Duration-dependent effects of the BDNF Val66Met polymorphism on anodal tDCS induced motor cortex plasticity in older adults: a group and individual perspective

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism and stimulation duration are thought to play an important role in modulating motor cortex plasticity induced by non-invasive brain stimulation (NBS). In the present study we sought to determine whether these factors interact or exert independent effects in older adults. Fifty-four healthy older adults (mean age = 66.85 years) underwent two counterbalanced sessions of 1.5 mA anodal transcranial direct current stimulation (atDCS), applied over left M1 for either 10 or 20 min. Single pulse transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability (CSE) before and every 5 min for 30 min following atDCS. On a group level, there was an interaction between stimulation duration and BDNF genotype, with Met carriers (n = 13) showing greater post-intervention potentiation of CSE compared to Val66Val homozygotes homozygotes (n = 37) following 20 min (p = 0.002) but not 10 min (p = 0.219) of stimulation. Moreover, Met carriers, but not Val/Val homozygotes, exhibited larger responses to TMS (p = 0.046) after 20 min atDCS, than following 10 min atDCS. On an individual level, two-step cluster analysis revealed a considerable degree of inter-individual variability, with under half of the total sample (42%) showing the expected potentiation of CSE in response to atDCS across both sessions. Intra-individual variability in response to different durations of atDCS was also apparent, with one-third of the total sample (34%) exhibiting LTP-like effects in one session but LTD-like effects in the other session. Both the inter-individual (p = 0.027) and intra-individual (p = 0.04) variability was associated with BDNF genotype. In older adults, the BDNF Val66Met polymorphism along with stimulation duration appears to play a role in modulating tDCS-induced motor cortex plasticity. The results may have implications for the design of NBS protocols for healthy and diseased aged populations.

Comparisons of anterior segment biometry between Chinese and Caucasians using anterior segment optical coherence tomography.

PURPOSE: To compare anterior segment parameters between eyes of Chinese and Caucasians using anterior segment optical coherence tomography and to evaluate the association between these parameters and anterior chamber angle width between the two ethnic groups. METHODS: 60 Chinese and 60 Caucasians, 30 with open angles and 30 with narrow angles (defined as Shaffer grade < or =2 in > or =3 quadrants during dark room gonioscopy) in each group, were consecutively enrolled. One eye of each subject was randomly selected for imaging in a completely darkened room. Measurements, including anterior chamber depth (ACD), scleral spur-to-scleral spur distance (anterior chamber width (ACW)), anterior chamber angle width, iris convexity and iris thickness, were compared between the groups. The associations between angle opening distance and biometric measurements were evaluated with univariate and multivariate regression analyses. RESULTS: There were no differences in age, axial length, anterior chamber angle measurements, pupil diameter and iris convexity between Chinese and Caucasians in both open-angle and narrow-angle groups. However, the ACD and ACW were smaller and the iris was thicker in Chinese. In the multivariate analysis, the ACD was the most influential biometric parameter for angle opening distance in both Chinese and Caucasians. After adjusting the effects of axial length, age and sex, ACD and ACW were significantly smaller in Chinese. CONCLUSIONS: Chinese eyes had smaller ACD, smaller ACW and greater iris thickness than Caucasians. ACD was the most influential parameter in determining the angle width in both ethnic groups.

Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.

METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.

RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.

CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Exploring the needs, concerns and knowledge of women diagnosed with gestational diabetes: A qualitative study

Objective
To explore the concerns, needs and knowledge of women diagnosed with Gestational Diabetes Mellitus (GDM).
Design
A qualitative study of women with GDM or a history of GDM.
Methods
Nineteen women who were both pregnant and recently diagnosed with GDM or post- natal with a recent history of GDM were recruited from outpatient diabetes care clinics. This qualitative study utilised focus groups. Participants were asked a series of open-ended questions to explore 1) current knowledge of GDM; 2) anxiety when diagnosed with GDM, and whether this changed overtime; 3) understanding and managing GDM and 4) the future impact of GDM. The data were analysed using a conventional content analysis approach.
Findings
Women experience a steep learning curve when initially diagnosed and eventually become skilled at managing their disease effectively. The use of insulin is associated with fear and guilt. Diet advice was sometimes complex and not culturally appropriate. Women appear not to be fully aware of the short or long-term consequences of a diagnosis of GDM.
Conclusions
Midwives and other Health Care Professionals need to be cognisant of the impact of a diagnosis of GDM and give individual and culturally appropriate advice (especially with regards to diet). High quality, evidence based information resources need to be made available to this group of women. Future health risks and lifestyle changes need to be discussed at diagnosis to ensure women have the opportunity to improve their health.

The large- and small-scale Ca IIK structure of the Milky Way from observations of Galactic and Magellanic sightlines

Aims. The large and small-scale (pc) structure of the Galactic interstellar medium can be investigated by utilising spectra of early-type stellar probes of known distances in the same region of the sky. This paper determines the variation in line strength of Ca ii at 3933.661 Å as a function of probe separation for a large sample of stars, including a number of sightlines in the Magellanic Clouds. 

