STrengthening the REporting of Genetic Association studies (STREGA): an extension of the STROBE Statement

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information into the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and issues of data volume that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE statement

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement

Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modeling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis.

Low Mannan-binding lectin serum levels are associated with complicated Crohn's disease and reactivity to oligomannan (ASCA)

OBJECTIVES: Mannan-binding lectin (MBL) acts as a pattern-recognition molecule directed against oligomannan, which is part of the cell wall of yeasts and various bacteria. We have previously shown an association between MBL deficiency and anti-Saccharomyces cerevisiae mannan antibody (ASCA) positivity. This study aims at evaluating whether MBL deficiency is associated with distinct Crohn's disease (CD) phenotypes. METHODS: Serum concentrations of MBL and ASCA were measured using ELISA (enzyme-linked immunosorbent assay) in 427 patients with CD, 70 with ulcerative colitis, and 76 healthy controls. CD phenotypes were grouped according to the Montreal Classification as follows: non-stricturing, non-penetrating (B1, n=182), stricturing (B2, n=113), penetrating (B3, n=67), and perianal disease (p, n=65). MBL was classified as deficient (<100 ng/ml), low (100-500 ng/ml), and normal (500 ng/ml). RESULTS: Mean MBL was lower in B2 and B3 CD patients (1,503+/-1,358 ng/ml) compared with that in B1 phenotypes (1,909+/-1,392 ng/ml, P=0.013). B2 and B3 patients more frequently had low or deficient MBL and ASCA positivity compared with B1 patients (P=0.004 and P<0.001). Mean MBL was lower in ASCA-positive CD patients (1,562+/-1,319 ng/ml) compared with that in ASCA-negative CD patients (1,871+/-1,320 ng/ml, P=0.038). In multivariate logistic regression modeling, low or deficient MBL was associated significantly with B1 (negative association), complicated disease (B2+B3), and ASCA. MBL levels did not correlate with disease duration. CONCLUSIONS: Low or deficient MBL serum levels are significantly associated with complicated (stricturing and penetrating) CD phenotypes but are negatively associated with the non-stricturing, non-penetrating group. Furthermore, CD patients with low or deficient MBL are significantly more often ASCA positive, possibly reflecting delayed clearance of oligomannan-containing microorganisms by the innate immune system in the absence of MBL.

Continental-scale temperature variability during the past two millennia

Past global climate changes had strong regional expression. To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia. The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century. At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them. There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century. The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions. Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years.

The Swiss-Austrian Alliance for Mountain Research

Switzerland and Austria are committed to addressing sustainable mountain development in Europe through a joint effort. In June 2013, more than 140 researchers as well as representatives of the 2 countries' funding ministries participated in the “Mountain Days” event in Mittersill, Austria, thereby marking the official launch of the Swiss-Austrian Alliance. The resulting Mittersill Commitment Paper highlights 8 research areas and calls for international cooperation between mountain researchers, institutions, and governments.

Endocardial Ablation to Eliminate Epicardial Arrhythmia Substrate in Scar-Related Ventricular Tachycardia

OBJECTIVES We evaluated the feasibility and safety of epicardial substrate elimination using endocardial radiofrequency (RF) delivery in patients with scar-related ventricular tachycardia (VT). BACKGROUND Epicardial RF delivery is limited by fat or associated with bleeding, extra-cardiac damages, coronary vessels and phrenic nerve injury. Alternative ablation approaches may be desirable. METHODS Forty-six patients (18 ischemic cardiomyopathy [ICM], 13 non-ischemic dilated cardiomyopathy [NICM], 15 arrhythmogenic right ventricular cardiomyopathy [ARVC]) with sustained VT underwent combined endo- and epicardial mapping. All patients received endocardial ablation targeting local abnormal ventricular activities in the endocardium (Endo-LAVA) and epicardium (Epi-LAVA), followed by epicardial ablation if needed. RESULTS From a total of 173 endocardial ablations targeting Epi-LAVA at the facing site, 48 (28%) applications (ICM: 20/71 [28%], NICM: 3/39 [8%], ARVC: 25/63 [40%]) successfully eliminated the Epi-LAVA. Presence of Endo-LAVA, most delayed and low bipolar amplitude of Epi-LAVA, low unipolar amplitude in the facing endocardium, and Epi-LAVA within a wall thinning area at CT scan were associated with successful ablation. Endocardial ablation could abolish all Epi-LAVA in 4 ICM and 2 ARVC patients, whereas all patients with NICM required epicardial ablation. Endocardial ablation was able to eliminate Epi-LAVA at least partially in 15 (83%) ICM, 2 (13%) NICM, and 11 (73%) ARVC patients, contributing to a potential reduction in epicardial RF applications. Pericardial bleeding occurred in 4 patients with epicardial ablation. CONCLUSIONS Elimination of Epi-LAVA using endocardial RF delivery is feasible and may be used first to reduce the risk of epicardial ablation.

