Climate changes reconstructed from a glacial lake in High Central Asiaover the past two millennia

Climatic changes in Arid Central Asia (ACA) over the past two millennia have been widely concerned. However, less attention has been paid to those in the High Central Asia (HCA), where the Asian water tower nurtures the numerous oases by glacier and/or snow melt. Here, we present a new reconstruction of the temperature and precipitation change over the past two millennia based on grain size of a well-dated glacial lake sediment core in the central of southern Tianshan Mountains. The results show that the glacial lake catchment has experienced cold-wet climate conditions during the Dark Age Cold Period (&sim;300&ndash;600 AD; DACP) and the Little Ice Age (&sim;1300&ndash;1870 AD; LIA), whereas warm-dry conditions during the Medieval Warm Period (&sim;700&ndash;1270 AD; MWP). Integration of our results with those of previously published lake sediment records, stalagmite &delta;18O records, ice core net accumulation rates, tree-ring based temperature reconstructions, and mountain glacier activities suggest that there has a broadly similar hydroclimatic pattern over the HCA areas on centennial time scale during the past two millennia. Comparison between hydroclimatic pattern of the HCA and that of the ACA areas suggests a prevailing &#39;warm-dry and cold-wet&#39; hydroclimatic pattern over the whole westerlies-dominated central Asia areas during the past two millennia. We argue that the position and intensity of the westerlies, which are closely related to the phase of the North Atlantic Oscillation (NAO), and the strength of the Siberian High pressure (SH), could have jointly modulated the late Holocene central Asia hydroclimatic changes.<br /

Pressure RElieving Support SUrfaces: a Randomised Evaluation 2 (PRESSURE 2): study protocol for a randomised controlled trial

Background Pressure ulcers represent a major burden to patients, carers and the healthcare system, affecting approximately 1 in 17 hospital and 1 in 20 community patients. They impact greatly on an individual’s functional status and health-related quality of life. The mainstay of pressure ulcer prevention practice is the provision of pressure redistribution support surfaces and patient repositioning. The aim of the PRESSURE 2 study is to compare the two main mattress types utilised within the NHS: high-specification foam and alternating pressure mattresses, in the prevention of pressure ulcers. Methods/Design PRESSURE 2 is a multicentre, open-label, randomised, double triangular, group sequential, parallel group trial. A maximum of 2954 ‘high-risk’ patients with evidence of acute illness will be randomised on a 1:1 basis to receive either a high-specification foam mattress or alternating-pressure mattress in conjunction with an electric profiling bed frame. The primary objective of the trial is to compare mattresses in terms of the time to developing a new Category 2 or above pressure ulcer by 30 days post end of treatment phase. Secondary endpoints include time to developing new Category 1 and 3 or above pressure ulcers, time to healing of pre-existing Category 2 pressure ulcers, health-related quality of life, cost-effectiveness, incidence of mattress change and safety. Validation objectives are to determine the responsiveness of the Pressure Ulcer Quality of Life-Prevention instrument and the feasibility of having a blinded endpoint assessment using photography. The trial will have a maximum of three planned analyses with unequally spaced reviews at event-driven coherent cut-points. The futility boundaries are constructed as non-binding to allow a decision for stopping early to be overruled by the Data Monitoring and Ethics Committee. Discussion The double triangular, group sequential design of the PRESSURE 2 trial will provide an efficient design through the possibility of early stopping for demonstrating either superiority, inferiority of mattresses or futility of the trial. The trial optimises the potential for producing robust clinical evidence on the effectiveness of two commonly used mattresses in clinical practice earlier than in a conventional design

Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens

<p>Abstract</p> <p>Background</p> <p>Avian pathogenic <it>Escherichia coli </it>(APEC) is detrimental to poultry health and its zoonotic potential is a food safety concern. Regulation of antimicrobials in food-production animals has put greater focus on enhancing host resistance to bacterial infections through genetics. To better define effective mechanism of host resistance, global gene expression in the spleen of chickens, harvested at two times post-infection (PI) with APEC, was measured using microarray technology, in a design that will enable investigation of effects of vaccination, challenge, and pathology level.</p> <p>Results</p> <p>There were 1,101 genes significantly differentially expressed between severely infected and non-infected groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between mildly infected and non-infected groups on either time point. Between birds exhibiting mild and severe pathology, there were 2 significantly differentially expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology had more genes with increased expression than decreased expression levels. Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine signaling, were represented between challenged and non-challenged groups. Vaccination had, surprisingly, no detectible effect on gene expression, although it significantly protected the birds from observable gross lesions. Functional characterization of significantly expressed genes revealed unique gene ontology classifications during each time point, with many unique to a particular treatment or class contrast.</p> <p>Conclusions</p> <p>More severe pathology caused by APEC infection was associated with a high level of gene expression differences and increase in gene expression levels. Many of the significantly differentially expressed genes were unique to a particular treatment, pathology level or time point. The present study not only investigates the transcriptomic regulations of APEC infection, but also the degree of pathology associated with that infection. This study will allow for greater discovery into host mechanisms for disease resistance, providing targets for marker assisted selection and advanced drug development.</p