Methods. FLAMES-GIRAFFE data taken with the Very Large Telescope towards early-type stars in 3 Galactic and 4 Magellanic open clusters in Ca ii are used to obtain the velocity, equivalent width, column density, and line width of interstellar Galactic calcium for a total of 657 stars, of which 443 are Magellanic Cloud sightlines. In each cluster there are between 43 and 111 stars observed. Additionally, FEROS and UVES Ca ii K and Na i D spectra of 21 Galactic and 154 Magellanic early-type stars are presented and combined with data from the literature to study the calcium column density - parallax relationship. 

Results. For the four Magellanic clusters studied with FLAMES, the strength of the Galactic interstellar Ca ii K equivalent width on transverse scales from ∼0.05-9 pc is found to vary by factors of ∼1.8-3.0, corresponding to column density variations of ∼0.3-0.5 dex in the optically-thin approximation. Using FLAMES, FEROS, and UVES archive spectra, the minimum and maximum reduced equivalent widths for Milky Way gas are found to lie in the range ∼35-125 mÅ and ∼30-160 mÅ for Ca ii K and Na i D, respectively. The range is consistent with a previously published simple model of the interstellar medium consisting of spherical cloudlets of filling factor ∼0.3, although other geometries are not ruled out. Finally, the derived functional form for parallax (π) and Ca ii column density (N_CaII) is found to be π(mas) = 1 / (2.39 × 10^-13 × N_CaII (cm^-2) + 0.11). Our derived parallax is ∼25 per cent lower than predicted by Megier et al. (2009, A&A, 507, 833) at a distance of ∼100 pc and ∼15 percent lower at a distance of ∼200 pc, reflecting inhomogeneity in the Ca ii distribution in the different sightlines studied.

“Islands” in Holocene forests: implications for forest openness, landscape clearance and “culture-steppe” species

Human activity has undoubtedly had a major impact on Holocene forested ecosystems, with the concurrent expansion of plants and animals associated with cleared landscapes and pasture, also known as 'culture-steppe'. However, this anthropogenic perspective may have underestimated the contribution of autogenic disturbance (e.g. wind-throw, fire), or a mixture of autogenic and anthropogenic processes, within early Holocene forests. Entomologists have long argued that the north European primary forest was probably similar in structure to pasture woodland. This idea has received support from the conservation biologist Frans Vera, who has recently strongly argued that the role of large herbivores in maintaining open forests in the primeval landscapes of Europe has been seriously underestimated. This paper reviews this debate from a fossil invertebrate perspective and looks at several early Holocene insect assemblages. Although wood taxa are indeed important during this period, species typical of open areas and grassland and dung beetles, usually associated with the dung of grazing animals, are persistent presences in many early woodland faunas. We also suggest that fire and other natural disturbance agents appear to have played an important ecological role in some of these forests, maintaining open areas and creating open vegetation islands within these systems. More work, however, is required to ascertain the role of grazing animals, but we conclude that fossil insects have a significant contribution to make to this debate. This evidence has fundamental implications in terms of how the palaeoecological record is interpreted, particularly by environmental archaeologists and palaeoecologists who may be more interested in identifying human-environment interactions rather than the ecological processes which may be preserved within palaeoecological records.

Computational challenges in atomic, molecular and optical physics

Six challenges are discussed. These are the laser-driven helium atom; the laser-driven hydrogen molecule and hydrogen molecular ion: electron scattering (with ionization) from one-electron atoms; the vibrational and rotational structure of molecules such as H-3(+) and water at their dissociation limits; laser- heated clusters; and quantum degeneracy and Bose-Einstein condensation. The first four concern fundamental few-body systems where use of high-performance computing (HPC) is currently making possible accurate modelling from first principles. This leads to reliable predictions and support for laboratory experiment as well as true understanding of the dynamics. Important aspects of these challenges addressable only via a terascale facility are set out. Such a facility makes the last two challenges in the above list meaningfully accessible for the first time, and the scientific interest together with the prospective role for HPC in these is emphasized.

Depressed mood and dietary fish intake: Direct relationship or indirect relationship as a result of diet and lifestyle?

