Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58–86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. −0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e′ 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s′ −0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction

Adverse effect of diabetes and hyperglycaemia on arterial stiffness in Europeans, South Asians, and African Caribbeans in the SABRE study

OBJECTIVES: Ethnic minority groups in the UK experience marked differences in cardiovascular disease risk. We investigated differences in arterial central haemodynamics, stiffness, and load in a tri-ethnic population-based cohort. METHODS: A total of 1312 participants (70 ± 6 years) underwent echocardiography and measurement of brachial and central blood pressure to assess central arterial haemodynamics including central pulse pressure (cPP), arterial stiffness [cPP/stroke volume (SV)], systemic vascular resistance (SVR), and load (Ea). RESULTS: Brachial and central SBPs were similar in all ethnic groups. Compared with Europeans, cPP, cPP/SV, and Ea were higher in South Asians. In contrast, cPP/SV was lower in African Caribbeans despite higher mean arterial pressure, higher SVR, and higher diabetes prevalence. cPP/SV and Ea remained significantly higher in South Asians and significantly lower in African Caribbeans after multivariate adjustment. Diabetes and higher HbA1c were more strongly associated with higher cPP/SV in South Asians than in Europeans (Pinteraction = 0.045 and 0.005, respectively); higher HbA1c was also more strongly associated with increased Ea in South Asians than Europeans (Pinteraction = 0.01). There was no evidence of an interaction between glycaemia and cPP/SV in African Caribbeans. CONCLUSIONS: Compared with Europeans, South Asians have unfavorable arterial function. Diabetes and hyperglycaemia have a more deleterious effect on cPP/SV and Ea in South Asians. In contrast, African Caribbeans have more favourable arterial function than Europeans and South Asians. These differences may contribute to the differential ethnic rates of cardiovascular disease

Arterial pressure: agreement between a brachial cuff-based device and radial tonometry

Objectives: Aortic (central) blood pressure (BP) differs from brachial BP and may be a superior predictor of cardiovascular events. However, its measurement is currently restricted to research settings, owing to a moderate level of operator dependency. We tested a new noninvasive device in a large UK cohort. The device estimates central BP using measurements obtained with an upper arm cuff inflated to suprasystolic pressure. We compared these estimates with those obtained using radial tonometry as well as with invasively acquired measurements of aortic BP in a limited number of individuals. Methods: Consecutive cuff-based and tonometry-based estimates of the pressure waveform and the central BP were obtained from 1107 individuals (70 ± 6 years). Short-term and long-term reproducibility studies were performed on 28 individuals. Simultaneous cuff-based and invasively measured pressure traces were acquired and compared in an additional six individuals (65 ± 20 years). Results: Central systolic BP, as estimated by the cuff-based device, was found to be highly reproducible (coefficient of variation 4 and 8% for short and long-term reproducibility, respectively) and was comparable to that estimated by tonometry (average difference 3 ± 6 mmHg, intraclass correlation coefficient = 0.91). The cuff-based pressure waveforms were similar to those acquired invasively (cross-correlation coefficient 0.93), and the difference in the estimated central systolic BP was −5 ± 8 mmHg (P = 0.2). Conclusion: Cuff-based devices show promise to simplify the measurement of central BP, whilst maintaining a similar fidelity to tonometry. This could lead to improved adoption of estimates of central BP in clinical practice

Feasibility and reproducibility of left ventricular rotation by speckle tracking echocardiography in elderly individuals and the impact of different software

Background Changes in ventricular rotation measured by two-dimensional speckle tracking echocardiography (2DSTE) are early indicators of cardiac disease. Data on the clinical feasibility of this important measure are scarce and there is no information on the comparability of different software versions. We assessed the feasibility, reproducibility and within patient temporal variability of 2DSTE in a large community based sample of older adults. We additionally compared 2DSTE results to those generated by 3DSTE. Methods and results 1408 participants underwent transthoracic echocardiography. Using Philips Qlab 8.1 peak LV rotation at either the base or the apex was analysable in 432 (31%) participants. Peak twist measurements were achieved in 274 (20%) participants. 66 participants were randomly selected for the reproducibility study. 20 additional participants had scans 4–6 weeks apart for temporal variability and 3D echocardiography to assess the agreement between 2DSTE and 3DSTE. Reproducibility was evaluated using the intraclass coefficient of correlation (ICC). Better reproducibility for rotation and twist were obtained when measured at the endocardium, and when using more recent software versions, Peak twist and rotation were significantly different using two versions of the same software. Agreement with 3DSTE was better using newer software. Conclusion Feasibility of 2DSTE is low in this cohort of elderly individuals severely limiting its utility in clinical settings. However if high quality images can be acquired assessment of ventricular rotation by 2DSTE is reproducible. Caution should be taken when comparing measurements of ventricular rotation by software from different vendors or different versions of software from the same vendor

