The Ethical Implications of Using Genetic Information in Personnel Selection

Biology, during the last decade in particular, is making substantial headway into our social theories of business and behavior. While the social sciences rush to keep up with the advancement of knowledge, we highlight the need for an ethics discussion to also keep pace. Although the implications to theory are important, our focus is on how new knowledge has the capacity to alter the formulation and practice of business policy, which we believe is potentially profound. Furthermore, the ethicality of a set of issues can depend heavily on one’s perspective, and differing views may not always be compatible. With this in mind, we discuss the ways in which one area of emerging biological knowledge—behavioral genetics—invites a rethinking of the nuances of four long-standing topic areas of business ethics surrounding personnel selection; and we do so from two perspectives—that of the employer and of the job seeker. The four ethical topics are (a) the static (mostly) nature of genetic information that is out of an individual’s control, (b) faking and lying during selection processes, (c) privacy, and (d) stigmatization of minority groups

Evaluation of the effectiveness and cost-effectiveness of Families for Health V2 for the treatment of childhood obesity : study protocol for a randomized controlled trial

Background: Effective programs to help children manage their weight are required. Families for Health focuses on a parenting approach, designed to help parents develop their parenting skills to support lifestyle change within the family. Families for Health V1 showed sustained reductions in overweight after 2 years in a pilot evaluation, but lacks a randomized controlled trial (RCT) evidence base. Methods/design: This is a multi-center, investigator-blind RCT, with parallel economic evaluation, with a 12-month follow-up. The trial will recruit 120 families with at least one child aged 6 to 11 years who is overweight (≥91st centile BMI) or obese (≥98th centile BMI) from three localities and assigned randomly to Families for Health V2 (60 families) or the usual care control (60 families) groups. Randomization will be stratified by locality (Coventry, Warwickshire, Wolverhampton). Families for Health V2 is a family-based intervention run in a community venue. Parents/carers and children attend parallel groups for 2.5 hours weekly for 10 weeks. The usual care arm will be the usual support provided within each NHS locality. A mixed-methods evaluation will be carried out. Child and parent participants will be assessed at home visits at baseline, 3-month (post-treatment) and 12-month follow-up. The primary outcome measure is the change in the children’s BMI z-scores at 12 months from the baseline. Secondary outcome measures include changes in the children’s waist circumference, percentage body fat, physical activity, fruit/vegetable consumption and quality of life. The parents’ BMI and mental well-being, family eating/activity, parent–child relationships and parenting style will also be assessed. Economic components will encompass the measurement and valuation of service utilization, including the costs of running Families for Health and usual care, and the EuroQol EQ-5D health outcomes. Cost-effectiveness will be expressed in terms of incremental cost per quality-adjusted life year gained. A de novo decision-analytic model will estimate the lifetime cost-effectiveness of the Families for Health program. Process evaluation will document recruitment, attendance and drop-out rates, and the fidelity of Families for Health delivery. Interviews with up to 24 parents and children from each arm will investigate perceptions and changes made. Discussion: This paper describes our protocol to assess the effectiveness and cost-effectiveness of a parenting approach for managing childhood obesity and presents challenges to implementation. Trial registration: Current Controlled Trials ISRCTN4503220

Library Design in Combinatorial Chemistry by Monte Carlo Methods

Strategies for searching the space of variables in combinatorial chemistry experiments are presented, and a random energy model of combinatorial chemistry experiments is introduced. The search strategies, derived by analogy with the computer modeling technique of Monte Carlo, effectively search the variable space even in combinatorial chemistry experiments of modest size. Efficient implementations of the library design and redesign strategies are feasible with current experimental capabilities.Comment: 5 pages, 3 figure

Biomass burning aerosol over the Amazon: analysis of aircraft, surface and satellite observations using a global aerosol model

Vegetation fires emit large quantities of aerosol into the atmosphere, impacting regional air quality and climate. Previous work has used comparisons of simulated and observed aerosol optical depth (AOD) in regions heavily impacted by fires to suggest that emissions of aerosol particles from fires may be underestimated by a factor of 2–5. Here we use surface, aircraft and satellite observations made over the Amazon during September 2012, along with a global aerosol model to improve understanding of aerosol emissions from vegetation fires. We apply three different satellite-derived fire emission datasets (FINN, GFED, GFAS) in the model. Daily mean aerosol emissions in these datasets vary by up to a factor of 3.7 over the Amazon during this period, highlighting the considerable uncertainty in emissions. We find variable agreement between the model and observed aerosol mass concentrations. The model reproduces observed aerosol concentrations over deforestation fires well in the western Amazon during dry season conditions with FINN or GFED emissions and during dry–wet transition season conditions with GFAS emissions. In contrast, the model underestimates aerosol concentrations over savanna fires in the Cerrado environment east of the Amazon Basin with all three fire emission datasets. The model generally underestimates AOD compared to satellite and ground stations, even when the model reproduces the observed vertical profile of aerosol mass concentration. We suggest it is likely caused by uncertainties in the calculation of AOD, which are as large as ∼90 %, with the largest sensitivities due to uncertainties in water uptake and relative humidity. Overall, we do not find evidence that particulate emissions from fires are systematically underestimated in the Amazon region and we caution against using comparison with AOD to constrain particulate emissions from fires

FoxP1 marks medium spiny neurons from precursors to maturity and is required for their differentiation

Identifying the steps involved in striatal development is important both for understanding the striatum in health and disease, and for generating protocols to differentiate striatal neurons for regenerative medicine. The most prominent neuronal subtype in the adult striatum is the medium spiny projection neuron (MSN), which constitutes more than 85% of all striatal neurons and classically expresses DARPP-32. Through a microarray study of genes expressed in the whole ganglionic eminence (WGE: the developing striatum) in the mouse, we identified the gene encoding the transcription factor Forkhead box protein P1 (FoxP1) as the most highly up-regulated gene, thus providing unbiased evidence for the association of FoxP1 with MSN development. We also describe the expression of FoxP1 in the human fetal brain over equivalent gestational stages. FoxP1 expression persisted through into adulthood in the mouse brain, where it co-localised with all striatal DARPP-32 positive projection neurons and a small population of DARPP-32 negative cells. There was no co-localisation of FoxP1 with any interneuron markers. FoxP1 was detectable in primary fetal striatal cells following dissection, culture, and transplantation into the adult lesioned striatum, demonstrating its utility as an MSN marker for transplantation studies. Furthermore, DARPP-32 expression was absent from FoxP1 knock-out mouse WGE differentiated in vitro, suggesting that FoxP1 is important for the development of DARPP-32-positive MSNs. In summary, we show that FoxP1 labels MSN precursors prior to the expression of DARPP-32 during normal development, and in addition suggest that FoxP1 labels a sub-population of MSNs that are not co-labelled by DARPP-32. We demonstrate the utility of FoxP1 to label MSNs in vitro and following neural transplantation, and show that FoxP1 is required for DARPP-32 positive MSN differentiation in vitro

Global and regional trends in particulate air pollution and attributable health burden over the past 50 years

Long-term exposure to ambient particulate matter (PM2.5, mass of particles with an aerodynamic dry diameter of < 2.5 μm) is a major risk factor to the global burden of disease. Previous studies have focussed on present day or future health burdens attributed to ambient PM2.5. Few studies have estimated changes in PM2.5 and attributable health burdens over the last few decades, a period where air quality has changed rapidly. Here we used the HadGEM3-UKCA coupled chemistry-climate model, integrated exposure-response relationships, demographic and background disease data to provide the first estimate of the changes in global and regional ambient PM2.5 concentrations and attributable health burdens over the period 1960 to 2009. Over this period, global mean population-weighted PM2.5 concentrations increased by 38%, dominated by increases in China and India. Global attributable deaths increased by 89% to 124% over the period 1960 to 2009, dominated by large increases in China and India. Population growth and ageing contributed mostly to the increases in attributable deaths in China and India, highlighting the importance of demographic trends. In contrast, decreasing PM2.5 concentrations and background disease dominated the reduction in attributable health burden in Europe and the United States. Our results shed light on how future projected trends in demographics and uncertainty in the exposure–response relationship may provide challenges for future air quality policy in Asia

Large air quality and human health impacts due to Amazon forest and vegetation fires

Vegetation fires across the tropics emit fine particulate matter (PM2.5) to the atmosphere, degrading regional air quality and impacting human health. Extensive vegetation fires occur regularly across the Amazon basin, but there have been no detailed assessments of the impacts on air quality or human health. We used updated exposure-response relationships and a regional climate-chemistry model, evaluated against a comprehensive set of observational data, to provide the first in-depth assessment of the potential public health benefits due to fire prevention across the Amazon Basin. We focused on 2012, a year with emissions similar to the 11-year average (2008 to 2018). Vegetation fires contributed >80% of simulated dry season mean surface PM2.5 in the western Amazon region particularly in Bolivia and Brazilian states of Rondônia, Acre, and Mato Grosso. We estimate that the prevention of vegetation fires would have averted 16 800 (95UI: 16 300–17 400) premature deaths and 641 000 (95UI: 551 900–741 300) disability adjusted life years (DALYs) across South America, with 26% of the avoided health burden located within the Amazon Basin. The health benefits of fire prevention in the Amazon are comparable to those found in Equatorial Asia

Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes

BACKGROUND: DNA methylation and the Polycomb repression system are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. RESULTS: By genome-wide mapping of the Polycomb Repressive Complex 2-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and Polycomb Repressive Complex 2 from Polycomb target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. CONCLUSIONS: An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining Polycomb Repressive Complex 2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease

Adherence to Antiretroviral Therapy among HIV Infected Children Measured by Caretaker Report, Medication Return, and Drug Level in Dar Es Salaam, Tanzania.

Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline