Clear Statistical Evidence Research Articles

Strength of statistical evidence for the efficacy of cancer drugs: a Bayesian reanalysis of randomized trials supporting Food and Drug Administration approval

ObjectivesTo quantify the strength of statistical evidence of randomized controlled trials (RCTs) for novel cancer drugs approved by the Food and Drug Administration in the last 2 decades. Study Design and SettingWe used data on overall survival (OS), progression-free survival, and tumor response for novel cancer drugs approved for the first time by the Food and Drug Administration between January 2000 and December 2020. We assessed strength of statistical evidence by calculating Bayes factors (BFs) for all available endpoints, and we pooled evidence using Bayesian fixed-effect meta-analysis for indications approved based on 2 RCTs. Strength of statistical evidence was compared among endpoints, approval pathways, lines of treatment, and types of cancer. ResultsWe analysed the available data from 82 RCTs corresponding to 68 indications supported by a single RCT and 7 indications supported by 2 RCTs. Median strength of statistical evidence was ambiguous for OS (BF = 1.9; interquartile range [IQR] 0.5–14.5), and strong for progression-free survival (BF = 24,767.8; IQR 109.0–7.3 × 106) and tumor response (BF = 113.9; IQR 3.0–547,100). Overall, 44 indications (58.7%) were approved without clear statistical evidence for OS improvements and 7 indications (9.3%) were approved without statistical evidence for improvements on any endpoint. Strength of statistical evidence was lower for accelerated approval compared to nonaccelerated approval across all 3 endpoints. No meaningful differences were observed for line of treatment and cancer type. This analysis is limited to statistical evidence. We did not consider nonstatistical factors (eg, risk of bias, quality of the evidence). ConclusionBFs offer novel insights into the strength of statistical evidence underlying cancer drug approvals. Most novel cancer drugs lack strong statistical evidence that they improve OS, and a few lack statistical evidence for efficacy altogether. These cases require a transparent and clear explanation. When evidence is ambiguous, additional postmarketing trials could reduce uncertainty.

Conditional versus non-conditional incentives to maximise return of participant completed questionnaires in clinical trials: a cluster randomised study within a trial

BackgroundHigh participant retention enhances the validity of clinical trials. A monetary incentive can increase retention, but it is not known if when it is provided and if it is conditional matters. We aimed to determine whether there was a difference in the number of follow-up trial questionnaires returned when a monetary (gift voucher) incentive was given to participants at recruitment (non-conditional), compared to informing participants at recruitment that the incentive would be given only once their 14-day daily diary (questionnaire) had been returned (conditional).MethodA cluster randomised study within a trial embedded within the Antivirals for influenza-Like Illness, An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) Trial. Matched site pairs (GP practices) were randomised using computer-generated random numbers, to either a non-conditional or conditional monetary voucher incentive (only once their 14-day daily diary (questionnaire) had been returned. Sites were matched on previous recruitment levels and practice list size. Analyses were conducted according to randomised groups irrespective of compliance with a two-sided 5% level statistical significance level. The main analysis of the primary outcome (site proportion of diaries returned) was linear regression accounting for site pair (using cluster-robust variance). Additional weighted, paired and non-parametric sensitivity analyses were conducted. Secondary outcomes were the site average number of completed pages, time to return diary, and cost related to the incentive (administration and postage).ResultsOf the 42 randomised sites (21 for each intervention), only 28 recruited at least one participant with only 10 practice pairs recruiting participants at both constituent sites. Raw diaries return proportions were 0.58 (127/220) and 0.73 (91/125) for non-conditional and conditional incentive groups. Regression analysis adjusted for site pair showed no significant difference in returns, − 0.09, (95% CI, − 0.29, 0.10, p = 0.34); when weighted, there was still no clear difference: 0.15 (95% CI, − 0.02, 0.31, p = 0.07). There was no clear statistical evidence of a difference in time taken to return questionnaires, nor the proportion of pages completed, by the intervention group in the main analyses (all p > 0.05). The conditional incentive was approximately £23 cheaper per diary returned based upon observed data.ConclusionThere was no clear evidence of a statistically significant difference in the proportion of participant-completed diaries returned between conditional or non-conditional incentive groups. The time to questionnaire return and completeness of the returned questionnaires were similar in both groups. There was substantial statistical uncertainty in the findings. Some of the sensitivity analyses suggested that a meaningful benefit of a conditional incentive of a magnitude that would be meaningful was plausible. The conditional approach costs less in cash terms.

