Variability in Fetal Fraction Estimation: Comparing Fetal Fractions Reported by Noninvasive Prenatal Testing Providers Globally.

BACKGROUND: Fetal fraction (FF) measurement is considered important for reliable noninvasive prenatal testing (NIPT). Using minimal FF threshold as a quality parameter is under debate. We evaluated the variability in reported FFs of individual samples between providers and laboratories and within a single laboratory. METHODS: Genomic quality assessment and European Molecular Genetics Quality Network provide joint proficiency testing for NIPT. We compared reported FFs across all laboratories and stratified according to test methodologies. A single sample was sequenced repeatedly and FF estimated by 2 bioinformatics methods: Veriseq2 and SeqFF. Finally, we compared FFs by Veriseq and SeqFF in 87 351 NIPT samples. RESULTS: For each proficiency test sample we observed a large variability in reported FF, SDs and CVs ranging from 1.7 to 3.6 and 17.0 to 35.8, respectively. FF measurements reported by single nucleotide polymorphism-based methods had smaller SDs (0.5 to 2.4) compared to whole genome sequencing-based methods (1.8 to 2.9). In the internal quality assessment, SDs were similar between SeqFF (SD 1.0) and Veriseq v2 (SD 0.9), but mean FF by Veriseq v2 was higher compared to SeqFF (9.0 vs 6.4, P 0.001). In patient samples, reported FFs were on average 1.12-points higher in Veriseq than in SeqFF (P 0.001). CONCLUSIONS: Current methods do not allow for a reliable and consistent FF estimation. Our data show estimated FF should be regarded as a laboratory-specific range, rather than a precise number. Applying strict universal minimum thresholds might result in unnecessary test failures and should be used with caution.

Mapping Inequities in Digital Health Technology Within the World Health Organization's European Region Using PROGRESS PLUS: Scoping Review.

BACKGROUND: The use of digital technologies within health care rapidly increased as services transferred to web-based platforms during the COVID-19 pandemic. Inequalities in digital health across the domains of equity are not routinely examined; yet, the long-term integration of digitally delivered services needs to consider such inequalities to ensure equitable benefits. OBJECTIVE: This scoping review aimed to map inequities in access, use, and engagement with digital health technologies across equity domains. METHODS: We searched 4 electronic databases (MEDLINE, ASSIA, PsycINFO, and Scopus) for quantitative and mixed methods reviews and meta-analyses published between January 2016 and May 2022. Reviews were limited to those that included studies from the World Health Organization's European region. Extracted data were mapped against Cochrane's PROGRESS PLUS (place of residence, race, ethnicity, culture, and language, occupation, gender and sex, religion, education, socioeconomic status, social capital, and other characteristics) dimensions of equity. RESULTS: In total, 404 unique citations were identified from the searches, and 2 citations were identified from other sources. After eligibility assessment, 22 reviews were included. Consistent evidence was found showing higher access to digital health technologies among patients who were of White ethnicity, were English speaking, and had no disability. There were no reviews that explored differences in access to digital health care by age, gender and sex, occupation, education, or homeless or substance misuse. Higher use of digital health technologies was observed among populations that were White, English speaking, younger, with a higher level of education, of higher economic status, and residents in urban areas. No clear evidence of differences in the use of digital technologies by occupation, gender and sex, disability, or homeless or substance misuse was found, nor was clear evidence found in the included reviews on inequalities in the engagement with digital technologies. Finally, no reviews were identified that explored differences by place of residence. CONCLUSIONS: Despite awareness of the potential impact of inequalities in digital health, there are important evidence gaps across multiple equity domains. The development of a common framework for evaluating digital health equity in new health initiatives and consistency in reporting findings is needed.

The impacts and effectiveness of support for people bereaved through advanced illness: A systematic review and thematic synthesis.

