Measuring vertebrate telomeres: applications and limitations

Telomeres are short tandem repeated sequences of DNA found at the ends of eukaryotic chromosomes that function in stabilizing chromosomal end integrity. In vivo studies of somatic tissue of mammals and birds have shown a correlation between telomere length and organismal age within species, and correlations between telomere shortening rate and lifespan among species. This result presents the tantalizing possibility that telomere length could be used to provide much needed information on age, ageing and survival in natural populations where longitudinal studies are lacking. Here we review methods available for measuring telomere length and discuss the potential uses and limitations of telomeres as age and ageing estimators in the fields of vertebrate ecology, evolution and conservation

Compulsivity is measurable across distinct psychiatric symptom domains and is associated with familial risk and reward-related attentional capture.

BACKGROUND: Compulsivity can be seen across various mental health conditions and refers to a tendency toward repetitive habitual acts that are persistent and functionally impairing. Compulsivity involves dysfunctional reward-related circuitry and is thought to be significantly heritable. Despite this, its measurement from a transdiagnostic perspective has received only scant research attention. Here we examine both the psychometric properties of a recently developed compulsivity scale, as well as its relationship with compulsive symptoms, familial risk, and reward-related attentional capture. METHODS: Two-hundred and sixty individuals participated in the study (mean age = 36.0 [SD = 10.8] years; 60.0% male) and completed the Cambridge-Chicago Compulsivity Trait Scale (CHI-T), along with measures of psychiatric symptoms and family history thereof. Participants also completed a task designed to measure reward-related attentional capture (n = 177). RESULTS: CHI-T total scores had a normal distribution and acceptable Cronbach's alpha (0.84). CHI-T total scores correlated significantly and positively (all p < 0.05, Bonferroni corrected) with Problematic Usage of the Internet, disordered gambling, obsessive-compulsive symptoms, alcohol misuse, and disordered eating. The scale was correlated significantly with history of addiction and obsessive-compulsive related disorders in first-degree relatives of participants and greater reward-related attentional capture. CONCLUSIONS: These findings suggest that the CHI-T is suitable for use in online studies and constitutes a transdiagnostic marker for a range of compulsive symptoms, their familial loading, and related cognitive markers. Future work should more extensively investigate the scale in normative and clinical cohorts, and the role of value-modulated attentional capture across compulsive disorders

The impact generated by public and charity-funded research in the UK: A systematic literature review

Objective: To identify, synthesize and critically assess the empirical evidence of the impact generated by public and charity funded health research in the United Kingdom. Methods: We conducted a systematic literature review of the empirical evidence published in English in peer-reviewed journals between 2006 and 2017. Studies meeting the inclusion criteria were selected and their findings were analysed using the Payback Framework into five main categories: knowledge, benefits to future research and research use, benefits from informing policy and product development, health and health sector benefits and broader economic benefits. We assessed the studies for risk of selection, reporting and funding bias. Results: Thirteen studies met the inclusion criteria. The majority of the studies (10 out of 13) assessed impact at multiple domains including the main 5 key themes of the Payback Framework. All of them showed a positive impact of funded research on outcomes. Of those studies, one presented low risk of bias (8%), 6 studies were classified as presenting moderate risk of bias (46%) and 6 studies presented high risk of bias (46%). Conclusions: Empirical evidence on the impact of public and charity funded research is still limited and subject to funding and selection bias. More work is needed to establish the causal effects of funded research on academic outcomes, policy, practice and the broader economy

Reward-related attentional capture and cognitive inflexibility interact to determine greater severity of compulsivity-related problems.

BACKGROUND AND OBJECTIVES: Neurocognitive processes are key drivers of addictive and compulsive disorders. The current study examined whether reward-related attentional capture and cognitive inflexibility are associated with impulsive and/or compulsive personality traits, and whether these cognitive characteristics interact to predict greater compulsivity-related problems across obsessive-compulsive and drinking behaviors. METHODS: One-hundred and seventy-three participants (mean age = 34.5 years, S.D = 8.4, 42% female) completed an online visual search task to measure reward-related attentional capture and its persistence following reversal of stimulus-reward contingencies. Participants also completed questionnaires to assess trait impulsivity, compulsivity, alcohol use, and obsessive-compulsive behaviors. RESULTS: Greater reward-related attentional capture was associated with trait compulsivity, over and above all impulsivity dimensions, while greater cognitive inflexibility was associated with higher negative urgency (distress-elicited impulsivity). Reward-related attentional capture and cognitive inflexibility interacted to predict greater compulsivity-related problems among participants who reported obsessive-compulsive behaviors in the past month (n = 57) as well as current drinkers (n = 88). Follow-up analyses showed that, for OCD behaviors, this interaction was driven by an association between higher reward-related attentional capture and more problematic behaviors among cognitively inflexible participants only. For drinking, the same pattern was seen, albeit at trend level. LIMITATIONS: This study includes a non-clinical, online sample and is cross-sectional, thus its findings need to be interpreted with these limitations in mind. CONCLUSIONS: Reward-related attentional capture and cognitive flexibility are related to trait compulsivity and impulsivity (negative urgency) respectively, and interact to determine more problematic behaviors

Immunotherapy of lung cancer: An update

In Germany lung cancer is the leading cause of cancer-associated death in men. Surgery, chemotherapy and radiation may enhance survival of patients suffering from lung cancer but the enhancement is typically transient and mostly absent with advanced disease; eventually more than 90% of lung cancer patients will die of disease. New approaches to the treatment of lung cancer are urgently needed. Immunotherapy may represent one new approach with low toxicity and high specificity but implementation has been a challenge because of the poor antigenic characterization of these tumors and their ability to escape immune responses. Several different immunotherapeutic treatment strategies have been developed. This review examines the current state of development and recent advances with respect to non-specific immune stimulation, cellular immunotherapy ( specific and non-specific), therapeutic cancer vaccines and gene therapy for lung cancer. The focus is primarily placed on immunotherapeutic cancer treatments that are already in clinical trial or well progressed in preclinical studies. Although there seems to be a promising future for immunotherapy in lung cancer, presently there is not standard immunotherapy available for clinical routine

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Adipocyte-specific protein tyrosine phosphatase 1B deletion increases lipogenesis, adipocyte cell size and is a minor regulator of glucose homeostasis

Peer reviewedPublisher PD

High-Resolution, In Vivo Magnetic Resonance Imaging of Drosophila at 18.8 Tesla

High resolution MRI of live Drosophila was performed at 18.8 Tesla, with a field of view less than 5 mm, and administration of manganese or gadolinium-based contrast agents. This study demonstrates the feasibility of MR methods for imaging the fruit fly Drosophila with an NMR spectrometer, at a resolution relevant for undertaking future studies of the Drosophila brain and other organs. The fruit fly has long been a principal model organism for elucidating biology and disease, but without capabilities like those of MRI. This feasibility marks progress toward the development of new in vivo research approaches in Drosophila without the requirement for light transparency or destructive assays

Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences