Climate change impacts and adaptation to permafrost change in High Mountain Asia: a comprehensive review

Changing climatic conditions in High Mountain Asia (HMA), especially regional warming and changing precipitation patterns, have led to notable effects on mountain permafrost. Comprehensive knowledge of mountain permafrost in HMA is mostly limited to the mountains of the Qinghai-Tibetan Plateau, with a strong cluster of research activity related to critical infrastructure providing a basis for related climate adaptation measures. Insights related to the extent and changing characteristics of permafrost in the Hindu Kush Himalaya (HKH), are much more limited. This study provides the first comprehensive review of peer-reviewed journal articles, focused on hydrological, ecological, and geomorphic impacts associated with thawing permafrost in HMA, as well as those examining adaptations to changes in mountain permafrost. Studies reveal a clear warming trend across the region, likely resulting in increased landslide activity, effects on streamflow, soil saturation and subsequent vegetation change. Adaptation strategies have been documented only around infrastructure megaprojects as well as animal herding in China. While available research provides important insight that can inform planning in the region, we also identify a need for further research in the areas of hazards related to changing permafrost as well as its effect on ecosystems and subsequently livelihoods. We suggest that future planning of infrastructure in HMA can rely on extrapolation of already existing knowledge within the region to reduce risks associated with warming permafrost. We highlight key research gaps as well as specific areas where insights are limited. These are areas where additional support from governments and funders is urgently needed to enhance regional collaboration to sufficiently understand and effectively respond to permafrost change in the HKH region

By Us and For Us: A Story of Early Childhood Development Systems Change and Results in a Rural Context

Since 2007, the Neil and Louise Tillotson Fund — a donor-advised fund of the New Hampshire Charitable Foundation — has invested in early childhood development in Coös County — New Hampshire’s largest and most rural and economically disadvantaged county. Community providers from a range of disciplines formed strong professional relationships and agreed on common goals and evidence-based strategies to improve services for children and families. This article describes how local community members joined forces with the fund to create an integrated early childhood development system for Coös’ children and families. It provides background on the investment and initiative strategy, summarizes key results, and outlines lessons for funders and others pursuing systems change efforts in early learning, in rural areas, or more broadly. With increasing interest in strategies to promote childhood resilience, school readiness, and community revitalization, Coös County’s rural story of relationship and community systems change can inform the field

Extracting Proofs from Tabled Proof Search

We consider the problem of model checking specifications involving co-inductive definitions such as are available for bisimulation. A proof search approach to model checking with such specifications often involves state exploration. We consider four different tabling strategies that can minimize such exploration significantly. In general, tabling involves storing previously proved subgoals and reusing (instead of reproving) them in proof search. In the case of co-inductive proof search, tables allow a limited form of loop checking, which is often necessary for, say, checking bisimulation of non-terminating processes. We enhance the notion of tabled proof search by allowing a limited deduction from tabled entries when performing table lookup. The main problem with this enhanced tabling method is that it is generally unsound when co-inductive definitions are involved and when tabled entries contain unproved entries. We design a proof system with tables and show that by managing tabled entries carefully, one would still be able to obtain a sound proof system. That is, we show how one can extract a post-fixed point from a tabled proof for a co-inductive goal. We then apply this idea to the technique of bisimulation ''up-to'' commonly used in process algebra

The 'global city' misconceived: the myth of 'global management' in transnational service firms

The ‘global city hypothesis' proposed by Saskia Sassen – and subsequently developed by Manuel Castells and others in the theory of a globalized urban network – has in recent years formed the basis for the argument that power and control in transnational firms (TNCs) is primarily situated in global head-offices. Such offices are located in key urban centres such as London, New York or Tokyo where global managerial power is ultimately wielded and where senior managers make strategic decisions about transnational business activity. This paper takes issue with this theoretical legacy, arguing that the idea of strong centralised managerial power and control in contemporary TNCs is far more complex than this literature suggests. It explores how managerial control in some of the supposedly most globalized of business service industries – investment banking and management consultancy – cannot be understood as being centralised in global headquarter offices, and nor does it purely reside with a few senior managers at the top of the transnational organisation. Rather, it argues that managerial control in TNCs is diffused throughout a transnational network of management-level employees, and that strategic power in transnational firms resides with a larger and more dispersed group of actors than has been previously suggested. These arguments are developed through analysis of qualitative research into the managerial strategies and practices of senior business practitioners in the transnational investment banking and management consultancy industries. In presenting qualitative data from interviews with senior management in transnational corporate head offices, the paper thus examines the decision-making process of global management practice and unpacks the complex context in which transnational corporate strategy develops in such firms

Non-HDL or LDL cholesterol in heterozygous familial hypercholesterolaemia: findings of the Simon Broome Register

