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Genetic causes for ageing are traditionally investigated within a species. Yet, the lifecycles of many organisms intersect. Additional evolutionary and genetic causes of ageing, external to a focal species/organism, may thus be overlooked. Here, we introduce the phrase and concept of age-distorters and its evidence. Age-distorters carry ageing interfering genes, used to manipulate the biological age of other entities upon which the reproduction of age-distorters relies, e.g. age-distorters bias the reproduction/maintenance trade-offs of cells/organisms for their own evolutionary interests. Candidate age-distorters include viruses, parasites and symbionts, operating through specific, genetically encoded interferences resulting from co-evolution and arms race between manipulative non-kins and manipulable species. This interference results in organismal ageing when age-distorters prompt manipulated organisms to favor their reproduction at the expense of their maintenance, turning these hosts into expanded disposable soma. By relying on reproduction/maintenance trade-offs affecting disposable entities, which are left ageing to the reproductive benefit of other physically connected lineages with conflicting evolutionary interests, the concept of age-distorters expands the logic of the Disposable Soma theory beyond species with fixed germen/soma distinctions. read more Moreover, acknowledging age-distorters as external sources of mutation accumulation and antagonistic pleiotropic genes expands the scope of the mutation accumulation and of the antagonistic pleiotropy theories.The first paper on “inflammaging” published in 2001 paved the way for a unifying theory on how and why aging turns out to be the main risk factor for the development of the most common age-related diseases (ARDs). The most exciting challenge on this topic was explaining how systemic inflammation steeps up with age and why it shows different rates among individuals of the same chronological age. The “epigenetic revolution” in the past twenty years conveyed that the assessment of the individual genetic make-up is not enough to depict the trajectories of age-related inflammation. Accordingly, others and we have been focusing on the role of non-coding RNA, i.e. microRNAs (miRNAs), in inflammaging. The results obtained in the latest 10 years underpinned the key role of a miRNA subset that we have called inflammamiRs, owing to their ability to master (NF-κB)-driven inflammatory pathways. In this review, we will focus on two inflammamiRs, i.e. miR-21-5p and miR-146a-5p, which target a variety of molecules belonging to the NF-κB/NLRP3 pathways. The interplay between miR-146a-5p and IL-6 in the context of aging and ARDs will also be highlighted. We will also provide the most relevant evidence suggesting that circulating inflammamiRs, along with IL-6, can measure the degree of inflammaging.

Most literature on optimal group-sequential designs focuses on minimising the expected sample size. We highlight other factors for consideration.

We discuss several quantities less-often considered in adaptive design the median and standard deviation of the random required sample size, and the probability of committing an interim error. We consider how the optimal timing of interim analyses changes when these quantities are accounted for.

Incorporating the standard deviation of the required sample size into an optimality framework, we demonstrate how and when this quantity means using a group-sequential approach is not optimal. The optimal timing of an interim analysis is shown to be highly dependent on the pre-specified preference for minimising the expected sample size relative to its standard deviation.

Examining multiple factors, which measure the advantages and disadvantages of group-sequential designs, helps determine the best design for a specific trial.

Examining multiple factors, which measure the advantages and disadvantages of group-sequential designs, helps determine the best design for a specific trial.Background Daily self-weighing (DSW) may be an effective harm-reduction intervention to disrupt continued weight gain. Self-Weighing for Obesity Management in Primary Care (SWOP) is a 24-month randomized controlled trial in 400 adults with obesity (BMI kg/m2 ≥ 30) receiving primary care through a clinical network affiliated with an academic medical center. Objective To test DSW as a potentially scalable way to deter age-related weight gain among primary care patients with obesity. Methods Randomized-controlled trial with two conditions DSW (instruction to weigh daily and provision of a web-enabled digital scale with graphical weight feedback) or Standard Care (receive a monetary gift card equivalent to value of the scale). Both groups receive standardized weight management educational material. SWOP will test the causal effect of assignment to DSW (Aim 1) and adherence to DSW (Aim 2) on weight (primary outcome) and adoption of weight management practices (secondary outcomes), as well as evaluate the cost-effectiveness of DSW compared to standard care (Aim 3). Findings may inform clinical guidelines for weight management by providing evidence that DSW attenuates continued age-related weight gain among adults with obesity. This trial is registered with ClinicalTrials.gov (NCT04044794).Background Opioid analgesics are frequently initiated for chronic and acute pain despite weak evidence of benefit, although prescribing rates of some analgesics decreased in the context of the epidemic. In some populations, up to a quarter of opioid naïve persons prescribed opioids for non-cancer pain develop prescription opioid use disorder (OUD). Audit and feedback interventions rely on constructive use of routinely collected data to align professional behaviours and clinical practice with best evidence. These interventions have been shown to help reduce inappropriate initiation. However, effectiveness and acceptability of individualized “portraits” of physicians’ prescribing patterns, to reduce inappropriate initiation of opioid analgesics to opioid naïve persons, have not been evaluated. Methods REDONNA is a mixed-methods randomized study testing the effectiveness of individualized prescribing Portraits to reduce inappropriate initiation of opioid analgesics. This intervention to improve safety of opioid prescribing in primary care in British Columbia (BC), Canada involves mailing individual prescribing portraits to an ‘early group’ of 2604 family physicians, followed in 6 months by a mailing to 2553 family physicians in the ‘delayed group’.