in thousands of patients is significant, even with the use of public genome resources. For example, the manual design of oligonucleotide primers for all exons of the 10 Leber's congenital amaurosis (LCA) genes (149 exons) represents a significant information management challenge. The Transcript Annotation Prioritization and Screening System (TrAPSS) is designed to accelerate mutation screening by (1) providing a gene-based local cache of candidate disease genes in a genomic context, (2) automating tasks associated with optimizing candidate disease gene screening and information management, and (3) providing the implementation of an algorithmic technique to utilize large amounts of heterogeneous genome annotation (e.g. conserved protein functional domains) so as to prioritize candidate genes.

Prioritizing regions of candidate genes for efficient mutation screening.

The availability of the complete sequence of the human genome has dramatically facilitated the search for disease-causing sequence variations. In fact, the rate-limiting step has shifted from the discovery and characterization of candidate genes to the actual screening of human populations and the subsequent interpretation of observed variations. In this study we tested the hypothesis that some segments of candidate genes are more likely than others to contain disease-causing variations and that these segments can be predicted bioinformatically. A bioinformatic technique, prioritization of annotated regions (PAR), was developed to predict the likelihood that a specific coding region of a gene will harbor a disease-causing mutation based on conserved protein functional domains and protein secondary structures. This method was evaluated by using it to analyze 710 genes that collectively harbor 4,498 previously identified mutations. Nearly 50% of the genes were recognized as disease-associated after screening only 9% of the complete coding sequence. The PAR technique identified 90% of the genes as containing at least one mutation, with less than 40% of the screening resources that traditional approaches would require. These results suggest that prioritization strategies such as PAR can accelerate disease-gene identification through more efficient use of screening resources.

Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study.

OBJECTIVE: Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. RESEARCH DESIGN AND METHODS: We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. RESULTS: Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7-87.8) and 98.7% specificity (95%CI 97.9-99.4) (AUC 0.94 [95%CI 0.89-1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6-99.8], specificity 92.0% [95%CI: 90.3-93.7]). CONCLUSIONS: In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa.

Features of home and neighbourhood and the liveability of older South Africans.

While older people live in developing countries, little is known about the relative importance of features of their communities in influencing their liveability. We examine components of home and neighbourhood among older South Africans. Linear regression analyses revealed that features of home (basic amenities, household composition, financial status and safety) and neighbourhood (ability to shop for groceries, participate in organizations and feel safe from crime) are significantly associated with life satisfaction. Approaches to liveability that are person-centred and also set within contexts beyond home and neighbourhood are needed to address boundaries between home and neighbourhood; incorporate personal resources into liveability models and import broader environmental contexts such as health and social policy.