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Introduction: Widespread vaccination against COVID-19 is one of the most effective ways to control, and ideally, end the global COVID-19 pandemic. Vaccine hesitancy and vaccine rates vary widely across countries and populations and are influenced by complex sociocultural, political, economic and psychological factors. Community engagement is an integral strategy within immunisation campaigns and has been shown to improve vaccine acceptance. As evidence on community engagement to support COVID-19 vaccine uptake is emerging and constantly changing, research that lessens the knowledge-to-practice gap by providing regular and up-to-date evidence on current best-practice is essential., Methods and Analysis: A living systematic review will be conducted which includes an initial systematic review and bimonthly review updates. Searching and screening for the review and subsequent updates will be done in four streams: a systematic search of six databases, grey literature review, preprint review and citizen sourcing. The screening will be done by a minimum of two reviewers at title/abstract and full-text in Covidence, a systematic review management software. Data will be extracted across predefined fields in an excel spreadsheet that includes information about article characteristics, context and population, community engagement approaches, and outcomes. Synthesis will occur using the convergent integrated approach. We will explore the potential to quantitatively synthesise primary outcomes depending on heterogeneity of the studies., Ethics and Dissemination: The initial review and subsequent bimonthly searches and their results will be disseminated transparently via open-access methods. Quarterly briefs will be shared on the reviews' social media platforms and across other interested networks and repositories. A dedicated web link will be created on the Community Health-Community of Practice site for sharing findings and obtaining feedback. A mailing list will be developed and interested parties can subscribe for updates., Prospero Registration Number: CRD42022301996., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Community engagement (CE) has been increasingly implemented across health interventions, including for maternal and newborn health (MNH). This may take various forms, from participatory women's groups and community health committees to public advocacy days. While research suggests a positive influence of CE on MNH outcomes, such as mortality or care-seeking behaviour, there is a need for further evidence on the processes of CE in different settings in order to inform the future development and implementation of CE across programmes. Communication is an integral component of CE serving as a link between the programme and community. The aim of the realist review described in this protocol is to understand how, why, to what extent, and for whom CE contributes to intended and unintended outcomes in MNH programming, focusing on the communication components of CE., Methods: Realist review methodology will be used to provide a causal understanding of what communication for CE interventions in MNH programming work, for whom, to what extent, why, and how. This will be done by developing and refining programme theories on communications for CE in MNH through a systematic review of the literature and engaging key experts for input and feedback. By extrapolating context-mechanism-outcome configurations, this review seeks to understand how certain contexts trigger or inhibit specific mechanisms and what outcomes this interaction generates when communication in CE interventions is used in MNH programming., Discussion: A realist philosophy is well-suited to address the aims of this study because of the complex nature of CE. The review findings will be used to inform a realist evaluation case study of CE for an MNH programme in order to ascertain transferable findings that can inform and guide engagement activities in various settings. Findings will also be shared with stakeholders and experts involved in the consultative processes of the review (through workshops or policy briefs) in order to ensure the relevance of these findings to policy and practice., Systematic Review Registration: PROSPERO CRD42022293564., (© 2022. The Author(s).)

Introduction: Maternity waiting homes (MWHs) link pregnant women to skilled birth attendance at health facilities. Research suggests that some MWH-facility birth interventions are more success at meeting the needs and expectations of their intended users than others. We aimed to develop theory regarding what resources work to support uptake and scale-up of MHW-facility birth interventions, how, for whom, in what contexts and why., Methods: A four-step realist review was conducted which included development of an initial programme theory; searches for evidence; selection, appraisal and extraction of data; and analysis and data synthesis., Results: A programme theory was developed from 106 secondary sources and 12 primary interviews with MWH implementers. The theory demonstrated that uptake and scale-up of the MWH-facility birth intervention depends on complex interactions between three adopter groups: health system stakeholders, community gatekeepers and pregnant women and their families. It describes relationships between 19 contexts, 11 mechanisms and 31 outcomes accross nine context-mechanism-outcome configurations (CMOCs) which were grouped into 3 themes: (1) Engaging stakeholders to develop, integrate, and sustain MWH-facility birth interventions, (2) Promoting and enabling MWH-facility birth utilisation and (3) Creating positive and memorable MWH-facility birth user experiences. Belief, trust, empowerment, health literacy and perceptions of safety, comfort and dignity were mechanisms that supported diffusion and adoption of the intervention within communities and health systems. Examples of resources provided by implementers to trigger mechanisms associated with each CMOC were identified., Conclusions: Implementers of MWHs cannot merely assume that communities will collectively value an MWH-facility birth experience over delivery at home. We posit that MWH-facility birth interventions become vulnerable to under-utilisation when implementers fail to: (1) remove barriers that hinder women's access to MWH and (2) ensure that conditions and interactions experienced within the MWH and its affiliated health facility support women to feel treated with compassion, dignity and respect., Prospero Registration Number: CRD42020173595., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Understanding how pandemics differentially impact on the socio-protective and psychological outcomes of males and females is important to develop more equitable public health policies. We assessed whether males and females differed on measures of major depression and generalized anxiety during the COVID-19 the pandemic, and if so, which sociodemographic, pandemic, and psychological variables may affect sex differences in depression and anxiety., Methods: Participants were a nationally representative sample of Irish adults (N = 1,032) assessed between April 30 th to May 19 th , 2020, during Ireland's first COVID-19 nationwide quarantine. Participants completed self-report measures of anxiety (GAD-7) and depression (PHQ-9), as well as 23 sociodemographic pandemic-related, and psychological variables. Sex differences on measures of depression and anxiety were assessed using binary logistic regression analysis and differences in sociodemographic, pandemic, and psychological variables assessed using chi-square tests of independence and independent samples t-tests., Results: Females were significantly more likely than males to screen positive for major depressive disorder (30.6% vs. 20.7%; χ 2 (1) = 13.26, p < .001, OR = 1.69 [95% CI = 1.27, 2.25]), and generalised anxiety disorder (23.3% vs. 14.4%; χ 2 (1) = 13.42, p < .001, OR = 1.81 [95% CI = 1.31, 2.49]). When adjusted for all other sex-varying covariates however, sex was no longer significantly associated with screening positive for depression (AOR = 0.80, 95% CI = 0.51, 1.25) or GAD (AOR = 0.97, 95% CI = 0.60, 1.57)., Conclusion: Observed sex-differences in depression and anxiety during the COVID-19 pandemic in the Republic of Ireland are best explained by psychosocial factors of COVID-19 related anxiety, trait neuroticism, lower sleep quality, higher levels of loneliness, greater somatic problems, and, in the case of depression, increases in childcaring responsibilities and lower trait consciousnesses. Implications of these findings for public health policy and interventions are discussed., (© 2022. The Author(s).)