Relational Contracts and Organizational Capabilities

A large literature identifies unique organizational capabilities as a potent source of competitive advantage, yet our knowledge of why capabilities fail to diffuse more rapidly—particularly in situations in which competitors apparently have strong incentives to adopt them and a well-developed understanding of how they work—remains incomplete. In this paper we suggest that competitively significant capabilities often rest on managerial practices that in turn rely on relational contracts (i.e., informal agreements sustained by the shadow of the future). We argue that one of the reasons these practices may be difficult to copy is that effective relational contracts must solve the twin problems of credibility and clarity and that although credibility might, in principle, be instantly acquired, clarity may take time to develop and may interact with credibility in complex ways so that relational contracts may often be difficult to build

The Pediatric Obsessive-Compulsive Disorder Treatment Study II: rationale, design and methods

This paper presents the rationale, design, and methods of the Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II), which investigates two different cognitive-behavior therapy (CBT) augmentation approaches in children and adolescents who have experienced a partial response to pharmacotherapy with a serotonin reuptake inhibitor for OCD. The two CBT approaches test a "single doctor" versus "dual doctor" model of service delivery. A specific goal was to develop and test an easily disseminated protocol whereby child psychiatrists would provide instructions in core CBT procedures recommended for pediatric OCD (e.g., hierarchy development, in vivo exposure homework) during routine medical management of OCD (I-CBT). The conventional "dual doctor" CBT protocol consists of 14 visits over 12 weeks involving: (1) psychoeducation, (2), cognitive training, (3) mapping OCD, and (4) exposure with response prevention (EX/RP). I-CBT is a 7-session version of CBT that does not include imaginal exposure or therapist-assisted EX/RP. In this study, we compared 12 weeks of medication management (MM) provided by a study psychiatrist (MM only) with two types of CBT augmentation: (1) the dual doctor model (MM+CBT); and (2) the single doctor model (MM+I-CBT). The design balanced elements of an efficacy study (e.g., random assignment, independent ratings) with effectiveness research aims (e.g., differences in specific SRI medications, dosages, treatment providers). The study is wrapping up recruitment of 140 youth ages 7–17 with a primary diagnosis of OCD. Independent evaluators (IEs) rated participants at weeks 0,4,8, and 12 during acute treatment and at 3,6, and 12 month follow-up visits

Measuring Anxiety in Youth with Learning Disabilities: Reliability and Validity of the Multidimensional Anxiety Scale for Children (MASC)

Youth with learning disabilities (LD) are at an increased risk for anxiety disorders and valid measures of anxiety are necessary for assessing this population. We investigated the psychometric properties of the Multidimensional Anxiety Scale for Children (MASC; March in Multidimensional anxiety scale for children. Multi-Health Systems, North Tonawanda, 1998) in 41 adolescents (ages 11– 17 years) with LD. Youth and parents completed the MASC and were administered the semi-structured Anxiety Disorders Interview Schedule: Child and Parent Versions (ADIS: C/P; Silverman and Albano in The Anxiety Disorders Interview Schedule for DSM-IV-Child and Parent Versions. Psychological Corporation, San Antonio, 1996). Results found that child and parent reports of Social Anxiety on the MASC closely corresponded with ADIS-generated social phobia diagnoses, and parent total scores discriminated well among youth with and without any anxiety disorder. A multi-method multi-trait matrix provided evidence of the construct validity of the MASC total score for both parent and child reports. Our findings provide empirical evidence that parent and child versions of the MASC are useful for assessing anxiety in youth with LD

Benthic community structure and ecosystem functions in above- and below-waterfall pools in Borneo

Waterfalls are geomorphic features that often partition streams into discrete zones. Our study examined aquatic communities, litter decomposition and periphyton growth rates for above- and below-waterfall pools in Ulu Temburong National Park, Brunei. We observed higher fish densities in below-waterfall pools (0.24 fish m−2 vs. 0.02 fish m−2 in above-waterfall pools) and higher shrimp abundance in above-waterfall pools (eight shrimp/pool vs. less than one shrimp/pool in below-waterfall pools). However, macroinvertebrate densities (excluding shrimp) were similar among both pool types. Ambient periphyton was higher in below-waterfall pools in 2013 (4.3 vs. 2.8 g m−2 in above-waterfall pools) and 2014 (4.8 vs. 3.4 g m−2 in above-waterfall pools), while periphyton growth rates varied from 0.05 to 0.26 g m−2 days−1 and were significantly higher in below-waterfall pools in 2014. Leaf litter decomposition rates (0.001 to 0.024 days−1) did not differ between pool types, suggesting that neither shrimp nor fish densities had consistent impacts on this ecosystem function. Regardless, this research demonstrates the varied effects of biotic and abiotic factors on community structure and ecosystem function. Our results have highlighted the importance of discontinuities, such as waterfalls, in tropical streams.</p

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation