Showing papers by "University of Vermont published in 2014"

Rarefaction and extrapolation with Hill numbers: a framework for sampling and estimation in species diversity studies

Abstract: Quantifying and assessing changes in biological diversity are central aspects of many ecological studies, yet accurate methods of estimating biological diversity from sampling data have been elusive. Hill numbers, or the effective number of species, are increasingly used to characterize the taxonomic, phylogenetic, or functional diversity of an assemblage. However, empirical estimates of Hill numbers, including species richness, tend to be an increasing function of sampling effort and, thus, tend to increase with sample completeness. Integrated curves based on sampling theory that smoothly link rarefaction (interpolation) and prediction (extrapolation) standardize samples on the basis of sample size or sample completeness and facilitate the comparison of biodiversity data. Here we extended previous rarefaction and extrapolation models for species richness (Hill number q D, where q ¼ 0) to measures of taxon diversity incorporating relative abundance (i.e., for any Hill number q D, q . 0) and present a unified approach for both individual-based (abundance) data and sample- based (incidence) data. Using this unified sampling framework, we derive both theoretical formulas and analytic estimators for seamless rarefaction and extrapolation based on Hill numbers. Detailed examples are provided for the first three Hill numbers: q ¼ 0 (species richness), q ¼ 1 (the exponential of Shannon's entropy index), and q ¼ 2 (the inverse of Simpson's concentration index). We developed a bootstrap method for constructing confidence intervals around Hill numbers, facilitating the comparison of multiple assemblages of both rarefied and extrapolated samples. The proposed estimators are accurate for both rarefaction and short-range extrapolation. For long-range extrapolation, the performance of the estimators depends on both the value of q and on the extrapolation range. We tested our methods on simulated data generated from species abundance models and on data from large species inventories. We also illustrate the formulas and estimators using empirical data sets from biodiversity surveys of temperate forest spiders and tropical ants.

Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents.

Abstract: 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P = 0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P = 0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. Conclusions Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.)

Antidepressants for smoking cessation

Abstract: © 2014 The Cochrane Collaboration. Background: There are at least three reasons to believe antidepressants might help in smoking cessation. Firstly, nicotine withdrawal may produce depressive symptoms or precipitate a major depressive episode and antidepressants may relieve these. Secondly, nicotine may have antidepressant effects that maintain smoking, and antidepressants may substitute for this effect. Finally, some antidepressants may have a specific effect on neural pathways (e.g. inhibiting monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic receptors) underlying nicotine addiction. Objectives: The aim of this review is to assess the effect and safety of antidepressant medications to aid long-term smoking cessation. The medications include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide; nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline; sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine. Search methods: We searched the Cochrane Tobacco Addiction Group Specialised Register which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other reviews and meeting abstracts, in July 2013. Selection criteria: We considered randomized trials comparing antidepressant medications to placebo or an alternative pharmacotherapy for smoking cessation. We also included trials comparing different doses, using pharmacotherapy to prevent relapse or re-initiate smoking cessation or to help smokers reduce cigarette consumption. We excluded trials with less than six months follow-up. Data collection and analysis: We extracted data and assessed risk of bias using standard methodological procedures expected by the Cochrane Collaboration. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Main results: Twenty-four new trials were identified since the 2009 update, bringing the total number of included trials to 90. There were 65 trials of bupropion and ten trials of nortriptyline, with the majority at low or unclear risk of bias. There was high quality evidence that, when used as the sole pharmacotherapy, bupropion significantly increased long-term cessation (44 trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to 1.76). There was moderate quality evidence, limited by a relatively small number of trials and participants, that nortriptyline also significantly increased long-term cessation when used as the sole pharmacotherapy (six trials, N = 975, RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4 trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy (NRT) provides an additional long-term benefit. Based on a limited amount of data from direct comparisons, bupropion and nortriptyline appear to be equally effective and of similar efficacy to NRT (bupropion versus nortriptyline 3 trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N = 4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline and NRT). Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (N = 1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant increase in the rate of serious adverse events amongst participants taking bupropion, though the confidence interval only narrowly missed statistical significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation. There was no evidence of a significant effect for selective serotonin reuptake inhibitors on their own (RR 0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1 sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70, 95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5 selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22, 95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N = 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N = 120, RR 0.70, 95% CI 0.24 to 2.07). Authors' conclusions: The antidepressants bupropion and nortriptyline aid long-term smoking cessation. Adverse events with either medication appear to rarely be serious or lead to stopping medication. Evidence suggests that the mode of action of bupropion and nortriptyline is independent of their antidepressant effect and that they are of similar efficacy to nicotine replacement. Evidence also suggests that bupropion is less effective than varenicline, but further research is needed to confirm this finding. Evidence suggests that neither selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase inhibitors aid cessation.

What are we doing here? Analyzing fifteen years of energy scholarship and proposing a social science research agenda

Abstract: Social science related disciplines, methods, concepts, and topics remain underutilized, and perhaps underappreciated, in contemporary energy studies research. To make this case, the article offers both quantitative and qualitative data. It begins with the quantitative part, providing a content analysis of 4444 research articles involving 9549 authors and 90,079 references (from a smaller subsample) published in three leading energy journals from 1999 to 2013. Within this vast sample, only 19.6 percent of authors reported training in any social science discipline, and less than 0.3 percent of authors reported disciplinary affiliations in areas such as history, psychology, anthropology, and communication studies. Only 12.6 percent of articles utilized qualitative methods and less than 5 percent of citations were to social science and humanities journals. The article then shifts to the qualitative part, where it proposes a variety of methodological and topical areas, along with 75 research questions, that could deepen and broaden energy research, connected in part to all of the articles in this special (inaugural) issue of Energy Research & Social Science (ERSS). Readers from all disciplines are encouraged to read it—especially the parts dealing with areas and concepts outside of their own areas of expertise.

Assemblage Time Series Reveal Biodiversity Change but Not Systematic Loss

Abstract: The extent to which biodiversity change in local assemblages contributes to global biodiversity loss is poorly understood. We analyzed 100 time series from biomes across Earth to ask how diversity within assemblages is changing through time. We quantified patterns of temporal α diversity, measured as change in local diversity, and temporal β diversity, measured as change in community composition. Contrary to our expectations, we did not detect systematic loss of α diversity. However, community composition changed systematically through time, in excess of predictions from null models. Heterogeneous rates of environmental change, species range shifts associated with climate change, and biotic homogenization may explain the different patterns of temporal α and β diversity. Monitoring and understanding change in species composition should be a conservation priority.

Loss-of-function mutations in APOC3, triglycerides, and coronary disease

Abstract: Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10 − 20 ), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10 − 10 ). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10 − 6 ). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.)

TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKɛ supports the anabolic demands of dendritic cell activation

Abstract: The ligation of Toll-like receptors (TLRs) leads to rapid activation of dendritic cells (DCs). However, the metabolic requirements that support this process remain poorly defined. We found that DC glycolytic flux increased within minutes of exposure to TLR agonists and that this served an essential role in supporting the de novo synthesis of fatty acids for the expansion of the endoplasmic reticulum and Golgi required for the production and secretion of proteins that are integral to DC activation. Signaling via the kinases TBK1, IKKɛ and Akt was essential for the TLR-induced increase in glycolysis by promoting the association of the glycolytic enzyme HK-II with mitochondria. In summary, we identified the rapid induction of glycolysis as an integral component of TLR signaling that is essential for the anabolic demands of the activation and function of DCs.

Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update

Abstract: Purpose To provide evidence-based recommendations to practicing oncologists, surgeons, and radiation therapy clinicians to update the 2005 clinical practice guideline on the use of sentinel node biopsy (SNB) for patients with early-stage breast cancer. Methods The American Society of Clinical Oncology convened an Update Committee of experts in medical oncology, pathology, radiation oncology, surgical oncology, guideline implementation, and advocacy. A systematic review of the literature was conducted from February 2004 to January 2013 in Medline. Guideline recommendations were based on the review of the evidence by Update Committee. Results This guideline update reflects changes in practice since the 2005 guideline. Nine randomized clinical trials (RCTs) met systematic review criteria for clinical questions 1 and 2; 13 cohort studies informed clinical question 3. Recommendations Women without sentinel lymph node (SLN) metastases should not receive axillary lymph node dissection (ALND). Women with one to t...

The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Why Are Job Seekers Attracted by Corporate Social Performance? Experimental and Field Tests of Three Signal-Based Mechanisms

Abstract: Research on employee recruitment has shown that an organization's corporate social performance (CSP) affects its attractiveness as an employer, but the underlying mechanisms and processes through which this occurs are poorly understood. We propose that job seekers receive signals from CSP that inform three signal-based mechanisms that ultimately affect organizational attractiveness: job seekers' anticipated pride from being affiliated with the organization, their perceived value fit with the organization, and their expectations about how the organization treats its employees. We hypothesized that these signal-based mechanisms mediate the relationships between CSP and organizational attractiveness, focusing on two aspects of CSP: an organization's community involvement and pro-environmental practices. In an experiment (n 180), we manipulated CSP via a company's web pages. In a field study (n 171), we measured CSP content in the recruitment materials used by organizations at a job fair and job seekers' perceptions of the organizations' CSP. Results provided support for the signal-based mechanisms, and we discuss the implications for theory, future research, and practice

Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations

Abstract: RESULTS There were 338 adjudicated events (192 CHD events, 146 strokes). The observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a 10-year predicted atherosclerotic CVD risk of less than 5% was 1.9 (95% CI, 1.3-2.7) and 1.9, respectively, risk of 5% to less than 7.5% was 4.8 (95% CI, 3.4-6.7) and 4.8, risk of 7.5% to less than 10% was 6.1 (95% CI, 4.4-8.6) and 6.9, and risk of 10% or greater was 12.0 (95% CI, 10.6-13.6) and 15.1 (Hosmer-Lemeshow χ 2 = 19.9, P = .01). The C index was 0.72 (95% CI, 0.70-0.75). There were 234 atherosclerotic CVD events (120 CHD events, 114 strokes) among Medicare-linked participants and the observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a predicted risk of less than 7.5% was 5.3 (95% CI, 2.8-10.1) and 4.0, respectively, risk of 7.5% to less than 10% was 7.9 (95% CI, 4.6-13.5) and 6.4, and risk of 10% or greater was 17.4 (95% CI, 15.3-19.8) and 16.4 (Hosmer-Lemeshow χ 2 =5 .4,P = .71). The C index was 0.67 (95% CI, 0.64-0.71). CONCLUSIONS AND RELEVANCE In this cohort of US adults for whom statin initiation is considered based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year atherosclerotic CVD risks were similar, indicating that these risk equations were well calibrated in the population for which they were designed to be used, and demonstrated moderate to good discrimination.

Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome

Abstract: In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period. Results Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P = 0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P = 0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups. Conclusions As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.)

Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial

Abstract: Summary Background Chemoimmunotherapy has led to improved numbers of patients achieving disease response, and longer overall survival in young patients with chronic lymphocytic leukaemia; however, its application in elderly patients has been restricted by substantial myelosuppression and infection. We aimed to assess safety and activity of ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase (BTK), in treatment-naive patients aged 65 years and older with chronic lymphocytic leukaemia. Methods In our open-label phase 1b/2 trial, we enrolled previously untreated patients at clinical sites in the USA. Eligible patients were aged at least 65 years, and had symptomatic chronic lymphocytic leukaemia or small lymphocytic lymphoma requiring therapy. Patients received 28 day cycles of once-daily ibrutinib 420 mg or ibrutinib 840 mg. The 840 mg dose was discontinued after enrolment had begun because comparable activity of the doses has been shown. The primary endpoint was the safety of the dose-fixed regimen in terms of frequency and severity of adverse events for all patients who received treatment. This study is registered with ClinicalTrials.gov, number NCT01105247. Findings Between May 20, 2010, and Dec 18, 2012, we enrolled 29 patients with chronic lymphocytic leukaemia and two patients with small lymphocytic lymphoma. Median age was 71 years (range 65–84), and 23 (74%) patients were at least 70 years old. Toxicity was mainly of mild-to-moderate severity (grade 1–2). 21 (68%) patients had diarrhoea (grade 1 in 14 [45%] patients, grade 2 in three [10%] patients, and grade 3 in four [13%] patients). 15 (48%) patients developed nausea (grade 1 in 12 [39%] patients and grade 2 in three [10%] patients). Ten (32%) patients developed fatigue (grade 1 in five [16%] patients, grade 2 in four [13%] patients, and grade 3 in one [3%] patient). Three (10%) patients developed grade 3 infections, although no grade 4 or 5 infections occurred. One patient developed grade 3 neutropenia, and one developed grade 4 thrombocytopenia. After a median follow-up of 22·1 months (IQR 18·4–23·2), 22 (71%) of 31 patients achieved an objective response (95% CI 52·0–85·8); four patients (13%) had a complete response, one patient (3%) had a nodular partial response, and 17 (55%) patients had a partial response. Interpretation The safety and activity of ibrutinib in elderly, previously untreated patients with symptomatic chronic lymphocytic leukaemia, or small lymphocytic lymphoma is encouraging, and merits further investigation in phase 3 trials. Funding Pharmacyclics, Leukemia and Lymphoma Society, D Warren Brown Foundation, Mr and Mrs Michael Thomas, Harry Mangurian Foundation, P50 CA140158 to Prof J C Byrd MD.

An official European Respiratory Society statement on physical activity in COPD

Abstract: This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 ''Rehabilitation and Chronic Care'' determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5-8 years).

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

Abstract: The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases.

mHealth: A Mechanism to Deliver More Accessible, More Effective Mental Health Care

Abstract: The increased popularity and functionality of mobile devices has a number of implications for the delivery of mental health services. Effective use of mobile applications has the potential to (a) increase access to evidence-based care; (b) better inform consumers of care and more actively engage them in treatment; (c) increase the use of evidence-based practices; and (d) enhance care after formal treatment has concluded. The current paper presents an overview of the many potential uses of mobile applications as a means to facilitate ongoing care at various stages of treatment. Examples of current mobileapplicationsinbehaviouraltreatmentandresearcharedescribed,andtheimplicationsofsuchuses are discussed. Finally, we provide recommendations for methods to include mobile applications into current treatment and outline future directions for evaluation. Copyright © 2013 John Wiley & Sons, Ltd. Key Practitioner Message:  Mobile devices are becoming increasingly common among the adult population and have tremendous potential to advance clinical care.  Mobile applications have the potential to enhance clinical care at stages of treatment—from engaging patients in clinical care to facilitating adherence to practices and in maintaining treatment gains.  Research is needed to validate the efficacy and effectiveness of mobile applications in clinical practice.  Research on such devices must incorporate assessments of usability and adherence in addition to their incremental benefit to treatment.

