Carbs versus fat does it really matter for maintaining lost weight?, bioRxiv, 2018-11-28
The most read article of 2018 published in The BMJ (httpsdoi.org10.1136bmj.k4583) claimed that restricting dietary carbohydrates offers a metabolic advantage to burn more calories and thereby help patients maintain lost weight. However, analyzing the data according to the original pre-registered statistical plan resulted in no statistically significant effects of diet composition on energy expenditure. The large reported diet effects on energy expenditure calculated using the revised analysis plan depended on data from subjects with excessive amounts of unaccounted energy. Adjusting the data to be commensurate with energy conservation resulted in a diet effect that was less than half the value reported in The BMJ paper. Furthermore, the measured daily average CO2 production rates were not significantly different between the diets and the reported expenditure differences were due to inaccurate calculations based on false assumptions about diet adherence.
biorxiv physiology 200-500-users 2018Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes A 2-year Non-randomized Clinical Trial, bioRxiv, 2018-11-28
ABSTRACTOBJECTIVEStudies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We aim to assess the effects of a continuous care intervention (CCI) on retention, glycemic control, weight, body composition, cardiovascular, liver, kidney, thyroid, inflammatory markers, diabetes medication usage and disease outcomes at 2 years in adults with type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSAn open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively.RESULTSSignificant changes from baseline to 2 years in the CCI group included HbA1c (−12% from 7.7±0.1%); fasting glucose (−18% from 163.67±3.90 mgdL); fasting insulin (−42% from 27.73±1.26 pmol L-1); weight (−10% from 114.56±0.60 kg); systolic blood pressure (−4% from 131.7±0.9 mmHg); diastolic blood pressure (−4% from 81.8±0.5 mmHg); triglycerides (−22% from 197.2±9.1 mgdL); HDL-C (+19% from 41.8±0.9 mgdL), and liver alanine transaminase (−21% from 29.16±0.97 UL). Spine bone mineral density in the CCI group was unchanged. Glycemic control medication use (excluding metformin) among CCI participants declined (from 56.9% to 26.8%, P=1.3×10-11) including prescribed insulin (−62%) and sulfonylureas (−100%). The UC group had no significant changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also significant resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p-values <0.00012.CONCLUSIONSThe CCI sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity, with no adverse effect on bone health.TRIAL REGISTRATIONClinicaltrials.gov <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=clintrialgov xlinkhref=NCT02519309>NCT02519309<jatsext-link>
biorxiv clinical-trials 200-500-users 2018Base editing generates substantial off-target single nucleotide variants, bioRxiv, 2018-11-27
AbstractGenome editing tools including CRISPRCas9 and base editors hold great promise for correcting pathogenic mutations. Unbiased genome-wide off-target effects of the editing in mammalian cells is required before clinical applications, but determination of the extent of off-target effects has been difficult due to the existence of single nucleotide polymorphisms (SNPs) in individuals. Here, we developed a method named GOTI (Genome-wide Off-target analysis by Two-cell embryo Injection) to detect off-target mutations without interference of SNPs. We applied GOTI to both the CRISPR-Cas9 and base editing (BE3) systems by editing one blastomere of the two-cell mouse embryo and then compared whole genome sequences of progeny-cell populations at E14.5 stage. Sequence analysis of edited and non-edited cell progenies showed that undesired off-target single nucleotide variants (SNVs) are rare (average 10.5) in CRISPR-edited mouse embryos, with a frequency close to the spontaneous mutation rate. By contrast, BE3 editing induced over 20-fold higher SNVs (average 283), raising the concern of using base-editing approaches for biomedical application.
biorxiv genomics 100-200-users 2018Climate or disturbance temperate forest structural change and carbon sink potential, bioRxiv, 2018-11-27
ABSTRACTAnticipating forest responses to changing climate and disturbance regimes requires understanding long-term successional processes and aggregating these local processes into global relevance. Estimates of existing forest structure and biomass are improving globally; however, vegetation models continue to show substantial spread in predictions of future land carbon uptake and the roles of forest structural change and demography are increasingly being recognized as important. To identify mechanisms that drive change in tree size, density, and carbon, we need a better understanding of forest structural trajectories and the factors that affect those trajectories. Here we reveal a coherent, cyclic pattern of structural change in temperate forests, as predicted by successional theory, and identify significant sensitivity to climatic precipitation and temperature anomalies using large datasets and empirical modeling. For example, in the eastern US above average temperature (+1°C) was associated with a 27% (−0.4±0.1 Mg C ha-1 yr-1) reduction in productivity attributed to higher rates of disease (+23%), weather disturbance (+57%), and sapling mortality. Projections of future vegetative carbon sink potential suggests biomass would be lowest on managed lands (72±2 Mg C ha-1) and highest when larger trees survive in undisturbed conditions (153±21 Mg C ha-1). Overall, the indirect effects of disturbance and mortality were considerably larger than the direct effects of climate on productivity when predicting future vegetative carbon sinks. Results provide robust comparisons for global vegetation models, and valuable projections for management and carbon mitigation efforts.
biorxiv ecology 0-100-users 2018Naught all zeros in sequence count data are the same, bioRxiv, 2018-11-27
AbstractDue to the advent and utility of high-throughput sequencing, modern biomedical research abounds with multivariate count data. Yet such sequence count data is often extremely sparse; that is, much of the data is zero values. Such zero values are well known to cause problems for statistical analyses. In this work we provide a systematic description of different processes that can give rise to zero values as well as the types of methods for addressing zeros in sequence count studies. Importantly, we systematically review how various models perform on each type of zero generating process. Our results demonstrate that zero-inflated models can have substantial biases in both simulated and real data settings. Additionally, we find that zeros due to biological absences can, for many applications, be approximated as originating from under sampling. Beyond these results, this work provides a paired categorization scheme for models and zero generating processes to facilitate discussions and future research into the analysis of sequence count data.
biorxiv bioinformatics 100-200-users 2018