It is well recognized that clearance of bacterial infection within the dental pulp precedes pulpal regeneration. However, although the regenerative potential of the human dental pulp has been investigated extensively, its antimicrobial potential remains to be examined in detail. In the current study bactericidal assays were used to demonstrate that the secretome of dental pulp multipotent mesenchymal stromal cells (MSCs) has direct antibacterial activity against the archetypal Gram-positive and Gram-negative bacteria, Staphylococcus aureus and Escherichia coli, respectively, as well as the oral pathogens Streptococcus mutans, Lactobacillus acidophilus, and Fusobacterium nucleatum. Furthermore, a cytokine/growth factor array, enzyme-linked immunosorbent assays, and antibody blocking were used to show that cytokines and growth factors present in the dental pulp MSC secretome, including hepatocyte growth factor, angiopoietin-1, IL-6, and IL-8, contribute to this novel antibacterial activity. This study elucidated a novel and diverse antimicrobial secretome from human dental pulp MSCs, suggesting that these cells contribute to the antibacterial properties of the dental pulp. With this improved understanding of the secretome of dental pulp MSCs and its novel antibacterial activity, new evidence for the ability of the dental pulp to fight infection and restore functional competence is emerging, providing further support for the biological basis of pulpal repair and regeneration., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Current data on the prevalence and psychosocial correlates of sexual violence in the Republic of Ireland is lacking, with the most recent sexual abuse and violence survey dating back to 2001. The current study sought to identify what proportion of Irish adults have experienced sexual violence, if there are sex differences in exposure to different forms of sexual violence, and to what extent different forms of sexual violence are associated with adverse psychosocial outcomes. To achieve these objectives, we carried out a nationally representative sample of Irish adults ( N = 1,020) completed self-report measures of history of sexual violence and mental health. Results suggest that approximately one-in-three (34.4%) Irish adults experienced some form of sexual violence, including 14.8% who were sexually assaulted (raped) and 31.1% who were sexually harassed. Women were significantly more likely than men to have experienced all forms of sexual violence ( ps < .001), with the exception of sexual assault by a parent or guardian. All forms of sexual violence were associated with an increased likelihood of serious mental health problems, with sexual assault by a parent/guardian associated with several other psychosocial outcomes in life, including education achievement, history of being taken into state care, salary, and employment status. Sexual violence is a common experience in the general population and women are disproportionately affected (1-in-2 women versus 1-in-5 men). Additional resources to increase mental health care among survivors of sexual violence is urgently needed. How our findings compare to Ireland's previous sexual abuse and violence survey and the implications of our findings for policy are discussed.

A simple, non-invasive, colour-based carbon dioxide (CO 2 ) indicator is described. The indicator provides an indirect response to the rapid, aerobic microbial colonisation of an underlying wound when used in conjunction with an occlusive ( i.e. sealed) dressing. The indicator has potential as an early warning indicator of infection in chronic wounds.

Background: Antenatal care (ANC) and postnatal care (PNC) are critical opportunities for women, babies and parents/families to receive quality care and support from health services. Community-based interventions may improve the accessibility, availability, and acceptance of this vital care. For example, community mobilization strategies have been used to involve and collaborate with women, families and communities to improve maternal and newborn health., Objective: To synthesize existing reviews of evidence on community mobilization strategies that strengthen support for appropriate and timely use of ANC and PNC., Methods: Six databases (MEDLINE, Embase, CINAHL, PsychINFO, Cochrane Library, PROSPERO) were searched for published reviews that describe community mobilization related strategies for ANC and/or PNC. Reviews were eligible for inclusion if they described any initiatives or strategies targeting the promotion of ANC and/or PNC uptake that included an element of community mobilization in a low- or middle-income country (LMIC), published after 2000. Included reviews were critically appraised according to the Joanna Briggs Institute (JBI) Checklist for Systematic Reviews and Evidence Syntheses. This review of reviews was conducted following JBI guidelines for undertaking and reporting umbrella reviews., Results: In total 23 papers, representing 22 reviews were included. While all 22 reviews contained some description of community mobilization and ANC/PNC, 13 presented more in-depth details on the community mobilization processes and relevant outcomes. Seventeen reviews focused on ANC, four considered both ANC and PNC, and only one focused on PNC. Overall, 16 reviews reported at least one positive association between community mobilization activities and ANC/PNC uptake, while five reviews presented primary studies with no statistically significant change in ANC uptake and one included a primary study with a decrease in use of antenatal facilities. The community mobilization activities described by the reviews ranged from informative, passive communication to more active, participatory approaches that included engaging individuals or consulting local leaders and community members to develop priorities and action plans., Conclusions: While there is considerable momentum around incorporating community mobilization activities in maternal and newborn health programs, such as improving community support for the uptake of ANC and PNC, there is limited evidence on the processes used. Furthermore, the spectrum of terminology and variation in definitions should be harmonized to guide the implementation and evaluation efforts., Competing Interests: Competing interests: The authors completed the ICMJE Declaration of Interest form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Background: Given the unprecedented nature of the COVID-19 pandemic, the Irish health system required the redeployment of public sector staff and the recruitment of dedicated contact tracing staff in the effort to contain the spread of the virus. Contact tracing is crucial for effective disease control and is normally carried out by public health teams. Contact tracing staff are provided with rapid intensive training but are operating in a dynamic environment where processes and advice are adapting continuously. Real-time data is essential to inform strategy, coordinate interconnected processes, and respond to needs . Given that many contact tracers have been newly recruited or redeployed, they may not have significant experience in healthcare and may experience difficulties in managing the anxieties and emotional distress of the public. Aim: (i) identify emerging needs and issues and feed this information back to the Health Service Executive for updates to the COVID-19 Contact Management Programme (CMP); (ii) understand the psychological impact on contact tracers and inform the development of appropriate supports. Methods: We will use a mixed-methods approach. A brief online survey will be administered at up to three time points during 2021 to measure emotional exhaustion, anxiety, general health, and stress of contact tracing staff, identify tracing systems or processes issues, as well as issues of concern and confusion among the public. Interviews will also be conducted with a subset of participants to achieve a more in-depth understanding of these experiences. Observations may be conducted in contact tracing centres to document processes, practices, and explore any local contextual issues. Impact: Regular briefs arising from this research with data, analysis, and recommendations will aim to support the work of the CMP to identify problems and implement solutions. We will deliver regular feedback on systems issues; challenges; and the psychological well-being of contact tracing staff., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 O'Donovan R et al.)

Below-knee amputation remains the most common level of amputation in patients with lower extremity gangrene and critical limb ischemia. Failure to heal, requiring additional operative debridement or conversion to an above-knee amputation remains a significant cause of patient morbidity. There remains no definitive diagnostic test that can accurately predict healing of the amputation site. We report a case utilizing a hybrid technique of retrograde transamputation revascularization via balloon angioplasty. This proximal, retrograde approach allows for relatively easy crossing and treatment of the infrainguinal chronic total occlusions (CTOs), improving arterial inflow for optimal wound healing., (Copyright © 2021. Published by Elsevier Inc.)

