Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease

Background: Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention. Methods: One hundred forty-two participants with stage 3–4 chronic kidney disease (CKD) (eGFR 25–60 mL/min/1.73 m2) were included. Subjects were randomised to either a Control group (standard nephrological care [n = 68]) or a Lifestyle Intervention group (12 months of primarily aerobic based exercise training [n = 74]). Four eGFR formulae were compared at baseline and after 12 months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys. Results: Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5 ± 8.9 ml/min/1.73m2. Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9 ± 8.5 ml/min/1.73m2. There were no significant baseline differences between the two groups. Lean mass (r = 0.319, p  <  0.01) and grip strength (r = 0.391, p  <  0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+ 1.9 ± 1.8 METs, p  <  0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12 months. CKD-EPIcys was considerably lower in both groups at both baseline and 12 months than CKD-EPIcr (Control = − 10.5 ± 9.1 and − 13.1 ± 11.8, and Lifestyle Intervention = − 7.9 ± 8.6 and − 8.4 ± 12.3 ml/min/1.73 m2), CKD-EPIcr-cys (Control = − 3.6 ± 3.7 and − 4.5 ± 4.5, and Lifestyle Intervention = − 3.6 ± 3.7 and − 2.5 ± 5.5 ml/min/1.73 m2) and MDRDcr (Control = − 9.3 ± 8.4 and − 12.0 ± 10.7, Lifestyle Intervention = − 6.4 ± 8.4 and − 6.9 ± 11.2 ml/min/1.73 m2). Conclusions: In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12 months of exercise training. Trial registration: The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered)

Adapting the Australian livestock and wheat farms to climate change: value of adaptation at cross-regional scale

The GRAZPLAN biophysical models were used to simulate the dynamics of coupled climate-soil-grassland-livestock systems at 25 representative farms across Australia’s extensive grazing region under historical and a range of projected climates (4 GCMs at 2030, 2050 and 2070 under SRES A2 scenario). The modelling analysis suggests that primary production of grasslands and livestock are likely to decrease across most of southern Australia’s grazing lands under future climate. By including changes in on-farm management in our models we were able to evaluate the effectiveness of certain adaptation options. Options considered individually were not always effective but a combination of Incremental grassland management and animal genetic improvement options (currently available to graziers) was able to offset productivity declines at cross-regional scale. Through implementation of the optimal combination of adaptation options, profitability across southern Australia was shown to increase by +69%, +84% and +116% in 2030, 2050, and 2070, compared to no adaptation. Optimal systemic adaptation could make addition of $A 2.00 billion in 2030,$A 2.10 billion in 2050, and $A 2.12 billion in 2070 to industry with current farm management. In comparison with historical production, adaptation value to industry would be$A 1.51 billion in 2030, $A 1.51 billion in 2050, and$A 1.12 billion in 2070 (all for a full adaption). If the most-profitable combination of adaptations is used at the baseline instead of the current-practice, then the optimal combinations of grassland adaptations would provide a further increase in operating profitability at 28%, 28%, and 16% of sites in 2030, 2050, and 2070. If the livestock genetic adaptations –cannot be adopted at the present for lack of seed stock – are also included, the optimal systemic adaptations would be more profitable than the alternative baseline including grassland management options at 60%, 56%, and 48% of the locations in 2030, 2050, and 2070. We discuss 3 conceptual issues which arose during our study: (i) how to estimate impact when current management is environmentally infeasible under future climates; (ii) estimating the effectiveness of combinations of adaptations, only some of which are currently available to graziers; and (iii) dealing with the tension between modelling best-practice systems, so that present and future can be compared, versus modelling typical practice for economic valuation

Mapping interactions between the sustainable development goals: lessons learned and ways forward

Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones (“trade-offs”) and positive ones (“co-benefits”). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions

Loss of MITF expression during human embryonic stem cell differentiation disrupts retinal pigment epithelium development and optic vesicle cell proliferation

