Explore the vast range of titles available.

Influenza vaccine effectiveness (VE) can vary by type and subtype. Over the past decade, the test-negative design has emerged as a valid method for estimation of VE. In this design, VE is calculated as 100% × (1 – odds ratio) for vaccine receipt in influenza cases versus test-negative controls. We did a systematic review and meta-analysis to estimate VE by type and subtype. In this systematic review and meta-analysis, we searched PubMed and Embase from Jan 1, 2004, to March 31, 2015. Test-negative design studies of influenza VE were eligible if they enrolled outpatients on the basis of predefined illness criteria, reported subtype-level VE by season, used PCR to confirm influenza, and adjusted for age. We excluded studies restricted to hospitalised patients or special populations, duplicate reports, interim reports superseded by a final report, studies of live-attenuated vaccine, and studies of prepandemic seasonal vaccine against H1N1pdm09. Two reviewers independently assessed titles and abstracts to identify articles for full review. Discrepancies in inclusion and exclusion criteria and VE estimates were adjudicated by consensus. Outcomes were VE against H3N2, H1N1pdm09, H1N1 (pre-2009), and type B. We calculated pooled VE using a random-effects model. We identified 3368 unduplicated publications, selected 142 for full review, and included 56 in the meta-analysis. Pooled VE was 33% (95% CI 26–39; I2=44·4) for H3N2, 54% (46–61; I2=61·3) for type B, 61% (57–65; I2=0·0) for H1N1pdm09, and 67% (29–85; I2=57·6) for H1N1; VE was 73% (61–81; I2=31·4) for monovalent vaccine against H1N1pdm09. VE against H3N2 for antigenically matched viruses was 33% (22–43; I2=56·1) and for variant viruses was 23% (2–40; I2=55·6). Among older adults (aged >60 years), pooled VE was 24% (−6 to 45; I2=17·6) for H3N2, 63% (33–79; I2=0·0) for type B, and 62% (36–78; I2=0·0) for H1N1pdm09. Influenza vaccines provided substantial protection against H1N1pdm09, H1N1 (pre-2009), and type B, and reduced protection against H3N2. Vaccine improvements are needed to generate greater protection against H3N2 than with current vaccines. None.

In the United States, gonadectomy is common and widely promoted as a component of responsible pet ownership. The recent publication of several studies examining the effect of gonadectomy on future health has challenged long-held assumptions and recommendations for gonadectomy in companion animals. The purpose of this study was to characterize the associations between gonadectomy and two outcomes: overweight/obesity and orthopedic injuries, in a large prospective study of Golden Retrievers. Age at gonadectomy was divided into four categories: intact (reference), ≤ 6 months, > 6 months ‒ ≤ 12 months, and > 12 months. Dogs with a Purina Body Condition Score of 7 or greater were classified as overweight or obese. Orthopedic injuries considered were the first instance of veterinary-reported cranial cruciate ligament injury and clinically evident osteoarthritis. We performed survival analyses on a cohort of Golden Retrievers to estimate the associations of interest using proportional hazards. We adjusted for age at study enrollment, owner-reported activity level, and dog's sex. Compared to intact dogs, all gonadectomy age categories showed increased risk for the development of overweight/obesity. (≤ 6 months, HR: 1.81, 95% CI: 1.36-2.40), p-value: <0.0001; 6 months to ≤ 12 months, HR: 2.21, 95% CI: 1.77-2.73, p-value: < 0.0001; > 12 months, HR: 1.56, 95% CI: 1.24-1.96, p-value: 0.0001). Compared to intact dogs, dogs who were ≤ 6 months at gonadectomy had increased risk for orthopedic injury (HR: 4.06, 95% CI: 2.15-7.67, p-value: <0.00001). This study presents prospectively acquired data demonstrating that gonadectomy is a risk factor for both overweight/obesity and chronic non-traumatic orthopedic injuries in a prospective cohort of Golden Retrievers. Our data suggest that gonadectomy at any age is a risk factor for overweight or obesity, but delaying gonadectomy until dogs are at least 6-12 months of age may help to decrease the risk for orthopedic injury.

Diagnostic testing for respiratory syncytial virus (RSV) is not routinely performed in adults. We estimated medically attended RSV seasonal incidence in a community cohort of adults ≥50 years old during four influenza seasons (2006-07 through 2009-10). Patients seeking care for acute respiratory illness (ARI) were prospectively enrolled and tested for RSV by multiplex RT-PCR. Results from enrolled patients were used to estimate projected cases among non-enrolled patients with ARI. The seasonal incidence of medically attended RSV was the sum of actual and projected cases divided by the community cohort denominator. Since each enrollment period did not include the entire RSV season, incidence estimates were adjusted to account for the statewide proportion of RSV occurring outside the study enrollment period. There were 16,088 to 17,694 adults in the cohort each season and 164 RSV cases in all 4 seasons. The overall seasonal incidence of medically attended RSV was 154 episodes (95% CI, 132-180) per 10,000 persons; the incidence was highest in 2007-08 (179) and lowest in 2006-07 (110). Among persons 50-59, 60-69, and ≥70 years old, RSV incidence was 124 (95% CI, 99-156), 147 (95% CI, 110-196), and 199 (95% CI, 153-258), respectively. The incidence of medically attended RSV increased with age and was similar during four seasons.