Background: Stakeholder and community engagement promotes collaboration and gives service users an opportunity to actively participate in the care they receive. Recognizing this potential, The Network for Improving Quality of Care for maternal, newborn and child health aimed to identify tools and operational guidance to integrate stakeholder and community engagement into quality improvement (QI) implementation., Methods: A mapping, consisting of a literature review and an open call through email and listservers, for implementation tools was conducted. Materials were included if they provided guidance on stakeholder and community engagement aligned to the Network's QI framework comprising seven phases. Screening of tools was done by two reviewers., Results: The literature search and the call for tools returned 197 documents with 70 tools included after screening. Most included tools (70%) were published after 2010. International organizations were the most frequently cited authors of tools. Only 15 tools covered all seven phases of the QI framework; few tools covered the more 'technical' phase of the QI framework: adapting standards and refining strategies., Conclusion: The quantity of tools and their varied characteristics including types of stakeholder and community engagement processes across the QI framework confirms that engagement cannot be captured in a 'one-size-fits-all' formula. Many tools were designed with a generic focus to allow for adaption and use in different settings and sectors. Country programmes looking to strengthen engagement approaches can take advantage of available tools through an online portal on the WHO website and adapt them to meet their specific needs and context., Public Involvement: Programme implementers provided tools and resources during data collection., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Humanitarian workers are at an elevated risk of occupational trauma exposure and its associated psychological consequences, and experience increased levels of anxiety, depression, and post-traumatic stress disorder (PTSD) compared to the general population. Psychological first aid (PFA) aims to prevent acute distress reactions from developing into long-term distress by instilling feelings of safety, calmness, self- and community efficacy, connectedness and hope. Group PFA (GPFA) delivers PFA in a group or team setting. This research sought to understand 'What works, for whom, in what context, and why for group psychological first aid for humanitarian workers, including volunteers?' A rapid realist review (RRR) was conducted. Initial theories were generated to answer the question and were subsequently refined based on 15 documents identified through a systematic search of databases and grey literature, in addition to the inputs from a core reference panel and two external experts in GPFA. The findings generated seven programme theories that addressed the research question and offered consideration for the implementation of GPFA for the humanitarian workforce across contexts and age groups. GPFA enables individuals to understand their natural reactions, develop adaptive coping strategies, and build social connections that promote a sense of belonging and security. The integrated design of GPFA ensures that individuals are linked to additional supports and have their basic needs addressed. While the evidence is sparce on GPFA, its ability to provide support to humanitarian workers is promising.

Background: Capacity strengthening of primary health care workers is widely used as a means to strengthen health service delivery, particularly in low- and middle-income countries. Despite the widespread recognition of the importance of capacity strengthening to improve access to quality health care, how the term 'capacity strengthening' is both used and measured varies substantially across the literature. This scoping review sought to identify the most common domains of individual capacity strengthening, as well as their most common forms of measurement, to generate a better understanding of what is meant by the term 'capacity strengthening' for primary health care workers., Methods: Six electronic databases were searched for studies published between January 2000 and October 2020. A total of 4474 articles were screened at title and abstract phase and 323 full-text articles were reviewed. 55 articles were ultimately identified for inclusion, covering various geographic settings and health topics., Results: Capacity strengthening is predominantly conceptualised in relation to knowledge and skills, as either sole domains of capacity, or used in combination with other domains including self-efficacy, practices, ability, and competencies. Capacity strengthening is primarily measured using pre- and post-tests, practical evaluations, and observation. These occur along study-specific indicators, though some pre-existing, validated tools are also used., Conclusion: The concept of capacity strengthening for primary health care workers reflected across a number of relevant frameworks and theories differs from what is commonly seen in practice. A framework of individual capacity strengthening across intra-personal, inter-personal, and technical domains is proposed, as an initial step towards building a common consensus of individual capacity strengthening for future work.

Background: As the use of minimally invasive techniques in colorectal surgery has become increasingly prevalent, concerns remain about the oncologic effectiveness and long-term outcomes of minimally invasive low anterior resection (MI-LAR) for the treatment of rectal cancer., Study Design: The 2010-2015 National Cancer Database (NCDB) Participant Data Use File was queried for patients undergoing elective open LAR (OLAR) or MI-LAR for rectal adenocarcinoma. A 1:1 propensity match was performed on the basis of demographics, comorbidity, and tumor characteristics. Outcomes were compared between groups and Cox proportional hazard modeling was performed to identify independent predictors of mortality. A subset analysis was performed on high-volume academic centers., Results: 35,809 patients undergoing LAR were identified of whom 18,265 (51.0%) underwent MI-LAR. After propensity matching, patients receiving MI-LAR were less likely to have a positive circumferential radial margin (CRM) (5.5% vs. 6.6%, p = 0.0094) or a positive distal margin (3.6% vs. 4.6%, p = 0.0022) and had decreased 90-day all-cause mortality (2.0% vs. 2.6%, p = 0.0238). MI-LAR resulted in decreased hospital length of stay (5 vs. 6 days, p < 0.0001) but a greater rate of 30-day readmission (7.6% vs. 6.5%, p = 0.0054). Long-term overall survival was improved with MI-LAR (79% vs. 76%, p < 0.0001). Cox proportional hazard modeling demonstrated a decreased risk of mortality with MI-LAR (HR 0.859, 95% CI 0.788-0.937)., Conclusion: MI-LAR is associated with improvement in CRM clearance and long-term survival. In the hands of experienced surgeons with advanced laparoscopy skills, MI-LAR appears safe and effective technique for the management of rectal cancer.

Introduction: Community engagement has been considered a fundamental component of past outbreaks, such as Ebola. However, there is concern over the lack of involvement of communities and 'bottom-up' approaches used within COVID-19 responses thus far. Identifying how community engagement approaches have been used in past epidemics may support more robust implementation within the COVID-19 response., Methodology: A rapid evidence review was conducted to identify how community engagement is used for infectious disease prevention and control during epidemics. Three databases were searched in addition to extensive snowballing for grey literature. Previous epidemics were limited to Ebola, Zika, SARS, Middle East respiratory syndromeand H1N1 since 2000. No restrictions were applied to study design or language., Results: From 1112 references identified, 32 articles met our inclusion criteria, which detail 37 initiatives. Six main community engagement actors were identified: local leaders, community and faith-based organisations, community groups, health facility committees, individuals and key stakeholders. These worked on different functions: designing and planning, community entry and trust building, social and behaviour change communication, risk communication, surveillance and tracing, and logistics and administration., Conclusion: COVID-19's global presence and social transmission pathways require social and community responses. This may be particularly important to reach marginalised populations and to support equity-informed responses. Aligning previous community engagement experience with current COVID-19 community-based strategy recommendations highlights how communities can play important and active roles in prevention and control. Countries worldwide are encouraged to assess existing community engagement structures and use community engagement approaches to support contextually specific, acceptable and appropriate COVID-19 prevention and control measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Close-to-community (CTC) health service providers are a cost-effective and important resource in the promotion of and increasing access to health services. However, many CTC provider programmes suffer from high rates of de-motivation and attrition due to inadequate support systems. Recent literature has identified the lack of rigorous approaches towards measuring and monitoring motivation among CTC providers as an important gap. Building on scales used in previous studies, we set out to develop a short, simple-to-administer scale to monitor and measure indicators of CTC provider motivation across CTC programmes implemented in six countries: Ethiopia, Kenya, Malawi, Mozambique, Indonesia, and Bangladesh., Methods: We used focus group discussions (n = 18) and interviews (n = 106) conducted with CTC providers across all six countries, applying thematic analysis techniques to identify key determinants of motivation across these contexts. These themes were then used to carry out a systematic search of the literature, to identify existing scales or questionnaires developed for the measurement of these themes. A composite 24-item scale was then administered to CTC providers (n = 695) across the six countries. Survey responses were subsequently randomly assigned to one of two datasets: the first for scale refinement, using exploratory techniques, and the second for factorial validation. Confirmatory factor analysis was applied to both datasets., Results: Results suggest a 12-item, four-factor structure, measuring community commitment, organisational commitment, job satisfaction, and work conscientiousness as common indicators of motivation among CTC providers across the six countries., Conclusions: Consistent with previous studies, findings support the inclusion of job satisfaction, organisational commitment, and work conscientiousness within the CTC Provider Motivation Indicator Scale. In addition, findings further supported the addition of a fourth, community commitment, sub-scale. Practical applications of the revised scale, including how it can be applied to monitor motivation levels within CTC provider programming, are discussed.

