Metabolic profiling of aortic stenosis and hypertrophic cardiomyopathy identifies mechanistic contrasts in substrate utilization.

Aortic stenosis (AS) and hypertrophic cardiomyopathy (HCM) are distinct disorders leading to left ventricular hypertrophy (LVH), but whether cardiac metabolism substantially differs between these in humans remains to be elucidated. We undertook an invasive (aortic root, coronary sinus) metabolic profiling in patients with severe AS and HCM in comparison with non-LVH controls to investigate cardiac fuel selection and metabolic remodeling. These patients were assessed under different physiological states (at rest, during stress induced by pacing). The identified changes in the metabolome were further validated by metabolomic and orthogonal transcriptomic analysis, in separately recruited patient cohorts. We identified a highly discriminant metabolomic signature in severe AS in all samples, regardless of sampling site, characterized by striking accumulation of long-chain acylcarnitines, intermediates of fatty acid transport across the inner mitochondrial membrane, and validated this in a separate cohort. Mechanistically, we identify a downregulation in the PPAR-α transcriptional network, including expression of genes regulating fatty acid oxidation (FAO). In silico modeling of ß-oxidation demonstrated that flux could be inhibited by both the accumulation of fatty acids as a substrate for mitochondria and the accumulation of medium-chain carnitines which induce competitive inhibition of the acyl-CoA dehydrogenases. We present a comprehensive analysis of changes in the metabolic pathways (transcriptome to metabolome) in severe AS, and its comparison to HCM. Our results demonstrate a progressive impairment of ß-oxidation from HCM to AS, particularly for FAO of long-chain fatty acids, and that the PPAR-α signaling network may be a specific metabolic therapeutic target in AS.

A Retrospective Analysis of the Disruptions in the HIV Continuum of Care During the COVID-19 Pandemic: Lessons From a Clinic-Based Study.

BACKGROUND: The COVID-19 pandemic profoundly affected healthcare services, including HIV patient care. This study assessed the impact of the pandemic on diverse aspects of care for individuals living with HIV (PLWH). METHODS: Patient data from 2019 to 2021 were collected using the Cascades template, provided by the New York State Department of Health, focusing on viral testing and suppression outcomes. Age, ethnicity, sex, and race were considered variables and analyzed via chi-square analysis, logistic regression model, and F test. RESULTS: The pandemic significantly reduced viral testing in 2020 due to restrictions and closures, but telemedicine and tele-pharmacy helped maintain care. Age was a crucial factor, predicting higher viral testing and suppression odds for older individuals, but no significant differences were observed between patient gender, race, or ethnicity in obtaining viral testing or achieving suppression. CONCLUSIONS: While limitations existed, this study provides insights into sustaining care during crises, highlighting the importance of innovative healthcare delivery methods and age-sensitive approaches for PLWH.

Nitrogen Critical Loads: Critical Reflections on Past Experiments, Ecological Endpoints, and Uncertainties.

Nitrogen Critical Loads (NCL), as purported ecological dose-response outcomes for nitrogen deposition from anthropogenic sources, play a central role in environmental policies around the world. In the Netherlands, these NCL are used to assess, via calculations using the model AERIUS, to what extent NCL are exceeded for different habitats as a result of different sources such as industry, agriculture, traffic. NCL are, however, not well defined, and are subject to hitherto unrecognized forms of uncertainty. We will address this with reference to a number of key studies that forms the basis for several NCL. We will subsequently propose amendments that could be applicable to future nitrogen studies and their enhanced relevancy in decision making.

Higher Author Fees in Gastroenterology Journals Are Not Associated with Faster Processing Times or Higher Impact.

