Poor glycaemic control and ectopic fat deposition mediates the increased risk of non-alcoholic steatohepatitis in high-risk populations with type 2 diabetes: Insights from Bayesian-network modelling.

Background: An estimated 55.5% and 37.3% of people globally with type 2 diabetes (T2D) will have concomitant non-alcoholic fatty liver disease (NAFLD) and the more severe fibroinflammatory stage, non-alcoholic steatohepatitis (NASH). NAFLD and NASH prevalence is projected to increase exponentially over the next 20 years. Bayesian Networks (BNs) offer a powerful tool for modelling uncertainty and visualising complex systems to provide important mechanistic insight. Methods: We applied BN modelling and probabilistic reasoning to explore the probability of NASH in two extensively phenotyped clinical cohorts: 1) 211 participants with T2D pooled from the MODIFY study & UK Biobank (UKBB) online resource; and 2) 135 participants without T2D from the UKBB. MRI-derived measures of visceral (VAT), subcutaneous (SAT), skeletal muscle (SMI), liver fat (MRI-PDFF), liver fibroinflammatory change (liver cT1) and pancreatic fat (MRI-PDFF) were combined with plasma biomarkers for network construction. NASH was defined according to liver PDFF >5.6% and liver cT1 >800ms. Conditional probability queries were performed to estimate the probability of NASH after fixing the value of specific network variables. Results: In the T2D cohort we observed a stepwise increase in the probability of NASH with each obesity classification (normal weight: 13%, overweight: 23%, obese: 36%, severe obesity: 62%). In the T2D and non-T2D cohorts, elevated (vs. normal) VAT conferred a 20% and 1% increase in the probability of NASH, respectively, while elevated SAT caused a 7% increase in NASH risk within the T2D cohort only. In those with T2D, reducing HbA1c from the 'high' to 'low' value reduced the probability of NASH by 22%. Conclusion: Using BNs and probabilistic reasoning to study the probability of NASH, we highlighted the relative contribution of obesity, ectopic fat (VAT and liver) and glycaemic status to increased NASH risk, namely in people with T2D. Such modelling can provide insights into the efficacy and magnitude of public health and pharmacological interventions to reduce the societal burden of NASH.

Plio-Pleistocene history and phylogeography of Acacia senegal in dry woodlands and savannahs of sub-Saharan tropical Africa: evidence of early colonisation and recent range expansion.

Drylands are extensive across sub-Saharan Africa, socio-economically and ecologically important yet highly sensitive to environmental changes. Evolutionary history, as revealed by contemporary intraspecific genetic variation, can provide valuable insight into how species have responded to past environmental and population changes and guide strategies to promote resilience to future changes. The gum arabic tree (Acacia senegal) is an arid-adapted, morphologically diverse species native to the sub-Saharan drylands. We used variation in nuclear sequences (internal transcribed spacer (ITS)) and two types of chloroplast DNA (cpDNA) markers (PCR-RFLP, cpSSR) to study the phylogeography of the species with 293 individuals from 66 populations sampled across its natural range. cpDNA data showed high regional and rangewide haplotypic diversity (h(T(cpSSR))=0.903-0.948) and population differentiation (G(ST(RFLP))=0.700-0.782) with a phylogeographic pattern that indicated extensive historical gene flow via seed dispersal. Haplotypes were not restricted to any of the four varieties, but showed significant geographic structure (G(ST(cpSSR))=0.392; R(ST)=0.673; R(ST)>R(ST) (permuted)), with the major division separating East and Southern Africa populations from those in West and Central Africa. Phylogenetic analysis of ITS data indicated a more recent origin for the clade including West and Central African haplotypes, suggesting range expansion in this region, possibly during the Holocene humid period. In conjunction with paleobotanical evidence, our data suggest dispersal to West Africa, and across to the Arabian Peninsula and Indian subcontinent, from source populations located in the East African region during climate oscillations of the Plio-Pleistocene.

Micropatterning of polymer brushes: grafting from dewetting polymer films for biological applications.