Objective: The management of patients with combined severe carotid artery and coronary artery disease (CAD) is controversial. Transcarotid stenting with flow reversal (TCAR) is a novel hybrid technique for carotid revascularization. We sought to investigate the safety and feasibility of simultaneous TCAR and coronary artery bypass grafting (CABG) for concomitant carotid and CAD., Methods: A single-institution, retrospective study of patients with critical carotid artery stenosis and symptomatic CAD who underwent simultaneous TCAR-CABG was completed. The primary outcomes were technical success, perioperative stroke, death, and hemorrhage., Results: Four patients underwent TCAR-CABG. All patients were male with a mean age of 64. Technical success was achieved in all cases. There were no perioperative strokes or deaths. There were no reexplorations for hemorrhage., Conclusions: Transcarotid stenting with flow reversal-CABG is a technically feasible hybrid approach for simultaneous carotid and coronary revascularization. It should be part of the vascular surgeon's armamentarium for coexisting carotid and coronary disease. Further research focused on patient selection and perioperative antiplatelet management is warranted prior to the widespread adoption of this technique.

Realist evaluation, a methodology for exploring generative causation within complex health interventions to understand 'how, why and for whom' programmes work, is experiencing a surge of interest. Trends indicate that the proliferation in the use of this methodology also applies to research in low- and middle-income countries (LMICs). The value of using realist evaluation for project evaluation is also being noticed by non-governmental organisations (NGOs) and other programme implementers within such contexts. Yet, there is limited exploration of the use of realist evaluations in LMICs, especially their use by foreign researchers. This paper draws on the author's experience of conducting two realist evaluations across three different sub-Saharan African settings: Mundemu, Tanzania; Kabale, Uganda and Marsabit, Kenya. The realist evaluations were used as an operations research methodology to study two NGO community health programmes. This paper highlights four main challenges experienced by the author throughout the methodological process: (1) power imbalances prevalent during realist interviews, (2) working through translation and what this means for identfying Context-Mechanism-Outcome Configurations, (3) limited contextual familiarity and being an 'engaged researcher' and (4) the use or dependence on 'WEIRD' theories (i.e. theories based on the study of Western, Educated, Industrialized, Rich, Democratic people) within testing and refinement. Realist evaluation's enticing and straightforward slogan of finding 'what works, for whom and why' is in contrast to the complexity of the methodology used to generate these results (and often to the results themselves). Striking a balance between theory and pragmatism, while adhering to realist ontological underpinnings of generative causation and retroduction, is no easy task. This paper concludes by providing concrete recommendations for those who want to undertake a realist evaluation, with particular attention to cross-cultural settings, in light of the aforementioned challenges. In doing so, it aims to foster improved methodological rigour and help those engaging in this research methodology to work towards more appropriate and contextually relevant findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Atmospheric cold plasma (ACP) offers great potential for decontamination of food borne pathogens. This study examined the antimicrobial efficacy of ACP against a range of pathogens of concern to fresh produce comparing planktonic cultures, monoculture biofilms (Escherichia coli, Salmonella enterica, Listeria monocytogenes, Pseudomonas fluorescens) and mixed culture biofilms (Listeria monocytogenes and Pseudomonas fluorescens). Biotic and abiotic surfaces commonly occurring in the fresh food industry were investigated. Microorganisms showed varying susceptibility to ACP treatment depending on target and process factors. Bacterial biofilm populations treated with high voltage (80 kV) ACP were reduced significantly (p < 0.05) in both mono- and mixed species biofilms after 60 s of treatment and yielded non-detectable levels after extending treatment time to 120 s. However, an extended time was required to reduce the challenge mixed culture biofilm of L. monocytogenes and P. fluorescens inoculated on lettuce, which was dependent on biofilm formation conditions and substrate. Contained treatment for 120 s reduced L. monocytogenes and P. fluorescens inoculated as mixed cultures on lettuce (p < 0.05) by 2.2 and 4.2 Log 10 CFU/ml respectively. When biofilms were grown at 4 °C on lettuce, there was an increased resistance to ACP treatment by comparison with biofilm grown at temperature abuse conditions of 15 °C. Similarly, L. monocytogenes and P. fluorescens exposed to cold stress (4 °C) for 1 h demonstrated increased tolerance to ACP treatment compared to non-stressed cells. These finding demonstrates that bacterial form, mono versus mixed challenges as well as environmental stress conditions play an important role in ACP inactivation efficacy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Scaling-up is essential to ensure universal access of effective health interventions. Scaling-up is a complex process, which occurs across diverse systems and contexts with no one-size-fits-all approach. To date, little attention has been paid to the process of scaling-up in how to make adaptations for local fit. The aim of this research is to develop theory on what actions can be used to make adaptations to health interventions for local fit when scaling-up across diverse contexts that will have practical application for implementers involved in scaling-up., Methods and Analysis: Given the complexity of this subject, a realist review methodology was selected. Specifically, realist review emphasises an iterative, non-linear process, whereby the review is refined as it progresses. The identification of how the context may activate mechanisms to achieve outcomes is used to generate theories on what works for whom in what circumstances. This protocol will describe the first completed stage of development of an initial programme theory framework, which identified potential actions, contexts, mechanisms and outcomes that could be used to make adaptations when scaling-up. It will then outline the methods for future stages of the review which will focus on identifying case examples of scale-up and adaptation in practice. This realist review consists of six stages: (i) clarifying scope and development of a theoretical framework, (ii) developing a search strategy, (iii) selection and appraisal, (iv) data extraction, (v) data synthesis and analysis and (vi) further theory refinement with stakeholders., Ethics and Dissemination: This review will develop theory on how adaptations can be made when scaling-up. Findings will be disseminated in a peer-reviewed journal and through stakeholder engagement as part of the research process. Ethical approval has been received through Health Policy and Management/Centre for Global Health Research Ethics Committee of Trinity College Dublin., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite little evidence for its effectiveness, the breath-actuated nebulizer (BAN) is the default albuterol delivery method in our pediatric emergency department., Objective: We compared the clinical efficacy of BAN and the metered-dose inhaler (MDI) in treating subjects patients 2 to 17 years of age who presented with mild to moderate asthma exacerbations., Methods: This is a randomized, nonblinded, noninferiority study conducted at a single pediatric tertiary care emergency department. Subjects presenting with a Pediatric Asthma Score ranging from 5 to 11 received albuterol by BAN or MDI via standard weight-based and symptom severity dosing protocols. Aerosolized ipratropium (via BAN) and intravenous magnesium sulfate were given when clinically indicated. The primary outcome was patient disposition. The noninferiority margin for the primary outcome was an admission rate difference ≤10%. Analyses were adjusted for confounders that were significant at p ≤ 0.10., Results: We enrolled 890 subjects between October 2014 and April 2015. BAN and MDI groups were comparable for age, gender, and race but not for pretreatment symptom severity; 51% in the MDI group had a Pediatric Asthma Score of moderate severity (8-11) vs. 63% in the BAN group (p < 0.003). Unadjusted admission rates were 11.9% for MDI and 12.8% for BAN, for an unadjusted risk difference of -0.9% (95% confidence interval -5% to 3%). After adjusting for baseline confounder severity, the risk difference was 2% (95% confidence interval -4% to 7%), which met the criteria for noninferiority., Conclusions: Albuterol therapy by MDI is noninferior to BAN for the treatment of mild to moderate asthma exacerbations in children 2 to 17 years of age., (Copyright © 2018 Elsevier Inc. All rights reserved.)