BACKGROUND: Bereavement support is a key component of palliative care, with different types of support recommended according to need. Previous reviews have typically focused on specialised interventions and have not considered more generic forms of support, drawing on different research methodologies. AIM: To review the quantitative and qualitative evidence on the effectiveness and impact of interventions and services providing support for adults bereaved through advanced illness. DESIGN: A mixed-methods systematic review was conducted, with narrative synthesis of quantitative results and thematic synthesis of qualitative results. The review protocol is published in PROSPERO ( www.crd.york.ac.uk/prospero , CRD42016043530). DATA SOURCES: The databases MEDLINE, Embase, PsycINFO, CINAHL and Social Policy and Practice were searched from 1990 to March 2019. Studies were included which reported evaluation results of bereavement interventions, following screening by two independent researchers. Study quality was assessed using GATE checklists. RESULTS: A total of 31 studies were included, reporting on bereavement support groups, psychological and counselling interventions and a mix of other forms of support. Improvements in study outcomes were commonly reported, but the quality of the quantitative evidence was generally poor or mixed. Three main impacts were identified in the qualitative evidence, which also varied in quality: 'loss and grief resolution', 'sense of mastery and moving ahead' and 'social support'. CONCLUSION: Conclusions on effectiveness are limited by small sample sizes and heterogeneity in study populations, models of care and outcomes. The qualitative evidence suggests several cross-cutting benefits and helps explain the impact mechanisms and contextual factors that are integral to the support.

Coping and wellbeing in bereavement: two core outcomes for evaluating bereavement support in palliative care.

BACKGROUND: Bereavement support is a core part of palliative care. However, the evidence base is limited by a lack of consistency in the outcomes used to evaluate services and models of support, which makes it difficult to compare approaches. Core Outcome Sets (COS) represent the minimum that should be measured in research into specific conditions or services. The aim of this study was to use a stakeholders' perspective to develop a COS for evaluating bereavement support for adults in adult palliative care settings. METHODS: A list of outcomes relevant to bereavement support was created following a systematic review of the quantitative and qualitative literature. At an expert workshop 21 stakeholders discussed their views on the most important outcomes and compared these to and critiqued the lists constructed from the review. These lists and discussions informed a two round international DELPHI survey (n = 240) designed to reach consensus on which outcomes/outcome dimensions should be included in the COS. To prioritise and validate the items emerging from the survey, participants at a subsequent consensus day ranked the relative importance of these items (n = 23). A final feedback exercise with these consensus day participants was conducted to confirm the selection of outcomes and dimensions. RESULTS: 'Ability to cope with grief' and 'Quality of life and mental wellbeing' were selected as two core outcomes. Twenty-one different dimensions to explore when assessing these outcomes were also identified. The coping related dimensions have been categorised as: Negative and overwhelming grief; Communication and connectedness; Understanding, accepting and finding meaning in grief; Finding balance between grief and life going forwards; Accessing appropriate support. Those relating to quality of life and wellbeing have been categorised as; Participation in work and/or regular activities; Relationships and social functioning; Positive mental wellbeing and Negative mental and emotional state. CONCLUSION: This COS outlines a more consistent way forward for bereavement researchers and practitioners, whilst also orientating towards public health and resilience-based approaches to bereavement care. Further work is planned to identify and develop measures which are specific to this core outcome set, and which will facilitate the future comparability of bereavement services and interventions.

Truncation of GdpP mediates ß-lactam resistance in clinical isolates of Staphylococcus aureus.

OBJECTIVES: High-level ß-lactam resistance in MRSA is mediated in the majority of strains by a mecA or mecC gene. In this study, we identified 10 mec gene-negative MRSA human isolates from Austria and 11 bovine isolates from the UK showing high levels of ß-lactam resistance and sought to understand the molecular basis of the resistance observed. METHODS: Different antimicrobial resistance testing methods (disc diffusion, Etest and VITEK® 2) were used to establish the ß-lactam resistance profiles for the isolates and the isolates were further investigated by WGS. RESULTS: A number of mutations (including novel ones) in PBPs, AcrB, YjbH and the pbp4 promoter were identified in the resistant isolates, but not in closely related susceptible isolates. Importantly, a truncation in the cyclic diadenosine monophosphate phosphodiesterase enzyme, GdpP, was identified in 7 of the 10 Austrian isolates and 10 of the 11 UK isolates. Complementation of four representative isolates with an intact copy of the gdpP gene restored susceptibility to penicillins and abolished the growth defects caused by the truncation. CONCLUSIONS: This study reports naturally occurring inactivation of GdpP protein in Staphylococcus aureus of both human origin and animal origin, and demonstrates clinical relevance to a previously reported association between this truncation and increased ß-lactam resistance and impaired bacterial growth in laboratory-generated mutants. It also highlights possible limitations of genomic determination of antibiotic susceptibility based on single gene presence or absence when choosing the appropriate antimicrobial treatment for patients.

Adherence to exercise referral schemes by participants - what do providers and commissioners need to know? A systematic review of barriers and facilitators.

BACKGROUND: Physical inactivity levels are rising worldwide with major implications for the health of the population and the prevalence of non-communicable diseases. Exercise referral schemes (ERS) continue to be a popular intervention utilised by healthcare practitioners to increase physical activity. We undertook a systematic review of views studies in order to inform guidance from the UK National Institute of Health and Care Excellence (NICE) on exercise referral schemes to promote physical activity. This paper reports on the participant views identified, to inform those seeking to refine schemes to increase attendance and adherence. METHODS: Fifteen databases and a wide range of websites and grey literature sources were searched systematically for publications from 1995 to June 2013. In addition, a range of supplementary methods including, a call for evidence by NICE, contacting authors, reference list checking and citation tracking were utilised to identify additional research. Studies were included where they detailed schemes for adults aged 19 years or older who were 'inactive' (i.e. they are not currently meeting UK physical activity guidelines). Study selection was conducted independently in duplicate. Quality assessment was undertaken by one reviewer and checked by a second, with 20 % of papers being considered independently in duplicate. Papers were coded in qualitative data analysis software Atlas.ti. This review was reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement). RESULTS: Evidence from 33 UK-relevant studies identified that support from providers, other attendees and family was an important facilitator of adherence and 'making exercise a habit' post programme, as was the variety and personalised nature of sessions offered. Barriers to attendance included the inconvenient timing of sessions, their cost and location. An intimidating gym atmosphere, a dislike of the music and TV and a lack of confidence in operating gym equipment were frequently reported. CONCLUSIONS: These findings provide valuable insights that commissioners and providers should consider. The main themes were consistent across a large number of studies and further research should concentrate on programmes that reflect these findings.

"It still haunts me whether we did the right thing": a qualitative analysis of free text survey data on the bereavement experiences and support needs of family caregivers.

BACKGROUND: Research suggests that there may be bereavement experiences and support needs which are specific to family caregivers providing end of life care (EoLC), although this remains an under-researched area. This paper focuses on themes relating to bereavement which were derived from an analysis of free text survey responses collected in a research priority setting exercise for palliative and EoLC. METHODS: The priority setting exercise involved a public survey, designed to generate research priorities. Rather than identify research topics, many people instead described their experiences and raised more general questions relating to palliative and end of life care. To explore these experiences and perspectives a supplementary thematic analysis was conducted on the survey responses. 1403 respondents took part, including patients, current and bereaved carers, health and social care professionals, volunteers and members of the public. RESULTS: Several grief issues were identified, which seem specific to the experiences of family caregivers. Responses demonstrated a relationship between death experiences, feelings of guilt and bereavement outcomes for some family caregivers, as well as caregiver experiences of a "void" created by the withdrawal of professional support after death. Communication and support needs were also identified by participants. CONCLUSION: This analysis provides further evidence of some of the specific effects that caring for a loved one at the end of life can have on bereavement experiences. Finding ways of improving communication around the time of death and effective follow up approaches post death could help to address some of these issues.

A novel hybrid SCCmec-mecC region in Staphylococcus sciuri.

OBJECTIVES: Methicillin resistance in Staphylococcus spp. results from the expression of an alternative penicillin-binding protein 2a (encoded by mecA) with a low affinity for ß-lactam antibiotics. Recently, a novel variant of mecA known as mecC (formerly mecALGA251) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified two Staphylococcus sciuri subsp. carnaticus isolates from bovine infections that harbour three different mecA homologues: mecA, mecA1 and mecC. METHODS: We subjected the two isolates to whole-genome sequencing to further understand the genetic context of the mec-containing region. We also used PCR and RT-PCR to investigate the excision and expression of the SCCmec element and mec genes, respectively. RESULTS: Whole-genome sequencing revealed a novel hybrid SCCmec region at the orfX locus consisting of a class E mec complex (mecI-mecR1-mecC1-blaZ) located immediately downstream of a staphylococcal cassette chromosome mec (SCCmec) type VII element. A second SCCmec attL site (attL2), which was imperfect, was present downstream of the mecC region. PCR analysis of stationary-phase cultures showed that both the SCCmec type VII element and a hybrid SCCmec-mecC element were capable of excision from the genome and forming a circular intermediate. Transcriptional analysis showed that mecC and mecA, but not mecA1, were both expressed in liquid culture supplemented with oxacillin. CONCLUSIONS: Overall, this study further highlights that a range of staphylococcal species harbour the mecC gene and furthers the view that coagulase-negative staphylococci associated with animals may act as reservoirs of antibiotic resistance genes for more pathogenic staphylococcal species.