Inactivating mutations in NPC1L1 and protection from coronary heart disease

Abstract: Ezetimibe lowers plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1) protein. However, whether such inhibition reduces the risk of coronary heart disease is not known. Human mutations that inactivate a gene encoding a drug target can mimic the action of an inhibitory drug and thus can be used to infer potential effects of that drug.We sequenced the exons of NPC1L1 in 7364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry. We identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, we genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with coronary heart disease and in 68,412 controls. We tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease.With sequencing, we identified 15 distinct NPC1L1 inactivating mutations; approximately 1 in every 650 persons was a heterozygous carrier for 1 of these mutations. Heterozygous carriers of NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg per deciliter (0.31 mmol per liter) lower than that in noncarriers (P=0.04). Carrier status was associated with a relative reduction of 53% in the risk of coronary heart disease (odds ratio for carriers, 0.47; 95% confidence interval, 0.25 to 0.87; P=0.008). In total, only 11 of 29,954 patients with coronary heart disease had an inactivating mutation (carrier frequency, 0.04%) in contrast to 71 of 83,140 controls (carrier frequency, 0.09%).Naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease. (Funded by the National Institutes of Health and others.).

Atrial Fibrillation and the Risk of Myocardial Infarction

Abstract: Importance Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF) However, the extent to which AF is a risk factor for MI has not been investigated Objective To examine the risk of incident MI associated with AF Design, Setting, and Participants A prospective cohort of 23 928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009 Main Outcomes and Measures Expert-adjudicated total MI events (fatal and nonfatal) Results Over 69 years of follow-up (median 45 years), 648 incident MI events occurred In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 196 [95% CI, 152-252]) This association remained significant (HR, 170 [95% CI, 126-230]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure–lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 216 [95% CI, 141-331]) than in men (HR, 139 [95% CI, 091-210]) and in blacks (HR, 253 [95% CI, 167-386]) than in whites (HR, 126 [95% CI, 083-193]); for interactions, P = 03 and P = 02, respectively On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger ( P = 44 Conclusions and Relevance AF is independently associated with an increased risk of incident MI, especially in women and blacks These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI

Neuropsychosocial profiles of current and future adolescent alcohol misusers

Abstract: Many factors have been proposed as contributors to risk of alcohol abuse, but quantifying their influence has been difficult; here a longitudinal study of a large sample of adolescents and machine learning are used to generate models of predictors of current and future alcohol abuse, assessing the relative contribution of many factors, including life history, individual personality differences, brain structure and genotype. Many factors have been identified as contributors to risk of alcohol abuse but their relative importance has been difficult to quantify. Robert Whelan et al. constructed models of current and future adolescent binge drinking using data from the IMAGEN project, a study of risk-taking behaviour in more than 2,000 teenagers recruited at age 14 from the United Kingdom, Ireland, France and Germany. The authors used machine learning to generate models of predictors of current and future alcohol abuse, assessing the contribution of many factors including life history, individual personality differences, brain structure and genotype. A key finding of the study was that personality factors were, surprisingly, not particularly useful predictors of future alcohol misuse. In contrast, neurodevelopmental immaturity, certain structural and functional indicators in the brain, sexual experience and prenatal alcohol exposure were associated with current and future binge drinking. A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

A methodology for adaptable and robust ecosystem services assessment

Abstract: Ecosystem Services (ES) are an established conceptual framework for attributing value to the benefits that nature provides to humans. As the promise of robust ES-driven management is put to the test, shortcomings in our ability to accurately measure, map, and value ES have surfaced. On the research side, mainstream methods for ES assessment still fall short of addressing the complex, multi-scale biophysical and socioeconomic dynamics inherent in ES provision, flow, and use. On the practitioner side, application of methods remains onerous due to data and model parameterization requirements. Further, it is increasingly clear that the dominant “one model fits all” paradigm is often ill-suited to address the diversity of real-world management situations that exist across the broad spectrum of coupled human-natural systems. This article introduces an integrated ES modeling methodology, named ARIES (ARtificial Intelligence for Ecosystem Services), which aims to introduce improvements on these fronts. To improve conceptual detail and representation of ES dynamics, it adopts a uniform conceptualization of ES that gives equal emphasis to their production, flow and use by society, while keeping model complexity low enough to enable rapid and inexpensive assessment in many contexts and for multiple services. To improve fit to diverse application contexts, the methodology is assisted by model integration technologies that allow assembly of customized models from a growing model base. By using computer learning and reasoning, model structure may be specialized for each application context without requiring costly expertise. In this article we discuss the founding principles of ARIES - both its innovative aspects for ES science and as an example of a new strategy to support more accurate decision making in diverse application contexts.