Previous studies have suggested an association between depressed mood and the dietary intake of fish. In all cases, however, dietary fish intake has been considered at the exclusion of all other aspects of the diet. This analysis investigates associations between depressed mood and dietary fish intake, while also concurrently investigating intake of a number of other dietary components. The analysis is conducted on data from 10,602 men from Northern Ireland and France screened for inclusion into the PRIME cohort study. Depressed mood was assessed using a self-report questionnaire based on the Welsh Pure Depression sub-scale of the Minnesota Multiphasic Personality Inventory, diet was assessed using a Food Frequency Questionnaire, and limited demographics were also measured. Using regression, depressed mood is initially inversely associated with dietary fish intake. On inclusion of all other dietary variables, the strength of this relationship reduces but remains, and significant associations with a number of other foods are also found. On additional inclusion of all demographic variables, the strength of the above relationships again reduces, and associations with various measures of socio-economic status and education are also significant. These findings suggest that depressed mood is associated with fish intake both directly, and indirectly as part of a diet that is associated with depression and as part of a lifestyle that is associated with depression. Additional support for these conclusions is also provided in the pattern of associations between depressed mood and diet in the two countries. The relative contributions of fish intake to depressed mood both directly and indirectly are yet to be determined. However, while diet is not measured and until lifestyle can be adequately measured, the potential roles of diet and lifestyle in the association between depressed mood and dietary fish intake should not be ignored.

Monoamines and decision making during contests in the hermit crab Pagurus bernhardus

During fights animals are expected to make a series of strategic decisions that involve interactions between information about the contest and the individual's nervous system that produce a change in behaviour. Biogenic monoamines such as serotonin ('5-HT') and dopamine are thought to prime decision-making centres for appropriate responses during aggressive interactions in crustaceans, and circulating levels vary both between individuals and during agonistic encounters. Aminergenic systems operate in diverse animal taxa and in this study we assayed circulating levels of S-HT and dopamine following shell fights in the common European hermit crab, Pagurus bernhardus. The two roles in these fights, attacker and defender, perform different activities but, in both, S-HT increased and dopamine declined in response to engaging in a fight. In defenders but not attackers, giving up was correlated with low 5-HT and dopamine. In attackers, motivation to initiate a fight was positively correlated with dopamine levels. Circulating monoamines are therefore involved in decision making during these aggressive encounters. (c) 2007 The Association for the Study of Animal Behaviour Published by Elsevier Ltd. All rights reserved.

Identifying strategies to maximise recruitment and retention of practices and patients in a multicentre randomised controlled trial of an intervention to optimise secondary prevention for coronary heart disease in primary care.

Background Recruitment and retention of patients and healthcare providers in randomised controlled trials (RCTs) is important in order to determine the effectiveness of interventions. However, failure to achieve recruitment targets is common and reasons why a particular recruitment strategy works for one study and not another remain unclear. We sought to describe a strategy used in a multicentre RCT in primary care, to report researchers’ and participants’ experiences of its implementation and to inform future strategies to maximise recruitment and retention. Methods In total 48 general practices and 903 patients were recruited from three different areas of Ireland to a RCT of an intervention designed to optimise secondary prevention of coronary heart disease. The recruitment process involved telephoning practices, posting information, visiting practices, identifying potential participants, posting invitations and obtaining consent. Retention involved patients attending reviews and responding to questionnaires and practices facilitating data collection. Results We achieved high retention rates for practices (100%) and for patients (85%) over an 18-month intervention period. Pilot work, knowledge of the setting, awareness of change in staff and organisation amongst participant sites, rapid responses to queries and acknowledgement of practitioners’ contributions were identified as being important. Minor variations in protocol and research support helped to meet varied, complex and changing individual needs of practitioners and patients and encouraged retention in the trial. A collaborative relationship between researcher and practice staff which required time to develop was perceived as vital for both recruitment and retention. Conclusions Recruiting and retaining the numbers of practices and patients estimated as required to provide findings with adequate power contributes to increased confidence in the validity and generalisability of RCT results. A continuous dynamic process of monitoring progress within trials and tailoring strategies to particular circumstances, whilst not compromising trial protocols, should allow maximal recruitment and retention.

Effect of Mix Proportions on Rheological and Hardened Properties of Composite Cement Pastes

There is an increasing need to identify the effect of mix composition on the rheological properties of composite cement pastes using simple tests to determine the fluidity, the cohesion and other mechanical properties of grouting applications such as compressive strength. This paper reviews statistical models developed using a fractional factorial design which was carried out to model the influence of key parameters on properties affecting the performance of composite cement paste. Such responses of fluidity included mini-slump, flow time using Marsh cone and cohesion measured by Lombardi plate meter and unit weight, and compressive strength at 3 d, 7 d and 28 d. The models are valid for mixes with 0.35 to 0.42 water-to-binder ratio (W/B), 10% to 40% of pulverised fuel ash (PFA) as replacement of cement by mass, 0.02 to 0.06% of viscosity enhancer admixture (VEA), by mass of binder, and 0.3 to 1.2% of superplasticizer (SP), by mass of binder. The derived models that enable the identification of underlying primary factors and their interactions that influence the modelled responses of composite cement paste are presented. Such parameters can be useful to reduce the test protocol needed for proportioning of composite cement paste. This paper attempts also to demonstrate the usefulness of the models to better understand trade-offs between parameters and compare the responses obtained from the various test methods which are highlighted. The multi parametric optimization is used in order to establish isoresponses for a desirability function of cement composite paste. Results indicate that the replacement of cement by PFA is compromising the early compressive strength and up 26%, the desirability function decreased.