On the move:Exploring the impact of residential mobility on cannabis use

AbstractA large literature exists suggesting that residential mobility leads to increased participation in risky health behaviours such as cannabis use amongst youth. However, much of this work fails to account for the impact that underlying differences between mobile and non-mobile youth have on this relationship. In this study we utilise multilevel models with longitudinal data to simultaneously estimate between-child and within-child effects in the relationship between residential mobility and cannabis use, allowing us to determine the extent to which cannabis use in adolescence is driven by residential mobility and unobserved confounding. Data come from a UK cohort, The Avon Longitudinal Study of Parents and Children. Consistent with previous research we find a positive association between cumulative residential mobility and cannabis use when using multilevel extensions of conventional logistic regression models (log odds: 0.94, standard error: 0.42), indicating that children who move houses are more likely to use cannabis than those who remain residentially stable. However, decomposing this relationship into within- and between-child components reveals that the conventional model is underspecified and misleading; we find that differences in cannabis use between mobile and non-mobile children are due to underlying differences between these groups (between-child log odds: 3.56, standard error: 1.22), not by a change in status of residential mobility (within-child log odds: 1.33, standard error: 1.02). Our findings suggest that residential mobility in the teenage years does not place children at an increased risk of cannabis use throughout these years

Fine-Tuning of PI3K/AKT Signalling by the Tumour Suppressor PTEN Is Required for Maintenance of Flight Muscle Function and Mitochondrial Integrity in Ageing Adult Drosophila melanogaster

Insulin/insulin-like growth factor signalling (IIS), acting primarily through the PI3-kinase (PI3K)/AKT kinase signalling cassette, plays key evolutionarily conserved regulatory roles in nutrient homeostasis, growth, ageing and longevity. The dysfunction of this pathway has been linked to several age-related human diseases including cancer, Type 2 diabetes and neurodegenerative disorders. However, it remains unclear whether minor defects in IIS can independently induce the age-dependent functional decline in cells that accompany some of these diseases or whether IIS alters the sensitivity to other aberrant signalling. We identified a novel hypomorphic allele of PI3K’s direct antagonist, Phosphatase and tensin homologue on chromosome 10 (Pten), in the fruit fly, Drosophila melanogaster. Adults carrying combinations of this allele, Pten5, combined with strong loss-of-function Pten mutations exhibit subtle or no increase in mass, but are highly susceptible to a wide range of stresses. They also exhibit dramatic upregulation of the oxidative stress response gene, GstD1, and a progressive loss of motor function that ultimately leads to defects in climbing and flight ability. The latter phenotype is associated with mitochondrial disruption in indirect flight muscles, although overall muscle structure appears to be maintained. We show that the phenotype is partially rescued by muscle-specific expression of the Bcl-2 homologue Buffy, which in flies, maintains mitochondrial integrity, modulates energy homeostasis and suppresses cell death. The flightless phenotype is also suppressed by mutations in downstream IIS signalling components, including those in the mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway, suggesting that elevated IIS is responsible for functional decline in flight muscle. Our data demonstrate that IIS levels must be precisely regulated by Pten in adults to maintain the function of the highly metabolically active indirect flight muscles, offering a new system to study the in vivo roles of IIS in the maintenance of mitochondrial integrity and adult ageing

Exploring the feasibility of utilizing limited gene panel circulating tumor DNA clearance as a biomarker in patients with locally advanced non-small cell lung cancer

INTRODUCTION: Circulating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC. METHODS: Plasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst RESULTS: Twenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01). CONCLUSIONS: Although it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer

Measurements of stratospheric constituents by ISAMS

ISAMS is a limb sounding radiometer flying on the UARS, and designed to measure temperature, pressure, O3, CO, NO, NO2, N2O5, HNO3, CH4, H2O, N2O, and aerosol. Its capabilities are described, together with the present status of validation of its data products, and plans for future improvement