Vital Statistics of Iowa in Brief, 2013

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

A Multi-SNP Locus-Association Method Reveals a Substantial Fraction of the Missing Heritability.

There are many known examples of multiple semi-independent associations at individual loci; such associations might arise either because of true allelic heterogeneity or because of imperfect tagging of an unobserved causal variant. This phenomenon is of great importance in monogenic traits but has not yet been systematically investigated and quantified in complex-trait genome-wide association studies (GWASs). Here, we describe a multi-SNP association method that estimates the effect of loci harboring multiple association signals by using GWAS summary statistics. Applying the method to a large anthropometric GWAS meta-analysis (from the Genetic Investigation of Anthropometric Traits consortium study), we show that for height, body mass index (BMI), and waist-to-hip ratio (WHR), 3%, 2%, and 1%, respectively, of additional phenotypic variance can be explained on top of the previously reported 10% (height), 1.5% (BMI), and 1% (WHR). The method also permitted a substantial increase (by up to 50%) in the number of loci that replicate in a discovery-validation design. Specifically, we identified 74 loci at which the multi-SNP, a linear combination of SNPs, explains significantly more variance than does the best individual SNP. A detailed analysis of multi-SNPs shows that most of the additional variability explained is derived from SNPs that are not in linkage disequilibrium with the lead SNP, suggesting a major contribution of allelic heterogeneity to the missing heritability.

Maximum likelihood Linear Programming Data Fusion for Speaker Recognition

Biometric system performance can be improved by means of data fusion. Several kinds of information can be fused in order to obtain a more accurate classification (identification or verification) of an input sample. In this paper we present a method for computing the weights in a weighted sum fusion for score combinations, by means of a likelihood model. The maximum likelihood estimation is set as a linear programming problem. The scores are derived from a GMM classifier working on a different feature extractor. Our experimental results assesed the robustness of the system in front a changes on time (different sessions) and robustness in front a change of microphone. The improvements obtained were significantly better (error bars of two standard deviations) than a uniform weighted sum or a uniform weighted product or the best single classifier. The proposed method scales computationaly with the number of scores to be fussioned as the simplex method for linear programming.

At-risk drinking and drug use among patients seeking care in an emergency department.

OBJECTIVE: This study reports the frequency of alcohol use and associated tobacco and drug use among emergency department (ED) patients, in order to increase physician awareness and treatment of women and men seeking care in ED settings. METHOD: All adults seen in the ED at the University Hospital in Lausanne, Switzerland, between 11 AM and 11 PM were screened by direct interview for at-risk drinking, tobacco use, drug use, and depression during an 18-month period. RESULTS: A total of 8,599 patients (4,006 women and 4,593 men) participated in the screening procedure and provided full data on the variables in our analysis. The mean age was 51.9 years for women and 45.0 years for men; 57.5% (n = 2,304) of women and 58.5% (n = 2,688) of men were being treated for trauma. Based on guidelines of the National Institute on Alcohol Abuse and Alcoholism, 13.1% (n = 523) of the women were at-risk drinkers, 57.3% (n = 2,301) were low-risk drinkers, and 29.6% (n = 1,182) were abstinent. Among men, 32.8% (n = 1,507) met criteria for at-risk drinking, 51.8% (n = 2,380) met criteria for low-risk drinking, and 15.4% (n = 706) were abstinent. Younger individuals (ages 18-30) had significantly higher rates of episodic heavy drinking episodes, whereas at-risk older patients were more likely to drink on a daily basis. A binary model found that women and men who drank at at-risk levels are more likely to use tobacco (odds ratio [OR] = 2.48, 95% confidence interval [CI]: 2.0-3.08) and illicit drugs (OR = 5.91, CI: 3.32- 10.54) compared with abstinent and low-risk drinkers. CONCLUSIONS: This study supports systematic alcohol screening of women and men seen in EDs and suggests that patterns of alcohol and drug use vary by age and gender.

