Opinions on registering trial details: a survey of academic researchers

<p>Abstract</p> <p>Background</p> <p>The World Health Organization (WHO) has established a set of items related to study design and administrative information that should build the minimum set of data in a study register. A more comprehensive data set for registration is currently developed by the Ottawa Group. Since nothing is known about the attitudes of academic researchers towards prospective study registration, we surveyed academic researchers about their opinion regarding the registration of study details proposed by the WHO and the Ottawa Group.</p> <p>Methods</p> <p>This was a web-based survey of academic researchers currently running an investigator-initiated clinical study which is registered with clinicaltrials.gov. In July 2006 we contacted 1299 principal investigators of clinical studies by e-mail explaining the purpose of the survey and a link to access a 52-item questionnaire based on the proposed minimum data set by the Ottawa Group. Two reminder e-mails were sent each two weeks apart. Association between willingness to disclose study details and study phase was assessed using the chi-squared test for trend. To explore the potential influence of non-response bias we used logistic regression to assess associations between factors associated with non-response and the willingness to register study details.</p> <p>Results</p> <p>Overall response was low as only 282/1299 (22%) principal investigators participated in the survey. Disclosing study documents, in particular the study protocol and financial agreements, was found to be most problematic with only 31% of respondents willing to disclose these publicly. Consequently, only 34/282 (12%) agreed to disclose all details proposed by the Ottawa Group. Logistic regression indicated no association between characteristics of non-responders and willingness to disclose details.</p> <p>Conclusion</p> <p>Principal investigators of non-industry sponsored studies are reluctant to disclose all data items proposed by the Ottawa Group. Disclosing the study protocol and financial agreements was found to be most problematic. Future discussions on trial registration should not only focus on industry but also on academic researchers.</p

An analytical solution for the settlement of stone columns beneath rigid footings

This paper presents a new approximate solution to study the settlement of rigid footings resting on a soft soil improved with groups of stone columns. The solution development is fully analytical, but finite element analyses are used to verify the validity of some assumptions, such as a simplified geometric model, load distribution with depth and boundary conditions. Groups of stone columns are converted to equivalent single columns with the same cross-sectional area. So, the problem becomes axially symmetric. Soft soil is assumed as linear elastic but plastic strains are considered in the column using the Mohr-Coulomb yield criterion and a non-associated flow rule, with a constant dilatancy angle. Soil profile is divided into independent horizontal slices and equilibrium of stresses and compatibility of deformations are imposed in the vertical and horizontal directions. The solution is presented in a closed form and may be easily implemented in a spreadsheet. Comparisons of the proposed solution with numerical analyses show a good agreement for the whole range of common values, which confirms the validity of the solution and its hypotheses. The solution also compares well with a small scale laboratory test available in literature

The association between leukocytes and sperm quality is concentration dependent

<p>Abstract</p> <p>Background</p> <p>To evaluate the association between leukocytes (polymorphonuclear granulocytes -PMNL) and semen parameters at different leukocyte concentrations.</p> <p>Methods</p> <p>This was a retrospective clinical study at a university hospital andrology clinic. Semen samples from infertile men were analyzed for sperm morphology and motility according to seminal leukocytes (PMNL) concentration (category A: >0 to <0.25 × 10(6)/mL; category B: >0.25 to <0.5 × 10(6)/mL; category C: >0.5 to <0.75 × 10(6)/mL; category D: >0.75 to <1.0 × 10(6)/mL, category E: >1 × 10(6)/mL).</p> <p>Results</p> <p>The percentage of sperm with normal morphology increased significantly from category A (14%) to category D (19%) but decreased in category E to levels (14%) similar to those in category A. Motility grades a and a+b (combined) also increased from category A (12%, 20%) to category D (18.0%, 28.5%) and decreased in category E (11%, 20.5%) to levels similar to those in category A. Sperm deformities and motility grades c and d increased progressively in all categories.</p> <p>Summary</p> <p>Leukocytes had a positive association with normal morphology and progressive motility in semen samples at a concentration of 0-1 × 10(6)/mL. The findings suggest that the association between leukocytes (PMNL) and semen quality might be concentration dependent.</p

Infrastructures of empire: towards a critical geopolitics of media and information studies

