Search

Objectives: To map organisational interventions for workplace suicide prevention, identifying the effects, mechanisms, moderators, implementation and economic costs, and how interventions are evaluated. Background: Suicide is a devastating event that can have a profound and lasting impact on the individuals and families affected, with the highest rates found among adults of work age. Employers have a legal and ethical responsibility to provide a safe working environment for their employees, which includes addressing the issue of suicide and promoting mental health and well-being. Methods: A realist perspective was taken, to identify within organisational suicide prevention interventions, what works, for whom and in what circumstances. Published and unpublished studies in six databases were searched. To extract and map data on the interventions the Effect, Mechanism, Moderator, Implementation, Economic (EMMIE) framework was used. Mechanisms were deductively analysed against Bronfenbrenner's socio-ecological model. Results: From 3187 records screened, 46 papers describing 36 interventions within the military, healthcare, the construction industry, emergency services, office workers, veterinary surgeons, the energy sector and higher education. Most mechanisms were aimed at the individual's immediate environment, with the most common being education or training on recognising signs of stress, suicidality or mental illness in oneself. Studies examined the effectiveness of interventions in terms of suicide rates, suicidality or symptoms of mental illness, and changes in perceptions, attitudes or beliefs, with most reporting positive results. Few studies reported economic costs but those that did suggested that the interventions are cost-effective. Conclusions: It seems likely that organisational suicide prevention programmes can have a positive impact on attitudes and beliefs towards suicide as well reducing the risk of suicide. Education, to support individuals to recognise the signs and symptoms of stress, mental ill health and suicidality in both themselves and others, is likely to be an effective starting point for successful interventions. [ABSTRACT FROM AUTHOR]

Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Inhaled antibiotics control chronic airway infection and maintain respiratory health in cystic fibrosis (CF). Given variation in patient responses to inhaled antibiotics, the ability to identify distinct responder phenotypes would facilitate the delivery of personalized care. Previously, a 10-gene panel was identified, measured directly from blood leukocytes, which predicted host response to intravenous antibiotic treatment during pulmonary exacerbations. In the current study, we tested whether the same panel predicted clinical response in subjects receiving a month of inhaled antibiotic therapy with aztreonam lysine (AZLI; Cayston®). A small cohort of CF subjects infected with Pseudomonas aeruginosa were enrolled at baseline health, prior to initiating one month's treatment with AZLI using the Altera® nebulizer system. Eighteen CF subjects underwent blood leukocyte gene panel measurements, sputum quantitative microbiology, spirometry, and C-reactive protein (CRP) measurement prior to onset and at completion of 4 weeks of AZLI therapy. Mean absolute improvement in percent predicted Forced Expiratory Volume in one second (ppFEV1) was 3%. Significant reductions in sputum bacterial colony counts were detected with treatment. CRP increased following treatment. While single genes within the panel did not change significantly following treatment, the analysis of multigene panel data demonstrated that HCA112 gene predicted ppFEV1 improvement. Hierarchical clustering based on gene expression yielded two distinctive molecular clusters before and after AZLI therapy. In conclusion, peripheral blood leukocyte genes quantifying inflammation are associated with responses to inhaled antibiotic therapy. Molecular quantification of systemic inflammation may indicate subgroups of CF subjects with variations in underlying inflammation and with variable clinical responses to inhaled antibiotics. Given the size limitation of the study, larger studies are needed in order to evaluate whether molecular measures may add precision to the determination of infectious and inflammatory outcomes following courses of inhaled antimicrobial therapies. Clinical Trials.gov Identifier: NCT01736839. [ABSTRACT FROM AUTHOR]