While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients. Profiling of (Pro-Lys)-ABP bound proteases revealed that most of hyperactive proteases from IBD secretome are clustered at 28-kDa. We identified seven active proteases: the serine proteases cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3 A, and thrombin and the aminopeptidase B. Only cathepsin G and thrombin were overactive in supernatants from IBD patient tissues compared to healthy controls. Gene expression analysis highlighted the transcription of genes encoding these proteases into intestinal mucosae. The functional ABP-targeted proteomic approach that we have used to identify active proteases in human colonic samples bears directly on the understanding of the role these enzymes may play in the pathophysiology of IBD.

Aim: To determine the proportion of pregnant women vaccinated with the pertussis booster in the third trimester of their pregnancy, and explore factors influencing coverage., Methods: A clinical audit was undertaken at Rotorua hospital using electronic databases to determine pertussis immunisation among women who birthed from 25 March to 25 April, 2017 (n=111). Lead maternity carers (LMCs) were surveyed to assess knowledge of the vaccine and explore suggestions to increase vaccination coverage., Results: Only 44% (n=49) of women were vaccinated in 2017. Women 25 years and under, and women from Rotorua were less likely to be vaccinated. A woman not being recalled to the GP for vaccination was the biggest reason for not being vaccinated (n=27). Every woman in Taupo/Turangi was recalled in pregnancy, leading to greater vaccine uptake compared to women in Rotorua., Conclusion: Overall, the proportion of pregnant women vaccinated for pertussis continue to be low with coverage being disproportionally lower for younger women. The integrated healthcare approach in Taupo/Turangi has resulted in improved vaccine uptake. Interventions that allow general practitioners, LMCs and primary health organisations to work together can improve vaccination rates of pregnant mothers in New Zealand., Competing Interests: Nil.

Bilateral recurrence of atrial myxoma has been reported only a few times. We describe the case of a 41-year-old woman who had undergone left atrial myxoma resection and presented 9 years later with myxomas in both atria. The patient underwent successful resection of both masses with resolution of symptoms. We discuss the phenomenon of recurrent biatrial myxoma.

Background: Practice guidelines differ in their support of adjuvant chemotherapy use in patients who received preoperative chemoradiation for rectal cancer., Objective: The purpose of this study was to evaluate the impact of adjuvant chemotherapy among patients with locally advanced rectal cancer who received neoadjuvant chemoradiation and surgery., Design: This was a retrospective study. Multivariable Cox proportional hazard modeling was used to evaluate the adjusted survival differences., Settings: Data were collected from the National Cancer Database., Patients: Adults with pathologic stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation and surgery were included., Main Outcome Measures: Overall survival was measured., Results: Among 12,696 patients included, 4023 (32%) received adjuvant chemotherapy. The use of adjuvant chemotherapy increased over the study period from 23% to 36%. Although older age and black race were associated with a lower likelihood of receiving adjuvant chemotherapy, patients with higher education level and stage III disease were more likely to receive adjuvant chemotherapy (all p < 0.05). At 7 years, overall survival was improved among patients who received adjuvant chemotherapy (60% vs. 55%; p < 0.001). After risk adjustment, the use of adjuvant chemotherapy was associated with improved survival (HR = 0.81 (95% CI, 0.72-0.91); p < 0.001). In the subgroup of patients with stage II disease, survival was also improved among patients who received adjuvant chemotherapy (68% vs 58% at 7 y; p < 0.001; HR = 0.70 (95% CI, 0.57-0.87); p = 0.002). Among patients with stage III disease, the use of adjuvant chemotherapy was associated with a smaller but persistent survival benefit (56% vs 51% at 7 y; p = 0.017; HR = 0.85 (95% CI, 0.74-0.98); p = 0.026)., Limitations: The study was limited by its potential for selection bias and inability to compare specific chemotherapy regimens., Conclusions: The use of adjuvant chemotherapy among patients with rectal cancer who received preoperative chemoradiation conferred a survival benefit. This study emphasizes the importance of adjuvant chemotherapy in the management of rectal cancer and advocates for its increased use in the setting of neoadjuvant therapy. See Video Abstract at http://link.lww.com/DCR/A428.

Background: It is estimated that over one billion persons worldwide have some form of disability. However, there is lack of knowledge and prioritisation of how to serve the needs and provide opportunities for people with disabilities. The community-based rehabilitation (CBR) guidelines, with sufficient and sustained support, can assist in providing access to rehabilitation services, especially in less resourced settings with low resources for rehabilitation. In line with strengthening the implementation of the health-related CBR guidelines, this study aimed to determine what workforce characteristics at the community level enable quality rehabilitation services, with a focus primarily on less resourced settings., Methodology: This was a two-phase review study using (1) a relevant literature review informed by realist synthesis methodology and (2) Delphi survey of the opinions of relevant stakeholders regarding the findings of the review. It focused on individuals (health professionals, lay health workers, community rehabilitation workers) providing services for persons with disabilities in less resourced settings., Results: Thirty-three articles were included in this review. Three Delphi iterations with 19 participants were completed. Taken together, these produced 33 recommendations for developing health-related rehabilitation services. Several general principles for configuring the community rehabilitation workforce emerged: community-based initiatives can allow services to reach more vulnerable populations; the need for supportive and structured supervision at the facility level; core skills likely include case management, social protection, monitoring and record keeping, counselling skills and mechanisms for referral; community ownership; training in CBR matrix and advocacy; a tiered/teamwork system of service delivery; and training should take a rights-based approach, include practical components, and involve persons with disabilities in the delivery and planning., Conclusion: This research can contribute to implementing the WHO guidelines on the interaction between the health sector and CBR, particularly in the context of the Framework for Action for Strengthening Health Systems, in which human resources is one of six components. Realist syntheses can provide policy makers with detailed and practical information regarding complex health interventions, which may be valuable when planning and implementing programmes.

The present study examined the removal of phosphorus following electrocoagulation post-treatment using a sample from a commercial firm. Samples were subjected to column chromatography using Octolig® a polyethylenediimine covalently attached to high-surface-area silica. Two commercial samples with significantly different phosphorus concentrations were evaluated: 10.2 ppm from polyphosphates and raw sample of 983 ppm P. After passing over Octolig®, the sample phosphate concentration was reduced to values of <0.05 ppm P.

There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad-spectrum antibiotics and health-related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio-active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food- and healthcare-associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action., (© 2017 The Society for Applied Microbiology.)