In this novel platform, a micropatterned polymer brush was obtained by grafting poly(poly(ethylene glycol) methyl ether methacrylate) (poly(PEGMA)) from a thin macroinitiator film using atom transfer radical polymerization (ATRP). A pattern of holes was formed in the macroinitiator film by taking advantage of its spontaneous dewetting above the glass transition temperature from a bottom polystyrene film, driven by unfavorable intermolecular forces. Patterning by dewetting can be achieved at length-scales from a few hundred nanometers to several tens of micrometers, by simply thermally annealing the bilayer above the glass transition temperature of the polymer. This approach is substrate-independent, as polymer films can be cast onto surfaces of different size, shape, or material. As a demonstration of its potential, proteins, and individual cells were attached on targeted bioadhesive polystyrene areas of the micropatterns within poly(PEGMA) protein-repellent brushes. We anticipate this approach will be suitable for the patterning of brushes, especially for biomedical applications such as in the study of single cells and of cell cocultures.

Examining ecosystem services and disservices through deliberative socio-cultural valuation.

The deliberative socio-cultural valuation of ecosystem services (ES) and disservices (EDS) is an understudied area of ES and EDS research. Participatory methods have been applied to ES and EDS valuation, but little is known on how these approaches could reveal and form shared values and impact decision-making. This paper presents the deliberative socio-cultural valuation of the Jose Rizal Plaza in Calamba City, The Philippines. The study aimed to assess how stakeholders value the ES and EDS of the park and examine how these values change in different situations. Online focus groups were carried out, and in each, the participants were asked to distribute importance and concern points to the various park ES and EDS, respectively. The valuation exercise was performed six times, changing the source and constituency of the valuation, and introducing discussions. Results confirm significant differences in the values assigned to several ES and EDS across the valuation exercises. Varying the sources and constituencies proved useful in revealing the participants' shared assigned values. The participants share a high appreciation for enjoyment and spending free time, sports and physical fitness, relaxation and mental recreation, social relationships, and local identity and cultural heritage. For EDS, they share a significant concern only for the risk of anti-social behaviour. This type of valuation could be further explored using other parks and cities to test if it will have consistent results. For the Jose Rizal Plaza, spaces for sports should be maintained and security should be improved.

Vitamin D deficiency predicts latent TB reactivation independent of preventive therapy: a longitudinal study.

BACKGROUND: Vitamin D deficiency is associated with progression of latent tuberculosis (TB) infection to active disease. The impact of preventive therapy on this association is unknown.METHOD: Serum 25-hydroxyvitamin D (25(OH)D) levels were retrospectively linked to adults diagnosed with latent TB between April 2010 and January 2019 in a hospital in London, UK. Individuals in the cohort who progressed to active TB were identified by matching to a national notification register. A logistic regression model was used to examine baseline vitamin D deficiency and use of preventive therapy with subsequent incidence of TB disease.RESULTS: Of 1509 latently infected individuals with 3902 patient-years of follow-up, 687 (45.5%) were identified as vitamin D deficient and 691 (45.8%) individuals had a LTBI regimen prescribed. There were 29 (1.9%) instances of TB reactivation. On multivariate analysis, profound (<25 nmol/L) vitamin D deficiency (aHR 5.68, 95%CI 2.18-14.82; P = 0.0003) and the absence of preventive therapy (aHR 3.84, 95%CI 1.46-10.08; P = 0.006) were associated with progression to active TB disease. There was no evidence that preventive therapy modified the association between vitamin D status and TB reactivation.CONCLUSION: Our results show an independent association between vitamin D deficiency and progression from latent TB infection to active disease.

Patterns of time use among regional and rural adolescent girls: Associations with correlates of physical activity and health-related quality of life.

OBJECTIVES: To describe patterns of time use among regional and rural adolescent girls and compare identified clusters with respect to correlates of physical activity (PA) and health-related quality of life (HRQoL). DESIGN: Cross-sectional PA and lifestyle survey. METHODS: Data were from Year 7-9 adolescent girls (aged 12-15 years) from 16 schools involved in a cluster-randomised trial in regional and rural Victoria, Australia (n=494). Time use data were collected using 24-h Previous Day Physical Activity Recall (PDPAR-24) questionnaire, collapsed into 17 categories of time use. Differences between time use clusters with regard to demographics, correlates of PA and HRQoL measured using PedsQL 4.0 Generic Core Scales, were investigated. RESULTS: Two time use clusters were identified and were associated with correlates of PA and HRQoL. Girls who spent significantly more time in teams sports, non-team sports, school classes, watching TV and sleeping had higher levels of positively aligned PA correlates (e.g. self-efficacy, perceived sports competence) and HRQoL than girls characterised with high levels of computer use and video gaming. CONCLUSIONS: These findings highlight how different activity patterns of regional and rural girls affect HRQoL and can inform future intervention strategies to improve PA levels and HRQoL. Clusters characterised by low levels of PA and high computer use and video gaming require targeted interventions to address barriers to their participation.