Aortic dissection induced by vascular endothelial growth factor inhibitors.

Vascular endothelial growth factor (VEGF) contributes to angiogenesis and vasculogenesis. The occurrence and progression of tumors are accompanied by angiogenesis. Vascular endothelial growth factor inhibitors (VEGFI) have been used in anti-tumor treatment. However, aortic dissection (AD) is one of the VEGFI-associated adverse reactions with cute onset, rapid progression, and high case fatality rate. We collected case reports of VEGFI related to aortic dissection in PubMed and CNKI (China National Knowledge Infrastructure) from inception to 28 April 2022. Seventeen case reports were selected. The medication included sunitinib, sorafenib, pazopanib, axitinib, apatinib, anlotinib, bevacizumab, and ramucirumab. This review discusses the pathology, risk factors, diagnosis, and treatment of AD. Vascular endothelial growth factor inhibitors are related to aortic dissection. Although current literature lacks clear statistical evidence on the population, we offer points to encourage further confirmation of the best methods of care for these patients.

Making Industrialization in Africa Sustainable

As my own country, China has shown, strong growth in the manufacturing industry is a key driver of sustainable development. It has a significant impact on economic and social well-being, as a recent report by the United Nations Industrial Development Organization (UNIDO) demonstrates. The report looks at data across all countries and plots manufacturing value-added per capita, along with competitiveness, against indicators on poverty, inequality, health, education, employment, and human development. The results provide clear statistical evidence on how closely the process of industrialization is connected to improvements in people’s living conditions and their quality of life.

Complementary Experimental Methods in Genetics Open Up New Avenues of Research to Elucidate the Pathogenesis of Periodontitis.

A complex disease such as periodontitis is the sum of environmental and genetic effects. The personal genetic constitution interacts with the effects of internal and external risk factors like smoking, oral hygiene, malnutrition, emotional stress, and age. Accordingly, individuals who live in the same environmental context and share comparable lifestyle habits have different disease risks. Genetic research offers the identification of DNA sequence variants that have a causal role in disease etiology and allows the identification of disease relevant immune and metabolic pathways that contribute to disease susceptibility and pathogenesis in specific situations. Real advances have been made in genetic medical research in the last years. Starting from candidate gene association studies, new approaches were employed that have expanded the study design of genomewide association studies to genomewide meta-analyses and gene x environment interaction studies. Cost efficient whole-exome and whole-genome sequencing of patients with rare severe forms of periodontitis has the potential to identify genes and pathways with a direct role in the pathogenesis of common forms. In parallel, animal models were developed that use genetically highly diverse mouse lines to identify risk genes of human diseases. This chapter presents the main studies and the identified susceptibility genes that have clear statistical evidence. In addition, it describes pioneering studies that used advanced methods in experimental dental research, opening up new avenues of research. Although the knowledge of the genetic architecture of periodontitis is still in its infancy, genetic research is building the basis for future works with the potential to advance dental medicine in ways that will determine the various causes of periodontal diseases. This knowledge may eventually allow making predictions about disease risk for individual patients and leading to diagnosis and treatments that do not treat the symptoms but heal the disease.

Solder Joint Reliability Risk Estimation by AI-Assisted Simulation Framework with Genetic Algorithm to Optimize the Initial Parameters for AI Models

Solder joint fatigue is one of the critical failure modes in ball-grid array packaging. Because the reliability test is time-consuming and geometrical/material nonlinearities are required for the physics-driven model, the AI-assisted simulation framework is developed to establish the risk estimation capability against the design and process parameters. Due to the time-dependent and nonlinear characteristics of the solder joint fatigue failure, this research follows the AI-assisted simulation framework and builds the non-sequential artificial neural network (ANN) and sequential recurrent neural network (RNN) architectures. Both are investigated to understand their capability of abstracting the time-dependent solder joint fatigue knowledge from the dataset. Moreover, this research applies the genetic algorithm (GA) optimization to decrease the influence of the initial guessings, including the weightings and bias of the neural network architectures. In this research, two GA optimizers are developed, including the “back-to-original” and “progressing” ones. Moreover, we apply the principal component analysis (PCA) to the GA optimization results to obtain the PCA gene. The prediction error of all neural network models is within 0.15% under GA optimized PCA gene. There is no clear statistical evidence that RNN is better than ANN in the wafer level chip-scaled packaging (WLCSP) solder joint reliability risk estimation when the GA optimizer is applied to minimize the impact of the initial AI model. Hence, a stable optimization with a broad design domain can be realized by an ANN model with a faster training speed than RNN, even though solder fatigue is a time-dependent mechanical behavior.

High Net Worth Individual Investors: The Influencing Power and Position in Equity Markets

As the High Net worth (HNI) Investors mount in the financial markets with great financial power, their footprint is clearly directing the Retail Investors. During the last decade Indian HNI Investor’s exposure to the Mutual Funds and Primary Equity Market is not just substantial but also provides an early base to potential and stable capital Markets. Growth and sustainability of capital markets depend on wider participation of Retail Investors. The study concludes that Retail Investors are investing under the influence of HNI Investors Investments and the interaction of HNI and Institutional Investors is impacting them in a positive manner. There is a clear statistical evidence of HNI Investors influence on the investments of Retail Investors either in the primary market or the secondary market. Index Terms: HNI Investors, Proprietary Trading, Assets under Management, IPO Subscription

Responsible Leadership and Reputation Management During a Crisis: The Cases of Delta and United Airlines

This study argues that actions taken during a crisis within the responsibility compass impacts reputation. The lens of responsible leadership was chosen from among the different foci of leadership scholarship because of its emphasis on relational and ethical dimensions. The focus of this study was the actions undertaken by the CEOs of United and Delta Airlines after the forceful removal of the passengers and its influence on the reputation capital as measured by the changes in the respective share prices of the airlines. The overarching question was whether there was clear statistical evidence that linked the actions undertaken as part of the crisis management efforts and the reputation of the airlines. Findings from this study suggest that actions taken as part of responsible leadership compass explained the variations in the share prices. In the case of United Airlines almost 70% of the variations in the share prices could be explained by responsible leadership, whereas in the case Delta airlines only 50.6% of the variations in the share value could be predicted based on the role of leadership in crisis management.

Assessment of fatigue severity and neurocognitive functions in the real setting of Ramadan in patients with type 2 diabetes mellitus

ObjectivesType 2 diabetes mellitus (T2DM) is linked with a risk of dementia and decline in neurocognitive function. The current observational case-control study was conducted to evaluate the effect of fasting during Ramadan on cognitive functions and fatigue severity in T2DM patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB). MethodsThis research was conducted at King Saud University Medical city, on 82 subjects including 43 control and 39 T2DM patients of both genders. The standardized Fatigue Severity Scale (FSS) and tests from CANTAB, including the Motor Screening Task (MOT), Spatial Span (SSP) and Intra-Extra Dimensional Set Shift (IED) were recorded during 3rd week and 2–3 weeks after Ramadan under controlled environmental conditions. Neurocognitive functions were recorded through CANTAB. ResultsIED errors (24.43 vs 50.73, p = 0.007), MOT mean and median latency (1466.32 vs 1120.27, p = 0.002) were significantly higher in T2DM than controls. IED stages completed (7.43 vs 8.69, p = 0.003) and SSP Span length were significantly lower in T2DM than controls (4.13 vs 4.82, p = 0.059). The significant differences between T2DM patients and controls persisted in the post. T2DM patients made more errors and completed less IED stages than did the controls, indicating that a worsened flexibility of attention relative to controls. Moreover, T2DM patients exhibited longer latencies in MOT, indicating poor motor performance. A comparison of performances by T2DM patients on FSS and CANTAB during and after Ramadan showed that fasting substantially increased fatigue scales, motor performance, and working-memory capacity. ConclusionsPatients with T2DM have impaired cognitive functions including poor motor performance, low flexibility of attention, and poor working memory capacity compared to healthy control subjects during and also in post Ramadan period. However, there is no clear statistical evidence that the cognitive functions (except for SSP SL scores) and fatigue severity of T2DM subjects differ between Ramadan and after Ramadan in both T2DM and controls.

A Regulated Market Under Sanctions: On Tail Dependence Between Oil, Gold, and Tehran Stock Exchange Index

We demonstrate that the tail dependence should always be taken into account as a proxy for systematic risk of loss for investments. We provide the clear statistical evidence of that the structure of investment portfolios on a regulated market should be adjusted to the price of gold. Our finding suggests that the active bartering of oil for goods would prevent collapsing the national market facing international sanctions.

Smoking Cessation Pharmacotherapy Based on Genetically-Informed Biomarkers: What is the Evidence?

Pharmacogenomic studies have used genetic variants to identify smokers likely to respond to pharmacological treatments for smoking cessation. We performed a systematic review and meta-analysis of primary and secondary analyses of trials of smoking cessation pharmacotherapies. Eligible were trials with data on a priori selected single nucleotide polymorphisms, replicated non-single nucleotide polymorphisms, and/or the nicotine metabolite ratio. We estimated the genotype × treatment interaction as the ratio of risk ratios (RRR) for treatment effects across genotype groups. We identified 18 trials (N = 9017 participants), including 40 active (bupropion, nicotine replacement therapy [NRT], varenicline, or combination therapies) versus placebo comparisons and 16 active versus active comparisons. There was statistical evidence of heterogeneity across rs16969968 genotypes in CHRNA5 with regard to both 6-month abstinence and end-of-treatment abstinence in non-Hispanic black smokers and end-of-treatment abstinence in non-Hispanic white smokers. There was also heterogeneity across rs1051730 genotypes in CHRNA3 with regard to end-of-treatment abstinence in non-Hispanic white smokers. There was no clear statistical evidence for other genotype-by-treatment combinations. Compared with placebo, NRT was more effective among non-Hispanic black smokers with rs16969968-GG with regard to both 6-month abstinence (RRR for GG vs. GA or AA, 3.51; 95% confidence interval [CI] = 1.19 to 10.30) and end-of-treatment abstinence (RRR for GG vs. GA or AA, 5.84; 95% CI = 1.89 to 18.10). Among non-Hispanic white smokers, NRT effectiveness relative to placebo was comparable across rs1051730 and rs169969960 genotypes. We did not identify widespread differential effects of smoking cessation pharmacotherapies based on genotype. The quality of the evidence is generally moderate. Although we identified some evidence of genotype × treatment interactions, the vast majority of analyses did not provide evidence of differential treatment response by genotype. Where we find some evidence, these results should be considered preliminary and interpreted with caution because of the small number of contributing trials per genotype comparison, the wide confidence intervals, and the moderate quality of evidence. Prospective trials and individual-patient data meta-analyses accounting for heterogeneity of treatment effects through modeling are needed to assess the clinical utility of genetically informed biomarkers to guide pharmacotherapy choice for smoking cessation.

Observed Propagation Route of VLF Transmitter Signals in the Magnetosphere

AbstractSignals of powerful ground transmitters at various places have been detected by satellites in near‐Earth space. The study on propagation mode, ducted or nonducted, has attracted much attentions for several decades. Based on the statistical results from Van Allen Probes (data from October 2012 to March 2017) and DEMETER satellite (from January 2006 to December 2007), we present the ground transmitter signals distributed clearly in ionosphere and magnetosphere. The observed propagation route in the meridian plane in the magnetosphere for each of various transmitters from the combination of DEMETER and Van Allen Probes data in nighttime is revealed for the first time. We use realistic ray tracing simulation and compare simulation results against Van Allen Probes and DEMETER observation. By comparison we demonstrate that the observed propagation route, with partial deviation from the field lines corresponding to ground stations, provides direct and clear statistical evidence that the nonducted propagation mode plays a main role, although with partial contribution from ducted propagation. The propagation characteristics of VLF transmitter signals in the magnetosphere are critical for quantitatively assessing their contribution to energetic electron loss in radiation belts.

Improvement of the Dengue Virus (DENV) Nonhuman Primate Model via a Reverse Translational Approach Based on Dengue Vaccine Clinical Efficacy Data against DENV-2 and -4.

ABSTRACTRecent data obtained with the live-attenuated tetravalent dengue CYD-TDV vaccine showed higher protective efficacy against dengue virus type 4 (DENV-4) than against DENV-2. In contrast, results from previous studies in nonhuman primates predicted comparable high levels of protection against each serotype. Maximum viral loads achieved in macaques by subcutaneous inoculation of DENV are generally much lower than those observed in naturally dengue virus-infected humans. This may contribute to an overestimation of vaccine efficacy. Using more-stringent DENV infection conditions consisting of the intravenous inoculation of 107 50% cell culture infectious doses (CCID50) in CYD-TDV-vaccinated macaques, complete protection (i.e., undetectable viral RNA) was achieved in all 6 monkeys challenged with DENV-4 and in 6/18 of those challenged with DENV-2, including transiently positive animals. All other infected macaques (12/18) developed sustained DENV-2 RNAemia (defined as detection of viral RNA in serum samples) although 1 to 3 log10 units below the levels achieved in control animals. Similar results were obtained with macaques immunized with either CYD-TDV or monovalent (MV) CYD-2. This suggests that partial protection against DENV-2 was mediated mainly by CYD-2 and not by the other CYDs. Postchallenge induction of strong anamnestic responses, suggesting efficient vaccine priming, likely contributed to the reduction of DENV-2 RNAemia. Finally, an inverse correlation between DENV RNA titers postchallenge and vaccine-induced homotypic neutralizing antibody titers prechallenge was found, emphasizing the key role of these antibodies in controlling DENV infection. Collectively, these data show better agreement with reported data on CYD-TDV clinical vaccine efficacy against DENV-2 and DENV-4. Despite inherent limitations of the nonhuman primate model, these results reinforce its value in assessing the efficacy of dengue vaccines.IMPORTANCE The nonhuman primate (NHP) model is the most widely recognized tool for assessing the protective activity of dengue vaccine candidates, based on the prevention of postinfection DENV viremia. However, its use has been questioned after the recent CYD vaccine phase III trials, in which moderate protective efficacy against DENV-2 was reported, despite full protection against DENV-2 viremia previously being demonstrated in CYD-vaccinated monkeys. Using a reverse translational approach, we show here that the NHP model can be improved to achieve DENV-2 protection levels that show better agreement with clinical efficacy. With this new model, we demonstrate that the injection of the CYD-2 component of the vaccine, in either a monovalent or a tetravalent formulation, is able to reduce DENV-2 viremia in all immunized animals, and we provide clear statistical evidence that DENV-2-neutralizing antibodies are able to reduce viremia in a dose-dependent manner.

Driving to safety: How many miles of driving would it take to demonstrate autonomous vehicle reliability?

How safe are autonomous vehicles? The answer is critical for determining how autonomous vehicles may shape motor vehicle safety and public health, and for developing sound policies to govern their deployment. One proposed way to assess safety is to test drive autonomous vehicles in real traffic, observe their performance, and make statistical comparisons to human driver performance. This approach is logical, but it is practical? In this paper, we calculate the number of miles of driving that would be needed to provide clear statistical evidence of autonomous vehicle safety. Given that current traffic fatalities and injuries are rare events compared to vehicle miles traveled, we show that fully autonomous vehicles would have to be driven hundreds of millions of miles and sometimes hundreds of billions of miles to demonstrate their reliability in terms of fatalities and injuries. Under even aggressive testing assumptions, existing fleets would take tens and sometimes hundreds of years to drive these miles—an impossible proposition if the aim is to demonstrate their performance prior to releasing them on the roads for consumer use. These findings demonstrate that developers of this technology and third-party testers cannot simply drive their way to safety. Instead, they will need to develop innovative methods of demonstrating safety and reliability. And yet, the possibility remains that it will not be possible to establish with certainty the safety of autonomous vehicles. Uncertainty will remain. Therefore, it is imperative that autonomous vehicle regulations are adaptive—designed from the outset to evolve with the technology so that society can better harness the benefits and manage the risks of these rapidly evolving and potentially transformative technologies.

Evidence for seasonal reproduction in UK domestic cats.

The aims of this study were to analyse a large body of data obtained by the Royal Society for the Prevention of Cruelty to Animals (RSPCA) Greater Manchester Animal Hospital on the breeding pattern of owned domestic cats in the UK, and to provide clear statistical evidence of whether seasonal variation remains present in temperate climates. The total number of cats spayed and the number of cats found to be pregnant were recorded on a monthly basis from December 2005 to July 2014 by the RSPCA Greater Manchester Animal Hospital. The percentage of cats found to be pregnant was calculated for each month and the 8.5 years of data were binned into calendar months. The mean and SD of the monthly pregnancy rate was calculated for each calendar month bin, as was the difference between the mean percentage of detected pregnancies and the global mean. The Z score for each month's difference was then calculated. Data were available for 5414 cats neutered during the 8.5 consecutive years of this study. A global average of 8.9% of cats spayed were found to be pregnant. The mean calendar month pregnancy rate exhibited a very significant variation, with the highest positive deviation being in April (Z score +2.9) and the highest negative deviation being in November/December (Z score -4.5). When aggregated into 3 month averages, an extremely significant difference between 'spring' and 'winter' months of >7 SE (P <<0.01) was found. This study provides clear statistical evidence, from a large data set, that seasonal breeding patterns are still present under UK temperate conditions. We discuss the impact that this has on charity rescue shelters and propose that a campaign targeted at clients of animal welfare charities encouraging autumn neutering will be the most cost-effective method of cat population control, and help relieve the demand on welfare charity resources.

The Effect of Environmental Activism on the Long-run Market Value of a Company: A Case Study

This paper investigates the impact of activism on a large, powerful corporation in Tasmania. Gunns Ltd was a large woodchip processor in Tasmania that fought a long-running battle with environmental activists regarding Gunns’ logging and processing activities. The study focuses on events in 2004–2005, when Gunns applied to build a pulp mill in rural northern Tasmania and began a legal case against activists. The research question is whether there is clear statistical evidence that these events were important, as is widely believed, in the ultimate failure of Gunns in (Annual Report 2011, Gunns Ltd, Tasmania, available from: http://www.asx.com.au [11/04/14]), just 6 years after being the largest and one of the most financially successful Tasmanian companies. We use a mixed methods approach that combines a detailed narrative informed by theory, to examine issues of corporate social responsibility (CSR) and ethical behaviour, with an econometric time series analysis of the impact of activism on the market value of Gunns. Our analysis supports the contention that the events in 2004–2005 played a significant part in the decline of the long-run market value of Gunns over the subsequent period, through to its failure in 2011. We discuss the underlying causes for Gunns’ failure in terms of agency, stakeholder, legitimacy and leadership theories. Research frequently assesses effects such as those in the Gunns’ case through solely qualitative means. This paper integrates a quantitative analysis into a detailed qualitative narrative and theoretical interpretation of events, to provide additional precision to its findings. It contributes to research in CSR and the impact of activism.

The association of rs1051730 genotype on adherence to and consumption of prescribed nicotine replacement therapy dose during a smoking cessation attempt

IntroductionWhile nicotine replacement therapy (NRT) is an effective pharmacological smoking cessation treatment, its efficacy is influenced by adherence to and consumption of the prescribed dose. The genetic variant rs1051730 in the nicotinic receptor gene cluster CHRNA5-A3-B4 influences smoking quantity. The aim of this study was to explore the impact of rs1051730 genotype on adherence to and consumption of NRT prescription following a smoking cessation attempt. MethodsSecondary analysis of data from a pharmacogenetic smoking cessation trial. Participants (n=448) were prescribed a daily dose of NRT for four weeks post quit attempt, and monitored during weekly clinic visits. Outcome measures were NRT prescription adherence rate (%) and average daily NRT consumption (mg) at 7- and 28-days after the quit attempt. ResultsAn association between rs1051730 genotype and both outcome measures was observed at 7-days after the quit date. Each copy of the minor allele corresponded to a 2.9% decrease in adherence to prescribed NRT dose (P=0.044), and a 1.0mg decrease in daily NRT consumption (P=0.026). Adjusting for number of cigarettes smoked during this period only slightly attenuated these associations. There was no clear statistical evidence of an association between genotype and adherence or consumption at 28-days. ConclusionsThis is the first study to evaluate the impact of rs1051730 genotype on consumption of and adherence to NRT prescription during a smoking cessation attempt. We observed an association between this variant and both outcome measures at 7-days; however, this was only moderate. These findings require replication in an independent sample.

Role of Crassicauda sp. in natural mortality of pantropical spotted dolphins Stenella attenuata: a reassessment

Evaluating the effect of parasites on population size is essential for designing management and conservation plans of wild animal populations. Although knowledge in this area is scarce in cetaceans, current evidence suggests that species of the nematode genus Crassicauda may play an important regulatory role in some populations. In the present study, a semiparametric regression technique was applied to a previously published dataset to re-examine the role of Crassicauda sp. in natural mortality of pantropical spotted dolphins Stenella attenuata. The resulting model indicated parasite-induced mortality at ages between 6.5 and 9 yr and at roughly 12 yr. The maximum mortality estimates obtained could represent 2 to 4% of natural mortality in dolphins 6 to 8 yr old. This estimate is substantially smaller than previously published values, but in contrast with previous research, our model provides clear statistical evidence for parasite-induced mortality because the bootstrapped 95% confidence intervals of the estimated mortality rates excluded the 0 value. We also evaluated, through simulations, how potential sampling biases of infected dolphins could overestimate parasite-induced mortality. Small differences in sampling selectivity between infected and uninfected animals could substantially reduce the mortality estimates. However, the simulated models also supported the notion of statistically significant mortality in juvenile dolphins. Given that dolphins older than 16 yr were poorly represented in the dataset, further research is needed to establish whether Crassicauda sp. causes meaningful mortality for population dynamics among adult individuals.

The GALEX Arecibo SDSS Survey – VIII. Final data release. The effect of group environment on the gas content of massive galaxies

We present the final data release from the GALEX Arecibo SDSS Survey (GASS), a large Arecibo program that measured the HI properties for an unbiased sample of ~800 galaxies with stellar masses greater than 10^10 Msun and redshifts 0.025<z<0.05. This release includes new Arecibo observations for 250 galaxies. We use the full GASS sample to investigate environmental effects on the cold gas content of massive galaxies at fixed stellar mass. The environment is characterized in terms of dark matter halo mass, obtained by cross-matching our sample with the SDSS group catalog of Yang et al. Our analysis provides, for the first time, clear statistical evidence that massive galaxies located in halos with masses of 10^13-10^14 Msun have at least 0.4 dex less HI than objects in lower density environments. The process responsible for the suppression of gas in group galaxies most likely drives the observed quenching of the star formation in these systems. Our findings strongly support the importance of the group environment for galaxy evolution, and have profound implications for semi-analytic models of galaxy formation, which currently do not allow for stripping of the cold interstellar medium in galaxy groups.

Results of Mannerfelt wrist arthrodesis for rheumatoid arthritis in relation to the position of the fused wrist

The wrist is involved early in rheumatoid arthritis and is often severely affected. A stable wrist is crucial to good hand function, which often necessitates a fusion. One of the most commonly used techniques in rheumatoid patients is the Mannerfelt arthrodesis. In this retrospective study the outcome and the patient's subjective satisfaction are presented and compared to other techniques. Also the influence of the position of the wrist following a fusion procedure is analysed. Thirty-four wrists were retrospectively analysed using radiological measurements, functional scores such as the Disabilities of the Arm, Shoulder and Hand (DASH) and a pain assessment. The objective function of the hand with the fused wrist was assessed. In 92.6% of wrists the patients rated their satisfaction as good or excellent. The mean DASH score post-operatively was 63.3. Of the wrists, 17 were fixed in a median flexed position of 13° and 17 wrists in a median extended position of 8°. There was no statistically significant correlation between the position of the wrist and the satisfaction or objective function. The rate of fusion was 94.1%. The Mannerfelt arthrodesis achieves good results and provides a high rate of satisfaction and pain relief in our study. It has major advantages compared to other wrist fusion techniques in the rheumatoid patient. We could not show clear statistical evidence for better results in either a flexed or an extended position, but the ratings of the patients indicated better subjective results with a slightly extended position of the arthrodesis.