BACKGROUND: Publications are an important component of academic careers. AIMS: We investigated the financial costs to authors for submitting and publishing manuscripts in gastroenterology (GI) journals in the United States (US), United Kingdom (UK), and elsewhere. METHODS: This was a cross-sectional study carried out from 11/1/2020 to 12/31/2020. We used the SCImago Journal and Country Rankings site to compile a list of gastroenterology and hepatology journals to analyze. We gathered information on the journals' Hirsch indices (h indices), SCImago Journal Rank (SJR), Impact Factor (IF), and base countries as of 2019, processing and publication fees, open access fees, time to first decision, and time from acceptance to publication. We used t-testing and linear regression modeling to evaluate the effect of geography and journal quality metrics on processing fees and times. RESULTS: We analyzed 97 GI journals, of which 51/97 (52.6%) were based in the US/UK while the other 46/97 (47.4%) were based elsewhere. The mean IF (5.67 vs 3.53, p = 0.08), h index (90.5 vs 41.8, p < 0.001), and SJR (1.82 vs 0.83, p < 0.001) for the US/UK journals were higher than those for non-US/UK journals. We also found that 11/51 (21.6%) of US/UK journals and 15/46 (32.6%) of non-US/UK journals had mandatory processing and publication fees. These tended to be significantly larger in the US/UK group than in the non-US/UK group (USD 2380 vs USD 1470, p = 0.04). CONCLUSIONS: Publication-related fees may preclude authors from smaller or socioeconomically disadvantaged institutions and countries from publishing and disseminating their work.

Fellowship program directors and trainees across the United States find parental leave policies to be inconsistent, inaccessible, and inadequate.

INTRODUCTION: Determine the consistency, accessibility, and adequacy of parental leave policies for adult and pediatric medicine fellowship programs. METHODS: We administered a 40-question survey to fellowship program directors (PDs) and trainees in adult and pediatric cardiology, hematology/oncology, gastroenterology, and pulmonology/critical care fellowship programs in the United States. We used Chi-square tests to compare proportions for categorical variables and t-tests to compare means for continuous variables. RESULTS: A total of 190 PDs from 500 programs (38.0%) and 236 trainees from 142 programs (28.4%) responded. Most respondents did not believe that parental leave policies were accessible publicly (322/426; 75.6%), on password-protected intranet (343/426; 80.5%), or upon request (240/426; 56.3%). The PDs and trainees broadly felt that parental leave for fellows should be 5-10 weeks (156/426; 36.6%) or 11-15 weeks (165/426; 38.7%). A majority of PDs felt that there was no increased burden upon other fellows (122/190; 64.2%) or change in overall well-being (110/190; 57.9%). When asked about the biggest barrier to parental leave support, most PDs noted time constrains of fellowship (101/190; 53.1%) and the limited number of fellows (43/190; 22.6%). Trainees similarly selected the time constraints of training (88/236; 37.3%), but nearly one-fifth chose the culture in medicine (44/236; 18.6%). There were no statistically significant differences in answers based on the respondents' sex, specialty, or subspecialty. DISCUSSION: Parental leave policies are broadly in place, but did not feel these were readily accessible, standardized, or of optimum length. PDs and trainees noted several barriers that undermine support for better parental leave policies, including time constraints of fellowship, the limited number of fellows for coverage, and workplace culture. Standardization of parental leave policies is advisable to allow trainees to pursue fellowship training and care for their newborns without undermining their educational experiences.

Women remain underrepresented in leadership positions in academic gastroenterology throughout the United States.

BACKGROUND: Publication history is a key factor in securing academic promotion, but historical underrepresentation of women in gastroenterology may be an ongoing obstacle to achieving gender parity in leadership positions. METHODS: We carried out a cross-sectional study of gastroenterology programs in the United States, with data including faculty and trainee names, leadership positions, Hirsch indices, and year of first gastroenterology certification gathered from 1 February 2020 to 1 March 2020. Our outcomes of interest were: 1) sex representation in various leadership positions in academic gastroenterology departments; and 2) mean difference in Hirsch indices between men and women, for which we used univariate and multivariate regression models. RESULTS: Our cohort included 3655 faculty members and trainees across 163 academic gastroenterology programs in the United States. Women comprised 28.7% (1049/3655) of the cohort, including 713/2657 (26.8%) of faculty and 56/289 (19.4%) of all fellowship program directors and divisional/departmental chairs and chiefs. Male faculty had higher mean Hirsch indices compared to women (11.4 vs. 5.5, P<0.001), and when adjusted for year of first gastroenterology certification, men had a larger Hirsch index by 2.8 (95% confidence interval 1.3-4.1, P<0.001). Women were also underrepresented in various subspecialties of gastroenterology, particularly advanced endoscopy. CONCLUSIONS: Women in academic gastroenterology remain underrepresented in leadership positions and have lower Hirsch indices than men. Our findings may stem not only from differences in mentorship and career goals, but also from underlying structural factors that disadvantage women.

Can Sex and Seniority Predict the Quality of a Journal Reviewer's Manuscript Critique?