The bacterial pathogen responsible for causing Lyme disease, Borrelia burgdorferi, is an atypical Gram-negative spirochete that is transmitted to humans via the bite of an infected Ixodes tick. In diderms, peptidoglycan (PG) is sandwiched between the inner and outer membrane of the cell envelope. In many other Gram-negative bacteria, PG is bound by protein(s), which provide both structural integrity and continuity between envelope layers. Here, we present evidence of a peptidoglycan-associated protein (PAP) in B. burgdorferi. Using an unbiased proteomics approach, we identified Neutrophil Attracting Protein A (NapA) as a PAP. Interestingly, NapA is a Dps homologue, which typically functions to bind and protect cellular DNA from damage during times of stress. While B. burgdorferi NapA is known to be involved in the oxidative stress response, it lacks the critical residues necessary for DNA binding. Biochemical and cellular studies demonstrate that NapA is localized to the B. burgdorferi periplasm and is indeed a PAP. Cryo-electron microscopy indicates that mutant bacteria, unable to produce NapA, have structural abnormalities. Defects in cell-wall integrity impact growth rate and cause the napA mutant to be more susceptible to osmotic and PG-specific stresses. NapA-linked PG is secreted in outer membrane vesicles and augments IL-17 production, relative to PG alone. Using microfluidics, we demonstrate that NapA acts as a molecular beacon—exacerbating the pathogenic properties of B. burgdorferi PG. These studies further our understanding of the B. burgdorferi cell envelope, provide critical information that underlies its pathogenesis, and highlight how a highly conserved bacterial protein can evolve mechanistically, while maintaining biological function. Author summary: Diderms typically produce peptidoglycan-associated proteins (PAPs) to enhance structural integrity and continuity within the cell envelope. We have identified a PAP in B. burgdorferi with structural and sequence homology to the near ubiquitous bacterial protein Dps (DNA binding protein from starved bacteria). The B. burgdorferi Dps paralogue is incapable of binding DNA. Instead, it bolsters the protective properties of the PG layer, while playing an important role in host immune modulation. Collectively, our findings highlight the plasticity of bacterial proteins in that they may change how they perform a task despite maintaining the same basic biological function. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), a common complication in paediatric intensive care units (PICU), is associated with increased morbidity and mortality. In this single centre, prospective, observational cohort study, neutrophil gelatinase-associated lipocalin in urine (uNGAL) and plasma (pNGAL) and renal angina index (RAI), and combinations of these markers, were assessed for their ability to predict severe (stage 2 or 3) AKI in children and young people admitted to PICU. In PICU children and young people had initial and serial uNGAL and pNGAL measurements, RAI calculation on day 1, and collection of clinical data, including serum creatinine measurements. Primary outcomes were severe AKI and renal replacement therapy (RRT). Secondary outcomes were length of stay, hospital acquired infection and mortality. The area under the Receiver Operating Characteristic (ROC) curves and Youden index was used to determine biomarker performance and identify optimum cut-off values. Of 657 children recruited, 104 met criteria for severe AKI (15∙8%) and 47 (7∙2%) required RRT. Severe AKI was associated with increased length of stay, hospital acquired infection, and mortality. The area under the curve (AUC) for severe AKI prediction for Day 1 uNGAL, Day 1 pNGAL and RAI were 0.75 (95% Confidence Interval [CI] 0∙69, 0∙81), 0∙64 (95% CI 0∙56, 0∙72), and 0.73 (95% CI 0∙65, 0∙80) respectively. The optimal combination of measures was RAI and day 1 uNGAL, giving an AUC of 0∙80 for severe AKI prediction (95% CI 0∙71, 0∙88). In this heterogenous PICU cohort, urine or plasma NGAL in isolation had poorer prediction accuracy for severe AKI than in previously reported homogeneous populations. However, when combined together with RAI, they produced good prediction for severe AKI. [ABSTRACT FROM AUTHOR]

Albinism includes a group of inherited conditions that result in reduced melanin production. It has been documented across the world, with a high frequency in sub-Saharan Africa. There is very little published research about the lives of people with albinism, but available evidence shows that myths abound regarding their condition. They are feared, viewed with suspicion and believed to have supernatural powers. In this study we explored the links between beliefs, myths, traditions and positive/negative attitudes that surround people with albinism in Uganda. The study was located philosophically within Ubuntu—an Afrocentric worldview—and theoretically within the Common-Sense Model of self-regulation of health and illness that originates from the work of Leventhal in 2003. This qualitative study took place in eight districts of Busoga sub-region, Uganda between 2015 and 2017. Data collection comprised eight group discussions and 17 individual interviews with a range of informants, capturing the viewpoints of 73 participants. Findings lend support to previous research, highlighting the life-time discrimination and disadvantage experienced by many people with albinism. It shows that there is still much to be done to address the pervasive and potentially harmful beliefs and misconceptions about people with albinism. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is common in both geriatric cats and aging humans, and is pathologically characterised by chronic tubulointerstitial inflammation and fibrosis in both species. Cats with CKD may represent a spontaneously occurring, non-rodent animal model of human disease, however little is known of feline renal cell biology. In other species, TGF-β1 signalling in the proximal tubular epithelium is thought to play a key role in the initiation and progression of renal fibrosis. In this study, we first aimed to isolate and characterise feline proximal tubular epithelial cells (FPTEC), comparing them to human primary renal epithelial cells (HREC) and the human proximal tubular cell line HK-2. Secondly, we aimed to examine and compare the effect of human recombinant TGF-β1 on cell proliferation, pro-apoptotic signalling and genes associated with epithelial-to-mesenchymal transition (EMT) in feline and human renal epithelial cells. FPTEC were successfully isolated from cadaverous feline renal tissue, and demonstrated a marker protein expression profile identical to that of HREC and HK-2. Exposure to TGF-β1 (0–10 ng/ml) induced a concentration-dependent loss of epithelial morphology and alterations in gene expression consistent with the occurrence of partial EMT in all cell types. This was associated with transcription of downstream pro-fibrotic mediators, growth arrest in FPTEC and HREC (but not HK-2), and increased apoptotic signalling at high concentrations of TGF- β1. These effects were inhibited by the ALK5 (TGF-β1RI) antagonist SB431542 (5 μM), suggesting they are mediated via the ALK5/TGF-β1RII receptor complex. Taken together, these results suggest that TGF-β1 may be involved in epithelial cell dedifferentiation, growth arrest and apoptosis in feline CKD as in human disease, and that cats may be a useful, naturally occurring model of human CKD. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment for malaria in pregnancy (IPTp) is part of a multi-pronged strategy aimed at preventing malaria in pregnancy in areas of moderate to high transmission in sub-Saharan Africa. Despite being formally adopted as a malaria prevention policy over a decade ago, IPTp coverage has remained low. Recent demands for action have incorporated calls to strengthen IPTp monitoring and evaluation systems, including the use of routine data, to measure coverage, track implementation and identify roadblocks to improving uptake. Concerns about the quality of malaria indicators reported through routine information systems are well recognized, but there are few data on the realities of IPTp recording practices in frontline facilities or their entry into District Health Information Software (DHIS2). Methods: Drawing on fieldwork conducted in two malaria endemic sub-counties in Kenya, we explore how local adaptations and innovations employed by health workers and sub-country managers to cope with a range of health system constraints, shape recording practices and in turn, the measurement of IPTp. Data were collected through observations, interviews, and document reviews. Data analysis and interpretation was guided by thematic analysis approach. Results: Measurement of IPTp was undermined by health system constraints such as stock-out of drugs and human resource shortages. Coping strategies adopted by health workers to address these challenges ensured continuity in service delivery and IPTp data generation but had variable consequences on IPTp data quality. Unclear recording and reporting instructions also led to lack of standardization in IPTp data generation. The use of redundant tools created significant data burdens which undermined service delivery in general. Conclusions: There is need to integrate monthly reporting forms so as to remove redundancies which exacerbates workload for health workers and disrupts service delivery. Similarly, data collection instructions in registers and reporting forms need to be clarified to standardize IPTp data generation across health facilities. There is also need to address broader contextual factors such as stock-out of commodities and human resource shortages which undermine IPTp data generation process. [ABSTRACT FROM AUTHOR]

