A decision-based perspective for the design of methods for systems design

Organization of material, a definition of decision based design, a hierarchy of decision based design, the decision support problem technique, a conceptual model design that can be manufactured and maintained, meta-design, computer-based design, action learning, and the characteristics of decisions are among the topics covered

ABC for people with HIV: responses to sexual behaviour recommendations among people receiving antiretroviral therapy in Jinja, Uganda.

People living with HIV who are taking antiretroviral therapy (ART) are increasingly involved in 'positive prevention' initiatives. These are generally oriented to promoting abstinence, 'being faithful' (partner reduction) and condom use (ABC). We conducted a longitudinal qualitative study with people living with HIV using ART, who were provided with adherence education and counselling support by a Ugandan non-governmental organisation, The AIDS Support Organisation (TASO). Forty people were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic- or home-based) and HIV progression stage (early or advanced) and interviewed at enrollment and at 3, 6, 18 and 30 months. At initiation of ART, participants agreed to follow TASO's positive-living recommendations. Initially poor health prevented sexual activity. As health improved, participants prioritised resuming economic production and support for their children. With further improvements, sexual desire resurfaced and people in relationships cemented these via sex. The findings highlight the limitations of HIV prevention based on medical care/personal counselling. As ART leads to health improvements, social norms, economic needs and sexual desires increasingly influence sexual behaviour. Positive prevention interventions need to seek to modify normative and economic influences on sexual behaviour, as well as to provide alternatives to condoms

Factors Affecting Recruitment of Participants for Studies of Diabetes Technology in Newly Diagnosed Youth with Type 1 Diabetes: A Qualitative Focus Group Study with Parents and Children.

BACKGROUND: Relatively little is known about parents' or children's attitudes toward recruitment for, and participation in, studies of new diabetes technologies immediately after diagnosis. This study investigated factors affecting recruitment of participants for studies in newly diagnosed youth with type 1 diabetes. METHODS: Qualitative focus group study incorporating four recorded focus groups, conducted in four outpatient pediatric diabetes clinics in large regional hospitals in England. Participants comprised four groups of parents (n = 22) and youth (n = 17) with type 1 diabetes, purposively sampled on the basis of past involvement (either participation or nonparticipation) in an ongoing two-arm randomized trial comparing multiple daily injection with conventional continuous subcutaneous insulin infusion regimens from the onset of type 1 diabetes. RESULTS: Stress associated with diagnosis presents significant challenges in terms of study recruitment, with parents demonstrating varied levels of willingness to be approached soon after diagnosis. Additional challenges arise regarding the following: randomization when study arms are perceived as sharply differentiated in terms of therapy effectiveness; burdens arising from study participation; and the need to surrender new technologies following the end of the study. However, these challenges were mostly insufficient to rule out study participation. Participants emphasized the benefits and reassurance arising from support provided by staff and fellow study participants. CONCLUSIONS: Recruitment to studies of new diabetes technologies immediately after diagnosis in youth presents significant challenges, but these are not insurmountable. The stress and uncertainty arising from potential participation may be alleviated by personalized discussion with staff and peer support from fellow study participants.This work was supported by the National Institute of Health Research Cambridge Biomedical Research Centre; Wellcome Strategic Award (100574/Z/12/Z); Efficacy and Mechanism Evaluation, National Institutes for Health Research (#14/23/09); The Leona M. & Harry B. Helmsley Charitable Trust (#2016PG-T1D045); JDRF (#2-SRA- 2014-256-M-R).This is the final version of the article. It first appeared from Mary Ann Liebert via http://dx.doi.org/10.1089/dia.2016.015

Periosteum: biology, regulation, and response to osteoporosis therapies

Periosteum contains osteogenic cells that regulate the outer shape of bone and work in coordination with inner cortical endosteum to regulate cortical thickness and the size and position of a bone in space. Induction of periosteal expansion, especially at sites such as the lumbar spine and femoral neck, reduces fracture risk by modifying bone dimensions to increase bone strength. The cell and molecular mechanisms that selectively and specifically activate periosteal expansion, as well as the mechanisms by which osteoporosis drugs regulate periosteum, remain poorly understood. We speculate that an alternate strategy to protect human bones from fracture may be through targeting of the periosteum, either using current or novel agents. In this review, we highlight current concepts of periosteal cell biology, including their apparent differences from endosteal osteogenic cells, discuss the limited data regarding how the periosteal surface is regulated by currently approved osteoporosis drugs, and suggest one potential means through which targeting periosteum may be achieved. Improving our understanding of mechanisms controlling periosteal expansion will likely provide insights necessary to enhance current and develop novel interventions to further reduce the risk of osteoporotic fractures

Genetic and biochemical interactions between the bacterial replication initiator DnaA and the nucleoid-associated protein Rok in

