Meta-analysis of variation suggests that embracing variability improves both replicability and generalizability in preclinical research

The replicability of research results has been a cause of increasing concern to the scientific community. The long-held belief that experimental standardization begets replicability has also been recently challenged, with the observation that the reduction of variability within studies can lead to idiosyncratic, lab-specific results that cannot be replicated. An alternative approach is to, instead, deliberately introduce heterogeneity, known as "heterogenization" of experimental design. Here, we explore a novel perspective in the heterogenization program in a meta-analysis of variability in observed phenotypic outcomes in both control and experimental animal models of ischemic stroke. First, by quantifying interindividual variability across control groups, we illustrate that the amount of heterogeneity in disease state (infarct volume) differs according to methodological approach, for example, in disease induction methods and disease models. We argue that such methods may improve replicability by creating diverse and representative distribution of baseline disease state in the reference group, against which treatment efficacy is assessed. Second, we illustrate how meta-analysis can be used to simultaneously assess efficacy and stability (i.e., mean effect and among-individual variability). We identify treatments that have efficacy and are generalizable to the population level (i.e., low interindividual variability), as well as those where there is high interindividual variability in response; for these, latter treatments translation to a clinical setting may require nuance. We argue that by embracing rather than seeking to minimize variability in phenotypic outcomes, we can motivate the shift toward heterogenization and improve both the replicability and generalizability of preclinical research

Transcranial Magnetic Stimulation for Positive Symptoms in Schizophrenia: A Systematic Review

© 2019 S. Karger AG, Basel. Copyright: All rights reserved. Transcranial magnetic stimulation (TMS) has been proposed as a potential treatment add-on for positive symptoms in schizophrenia. To summarize the current evidence for its efficacy, we reviewed clinical trials from the last 20 years that investigated TMS for positive symptoms. We performed a search on the PubMed database for clinical trials that used TMS for the treatment of positive symptoms published in peer-reviewed journals. We excluded reviews, case reports, and opinion papers. Of the 30 studies included, the majority (n = 25) investigated auditory verbal hallucinations. Twelve studies found evidence for a positive treatment effect of TMS on positive symptoms, while 18 did not find enough evidence to conclude that TMS is effective for positive symptoms. However, the small sample size of the majority of studies is a limiting factor for the reliability of previous findings. In conclusion, evidence for an effect of TMS on positive symptoms was mixed. Since most of the studies were performed in patients with auditory verbal hallucinations, further research of TMS for other positive symptoms including thought disorder and delusions is warranted

Learning jQuery 3: build interesting, interactive sites using jQuery by automating common tasks and simplifying the complicated ones

Uptake studies on CuO NP, CuO MP and CuCl2 in HeLa S3 cells. (PPTX 71 kb