The handling of missing data in molecular epidemiologic studies

Background: Molecular epidemiologic studies face a missing data problem as biospecimen data are often collected on only a proportion of subjects eligible for study. Methods: We investigated all molecular epidemiologic studies published in CEBP in 2009 to characterize the prevalence of missing data and to elucidate how the issue was addressed. We considered multiple imputation (MI), a missing data technique that is readily available and easy to implement, as a possible solution. Results: While the majority of studies had missing data, only 16% compared subjects with and without missing data. Furthermore, 95% of the studies with missing data performed a complete-case (CC) analysis, a method known to yield biased and inefficient estimates. Conclusions: Missing data methods are not customarily being incorporated into the analyses of molecular epidemiologic studies. Barriers may include a lack of awareness that missing data exists, particularly when availability of data is part of the inclusion criteria; the need for specialized software; and a perception that the CC approach is the gold standard. Standard MI is a reasonable solution that is valid when the data are missing at random (MAR). If the data are not missing at random (NMAR) we recommend MI over CC when strong auxiliary data are available. MI, with the missing data mechanism specified, is another alternative when the data are NMAR. In all cases, it is recommended to take advantage of MI’s ability to account for the uncertainty of these assumptions. Impact: Missing data methods are underutilized, which can deleteriously affect the interpretation of results

Comparative Analysis of Old-Age Mortality Estimations in Africa

Survival to old ages is increasing in many African countries. While demographic tools for estimating mortality up to age 60 have improved greatly, mortality patterns above age 60 rely on models based on little or no demographic data. These estimates are important for social planning and demographic projections. We provide direct estimations of older-age mortality using survey data.Since 2005, nationally representative household surveys in ten sub-Saharan countries record counts of living and recently deceased household members: Burkina Faso, Côte d'Ivoire, Ethiopia, Namibia, Nigeria, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. After accounting for age heaping using multiple imputation, we use this information to estimate probability of death in 5-year intervals ((5)q(x)). We then compare our (5)q(x) estimates to those provided by the World Health Organization (WHO) and the United Nations Population Division (UNPD) to estimate the differences in mortality estimates, especially among individuals older than 60 years old.We obtained information on 505,827 individuals (18.4% over age 60, 1.64% deceased). WHO and UNPD mortality models match our estimates closely up to age 60 (mean difference in probability of death -1.1%). However, mortality probabilities above age 60 are lower using our estimations than either WHO or UNPD. The mean difference between our sample and the WHO is 5.9% (95% CI 3.8-7.9%) and between our sample is UNPD is 13.5% (95% CI 11.6-15.5%). Regardless of the comparator, the difference in mortality estimations rises monotonically above age 60.Mortality estimations above age 60 in ten African countries exhibit large variations depending on the method of estimation. The observed patterns suggest the possibility that survival in some African countries among adults older than age 60 is better than previously thought. Improving the quality and coverage of vital information in developing countries will become increasingly important with future reductions in mortality

Could Nintendo’s Animal Crossing be a tool for conservation messaging?

1. The current extinction crisis demands worldwide commitment to conservation across all sectors of society. By transcending the traditional disciplinary boundaries, conservationists can reach new audiences to communicate pro-conservation knowledge, education, and awareness messages. 2. There are approximately 2.7 billion video-gamers worldwide, with millions more joining as a result of global lockdowns. In March 2020, Animal Crossing New Horizons was released by Nintendo, fast becoming the second-best selling video game ever in Japan, and selling over 26.4 million units worldwide. Unlike many popular video games, its unique premise involves players creating an island, growing vegetation, catching wildlife, and donating fossils and species to a museum. The game has been praised for its positivity, escapism, and measurable benefits to mental wellbeing. 3. Here, we articulate how different features of the game, including the islands, their biodiversity and inhabitants, encourage players to exhibit pro-conservation behaviours and attitudes (e.g. recycling litter, or planting a diversity of flowers), as well as improving players’ knowledge about the diversity of relatively little known taxa (marine and freshwater fishes and invertebrates). We also highlight where pitfalls exist (e.g. encouraging the collection of threatened species). We principally frame these discussions in the context of Japan's cultural relationship with the natural world, including its history of insect-collecting and its management of green spaces. We conclude by outlining some recommendations about potential improvements to future releases, or for similar games, that could further promote conservation messaging. 4. This perspective sheds light on the avenues through which Animal Crossing: New Horizons encourages pro-conservation knowledge, attitudes, and behaviours of its international audience, with potential for these experiences to translate into real-world conservation actions. During a critical time in humanity’s history, video-gaming could therefore provide a huge opportunity for communicating conservation messages to billions of people worldwide

The Handling of Missing Data in Molecular Epidemiology Studies

Molecular epidemiology studies face a missing data problem, as biospecimen or imaging data are often collected on only a proportion of subjects eligible for study. We investigated all molecular epidemiology studies published as Research Articles, Short Communications, or Null Results in Brief in Cancer Epidemiology, Biomarkers & Prevention from January 1, 2009, to March 31, 2010, to characterize the extent that missing data were present and to elucidate how the issue was addressed. Of 278 molecular epidemiology studies assessed, most (95%) had missing data on a key variable (66%) and/or used availability of data (often, but not always the biomarker data) as inclusion criterion for study entry (45%). Despite this, only 10% compared subjects included in the analysis with those excluded from the analysis and 88% with missing data conducted a complete-case analysis, a method known to yield biased and inefficient estimates when the data are not missing completely at random. Our findings provide evidence that missing data methods are underutilized in molecular epidemiology studies, which may deleteriously affect the interpretation of results. We provide practical guidelines for the analysis and interpretation of molecular epidemiology studies with missing data

Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome

There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV‐6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV‐6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double‐blind, placebo‐controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI‐20) and Fatigue Severity Scale (FSS) scores, self‐reported cognitive function, and physician‐determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI‐20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI‐20 mental fatigue subscore ( P  = 0.039), FSS score ( P  = 0.006), and cognitive function ( P  = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders ( P  = 0.029). In the VGCV arm, monocyte counts decreased ( P  < 0.001), neutrophil counts increased ( P  = 0.037) and cytokines were more likely to evolve towards a Th1‐profile ( P  < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100139/1/jmv23713.pd

Self-perceived physical health predicts cardiovascular disease incidence and death among postmenopausal women

BACKGROUND: Physical and Mental Component Summary (PCS, MCS, respectively) scales of SF- 36 health-related-quality-of-life have been associated with all-cause and cardiovascular disease (CVD) mortality. Their relationships with CVD incidence are unclear. This study purpose was to test whether PCS and/or MCS were associated with CVD incidence and death. METHODS: Postmenopausal women (aged 50–79 years) in control groups of the Women’s Health Initiative clinical trials (n = 20,308) completed the SF-36 and standardized questionnaires at trial entry. Health outcomes, assessed semi-annually, were verified with medical records. Cox regressions assessed time to selected outcomes during the trial phase (1993–2005). RESULTS: A total of 1075 incident CVD events, 204 CVD-specific deaths, and 1043 total deaths occurred during the trial phase. Women with low versus high baseline PCS scores had less favorable health profiles at baseline. In multivariable models adjusting for baseline confounders, participants in the lowest PCS quintile (reference = highest quintile) exhibited 1.8 (95%CI: 1.4, 2.3), 4.7 (95%CI: 2.3, 9.4), and 2.1 (95%CI: 1.7, 2.7) times greater risk of CVD incidence, CVD-specific death, and total mortality, respectively, by trial end; whereas, MCS was not significantly associated with CVD incidence or death. CONCLUSION: Physical health, assessed by self-report of physical functioning, is a strong predictor of CVD incidence and death in postmenopausal women; similar self-assessment of mental health is not. PCS should be evaluated as a screening tool to identify older women at high risk for CVD development and death

Corrigendum to “Oxidative Stress Alters the Profile of Transcription Factors Related to Early Development on In Vitro

High oxygen levels during in vitro culture (IVC) can induce oxidative stress through accumulation of reactive oxygen species (ROS), negatively affecting embryo development. This study evaluated the effect of different O2 tensions during IVC on bovine blastocyst development and transcriptional status, considering transcription factors that play an essential role during early embryo development. For this purpose, embryos were produced in vitro by conventional protocols and cultured in two different oxygen tensions, physiological (5%) and atmospheric (20%). Expanded blastocysts were subjected to transcript quantitation analysis by RT-qPCR with Biomark™ HD System (Fluidigm, US), using 67 TaqMan assays specific for Bos taurus. Differences were observed in genes related to oxidation-reduction processes, DNA-dependent transcription factors, and factors related to important functional pathways for embryo development. Blastocyst rate was higher in the 5% O2 group and the number of cells was assessed, with the 5% O2 group having a higher number of cells. ROS concentration was evaluated, with a higher ROS presence in the 20% O2 group. Taken together, these results allow us to conclude that IVC of embryos at atmospheric O2 tension affects the expression of important transcription factors involved in multiple cell biology pathways that can affect embryo development, quality, and viability

Genome-Wide Association Analysis in Asthma Subjects Identifies SPATS2L as a Novel Bronchodilator Response Gene

Bronchodilator response (BDR) is an important asthma phenotype that measures reversibility of airway obstruction by comparing lung function (i.e. FEV1) before and after the administration of a short-acting β2-agonist, the most common rescue medications used for the treatment of asthma. BDR also serves as a test of β2-agonist efficacy. BDR is a complex trait that is partly under genetic control. A genome-wide association study (GWAS) of BDR, quantified as percent change in baseline FEV1 after administration of a β2-agonist, was performed with 1,644 non-Hispanic white asthmatic subjects from six drug clinical trials: CAMP, LOCCS, LODO, a medication trial conducted by Sepracor, CARE, and ACRN. Data for 469,884 single-nucleotide polymorphisms (SNPs) were used to measure the association of SNPs with BDR using a linear regression model, while adjusting for age, sex, and height. Replication of primary P-values was attempted in 501 white subjects from SARP and 550 white subjects from DAG. Experimental evidence supporting the top gene was obtained via siRNA knockdown and Western blotting analyses. The lowest overall combined P-value was 9.7E-07 for SNP rs295137, near the SPATS2L gene. Among subjects in the primary analysis, those with rs295137 TT genotype had a median BDR of 16.0 (IQR = [6.2, 32.4]), while those with CC or TC genotypes had a median BDR of 10.9 (IQR = [5.0, 22.2]). SPATS2L mRNA knockdown resulted in increased β2-adrenergic receptor levels. Our results suggest that SPATS2L may be an important regulator of β2-adrenergic receptor down-regulation and that there is promise in gaining a better understanding of the biological mechanisms of differential response to β2-agonists through GWAS