nvasive spergillosis (IA), primarily caused by Aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. Investigations of neutrophil-hypha interaction in vitro and in animal models of IA are limited by lack of temporal and spatial control over interactions. This study presents a new approach for studying neutrophil-hypha interaction at single cell resolution over time, which revealed an evasive fungal behavior triggered by interaction with neutrophils: Interacting hyphae performed de novo tip formation to form new hyphal branches, allowing the fungi to avoid the interaction point and continue invasive growth. Induction of this mechanism was independent of neutrophil NADPH oxidase activity and eutrophil xtracellular rap (NET) formation, but could be phenocopied by iron chelation and mechanical or physiological stalling of hyphal tip extension. The consequence of branch induction upon interaction outcome depends on the number and activity of neutrophils available: In the presence of sufficient neutrophils branching makes hyphae more vulnerable to destruction, while in the presence of limited neutrophils the interaction increases the number of hyphal tips, potentially making the infection more aggressive. This has direct implications for infections in neutrophil-deficient patients and opens new avenues for treatments targeting fungal branching. [ABSTRACT FROM AUTHOR]

Purpose: Understanding caregivers’ experiences of care can identify barriers to timely and good quality care, and support the improvement of services. We aimed to explore caregivers’ experiences and perceptions of pathways to care, from first access through various levels of health service, for seriously ill and injured children in Cape Town, South Africa, in order to identify areas for improvement. Methods: Semi-structured, qualitative interviews were conducted with primary caregivers of children who were admitted to paediatric intensive care or died in the health system prior to intensive care admission. Interviews explored caregivers’ experiences from when their child first became ill, through each level of health care to paediatric intensive care or death. A maximum variation sample of transcripts was purposively sampled from a larger cohort study based on demographic characteristics, child diagnosis, and outcome at 30 days; and analysed using the method of constant comparison. Results: Of the 282 caregivers who were interviewed in the larger cohort study, 45 interviews were included in this qualitative analysis. Some caregivers employed ‘tactics’ to gain quicker access to care, including bypassing lower levels of care, and negotiating or demanding to see a healthcare professional ahead of other patients. It was sometimes unclear how to access emergency care within facilities; and non-medical personnel informally judged illness severity and helped or hindered quicker access. Caregivers commonly misconceived ambulances to be slow to arrive, and were concerned when ambulance transfers were seemingly not prioritised by illness severity. Communication was often good, but some caregivers experienced language difficulties and/or criticism. Conclusions: Interventions to improve child health care could be based on: reorganising the reception of seriously ill children and making the emergency route within healthcare facilities clear; promoting caregivers’ use of ambulances and prioritising transfers according to illness severity; addressing language barriers, and emphasising the importance of effective communication to healthcare providers. [ABSTRACT FROM AUTHOR]

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. [ABSTRACT FROM AUTHOR]

Importance: Capillary refill time (CRT) is widely recommended as part of the routine assessment of unwell children. Objective: To determine the diagnostic value of capillary refill time for a range of serious outcomes in children. Methods: We searched Medline, Embase and CINAHL from inception to June 2014. We included studies that measured both capillary refill time and a relevant clinical outcome such as mortality, dehydration, meningitis, or other serious illnesses in children aged up to 18 years of age. We screened 1,265 references, of which 24 papers were included in this review. Where sufficient studies were available, we conducted meta-analysis and constructed hierarchical summary ROC curves. Results: Meta-analysis on the relationship between capillary refill time and mortality resulted in sensitivity of 34.6% (95% CI 23.9 to 47.1%), specificity 92.3% (88.6 to 94.8%), positive likelihood ratio 4.49 (3.06 to 6.57), and negative likelihood ratio 0.71 (0.60 to 0.84). Studies of children attending Emergency Departments with vomiting and diarrhea showed that capillary refill time had specificity of 89 to 94% for identifying 5% dehydration, but sensitivity ranged from 0 to 94%. This level of heterogeneity precluded formal meta-analysis of this outcome. Meta-analysis was not possible for other outcomes due to insufficient data, but we found consistently high specificity for a range of outcomes including meningitis, sepsis, admission to hospital, hypoxia, severity of illness and dengue. Conclusions: Our results show that capillary refill time is a specific sign, indicating that it can be used as a “red-flag”: children with prolonged capillary refill time have a four-fold risk of dying compared to children with normal capillary refill time. The low sensitivity means that a normal capillary refill time should not reassure clinicians. [ABSTRACT FROM AUTHOR]