Attenuated Salmonella Typhimurium lacking the pathogenicity island-2 type 3 secretion system grow to high bacterial numbers inside phagocytes in mice.

Intracellular replication within specialized vacuoles and cell-to-cell spread in the tissue are essential for the virulence of Salmonella enterica. By observing infection dynamics at the single-cell level in vivo, we have discovered that the Salmonella pathogenicity island 2 (SPI-2) type 3 secretory system (T3SS) is dispensable for growth to high intracellular densities. This challenges the concept that intracellular replication absolutely requires proteins delivered by SPI-2 T3SS, which has been derived largely by inference from in vitro cell experiments and from unrefined measurement of net growth in mouse organs. Furthermore, we infer from our data that the SPI-2 T3SS mediates exit from infected cells, with consequent formation of new infection foci resulting in bacterial spread in the tissues. This suggests a new role for SPI-2 in vivo as a mediator of bacterial spread in the body. In addition, we demonstrate that very similar net growth rates of attenuated salmonellae in organs can be derived from very different underlying intracellular growth dynamics.

The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella.

Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its importance to virulence. In this study we have explored the contribution of the bacterial cytoskeleton to the ability of Salmonella to express and assemble virulence factors and cause disease. The bacterial actin-like protein MreB polymerises into helical filaments and interacts with other cytoskeletal elements including MreC to control cell-shape. As mreB appears to be an essential gene, we have constructed a viable ΔmreC depletion mutant in Salmonella. Using a broad range of independent biochemical, fluorescence and phenotypic screens we provide evidence that the Salmonella pathogenicity island-1 type three secretion system (SPI1-T3SS) and flagella systems are down-regulated in the absence of MreC. In contrast the SPI-2 T3SS appears to remain functional. The phenotypes have been further validated using a chemical genetic approach to disrupt the functionality of MreB. Although the fitness of ΔmreC is reduced in vivo, we observed that this defect does not completely abrogate the ability of Salmonella to cause disease systemically. By forcing on expression of flagella and SPI-1 T3SS in trans with the master regulators FlhDC and HilA, it is clear that the cytoskeleton is dispensable for the assembly of these structures but essential for their expression. As two-component systems are involved in sensing and adapting to environmental and cell surface signals, we have constructed and screened a panel of such mutants and identified the sensor kinase RcsC as a key phenotypic regulator in ΔmreC. Further genetic analysis revealed the importance of the Rcs two-component system in modulating the expression of these virulence factors. Collectively, these results suggest that expression of virulence genes might be directly coordinated with cytoskeletal integrity, and this regulation is mediated by the two-component system sensor kinase RcsC.

A Staphylococcus xylosus isolate with a new mecC allotype.

Recently, a novel variant of mecA known as mecC (mecA(LGA251)) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified a Staphylococcus xylosus isolate that harbors a new allotype of the mecC gene, mecC1. Whole-genome sequencing revealed that mecC1 forms part of a class E mec complex (mecI-mecR1-mecC1-blaZ) located at the orfX locus as part of a likely staphylococcal cassette chromosome mec element (SCCmec) remnant, which also contains a number of other genes present on the type XI SCCmec.

Intracellular sequestration of the NKG2D ligand ULBP3 by human cytomegalovirus.

Human CMV (HCMV) encodes multiple genes that control NK cell activation and cytotoxicity. Some of these HCMV-encoded gene products modulate NK cell activity as ligands expressed at the cell surface that engage inhibitory NK cell receptors, whereas others prevent the infected cell from upregulating ligands that bind to activating NK cell receptors. A major activating NKR is the homodimeric NKG2D receptor, which has eight distinct natural ligands in humans. It was shown that HCMV is able to prevent the surface expression of five of these ligands (MIC A/B and ULBP1, 2, and 6). In this article, we show that the HCMV gene product UL142 can prevent cell surface expression of ULBP3 during infection. We further show that UL142 interacts with ULBP3 and mediates its intracellular retention in a compartment that colocalizes with markers of the cis-Golgi complex. In doing so, UL142 prevents ULBP3 trafficking to the surface and protects transfected cells from NK-mediated cytotoxicity. This is the first description of a viral gene able to mediate downregulation of ULBP3.