Origins of Shared Genetic Variation in African Cichlids

Cichlid fishes have evolved tremendous morphological and behavioral diversity in the waters of East Africa. Within each of the Great Lakes Tanganyika, Malawi, and Victoria, the phenomena of hybridization and retention of ancestral polymorphism explain allele sharing across species. Here, we explore the sharing of single nucleotide polymorphisms (SNPs) between the major East African cichlid assemblages. A set of approximately 200 genic and nongenic SNPs was ascertained in five Lake Malawi species and genotyped in a diverse collection of 160 species from across Africa. We observed segregating polymorphism outside of the Malawi lineage for more than 50% of these loci; this holds similarly for genic versus nongenic SNPs, as well as for SNPs at putative CpG versus non-CpG sites. Bayesian and principal component analyses of genetic structure in the data demonstrate that the Lake Malawi endemic flock is not monophyletic and that river species have likely contributed significantly to Malawi genomes. Coalescent simulations support the hypothesis that river cichlids have transported polymorphism between lake assemblages. We observed strong genetic differentiation between Malawi lineages for approximately 8% of loci, with contributions from both genic and nongenic SNPs. Notably, more than half of these outlier loci between Malawi groups are polymorphic outside of the lake. Cichlid fishes have evolved diversity in Lake Malawi as new mutations combined with standing genetic variation shared across East Africa.

Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease

BACKGROUND About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. METHODS Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. RESULTS Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). CONCLUSION The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.

Fractionated stereotactic radiotherapy with static field conformal and non coplanar arcs for pediatric patients with craniopharyngioma: analysis of long term visual outcome and endocrine toxicity

We assessed the efficacy and the toxicity for pediatric craniopharyngioma patients of fractionated stereotactic radiotherapy (FSRT). Between May 2000 and May 2009, 9 patients (male to female ratio, 5:4) with craniopharyngiomas underwent FSRT (median dose, 54 Gy). Among the 9 patients, 6 received radiation therapy (RT) for recurrent tumors and 3 for residual disease as adjuvant therapy after incomplete surgery. Median tumor 3 volume was 2.3 cm (range, 0.1-5.8). The median target coverage was 93.7% (range 79.3-99.8%). The median conformity index was 0.94 (range, 0.6-1.4). Dose to the hippocampal region was assessed for all patients. After a median follow-up of 62.5 months (range, 32-127)the treated volume decreased in size in four of eight patients (50%). One patient was lost to follow-up. Local control and survival rates at 3 years were 100% and there were no marginal relapses. One patient, with a chronic bilateral papillary oedema after surgery, visual defect deteriorated after FSRT to a complete hemianopsia. One male patient with normal pituitary function before FSRT presented with precocious puberty at the age of 7.4 years, 24 months after FSRT. Four patients (50%) were severely obese at their last visit. FSRT is a safe treatment option for craniopharyngioma after incomplete resection.

Site- and species-specific responses of forest growth to climate across the European continent

Aim To evaluate the climate sensitivity of model-based forest productivity estimates using a continental-scale tree-ring network. Location Europe and North Africa (30–70° N, 10° W–40° E). Methods We compiled close to 1000 annually resolved records of radial tree growth for all major European tree species and quantified changes in growth as a function of historical climatic variation. Sites were grouped using a neural network clustering technique to isolate spatiotemporal and species-specific climate response patterns. The resulting empirical climate sensitivities were compared with the sensitivities of net primary production (NPP) estimates derived from the ORCHIDEE-FM and LPJ-wsl dynamic global vegetation models (DGVMs). Results We found coherent biogeographic patterns in climate response that depend upon (1) phylogenetic controls and (2) ambient environmental conditions delineated by latitudinal/elevational location. Temperature controls dominate forest productivity in high-elevation and high-latitude areas whereas moisture sensitive sites are widespread at low elevation in central and southern Europe. DGVM simulations broadly reproduce the empirical patterns, but show less temperature sensitivity in the boreal zone and stronger precipitation sensitivity towards the mid-latitudes. Main conclusions Large-scale forest productivity is driven by monthly to seasonal climate controls, but our results emphasize species-specific growth patterns under comparable environmental conditions. Furthermore, we demonstrate that carry-over effects from the previous growing season can significantly influence tree growth, particularly in areas with harsh climatic conditions – an element not considered in most current-state DGVMs. Model–data discrepancies suggest that the simulated climate sensitivity of NPP will need refinement before carbon-cycle climate feedbacks can be accurately quantified.

Metabotropic glutamate receptor 5 binding in patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disabling, mostly chronic, psychiatric condition with significant social and economic impairments and is a major public health issue. However, numerous patients are resistant to currently available pharmacological and psychological interventions. Given that recent animal studies and magnetic resonance spectroscopy research points to glutamate dysfunction in OCD, we investigated the metabotropic glutamate receptor 5 (mGluR5) in patients with OCD and healthy controls. We determined mGluR5 distribution volume ratio (DVR) in the brain of ten patients with OCD and ten healthy controls by using [11C]ABP688 positron-emission tomography. As a clinical measure of OCD severity, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was employed. We found no significant global difference in mGluR5 DVR between patients with OCD and healthy controls. We did, however, observe significant positive correlations between the Y-BOCS obsession sub-score and mGluR5 DVR in the cortico-striatal-thalamo-cortical brain circuit, including regions of the amygdala, anterior cingulate cortex, and medial orbitofrontal cortex (Spearman's ρ's⩾ = 0.68, p < 0.05). These results suggest that obsessions in particular might have an underlying glutamatergic pathology related to mGluR5. The research indicates that the development of metabotropic glutamate agents would be useful as a new treatment for OCD.

A compendium of strategies to prevent healthcare-associated infections in acute care hospitals: 2014 updates

Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. They are the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS).