Publications

The role of outdoor and indoor air quality in the spread of SARS-CoV-2: Overview and recommendations by the research group on COVID-19 and particulate matter (RESCOP commission)

Appraisal of umbrella reviews on vaccines

Umbrella reviews are systematic reviews of all systematic reviews on a given question and can provide a higher-level view of current available evidence on broad research topics. Given the importance and possible consequences of the insights derived from umbrella reviews, it is fundamental to ensure accurate, comprehensive reporting and methodological rigor in these papers. Here, we present the potential and limitations of these evolving evidence synthesis tools by looking at umbrella reviews published on vaccine research. Vaccines are essential tools in modern medicine for preventing disease and promoting public health. The scientific literature on vaccines grows rapidly as researchers work to improve existing vaccines and develop new ones. More than half a million scientific papers on vaccines have already been published, including several thousands of systematic reviews that aim to appraise and summarize this growing literature. However, as the published systematic reviews are only able to cover a small proportion of the literature it is important to also provide higher-level evidence syntheses. and discuss further improvements that could be made to integrate evidence on vaccines.

Implementing IPsec

The IP security protocols are sufficiently mature to benefit from multiple independent implementations and worldwide deployment. Towards that goal, we implemented the protocols for the BSD/OS, Linux, OpenBSD and NetBSD. While some differences in the implementations exist due to the differences in the underlying operating system structures, the design philosophy is common. A radix tree, namely the one used by the BSD code for routing purposes, is used to implement the policy engine; a transform table switch is used to make addition of security transformations an easy process; a lightweight kernel-user communication mechanism is used to pass key material and other configuration information from user space to kernel space, and to report asynchronous events such as requests for new keys from the kernel space to a user-level keying daemon; and two distinct ways of intercepting outgoing packets and applying the IPsec transformations to them are employed. The techniques used in our implementations are explained, differences in approaches are analysed, and hints are given to potential future implementers of new transforms.

JAMA

Confidence and precision increase with high statistical power

When null hypothesis significance testing is unsuitable for research: a reassessment

Abstract Null hypothesis significance testing (NHST) has several shortcomings that are likely contributing factors behind the widely debated replication crisis of psychology, cognitive neuroscience and biomedical science in general. We review these shortcomings and suggest that, after about 60 years of negative experience, NHST should no longer be the default, dominant statistical practice of all biomedical and psychological research. Different inferential methods (NHST, likelihood estimation, Bayesian methods, false-discovery rate control) may be most suitable for different types of research questions. Whenever researchers use NHST they should justify its use, and publish pre-study power calculations and effect sizes, including negative findings. Studies should optimally be pre-registered and raw data published. The current statistics lite educational approach for students that has sustained the widespread, spurious use of NHST should be phased out. Instead, we should encourage either more in-depth statistical training of more researchers and/or more widespread involvement of professional statisticians in all research.

JAMA

JAMA

Cortical representation of olfactory bulb input revealed by retrograde mono-transsynaptic labeling

No abstract is provided for this article.

Source Missing From Infographic

Kaiser Family Foundation; Adam Wexler, MPP; Alison Valentine; Jennifer Kates, PhD; Anne Jankiewicz; David Rousseau, MPH

Reconfigurable Future

Predicting the future is notoriously hard. Sometimes I feel that the only real guarantee is that the future will happen, and that someone will point out how it’s not like what was predicted. Nevertheless, we seem intent on trying to figure out what will happen, and worse yet, recording these views so they can be later used against us. So here I go... Scaling has been driving the whole electronics industry, allowing it to produce chips with more transistors at a lower cost. But this trend is a double-edged sword: We not only need to figure out more complex devices, which people want, but we also must determine which complex devices lots of people want, as we have to sell many, many chips to amortize the significant design cost.

Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study

Although limited in quantity, existing randomised trial evidence on exercise interventions suggests that exercise and many drug interventions are often potentially similar in terms of their mortality benefits in the secondary prevention of coronary heart disease, rehabilitation after stroke, treatment of heart failure, and prevention of diabetes.

Selective discussion and transparency in microarray research findings for cancer outcomes

Guidance to best tools and practices for systematic reviews

Abstract Data continue to accumulate indicating that many systematic reviews are methodologically flawed, biased, redundant, or uninformative. Some improvements have occurred in recent years based on empirical methods research and standardization of appraisal tools; however, many authors do not routinely or consistently apply these updated methods. In addition, guideline developers, peer reviewers, and journal editors often disregard current methodological standards. Although extensively acknowledged and explored in the methodological literature, most clinicians seem unaware of these issues and may automatically accept evidence syntheses (and clinical practice guidelines based on their conclusions) as trustworthy. A plethora of methods and tools are recommended for the development and evaluation of evidence syntheses. It is important to understand what these are intended to do (and cannot do) and how they can be utilized. Our objective is to distill this sprawling information into a format that is understandable and readily accessible to authors, peer reviewers, and editors. In doing so, we aim to promote appreciation and understanding of the demanding science of evidence synthesis among stakeholders. We focus on well‐documented deficiencies in key components of evidence syntheses to elucidate the rationale for current standards. The constructs underlying the tools developed to assess reporting, risk of bias, and methodological quality of evidence syntheses are distinguished from those involved in determining overall certainty of a body of evidence. Another important distinction is made between those tools used by authors to develop their syntheses as opposed to those used to ultimately judge their work. Exemplar methods and research practices are described, complemented by novel pragmatic strategies to improve evidence syntheses. The latter include preferred terminology and a scheme to characterize types of research evidence. We organize best practice resources in a Concise Guide that can be widely adopted and adapted for routine implementation by authors and journals. Appropriate, informed use of these is encouraged, but we caution against their superficial application and emphasize their endorsement does not substitute for in‐depth methodological training. By highlighting best practices with their rationale, we hope this guidance will inspire further evolution of methods and tools that can advance the field.

An empirical assessment of transparency and reproducibility-related research practices in the social sciences (2014-2017)

Serious concerns about research quality have catalyzed a number of reform initiatives intended to improve transparency and reproducibility and thus facilitate self-correction, increase efficiency, and enhance research credibility. Meta-research has evaluated the merits of some individual initiatives; however, this may not capture broader trends reflecting the cumulative contribution of these efforts. In this study, we manually examined a random sample of 250 articles in order to estimate the prevalence of a range of transparency and reproducibility-related indicators in the social sciences literature published between 2014-2017. Few articles indicated availability of materials (16/151, 11% [95% confidence interval, 7% to 16%]), protocols (0/156, 0% [0% to 1%]), raw data (11/156, 7% [2% to 13%]), or analysis scripts (2/156, 1% [0% to 3%]), and no studies were pre-registered (0/156, 0% [0% to 1%]). Some articles explicitly disclosed funding sources (or lack of; 74/236, 31% [25% to 37%]) and some declared no conflicts of interest (36/236, 15% [11% to 20%]). Replication studies were rare (2/156, 1% [0% to 3%]). Few studies were included in evidence synthesis via systematic review (17/151, 11% [7% to 16%]) or meta-analysis (2/151, 1% [0% to 3%]). Less than half the articles were publicly available (101/250, 40% [34% to 47%]). Minimal adoption of transparency and reproducibility-related research practices could be undermining the credibility and efficiency of social science research. The present study establishes a baseline that can be revisited in the future to assess progress.

Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration

The rapid and continuing progress in gene discovery for complex diseases is fueling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by previous reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.

Cache performance of operating system and multiprogramming workloads

Large caches are necessary in current high-performance computer systems to provide the required high memory bandwidth. Because a small decrease in cache performance can result in significant system performance degradation, accurately characterizing the performance of large caches is important. Although measurements on actual systems have shown that operating systems and multiprogramming can affect cache performance, previous studies have not focused on these effects. We have developed a program tracing technique called ATUM (Address Tracing Using Microcode) that captures realistic traces of multitasking workloads including the operating system. Examining cache behavior using these traces from a VAX processor shows that both the operating system and multiprogramming activity significantly degrade cache performance, with an even greater proportional impact on large caches. From a careful analysis of the causes of this degradation, we explore various techniques to reduce this loss. While seemingly little can be done to mitigate the effect of system references, multitasking cache miss activity can be substantially reduced with small hardware additions.

How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 RCTs assessing exercise and medication effects on systolic blood pressure

Objective To compare the effect of exercise regimens and medications on systolic blood pressure (SBP). Data sources Medline (via PubMed) and the Cochrane Library. Eligibility criteria Randomised controlled trials (RCTs) of angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-2 receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs) and diuretics were identified from existing Cochrane reviews. A previously published meta-analysis of exercise interventions was updated to identify recent RCTs that tested the SBP-lowering effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions (up to September 2018). Design Random-effects network meta-analysis. Outcome Difference in mean change from baseline SBP between comparator treatments (change from baseline in one group minus that in the other group) and its 95% credible interval (95% CrI), measured in mmHg. Results We included a total of 391 RCTs, 197 of which evaluated exercise interventions (10 461 participants) and 194 evaluated antihypertensive medications (29 281 participants). No RCTs compared directly exercise against medications. While all medication trials included hypertensive populations, only 56 exercise trials included hypertensive participants (≥140 mmHg), corresponding to 3508 individuals. In a 10% random sample, risk of bias was higher in exercise RCTs, primarily due to lack of blinding and incomplete outcome data. In analyses that combined all populations, antihypertensive medications achieved higher reductions in baseline SBP compared with exercise interventions (mean difference −3.96 mmHg, 95% CrI −5.02 to −2.91). Compared with control, all types of exercise (including combination of endurance and resistance) and all classes of antihypertensive medications were effective in lowering baseline SBP. Among hypertensive populations, there were no detectable differences in the SBP-lowering effects of ACE-I, ARB, β-blocker and diuretic medications when compared with endurance or dynamic resistance exercise. There was no detectable inconsistency between direct and indirect comparisons. Although there was evidence of small-study effects, this affected both medication and exercise trials. Conclusions The effect of exercise interventions on SBP remains under-studied, especially among hypertensive populations. Our findings confirm modest but consistent reductions in SBP in many studied exercise interventions across all populations but individuals receiving medications generally achieved greater reductions than those following structured exercise regimens. Assuming equally reliable estimates, the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications. Generalisability of these findings to real-world clinical settings should be further evaluated.