Attitude or access: reasons for not attending mammography in Northern Ireland.

Maximizing the uptake of mammography among the eligible population will be critical to the success of the national breast cancer screening programme. Although compliance may vary for different reasons from area to area, it has been suggested that making screening clinics more accessible may be an effective means of enhancing uptake. In the present study we undertook 600 interviews with women who had been invited for mammography to determine the main reasons given by women in Northern Ireland for not attending for mammography when invited, how these may have related to access factors and to discover their views on how the service might be improved. The most frequently cited reasons for non-attendance were related to feelings of indifference or ignorance of screening issues and to fear of pain or embarrassment. Although more non-attenders did not have access to private transport, few women (23/600) expressed a preference for more accessible clinics. The fact that non-attenders were more likely not to have had a recent cervical smear, adds weight to the notion that attitudes rather than access played the predominant role in influencing uptake in this sample. We have concluded that investment in flexible mobile screening units cannot replace the continued need for delivering effective advocacy to eligible women.

Enhancing mammography uptake: who do women listen to?

Previous work has established that women who attend for mammography differ from non-attenders in a number of socio-demographic and attitudinal characteristics. The present study was conducted to determine whether women who attended for mammography differed from non-attenders in a number of key areas: (1) in how they obtained information about screening; (2) in their understanding of the disease and basic screening precepts; and (3) in the extent to which they perceived their general practitioners (GPs) and other members of the primary case team, such as practice nurses, had actively promoted the programme. Three hundred attenders and 300 non-attenders were interviewed in their own homes using a structured questionnaire. Only 5% of women interviewed had ever asked their GP for any advice about breast screening, and only 18% recalled their family doctor every discussing or raising the subject with them. Although attenders and non-attenders differed significantly in their understanding of the scope and purpose of screening, both groups obtained information more often from friends and relatives and broadcast media than from official sources. Attenders were more likely to cite material in the GP's surgery as an important source of information (chi 2 = 5.1, p = 0.02). Attenders were marginally more likely than non-attenders to have previously attended a well-woman clinic in primary care (chi 2 = 3.1, p = 0.08) and were more likely to say that such clinics were being offered by their family doctor (chi 2 = 9.8, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of plasma and synovial fluid profiles of standard and controlled-release formulations of ketoprofen in patients with rheumatoid arthritis.

The plasma and synovial fluid profiles of standard and controlled-release formulations of ketoprofen were compared in 8 patients with rheumatoid arthritis. During chronic dosing with both forms of ketoprofen, peak drug concentrations were lower and occurred later in the synovial fluid than in the plasma. These findings were more pronounced in the case of the controlled-release formulation. The apparent elimination half-life of standard ketoprofen in synovial fluid was prolonged compared to its half-life in plasma, a finding which has not been previously documented. This may explain the clinical observation that, despite a very short plasma elimination half-life, standard ketoprofen exerts a satisfactory therapeutic effect when given twice daily. There was no accumulation of ketoprofen from either formulation in synovial fluid after steady state had been achieved. It is suggested that future pharmacological studies with anti-inflammatory agents should include both synovial fluid and plasma concentration data.

Is choice of general practitioner important for patients having coronary artery investigations?

OBJECTIVE: To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN: Postal questionnaire survey. SETTING: Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS: All (962) GPs. MAIN MEASURES: The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS: 541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION: GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.

Computer assisted learning (CAL) of oral manifestations of HIV disease.

General dental practitioners (GDPs) in the UK may wish additional education on relevant aspects of human immunodeficiency virus (HIV) disease. The aim of the present study was to develop and assess a computer assisted learning package on the oral manifestations of HIV disease of relevance to GDPs. A package was developed using a commercially-available software development tool and assessed by a group of 75 GDPs interested in education and computers. Fifty-four (72%) of the GDPs completed a self-administered questionnaire of their opinions of the package. The majority reported the package to be easy to load and run, that it provided clear instructions and displays, and that it was a more effective educational tool than videotapes, audiotapes, professional journals and textbooks, and of similar benefit as post-graduate courses. The GDPs often commented favourably on the effectiveness of the clinical images and use of questions and answers, although some had criticisms of these and other aspects of the package. As a consequence of this investigation the package has been modified and distributed to GDPs in England and Wales.