PURPOSE: To evaluate reviewers' timeliness and review quality for the International Journal of Radiation Oncology, Biology, Physics (IJROBP) by sex and seniority. METHODS AND MATERIALS: The IJROBP editorial office provided data on 3962 individuals invited to review manuscripts from 2011 through 2014. We identified 1657 reviewers who had been invited to provide a review on at least 3 occasions during the study period and compared review timeliness and scoring between male and female reviewers. We confirmed the reviewers' sex after having unblinded their names based on our personal acquaintance with them and via an Internet search on their department websites. We then did a subset analysis of 124 US-based reviewers who had returned a "major revision" decision. We used the Review Quality Instrument (RQI) to rate their reviews. We used odds ratios and t tests to look for differences in mean RQI scores and factors that might be associated with quality-in particular, Hirsch indices (h indices) and year of first certification. RESULTS: Of the 1657 reviewers of interest, 1245 (75.1%) were men and 412 (24.9%) were women. We found no statistically significant differences between men and women in the time to respond to invitations. There were no statistically significant differences in timeliness or review reminders based on sex. Our subset analysis showed no difference in quality (RQI scores) based on the reviewers' sex, h index, or year of first certification. CONCLUSIONS: Women and men render reviews of equal quality regardless of seniority and h index, yet women have been invited less frequently to review. This is likely because of the underrepresentation of women in radiation oncology. A more balanced academic population is needed to address this continuing disparity of women's representation in academic publishing.

Racial Disparities in COVID-19 Hospitalization and In-hospital Mortality at the Height of the New York City Pandemic.

OBJECTIVES: Investigate whether or not race is associated with differences in hospitalization and survival to discharge among patients with coronavirus disease-2019 (COVID-19) at the height of the pandemic in New York City (NYC). METHODS: Single-center retrospective cohort study of COVID-19 patients hospitalized at our university-affiliated NYC hospital from 3/10/20 through 4/13/20 with follow-up to 5/1/20. Our primary endpoint was hospitalization rate among patients with confirmed COVID-19 compared with the regional population based on race. Our secondary endpoint survival to discharge among hospitalized COVID-19 patients. NYC Department of Health data were used to calculate hospitalization odds ratios. Chi-square and t tests were used to compare categorial and continuous variables, respectively. Cox proportional hazards regression and predictive analysis were used to investigate our endpoints further. RESULTS: Our cohort of 734 patients included 355 women (48.4%), 372 Blacks (50.7%), 214 Whites (29.2%), and 92 Hispanics (12.5%) in our analysis. Blacks were nearly twice as likely as Whites to require hospitalization for COVID-19 (OR 1.89, 95% CI, 1.59-2.24, p < 0.001). Hispanics were also more likely to suffer in-hospital mortality from COVID-19 compared with Whites (HR 1.84; 95% CI 1.21-2.80; p = 0.005). There was a non-significant increased hazard of in-hospital mortality among Blacks when compared with Whites (HR, 1.30; 95% CI, 0.95-1.78; p = 0.09). CONCLUSIONS AND RELEVANCE: Blacks were more likely than Whites to require hospitalization for COVID-19 while Hispanics were more likely to experience in-hospital mortality. Further investigation into the socioeconomic factors underlying racial disparities in COVID-19 survival and severity requiring hospitalization is needed on a national scale.

Endoscopic Ultrasound-Guided Fine Needle Biopsy Needles Provide Higher Diagnostic Yield Compared to Endoscopic Ultrasound-Guided Fine Needle Aspiration Needles When Sampling Solid Pancreatic Lesions: A Meta-Analysis.

BACKGROUND/AIMS: Studies comparing the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for solid pancreatic lesions have been inconclusive with no clear superiority. The aim of this meta-analysis was to compare the diagnostic accuracy and safety between the two sampling techniques. METHODS: We performed a systematic search of randomized controlled trials published between 2012 and 2019. The primary outcome was overall diagnostic accuracy. Secondary outcomes included adverse event rates, cytopathologic and histopathologic accuracy, and the mean number of passes required to obtain adequate tissue between FNA and FNB needles. Fixed and random effect models with pooled estimates of target outcomes were developed. RESULTS: Eleven studies involving 1,365 participants were included for analysis. When compared to FNB, FNA had a significant reduction in diagnostic accuracy (81% and 87%, p=0.005). In addition, FNA provided reduced cytopathologic accuracy (82% and 89%, p=0.04) and an increased number of mean passes required compared to FNB (2.3 and 1.6, respectively, p<0.0001). There was no difference in adverse event rate between FNA and FNB needles (1.8% and 2.3% respectively, p=0.64). CONCLUSION: FNB provides superior diagnostic accuracy without compromising safety when compared to FNA. FNB should be readily considered by endosonographers when evaluating solid pancreatic masses.

