An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Race-to-the-bottom or -top at home or abroad: Health and safety standards and the multinational firm

We develop a model to illustrate potential complexities in the relationship between corporate geographical diversification and the health and safety (H&S) standards set in national jurisdictions. A firm, that initially has a plant in its home country, may choose to also have one or two foreign plants in order to improve its bargaining position versus local governments, and so ensure reduced H&S standards, i.e. a race-to-the-bottom. However, contrary to the main focus of the popular debate on this topic, we note the potential for the race-to-the-bottom tendency to be exerted on H&S standards in the multinational company’s home rather than host country, and also for an upward push on H&S to instead result.

The Copenhagen principles on the handling of detainees: implications for the procedural regulation of internment

The Copenhagen Principles on the Handling of Detainees in International Military Operations were released in October 2012 after a five-year long process involving states and certain organizations. The Principles address a number of issues concerning the handling and transfer of detainees. They apply in military operations conducted by states abroad in the context of non-international armed conflicts and peace operations. This article focuses on those principles that address the procedural regulation of internment (ie preventive, security detention), as it is here that the current law is particularly unclear. On the one hand, the treaty provisions applicable in non-international armed conflicts contain no rules on the procedural regulation of internment, in comparison with the law of international armed conflict. On the other hand, the relevant rules under international human rights law (IHRL) appear derogable in such situations. This article demonstrates that the approach taken to this issue in the Copenhagen Principles is one which essentially draws on the procedural rules applicable to civilian internment in the international armed conflicts. These rules adopt standards that are lower than those under IHRL. Reference is then made to other recent practice, which illustrates that the Copenhagen Principles do not apply in a legal vacuum. In particular, two recent judicial developments highlight the continued relevance of human rights law and domestic law, respectively, in regulating detention operations in the context of international military operations. Compliance with the Copenhagen Principles may not, therefore, be sufficient for detention to be lawful.

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene 1-3.

BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.

A study of anticipatory non-autonomous systems

Rhythms are manifested ubiquitously in dynamical biological processes. These fundamental processes which are necessary for the survival of living organisms include metabolism, breathing, heart beat, and, above all, the circadian rhythm coupled to the diurnal cycle. Thus, in mathematical biology, biological processes are often represented as linear or nonlinear oscillators. In the framework of nonlinear and dissipative systems (ie. the flow of energy, substances, or sensory information), they generate stable internal oscillations as a response to environmental input and, in turn, utilise such output as a means of coupling with the environment.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Temporality, cultural biography and seasonality: rethinking time in wetland archaeology

Wetland archaeology is uniquely well placed to investigate questions of chronology, temporality, life-cycles and seasonality. Beyond the usual archaeological approaches to time (eg seriation, typology and stratigraphy), most wetland archaeological investigations have access to a ready supply of samples (ie wood, peat and organic deposits) for absolute scientific dating, particularly radiocarbon and dendrochronology. Indeed, the success of dendrochronology in revealing dynamic sequences of site and regional occupation, use and abandonment are well known. Investigating wetland archaeological sites, environmental archaeologists have used the evidence of insects' plant remains, seeds and even testate amoeba to establish the season, or months, of a site's occupation. Soil micromorphologists have carried out innovative studies of settlement deposits to reconstruct the chronological sequences of processes and events leading to their formation. In brief, wetland archaeology has become adept at calibrating past times.

Bioethics through the telescope: institutional ethics in the NHS

The article argues for a broader conception of bioethics. The principles that dominate current thinking are generally individualistic and do not represent the real world inhabited by patients, doctors, hospitals and the NHS as a whole. Rather than focus almost exclusively on the micro-end of the analytical spectrum, bioethics, and medical lawyers in particular, should take the institutional dimensions of health and health care more seriously, ie use a telescope to understand the dynamics that drive the subject, not just a microscope.

Proximity, strategic groups and reputation: an exploratory study of reputation in higher education

This paper explores the idea that stakeholder proximity, that is, how much/little experience a stakeholder has with a focal organization, impacts the extent to which stakeholders rely on strategic group characteristics as an anchor when judging the reputation of higher education institutions. We synthesize theories from psychology (ie, cognitive categorization theory) and management (ie, strategic group theory) to explore how stakeholder proximity may influence the formation of organizational reputation. Specifically, we examine how the proximity of three key stakeholders (N=1,049; prospective students, parents of students and hiring managers of new graduates) influences the perceived strategic character and generalized favorability of three distinct groups of post-secondary institutions (research-intensive universities, teaching-intensive universities and career colleges). Our results suggest that high proximity stakeholders rely less on strategic group characteristics, while reputation at a strategic group level is suggested to have greater influence on stakeholders who have less direct experience of and low proximity to an organization. Interestingly, our findings reveal some consistent differences between perceptions of prospective students and hiring managers that pose important theoretical questions about the role and impact of direct experiences in the reputation-building process, while also suggesting that higher education institutions may benefit significantly from differentiated marketing strategies according to issues of proximity.