Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

Soil acidity - high rainfall pastures.

Aims of the Project (i) To establish the current pH of the cultivated soils of the high rainfall areas of south-west Western Australia, and the extent to which pH has altered since clearing. (ii) To examine the responsiveness of old land pastures with low current soil pH levels (\u3c 5.5 water) to applied lime. (iii) To relate the responsiveness of subterranean clover-based pastures to measured soil parameters. 80BU14, 81AL10, 81AL12, 81BU18, 81BY18, 81BY25, 81BY26, 82AL4, 82AL5, 82AL55, 82BU7, 82HA35, 82HA36, 82PE1, 82MA20, 83AL7, 83AL9, 83AL10, 83ALll, 83BY29, 84BU9, 84BU10, 84BY37, 84HA21, 84HA37, 84MA21

Soil acidity - high rainfall pastures

A. Lime on old land pastures. 80BU13, 80BU14, 80BU15, 80BU16, 80BU17, 80BY7, 80BY16, 81AL10, 81AL11, 8IAL12, 81AL13, 81AL14, 81AL15, 81AL16, 81BU18, 81BY15, 81BY16, 81BY17, 81BY18, 81BY19, 81BY24, 81BY25, 81BY16, 81MA12, 81W9, 81Wl0, 81Wll, 82AL2, 82AL3, 82AL4, 82ALS, 82AL6, 82ALSS, 82BU6, 82BU7, 82BU8, 82BY37, 82HA35, 82HA36, 82HA38, 82MA20, 82PE1, 83AL7, 83AL8, 83AL9, 83AL10, 83AL11, 83AL12, 83AL13, 83AL14, 83BU20, 83BU24, 83BU25, 83BU26, 83BY29, 83HA19, 83HA40, 83HA41. B. Lime on new land pastures 82AL7, 82AL8

Oscillatory oblique stagnation-point flow toward a plane wall

Two-dimensional oscillatory oblique stagnation-point flow toward a plane wall is investigated. The problem is a eneralisation of the steady oblique stagnation-point flow examined by previous workers. Far from the wall, the flow is composed of an irrotational orthogonal stagnation-point flow with a time-periodic strength, a simple shear flow of constant vorticity, and a time-periodic uniform stream. An exact solution of the Navier-Stokes equations is sought for which the flow streamfunction depends linearly on the coordinate parallel to the wall. The problem formulation reduces to a coupled pair of partial differential equations in time and one spatial variable. The first equation describes the oscillatory orthogonal stagnation-point flow discussed by previous workers. The second equation, which couples to the first, describes the oblique component of the flow. A description of the flow velocity field, the instantaneous streamlines, and the particle paths is sought through numerical solutions of the governing equations and via asymptotic analysis

Soil acidity - high rainfall pastures. Lime on old land pastures - field & glasshouse experiments

Soil Acidity - High Rainfall Pastures (funded by the Australian Meat Research Committee). Lime on old land pastures. 1. Field experiments - 80BU13, 80BU14, 81AL10, 81AL12, 81AL16, 81BU18, 81BY18, 81BY19, 81BY25, 81BY26, 82AL4, 82AL5, 82AL55, 82BU7, 82BU8, 82HA35, 82HA36, 82PE1, 83AL7, 83AL9, 83AL10, 83AL11, 83AL13, 83AL14, 83BU25, 83BU26, 83BY29, 83HA19, 83HA41, 84BU9, 84BY36, 84BY37, 84HA21. 2. Glasshouse experiments - 84GL4. Investigation of factors involved in lime responses on a new land acid peaty sand. 84GL7, 84GL8. Investigation of factors involved in lime responses on old land high rainfall area pastures

Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes

Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxylate-containing, bicyclic compounds, considered as penicillin analogs with an additional free thiol. Here, we show both L- and D-BTZ enantiomers are micromolar competitive βLIs of all MBL classes in vitro, with Ki sof6-15 μM or 36-84 μM for subclass B1 MBLs (IMP-1 and BcII, respectively), and 10-12 μM for the B3 enzyme L1. Against the B2 MBL Sfh-I, the L-BTZ enantiomers exhibit 100-fold lower Ki s (0.26-0.36 μM) than D-BTZs (26-29 μM). Importantly, cell-based time-kill assays show BTZs restore β-lactam susceptibility of Escherichia coli-producing MBLs (IMP-1, Sfh-1, BcII, and GOB-18) and, significantly, an extensively drug-resistant Stenotrophomonas maltophilia clinical isolate expressing L1. BTZs therefore inhibit the full range of MBLs and potentiate β-lactam activity against producer pathogens. X-ray crystal structures reveal insights into diverse BTZ binding modes, varying with orientation of the carboxylate and thiol moieties. BTZs bind the di-zinc centers of B1 (IMP-1; BcII) and B3 (L1) MBLs via the free thiol, but orient differently depending upon stereochemistry. In contrast, the L-BTZ carboxylate dominates interactions with the monozinc B2 MBL Sfh-I, with the thiol uninvolved. D-BTZ complexes most closely resemble β-lactam binding to B1 MBLs, but feature an unprecedented disruption of the D120-zinc interaction. Cross-class MBL inhibition therefore arises from the unexpected versatility of BTZ binding.Fil: Hinchliffe, Philip. University of Bristol; Reino UnidoFil: Gonzalez, Javier Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mojica, María. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Gonzalez, Javier Marcelo. Universidad Nacional de Santiago del Estero. Instituto de Bionanotecnología del Noa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Bionanotecnología del Noa; ArgentinaFil: Castillo, Valerie. Universidad de la República; UruguayFil: Saiz Garcia, Cecilia. Universidad de la República; UruguayFil: Kosmopoulou, Magda. University of Bristol; Reino UnidoFil: Tooke, Catherine. University of Bristol; Reino UnidoFil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mahler, Graciela. Universidad de la República; UruguayFil: Bonomo, Robert. Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Estados Unidos. Case Western Reserve University; Estados UnidosFil: Vila, Alejandro Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Spencer, James. University of Bristol; Reino Unid

Who Owns the Data? Open Data for Healthcare.

Research on large shared medical datasets and data-driven research are gaining fast momentum and provide major opportunities for improving health systems as well as individual care. Such open data can shed light on the causes of disease and effects of treatment, including adverse reactions side-effects of treatments, while also facilitating analyses tailored to an individual's characteristics, known as personalized or "stratified medicine." Developments, such as crowdsourcing, participatory surveillance, and individuals pledging to become "data donors" and the "quantified self" movement (where citizens share data through mobile device-connected technologies), have great potential to contribute to our knowledge of disease, improving diagnostics, and delivery of -healthcare and treatment. There is not only a great potential but also major concerns over privacy, confidentiality, and control of data about individuals once it is shared. Issues, such as user trust, data privacy, transparency over the control of data ownership, and the implications of data analytics for personal privacy with potentially intrusive inferences, are becoming increasingly scrutinized at national and international levels. This can be seen in the recent backlash over the proposed implementation of care.data, which enables individuals' NHS data to be linked, retained, and shared for other uses, such as research and, more controversially, with businesses for commercial exploitation. By way of contrast, through increasing popularity of social media, GPS-enabled mobile apps and tracking/wearable devices, the IT industry and MedTech giants are pursuing new projects without clear public and policy discussion about ownership and responsibility for user-generated data. In the absence of transparent regulation, this paper addresses the opportunities of Big Data in healthcare together with issues of responsibility and accountability. It also aims to pave the way for public policy to support a balanced agenda that safeguards personal information while enabling the use of data to improve public health