1.° Hilperici tractatus de arte calculatoria : praemittitur calendarium ad usum Cisterciensium. — 2.° Ratio Gaii Caesaris de ordine anni per duodecim menses. — 3.° Bedae opusculum de loquela digitorum. — 4.° Expositio tabulae de luna quotidiè per rationem epactarum invenienda. — 5.° Excerptum ex etymologiis Isidori, de coelo ejusque luminaribus. — 6.° Carmen de temporibus anni. — 7.° Ratio epactarum. — 8.° Anonymi expositio super tabulam Dionysii Exigui, Abbatis. — 9.° Fragmentum Macrobii de mensura terrae. — 10.° Anonymi figurata expositio duodecim signorum zodiaci. — 11.° Scholium de temporibus et aetatibus mundi. — 12.° Alcuini opusculum de vita Antichristi. — 13.° Hieronymus de quindecim signis praecedentibus diem judicii. — 14.° Beda de die judicii. — 15.° Anonymi chronicon in epitomen contractum, et à mundi creatione ad Leonis III. imperium productum. — 16.° Provincialis Romanae Ecclesiae fragmentum.

Colbertinus

Protocol for a systematic review on the extent of non-publication of research studies and associated study characteristics.

BACKGROUND: Methodological research has found that non-published studies often have different results than those that are published, a phenomenon known as publication bias. When results are not published, or are published selectively based on the direction or the strength of the findings, healthcare professionals and consumers of healthcare cannot base their decision-making on the full body of current evidence. METHODS: As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:1. To determine the proportion and/or rate of non-publication of studies by systematically reviewing methodological research projects that followed up a cohort of studies that a. received research ethics committee (REC) approval,b. were registered in trial registries, orc. were presented as abstracts at conferences.2. To assess the association of study characteristics (for example, direction and/or strength of findings) with likelihood of full publication.To identify reports of relevant methodological research projects we will conduct electronic database searches, check reference lists, and contact experts. Published and unpublished projects will be included. The inclusion criteria are as follows:a. RECs: methodological research projects that examined the subsequent proportion and/or rate of publication of studies that received approval from RECs;b. Trial registries: methodological research projects that examine the subsequent proportion and/or rate of publication of studies registered in trial registries;c. Conference abstracts: methodological research projects that examine the subsequent proportion and/or rate of full publication of studies which were initially presented at conferences as abstracts.Primary outcomes: Proportion/rate of published studies; time to full publication (mean/median; cumulative publication rate by time).Secondary outcomes: Association of study characteristics with full publication.The different questions (a, b, and c) will be investigated separately. Data synthesis will involve a combination of descriptive and statistical summaries of the included methodological research projects. DISCUSSION: Results are expected to be publicly available in mid 2013.

Trends over time of virological and immunological characteristics in the Swiss HIV Cohort Study.

BACKGROUND: The long-term outcome of antiretroviral therapy (ART) is not assessed in controlled trials. We aimed to analyse trends in the population effectiveness of ART in the Swiss HIV Cohort Study over the last decade. METHODS: We analysed the odds of stably suppressed viral load (ssVL: three consecutive values <50 HIV-1 RNA copies/mL) and of CD4 cell count exceeding 500 cells/μL for each year between 2000 and 2008 in three scenarios: an open cohort; a closed cohort ignoring the influx of new participants after 2000; and a worst-case closed cohort retaining lost or dead patients as virological failures in subsequent years. We used generalized estimating equations with sex, age, risk, non-White ethnicity and era of starting combination ART (cART) as fixed co-factors. Time-updated co-factors included type of ART regimen, number of new drugs and adherence to therapy. RESULTS: The open cohort included 9802 individuals (median age 38 years; 31% female). From 2000 to 2008, the proportion of participants with ssVL increased from 37 to 64% [adjusted odds ratio (OR) per year 1.16 (95% CI 1.15-1.17)] and the proportion with CD4 count >500 cells/μL increased from 40 to >50% [OR 1.07 (95% CI 1.06-1.07)]. Similar trends were seen in the two closed cohorts. Adjustment did not substantially affect time trends. CONCLUSIONS: There was no relevant dilution effect through new participants entering the open clinical cohort, and the increase in virological/immunological success over time was not an artefact of the study design of open cohorts. This can partly be explained by new treatment options and other improvements in medical care.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Vital Statistics of Iowa in Brief, 2014

This publication is an historical recording of the most requested statistics on vital events and is a source of information that can be used in further analysis.

Virological and immunological responses to efavirenz or boosted lopinavir as first-line therapy for patients with HIV.

BACKGROUND: Efavirenz and lopinavir boosted with ritonavir are both recommended as first-line therapies for patients with HIV when combined with two nucleoside reverse transcriptase inhibitors. It is uncertain which therapy is more effective for patients starting therapy with an advanced infection. METHODS: We estimated the relative effect of these two therapies on rates of virological and immunological failure within the Swiss HIV Cohort Study and considered whether estimates depended on the CD4(+) T-cell count when starting therapy. We defined virological failure as either an incomplete virological response or viral rebound after viral suppression and immunological failure as failure to achieve an expected CD4(+) T-cell increase calculated from EuroSIDA statistics. RESULTS: Patients starting efavirenz (n=660) and lopinavir (n=541) were followed for a median of 4.5 and 3.1 years, respectively. Virological failure was less likely for patients on efavirenz, with the adjusted hazard ratio (95% confidence interval) of 0.63 (0.50-0.78) then multiplied by a factor of 1.00 (0.90-1.12) for each 100 cells/mm(3) decrease in CD4(+) T-cell count below the mean when starting therapy. Immunological failure was also less likely for patients on efavirenz, with the adjusted hazard ratio of 0.68 (0.51-0.91) then multiplied by a factor of 1.29 (1.14-1.46) for each 100 cells/mm(3) decrease in CD4(+) T-cell count below the mean when starting therapy. CONCLUSIONS: Virological failure is less likely with efavirenz regardless of the CD4(+) T-cell count when starting therapy. Immunological failure is also less likely with efavirenz; however, this advantage disappears if patients start therapy with a low CD4(+) T-cell count.

Rate of undesirable events at beginning of academic year: retrospective cohort study.

OBJECTIVE: To determine whether an increase in the rate of undesirable events occurs after care provided by trainees at the beginning of the academic year. DESIGN: Retrospective cohort study using administrative and patient record data. SETTING: University affiliated hospital in Melbourne, Australia. PARTICIPANTS: 19,560 patients having an anaesthetic procedure carried out by first to fifth year trainees starting work for the first time at the hospital over a period of five years (1995-2000). MAIN OUTCOME MEASURES: Absolute event rates, absolute rate reduction, and rate ratios of undesirable events. RESULTS: The rate of undesirable events was higher at the beginning of the academic year compared with the rest of the year (absolute event rate 137 v 107 per 1000 patient hours, relative rate reduction 28%, P<0.001). The overall adjusted rate ratio for undesirable events was 1.40, 95% confidence interval 1.24 to 1.58. This excess risk was seen for all residents, regardless of their level of seniority. The excess risk decreased progressively after the first month, and the trend disappeared fully after the fourth month of the year (rate ratio for fourth month 1.21, 0.93 to 1.57). The most important decreases were for central and peripheral nerve injuries (relative difference 82%), inadequate oxygenation of the patient (66%), vomiting/aspiration in theatre (53%), and technical failures of tracheal tube placement (49%). CONCLUSIONS: The rate of undesirable events was greater among trainees at the beginning of the academic year regardless of their level of clinical experience. This suggests that several additional factors, such as knowledge of the working environment, teamwork, and communication, may contribute to the increase.

The branch-site test of positive selection is surprisingly robust but lacks power under synonymous substitution saturation and variation in GC

Positive selection is widely estimated from protein coding sequence alignments by the nonsynonymous-to-synonymous ratio omega. Increasingly elaborate codon models are used in a likelihood framework for this estimation. Although there is widespread concern about the robustness of the estimation of the omega ratio, more efforts are needed to estimate this robustness, especially in the context of complex models. Here, we focused on the branch-site codon model. We investigated its robustness on a large set of simulated data. First, we investigated the impact of sequence divergence. We found evidence of underestimation of the synonymous substitution rate for values as small as 0.5, with a slight increase in false positives for the branch-site test. When dS increases further, underestimation of dS is worse, but false positives decrease. Interestingly, the detection of true positives follows a similar distribution, with a maximum for intermediary values of dS. Thus, high dS is more of a concern for a loss of power (false negatives) than for false positives of the test. Second, we investigated the impact of GC content. We showed that there is no significant difference of false positives between high GC (up to similar to 80%) and low GC (similar to 30%) genes. Moreover, neither shifts of GC content on a specific branch nor major shifts in GC along the gene sequence generate many false positives. Our results confirm that the branch-site is a very conservative test.

Oral flurbiprofen metabolic ratio assessment using a single-point dried blood spot.

We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administration. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. FLB's apparent clearance values decreased by 35% in plasma and DBS during session 2 and increased by 75% in plasma and by 30% in DBS during session 3. Good correlations were observed between MRs calculated from urine, plasma, and DBS samples.