Collaboration between local health and local government agencies for health improvement.

BACKGROUND: In many countries, national, regional and local inter- and intra-agency collaborations have been introduced to improve health outcomes. Evidence is needed on the effectiveness of locally developed partnerships which target changes in health outcomes and behaviours. OBJECTIVES: To evaluate the effects of interagency collaboration between local health and local government agencies on health outcomes in any population or age group. SEARCH METHODS: We searched the Cochrane Public Health Group Specialised Register, AMED, ASSIA, CENTRAL, CINAHL, DoPHER, EMBASE, ERIC, HMIC, IBSS, MEDLINE, MEDLINE In-Process, OpenGrey, PsycINFO, Rehabdata, Social Care Online, Social Services Abstracts, Sociological Abstracts, TRoPHI and Web of Science from 1966 through to January 2012. 'Snowballing' methods were used, including expert contact, citation tracking, website searching and reference list follow-up. SELECTION CRITERIA: Randomized controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs) and interrupted time series (ITS) where the study reported individual health outcomes arising from interagency collaboration between health and local government agencies compared to standard care. Studies were selected independently in duplicate, with no restriction on population subgroup or disease. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed risk of bias for each study. MAIN RESULTS: Sixteen studies were identified (28,212 participants). Only two were considered to be at low risk of bias. Eleven studies contributed data to the meta-analyses but a narrative synthesis was undertaken for all 16 studies. Six studies examined mental health initiatives, of which one showed health benefit, four showed modest improvement in one or more of the outcomes measured but no clear overall health gain, and one showed no evidence of health gain. Four studies considered lifestyle improvements, of which one showed some limited short-term improvements, two failed to show health gains for the intervention population, and one showed more unhealthy lifestyle behaviours persisting in the intervention population. Three studies considered chronic disease management and all failed to demonstrate health gains. Three studies considered environmental improvements and adjustments, of which two showed some health improvements and one did not.Meta-analysis of three studies exploring the effect of collaboration on mortality showed no effect (pooled relative risk of 1.04 in favour of control, 95% CI 0.92 to 1.17). Analysis of five studies (with high heterogeneity) looking at the effect of collaboration on mental health resulted in a standardised mean difference of -0.28, a small effect favouring the intervention (95% CI -0.51 to -0.06). From two studies, there was a statistically significant but clinically modest improvement in the global assessment of function symptoms score scale, with a pooled mean difference (on a scale of 1 to 100) of -2.63 favouring the intervention (95% CI -5.16 to -0.10).For physical health (6 studies) and quality of life (4 studies) the results were not statistically significant, the standardised mean differences were -0.01 (95% CI -0.10 to 0.07) and -0.08 (95% CI -0.44 to 0.27), respectively. AUTHORS' CONCLUSIONS: Collaboration between local health and local government is commonly considered best practice. However, the review did not identify any reliable evidence that interagency collaboration, compared to standard services, necessarily leads to health improvement. A few studies identified component benefits but these were not reflected in overall outcome scores and could have resulted from the use of significant additional resources. Although agencies appear enthusiastic about collaboration, difficulties in the primary studies and incomplete implementation of initiatives have prevented the development of a strong evidence base. If these weaknesses are addressed in future studies (for example by providing greater detail on the implementation of programmes; using more robust designs, integrated process evaluations to show how well the partners of the collaboration worked together, and measurement of health outcomes) it could provide a better understanding of what might work and why. It is possible that local collaborative partnerships delivering environmental Interventions may result in health gain but the evidence base for this is very limited.Evaluations of interagency collaborative arrangements face many challenges. The results demonstrate that collaborative community partnerships can be established to deliver interventions but it is important to agree goals, methods of working, monitoring and evaluation before implementation to protect programme fidelity and increase the potential for effectiveness.

A scoping review of system-level mechanisms to prevent children being in out-of-home care.