Worldwide Patterns of Ancestry, Divergence, and Admixture in Domesticated Cattle

Abstract: The domestication and development of cattle has considerably impacted human societies, but the histories of cattle breeds and populations have been poorly understood especially for African, Asian, and American breeds. Using genotypes from 43,043 autosomal single nucleotide polymorphism markers scored in 1,543 animals, we evaluate the population structure of 134 domesticated bovid breeds. Regardless of the analytical method or sample subset, the three major groups of Asian indicine, Eurasian taurine, and African taurine were consistently observed. Patterns of geographic dispersal resulting from co-migration with humans and exportation are recognizable in phylogenetic networks. All analytical methods reveal patterns of hybridization which occurred after divergence. Using 19 breeds, we map the cline of indicine introgression into Africa. We infer that African taurine possess a large portion of wild African auroch ancestry, causing their divergence from Eurasian taurine. We detect exportation patterns in Asia and identify a cline of Eurasian taurine/indicine hybridization in Asia. We also identify the influence of species other than Bos taurus taurus and B. t. indicus in the formation of Asian breeds. We detect the pronounced influence of Shorthorn cattle in the formation of European breeds. Iberian and Italian cattle possess introgression from African taurine. American Criollo cattle originate from Iberia, and not directly from Africa with African ancestry inherited via Iberian ancestors. Indicine introgression into American cattle occurred in the Americas, and not Europe. We argue that cattle migration, movement and trading followed by admixture have been important forces in shaping modern bovine genomic variation.

Ecological Homogenization of Urban USA

Abstract: A visually apparent but scientifically untested outcome of land-use change is homogenization across urban areas, where neighborhoods in different parts of the country have similar patterns of roads, residential lots, commercial areas, and aquatic features. We hypothesize that this homogenization extends to ecological structure and also to ecosystem functions such as carbon dynamics and microclimate, with continental-scale implications. Further, we suggest that understanding urban homogenization will provide the basis for understanding the impacts of urban land-use change from local to continental scales. Here, we show how multi-scale, multi-disciplinary datasets from six metropolitan areas that cover the major climatic regions of the US (Phoenix, AZ; Miami, FL; Baltimore, MD; Boston, MA; Minneapolis–St Paul, MN; and Los Angeles, CA) can be used to determine how household and neighborhood characteristics correlate with land-management practices, land-cover composition, and landscape structure and ecosystem functions at local, regional, and continental scales.

Climate‐Smart Landscapes: Opportunities and Challenges for Integrating Adaptation and Mitigation in Tropical Agriculture

Abstract: 18 Bioversity International, Regional Office for the Americas, Recta Cali-Palmira km 17, Palmira, Colombia Abstract Addressing the global challenges of climate change, food security, and poverty alleviation requires enhancing the adaptive capacity and mitigation potential of agricultural landscapes across the tropics. However, adaptation and mitiga- tion activities tend to be approached separately due to a variety of technical, political, financial, and socioeconomic constraints. Here, we demonstrate that many tropical agricultural systems can provide both mitigation and adaptation benefits if they are designed and managed appropriately and if the larger land- scape context is considered. Many of the activities needed for adaptation and mitigation in tropical agricultural landscapes are the same needed for sustain- able agriculture more generally, but thinking at the landscape scale opens a new dimension for achieving synergies. Intentional integration of adaptation and mitigation activities in agricultural landscapes offers significant benefits that go beyond the scope of climate change to food security, biodiversity con- servation, and poverty alleviation. However, achieving these objectives will require transformative changes in current policies, institutional arrangements, and funding mechanisms to foster broad-scale adoption of climate-smart ap- proaches in agricultural landscapes.