Introduction: The proposed research is part of ongoing operations research within World Vision's Access: Infant and Maternal Health Programme. This study aims to identify key context features and underlying mechanisms through which community health committees build community capacity within the field of maternal and child health. This may help to improve programme implementation by providing contextually informed and explanatory findings for how community health committees work, what works best and for whom do they work for best for. Though frequently used within health programmes, little research is carried out on such committees' contribution to capacity building-a frequent goal or proposed outcome of these groups., Methods and Analysis: The scarce information that does exist often fails to explain 'how, why, and for whom' these committees work best. Since such groups typically operate within or as components of complex health interventions, they require a systems thinking approach and design, and thus so too does their evaluation. Using a mixed methods realist evaluation with intraprogramme case studies, this protocol details a proposed study on community health committees in rural Tanzania and Uganda to better understand underlying mechanisms through which these groups work (or do not) to build community capacity for maternal and child health. This research protocol follows the realist evaluation methodology of eliciting initial programme theories, to inform the field study design, which are detailed within. Thus far, the methodology of a realist evaluation has been well suited to the study of community health committees within these contexts. Implications for its use within these contexts are discussed within., Ethics and Dissemination: Institutional Review Boards and the appropriate research clearance bodies within Ireland, Uganda and Tanzania have approved this study. Planned dissemination activities include via academic and programme channels, as well as feedback to the communities in which this work occurs., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Good governance may result in strengthened performance of a health system. Coherent policies are essential for good health system governance. The overall aim of this research is to provide the best available scientific evidence on principles of good policy related leadership and governance of health related rehabilitation services in less resourced settings. This research was also conducted to support development of the World Health Organization's (WHO) Guidelines on health related rehabilitation., Methods: An innovative study design was used, comprising two methods: a systematic search and realist synthesis of literature, and a Delphi survey of expert stakeholders to refine and triangulate findings from the realist synthesis. In accordance with Pawson and Tilley's approach to realist synthesis, we identified context mechanism outcome pattern configurations (CMOCs) from the literature. Subsequently, these CMOCs were developed into statements for the Delphi survey, whereby 18 expert stakeholders refined these statements to achieve consensus on recommendations for policy related governance of health related rehabilitation., Results: Several broad principles emerged throughout formulation of recommendations: participation of persons with disabilities in policy processes to improve programme responsiveness, efficiency, effectiveness, and sustainability, and to strengthen service-user self-determination and satisfaction; collection of disaggregated disability statistics to support political momentum, decision-making of policymakers, evaluation, accountability, and equitable allocation of resources; explicit promotion in policies of access to services for all subgroups of persons with disabilities and service-users to support equitable and accessible services; robust inter-sectoral coordination to cultivate coherent mandates across governmental departments regarding service provision; and 'institutionalizing' programmes by aligning them with preexisting Ministerial models of healthcare to support programme sustainability., Conclusions: Alongside national policymakers, our policy recommendations are relevant for several stakeholders, including service providers and service-users. This research aims to provide broad policy recommendations, rather than a strict formula, in acknowledgement of contextual diversity and complexity. Accordingly, our study proposes general principles regarding optimal policy related governance of health related rehabilitation in less resourced settings, which may be valuable across diverse health systems and contexts.

Introduction: Understanding what enhances the motivation and performance of community health workers (CHWs) in humanitarian emergencies represents a key research gap within the field of human resources for health. This paper presents the research protocol for the Performance ImprovEment of CHWs in Emergency Settings (PIECES) research programme. Enhancing Learning and Research in Humanitarian Action (ELRHA) funded the development of this protocol as part of their Health in Humanitarian Crises (R2HC) call (No.19839). PIECES aims to understand what factors improve the performance of CHWs in level III humanitarian emergencies., Methods and Analysis: The suggested protocol uses a realist evaluation with multiple cases across the 3 country sites: Turkey, Iraq and Lebanon. Working with International Medical Corps (IMC), an initial programme theory was elicited through literature and document reviews, semistructured interviews and focus groups with IMC programme managers and CHWs. Based on this initial theory, this protocol proposes a combination of semistructured interviews, life histories and critical incident narratives, surveys and latent variable modelling of key constructs to explain how contextual factors work to trigger mechanisms for specific outcomes relating to IMC's 300+ CHWs' performance. Participants will also include programme staff, CHWs and programme beneficiaries. Realist approaches will be used to better understand 'what works, for whom and under what conditions' for improving CHW performance within humanitarian contexts., Ethics and Dissemination: Trinity College Dublin's Health Policy and Management/Centre for Global Health Research Ethics Committee gave ethical approval for the protocol development phase. For the full research project, additional ethical approval will be sought from: Université St. Joseph (Lebanon), the Ethics Committee of the Ministry of Health in Baghdad (Iraq) and the Middle East Technical University (Turkey). Dissemination activities will involve a mixture of research feedback, policy briefs, guidelines and recommendations, as well as open source academic articles., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: In 2010, the Ministry of Health and Sanitation in Sierra Leone launched their Free Health Care Initiative (FHCI) for pregnant and lactating mothers and children under-5. Despite an increase in the update of services, the inequitable distribution of health services and health facilities remain important factors underlying the poor performance of health systems to deliver effective services. This study identifies current gaps in service delivery across two rural locations served by the same District Health Management Team (DHMT)., Methods: We employed a cross-sectional household survey using a two-stage probability sampling method to obtain a sample of the population across two rural locations in Bonthe District: the riverine and the mainland. Overall, a total of 393 households across 121 villages were surveyed in the riverine and 397 households across 130 villages were sampled on the mainland. Maternal health, child health and sanitation indicators in Bonthe District were compared using Pearson Chi-Squared test with Yates' Continuity Correction across the two areas., Results: Women across the two regions self-reported significantly different uptake of family planning services. Children on the mainland had significantly greater rates of health facility based deliveries; being born in the presence of a skilled birth attendant; completed immunisation schedules; and higher rates of being brought to the health centre within 24 h of developing a fever or a suspected acute respiratory infection. Households on the mainland also reported significantly greater use of treated water and unrestricted access to a latrine., Conclusions: If the government of Sierra Leone is going to deliver on their promise to free health care for pregnant women and their children, and do so in a way that reduces inequalities, greater attention must be paid to the existing service delivery gaps within each District. This is particularly relevant to health policy post-Ebola, as it highlights the need for more contextualised service delivery to ensure equitable access for women and children.

Percutaneous interventions to maintain or re-establish patent vascular access are common and often necessary for patients on hemodialysis. This case illustrates an extremely rare but potentially devastating complication of one of these procedures: cerebrovascular insult due to paradoxical embolism in the setting of a patent foramen ovale.

Objective: In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity., Methods: Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference., Results: Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SI geometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10(-5) min(-1)/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use., Conclusion: In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

Background: The systematic involvement of project beneficiaries in community maternal and child health programmes remains low and limited, especially during the formative stages of the project cycle. Understanding how positive and negative feedbacks obtained from communities can subsequently be used to inform and iterate existing programmes is an important step towards ensuring the success of community health workers for maternal and child health programming and, ultimately, for improving health outcomes., Methods: The study took place over a period of 4 weeks in North Rukiga, Kabale District of southwestern Uganda. Using a cross-sectional qualitative study that employed an epistemological approach of phenomenology, nine focus group discussions and eight in-depth interviews were conducted with a total of 76 female participants across six different sites. Women were identified as either users or non-users of the maternal and child health programme. Purposeful sampling was employed to recruit women from six different locations within the programme catchment area. Translated and transcribed transcripts were subjected to a bottom-up thematic analysis using NVivo 10 Software, whereby themes were arrived at inductively., Results: Predominant themes emerging from the focus groups and key informant interviews identified early trends in programme strengths. Beneficiaries reported confidence in both the programme and the relationships they had forged with community health workers, exhibited pride in the knowledge they had received, and described improved spousal involvement. Beneficiaries also identified a number of programme challenges including barriers to adopting the behaviours promoted by the programme, and highlighted issues with programme dependency and perceived ownership. It also emerged that community health workers were not reaching the entire population of intended programme beneficiaries., Conclusions: This research provides support for the importance of an early-stage participatory evaluation of beneficiaries' perceptions of newly initiated health programmes. Our results support how evaluations conducted in the early phases of programme implementation can provide valuable, timely feedback as well as yield recommendations for programme adjustment or re-alignment, and in turn, better meet end-user expectations. Potential reasons for the observed lack of community participation in early stages of programme implementation are considered.

Aims: The main aim of this study was to determine the virucidal inactivation efficacy of an in-house-designed atmospheric pressure, nonthermal plasma jet operated at varying helium/oxygen feed gas concentrations against MS2 bacteriophage, widely employed as a convenient surrogate for human norovirus., Methods and Results: The effect of variation of percentage oxygen concentration in the helium (He) carrier gas was studied and found to positively correlate with MS2 inactivation rate, indicating a role for reactive oxygen species (ROS) in viral inactivation. The inactivation rate constant increased with increasing oxygen concentrations up to 0·75% O2 . 3 log10 (99·9%) reductions in MS2 viability were achieved after 3 min of exposure to the plasma source operated in a helium/oxygen (99·25% : 0·75%) gas mixture, with >7 log10 reduction after 9 min exposure., Conclusions: Atmospheric pressure, nonthermal plasmas may have utility in the rapid disinfection of virally contaminated surfaces for infection control applications., Significance and Impact of Study: The atmospheric pressure, nonthermal plasma jet employed in this study exhibits rapid virucidal activity against a norovirus surrogate virus, the MS2 bacteriophage, which is superior to previously published inactivation rates for chemical disinfectants., (© 2013 The Society for Applied Microbiology.)

Background: Community Health Workers are widely utilised in low- and middle-income countries and may be an important tool in reducing maternal and child mortality; however, evidence is lacking on their effectiveness for specific types of programmes, specifically programmes of a preventive nature. This review reports findings on a systematic review analysing effectiveness of preventive interventions delivered by Community Health Workers for Maternal and Child Health in low- and middle-income countries., Methods: A search strategy was developed according to the Evidence for Policy and Practice Information and Co-ordinating Centre's (EPPI-Centre) guidelines and systematic searching of the following databases occurred between June 8-11th, 2012: CINAHL, Embase, Ovid Nursing Database, PubMed, Scopus, Web of Science and POPLINE. Google, Google Scholar and WHO search engines, as well as relevant systematic reviews and reference lists from included articles were also searched. Inclusion criteria were: i) Target beneficiaries should be pregnant or recently pregnant women and/or children under-5 and/or caregivers of children under-5; ii) Interventions were required to be preventive and delivered by Community Health Workers at the household level. No exclusion criteria were stipulated for comparisons/controls or outcomes. Study characteristics of included articles were extracted using a data sheet and a peer tested quality assessment. A narrative synthesis of included studies was compiled with articles being coded descriptively to synthesise results and draw conclusions., Results: A total of 10,281 studies were initially identified and through the screening process a total of 17 articles detailing 19 studies were included in the review. Studies came from ten different countries and consisted of randomized controlled trials, cluster randomized controlled trials, before and after, case control and cross sectional studies. Overall quality of evidence was found to be moderate. Five main preventive intervention categories emerged: malaria prevention, health education, breastfeeding promotion, essential newborn care and psychosocial support. All categories showed some evidence for the effectiveness of Community Health Workers; however they were found to be especially effective in promoting mother-performed strategies (skin to skin care and exclusive breastfeeding)., Conclusions: Community Health Workers were shown to provide a range of preventive interventions for Maternal and Child Health in low- and middle-income countries with some evidence of effective strategies, though insufficient evidence is available to draw conclusions for most interventions and further research is needed.

Although a large number of single nucleotide polymorphism (SNP) markers covering the entire genome are needed to enable molecular breeding efforts such as genome wide association studies, fine mapping, genomic selection and marker-assisted selection in peach [Prunus persica (L.) Batsch] and related Prunus species, only a limited number of genetic markers, including simple sequence repeats (SSRs), have been available to date. To address this need, an international consortium (The International Peach SNP Consortium; IPSC) has pursued a coordinated effort to perform genome-scale SNP discovery in peach using next generation sequencing platforms to develop and characterize a high-throughput Illumina Infinium® SNP genotyping array platform. We performed whole genome re-sequencing of 56 peach breeding accessions using the Illumina and Roche/454 sequencing technologies. Polymorphism detection algorithms identified a total of 1,022,354 SNPs. Validation with the Illumina GoldenGate® assay was performed on a subset of the predicted SNPs, verifying ∼75% of genic (exonic and intronic) SNPs, whereas only about a third of intergenic SNPs were verified. Conservative filtering was applied to arrive at a set of 8,144 SNPs that were included on the IPSC peach SNP array v1, distributed over all eight peach chromosomes with an average spacing of 26.7 kb between SNPs. Use of this platform to screen a total of 709 accessions of peach in two separate evaluation panels identified a total of 6,869 (84.3%) polymorphic SNPs.The almost 7,000 SNPs verified as polymorphic through extensive empirical evaluation represent an excellent source of markers for future studies in genetic relatedness, genetic mapping, and dissecting the genetic architecture of complex agricultural traits. The IPSC peach SNP array v1 is commercially available and we expect that it will be used worldwide for genetic studies in peach and related stone fruit and nut species.

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of 'Golden Delicious', SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple.

High-throughput genome scans are important tools for genetic studies and breeding applications. Here, a 6K SNP array for use with the Illumina Infinium® system was developed for diploid sweet cherry (Prunus avium) and allotetraploid sour cherry (P. cerasus). This effort was led by RosBREED, a community initiative to enable marker-assisted breeding for rosaceous crops. Next-generation sequencing in diverse breeding germplasm provided 25 billion basepairs (Gb) of cherry DNA sequence from which were identified genome-wide SNPs for sweet cherry and for the two sour cherry subgenomes derived from sweet cherry (avium subgenome) and P. fruticosa (fruticosa subgenome). Anchoring to the peach genome sequence, recently released by the International Peach Genome Initiative, predicted relative physical locations of the 1.9 million putative SNPs detected, preliminarily filtered to 368,943 SNPs. Further filtering was guided by results of a 144-SNP subset examined with the Illumina GoldenGate® assay on 160 accessions. A 6K Infinium® II array was designed with SNPs evenly spaced genetically across the sweet and sour cherry genomes. SNPs were developed for each sour cherry subgenome by using minor allele frequency in the sour cherry detection panel to enrich for subgenome-specific SNPs followed by targeting to either subgenome according to alleles observed in sweet cherry. The array was evaluated using panels of sweet (n = 269) and sour (n = 330) cherry breeding germplasm. Approximately one third of array SNPs were informative for each crop. A total of 1825 polymorphic SNPs were verified in sweet cherry, 13% of these originally developed for sour cherry. Allele dosage was resolved for 2058 polymorphic SNPs in sour cherry, one third of these being originally developed for sweet cherry. This publicly available genomics resource represents a significant advance in cherry genome-scanning capability that will accelerate marker-locus-trait association discovery, genome structure investigation, and genetic diversity assessment in this diploid-tetraploid crop group.