PURPOSE OF REVIEW: The role of non-HDL-C in the identification and management of lipid disorders is not clearly defined, although UK guidelines recommend its wider use in assessing the need for lipid-lowering therapy and as a treatment target. RECENT FINDINGS: We examined the implications of the use of non-HDL-C as opposed to LDL-C in 253 people with hypercholesterolaemia before treatment and 573 after treatment in whom fasting total serum cholesterol, HDL-C and LDL-C had been recorded and the diagnosis of heterozygous familial hypercholesterolemia (heFH) was investigated by genetic testing. The difference and the limits of agreement between non-HDL-C and LDL-C calculated using the Friedewald formula were assessed in those with and without heFH-causing mutations. SUMMARY: There were 147 mutation-positive and 106 mutation-negative pretreatment participants and 395 mutation-positive and 178 mutation-negative patients receiving treatment. The difference between non-HDL-C and LDL-C pretreatment in mutation-positive people (mean LDL-C 7.73 mmol/l) was 0.67 mmol/l (95% CI 0.62-0.73) and posttreatment (mean LDL-C 4.71 mmol/l) was 0.62 mmol/l (95% CI 0.59-0.65) with wide limits of agreement of -0.02 to 1.37 and 0.07-1.18 mmol/l, respectively. Among patients with heterozygous familial hypercholesterolaemia, use of estimated LDL-C derived from non-HDL-C in place of calculated LDL-C may result in diagnostic misclassification and difficulty in assessing the true reduction in LDL-C with treatment, because of the wide inter-individual limits of agreement around the mean difference between non-HDL-C and LDL-C

Advanced sperm selection techniques for assisted reproduction (Review)

Background: Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) bring together gametes outside of the body to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly being employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are thought to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Advanced sperm selection strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques theoretically improve ART outcomes. Objectives: To evaluate the impact of advanced sperm selection techniques on ART outcomes. Search methods: Systematic search of electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Science Information Database (LILACS)), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (Web of Knowledge) and grey literature (OpenGrey) for relevant randomised controlled trials. We handsearched the reference lists of included studies and similar reviews. The search was conducted in May 2014. Selection criteria: We included randomised controlled trials (RCTs) comparing an advanced sperm selection technique versus standard IVF or ICSI or versus another advanced sperm selection technique. We excluded studies of sperm selection using ultra-high magnification (intracytoplasmic morphologically selected sperm injection, or IMSI), as they are the subject of a separate Cochrane review. Quasi-randomised and pseudo-randomised trials were excluded. Our primary outcome measure was live birth rate per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned, miscarriage per clinical pregnancy and fetal abnormality per clinical pregnancy. Data collection and analysis: Two review authors independently assessed eligibility of studies and risk of bias, and performed data extraction. Disagreements were resolved by consultation with a third review author. Study investigators were consulted to resolve other queries that arose. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We planned to combine studies using a fixed-effect model, if sufficient data were available. The quality of the evidence was evaluated using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. Main results: Two RCTs were included in the review. Both evaluated sperm selection by hyaluronanic acid binding for ICSI, but only one reported live births. No studies were identified that were related to surface charge selection, sperm apoptosis or sperm birefringence. One RCT compared hyaluronanic acid binding versus conventional ICSI. Live birth was not reported. Evidence was insufficient to show whether there was a difference between groups in clinical pregnancy rates (RR 1.01, 95% CI 0.84 to 1.22, one RCT, 482 women). This evidence was deemed to be of low quality, mainly as the result of poor reporting of methods and findings. Miscarriage data were unclear, and fetal abnormality rates were not reported. The other RCT compared two different hyaluronanic acid binding techniques, SpermSlow and physiological intracytoplasmic sperm injection (PISCI). Evidence was insufficient to indicate whether there was a difference between groups in rates of live birth (RR 1.16, 95% CI 0.65 to 2.05, one RCT, 99 women), clinical pregnancy (RR 1.07, 95% CI 0.67 to 1.71, one RCT, 99 women) or miscarriage (RR 0.76, 95% CI 0.24 to 2.44, one RCT, 41 women). The evidence for these comparisons was deemed to be of low quality, as it was limited by imprecision and poor reporting of study methods. Fetal abnormality rates were not reported. Authors' conclusions: Evidence was insufficient to allow review authors to determine whether sperm selected by hyaluronanic acid binding improve live birth or pregnancy outcomes in ART, and no clear data on adverse effects were available. Evidence was also insufficient to show whether there is a difference in efficacy between the hyaluronic acid binding methods SpermSlow and PICSI. No randomised evidence evaluating sperm selection by sperm apoptosis, sperm birefringence or surface charge was found. Further studies of suitable quality are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in clinical practice

Macrosystems ecology: Understanding ecological patterns and processes at continental scales

Macrosystems ecology is the study of diverse ecological phenomena at the scale of regions to continents and their interactions with phenomena at other scales. This emerging subdiscipline addresses ecological questions and environmental problems at these broad scales. Here, we describe this new field, show how it relates to modern ecological study, and highlight opportunities that stem from taking a macrosystems perspective. We present a hierarchical framework for investigating macrosystems at any level of ecological organization and in relation to broader and finer scales. Building on well-established theory and concepts from other subdisciplines of ecology, we identify feedbacks, linkages among distant regions, and interactions that cross scales of space and time as the most likely sources of unexpected and novel behaviors in macrosystems. We present three examples that highlight the importance of this multiscaled systems perspective for understanding the ecology of regions to continents

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study)

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).BackgroundHyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.MethodsTo determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus ≤5.5mg/dL and Ca × P product ≤55mg2/dL2, we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.ResultsComparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08mg/dL difference, P = 0.0006), higher serum calcium (0.63mg/dL difference, P < 0.0001), and lower Ca × P (6.1mg2/dL2 difference, P = 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28–4.37, P = 0.0058], and 15% to 20% more likely to attain goal Ca × P (OR 2.16, 95% CI 1.20–3.86, P = 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8–13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).ConclusionCalcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever