What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium?

Microalbuminuria is an important risk factor for cardiovascular disease and progressive renal impairment. This holds true in the general population and particularly in those with diabetes, in whom it is common and marks out those likely to develop macrovascular disease and progressive renal impairment. Understanding the pathophysiological mechanisms through which microalbuminuria occurs holds the key to designing therapies to arrest its development and prevent these later manifestations

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

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

Symptomatic congenital syphilis in a tertiary neonatal unit in Cape Town, South Africa: High morbidity and mortality in a preventable disease

Background. Despite preventive measures and effective treatment, congenital syphilis continues to impact significantly on neonatal morbidity and mortality. There has been no recent South African (SA) published literature reviewing congenital syphilis, particularly in the context of a tertiary neonatal setting.Objectives. To describe the clinical features of symptomatic neonates with congenital syphilis and to identify modifiable patient, clinical and health facility factors that contributed to syphilis infection.Methods. All positive serological tests for syphilis performed in neonates at Groote Schuur Hospital (GSH), Cape Town, SA, between 1 January 2011 and 31 December 2013 were obtained. Folders were reviewed, and neonates with clinical signs of congenital syphilis were included.Results. Of 50 symptomatic neonates, 19 (38%) died. Twenty-eight mothers (56%) were unbooked and therefore received no antenatal care. Most mothers (98%) were inadequately treated. Health worker-related failures included poor notification and partner tracing as well as failure to recheck syphilis serology after 32 weeks’ gestation in mothers who initially tested negative. Thirty-four neonates required intensive care unit admission. Two significant predictors of mortality were 1-minute and 5-minute Apgar scores <5. Hydrops fetalis was an independent risk factor for mortality, as were moderate to severely abnormal cranial ultrasound scan findings.Conclusions. Congenital syphilis in neonates admitted to the GSH neonatal unit was associated with substantial morbidity and mortality. The modifiable factors identified represent inadequate antenatal healthcare and health system failures. These factors are longstanding, highlighting the need to establish governance and audit processes and address the continuing socioeconomic and sociocultural barriers that mothers face as a way forward in ultimately eliminating this entirely preventable disease.

The use of data in resource limited settings to improve quality of care

Quality improvement is driven by benchmarking between and within institutions over time and the collaborative improvement efforts that stem from these comparisons. Benchmarking requires systematic collection and use of standardized data. Low- and middle-income countries (LMIC) have great potential for improvements in newborn outcomes but serious obstacles to data collection, analysis, and implementation of robust improvement methodologies exist. We review the importance of data collection, internationally recommended neonatal metrics, selected methods of data collection, and reporting. The transformation from data collection to data use is illustrated by several select data system examples from LMIC. Key features include aims and measures important to neonatal team members, co-development with local providers, immediate access to data for review, and multidisciplinary team involvement. The future of neonatal care, use of data, and the trajectory to reach global neonatal improvement targets in resource-limited settings will be dependent on initiatives led by LMIC clinicians and experts

Allosteric communication in class A β-lactamases occurs via cooperative coupling of loop dynamics

Understanding allostery in enzymes and tools to identify it, offer promising alternative strategies to inhibitor development. Through a combination of equilibrium and nonequilibrium molecular dynamics simulations, we identify allosteric effects and communication pathways in two prototypical class A β-lactamases, TEM-1 and KPC-2, which are important determinants of antibiotic resistance. The nonequilibrium simulations reveal pathways of communication operating over distances of 30 Å or more. Propagation of the signal occurs through cooperative coupling of loop dynamics. Notably, 50% or more of clinically relevant amino acid substitutions map onto the identified signal transduction pathways. This suggests that clinically important variation may affect, or be driven by, differences in allosteric behavior, providing a mechanism by which amino acid substitutions may affect the relationship between spectrum of activity, catalytic turnover and potential allosteric behavior in this clinically important enzyme family. Simulations of the type presented here will help in identifying and analyzing such differences

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

Efficiencies of recovery and extraction of trace DNA from non-porous surfaces

DNA recovery and extraction efficiencies are key considerations for trace DNA interpretation in casework, but prior studies have tended to focus on assessing these for body fluids rather than trace DNA. This study therefore examined the recovery and extraction of trace DNA using different collection methods from a range of non-porous surfaces relevant to crimes including homicides, terror attacks, and wildlife poaching. Direct extraction of DNA from solutions of a known concentration revealed absolute extraction efficiencies of ∼82%. When DNA was extracted from swabs seeded with the DNA solution, a similarly high efficiency of ∼85% was achieved from nylon-flocked swabs, with a lower efficiency of ∼55% from cotton swabs. However, when DNA was recovered from non-porous surfaces with swabs, ∼55% of DNA was still recovered from plastic knife handles, but lower efficiencies were achieved from the other substrates, particularly metal cable. Varied and poor recovery was observed using mini-tapes and requires further investigation. These results demonstrate that > 50% recovery efficiency of trace DNA is achievable with both swab types, although recovery rates may be affected by surface type and/or practitioner experience