Associations between self-referral and health behavior responses to genetic risk information

Background: Studies examining whether genetic risk information about common, complex diseases can motivate individuals to improve health behaviors and advance planning have shown mixed results. Examining the influence of different study recruitment strategies may help reconcile inconsistencies. Methods: Secondary analyses were conducted on data from the REVEAL study, a series of randomized clinical trials examining the impact of genetic susceptibility testing for Alzheimer’s disease (AD). We tested whether self-referred participants (SRPs) were more likely than actively recruited participants (ARPs) to report health behavior and advance planning changes after AD risk and APOE genotype disclosure. Results: Of 795 participants with known recruitment status, 546 (69%) were self-referred and 249 (31%) had been actively recruited. SRPs were younger, less likely to identify as African American, had higher household incomes, and were more attentive to AD than ARPs (all P < 0.01). They also dropped out of the study before genetic risk disclosure less frequently (26% versus 41%, P < 0.001). Cohorts did not differ in their likelihood of reporting a change to at least one health behavior 6 weeks and 12 months after genetic risk disclosure, nor in intentions to change at least one behavior in the future. However, interaction effects were observed where ε4-positive SRPs were more likely than ε4-negative SRPs to report changes specifically to mental activities (38% vs 19%, p < 0.001) and diets (21% vs 12%, p = 0.016) six weeks post-disclosure, whereas differences between ε4-positive and ε4-negative ARPs were not evident for mental activities (15% vs 21%, p = 0.413) or diets (8% versus 16%, P = 0.190). Similarly, ε4-positive participants were more likely than ε4-negative participants to report intentions to change long-term care insurance among SRPs (20% vs 5%, p < 0.001), but not ARPs (5% versus 9%, P = 0.365). Conclusions: Individuals who proactively seek AD genetic risk assessment are more likely to undergo testing and use results to inform behavior changes than those who respond to genetic testing offers. These results demonstrate how the behavioral impact of genetic risk information may vary according to the models by which services are provided, and suggest that how participants are recruited into translational genomics research can influence findings. Trial registration ClinicalTrials.gov NCT00089882 and NCT00462917 Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0124-0) contains supplementary material, which is available to authorized users

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis.

Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2))

The hand of Homo naledi

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like wrist and palm indicate a significant degree of climbing, despite the derived nature of many aspects of the hand and other regions of the postcranial skeleton in H. naledi

The nutritional status of people with alkaptonuria: An exploratory analysis suggests a protein/energy dilemma.

BackgroundAlkaptonuria (AKU) is a disorder of tyrosine/protein metabolism leading to accumulation of homogentisic acid. Clinical management historically recommended reducing dietary protein intake, especially in childhood, which has since been discredited in the literature. For the first time, analysis of baseline cross-sectional nutritional surveillance data from a large cohort of AKU patients is presented, which has clinical implications in all aspects of treatment planning.MethodSeventy-four patients (mean 55 years) admitted to the National Alkaptonuria Centre (NAC), underwent a global nutritional assessment, which included objective anthropometry, bioimpedance measures, habitual nutritional intake using a 7-day food diary and key nutritional biomarkers, including 24 hours urinary nitrogen, serum albumin, total protein and total 25-hydroxy vitamin D. All data was compared with cohort norms or recommended nutrient intakes for health (RNI). The potential beneficial impact of protein and anti-inflammatory nutrients such as vitamin C, selenium, and zinc were statistically interrogated against the AKU severity score index (AKUSSI)-a validated measure of disease progression stratified by age.ResultsFifty percent of AKU patients reported some level of protein restriction at some point in their lives. In comparison with national data sets, AKU patients present with significantly lower than predicted mid-upper arm circumference, grip strength, BMI, total energy and protein intake, and higher than predicted percentage body fat. They therefore meet the ESPEN criteria as "clinically undernourished." Severity fluctuates over the life course. No statistical association is identified between protein intake, expressed as %RNI or g/kg, or anti-inflammatory nutrients, including vitamin C as a high dose supplement on the severity of the disease, when correlated against the validated AKUSSI score.ConclusionAKU patients are at risk of protein depletion associated with a "perfect storm" of risk factors: historical, poorly evidenced recommendations to reduce total protein intake; limited mobility as the condition progresses, compromising muscle integrity; frequent hospital admissions for major surgery associated with multiple joint replacements, creating pinch points of high metabolic demand and the potential impact of the disease itself. As this is the first time this risk has been identified, the authors consider the dietetic implications of nitisinone treatment, which requires dietary protein control to manage the acquired tyrosinaemia. The lack of statistically significant evidence to support dietary manipulation of any kind to impede disease progression in AKU is demonstrated

Significance of herpesvirus immediate early gene expression in cellular immunity to cytomegalovirus infection

Interstitial pneumonia linked with reactivation of latent human cytomegalovirus due to iatrogenic immunosuppression can be a serious complication of bone marrow transplantation therapy of aplastic anaemia and acute leukaemia1. Cellular immunity plays a critical role in the immune surveillance of inapparent cytomegalovirus infections in man and the mouse1−7. The molecular basis of latency, however, and the interaction between latently or recurrently infected cells and the immune system of the host are poorfy understood. We have detected a so far unknown antigen in the mouse model. This antigen is found in infected cells in association with the expression of the herpesvirus 'immediate early' genes and is recognized by cytolytic T lymphocytes (CTL)8. We now demonstrate that an unexpectedly high proportion of the CTL precursors generated in vivo during acute murine cytomegalovirus infection are specific for cells that selectively synthesize immediate early proteins, indicating an immunodominant role of viral non-structural proteins

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Dynamical Cobordisms in General Relativity and String Theory

We describe a class of time-dependent solutions in string- or M-theory that are exact with respect to alpha-prime and curvature corrections and interpolate in physical space between regions in which the low energy physics is well-approximated by different string theories and string compactifications. The regions are connected by expanding "domain walls" but are not separated by causal horizons, and physical excitations can propagate between them. As specific examples we construct solutions that interpolate between oriented and unoriented string theories, and also between type II and heterotic theories. Our solutions can be weakly curved and under perturbative control everywhere and can asymptote to supersymmetric at late times.Comment: 35 pages, 5 figures, LaTeX v2: reference adde

Key stages in mammary gland development - Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ

Involution of the mammary gland is an essential process that removes the milk-producing epithelial cells when they become redundant at weaning. It is a two-step process that involves the death of the secretory epithelium and its replacement by adipo-cytes. During the first phase, remodelling is inhibited and apoptotic cells can be seen in the lumena of the alveoli. In the second phase, apoptosis is accompanied by remodelling of the surrounding stroma and re-differentiation of the adipocytes. Considerable effort has been directed towards understanding the molecular mechanisms of the involution process and this has resulted in the identification of the principal signalling pathways involved

Public consciousness and willingness to embrace ethical consumption of textile products in Mexico

The Mexican economy has been showing a continuous and arguably remarkable growth in the last decade, and it is expected that this strong economic growth is based on a balance between social equity, fiscal growth and environmental protection. This composite situation requires us to have a clear understanding of changes in consumer behaviour and their attitudes towards ethical consumerism in this region. With the use of a semi-structured questionnaire, this pilot study presented a detailed analysis of the consumer attitudes towards ethical consumerism in relation to their socio economic class levels in this region, the public consciousness and willingness to embrace ethical consumption of textile products in Mexico were thus determined. It is hoped that this knowledge provides the basis for the initiation of a framework of activities and measures to develop sustainable consumption habits and to educate consumers on the subject of ethical consumption

An experimental study on the response of blanket bog vegetation and water tables to ditch blocking

We studied the effect of ditch blocking on vegetation composition and water-table depths in a blanket peatland. Measurements were made for a period of four years (water tables) and five years (vegetation) in the inter-ditch areas of three experimental treatments: (i) open ditches, (ii) ditches blocked with closely-spaced dams and (iii) ditches partially infilled with peat and blocked with dams. It is often assumed that ditch blocking will lead to an increase in the abundance of Sphagnum and, potentially, a reduction in the abundance of sedges, particularly the cotton grasses. However, our data show no treatment effects on the abundance of either group. We did find an effect of time, with the abundance of both sedges and Sphagnum spp. varying significantly between some years. For the sedges there was no systematic change over time, while for the Sphagnum spp. abundance tended to increase through the study period. This systematic change was not related to a measure of the vigour of the sedges, although vigour was lower towards the end of the study compared to the beginning. Our vegetation data are consistent with our water-table data. As with plant type abundance, we did not find any statistically significant differences in water-table depths between treatments, both for annual averages and summer averages. We comment on why ditch blocking does not seem to have affected water tables and vegetation composition at our study site