Resequencing and fine-mapping of the chromosome 12q13-14 locus associated with multiple sclerosis refines the number of implicated genes

Multiple sclerosis (MS) is a common chronic inflammatory disease of the central nervous system. Susceptibility to the disease is affected by both environmental and genetic factors. Genetic factors include haplotypes in the histocompatibility complex (MHC) and over 50 non-MHC loci reported by genome-wide association studies. Amongst these, we previously reported polymorphisms in chromosome 12q13-14 with a protective effect in individuals of European descent. This locus spans 288 kb and contains 17 genes, including several candidate genes which have potentially significant pathogenic and therapeutic implications. In this study, we aimed to fine-map this locus. We have implemented a two-phase study: a variant discovery phase where we have used next-generation sequencing and two target-enrichment strategies [long-range polymerase chain reaction (PCR) and Nimblegen's solution phase hybridization capture] in pools of 25 samples; and a genotyping phase where we genotyped 712 variants in 3577 healthy controls and 3269 MS patients. This study confirmed the association (rs2069502, P = 9.9 × 10−11, OR = 0.787) and narrowed down the locus of association to an 86.5 kb region. Although the study was unable to pinpoint the key-associated variant, we have identified a 42 (genotyped and imputed) single-nucleotide polymorphism haplotype block likely to harbour the causal variant. No evidence of association at previously reported low-frequency variants in CYP27B1 was observed. As part of the study we compared variant discovery performance using two target-enrichment strategies. We concluded that our pools enriched with Nimblegen's solution phase hybridization capture had better sensitivity to detect true variants than the pools enriched with long-range PCR, whilst specificity was better in the long-range PCR-enriched pools compared with solution phase hybridization capture enriched pools; this result has important implications for the design of future fine-mapping studies.

High levels of BACH2 associated with lower levels of BCL2 transcript abundance in t(14;18)(q21;q34) translocation positive non-Hodgkin’s lymphoma

The t(14;18)(q21;q34) BCL2 translocation is a common genetic alteration in follicular and diffuse large B-cell lymphoma. However, it is not invariably associated with BCL2 gene overexpression due to undefined mechanisms that regulate expression from the proximal immunoglobulin heavy-chain (IgH) promoter. The BACH2 transcriptional repressor is able to modulate activity of this promoter. Here we have shown that, in tumor samples with BCL2 translocation, those with high levels of BACH2 had significantly lower BCL2 transcript abundance compared to those with low levels of BACH2. This indicates that BACH2 may be partially responsible for regulation of BCL2 expression from the t(14;18)(q21;q34) translocation.

Patellar tendinopathy in junior basketball players : a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years

Anterior knee pain is a common presenting complaint amongst adolescent athletes. We hypothesised that patellar tendinopathy may occur at a younger age than is generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to 18-year-old female (n=64) and male (n=70) basketball players and 29 control swimmers (17 female, 12 male) clinically and with ultrasonography. We found that of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds (11% in males, 2% in females). Twenty-six percent of the basketball players' patellar tendons contained an ultrasonographic hypoechoic region. Ultrasonographic abnormality was more prevalent in the oldest tertile of players (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic hypoechoic region nevertheless. This study indicates that patellar tendinopathy can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon abnormality is 3 times as common as clinical symptoms

Decision making under pressure : a behavioural economics perspective

This research investigates the decision making process of individuals from revealed preferences in extreme environments or life-and-death situations, from a behavioral economics perspective. The empirical analysis of revealed behavioral preferences shows how the individual decision making process can deviate from the standard self-interested or “homo economicus” model in non-standard situations. The environments examined include: elite athletes in FIFA World and Euro Cups; climbing on Everest and the Himalaya; communication during 9/11 and risk seeking after the 2011 Brisbane floods. The results reveal that the interaction of culture and environment has a significant impact on the decision process, as social behaviors and institutions are intimately intertwined, which govern the processes of human behavior and interaction. Additionally, that risk attitudes are not set and that immediate environmental factors can induce a significant shift in an individuals risk seeking behaviors.