Identifying which approaches can effectively reduce the need for out-of-home care for children is critically important. Despite the proliferation of different interventions and approaches globally, evidence summaries on this topic are limited. This study is a scoping review using a realist framework to explore what research evidence exists about reducing the number of children and young people in care. Searches of databases and websites were used to identify studies evaluating intervention effect on at least one of the following outcomes: reduction in initial entry to care; increase in family reunification post care. Data extracted from papers included type of study, outcome, type and level of intervention, effect, mechanism and moderator, implementation issues and economic (EMMIE) considerations. Data were coded by: primary outcome; level of intervention (community, policy, organisation, family or child); and type of evidence, using the realist EMMIE framework. This is the first example of a scoping review on any topic using this framework. Evaluated interventions were grouped and analysed according to system-level mechanism. We present the spread of evidence across system-level mechanisms and an overview of how each system-level mechanism might reduce the number of children in care. Implications and gaps are identified.

Enhanced virulence of Salmonella enterica serovar typhimurium after passage through mice.

The interaction between Salmonella enterica and the host immune system is complex. The outcome of an infection is the result of a balance between the in vivo environment where the bacteria survive and grow and the regulation of fitness genes at a level sufficient for the bacteria to retain their characteristic rate of growth in a given host. Using bacteriological counts from tissue homogenates and fluorescence microscopy to determine the spread, localization, and distribution of S. enterica in the tissues, we show that, during a systemic infection, S. enterica adapts to the in vivo environment. The adaptation becomes a measurable phenotype when bacteria that have resided in a donor animal are introduced into a recipient naïve animal. This adaptation does not confer increased resistance to early host killing mechanisms but can be detected as an enhancement in the bacterial net growth rate later in the infection. The enhanced growth rate is lost upon a single passage in vitro, and it is therefore transient and not due to selection of mutants. The adapted bacteria on average reach higher intracellular numbers in individual infected cells and therefore have patterns of organ spread different from those of nonadapted bacteria. These experiments help in developing an understanding of the influence of passage in a host on the fitness and virulence of S. enterica.

In vivo regulation of the Vi antigen in Salmonella and induction of immune responses with an in vivo-inducible promoter.

Salmonella enterica serovar Typhi, the agent of typhoid fever in humans, expresses the surface Vi polysaccharide antigen that contributes to virulence. However, Vi expression can also be detrimental to some key steps of S. Typhi infectivity, for example, invasion, and Vi is the target of protective immune responses. We used a strain of S. Typhimurium carrying the whole Salmonella pathogenicity island 7 (SPI-7) to monitor in vivo Vi expression within phagocytic cells of mice at different times after systemic infection. We also tested whether it is possible to modulate Vi expression via the use of in vivo-inducible promoters and whether this would trigger anti-Vi antibodies through the use of Vi-expressing live bacteria. Our results show that Vi expression in the liver and spleen is downregulated with the progression of infection and that the Vi-negative population of bacteria becomes prevalent by day 4 postinfection. Furthermore, we showed that replacing the natural tviA promoter with the promoter of the SPI-2 gene ssaG resulted in sustained Vi expression in the tissues. Intravenous or oral infection of mice with a strain of S. Typhimurium expressing Vi under the control of the ssaG promoter triggered detectable levels of all IgG subclasses specific for Vi. Our work highlights that Vi is downregulated in vivo and provides proof of principle that it is possible to generate a live attenuated vaccine that induces Vi-specific antibodies after single oral administration.

Collaboration between local health and local government agencies for health improvement.