Background: Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen. Methods: Pre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset. Results: There was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1–10.0)]. Conclusion: The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes. [ABSTRACT FROM AUTHOR]

Background: Clinical trials conducted in Africa often require substantial investments to support trial centres and public health facilities. Trial resources could potentially generate benefits for routine health service delivery but may have unintended consequences. Strengthening ethical practice requires understanding the potential effects of trial inputs on the perceptions and practices of routine health care providers. This study explores the influence of malaria vaccine trials on health service delivery in Ghana, Kenya and Burkina Faso. Methods: We conducted: audits of trial inputs in 10 trial facilities and among 144 health workers; individual interviews with frontline providers (n=99) and health managers (n=14); and group discussions with fieldworkers (n=9 discussions). Descriptive summaries were generated from audit data. Qualitative data were analysed using a framework approach. Results: Facilities involved in trials benefited from infrastructure and equipment upgrades, support with essential drugs, access to trial vehicles, and placement of additional qualified trial staff. Qualified trial staff in facilities were often seen as role models by their colleagues; assisting with supportive supervision and reducing facility workload. Some facility staff in place before the trial also received formal training and salary top-ups from the trials. However, differential access to support caused dissatisfaction, and some interviewees expressed concerns about what would happen at the end of the trial once financial and supervisory support was removed. Conclusion: Clinical trials function as short-term complex health service delivery interventions in the facilities in which they are based. They have the potential to both benefit facilities, staff and communities through providing the supportive environment required for improvements in routine care, but they can also generate dissatisfaction, relationship challenges and demoralisation among staff. Minimising trial related harm and maximising benefits requires careful planning and engagement of key actors at the outset of trials, throughout the trial and on its’ completion. [ABSTRACT FROM AUTHOR]

Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns. [ABSTRACT FROM AUTHOR]

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade. [ABSTRACT FROM AUTHOR]

An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. [ABSTRACT FROM AUTHOR]

This paper presents the results of a qualitative study to investigate the perceptions and experiences of health workers involved in a a cluster-randomized controlled trial of a novel intervention to improve health worker malaria case-management in 107 government health facilities in Kenya. The intervention involved sending text-messages about paediatric outpatient malaria case-management accompanied by ''motivating'' quotes to health workers' mobile phones. Ten malaria messages were developed reflecting recommendations from the Kenyan national guidelines. Two messages were delivered per day for 5 working days and the process was repeated for 26 weeks (May to October 2009). The accompanying quotes were unique to each message. The intervention was delivered to 119 health workers and there were significant improvements in correct artemether-lumefantrine (AL) management both immediately after the intervention (November 2009) and 6 months later (May 2010). In-depth interviews with 24 health workers were undertaken to investigate the possible drivers of this change. The results suggest high acceptance of all components of the intervention, with the active delivery of information in an on the job setting, the ready availability of new and stored text messages and the perception of being kept 'up to date' as important factors influencing practice. Applying the construct of stages of change we infer that in this intervention the SMS messages were operating primarily at the action and maintenance stages of behaviour change achieving their effect by creating an enabling environment and providing a prompt to action for the implementation of case management practices that had already been accepted as the clinical norm by the health workers. Future trials testing the effectiveness of SMS reminders in creating an enabling environment for the establishment of new norms in clinical practice as well as in providing a prompt to action for the implementation of the new case-management guidelines are justified. [ABSTRACT FROM AUTHOR]

Background: Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers. Methodology/Principal Findings: Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common. Conclusions/Significance: The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry. [ABSTRACT FROM AUTHOR]

