“Am I my genes?”: Questions of identity among individuals confronting genetic disease

Purpose: To explore many questions raised by genetics concerning personal identities that have not been fully investigated. Methods: We interviewed in depth, for 2 hours each, 64 individuals who had or were at risk for Huntington disease, breast cancer, or alpha-1 antitrypsin deficiency. Results: These individuals struggled with several difficult issues of identity. They drew on a range of genotypes and phenotypes (e.g., family history alone; mutations, but no symptoms; or symptoms). They often felt that their predicament did not fit preexisting categories well (e.g., “sick,” “healthy,” “disabled,” “predisposed”), due in part to uncertainties involved (e.g., unclear prognoses, since mutations may not produce symptoms). Hence, individuals varied in how much genetics affected their identity, in what ways, and how negatively. Factors emerged related to disease, family history, and other sources of identity. These identities may, in turn, shape disclosure, coping, and other health decisions. Conclusions: Individuals struggle to construct a genetic identity. They view genetic information in highly subjective ways, varying widely in what aspects of genetic information they focus on and how. These data have important implications for education of providers (to assist patients with these issues), patients, and family members; and for research, to understand these issues more fully

The Rossiter-McLaughlin effect in Exoplanet Research

The Rossiter-McLaughlin effect occurs during a planet's transit. It provides the main means of measuring the sky-projected spin-orbit angle between a planet's orbital plane, and its host star's equatorial plane. Observing the Rossiter-McLaughlin effect is now a near routine procedure. It is an important element in the orbital characterisation of transiting exoplanets. Measurements of the spin-orbit angle have revealed a surprising diversity, far from the placid, Kantian and Laplacian ideals, whereby planets form, and remain, on orbital planes coincident with their star's equator. This chapter will review a short history of the Rossiter-McLaughlin effect, how it is modelled, and will summarise the current state of the field before describing other uses for a spectroscopic transit, and alternative methods of measuring the spin-orbit angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI

Moderate Multiple Parentage and Low Genetic Variation Reduces the Potential for Genetic Incompatibility Avoidance Despite High Risk of Inbreeding

Background: Polyandry is widespread throughout the animal kingdom. In the absence of direct benefits of mating with different males, the underlying basis for polyandry is enigmatic because it can carry considerable costs such as elevated exposure to sexual diseases, physical injury or other direct fitness costs. Such costs may be balanced by indirect genetic benefits to the offspring of polyandrous females. We investigated polyandry and patterns of parentage in the spider Stegodyphus lineatus. This species experiences relatively high levels of inbreeding as a result of its spatial population structure, philopatry and limited male mating dispersal. Polyandry may provide an opportunity for post mating inbreeding avoidance that reduces the risk of genetic incompatibilities arising from incestuous matings. However, multiple mating carries direct fitness costs to females suggesting that genetic benefits must be substantial to counter direct costs. Methodology/Principal Findings: Genetic parentage analyses in two populations from Israel and a Greek island, showed mixed-brood parentage in approximately 50 % of the broods. The number of fathers ranged from 1–2 indicating low levels of multiple parentage and there was no evidence for paternity bias in mixed-broods from both populations. Microsatellite loci variation suggested limited genetic variation within populations, especially in the Greek island population. Relatedness estimates among females in the maternal generation and potentially interacting individuals were substantial indicating fullsib and half-sib relationships

Assortative Mating in Fallow Deer Reduces the Strength of Sexual Selection

Background: Assortative mating can help explain how genetic variation for male quality is maintained even in highly polygynous species. Here, we present a longitudinal study examining how female and male ages, as well as male social dominance, affect assortative mating in fallow deer (Dama dama) over 10 years. Assortative mating could help explain the substantial proportion of females that do not mate with prime-aged, high ranking males, despite very high mating skew. We investigated the temporal pattern of female and male matings, and the relationship between female age and the age and dominance of their mates. Results: The peak of yearling female matings was four days later than the peak for older females. Younger females, and especially yearlings, mated with younger and lower-ranking males than older females. Similarly, young males and lowerranking males mated with younger females than older males and higher-ranking males. Furthermore, the timing of matings by young males coincided with the peak of yearling female matings, whereas the timing of older male matings (irrespective of rank) coincided with the peak of older female matings. Conclusions: Assortative mating, through a combination of indirect and/or direct female mate choice, can help explain th

