Calcium supplements with or without vitamin D and risk of cardiovascular events : reanalysis of the Women's Health Initiative limited access dataset and meta-analysis

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Rounding, but not randomization method, non-normality, or correlation, affected baseline P-value distributions in randomized trials

Corrigendum: The authors regret that during the final manuscript sub-mission we provided an incorrect high resolution version ofFigure 7. We mistakenly provided a second copy of Appendix Figure 8 rather than the correct figure, which we havenow provided. We would like to apologise for any inconve-nience caused. Journal of Clinical Epidemiology (2020) Acknowledgements: The authors acknowledge the contribution of Professor Thomas Lumley who provided expert guidance in using the area under the curve of the cumulative distribution function of the baseline p-values for these analyses No specific funding was received for this study. MB receives salary support from the Health Research Council of New Zealand. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.The funders had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; and in the decision to submit the paper for publicationPeer reviewedPostprin

Identical summary statistics were uncommon in randomized trials and cohort studies

Acknowledgments We thank Dorit Naot and Susannah O'Sullivan for providing the animal raw data used in the simulations. Funding This research received no specific funding. MB is a recipient of an HRC Clinical Practitioners Fellowship. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors are independent of the HRC. The HRC had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.Peer reviewedPostprin

Calcium supplements and cancer risk : a meta-analysis of randomised controlled trials

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Effect of calcium supplements on risk of myocardial infarction and cardiovascular events : meta-analysis

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A randomised investigation of journal responses to academic and journalist enquiry about possible scientific misconduct

No specific funding was received for this study. MB receives salary support from the Health Research Council of New Zealand. The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. These funders had no role in the study design; collection, analysis, and interpretation of the data; writing of the report; and in the decision to submit the paper for publication.Peer reviewedPublisher PD

Estimated sweat loss, fluid and CHO intake, and sodium balance of male major junior, AHL, and NHL players during on-ice practices

Several previous studies have reported performance decrements in team sport athletes who dehydrated approximately 1.5–2% of their body mass (BM) through sweating. This study measured on-ice sweat loss, fluid intake, sodium balance, and carbohydrate (CHO) intake of 77 major junior (JR; 19 ± 1 years), 60 American Hockey League (AHL; 24 ± 4 years), and 77 National Hockey League (NHL; 27 ± 5 years) players. Sweat loss was calculated from pre- to post-exercise BM plus fluid intake minus urine loss. AHL (2.03 ± 0.62 L/hr) and NHL (2.02 ± 0.74 L/hr) players had higher sweat rates (p  .05). Sodium deficits (sodium loss − intake) were greater (p 2% BM) during 60 min of practice. However, ∼15%, 41%, and 48% of the JR, AHL, and NHL players, respectively, may have reached mild dehydration and increased risk of performance decrements in a 90-min practice

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm.METHODS: The study cohort comprised children (n = 128) with birthweight &lt;1500 g or gestational age &lt; 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models.RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02).CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.</p

Antiandrogens Act as Selective Androgen Receptor Modulators at the Proteome Level in Prostate Cancer Cells*

Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic responses dependent upon cellular context

Early protein intake predicts functional connectivity and neurocognition in preterm born children

© 2021, The Author(s). Nutritional intake can promote early neonatal brain development in very preterm born neonates (\u3c 32 weeks’ gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (β = 0.17; 95% CI 0.11, 0.23, p \u3c 0.001) but lower intakes of fat (β = − 0.06; 95% CI − 0.09, − 0.02, p = 0.001) and carbohydrates (β = − 0.03; 95% CI − 0.04, − 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (β = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (β = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (β = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children