Cognitive performance effects of nicotine and industry affiliation: a systematic review.

Background and aimsStudies assessing the cognitive performance effects of nicotine show inconsistent results and tobacco industry funding has been correlated with study outcomes. We conducted a systematic review of the primary literature assessing the cognitive performance effects of nicotine and assessed potential associations between tobacco and pharmaceutical industry affiliation and reported study conclusions.MethodsWe searched PubMed, EMBASE, PsycINFO, BIOSIS, and Web of Science for peer-reviewed journal articles published between 2009 and 2016 that: (1) were randomized controlled trials; (2) investigated the effects of nicotine on cognitive performance in a laboratory setting; (3) administered nicotine to healthy adults (18-60 years); and (4) included participants were nonsmokers or minimally deprived smokers (⩽2 hours of abstaining from smoking). Study disclosures and tobacco industry documents were reviewed to determine industry funding.ResultsSearches yielded 3,771 abstracts; 32 studies were included in the review. The majority of studies investigated the effects of nicotine on attention (n = 22). Nicotine had a non-uniform effect on attention: studies reported positive (41%; n = 9), mixed (41%; n = 9), and no effect (18%; n = 4). The majority of study authors had received prior tobacco industry funding (59%; n = 19), however over half of tobacco-industry funded authors did not report this (53%; n = 10).ConclusionsNicotine does not appear to be associated with consistent cognitive performance effects. Although no association was found between reported outcomes and tobacco or pharmaceutical industry funding, findings likely underestimate the influence of industry funding due to strict inclusion criteria and incomplete data on pharmaceutical industry funding.Clinical trial registrationNot applicable

Fabular: regression formulas as probabilistic programming

Regression formulas are a domain-specific language adopted by several R packages for describing an important and useful class of statistical models: hierarchical linear regressions. Formulas are succinct, expressive, and clearly popular, so are they a useful addition to probabilistic programming languages? And what do they mean? We propose a core calculus of hierarchical linear regression, in which regression coefficients are themselves defined by nested regressions (unlike in R). We explain how our calculus captures the essence of the formula DSL found in R. We describe the design and implementation of Fabular, a version of the Tabular schema-driven probabilistic programming language, enriched with formulas based on our regression calculus. To the best of our knowledge, this is the first formal description of the core ideas of R's formula notation, the first development of a calculus of regression formulas, and the first demonstration of the benefits of composing regression formulas and latent variables in a probabilistic programming language.Adam Ścibior received travel support from the DARPA PPAML programme. Marcin Szymczak was supported by Microsoft Research through its PhD Scholarship Programme.This is the author accepted manuscript. The final version is available from the Association of Computer Machinery via http://dx.doi.org/10.1145/2837614.283765

Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50–150 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 200 mg kg−1dose of cyclophosphamide. Tirapazamine (25 mg kg−1) in combination with cyclophosphamide (100 mg kg−1) produced an effect equivalent to a single 150 mg kg−1dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50–200 mg kg−1); AQ4N (50–200 mg kg−1) produced a more effective combination than tirapazamine (12.5–50 mg kg−1). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg−1) 6 h prior to cyclophosphamide (100 mg kg−1) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg−1). © 2000 Cancer Research Campaig

Asymmetry in skeletal distribution of mouse hematopoietic stem cell clones and their equilibration by mobilizing cytokines

Hematopoietic stem cells (HSCs) are able to migrate through the blood stream and engraft bone marrow (BM) niches. These features are key factors for successful stem cell transplantations that are used in cancer patients and in gene therapy protocols. It is unknown to what extent transplanted HSCs distribute throughout different anatomical niches in the BM and whether this changes with age. Here we determine the degree of hematopoietic migration at a clonal level by transplanting individual young and aged mouse HSCs labeled with barcoded viral vector, followed by assessing the skeletal distribution of hundreds of HSC clones. We detected highly skewed representation of individual clones in different bones at least 11 mo after transplantation. Importantly, a single challenge with the clinically relevant mobilizing agent granulocyte colony-stimulating factor (G-CSF) caused rapid redistribution of HSCs across the skeletal compartments. Old and young HSC clones showed a similar level of migratory behavior. Clonal make- up of blood of secondary recipients recapitulates the barcode composition of HSCs in the bone of origin. These data demonstrate a previously unanticipated high skeletal disequilibrium of the clonal composition of HSC pool long- term after transplantation. Our findings have important implications for experimental and clinical and stem cell transplantation protocols

Cognitive performance effects of nicotine and industry affiliation: a systematic review.

Background and aimsStudies assessing the cognitive performance effects of nicotine show inconsistent results and tobacco industry funding has been correlated with study outcomes. We conducted a systematic review of the primary literature assessing the cognitive performance effects of nicotine and assessed potential associations between tobacco and pharmaceutical industry affiliation and reported study conclusions.MethodsWe searched PubMed, EMBASE, PsycINFO, BIOSIS, and Web of Science for peer-reviewed journal articles published between 2009 and 2016 that: (1) were randomized controlled trials; (2) investigated the effects of nicotine on cognitive performance in a laboratory setting; (3) administered nicotine to healthy adults (18-60 years); and (4) included participants were nonsmokers or minimally deprived smokers (⩽2 hours of abstaining from smoking). Study disclosures and tobacco industry documents were reviewed to determine industry funding.ResultsSearches yielded 3,771 abstracts; 32 studies were included in the review. The majority of studies investigated the effects of nicotine on attention (n = 22). Nicotine had a non-uniform effect on attention: studies reported positive (41%; n = 9), mixed (41%; n = 9), and no effect (18%; n = 4). The majority of study authors had received prior tobacco industry funding (59%; n = 19), however over half of tobacco-industry funded authors did not report this (53%; n = 10).ConclusionsNicotine does not appear to be associated with consistent cognitive performance effects. Although no association was found between reported outcomes and tobacco or pharmaceutical industry funding, findings likely underestimate the influence of industry funding due to strict inclusion criteria and incomplete data on pharmaceutical industry funding.Clinical trial registrationNot applicable