A systematic review of patient reported factors associated with uptake and completion of cardiovascular lifestyle behaviour change

Background: Healthy lifestyles are an important facet of cardiovascular risk management. Unfortunately many individuals fail to engage with lifestyle change programmes. There are many factors that patients report as influencing their decisions about initiating lifestyle change. This is challenging for health care professionals who may lack the skills and time to address a broad range of barriers to lifestyle behaviour. Guidance on which factors to focus on during lifestyle consultations may assist healthcare professionals to hone their skills and knowledge leading to more productive patient interactions with ultimately better uptake of lifestyle behaviour change support. The aim of our study was to clarify which influences reported by patients predict uptake and completion of formal lifestyle change programmes. Methods: A systematic narrative review of quantitative observational studies reporting factors (influences) associated with uptake and completion of lifestyle behaviour change programmes. Quantitative observational studies involving patients at high risk of cardiovascular events were identified through electronic searching and screened against pre-defined selection criteria. Factors were extracted and organised into an existing qualitative framework. Results: 374 factors were extracted from 32 studies. Factors most consistently associated with uptake of lifestyle change related to support from family and friends, transport and other costs, and beliefs about the causes of illness and lifestyle change. Depression and anxiety also appear to influence uptake as well as completion. Many factors show inconsistent patterns with respect to uptake and completion of lifestyle change programmes. Conclusion: There are a small number of factors that consistently appear to influence uptake and completion of cardiovascular lifestyle behaviour change. These factors could be considered during patient consultations to promote a tailored approach to decision making about the most suitable type and level lifestyle behaviour change support

Reproducibility and repeatability of peripheral microvascular assessment using lontophoresis in conjunction with laser doppler imaging

Interrogation of peripheral vascular function is increasingly recognized as a noninvasive surrogate marker for coronary vascular function and carries with it important prognostic information regarding future cardiovascular risk. Laser Doppler imaging (LDI) is a completely noninvasive method for looking at peripheral microvascular function. We sought to look at reproducibility and repeatability of LDI-derived assessment of peripheral microvascular function between arms and 8 weeks apart. We used LDI in conjunction with iontophoretic application of ACh and SNP to look at endothelium-dependent and -independent microvascular function, respectively, in a mixture of women with cardiac syndrome X and healthy volunteers. We looked at variation between arms (n = 40) and variation at 8 weeks apart (n = 22). When measurements were corrected for skin resistance, there was nonsignificant variation between arms for ACh (2.7%) and SNP (3.8%) and nonsignificant temporal variation for ACh (3.5%) and SNP (4.7%). Construction of Bland-Altman plots reinforce that measurements have good repeatability. Elimination of the baseline perfusion response had deleterious effects on repeatability. LDI can be used to assess peripheral vascular response with good repeatability as long as measurements are corrected for skin resistance, which affects drug delivery. This has important implications for the future use of LDI

Evidence-based estimation of insulin resistance

Insulin resistance is a complex phenotype. Surrogate markers based on peripheral glucose and insulin (and in some cases NEFA) concentrations can provide, at best, moderate approximations to direct physiological measurements (Pearson r values 0.6–0.7). Where the focus is solely on insulin resistance, the evidence reviewed in the paper by Otten et al in this issue (DOI: 10.1007/s00125-014-3285-x) suggests that surrogate markers based on fasting samples alone are as valid as those that require multiple samples and an oral glucose load. This provides an evidence base for simplifying the design of some clinical studies