12 research outputs found

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∌99% of the euchromatic genome and is accurate to an error rate of ∌1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Sustainable consumption : examining a model for proactive and reactive sustainable consumption behaviour.

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    Studies have shown the impact of consumption on environment and the consequential societal and economic costs. While there is a wealth of literature on consumption drivers and resulting ecological degradation due to increasing consumption, more could be done to understand how to counter this trend and to make consumption sustainable. This study proposes a new integrated model to offer policy inputs on making consumption sustainable. The proposed model is based on a combined framework of the Theory of Planned Behaviour and the Model of Pro-environment Behaviour. In addition, two new scales, media effects scale and system factors, are developed in this study for validation to be included as the influence introduced by external factors. The survey was conducted in Singapore in end 2010 by gathering responses to a survey on-line and in person. This study is significant in its contribution of the validated integrated model of sustainable consumption and in moving policy makers’ attention from promoting reactive habits to cultivating proactive behaviours.​Master of Mass Communicatio

    Investigating the contextual influences shaping recycling behaviours

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    Though the Paris Agreement came into effect in 2016 to unite all nations to act now to achieve carbon-neutral earth by 2050, devastating climate change effects are increasing globally. Despite the renewed hope of international collaboration led by superpowers, concerted efforts are critically needed now to transform our current production and consumption modes to achieve the targeted carbon emission reductions. Personal motivators, coupled with team efforts, are needed even more so now to augment policies to nudge one toward living more sustainably to make a carbon-neutral world a reality in 2050. This thesis thus aimed to build a contextual influence model and contribute a framework to integrate theory and practice to identify contextual influences that can be used to effectively nudge one to willingly recycle as a pragmatic approach to minimise the post-consumption harm on the environment. The model was developed to identify the drivers for adults to recycle, with a secondary focus on the youth respondents who were identified as potential concerns or game changers in ensuring environmental sustainability. Adopting a system perspective, the influences on one’s recycling behaviours were investigated at three levels for an exploratory case study to validate the contextual influence model. Starting from the policy level, educational activities, recycling infrastructure, and the use of information and communication technology (ICT) and media were hypothesized to introduce contextual influence on the individuals to recycle. All three theoretical constructs from the self-determination theory – basic psychological needs theory (SDT-BPNT), the subjective norms, and controllability component constructs from the theory of planned behaviour (TPB), were selected with the collective efficacy construct, to measure the personal and people levels of influences on the adults to recycle. Financial factors and influences introduced by people and organisations interacting with the individuals were included as personal and people levels of influences respectively to enable a deeper understanding of the context at both levels. After completing the pre-test and pilot surveys in 2020, an online questionnaire survey was conducted by a commercial research company, engaged to gather responses from December 2020 to March 2021 in Singapore to establish the relative strengths of each construct as the hypothesized recycling behavioural antecedents in the contextual influence model (N=700). Data analysis results from the hierarchical linear regressions validated the contextual influence model and established the synergistic relationship between the three levels of contextual influences on the entire sample and the youth respondents whose responses were grouped on their age cohorts, gender, and marital status. The model validation contributed a simple operational framework for academia to integrate theory with practice for theory development. The additional media effects and circles of influences variables as precursors could stabilise the predictive strength of the subjective norm theoretical construct. Further statistical analyses using path analyses validated the theoretical constructs that, when driven by the respective hypothesized policy lever antecedent, could shape one’s inner determination, inner control, social feelings, and group dynamics and offer intrinsic and extrinsic policy intervention contexts. The competence construct was observed to be most impactful in shaping inner determination to recycle and could be more resilient to apply to practice. Policy level influences from the use of ICT and media; and people level influences from one’s circles of influences from interacting with other persons and organisations were also found to be strong drivers to shape recycling behaviours. These validated constructs could be utilised to augment theory applications in future studies and refine recycling policy design and delivery. The thesis concluded with recommendations from the model findings and the Singapore experience for policymakers and a discussion of future research directions. Among the suggestions included the use of theories like the SDT-BPNT to examine and improve policy design and delivery; and areas to examine current practices to adapt to the evolving social context due to the current pandemic. The need to manage the impact of disrupted services, like the closure of recycling infrastructure, was also discussed with alternatives, like designing and making available mobile applications to educate and inform people on recycling matters and empower the fulfillment of their competence needs. It is hoped that the current findings would be a useful reference for other Asian countries and a start of more theory and practice integration studies to make future efforts towards pro-environmental behaviours more impactful.Doctor of Philosoph

    A wavelet algorithm for the solution of the double layer potential equation over polygonal boundaries

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    In this paper we consider a piecewise linear collocation method for the solution of the double layer potential equation corresponding to Laplace's equation over polygonal domains. We give a wavelet algorithm for the computation of the corresponding stiffness matrix and for the solution of the arising matrix equation with no more than O(N x [logN]"8) arithmetic operations. The error of the resulting approximate solution is of order O(N"-"2 x [logN]"6). Finally, we give some remarks on the generalization of the algorithm to the piecewise cubic collocation and present numerical tests. (orig.)Available from TIB Hannover: RR 5549(106)+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10 -11 to 5.0 × 10 -21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10 -6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

    Empagliflozin in Patients with Chronic Kidney Disease

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    Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

    Outcomes from elective colorectal cancer surgery during the SARS‐CoV‐2 pandemic

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    Aim This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic. Method This was an international cohort study of patients undergoing elective resection of colon or rectal cancer without preoperative suspicion of SARS-CoV-2. Centres entered data from their first recorded case of COVID-19 until 19 April 2020. The primary outcome was 30-day mortality. Secondary outcomes included anastomotic leak, postoperative SARS-CoV-2 and a comparison with prepandemic European Society of Coloproctology cohort data. Results From 2073 patients in 40 countries, 1.3% (27/2073) had a defunctioning stoma and 3.0% (63/2073) had an end stoma instead of an anastomosis only. Thirty-day mortality was 1.8% (38/2073), the incidence of postoperative SARS-CoV-2 was 3.8% (78/2073) and the anastomotic leak rate was 4.9% (86/1738). Mortality was lowest in patients without a leak or SARS-CoV-2 (14/1601, 0.9%) and highest in patients with both a leak and SARS-CoV-2 (5/13, 38.5%). Mortality was independently associated with anastomotic leak (adjusted odds ratio 6.01, 95% confidence interval 2.58–14.06), postoperative SARS-CoV-2 (16.90, 7.86–36.38), male sex (2.46, 1.01–5.93), age >70 years (2.87, 1.32–6.20) and advanced cancer stage (3.43, 1.16–10.21). Compared with prepandemic data, there were fewer anastomotic leaks (4.9% versus 7.7%) and an overall shorter length of stay (6 versus 7 days) but higher mortality (1.7% versus 1.1%). Conclusion Surgeons need to further mitigate against both SARS-CoV-2 and anastomotic leak when offering surgery during current and future COVID-19 waves based on patient, operative and organizational risks

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

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