Racial Disparities with Esophageal Cancer Mortality at a High-Volume University Affiliated Center: An All ACCESS Invitation.

BACKGROUND: Esophageal cancer (EC) has a dismal prognosis with 5-year survival < 19%. Black patients with EC have higher mortality than white patients, but the cause of this disparity is unclear. We sought to investigate the impact of race upon overall mortality (OM) among EC patients at our institution. METHODS: We performed a single-center retrospective review of all patients diagnosed with EC between January 2010 through December 2016 with follow-up through October 2017. We compared the difference among categorical variables and mortality using Fisher's exact test. Odds ratios (OR) and hazard regression (HR) were constructed to analyze treatment options by race. The Kaplan-Meier method was used to plot OM curves by race. We also used a logistic regression analysis to construct a predictive model for mortality based on histology and race. RESULTS: We identified 77 patients (62% male) diagnosed with EC. There was no difference in treatments offered based on race. After adjusting for age, histology and stage, we found mortality was significantly higher in blacks when compared to whites (HR 14.07, 95% CI [2.33-129.70] p < 0.008). Our predictive model revealed that blacks had a higher probability of mortality at all stages of EC. CONCLUSIONS: We found race to be an independent risk factor for OM in EC patients. This likely reflects differences in healthcare utilization or access, as evidenced by higher prevalence of Stage IV EC in black patients. Continued investigation is needed to address this disparity locally and nationally.

Comparative outcomes of endoscopic ultrasound-guided cystogastrostomy for peripancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided cystogastrostomy has become the first-line treatment for symptomatic peripancreatic fluid collections. The aim of this study is to analyze the efficacy and safety of cystogastrostomy via a meta-analysis of the literature. METHODS: We performed a systematic search of PubMed and Medline databases for studies published from January 2005 to May 2018. We included randomized controlled trials along with retrospective and prospective observational studies reporting endoscopic ultrasound-guided cystogastrostomy stent placement for peripancreatic fluid collections. The primary outcome for our meta-analysis was complete peripancreatic fluid collection resolution on imaging. Our secondary outcomes included comparative efficacy and safety of the procedure for pseudocysts and walled-off pancreatic necrosis using metal and plastic stents. RESULTS: Seventeen articles involving 1708 patients met our inclusion criteria for meta-analysis. Based upon the random effects model, the pooled technical success rate of cystogastrostomy was 88% (95% confidence interval = 83-92 with I 2 = 85%). There was no difference in the technical success rate between pancreatic pseudocysts and walled-off pancreatic necrosis (91% and 86%, respectively p = nonsignificant). The adverse event rates for metal and plastic stents were equivalent (14% and 18%, respectively, p = nonsignificant). CONCLUSION: Endoscopic ultrasound-guided cystogastrostomy stents are effective in the treatment of pancreatic pseudocysts and walled-off pancreatic necrosis. We found no difference in technical success or adverse event rates of drainage based on peripancreatic fluid collection type or stent used.

Racial/Ethnic variations in morbidity and mortality in Adult Onset Still's Disease: An analysis of national dataset.

OBJECTIVES: Adult Onset Still's Disease (AOSD) is a rare autoinflammatory disorder. There is relatively little known about the impact of social determinants of health on its outcomes. Our goal is to describe the racial/ethnic variations, morbidity and mortality of AOSD hospitalized patients in the US. MATERIALS AND METHODS: Adult US hospitalized patients between 2009-13 from a nationwide inpatient sample (NIS) database with AOSD were identified using ICD-9 code 714.2. NIS is the largest all-payer US inpatient database with approximately 8 million hospitalizations yearly. Patients with other autoimmune diseases were excluded. We used descriptive statistics to summarize patient and hospital characteristics. We performed survey-weighted logistic regression models adjusting for confounders to study our primary outcome: in-hospital mortality. RESULTS: Between 2009-13, 5,820 AOSD patients were hospitalized with a mean age of 53.6 (SE-0.61) years. 3817 (65.6%) were female, 56% white and 3% Asian. Macrophage Activating Syndrome (1.7%), Disseminated Intravascular Coagulation (DIC-1.1%) and Thrombotic Thrombocytopenic Purpura (0.4%), respectively, complicated the hospital course. There were 154 inpatient deaths in study period (mortality 2.6%). Mean age of patients who died in hospital was higher (62.4 years ± 3.1) and 13.9% were Asians. Patients of Asian origin had significantly higher odds of in-hospital death compared to whites (aOR = 6.39, 95% CI 1.77-23.1, p = 0.005). Mortality was significantly higher for patients whose hospital course was complicated by DIC (aOR = 29.69, 95% CI 5.5-160.41, p = 0.006). CONCLUSIONS: In this national sample of patients hospitalized for AOSD, we found significant variations in In-hospital mortality.

Manipulating the Alpha Level Cannot Cure Significance Testing.

We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

Cyclooxygenase-2, Asymmetric Dimethylarginine, and the Cardiovascular Hazard From Nonsteroidal Anti-Inflammatory Drugs.

BACKGROUND: Large-scale, placebo-controlled trials established that nonsteroidal anti-inflammatory drugs confer a cardiovascular hazard: this has been attributed to depression of cardioprotective products of cyclooxygenase (COX)-2, especially prostacyclin. An alternative mechanism by which nonsteroidal anti-inflammatory drugs might constrain cardioprotection is by enhancing the formation of methylarginines in the kidney that would limit the action of nitric oxide throughout the vasculature. METHODS: Targeted and untargeted metabolomics were used to investigate the effect of COX-2 deletion or inhibition in mice and in osteoarthritis patients exposed to nonsteroidal anti-inflammatory drugs on the l-arginine/nitric oxide pathway. RESULTS: Analysis of the plasma and renal metabolome was performed in postnatal tamoxifen-inducible Cox-2 knockout mice, which exhibit normal renal function and blood pressure. This revealed no changes in arginine and methylarginines compared with their wild-type controls. Moreover, the expression of genes in the l-arginine/nitric oxide pathway was not altered in the renal medulla or cortex of tamoxifen inducible Cox-2 knockout mice. Therapeutic concentrations of the selective COX-2 inhibitors, rofecoxib, celecoxib, and parecoxib, none of which altered basal blood pressure or renal function as reflected by plasma creatinine, failed to elevate plasma arginine and methylarginines in mice. Finally, plasma arginine or methylarginines were not altered in osteoarthritis patients with confirmed exposure to nonsteroidal anti-inflammatory drugs that inhibit COX-1 and COX-2. By contrast, plasma asymmetrical dimethylarginine was increased in mice infused with angiotensin II sufficient to elevate blood pressure and impair renal function. Four weeks later, blood pressure, plasma creatinine, and asymmetrical dimethylarginine were restored to normal levels. The increase in asymmetrical dimethylarginine in response to infusion with angiotensin II in celecoxib-treated mice was also related to transient impairment of renal function. CONCLUSIONS: Plasma methylarginines are not altered by COX-2 deletion or inhibition but rather are elevated coincident with renal compromise.

Genome-Based Prediction of Time to Curd Induction in Cauliflower.

The development of cauliflower (Brassica oleracea var. botrytis) is highly dependent on temperature due to vernalization requirements, which often causes delay and unevenness in maturity during months with warm temperatures. Integrating quantitative genetic analyses with phenology modeling was suggested to accelerate breeding strategies toward wide-adaptation cauliflower. The present study aims at establishing a genome-based model simulating the development of doubled haploid (DH) cauliflower lines to predict time to curd induction of DH lines not used for model parameterization and test hybrids derived from the bi-parental cross. Leaf appearance rate and the relation between temperature and thermal time to curd induction were examined in greenhouse trials on 180 DH lines at seven temperatures. Quantitative trait loci (QTL) analyses carried out on model parameters revealed ten QTL for leaf appearance rate (LAR), five for the slope and two for the intercept of linear temperature-response functions. Results of the QTL-based phenology model were compared to a genomic selection (GS) model. Model validation was carried out on data comprising four field trials with 72 independent DH lines, 160 hybrids derived from the parameterization set, and 34 hybrids derived from independent lines of the population. The QTL model resulted in a moderately accurate prediction of time to curd induction (R2 = 0.42-0.51) while the GS model generated slightly better results (R2 = 0.52-0.61). Predictions of time to curd induction of test hybrids from independent DH lines were less precise with R2 = 0.40 for the QTL and R2 = 0.48 for the GS model. Implementation of juvenile-to-adult phase transition is proposed for model improvement.

Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging.

BACKGROUND: Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events. METHODS AND RESULTS: There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45-71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria-referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria. CONCLUSIONS: Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.

Review and Analysis of Publication Trends over Three Decades in Three High Impact Medicine Journals.

CONTEXT: Over the past three decades, industry sponsored research expanded in the United States. Financial incentives can lead to potential conflicts of interest (COI) resulting in underreporting of negative study results. OBJECTIVE: We hypothesized that over the three decades, there would be an increase in: a) reporting of conflict of interest and source of funding; b) percentage of randomized control trials c) number of patients per study and d) industry funding. DATA SOURCES AND STUDY SELECTION: Original articles published in three calendar years (1988, 1998, and 2008) in The Lancet, New England Journal of Medicine and Journal of American Medical Association were collected. DATA EXTRACTION: Studies were reviewed and investigational design categorized as prospective and retrospective clinical trials. Prospective trials were categorized into randomized or non-randomized and single-center or multi-center trials. Retrospective trials were categorized as registries, meta-analyses and other studies, mostly comprising of case reports or series. Study outcomes were categorized as positive or negative depending on whether the pre-specified hypothesis was met. Financial disclosures were researched for financial relationships and profit status, and accordingly categorized as government, non-profit or industry sponsored. Studies were assessed for reporting COI. RESULTS: 1,671 original articles were included in this analysis. Total number of published studies decreased by 17% from 1988 to 2008. Over 20 year period, the proportion of prospective randomized trials increased from 22 to 46% (p < 0.0001); whereas the proportion of prospective non-randomized trials decreased from 59% to 27% (p < 0.001). There was an increase in the percentage of prospective randomized multi-center trials from 11% to 41% (p < 0.001). Conversely, there was a reduction in non-randomized single-center trials from 47% to 10% (p < 0.001). Proportion of government funded studies remained constant, whereas industry funded studies more than doubled (17% to 40%; p < 0.0001). The number of studies with negative results more than doubled (10% to 22%; p<0.0001). While lack of funding disclosure decreased from 35% to 7%, COI reporting increased from 2% to 84% (p < 0.0001). CONCLUSION: Improved reporting of COI, clarity in financial sponsorship, increased publication of negative results in the setting of larger and better designed clinical trials represents a positive step forward in the scientific publications, despite the higher percentage of industry funded studies.

Quantitative trait loci controlling leaf appearance and curd initiation of cauliflower in relation to temperature.

KEY MESSAGE: QTL regions on chromosomes C06 and C09 are involved in temperature dependent time to curd induction in cauliflower. Temperature is the main environmental factor influencing curding time of cauliflower (Brassica oleracea var. botrytis). Temperatures above 20-22 °C inhibit development towards curding even in many summer cultivars. To identify quantitative trait loci (QTL) controlling curding time and its related traits in a wide range of different temperature regimes from 12 to 27 °C, a doubled haploid (DH) mapping population segregating for curding time was developed and days to curd initiation (DCI), leaf appearance rate (LAR), and final leaf number (FLN) were measured. The population was genotyped with 176 single nucleotide polymorphism (SNP) markers. Composite interval mapping (CIM) revealed repeatedly detected QTL for DCI on C06 and C09. The estimated additive effect increased at high temperatures. Significant QTL × environment interactions (Q × E) for FLN and DCI on C06 and C09 suggest that these hotspot regions have major influences on temperature mediated curd induction. 25 % of the DH lines did not induce curds at temperatures higher than 22 °C. Applying a binary model revealed a QTL with LOD >15 on C06. Nearly all lines carrying the allele of the reliable early maturing parental line (PL) on that locus induced curds at high temperatures while only half of the DH lines carrying the allele of the unreliable PL reached the generative phase during the experiment. Large variation in LAR was observed. QTL for LAR were detected repeatedly in several environments on C01, C04 and C06. Negative correlations between LAR and DCI and QTL co-localizations on C04 and C06 suggest that LAR has also effects on development towards curd induction.