How should we implement collaborative care for older people with depression? A qualitative study using normalisation process theory within the CASPER plus trial.

BACKGROUND: Depression in older people may have a prevalence as high as 20%, and is associated with physical co-morbidities, loss, and loneliness. It is associated with poorer health outcomes and reduced quality of life, and is under-diagnosed and under-treated. Older people may find it difficult to speak to their GPs about low mood, and GPs may avoid identifying depression due to limited consultation time and referral options for older patients. METHODS: A qualitative study nested within a randomised controlled trial for older people with moderate to severe depression: the CASPER plus Trial (Care for Screen Positive Elders). We interviewed patient participants, GPs, and case managers (CM) to explore patients' and professionals' views on collaborative care developed for older people, and how this model could be implemented at scale. Transcripts were analysed thematically using normalization process theory. RESULTS: Thirty-three interviews were conducted. Across the three data-sets, four main themes were identified based on the main principles of the Normalization Process Theory: understanding of collaborative care, interaction between patients and professionals, liaison between GPs and case managers, and the potential for implementation. CONCLUSIONS: A telephone-delivered intervention, incorporating behavioural activation, is acceptable to older people with depression, and is deliverable by case managers. The collaborative care framework makes sense to case managers and has the potential to optimize patient outcomes, but implementation requires integration in day to day general practice. Increasing GPs' understanding of collaborative care might improve liaison and collaboration with case managers, and facilitate the intervention through better support of patients. The CASPER plus model, delivering therapy to older adults with depression by telephone, offers the potential for implementation in a resource-poor health service.

Needles, Jabs and Jags: a qualitative exploration of barriers and facilitators to child and adult immunisation uptake among Gypsies, Travellers and Roma.

BACKGROUND: Gypsies, Travellers and Roma (referred to as Travellers) are less likely to access health services including immunisation. To improve immunisation rates, it is necessary to understand what helps and hinders individuals in these communities in taking up immunisations. This study had two aims. 1. Investigate the views of Travellers in the UK on the barriers and facilitators to acceptability and uptake of immunisations and explore their ideas for improving immunisation uptake; 2. Examine whether and how these responses vary across and within communities, and for different vaccines (childhood and adult). METHODS: This was a qualitative, cross-sectional interview study informed by the Social Ecological Model. Semi-structured interviews were conducted with 174 Travellers from six communities: Romanian Roma, English Gypsy/Irish Travellers (Bristol), English Gypsy (York), Romanian/Slovakian Roma, Scottish Show people (Glasgow) and Irish Traveller (London). The focus was childhood and selected adult vaccines. Data were analysed using the Framework approach. RESULTS: Common accounts of barriers and facilitators were identified across all six Traveller communities, similar to those documented for the general population. All Roma communities experienced additional barriers of language and being in a new country. Men and women described similar barriers and facilitators although women spoke more of discrimination and low literacy. There was broad acceptance of childhood and adult immunisation across and within communities, with current parents perceived as more positive than their elders. A minority of English-speaking Travellers worried about multiple/combined childhood vaccines, adult flu and whooping cough and described barriers to booking and attending immunisation. Cultural concerns about antenatal vaccines and HPV vaccination were most evident in the Bristol English Gypsy/Irish Traveller community. Language, literacy, discrimination, poor school attendance, poverty and housing were identified as barriers across different communities. Trustful relationships with health professionals were important and continuity of care valued. CONCLUSIONS: The experience of many Travellers in this study, and the context through which they make health decisions, is changing. This large study identified key issues that should be considered when taking action to improve uptake of immunisations in Traveller families and reduce the persistent inequalities in coverage. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20019630 .

Twelve tips for turning quality assurance data into undergraduate teaching awards: A quality improvement and student engagement initiative.

Data on teaching awards in undergraduate medical education are sparse. The benefits of an awards system may seem obvious at first glance. However, there are also potential problems relating to fairness, avoidance of bias, and alignment of the awards system with a wider strategy for quality improvement and curriculum development. Here, we report five- year single center experience with establishing undergraduate teaching awards in a large academic teaching hospital. Due to lack of additional funding we based our awards not on peer review but mainly on existing and very comprehensive quality assurance (QA) data. Our 12 tips describe practical points but also pitfalls with awards categories and criteria, advertising and disseminating the awards, the actual awards ceremony and finally embedding the awards in the hospital's wider strategy. To be truly successful, teaching awards and prizes need to be carefully considered, designed and aligned with a wider institutional strategy of rewarding enthusiastic educators.

Effect of Collaborative Care vs Usual Care on Depressive Symptoms in Older Adults With Subthreshold Depression: The CASPER Randomized Clinical Trial.

Importance: There is little evidence to guide management of depressive symptoms in older people. Objective: To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people. Design, Setting, and Participants: Randomized clinical trial conducted from May 24, 2011, to November 14, 2014, in 32 primary care centers in the United Kingdom among 705 participants aged 65 years or older with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) subthreshold depression; participants were followed up for 12 months. Interventions: Collaborative care (n=344) was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of 6 weekly sessions. The control group received usual primary care (n=361). Main Outcomes and Measures: The primary outcome was self-reported depression severity at 4-month follow-up on the 9-item Patient Health Questionnaire (PHQ-9; score range, 0-27). Included among 10 prespecified secondary outcomes were the PHQ-9 score at 12-month follow-up and the proportion meeting criteria for depressive disorder (PHQ-9 score ≥10) at 4- and 12-month follow-up. Results: The 705 participants were 58% female with a mean age of 77 (SD, 7.1) years. Four-month retention was 83%, with higher loss to follow-up in collaborative care (82/344 [24%]) vs usual care (37/361 [10%]). Collaborative care resulted in lower PHQ-9 scores vs usual care at 4-month follow-up (mean score with collaborative care, 5.36 vs with usual care, 6.67; mean difference, -1.31; 95% CI, -1.95 to -0.67; P < .001). Treatment differences remained at 12 months (mean PHQ-9 score with collaborative care, 5.93 vs with usual care, 7.25; mean difference, -1.33; 95% CI, -2.10 to -0.55). The proportions of participants meeting criteria for depression at 4-month follow-up were 17.2% (45/262) vs 23.5% (76/324), respectively (difference, -6.3% [95% CI, -12.8% to 0.2%]; relative risk, 0.83 [95% CI, 0.61-1.27]; P = .25) and at 12-month follow-up were 15.7% (37/235) vs 27.8% (79/284) (difference, -12.1% [95% CI, -19.1% to -5.1%]; relative risk, 0.65 [95% CI, 0.46-0.91]; P = .01). Conclusions and Relevance: Among older adults with subthreshold depression, collaborative care compared with usual care resulted in a statistically significant difference in depressive symptoms at 4-month follow-up, of uncertain clinical importance. Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy. Trial Registration: isrctn.org Identifier: ISRCTN02202951.

Statistical approaches for identifying heavy users of inpatient mental health services.

BACKGROUND: A lack of consensus exists concerning how to identify "heavy users" of inpatient mental health services. AIM: To identify a statistical approach that captures, in a clinically meaningful way, "heavy" users of inpatient services using number of admissions and total time spent in hospital. METHODS: "Simple" statistical methods (e.g. top 2%) and data driven methods (e.g. the Poisson mixture distribution) were applied to admissions made to adult acute services of a London mental health trust. RESULTS: The Poisson mixture distribution distinguished "frequent users" of inpatient services, defined as having 4 + admissions in the study period. It also distinguished "high users" of inpatient services, defined as having 52 + occupied bed days. Together "frequent" and "high" users were classified as "heavy users". CONCLUSIONS: Data driven criteria such as the Poisson mixture distribution can identify "heavy" users of inpatient services. The needs of this group require particular attention.

The association between waiting for psychological therapy and therapy outcomes as measured by the CORE-OM.

OBJECTIVES: To investigate the impact of waiting for psychological therapy on client well-being as measured by the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) global distress (GD) score. METHOD: Global distress scores were retrieved for all clients referred for psychological therapy in a secondary care mental health service between November 2006 and May 2013 and who had completed a CORE-OM at assessment and first session. GD scores for a subgroup of 103 clients who had completed a CORE-OM during the last therapy session were also reviewed. RESULTS: The study sample experienced a median wait of 41.14 weeks between assessment and first session. The relationship between wait time from referral acceptance to assessment, and assessment GD score was not significant. During the period between assessment and first session no significant difference in GD score was observed. Nevertheless 29.1% of the sample experienced reliable change; 16.0% of clients reliably improved and 13.1% reliably deteriorated whilst waiting for therapy. Demographic factors were not found to have a significant effect on the change in GD score between assessment and first session. Waiting time was associated with post-therapy outcomes but not to a degree which was meaningful. The majority of individuals (54.4%), regardless of whether they improved or deteriorated whilst waiting for therapy, showed reliable improvement at end of therapy as measured by the CORE-OM. CONCLUSION: The majority of GD scores remained stable while waiting for therapy; however, 29.1% of secondary care clients experienced either reliable improvement or deterioration. Irrespective of whether they improved, deteriorated or remained unchanged whilst waiting for therapy, most individuals who had a complete end of therapy assessment showed reliable improvements following therapy. PRACTITIONER POINTS: There was no significant difference in GD score between assessment and first session recordings. A proportion of clients (29.1%) showed reliable change, either improvement or deterioration, as measured by the GD score while waiting for therapy. Of the individuals with last session CORE-OMs (54.4%) showed significant improvement following therapy regardless of whether or not they experienced change while waiting for therapy. Limitations include: Problems of data quality, the data were from a routine data set and data were lost at each stage of the analysis. A focus on the CORE-OM limits exploration of the subjective experience of waiting for psychotherapy and the impact this has on psychological well-being.

Revealing hidden depression in older people: a qualitative study within a randomised controlled trial.

BACKGROUND: The prevalence of depressive symptoms in older people may be as high as 20 %. Depression in older people is associated with loss, loneliness and physical co-morbidities; it is known to be under-diagnosed and under-treated. Older people may find it difficult to speak to their GPs about low mood, and GPs may avoid identifying depression due to limited consultation time and referral options for older patients. METHODS: A nested qualitative study in a randomised controlled trial for older people with moderate to severe depression: the CASPER Plus Trial (Collaborative Care for Screen Positive Elders). We interviewed GPs, case managers (CM) and patient participants to explore perspectives and experiences of delivering and receiving a psychosocial intervention, developed specifically for older adults in primary care, within a collaborative care framework. Transcripts were analysed thematically using principles of constant comparison. RESULTS: Thirty three interviews were conducted and, across the three data-sets, four main themes were identified: revealing hidden depression, reducing the 'blind spots', opportunity to talk outside the primary care consultation and 'moving on' from depression. CONCLUSIONS: Depression in older people is commonly hidden, and may coexist with physical conditions that are prioritised by both patients and GPs. Being invited to participate in a trial about depression may allow older people to disclose their feelings, name the problem, and seek help. Offering older people an opportunity to talk outside the primary care consultation is valued by patients and GPs. A psychosocial intervention delivered by a case manager in the primary care setting may fill the gap in the care of older people with depression. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45842879 .

Differences between paediatric and adult presentation of ESKD in attainment of adult social goals.

BACKGROUND: Living with end-stage kidney disease (ESKD) is complex for young adults who experience difficulties with adherence to medications and attainment of social markers of adulthood. METHODS: We studied adult outcomes (education, employment and accommodation) and evaluated adherence in young adults (age 16-30 years) according to paediatric (<16 years) and adult presentation (16-30 years) of ESKD. Initial questionnaire surveys were undertaken with patients (n = 931) identified from the databases of 12 adult and two paediatric nephrology programmes in England. RESULTS: Young adults (n = 296, 52 % male, 79 % Caucasian and 73 % with functioning renal allograft) with a mean age at first presentation of ESKD and current age of 17 and 25 years, respectively, were surveyed, of whom 5 % still attended paediatric services. Outcomes of patients aged >23 years and in stable health (n = 146) were compared between paediatric and adult presentation, with 30 and 20 % of patients, respectively, registered as disabled (p = 0.02). Educational attainment, based on percentage of those not achieving the General Certificate of Secondary Education (GCSE) level for England, was lower in the paediatric presentation group than in the adult one (7 vs. 18 %, respectively; p = 0.04). Compared to adult presentation patients, paediatric presentation patients were less likely to have full or part time paid work (57 vs. 76 %; p = 0.2). They also tended to be less likely to be living independently, less likely to be living with a partner, and, if living with their parents, more likely to be living in rented accommodation. Only 10 % patients missed taking medication weekly or more often. A higher frequency of missing medication was related to dialysis patients (p = 0.05), who assigned lower importance to taking medication (p < 0.001). However, patients aged <23 years attached less importance to complying with advice about treatment and health (p = 0.02), especially those who presented with ESKD during childhood (p = 0.01). CONCLUSIONS: Among our study cohort, young adults who presented with ESKD during childhood have poorer social and educational attainment compared to their counterparts who presented in adulthood. Adherence to medications remains important to ESKD patients. However, young adults wish to have personal control over their own life and health and need additional support and healthcare advice from the multi-disciplinary team. Qualitative work is required to understand the meaning of these outcomes on the quality of life for each individual patient.

Exploring perceptions of and attitudes towards tanning with school children, parents/carers and educators in Wales: A mixed methods study protocol for the SunChat study.

BACKGROUND: Skin cancer comprises half of all cancers in England and Wales. Most skin cancers can be prevented with safer sun exposure. As over exposure as a child can greatly increase future skin cancer risk, early and accessible sun safety education and promotion of sun safe behaviours is critical. Scientists agree there is no such thing as a 'safe tan', yet the public, including children, often have positive perceptions of tanned skin. To protect against future skin cancer, it is important to understand and address these misconceptions. The Curriculum for Wales with its area for Health and Well-being, and autonomy for schools in designing curriculum content, presents an ideal way to facilitate this exploration. AIMS: Gather data regarding perceptions towards tanning to explore the perceived effects of a tan on health.Inform the development and testing of an educational toolkit for integration within the Curriculum for Wales to encourage positive health behaviours and attitudes of school children towards tanning and sun exposure. METHODS: SunChat is a mixed methods exploratory study comprising three work streams: Workshops with school children to understand their perceptions on tanning.An online multiple-choice survey with parents/carers to understand perceptions, attitudes and behaviours towards tanning both for themselves and their children.An informal focus group with primary school educators to explore challenges in engaging with the school community around the Health and Well-being Area in the Curriculum for Wales. DISCUSSION: To date, there has been no work in Wales exploring children's, parents/carers', and educators' perceptions of tanning and how healthier attitudes can be encouraged. This study will engage with participants to scope current perceptions on tanning and the perceived effects tanning has on health. Findings will feed into future toolkit and curriculum development for health in schools in Wales and beyond.

The National Bowel Cancer Screening Program--consequences for practice.

BACKGROUND: The Australian Government introduced the National Bowel Cancer Screening Program (NBCSP) in 2006, in which Australian residents are offered a faecal immunochemical test (FIT) for haemoglobin when they turn 50, 55 and 65 years. We describe waiting times, quality of existing colonoscopic services, and quality of documentation of ongoing surveillance activities in those with a positive FIT. METHODS: A retrospective review of case notes of patients undergoing colonoscopy in public tertiary hospitals in South Australia, identified through the NBCSP (pilot and phase 1 and 2 groups). RESULTS: Records on 433 patients were assessable, representing 65% of public NBCSP cases. Colonoscopy waiting times varied, with only 23% of patients undergoing colonoscopy within the 30 day benchmark. The polyp retrieval rate was 98.4%. Surveillance recommendations after a polyp result were considered appropriate in 55% cases; with inappropriate intervals usually being set too early (59%). Where structured recall systems were utilised, appropriateness of follow up surveillance significantly improved. CONCLUSION: Overall, quality of colonoscopy was good. Waiting times were delayed with a minority of cases meeting the benchmark 30 day waiting time. Recommended surveillance colonoscopy intervals deviated from the guidelines in nearly half of patients, with a tendency to colonoscope too frequently according to the guidelines. More structured recall systems would be expected to reduce this excessive workload.