Measuring the burden of disease in Shandong province : an adoption of the disability-adjusted life year [应用伤残调整寿命年测量山东省居民疾病负担]

Objective To estimate the burden of diseases in Shandong province by the means of DALY (Disability- adjusted life year) thus to investigate the key public health problems referencing for health policy making. Methods DALYs were calculated following the procedures developed for the Global Burden of Disease (GBD) study to ensure comparability. We measured YLLs using the mortality data of 19 Disease Surveillance Points (DSPs) in Shandong Province during 2000 and 2005. YLDs were estimated based on data for WPRO in the 2002 GBD study published by WHO. Results During this period, the average DALYs loss by all causes for the residents of DSPs in Shandong was 149.74 per thousand persons each year. Noncommunicable diseases accounted for 76.63% of the disability adjusted life years, communicable diseases and other disorders represented 14.13%, and injuries 9.24%. Nearly half of the DALYs (45%) happened among the elderly (60+). Malignant neoplasm was the number one cause of DALYs loss in the male, followed by neuropsychiatric disorder, injury, cerebrovascular disease, heart disease，etc. However, neuropsychiatric disorder possessed the largest single contributor to DALY in the female and followed by heart disease, malignant neoplasm, cerebrovascular disease and respiratory disease. Conclusion Non-communicable diseases such as circulatory diseases, neuropsychiatric disorders and malignant neoplasms were the main causes of disease burden in Shandong province. The importance of neuropsychiatric disorders was more striking and should be recognized properly. The lack of morbidity data is the main limitation of this study. Abstract in Chinese 目的 应用伤残调整寿命年测量山东省居民疾病负担,提出该地区主要卫生问题,为卫生决策提供科学依据. 方法 以山东省2000-2005年19个疾病监测点的死因监测资料为基础,利用世界卫生组织(WHO)提供的方法计算不同疾病在不同性别年龄人群所造成的伤残调整寿命年(DALYs),其中,YIJDs根据WHO公布的亚太区2002年疾病负担数据进行估算. 结果 2000-2005年山东省疾病监测系统居民因为早死和残疾年平均损失149.74个DALYs/千人,其中,76.6%的DALYs损失因慢性非传染性疾病所致,14.1%由传染性疾病等引起,9.2%因为意外伤害造成;接近1/2(45%)的DALYs损失发生在60岁以上人群;恶性肿瘤为造成男性居民DALYs损失的首位原因,其次为精神行为疾患、意外伤害、脑血管病和心脏病等,女性居民则以精神行为疾患为DALYs首位原因,其次为心脏病、恶性肿瘤、脑血管病和呼吸系统疾病. 结论 以循环系统疾病、精神行为疾惠和恶性肿瘤为首的慢性非传染性疾病为造成山东省疾病负担DALYs损失的主要原因.对于精神行为疾患的重要性的认识有待于进一步提高,研究的主要局限性在于发病率资料的缺乏.

Public Economics and the Assessment of Tourism Developments and Policies

Public economics covers both topics in welfare economic of social (as opposed to private) interest and aspects of public finance. This chapter considers the application of two methods of social economic evaluation of tourist developments, namely, social cost-benefit analysis and economic impact analysis. The role of social cost-benefit analysis in the assessment of tourism is illustrated by its application to the evaluation of inbound tourism. This is followed by a discussion of taxes on tourism and subsidies to promote it. The principle focus is on hotel room taxes. The analysis of taxes on tourism involves both public finance and welfare economics issues. The scope for and desirability of applying the user-pays principle to tourism is then examined.

A retrospective cohort study of Acticoat™ versus Silvazine™ in a paediatric population

We wished to determine whether changing our centre's practice of using Acticoat instead of Silvazine as our first-line burns dressing provided a better standard of care in terms of efficacy, cost and ease of use. A retrospective cohort study was performed examining 328 Silvazine treated patients from January 2000 to June 2001 and 241 Acticoat treated patients from July 2002 to July 2003. During those periods the respective dressings were used exclusively. There was no significant difference in age, %BSA and mechanism of burn between the groups. In the Silvazine group, 25.6% of children required grafting compared to 15.4% in the Acticoat group (p=0.001). When patients requiring grafting were excluded, the time taken for re-epithelialisation in the Acticoat group (14.9 days) was significantly less than that for the Silvazine group (18.3 days), p=0.047. There were more wounds requiring long term scar management in the Silvazine group (32.6%) compared to the Acticoat group (29.5%), however this was not significant. There was only one positive blood culture in each group, indicating that both Silvazine and Acticoat are potent antimicrobial agents. The use of Acticoat as our primary burns dressing has dramatically changed our clinical practice. Inpatients are now only 18% of the total admissions, with the vast majority of patients treated on an outpatient basis. In terms of cost, Acticoat was demonstrated to be less expensive over the treatment period than Silvazine . We have concluded that Acticoat is a safe, cost-effective, efficacious dressing that reduces the time for re-epithelialisation and the requirement for grafting and long term scar management, compared to Silvazine.

Chemo-enzymatic synthesis of unnatural amino acids

A general chemo-enzymatic process has been developed to prepare enantiomerically pure L- and D-amino acids in high yield by deracemisation of racemic starting materials. The method has been developed from initial academic studies to be a robust, scalable industrial process. Unnatural amino acids, in high optical purity, are a rapidly growing class of intermediates required for pharmaceuticals, agrochemicals and other fine chemical applications. However, no single method has proven sufficiently adaptable to prepare these compounds generally at large scale. Our approach uses an enantioselective oxidase biocatalyst and a non-selective chemical reducing agent to effect the stereoinversion of one enantiomer and can result in an enantiomeric excess of > 99 % from a starting racemate, and product yields over 90 %. The current approach compares very favourably to resolution methods which have a maximum single pass yield of 50 %. Efficient methods have been developed to adapt the biocatalyst used in this process towards new target compounds and to optimise key factors which improve the process efficiency and offer competitive economics at scale.

Dynamic modelling of long-term care decisions

This paper describes and analyzes research on the dynamics of long-term care and the policy relevance of identifying the sources of persistence in caregiving arrangements (including the effect of dynamics on parameter estimates, implications for family welfare, parent welfare, child welfare, and cost of government programs). We discuss sources and causes of observed persistence in caregiving arrangements including inertia/state dependence (confounded by unobserved heterogeneity) and costs of changing caregivers. We comment on causes of dynamics including learning/human capital accumulation; burnout; and game-playing. We suggest how to deal with endogenous geography; dynamics in discrete and continuous choices; and equilibrium issues (multiple equilibria, dynamic equilibria). We also present an overview of commonly used longitudinal data sets and evaluate their relative advantages/disadvantages. We also discuss other data issues related to noisy measures of wealth and family structure. Finally, we suggest some methods to handle econometric problems such as endogeneous geography. © 2014 Springer Science+Business Media New York.

Reliability of a wellness inventory for use among adolescent females aged 12-14 years

Background The wellness construct has application in a number of fields including education, healthcare and counseling, particularly with regard to female adolescents. The effective measurement of wellness in adolescents can assist researchers and practitioners in determining lifestyle behaviors in which they are lacking. Behavior change interventions can then be designed which directly aid in the promotion of these areas. Methods The 5-Factor Wellness Inventory (designed to measure the Indivisible Self model of wellness) is a popular instrument for measuring the broad aspects of wellness amongst adolescents. The instrument comprises 97 items contributing to 17 subscales, five dimension scores, four context scores, total wellness score, and a life satisfaction index. This investigation evaluated the test-retest (intra-rater) reliability of the 5 F-Wel instrument in repeated assessments (seven days apart) among adolescent females aged 12-14 years. Percentages of exact agreement for individual items, and the number of respondents who scored within +/-5, +/-7.5 and +/-10 points for total wellness and the five summary dimension scores were calculated. Results Overall, 46 (95.8%) participants responded with complete data and were included in the analysis. Item agreement ranged from 47.8% to 100% across the 97 items (median 69.9%, interquartile range 60.9%-73.9%). The percentage of respondents who scored within +/-5, +/-7.5 and +/-10 points for total wellness at the re-assessment was 87.0%, 97.8% and 97.8% respectively. The percentage of respondents who scored within +/-5, +/-7.5 and +/-10 for the domain scores at the reassessment ranged between 54.3-76.1%, 78.3-95.7% and 89.1-95.7% respectively across the five dimensions. Conclusions These findings suggest there was considerable variation in agreement between the two assessments on some individual items. However, the total wellness score and the five dimension summary scores remained comparatively stable between assessments.