Trends in healthy life expectancy in Hong Kong SAR 1996–2008

Although Hong Kong has one of the best life expectancy (LE) records in the world, second only to Japan for women, we know very little about the changes in the health status of the older adult population. Our article aims to provide a better understanding of trends in both chronic morbidity and disability for older men and women. The authors compute chronic morbidity-free and disability-free life expectancy and the proportion of both in relation to total LE using the Sullivan method to examine whether Hong Kong older adults are experiencing a compression of morbidity and disability and whether there is any gender difference in relation to mortality and morbidity. The results of this study show that Hong Kong women tend to outlive Hong Kong men but are also more likely to suffer from a ‘double disadvantage’, namely more years of life with more chronic morbidity and disability. There has also been a significant expansion of chronic morbidity, as chronic morbidity-free life expectancy (CMFLE) decreased substantially for both genders from 1996 to 2008. Although disability-free life expectancy (DFLE) increased during this period, it increased at a slower pace compared to LE. The proportion of life without chronic morbidity also declined remarkably during these 12 years. Among the advanced ages, the proportion of remaining life in good health without disability has decreased since 1996, indicating a relative expansion of disability

Retardation of arsenic transport through a Pleistocene aquifer

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic1. Holocene aquifers are the source of widespread arsenic poisoning across the region2, 3. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water4 and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport.National Science Foundation (U.S.) (NSF grant EAR09-11557)Swiss Agency for Development and Cooperation (Grant NAFOSTED 105-09-59-09 to CETASD, the Centre for Environmental Technology and Sustainable Development (Vietnam))National Institute of Environmental Health Sciences (NIEHS grant P42 ES010349)National Institute of Environmental Health Sciences (NIEHS grant P42 ES016454

Quantitative Mass Spectrometry Analysis Reveals Similar Substrate Consensus Motif for Human Mps1 Kinase and Plk1

Background Members of the Mps1 kinase family play an essential and evolutionarily conserved role in the spindle assembly checkpoint (SAC), a surveillance mechanism that ensures accurate chromosome segregation during mitosis. Human Mps1 (hMps1) is highly phosphorylated during mitosis and many phosphorylation sites have been identified. However, the upstream kinases responsible for these phosphorylations are not presently known. Methodology/Principal Findings Here, we identify 29 in vivo phosphorylation sites in hMps1. While in vivo analyses indicate that Aurora B and hMps1 activity are required for mitotic hyper-phosphorylation of hMps1, in vitro kinase assays show that Cdk1, MAPK, Plk1 and hMps1 itself can directly phosphorylate hMps1. Although Aurora B poorly phosphorylates hMps1 in vitro, it positively regulates the localization of Mps1 to kinetochores in vivo. Most importantly, quantitative mass spectrometry analysis demonstrates that at least 12 sites within hMps1 can be attributed to autophosphorylation. Remarkably, these hMps1 autophosphorylation sites closely resemble the consensus motif of Plk1, demonstrating that these two mitotic kinases share a similar substrate consensus. Conclusions/Significance hMps1 kinase is regulated by Aurora B kinase and its autophosphorylation. Analysis on hMps1 autophosphorylation sites demonstrates that hMps1 has a substrate preference similar to Plk1 kinase

Association between the NBS1 E185Q polymorphism and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>NBS1 is a key DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint that plays important roles in maintaining genomic stability. The <it>NBS1 </it>8360G>C (<it>Glu185Gln</it>) is one of the most commonly studied polymorphisms of the gene for their association with risk of cancers, but the results are conflicting.</p> <p>Methods</p> <p>We performed a meta-analysis using 16 eligible case-control studies (including 17 data sets) with a total of 9,734 patients and 10,325 controls to summarize the data on the association between the <it>NBS1 </it>8360G>C (E185Q) polymorphism and cancer risk.</p> <p>Results</p> <p>Compared with the common 8360GG genotype, the carriers of variant genotypes (i.e., 8360 GC/CC) had a 1.06-fold elevated risk of cancer (95% CI = 1.00–1.12, <it>P </it>= 0.05) in a dominant genetic model as estimated in a fixed effect model. However, the association was not found in an additive genetic model (CC <it>vs </it>GG) (odds ratio, OR = 0.98, 95% CI = 0.85–1.13, <it>P </it>= 0.78) nor in a recessive genetic model (CC <it>vs </it>GC +GG) (OR = 0.94, 95% CI = 0.82–1.07, <it>P </it>= 0.36). The effect of the 8360G>C (E185Q) polymorphism was further evaluated in stratification analysis. It was demonstrated that the increased risk of cancer associated with 8360G>C variant genotypes was more pronounced in the Caucasians (OR = 1.07, 95% CI = 1.01–1.14, <it>P </it>= 0.03).</p> <p>Conclusion</p> <p>Our meta-analysis suggests that the <it>NBS1 </it>E185Q variant genotypes (8360 <it>GC/CC</it>) might be associated with an increased risk of cancer, especially in Caucasians.</p