Pore-scale visualization of hydrogen storage in a sandstone at subsurface pressure and temperature conditions: Trapping, dissolution and wettability.

HYPOTHESIS: Underground hydrogen (H2) storage is a potentially viable solution for large-scale cyclic H2 storage; however, the behavior of H2 at subsurface pressure and temperature conditions is poorly known. This work investigates if the pore-scale displacement processes in H2-brine systems in a porous sandstone can be sufficiently well defined to enable effective and economic storage operations. In particular, this study investigates trapping, dissolution, and wettability of H2-brine systems at the pore-scale, at conditions that are realistic for subsurface H2 storage. EXPERIMENTS: We have performed in situ X-ray imaging during a flow experiment to investigate pore-scale processes during H2 injection and displacement in a brine saturated Bentheimer sandstone sample at temperature and pressure conditions representative of underground reservoirs. Two injection schemes were followed for imbibition: displacement of H2 with H2-equilibrated brine and with non-H2-equilibrated brine. The results from the two cycles were compared with each other. FINDINGS: The sandstone was found to be wetting to the brine and non-wetting to H2 after both displacement cycles, with average contact angles of 54° and 53° for H2-equilibrated and non-H2-equilibrated brine respectively. We also found a higher recovery of H2 (43.1%) when displaced with non-H2-equilibrated brine compared to that of H2-equilibrated brine (31.6%), indicating potential dissolution of H2 in the unequilibrated imbibing brine at reservoir conditions. Our results suggest that underground H2 storage may indeed be a suitable strategy for energy storage, but considerable further research is needed to fully comprehend the pore-scale interactions at reservoir conditions.

Changes in ciliary muscle thickness during accommodation in children.

PURPOSE: To investigate the morphology of the ciliary muscle during the act of accommodation in a population of children. METHODS: Thirty children aged 6 to 12 years were enrolled. Accommodative response was measured through habitual correction. Height was measured as a control variable. Central axial length was measured with the IOLMaster. Four images of the temporal ciliary muscle were taken with the Visante Optical Coherence Tomographer at three different stimulus levels (0, 4, and 6 D) while accommodative response was monitored concurrently with the PowerRefractor. Accommodative response monitoring was time-matched to ciliary muscle image capture, and the mean was calculated for 5 s surrounding this time point. Four cycloplegic images of the temporal ciliary muscle were also taken. Ciliary muscle thickness measurements were made at the point of maximum thickness (CMTMAX) and at 1 mm (CMT1), 2 mm (CMT2) and 3 mm (CMT3) posterior to the sclera spur. RESULTS: Increasing accommodative response was correlated with increases in the thickness of CMTMAX (p = <0.001) and CMT1 (p = <0.001) and decreases in the thickness of CMT3 (p = <0.001). Thicker values of CMTMAX under cycloplegic conditions were significantly correlated with values of CMTMAX (p = <0.001) and CMT1 (p = 0.001) while accommodating and approached significance in modeling CMT3 (p = 0.06). Mean axial length was correlated with the amount of thinning at CMT3 with accommodation (p = 0.002). Axial length was not significantly correlated with thickness values at CMTMAX (p = 0.7) or CMT1 (p = 0.6). CONCLUSIONS: In a manner similar to previous adult studies, ciliary muscle thickness at CMTMAX and CMT1 increased with accommodation and CMT3 thinned with accommodation. Further investigation is necessary to determine whether CMT2 is a "fulcrum" point along the length of the ciliary muscle where the net change with accommodation is always zero or whether that point varies across subjects or with varying levels of accommodative effort.

An RNA splicing enhancer that does not act by looping.

Out of the loop: Do the proteins bound to an enhancer site on pre-mRNA interact directly with the splice site by diffusion (looping), as is generally accepted, or does the intervening RNA play a role? By inserting a PEG linker between an enhancer sequence and alternative splice sites, the interaction of these two elements can be studied. Intervening RNA was essential for the enhancer activity, which rules out the looping model.

Switching Cytolytic Nanopores into Antimicrobial Fractal Ruptures by a Single Side Chain Mutation.

Disruption of cell membranes is a fundamental host defense response found in virtually all forms of life. The molecular mechanisms vary but generally lead to energetically favored circular nanopores. Here, we report an elaborate fractal rupture pattern induced by a single side-chain mutation in ultrashort (8-11-mers) helical peptides, which otherwise form transmembrane pores. In contrast to known mechanisms, this mode of membrane disruption is restricted to the upper leaflet of the bilayer where it exhibits propagating fronts of peptide-lipid interfaces that are strikingly similar to viscous instabilities in fluid flow. The two distinct disruption modes, pores and fractal patterns, are both strongly antimicrobial, but only the fractal rupture is nonhemolytic. The results offer wide implications for elucidating differential membrane targeting phenomena defined at the nanoscale.

Activated Polyhydroxyalkanoate Meshes Prevent Bacterial Adhesion and Biofilm Development in Regenerative Medicine Applications.

Regenerative medicine has become an extremely valuable tool offering an alternative to conventional therapies for the repair and regeneration of tissues. The re-establishment of tissue and organ functions can be carried out by tissue engineering strategies or by using medical devices such as implants. However, with any material being implanted inside the human body, one of the conundrums that remains is the ease with which these materials can get contaminated by bacteria. Bacterial adhesion leads to the formation of mature, alive and complex three-dimensional biofilm structures, further infection of surrounding tissues and consequent development of complicated chronic infections. Hence, novel tissue engineering strategies delivering biofilm-targeted therapies, while at the same time allowing tissue formation are highly relevant. In this study our aim was to develop surface modified polyhydroxyalkanoate-based fiber meshes with enhanced bacterial anti-adhesive and juvenile biofilm disrupting properties for tissue regeneration purposes. Using reactive and amphiphilic star-shaped macromolecules as an additive to a polyhydroxyalkanoate spinning solution, a synthetic antimicrobial peptide, Amhelin, with strong bactericidal and anti-biofilm properties, and Dispersin B, an enzyme promoting the disruption of exopolysaccharides found in the biofilm matrix, were covalently conjugated to the fibers by addition to the solution before the spinning process. Staphylococcus epidermidis is one of the most problematic pathogens responsible for tissue-related infections. The initial antibacterial screening showed that Amhelin proved to be strongly bactericidal at 12 µg/ml and caused >50% reductions of biofilm formation at 6 µg/ml, while Dispersin B was found to disperse >70% of pre-formed biofilms at 3 µg/ml. Regarding the cytotoxicity of the agents toward L929 murine fibroblasts, a CC50 of 140 and 115 µg/ml was measured for Amhelin and Dispersin B, respectively. Optimization of the electrospinning process resulted in aligned fibers. Surface activated fibers with Amhelin and Dispersin B resulted in 83% reduction of adhered bacteria on the surface of the fibers. Additionally, the materials developed were found to be cytocompatible toward L929 murine fibroblasts. The strategy reported in this preliminary study suggests an alternative approach to prevent bacterial adhesion and, in turn biofilm formation, in materials used in regenerative medicine applications such as tissue engineering.

Flowering Poration-A Synergistic Multi-Mode Antibacterial Mechanism by a Bacteriocin Fold.

Bacteriocins are a distinct family of antimicrobial proteins postulated to porate bacterial membranes. However, direct experimental evidence of pore formation by these proteins is lacking. Here we report a multi-mode poration mechanism induced by four-helix bacteriocins, epidermicin NI01 and aureocin A53. Using a combination of crystallography, spectroscopy, bioassays, and nanoscale imaging, we established that individual two-helix segments of epidermicin retain antibacterial activity but each of these segments adopts a particular poration mode. In the intact protein these segments act synergistically to balance out antibacterial and hemolytic activities. The study sets a precedent of multi-mode membrane disruption advancing the current understanding of structure-activity relationships in pore-forming proteins.

Engineering Chirally Blind Protein Pseudocapsids into Antibacterial Persisters.