Background Annual wellness testing is widely recommended for apparently healthy dogs, but there is little data to assist with distinguishing normal variation from clinically important changes. Objectives To define variability in biochemistry analytes between annual wellness tests in healthy Golden Retrievers. Animals Four hundred thirty‐four Golden Retrievers undergoing annual health assessments by their primary care veterinarians as part of a prospective cohort study. Methods Changes in 23 biochemistry analytes were calculated between year 1 and year 2 health checks for 196 dogs classified as healthy for ≥3 consecutive years. Using a direct nonparametric method, annual change intervals were constructed to define normal variability. A validation cohort of 238 dogs without a diagnosis of systemic disease for ≥3 consecutive years were compared with the reference and annual change intervals, and the proportions of dogs outside annual change intervals and a population‐based reference interval were compared by using a McNemar test. Results Annual change intervals were calculated based on 190 dogs after outlier removal. For all 23 analytes, >90% of dogs in the validation cohort were within the annual change interval. There were no significant differences in the classification by reference versus annual change intervals. Conclusions and Clinical Importance The annual change intervals met performance requirements for classification of dogs that did not develop systemic disease in the year following wellness testing as normal.

Background A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. Methods The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues. Results Adults with OI report lower general physical health status ( p  < .0001), exhibit a higher prevalence of auditory (58 % of sample versus 2–16 % of normalized population) and musculoskeletal (64 % of sample versus 1–3 % of normalized population) concerns than the general population, but report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain. Conclusions Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D. Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D. In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = -0.03, 95% Confidence Interval: -0.05, -0.006) and earlier first cow's milk exposure (beta = -0.04, 95% Confidence Interval: -0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92). We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.

Draft genomes of the fungal species Fusarium xylarioides, Teratosphaeria gauchensis and T. zuluensis are presented. In addition an annotation of the genome of Ceratocystis fimbriata is presented. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity and potential management strategies of these economically important fungi.

Background Coronary artery disease has been linked with genotypes for haptoglobin (Hp) which modulates extracorpuscular hemoglobin. We hypothesized that the Hp genotype would predict progression of coronary artery calcification (CAC), a marker of subclinical atherosclerosis. Methods CAC was measured three times in six years among 436 subjects with type 1 diabetes and 526 control subjects participating in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Hp typing was performed on plasma samples by polyacrylamide gel electrophoresis. Results The Hp 2-2 genotype predicted development of significant CAC only in subjects with diabetes who were free of CAC at baseline (OR: 1.95, 95% CI: 1.07-3.56, p = 0.03), compared to those without the Hp 2-2 genotype, controlling for age, sex, blood pressure and HDL-cholesterol. Hp 2 appeared to have an allele-dose effect on development of CAC. Hp genotype did not predict CAC progression in individuals without diabetes. Conclusions Hp genotype may aid prediction of accelerated coronary atherosclerosis in subjects with type 1 diabetes.

RSV was the most common viral agent causing acute respiratory illness in children 6 to 59 months old during the influenza season. Children in the 6-23 month age range had a higher incidence of RSV compared to those aged 24-59 months.Abstract Background.  Respiratory syncytial virus (RSV) and influenza are significant causes of seasonal respiratory illness in children. The incidence of influenza and RSV hospitalization is well documented, but the incidence of medically attended, laboratory-confirmed illness has not been assessed in a well defined community cohort. Methods.  Children aged 6–59 months with medically attended acute respiratory illness were prospectively enrolled during the 2006–2007 through 2009–2010 influenza seasons in a Wisconsin community cohort. Nasal swabs were tested for RSV and influenza by multiplex reverse-transcription polymerase chain reaction. The population incidence of medically attended RSV and influenza was estimated separately and standardized to weeks 40 through 18 of each season. Results.  The cohort included 2800–3073 children each season. There were 2384 children enrolled with acute respiratory illness; 627 (26%) were positive for RSV and 314 (13%) for influenza. The mean age was 28 months (standard deviation [SD] = 15) for RSV-positive and 38 months (SD = 16) for influenza-positive children. Seasonal incidence (cases per 10 000) was 1718 (95% confidence interval [CI], 1602–1843) for RSV and 768 (95% CI, 696–848) for influenza. Respiratory syncytial virus incidence was highest among children 6–11 (2927) and 12–23 months old (2377). Influenza incidence was highest (850) in children 24–59 months old. The incidence of RSV was higher than influenza across all seasons and age groups. Conclusions.  The incidence of medically attended RSV was highest in children 6–23 months old, and it was consistently higher than influenza. The burden of RSV remains high throughout the first 2 years of life.

Some of the most significant breakthroughs in the biological sciences this century will emerge from the development of next generation sequencing technologies. The ease of availability of DNA sequence made possible through these new technologies has given researchers opportunities to study organisms in a manner that was not possible with Sanger sequencing. Scientists will, therefore, need to embrace genomics, as well as develop and nurture the human capacity to sequence genomes and utilise the ’tsunami‘ of data that emerge from genome sequencing. In response to these challenges, we sequenced the genome of Fusarium circinatum, a fungal pathogen of pine that causes pitch canker, a disease of great concern to the South African forestry industry. The sequencing work was conducted in South Africa, making F. circinatum the first eukaryotic organism for which the complete genome has been sequenced locally. Here we report on the process that was followed to sequence, assemble and perform a preliminary characterisation of the genome. Furthermore, details of the computer annotation and manual curation of this genome are presented. The F. circinatum genome was found to be nearly 44 million bases in size, which is similar to that of four other Fusarium genomes that have been sequenced elsewhere. The genome contains just over 15 000 open reading frames, which is less than that of the related species, Fusarium oxysporum, but more than that for Fusarium verticillioides. Amongst the various putative gene clusters identified in F. circinatum, those encoding the secondary metabolites fumosin and fusarin appeared to harbour evidence of gene translocation. It is anticipated that similar comparisons of other loci will provide insights into the genetic basis for pathogenicity of the pitch canker pathogen. Perhaps more importantly, this project has engaged a relatively large group of scientists including students in a significant genome project that is certain to provide a platform for growth in this important area of research in the future.