Microphthalmia-associated transcription factor (MITF) is a master regulator of pigmented cell survival and differentiation with direct transcriptional links to cell cycle, apoptosis and pigmentation. In mouse, Mitf is expressed early and uniformly in optic vesicle (OV) cells as they evaginate from the developing neural tube, and null Mitf mutations result in microphthalmia and pigmentation defects. However, homozygous mutations in MITF have not been identified in humans; therefore, little is known about its role in human retinogenesis. We used a human embryonic stem cell (hESC) model that recapitulates numerous aspects of retinal development, including OV specification and formation of retinal pigment epithelium (RPE) and neural retina progenitor cells (NRPCs), to investigate the earliest roles of MITF. During hESC differentiation toward a retinal lineage, a subset of MITF isoforms was expressed in a sequence and tissue distribution similar to that observed in mice. In addition, we found that promoters for the MITF-A, -D and -H isoforms were directly targeted by Visual Systems Homeobox 2 (VSX2), a transcription factor involved in patterning the OV toward a NRPC fate. We then manipulated MITF RNA and protein levels at early developmental stages and observed decreased expression of eye field transcription factors, reduced early OV cell proliferation and disrupted RPE maturation. This work provides a foundation for investigating MITF and other highly complex, multi-purposed transcription factors in a dynamic human developmental model syste

Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen

How do women prepare for pregnancy? Preconception experiences of women attending antenatal services and views of health professionals

Copyright: © 2014 Stephenson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Main objective - To determine the extent to which women plan and prepare for pregnancy. Methods - Cross-sectional questionnaire survey of pregnant women attending three maternity services in London about knowledge and uptake of preconception care; including a robust measure of pregnancy planning, and phone interviews with a range of health care professionals. Main results - We recruited 1173/1288 (90%) women, median age of 32 years. 73% had clearly planned their pregnancy, 24% were ambivalent and only 3% of pregnancies were unplanned. 51% of all women and 63% of those with a planned pregnancy took folic acid before pregnancy. 21% of all women reported smoking and 61% reported drinking alcohol in the 3 months before pregnancy; 48% of smokers and 41% of drinkers reduced or stopped before pregnancy. The 51% of all women who reported advice from a health professional before becoming pregnant were more likely to adopt healthier behaviours before pregnancy [adjusted odds ratios for greatest health professional input compared with none were 2.34 (95% confidence interval 1.54–3.54) for taking folic acid and 2.18 (95% CI 1.42–3.36) for adopting a healthier diet before pregnancy]. Interviews with 20 health professionals indicated low awareness of preconception health issues, missed opportunities and confusion about responsibility for delivery of preconception care. Significance of the findings - Despite a high level of pregnancy planning, awareness of preconception health among women and health professionals is low, and responsibility for providing preconception care is unclear. However, many women are motivated to adopt healthier behaviours in the preconception period, as indicated by halving of reported smoking rates in this study. The link between health professional input and healthy behaviour change before pregnancy is a new finding that should invigorate strategies to improve awareness and uptake of pre-pregnancy health care, and bring wider benefits for public health.Department of Healt

Building adaptive capacity to cope with increasing vulnerability due to climatic change in Africa – A new approach

The world community faces many risks from climate change, with most scenarios indicating higher temperatures and more erratic rainfall in Africa. Predictions for southern Africa suggest a general decrease in total seasonal rainfall, accompanied by more frequent in-season dry spells that will significantly impact crop and livestock production, and hence economic growth in the region. The hardest hit will be the rural poor in the drier areas, where crop failure due to drought is already common and chronic food emergencies afflict the region in most years. Lessons can be learnt on how the rural poor currently cope with the vagaries of climate and these can be used to help them adapt their current production systems to the future threats of further climate change. But this assumes the institutions that work towards the economic empowerment of the rural poor have the requisite skills to understand their current coping strategies and how adaptation can be facilitated. A new initiative led by Midlands State University and the Zambian Meteorological Office proposes that improving the ability of institutions that train the ‘Future Change Agents’, who will subsequently support smallholder communities in adapting their agricultural practices to current climate variability, is the first step in building adaptive capacity to cope with future climate change. The capacity of African scientists, regional organizations and decision-makers in dealing with the issues of climate change and adaptation will be enhanced on a continuing basis, and the impacts of their agricultural development programs improve

SpikeletFCN: Counting Spikelets from Infield Wheat Crop Images Using Fully Convolutional Networks

Currently, crop management through automatic monitoring is growing momentum, but presents various challenges. One key challenge is to quantify yield traits from images captured automatically. Wheat is one of the three major crops in the world with a total demand expected to exceed 850 million tons by 2050. In this paper we attempt estimation of wheat spikelets from high-definition RGB infield images using a fully convolutional model. We propose also the use of transfer learning and segmentation to improve the model. We report cross validated Mean Absolute Error (MAE) and Mean Square Error (MSE) of 53.0, 71.2 respectively on 15 real field images. We produce visualisations which show the good fit of our model to the task. We also concluded that both transfer learning and segmentation lead to a very positive impact for CNN-based models, reducing error by up to 89%, when extracting key traits such as wheat spikelet counts