Structure prediction of crystals, surfaces and nanoparticles

We review the current techniques used in the prediction of crystal structures and their surfaces and of the structures of nanoparticles. The main classes of search algorithm and energy function are summarized, and we discuss the growing role of methods based on machine learning. We illustrate the current status of the field with examples taken from metallic, inorganic and organic systems. This article is part of a discussion meeting issue 'Dynamic in situ microscopy relating structure and function'

Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

Beyond rhetoric in debates about the ethics of marketing prescription medicines to consumers: The importance of vulnerability in people, situations and relationships

Background This article examines community responses to the marketing of prescription medicines. Historically, debates about such marketing have focused on alleged unscrupulousness of pharmaceutical companies and on the quality of information provided. 2 Methods Six focus groups were conducted in Sydney, Australia, three with older and three with younger community members. Analysis examined interactions between group members, the positions participants took up, conflicting arguments, and explanations for variation. Results Participants argued specifically rather than generally about consumer marketing of medicines. Neither the moral purpose of corporations nor the quality of information in advertisements was particularly important. Instead, pharmaceutical marketing was assessed in relation to vulnerabilities that existed in individual consumers, in doctors, in the contexts of illness and as a result of medications being potentially dangerous. Conclusions The critical ethical issue in prescription medicine marketing may be the existence of vulnerabilities and the responsibilities they may generate. We outline three possible policy responses suggested by these participants. Key words: DTCA, direct-to-consumer advertising, marketing, vulnerability, doctor-patient relationship, drug industryAustralian National Health and Medical Research Council (NHMRC) Grant 457497

Genetic testing in exercise and sport - have direct-to-consumer genetic tests come of age?

The general consensus amongst sport and exercise genetics researchers is that genetic tests based on current knowledge have little or no role to play in talent identifi cation or the individualised prescription of training to maximise performance or minimise injury risk. Despite this, genetic tests related to sport and exercise are widely available on a commercial basis. This study assessed commercially-available genetic tests related to sport and exercise currently marketed via the internet. Twenty-two companies were identified as providing direct-to-consumer (DTC) genetic tests marketed in relation to human sport or exercise performance or injury. The most commonly-tested variant was the R577X SNP in the ACTN3 gene, tested by 85% of the 13 companies that appear to present information about their genetic tests on websites - which corresponds with our assessment that ACTN3 R577X is currently the polymorphism with the strongest scientific evidence in support of an association with sport and exercise phenotypes. 54% of companies that present information about their genetic tests used panels of 2-21 variants, including several with very limited supporting scientific evidence. 46% of companies tested just a single variant, with very low ability to explain complex sport and exercise phenotypes. It is particularly disappointing that 41% of companies off ering DTC genetic tests related to exercise and sport did not appear to state publicly the genetic variants they assess, making scrutiny by academic scholars and consumers impossible. Companies off ering DTC genetic tests related to sport and exercise should ensure that they are responsible in their activities

Prediction of sarcomere mutations in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomere protein mutations in hypertrophic cardiomyopathy induce subtle cardiac structural changes before the development of left ventricular hypertrophy (LVH). We have proposed that myocardial crypts are part of this phenotype and independently associated with the presence of sarcomere gene mutations. We tested this hypothesis in genetic hypertrophic cardiomyopathy pre-LVH (genotype positive, LVH negative [G+LVH-]). METHODS AND RESULTS: A multicenter case-control study investigated crypts and 22 other cardiovascular magnetic resonance parameters in subclinical hypertrophic cardiomyopathy to determine their strength of association with sarcomere gene mutation carriage. The G+LVH- sample (n=73) was 29 ± 13 years old and 51% were men. Crypts were related to the presence of sarcomere mutations (for ≥1 crypt, β=2.5; 95% confidence interval [CI], 0.5-4.4; P=0.014 and for ≥2 crypts, β=3.0; 95% CI, 0.8-7.9; P=0.004). In combination with 3 other parameters: anterior mitral valve leaflet elongation (β=2.1; 95% CI, 1.7-3.1; P<0.001), abnormal LV apical trabeculae (β=1.6; 95% CI, 0.8-2.5; P<0.001), and smaller LV end-systolic volumes (β=1.4; 95% CI, 0.5-2.3; P=0.001), multiple crypts indicated the presence of sarcomere gene mutations with 80% accuracy and an area under the curve of 0.85 (95% CI, 0.8-0.9). In this G+LVH- population, cardiac myosin-binding protein C mutation carriers had twice the prevalence of crypts when compared with the other combined mutations (47 versus 23%; odds ratio, 2.9; 95% CI, 1.1-7.9; P=0.045). CONCLUSIONS: The subclinical hypertrophic cardiomyopathy phenotype measured by cardiovascular magnetic resonance in a multicenter environment and consisting of crypts (particularly multiple), anterior mitral valve leaflet elongation, abnormal trabeculae, and smaller LV systolic cavity is indicative of the presence of sarcomere gene mutations and highlights the need for further study

Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years

Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50–52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme

ANALYSIS OF FUNCTIONS FOR THE EXTRAPOLATION OF RHEOLOGICAL PHENOMENA OF PRESTRESSING STEEL

BACKGROUND: The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context. The article explores how these factors influenced attitudes and behaviours towards TMT in Kayin (Karen) State, Myanmar. METHODS: Semi-structured interviews were conducted with villagers from study villages (N = 31) and TMT project staff (N = 14) between March and July 2015. RESULTS: Community engagement consisted of a range of activities to communicate the local malaria situation (including anti-malarial drug resistance and asymptomatic malaria), the aims of the TMT project, and its potential benefits. Community engagement was seen by staff as integral to the TMT project as a whole and not a sub-set of activities. Attitudes towards TMT (including towards community engagement) showed that developing trusting relationships helped foster participation. After initial wariness, staff received hospitality and acceptance among villagers. Offering healthcare alongside TMT proved mutually beneficial for the study and villagers. A handful of more socially-mobile and wealthy community members were reluctant to participate. The challenges of community engagement included time constraints and the isolation of the community with its limited infrastructure and a history of conflict. CONCLUSIONS: Community engagement had to be responsive to the local community even though staff faced time constraints. Understanding the social context of engagement helped TMT to foster respectful and trusting relationships. The complex relationship between the local context and community engagement complicated evaluation of the community strategy. Nonetheless, the project did record high levels of population coverage.</p

Genomics as a practical tool in sport - have we reached the starting line?

The genetic component of athletic performance approximates 50%, depending on which specific element of performance is considered. Limited genetic testing is already available commercially and genetic tests are likely to become powerful tools to improve sport performance in the future. Currently, however, selection of athletes for training squads or competition based on genomic data is premature. Larger volumes of longitudinal data within individual sports are needed to determine the efficacy of using genomic data in the management of elite athletes via manipulation of training load and diet based on personal genomic information

An approximate model for cancellous bone screw fixation

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Taylor & Francis.This paper presents a finite element (FE) model to identify parameters that affect the performance of an improved cancellous bone screw fixation technique, and hence potentially improve fracture treatment. In cancellous bone of low apparent density, it can be difficult to achieve adequate screw fixation and hence provide stable fracture fixation that enables bone healing. Data from predictive FE models indicate that cements can have a significant potential to improve screw holding power in cancellous bone. These FE models are used to demonstrate the key parameters that determine pull-out strength in a variety of screw, bone and cement set-ups, and to compare the effectiveness of different configurations. The paper concludes that significant advantages, up to an order of magnitude, in screw pull-out strength in cancellous bone might be gained by the appropriate use of a currently approved calcium phosphate cement

Experiences of parenting and clinical intervention for mothers affected by personality disorder: a pilot qualitative study combining parent and clinician perspectives

Background: Evidence-based parenting programmes are recommended for the treatment of child mental health difficulties. Families with complex psychosocial needs show poorer retention and outcomes when participating in standard parenting programmes. The Helping Families Programme (HFP) is a 16-week community-based parenting intervention designed to meet the needs of these families, including families with parental personality disorder. This study aimed to explore the help seeking and participatory experiences of parents with a diagnosis of personality disorder. It further aimed to examine the acceptability of referral and intervention processes for the HFP from the perspectives of (i) clinicians referring into the programme; and (ii) referred parents. Method: Semi-structured interviews were conducted with parents recruited to receive HFP (n = 5) as part of a research case series and the referring NHS child and adolescent mental health service (CAMHS) clinicians (n = 5). Transcripts were analysed using Interpretive Phenomenological Analysis. Results: Four themes were identified for parents: (i) the experience of parenthood, (ii) being a parent affected by personality disorder, (iii) experience of the intervention, and (iv) qualities of helping. Three themes emerged for clinicians: (i) challenges of addressing parental need, (ii) experience of engaging parents with personality disorders and (iii) limited involvement during HFP. Comparison of parent and clinician themes led to the identification of two key interlinked themes: (i) concerns prior to receiving the intervention, and (ii) the challenges of working together without a mutual understanding. Conclusions: This pilot study identifies potentially significant challenges of working with parents affected by personality disorder and engaging them in HFP and other similar interventions. Results have important wider clinical implications by highlighting potential barriers to engagement and participation and providing insights on how these barriers might be overcome. Findings have been used to inform the referral and intervention processes of a pilot RCT and further intervention development