Migraine headache is a common and potentially debilitating disorder often treated by family physicians. Before diagnosing migraine, serious intracranial pathology must be ruled out. Treating acute migraine is challenging because of substantial rates of nonresponse to medications and difficulty in predicting individual response to a specific agent or dose. Data comparing different drug classes are relatively scarce. Abortive therapy should be used as early as possible after the onset of symptoms. Effective first-line therapies for mild to moderate migraine are nonprescription nonsteroidal anti-inflammatory drugs and combination analgesics containing acetaminophen, aspirin, and caffeine. Triptans are first-line therapies for moderate to severe migraine, or mild to moderate migraine that has not responded to adequate doses of simple analgesics. Triptans should be avoided in patients with vascular disease, uncontrolled hypertension, or hemiplegic migraine. Intravenous antiemetics, with or without intravenous dihydroergotamine, are effective therapies in an emergency department setting. Dexamethasone may be a useful adjunct to standard therapy in preventing short-term headache recurrence. Intranasal lidocaine may also have a role in relief of acute migraine. Isometheptene-containing compounds and intranasal dihydroergotamine are also reasonable therapeutic options. Medications containing opiates or barbiturates should be avoided for acute migraine. During pregnancy, migraine may be treated with acetaminophen or nonsteroidal anti-inflammatory drugs (prior to third trimester), or opiates in refractory cases. Acetaminophen, ibuprofen, intranasal sumatriptan, and intranasal zolmitriptan seem to be effective in children and adolescents, although data in these age groups are limited.

Objectives: We developed and implemented a process for routine HIV screening, and we report screening practices and acceptance among adolescents at a large, urban, pediatric emergency department (ED)., Methods: We surveyed health care providers regarding their knowledge and beliefs about HIV and generated a protocol for routine HIV screening. Free, routine, opt-out, HIV screening was offered for all adolescents (13-18 years of age) presenting for care in the ED. We studied ED HIV screening rates, rates of test acceptance among patients/ guardians, patients' reasons for opting out, and HIV prevalence. A computerized prompt in the electronic chart was introduced 5 months after initiation, to address low screening rates., Results: Of the 118 health care providers who responded to the preimplementation survey, 78% were unaware of the revised HIV testing guidelines and 58% predicted that routine screening would fail because of patient or guardian refusal. Of the 5399 patients who qualified for routine screening, 37% (2002) were offered opt-out screening. Of those, 13% opted out. Patients offered screening were more likely than patients not offered screening to be older (> or =15 years; P.002), female (P=.003), and nonwhite (P=.006). Older patients (> or =15 years of age) who were approached for screening were less likely to opt out (P=.002). Computerized prompting improved screening rates. One of the 1735 tests (0.57 per 1000 tests) performed yielded positive results for HIV., Conclusion: Adolescents and their guardians accept routine, optout, HIV screening, regardless of gender or race, and a computerized reminder enhances screening.

Aims: The aim of this study was to compare both the antimicrobial activity of terpinen-4-ol and tea tree oil (TTO) against clinical skin isolates of meticillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CoNS) and their toxicity against human fibroblast cells., Methods and Results: Antimicrobial activity was compared by using broth microdilution and quantitative in vitro time-kill test methods. Terpinen-4-ol exhibited significantly greater bacteriostatic and bactericidal activity, as measured by minimum inhibitory and bactericidal concentrations, respectively, than TTO against both MRSA and CoNS isolates. Although not statistically significant, time-kill studies also clearly showed that terpinen-4-ol exhibited greater antimicrobial activity than TTO. Comparison of the toxicity of terpinen-4-ol and TTO against human fibroblasts revealed that neither agent, at the concentrations tested, were toxic over the 24-h test period., Conclusions: Terpinen-4-ol is a more potent antibacterial agent against MRSA and CoNS isolates than TTO with neither agent exhibiting toxicity to fibroblast cells at the concentrations tested., Significance and Impact of the Study: Terpinen-4-ol should be considered for inclusion as a single agent in products formulated for topical treatment of MRSA infection. However, further work would initially be required to ensure that resistance would not develop with the use of terpinen-4-ol as a single agent.

In its development of cancer treatment services, Belfast City Hospital Trust has installed a vacuum drainage system for the control and containment of radioactive therapeutic waste.

The Drosophila gypsy insulator contains binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. Enhancer and silencer blocking require Su(Hw) recruitment of Mod(mdg4)-67.2, a BTB/POZ domain protein that interacts with Su(Hw) through a carboxyl-terminal acidic domain. Here we conducted mutational analyses of the Mod(mdg4)-67.2 BTB domain. We demonstrate that this domain is essential for insulator function, in part through direction of protein dimerization. Our studies revealed the presence of a second domain (DD) that contributes to Mod(mdg4)-67.2 dimerization when the function of the BTB domain is compromised. Additionally, we demonstrate that mutations in amino acids of the charged pocket in the BTB domain that retain dimerization of the mutated protein cause a loss of insulator function. In these cases, the mutant proteins failed to localize to chromosomes, suggesting a role for the BTB domain in chromosome association. Interestingly, replacement of the Mod(mdg4)-67.2 BTB domain with the GAF BTB domain produced a nonfunctional protein. Taken together, these data suggest that the Mod(mdg4)-67.2 BTB domain confers novel activities to gypsy insulator function.

This study reports on the synthesis of peptides containing C-terminal acylated gem-diamines and their utilization for the preparation of irreversible inactivators of the serine and cysteine proteinases. We have succeeded in obtaining an inhibitor Acetyl-Val-Pro-g-Val-CO-O-C(6)H(4)-NO(2) of neutrophil and pancreatic elastases that functions in a time-dependent manner, indicative of the action of an irreversible inactivator, functioning, most probably, through the formation of a long-lived acyl enzyme intermediate. In addition, we have demonstrated the irreversible inhibition of the cysteine proteinase bovine cathepsin B, by chloroacetyl and bromoacetyl derivatives of a dipeptide gem-diamine, Cbz-Phe-g-Ala-CO-CH(2)Hal (Hal = Br, Cl).

In this study, a series of N-chloro-acetylated dipeptides were synthesised by the application of Houghten's methodology of multiple analog peptide syntheses (MAPS). The peptides, all of which contain a C-terminal free acid, were tested as inactivators of bovine cathepsin B, in an attempt at exploiting the known and, amongst the cysteine proteinases, unique carboxy dipeptidyl peptidase activity of the protease. We have succeeded in obtaining a number of effective inactivators, the most potent of which-chloroacetyl-Leu-Leu-OH, inactivates the enzyme with an apparent second-order rate constant of 3.8 x 10(4)M(-1)min(-1). In contrast, the esterified analog, chloroacetyl-Leu-Leu-OMe, inactivates the enzyme some three orders of magnitude less efficiently, lending credence to our thesis that a free carboxylic acid moiety is an important determinant for inhibitor effectiveness. This preliminary study has highlighted a number of interesting features about the specificity requirements of the bovine proteinase and we believe that our approach has great potential for the rapid delineation of the subsite specificities of cathepsin B-like proteases from various species.