Henoch Schonlein Purpura (HSP) is the commonest systemic vasculitis of childhood typically presenting with a palpable purpuric rash and frequently involving the renal system. We are the first group to clinically assess, critically analyse and subsequently revise a nurse led monitoring pathway for this condition. A cohort of 102 children presenting with HSP to a secondary/tertiary level UK paediatric hospital over a five year period, were monitored using a nurse led care pathway. Using this cohort, the incidence (6.21 cases per 100,000 children per year) and natural disease course of HSP nephritis (46% initial renal inflammation; 9% subsequent renal referral; 1% renal biopsy and immunosuppression) was determined. Older patients were at higher risk of requiring a renal referral (renal referral 12.3 (8.4-13.5) years vs. normal outcome 6.0 (3.7-8.5) years; p<0.01). A normal urinalysis on day 7 had a 97% (confidence interval 90 to 99%) negative predictive value in predicting a normal renal outcome. Using this data and existing literature base, The Alder Hey Henoch Schonlein Purpura Pathway was developed, a revised pathway for the screening of poor renal outcome in HSP. This is based on a six-month monitoring period for all patients presenting with HSP, which importantly prioritises patients according to the urine findings on day 7 and thus intensively monitors those at higher risk of developing nephritis. The pathway could be easily adapted for use in different settings and resources. The introduction of a standardised pathway for the monitoring of HSP will facilitate the implementation of disease registries to further our understanding of the condition and permit future clinical trials. [ABSTRACT FROM AUTHOR]

Malaria in pregnancy (MiP) is associated with increased risks of maternal and foetal complications. The WHO recommends a package of interventions including intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), insecticide-treated nets and effective case management. However, with increasing SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent screening and treatment (IST) has recently been shown in Ghana to be as efficacious as SP-IPT. This study investigates two important requirements for effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge, and acceptance of the different strategies. Structured interviews with 134 ANC providers at 67 public health facilities in Ashanti Region, Ghana collected information on knowledge of the risks and preventative and curative interventions against MiP. Composite indicators of knowledge of SP-IPT, and case management of MiP were developed. Log binomial regression of predictors of provider knowledge was explored. Qualitative data were collected through in-depth interviews with fourteen ANC providers with some knowledge of IST to gain an indication of the factors influencing acceptance of the IST approach. 88.1% of providers knew all elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment policy for malaria in the first or second/third trimesters, respectively. Workshop attendance was a univariate predictor of each knowledge indicator. Qualitative findings suggest preference for prevention over cure, and increased workload may be barriers to IST implementation. However, a change in strategy in the face of SP resistance is likely to be supported; health of pregnant women is a strong motivation for ANC provider practice. If IST was to be introduced as part of routine ANC activities, attention would need to be given to improving the knowledge and practices of ANC staff in relation to appropriate treatment of MiP. Health worker support for any MiP intervention delivered through ANC clinics is critical. [ABSTRACT FROM AUTHOR]

Background: The currently recommended approach for preventing malaria in pregnancy (MiP), intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT), has been questioned due to the spread of resistance to SP. Whilst trials are underway to test the efficacy of future alternative approaches, it is important to start exploring the feasibility of their implementation. Methods and Findings: This study uses a discrete choice experiment (DCE) method to assess the potential resistance of health workers to changing strategies for control of MiP. In Ashanti region in Ghana, 133 antenatal clinic health workers were presented with 16 choice sets of two alternative policy options, each consisting of a bundle of six attributes representing certain clinical guidelines for controlling MiP (type of approach and drug used), possible associated maternal and neo-natal outcomes, workload and financial incentives. The data were analysed using a random effects logit model. Overall, staff showed a preference for a curative approach with pregnant women tested for malaria parasites and treated only if positive, compared to a preventive approach (OR 1.6; p = 0.001). Increasing the incidence of low birth weight or severe anaemia by 1% would reduce the odds of preferring an approach by 18% and 10% respectively. Midwives were more resistant to potential changes to current guidelines than lower-level cadres. Conclusions: In Ashanti Region, resistance to change by antenatal clinic workers from a policy of SP-IPT to IST would generally be low, and it would disappear amongst midwives if health outcomes for the mother and baby were improved by the new strategy. DCEs are a promising approach to identifying factors that will increase the likelihood of effective implementation of new interventions immediately after their efficacy has been proven. [ABSTRACT FROM AUTHOR]