BACKGROUND: In many countries, national, regional and local inter- and intra-agency collaborations have been introduced in order to improve health outcomes. Evidence is needed on the effectiveness of locally-developed partnerships which target changes in individual health outcomes and behaviours. OBJECTIVES: To evaluate the effects of interagency collaboration between local health and local government agencies on health outcomes. SEARCH STRATEGY: Twenty-five databases were searched using a highly sensitive search strategy. 'Snowballing' methods were also used, including expert contact, website searching and reference list follow up. SELECTION CRITERIA: Randomized controlled trials (RCTs), controlled clinical trials (CCTs), controlled before-and-after studies (CBAs) and interrupted time series (ITS) where the study reported on interagency collaboration between health and local government agencies. Studies were selected independently in duplicate by two of five authors. DATA COLLECTION AND ANALYSIS: From the team of five review authors, two authors independently conducted data extraction and assessed risk of bias for each study. MAIN RESULTS: Eleven studies were identified, presenting information on a total of 26,686 participants. Owing to the heterogeneity between studies a narrative synthesis was undertaken. The included studies covered a range of topics. Six studies examined mental health initiatives, of which one study showed health benefit; four showed modest improvement in one or more of the outcomes measured, but no clear overall health gain; and one study showed no evidence of health gain. Two studies were related to lifestyle improvements of which one failed to show health gains for the intervention population, while the other showed more unhealthy lifestyle behaviours persisting in the intervention population. Three studies were related to chronic disease management and all three failed to demonstrate health gains. AUTHORS' CONCLUSIONS: Collaboration between local health and local government is commonly considered best practice. However, the review did not identify any reliable evidence that inter­agency collaboration, compared to standard services, leads to health improvement. A few studies identified component benefits but these were not reflected in overall outcome scores and could have resulted from the use of significant additional resources. Although agencies appear enthusiastic about collaboration, methodological flaws in the primary studies and incomplete implementation of initiatives have prevented the development of a strong evidence base. If these flaws are addressed in future studies (for example by providing greater detail on the implementation of programs, using more robust designs, with integrated process evaluations and measurement of health outcomes) it could provide a better understanding of what might work and why.When updating this review, we will analyse any partnership or process evaluations of our included studies to try to identify markers of success in local collaborative partnerships that could inform policy developments in the future.

NHS Evidence - oral health.

NHS Evidence - oral health is one of over 30 specialist collections within the NHS Evidence library. Provided by the National Institute for Health and Clinical Excellence (NICE), NHS Evidence was launched in April 2009 with the aim of providing fast and easy access to evidence-based health and social care information.

Does Simian Virus 40 (SV40) Have a Role in UK Malignant Pleural Mesothelioma? No Role is Identified in a Sensitive RNA In Situ Hybridization Study on Potentially Affected Birth Cohorts.

BACKGROUND: Simian virus 40 (SV40)-contaminated polio vaccine was accidentally administered to about one-third of the UK population receiving polio vaccines between 1956 and 1962. SV40 was subsequently demonstrated to be a carcinogenic virus in experimental and animal models. Since then, the SV40 oncogenic protein large T antigen (SV40 Tag) has been shown to cause malignant transformation of asbestos-treated human pleural mesothelial cells and malignant pleural mesotheliomas in asbestos-exposed SV40 Tag transgenic mice. The present study was designed to investigate the possible association of SV40 Tag with human malignant pleural mesothelioma samples from birth cohorts of the UK population exposed to combined peak levels of asbestos and SV40-contaminated polio vaccines. MATERIALS AND METHODS: Tumor and background lung tissue microarrays prepared from archival surgical specimens of 139 pleural mesothelioma cases, collected over a period of 8 years (1998 to 2005), were analyzed. These represented birth cohorts overlapping with the period 1950 to 1960, exposed to a high level of both asbestos and SV40-contaminated live polio vaccines. SV40 Tag mRNA expression was investigated using a highly sensitive and specific SV40 Tag RNA in situ hybridization detection method on the basis of the novel RNAscope technology. RESULTS: SV40 Tag RNA was not detected in any of the 127 evaluable tumor cases, despite appropriate results obtained for the external positive and negative controls included. CONCLUSION: The complete absence of SV40 Tag mRNA in this large series of cases contradicts experimental evidence suggestive of SV40 link with asbestos-exposed malignant pleural mesotheliomas in the UK population. Alternative explanations of the negative findings are discussed to exclude possible confounding factors.

Criticality of plasma membrane lipids reflects activation state of macrophage cells.

Signalling is of particular importance in immune cells, and upstream in the signalling pathway many membrane receptors are functional only as complexes, co-locating with particular lipid species. Work over the last 15 years has shown that plasma membrane lipid composition is close to a critical point of phase separation, with evidence that cells adapt their composition in ways that alter the proximity to this thermodynamic point. Macrophage cells are a key component of the innate immune system, are responsive to infections and regulate the local state of inflammation. We investigate changes in the plasma membrane's proximity to the critical point as a response to stimulation by various pro- and anti-inflammatory agents. Pro-inflammatory (interferon γ, Kdo 2-Lipid A, lipopolysaccharide) perturbations induce an increase in the transition temperature of giant plasma membrane vesicles; anti-inflammatory interleukin 4 has the opposite effect. These changes recapitulate complex plasma membrane composition changes, and are consistent with lipid criticality playing a master regulatory role: being closer to critical conditions increases membrane protein activity.