Antimicrobial resistance stimulates the search for antimicrobial forms that may be less subject to acquired resistance. Here we report a conceptual design of protein pseudocapsids exhibiting a broad spectrum of antimicrobial activities. Unlike conventional antibiotics, these agents are effective against phenotypic bacterial variants, while clearing "superbugs" in vivo without toxicity. The design adopts an icosahedral architecture that is polymorphic in size, but not in shape, and that is available in both l and d epimeric forms. Using a combination of nanoscale and single-cell imaging we demonstrate that such pseudocapsids inflict rapid and irreparable damage to bacterial cells. In phospholipid membranes they rapidly convert into nanopores, which remain confined to the binding positions of individual pseudocapsids. This mechanism ensures precisely delivered influxes of high antimicrobial doses, rendering the design a versatile platform for engineering structurally diverse and functionally persistent antimicrobial agents.

Helminth Defense Molecules as Design Templates for Membrane Active Antibiotics.

A design template for membrane active antibiotics against microbial and tumor cells is described. The template is an amino acid sequence that combines the properties of helminth defense molecules, which are not cytolytic, with the properties of host-defense peptides, which disrupt microbial membranes. Like helminth defense molecules, the template folds into an amphipathic helix in both mammalian host and microbial phospholipid membranes. Unlike these molecules, the template exhibits antimicrobial and anticancer properties that are comparable to those of antimicrobial and anticancer antibiotics. The selective antibiotic activity of the template builds upon a functional synergy between three distinctive faces of the helix, which is in contrast to two faces of membrane-disrupting amphipathic structures. This synergy enables the template to adapt pore formation mechanisms according to the nature of the target membrane, inducing the lysis of microbial and tumor cells.

Training the public health workforce at the National School of Public Health: meeting Africa's needs.

PROBLEM: The inadequate number of trained public health personnel in Africa remains a challenge. In sub-Saharan Africa, the estimated workforce of public health practitioners is 1.3% of the world's health workforce addressing 25% of the world's burden of disease. APPROACH: To address this gap, the National School of Public Health at the then Medical University of Southern Africa created an innovative approach using distance learning components to deliver its public health programmes. Compulsory classroom teaching is limited to four two-week blocks. RELEVANT CHANGES: Combining mainly online components with traditional classroom curricula reduced limitations caused by geographical distances. At the same time, the curriculum was structured to contextualize continental health issues in both course work and research specific to students' needs. LESSONS LEARNED: The approach used by the National School of Public Health allows for a steady increase in the number of public health personnel in Africa. Because of the flexible e-learning components and African-specific research projects, graduates from 16 African countries could benefit from this programme. An evaluation showed that such programmes need to constantly motivate participants to reduce student dropout rates and computer literacy needs to be a pre-requisite for entry into the programme. Short certificate courses in relevant public health areas would be beneficial in the African context. This programme could be replicated in other regions of the continent.

An randomized controlled trial of Post-it® notes did not increase postal response rates in older depressed participants.

RATIONALE, AIMS AND OBJECTIVES: Our aim was to evaluate the effectiveness of a Post-it® note to increase response rates and shorten response times to a 4-month postal follow-up questionnaire sent to participants taking part in the Collaborative Care in Screen-Positive Elders (CASPER) trials. METHOD: Our trial was a two-arm randomized controlled trial comparing response rates to questionnaires with a printed Post-it® note (intervention) and without (control), nested in multi centred randomized controlled trials of older people with varying levels of depressive symptoms; the CASPER+ and CASPER Self Help for those At Risk of Depression (SHARD) trials. A total of 611 participants were eligible and randomized. The primary outcome was response rates, secondary outcomes were time to response and need for a reminder. RESULTS: Of 297 participants, 266 (89.6%) returned their 4-month questionnaire in the post-it note arm, compared with 282 of 314 participants (89.8%) in the control arm (OR = 0.97, 95% CI: 0.57, 1.65, P = 0.913). There were no statistically significant differences in time to respond or the need to be sent a reminder. Patients with a major depressive episode were more likely to return questionnaires with post-it notes (P of interaction = .019). CONCLUSION: There was no significant difference in response rates, time to response, or the need for a reminder between the intervention and control at 4-month follow up for older people with depressive symptoms. However, there was a significant interaction between the Post-it® note group and level of depression.