The Arab Uprisings of 2011 can be seen as a turning point for media and information studies scholars, many of whom newly discovered the region as a site for theories of digital media and social transformation. This work has argued that digital media technologies fuel or transform political change through new networked publics, new forms of connective action cultivating liberal democratic values. These works have, surprisingly, little to say about the United States and other Western colonial powers’ legacy of occupation, ongoing violence and strategic interests in the region. It is as if the Arab Spring was a vindication for the universal appeal of Western liberal democracy delivered through the gift of the Internet, social media as manifestation of the ‘technologies of freedom’ long promised by Cold War. We propose an alternate trajectory in terms of reorienting discussions of media and information infrastructures as embedded within the resurgence of idealized liberal democratic norms in the wake of the end of the Cold War. We look at the demise of the media and empire debates and ‘the rise of the BRICS’ (Brazil, Russia, India, China, South Africa) as modes of intra-imperial competition that complicate earlier Eurocentric narratives media and empire. We then outline the individual contributions for the special collection of essays

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans

Hypoxia has been associated with poor local tumour control and relapse in many cancer sites, including carcinoma of the prostate. This translational study tests whether breathing carbogen gas improves the oxygenation of human prostate carcinoma xenografts in mice and in human patients with prostate cancer. A total of 23 DU145 tumour-bearing mice, 17 PC3 tumour-bearing mice and 17 human patients with prostate cancer were investigated. Intrinsic susceptibility-weighted MRI was performed before and during a period of carbogen gas breathing. Quantitative R2* pixel maps were produced for each tumour and at each time point and changes in R2* induced by carbogen were determined. There was a mean reduction in R2* of 6.4% (P=0.003) for DU145 xenografts and 5.8% (P=0.007) for PC3 xenografts. In all, 14 human subjects were evaluable; 64% had reductions in tumour R2* during carbogen inhalation with a mean reduction of 21.6% (P=0.0005). Decreases in prostate tumour R2* in both animal models and human patients as a result of carbogen inhalation suggests the presence of significant hypoxia. The finding that carbogen gas breathing improves prostate tumour oxygenation provides a rationale for testing the radiosensitising effects of combining carbogen gas breathing with radiotherapy in prostate cancer patients

Common Variants in a Novel Gene, FONG on Chromosome 2q33.1 Confer Risk of Osteoporosis in Japanese

Osteoporosis is a common disease characterized by low bone mass, decreased bone quality and increased predisposition to fracture. Genetic factors have been implicated in its etiology; however, the specific genes related to susceptibility to osteoporosis are not entirely known. To detect susceptibility genes for osteoporosis, we conducted a genome-wide association study in Japanese using ∼270,000 SNPs in 1,747 subjects (190 cases and 1,557 controls) followed by multiple levels of replication of the association using a total of ∼5,000 subjects (2,092 cases and 3,114 controls). Through these staged association studies followed by resequencing and linkage disequilibrium mapping, we identified a single nucleotide polymorphism (SNP), rs7605378 associated with osteoporosis. (combined P = 1.51×10−8, odds ratio = 1.25). This SNP is in a previously unknown gene on chromosome 2q33.1, FONG. FONG is predicted to encode a 147 amino-acid protein with a formiminotransferase domain in its N-terminal (FTCD_N domain) and is ubiquitously expressed in various tissues including bone. Our findings would give a new insight into osteoporosis etiology and pathogenesis

Effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine on appetite, food intake and emotional processing in healthy volunteers

RATIONALE: The treatment of obesity is an increasing global health priority, yet few effective drug treatments are currently available. The discovery of novel anti-obesity therapies could be assisted by the validation of experimental (translational) medicine models in healthy volunteers that assess efficacy and safety at an early stage of drug development. OBJECTIVES: The aim of this study was to examine the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) in an experimental medicine model assessing both appetite and mood. METHODS: Using a between-subjects, double-blind, placebo-controlled design, 24 male and 24 female participants were randomly assigned to either placebo, 15- or 30-mg mCPP treatment groups. Lunch was eaten from a Universal Eating Monitor (UEM) that measured eating rate, and the participants completed the P1vital® Oxford Emotional Test Battery (ETB) and a series of appetite and mood ratings. RESULTS: mCPP reduced appetite and, in women, enhanced measures of satiation. The drug also enhanced memory for emotional material in the word recall and recognition memory tasks of the ETB. CONCLUSIONS: The results provide new insight into the effects of mCPP on appetite, satiety and memory in humans. In addition, our data provide an illustration of the value of measuring changes in appetite and mood in healthy volunteers to determine the potential efficacy and safety of novel anti-obesity drugs