The impact of computers in dental education.

Computer technology is increasingly influencing many aspects of our lives and will continue to do so in the future. This paper discusses the impact of computers in dentistry; how their use is radically changing the way practices are run and the way under/postgraduate dental education is evolving, by incorporating computer-aided learning (CAL) material as an efficient and convenient educational tool. Greater computer literacy may result in a future where there is a shift away from traditional centres of learning to computer conferencing and distance learning.

Locations for renal services--patient satisfaction surveys.

Renal services have been given priority in recent years in an attempt to align them with levels of provision in other European countries. A survey of patients receiving renal replacement therapy in the Northern Ireland Regional Centre, Belfast, was carried out to ascertain their views on services (survey I). After the establishment of a Northern Health and Social Services Board (NHSSB) sub-regional unit in 1995, the survey was repeated for patients attending the new unit (survey II). In survey I, 53% NHSSB patients responded. Travelling time to and from hospital was a major issue for the majority of patients, with 33% of haemodialysis patients receiving twice weekly treatment unwilling to attend more frequently, even if clinically advised to do so. In survey II, 60% of patients responded. Travel times to the sub-regional unit were significantly shorter and patients felt it provided a similar or better standard of service, compared with the regional centre. All the twice weekly haemodialysis patients would increase to thrice weekly if clinically advised to do so. The study underlines the importance of locating dialysis facilities closer to patients' homes.

The winds of change: psychiatric nursing in Czechoslovakia.

This article examines the current state of psychiatry and psychiatric nursing within the Czechoslovakian Republic and is the result of the author's invitation to teach on the first Postgraduate Diploma in Cognitive Behavioural Psychotherapy run in Czechoslovakia.

Caring for people with learning difficulties in Czechoslovakia.

In June 1992 a massive step forward was made in Czechoslovakia when the first school for people with learning difficulties was opened. This article examines the problems facing this school and the background to its creation.

Perceptions of local neighbourhood environments and their relationship to childhood overweight and obesity.

OBJECTIVES: To examine associations between parent and child perceptions of the local neighbourhood and overweight/obesity among children aged 5-6 and 10-12 y. DESIGN: Cross-sectional survey. SUBJECTS: In total, 291 families of 5-6-y-old and 919 families of 10-12-y-old children. MEASURES: Parent's perceptions of local neighbourhood and perceived child access to eight local destinations within walking distance of home; 10-12-y-old children's perception of local neighbourhood; socio-demographic characteristics (survey). Children's height and weight (measured). RESULTS: No perceptions of the local neighbourhood were associated with weight status among 5-6-y-old children. Among 10-12-y-old children, those whose parents agreed that there was heavy traffic in their local streets were more likely to be overweight or obese (OR=1.4, 95% CI=1.0-1.8), and those whose parents agreed that road safety was a concern were more likely to be obese (OR=3.9, 95% CI=1.0-15.2), compared to those whose parents disagreed with these statements. CONCLUSIONS: This study suggests that parental perceptions of heavy traffic on local streets and concern about road safety may be indirect influences on overweight and obesity among 10-12-y-old children. Future work should also consider perceptions of the neighbourhood related to food choice.

Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome.

A randomised, double-blind, placebo controlled study of morbidity and mortality was carried out using heparin, atenolol, and a combination of both drugs, in 214 patients with the intermediate coronary syndrome. During the trial period, transmural myocardial infarction developed in 9 (17%) out of 54 patients on placebo, 8 (13%) out of 60 on atenolol, 1 (2%) out of 51 on heparin, and 2 (4%) out of 49 on heparin and atenolol combined (p = 0.024). The improved prognosis in the heparin-treated patients was was maintained at follow-up. All five deaths occurred among patients who did not receive heparin. These results show that intravenous heparin therapy was of benefit in preventing myocardial infarction in patients with the intermediate coronary syndrome.

Computer-aided learning in prosthodontics.

Interactive video is computer-aided learning illustrated by still or moving video pictures. First introduced for the study of pathology, its application and potential in prosthodontics is reported in this article. Partial denture design was chosen as the first subject, since the systematic approach concept could easily be established by dividing the subject into five units that could individually be expanded and tested. Students are generally enthusiastic about computer-aided learning and there is considerable potential to further develop this type of learning process.