People’s perceptions about the importance of forests on Borneo

We ascertained villagers’ perceptions about the importance of forests for their livelihoods and health through 1,837 reliably answered interviews of mostly male respondents from 185 villages in Indonesian and Malaysian Borneo. Variation in these perceptions related to several environmental and social variables, as shown in classification and regression analyses. Overall patterns indicated that forest use and cultural values are highest among people on Borneo who live close to remaining forest, and especially among older Christian residents. Support for forest clearing depended strongly on the scale at which deforestation occurs. Deforestation for small-scale agriculture was generally considered to be positive because it directly benefits people’s welfare. Large-scale deforestation (e.g., for industrial oil palm or acacia plantations), on the other hand, appeared to be more context-dependent, with most respondents considering it to have overall negative impacts on them, but with people in some areas considering the benefits to outweigh the costs. The interviews indicated high awareness of negative environmental impacts of deforestation, with high levels of concern over higher temperatures, air pollution and loss of clean water sources. Our study is unique in its geographic and trans-national scale. Our findings enable the development of maps of forest use and perceptions that could inform land use planning at a range of scales. Incorporating perspectives such as these could significantly reduce conflict over forest resources and ultimately result in more equitable development processes.

The importance of good data, analysis and interpretation for showing the economics of reducing healthcare-associated infection

To the Editor—In a recent review article in Infection Control and Hospital Epidemiology, Umscheid et al1 summarized published data on incidence rates of catheter-associated bloodstream infection (CABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI), and ventilator- associated pneumonia (VAP); estimated how many cases are preventable; and calculated the savings in hospital costs and lives that would result from preventing all preventable cases. Providing these estimates to policy makers, political leaders, and health officials helps to galvanize their support for infection prevention programs. Our concern is that important limitations of the published studies on which Umscheid and colleagues built their findings are incompletely addressed in this review. More attention needs to be drawn to the techniques applied to generate these estimates...

Technology, Natural Resources and Economic Growth: Improving the Environment for a Greener Future

Description Through a combination of global data analysis and focused country level analysis, this timely book provides answers to the most pertinent country and industry specific questions defining the current relationship between technology, natural resources and economic growth. Contents Contents: Preface Part I: Global Analysis 1. Economic Growth and the Environment 2. Energy Substitution and Carbon Dioxide Emissions 3. Pollution, Natural Resources, and Economic Growth 4. Trade Openness and Environmental Quality 5. Environmental Productivity 6. Energy Price-induced Technological Change 7. Trade-induced Technological Change 8. Regional Economic Integration Part II: Country-Level Analysis 9. Emissions Trading in the United States 10. Increasing Returns to Pollution Abatement in the United States 11. Policy-induced Competitiveness in the United States 12. Trade Liberalization, Technology, and the Environment 13. Policy Implementation and its Effectiveness in China 14. Clean Technological Inventions in Japan 15. Intervention of Economic Policy and its Nonlinear Effects in Japan 16. The Next Emerging Giants: India and Africa 17. Conclusion Index Further information Through a combination of global data analysis and focused country level analysis, this timely book provides answers to the most pertinent country and industry specific questions defining the current relationship between technology, natural resources and economic growth. Shunsuke Managi takes a distinctive approach by focusing on the design and implementation of environmental regulations that encourage technological progress and, in doing so, looks at ways to ensure productivity improvements in the face of increasingly stringent environmental regulations and natural resource depletion. The findings in this important book demonstrate how successful environmental policies can contribute to efficiency by encouraging, rather than inhibiting, technological innovation. Technology, Natural Resources and Economic Growth will provide a valuable resource for a wide readership including postgraduate students, researchers, academics and policy makers working in the fields of environmental and ecological economics.

Determinants of eco-efficiency in the Chinese industrial sector

This study measures productive inefficiency within the context of multi-environmental pollution (eco-efficiency) in the Chinese industrial sector. The weighted Russell directional distance model is applied to measure eco-efficiency using production technology. The objective is to clarify how external factors affect eco-efficiency. The major findings are that both foreign direct investment and investment for pollution abatement improve eco-efficiency as measured by air pollutant substances. A levy system for wastewater discharge improves eco-efficiency as measured by wastewater pollutant substances. However, an air pollutant levy does not significantly affect eco-efficiency as measured by air pollutants.