Background: The adipocyte-derived hormone leptin influences the behaviour of a wide range of cell types and is now recognised as a pro-angiogenic and pro-inflammatory factor. In the vasculature, these effects are mediated in part through its direct leptin receptor (ObRb)-driven actions on endothelial cells (ECs) but the mechanisms responsible for these activities have not been established. In this study we sought to more fully define the molecular links between inflammatory and angiogenic responses of leptin-stimulated human ECs. Methodology/Principal Findings: Immunoblotting studies showed that leptin increased cyclo-oxygenase-2 (COX-2) expression (but not COX-1) in cultured human umbilical vein ECs (HUVEC) through pathways that depend upon activation of both p38 mitogen-activated protein kinase (p38MAPK) and Akt, and stimulated rapid phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) on Tyr1175. Phosphorylation of VEGFR2, p38MAPK and Akt, and COX-2 induction in cells challenged with leptin were blocked by a specific leptin peptide receptor antagonist. Pharmacological inhibitors of COX-2, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and p38MAPK abrogated leptin-induced EC proliferation (assessed by quantifying 5-bromo-2′-deoxyuridine incorporation, calcein fluorescence and propidium iodide staining), slowed the increased migration rate of leptin-stimulated cells (in vitro wound healing assay) and inhibited leptininduced capillary-like tube formation by HUVEC on Matrigel. Inhibition of VEGFR2 tyrosine kinase activity reduced leptinstimulated p38MAPK and Akt activation, COX-2 induction, and pro-angiogenic EC responses, and blockade of VEGFR2 or COX-2 activities abolished leptin-driven neo-angiogenesis in a chick chorioallantoic membrane vascularisation assay in vivo. Conclusions/Significance: We conclude that a functional endothelial p38MAPK/Akt/COX-2 signalling axis is required for leptin's pro-angiogenic actions and that this is regulated upstream by ObRb-dependent activation of VEGFR2. These studies identify a new function for VEGFR2 as a mediator of leptin-stimulated COX-2 expression and angiogenesis and have implications for understanding leptin's regulation of the vasculature in both non-obese and obese individuals. [ABSTRACT FROM AUTHOR]

Malaria in pregnancy (MiP) is associated with increased risks of maternal and foetal complications. The WHO recommends a package of interventions including intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), insecticide-treated nets and effective case management. However, with increasing SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent screening and treatment (IST) has recently been shown in Ghana to be as efficacious as SP-IPT. This study investigates two important requirements for effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge, and acceptance of the different strategies. Structured interviews with 134 ANC providers at 67 public health facilities in Ashanti Region, Ghana collected information on knowledge of the risks and preventative and curative interventions against MiP. Composite indicators of knowledge of SP-IPT, and case management of MiP were developed. Log binomial regression of predictors of provider knowledge was explored. Qualitative data were collected through in-depth interviews with fourteen ANC providers with some knowledge of IST to gain an indication of the factors influencing acceptance of the IST approach. 88.1% of providers knew all elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment policy for malaria in the first or second/third trimesters, respectively. Workshop attendance was a univariate predictor of each knowledge indicator. Qualitative findings suggest preference for prevention over cure, and increased workload may be barriers to IST implementation. However, a change in strategy in the face of SP resistance is likely to be supported; health of pregnant women is a strong motivation for ANC provider practice. If IST was to be introduced as part of routine ANC activities, attention would need to be given to improving the knowledge and practices of ANC staff in relation to appropriate treatment of MiP. Health worker support for any MiP intervention delivered through ANC clinics is critical.