We identified interactions between the conserved bacterial replication initiator and transcription factor DnaA and the nucleoid-associated protein Rok of Bacillus subtilis. DnaA binds directly to clusters of DnaA boxes at the origin of replication and elsewhere, including the promoters of several DnaA-regulated genes. Rok, an analog of H-NS from gamma-proteobacteria that affects chromosome architecture and of Lsr2 from Mycobacteria, binds A+T-rich sequences throughout the genome and represses expression of many genes. Using crosslinking and immunoprecipitation followed by deep sequencing (ChIP-seq), we found that DnaA was associated with eight previously identified regions containing clusters of DnaA boxes, plus 36 additional regions that were also bound by Rok. Association of DnaA with these additional regions appeared to be indirect as it was dependent on Rok and independent of the DNA-binding domain of DnaA. Gene expres sion and mutant analyses support a model in which DnaA and Rok cooperate to repress transcription of yxaJ, the yybNM operon and the sunA-bdbB operon. Our results indicate that DnaA modulates the activity of Rok. We postulate that this interaction might affect nucleoid architecture. Furthermore, DnaA might interact similarly with Rok analogues in other organisms.United States. Public Health Service (Grant GM41934

Are school-level factors associated with primary school students' experience of physical violence from school staff in Uganda?

BACKGROUND: The nature and structure of the school environment has the potential to shape children's health and well being. Few studies have explored the importance of school-level factors in explaining a child's likelihood of experiencing violence from school staff, particularly in low-resource settings such as Uganda. METHODS: To quantify to what extent a student's risk of violence is determined by school-level factors we fitted multilevel logistic regression models to investigate associations and present between-school variance partition coefficients. School structural factors, academic and supportive environment are explored. RESULTS: 53% of students reported physical violence from staff. Only 6% of variation in students' experience of violence was due to differences between schools and half the variation was explained by the school-level factors modelled. Schools with a higher proportion of girls are associated with increased odds of physical violence from staff. Students in schools with a high level of student perceptions of school connectedness have a 36% reduced odds of experiencing physical violence from staff, but no other school-level factor was significantly associated. CONCLUSION: Our findings suggest that physical violence by school staff is widespread across different types of schools in this setting, but interventions that improve students' school connectedness should be considered

Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial.

AIMS/HYPOTHESIS: The aim of this study was to compare the pharmacokinetics of two different concentrations of insulin aspart (B28Asp human insulin) in children aged 3-6 years with type 1 diabetes. METHODS: Young children with type 1 diabetes underwent an open-label, randomised, two-period crossover study in a clinical research facility, 2-6 weeks apart. In random order, diluted (1:5 dilution with saline [154 mmol/l NaCl]; 20 U/ml) or standard strength (100 U/ml) insulin aspart was administered via an insulin pump as a meal bolus and then overnight by closed-loop insulin delivery as determined by a model predictive algorithm. Plasma insulin was measured every 30-60 min from 17:00 hours on day 1 to 8:00 hours on day 2. We measured the time-to-peak insulin concentration (tmax), insulin metabolic clearance rate (MCR(I)) and background insulin concentration (ins(c)) using compartmental modelling. RESULTS: Eleven children (six male; age range 3.75-6.96 years, HbA1c 7.6% ± 1.3% [60 ± 14 mmol/mol], BMI standard deviation score 1.0 ± 0.8, duration of diabetes 2.2 ± 1.0 years, total daily dose 12.9 [10.6-16.5] U, fasting C-peptide concentration 5 [5-17.1] pmol/l; mean ± SD or median [interquartile range]) participated in the study. No differences between standard and diluted insulin were observed in terms of t max (59.2 ± 14.4 vs 61.6 ± 8.7) min for standard vs diluted, p = 0.59; MCR I (1.98 × 10(-2) ± 0.99 × 10(-2) vs 1.89 × 10(-2) ± 0.82 × 10(-2) 1/kg/min, p = 0.47), and ins c (34 [1-72] vs 23 [3-65] pmol/l, p = 0.66). However, t max showed less intersubject variability following administration of diluted aspart (SD 14.4 vs 8.7 min, p = 0.047). CONCLUSIONS/INTERPRETATION: Diluting insulin aspart does not change its pharmacokinetics. However, it may result in less variable absorption and could be used in young children with type 1 diabetes undergoing closed-loop insulin delivery. TRIAL REGISTRATION: Clinicaltrials.gov NCT01557634. FUNDING: FUNDING was provided by the JDRF, 7th Framework Programme of the European Union, Wellcome Trust Strategic Award and the National Institute for Health Research Cambridge Biomedical Research Centre.Funding was provided by the JDRF (grant number 22-2011- 668), 7th Framework Programme of the European Union (Spidiman project; grant agreement number 305343), Wellcome Trust Strategic Award (100574/Z/12/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-014-3483-6

Supervision and culture: Meetings at thresholds

Counsellors are required to engage in supervision in order to reflect on, reflexively review, and extend their practice. Supervision, then, might be understood as a partnership in which the focus of practitioners and supervisors is on ethical and effective practice with all clients. In Aotearoa/New Zealand, there has recently been interest in the implications for supervision of cultural difference, particularly in terms of the Treaty of Waitangi as a practice metaphor, and when non-Māori practitioners counsel Māori clients. This article offers an account of a qualitative investigation by a group of counsellors/supervisors into their experiences of supervision as cultural partnership. Based on interviews and then using writing-as-research, the article explores the playing out of supervision’s contribution to practitioners’ effective and ethical practice in the context of Aotearoa/New Zealand, showing a range of possible accounts and strategies and discussing their effects. Employing the metaphor of threshold, the article includes a series of reflections and considerations for supervision practice when attention is drawn to difference