Epidemiology, Public Health, and the Rhetoric of False Positives

BACKGROUND: As an observational science, epidemiology is regarded by some researchers as inherently flawed and open to false results. In a recent paper, Boffetta et al. [Boffetta P, McLaughlin JK, LaVecchia C, Tarone RE, Lipworth L, Blot WJ. False-positive results in cancer epidemiology: a plea for epistemological modesty. J Natl Cancer Inst 100:988-995 (2008)] argued that "epidemiology is particularly prone to the generation of false-positive results." They also said "the tendency to emphasize and over-interpret what appear to be new findings is commonplace, perhaps in part because of a belief that the findings provide information that may ultimately improve public health" and that "this tendency to hype new findings increases the likelihood of downplaying inconsistencies within the data or any lack of concordance with other sources of evidence." The authors supported these serious charges against epidemiology and epidemiologists with few examples. Although we acknowledge that false positives do occur, we view the position of Boffetta and colleagues on false positives as unbalanced and potentially harmful to public health. OBJECTIVE: We aim to provide a more balanced evaluation of epidemiology and its contribution to public health discourse. DISCUSSION: Boffetta and colleagues ignore the fact that false negatives may arise from the very processes that they tout as generating false-positive results. We further disagree with their proposition that false-positive results from a single study will lead to faulty decision making in matters of public health importance. In practice, such public health evaluations are based on all the data available from all relevant disciplines and never to our knowledge on a single study. CONCLUSIONS: The lack of balance by Boffetta and colleagues in their evaluation of the impact of false-positive findings on epidemiology, the charge that "methodological vigilance is often absent" in epidemiologists' interpretation of their own results, and the false characterization of how epidemiologic findings are used in societal decision making all undermine a major source of information regarding disease risks. We reaffirm the importance of epidemiologic evidence as a critical component of the foundation of public health protection

Alcohol content in the 'Hyper-Reality' MTV show 'Geordie Shore'

Aim: To quantify the occurrence of alcohol content, including alcohol branding, in the popular primetime television UK Reality TV show 'Geordie Shore' Series 11. Methods: A 1-min interval coding content analysis of alcohol content in the entire DVD Series 11 of 'Geordie Shore' (10 episodes). Occurrence of alcohol use, implied use, other alcohol reference/paraphernalia or branding was recorded. Results: All categories of alcohol were present in all episodes. 'Any alcohol' content occurred in 78%, 'actual alcohol use' in 30%, 'inferred alcohol use' in 72%, and all 'other' alcohol references occurred in 59% of all coding intervals (ACIs), respectively. Brand appearances occurred in 23% of ACIs. The most frequently observed alcohol brand was Smirnoff which appeared in 43% of all brand appearances. Episodes categorized as suitable for viewing by adolescents below the legal drinking age of 18 years comprised of 61% of all brand appearances. Conclusions: Alcohol content, including branding, is highly prevalent in the UK Reality TV show 'Geordie Shore' Series 11. Two-thirds of all alcohol branding occurred in episodes age-rated by the British Board of Film Classification (BBFC) as suitable for viewers aged 15 years. The organizations OfCom, Advertising Standards Authority (ASA) and the Portman Group should implement more effective policies to reduce adolescent exposure to on-screen drinking. The drinks industry should consider demanding the withdrawal of their brands from the show. Short Summary: Alcohol content, including branding, is highly prevalent in the MTV reality TV show 'Geordie Shore' Series 11. Current alcohol regulation is failing to protect young viewers from exposure to such content

Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM. Material and Methods A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs). Results Continuous change in muscle quality was independently associated with change in absolute (β = 0.015; p = 0.019) and relative (β = 0.200; p = 0.005) VO2peak, and TTE (β = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (β = 0.050; p = 0.005) and relative (β = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05). Discussion: The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Estimating retention benchmarks for salvage logging to protect biodiversity

S.T. was supported by the Humboldt-Foundation and by the MOST (Ministry of Science and Technology) Taiwan Research Fellowship to work with A.C. at National Tsing Hua University, Taiwan. S.T. received funds from the Gregor Louisoder Environmental Foundation. A.B.L. received funds from the Humboldt-Foundation.Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 75 ± 7% (mean ± SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 ± 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups.Open Access funding enabled and organized by Projekt DEA

The multiple facets of the Hsp90 machine

International audienceThe Ninth International Conference on the Hsp90 Chaperone Machine concluded in October 2018, in Leysin, Switzerland. The program highlighted findings in various areas, including integrated insight into molecular mechanism of Hsp90, cochaperones, and clients’ structure and function.Heat shock protein-90 (Hsp90) is a molecular chaperone critical for the folding, stability, and activity of client proteins 1. Hsp90 and its orthologs, including bacterial HtpG, mitochondrial TRAP1 and endoplasmic reticulum Grp94, exist as dimers, hydrolyze ATP, and cycle between distinct conformational states. Hsp90 preferentially binds proteins in near native states facilitating their remodeling for protein interactions and signaling. At the 9th International Conference on the Hsp90 Chaperone Machine approximately one-third of the attendees shared their data on Hsp90 structure and function through short talks (Figure 1). Here, we distill and summarize their finding

Repeatability and validity of a standardised maximal step-up test for leg function-a diagnostic accuracy study

<p>Abstract</p> <p>Background</p> <p>Objectively assessed physical performance is a strong predictor for morbidity and premature death and there is an increasing interest in the role of sarcopenia in many chronic diseases. There is a need for robust and valid functional tests in clinical practice. Therefore, the repeatability and validity of a newly developed maximal step up test (MST) was assessed.</p> <p>Methods</p> <p>The MST, assessing maximal step-up height (MSH) in 3-cm increments, was evaluated in 60 healthy middle-aged subjects, 30 women and 30 men. The repeatability of MSH and the correlation between MSH and isokinetic knee extension peak torque (IKEPT), self-reported physical function (SF-36, PF), patient demographics and self-reported physical activity were investigated.</p> <p>Results</p> <p>The repeatability between occasions and between testers was 6 cm. MSH (range 12-45 cm) was significantly correlated to IKEPT, (<it>r </it>= 0.68, <it>P </it>< 0.001), SF-36 PF score, (<it>r </it>= 0.29, <it>P </it>= 0.03), sex, age, weight and BMI. The results also show that MSH above 32 cm discriminates subjects in our study with no limitation in self-reported physical function.</p> <p>Conclusions</p> <p>The standardised MST is considered a reliable leg function test for clinical practice. The MSH was related to knee extension strength and self-reported physical function. The precision of the MST for identification of limitations in physical function needs further investigation.</p

Does the risk of cerebral palsy increase or decrease with increasing gestational age?

BACKGROUND: It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective. METHODS: We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy. RESULTS: Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation. CONCLUSIONS: The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy

Structure and function of a broad-specificity chitin deacetylase from <i>Aspergillus nidulans </i>FGSC A4

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