Inequity in rehabilitation interventions after hip fracture: a systematic review.

OBJECTIVE: to determine the extent to which equity factors contributed to eligibility criteria of trials of rehabilitation interventions after hip fracture. We define equity factors as those that stratify healthcare opportunities and outcomes. DESIGN: systematic search of MEDLINE, Embase, CINHAL, PEDro, Open Grey, BASE and ClinicalTrials.gov for randomised controlled trials of rehabilitation interventions after hip fracture published between 1 January 2008 and 30 May 2018. Trials not published in English, secondary prevention or new models of service delivery (e.g. orthogeriatric care pathway) were excluded. Duplicate screening for eligibility, risk of bias (Cochrane Risk of Bias Tool) and data extraction (Cochrane's PROGRESS-Plus framework). RESULTS: twenty-three published, eight protocol, four registered ongoing randomised controlled trials (4,449 participants) were identified. A total of 69 equity factors contributed to eligibility criteria of the 35 trials. For more than 50% of trials, potential participants were excluded based on residency in a nursing home, cognitive impairment, mobility/functional impairment, minimum age and/or non-surgical candidacy. Where reported, this equated to the exclusion of 2,383 out of 8,736 (27.3%) potential participants based on equity factors. Residency in a nursing home and cognitive impairment were the main drivers of these exclusions. CONCLUSION: the generalisability of trial results to the underlying population of frail older adults is limited. Yet, this is the evidence base underpinning current service design. Future trials should include participants with cognitive impairment and those admitted from nursing homes. For those excluded, an evidence-informed reasoning for the exclusion should be explicitly stated. PROSPERO: CRD42018085930.

A Classic Case of Panton-Valentine Leucocidin MethicillinResistant Staphylococcus Aureus (PVL-MRSA)

Strains of Staphylococcus aureus capable of producing Panton-Valentine leucocidin (PVL-SA) are increasingly implicated in commnity acquired infection. The key principles of preventing and controlling the spread of infection in the community setting centre on early suspicion, rapid diagnosis and appropriate treatment.

Visualising the past - An evaluation of processes and sequences for fingermark recovery from old documents.

This study aimed to collect data on the effectiveness of most of the fingermark visualisation reagents currently used on porous surfaces on fingermarks aged for up to 90 years, significantly extending the timescales for which such information exists. A limited subset of the variables associated with processing of old fingermarks was explored, with a focus on the use of 1,8 diazafluoren-9-one (DFO), 1,2-indandione, ninhydrin, and physical developer. These techniques were used in sequence on batches of cheques between 11 and 32 years old, and on documents dating from the 1920s and 1940s. The potential for applying a physical developer enhancement process (blue toning) as the final step in the sequence was also explored. The benefits of using processing sequences on porous items were clearly demonstrated, with all processes in the sequence adding value in terms of additional marks found on the cheques up to 32 years old. In addition, physical developer was found to be capable of developing fingermarks up to 90 years old, whereas the amino acid reagents appear less effective on documents of 70 years and older. An experimental physical developer formulation with reduced environmental impact was found to be as effective as the existing process in these experiments. Blue toning was found to visualise an additional 10-25% of marks, and its wider use after silver-based deposition processes is recommended based on the evidence from this study.

Novel associations between blood DNA methylation and body mass index in middle-aged and older adults.

BACKGROUND/OBJECTIVES: There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time. SUBJECTS/METHODS: Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-analysis. RESULTS: Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10-7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10-7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study. CONCLUSIONS: Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism.

Standardized programming to reduce the burden of inappropriate therapies in implantable cardioverter defibrillators - Single centre follow up results.

BACKGROUND: Current algorithms and device morphology templates have been proposed in current Implantable Cardioverter-Defibrillators (ICDs) to minimize inappropriate therapies (ITS), but this has not been completely successful. AIM: Assess the impact of a deliberate strategy of using an atrial lead implant with standardized parameters; based on all current ICD discriminators and technologies, on the burden of ITS. METHOD: A retrospective single-centre analysis of 250 patients with either dual chamber (DR) ICDs or biventricular ICDs (CRTDs) over a (41.9 ± 27.3) month period was performed. The incidence of ITS on all ICD and CRTD patients was chronicled after the implementation of standardized programming. RESULTS: 39 events of anti-tachycardial pacing (ATP) and/or shocks were identified in 20 patients (8% incidence rate among patients). The total number of individual therapies was 120, of which 34% were inappropriate ATP, and 36% were inappropriate shocks. 11 patients of the 250 patients received ITS (4.4%). Of the 20 patients, four had ICDs for primary prevention and 16 for a secondary prevention. All the episodes in the primary indication group were inappropriate, while seven patients (43%) of the secondary indication group experienced inappropriate therapies. CONCLUSIONS: The burden of ITS in the population of patients receiving ICDs was 4.4% in the presence of atrial leads. The proposed rationalized programming criteria seems an effective strategy to minimize the burden of inappropriate therapies and will require further validation.

Transgressive women don't deserve protection: young men's narratives of sexual violence against women in rural Papua New Guinea.

Sexual violence against women and girls is commonplace in Papua New Guinea (PNG). While the experiences of women are rightly given central place in institutional responses to sexual violence, the men who perpetrate violence are often overlooked, an oversight that undermines the effectiveness of prevention efforts. This paper draws on interviews conducted with young men as part of a qualitative longitudinal study of masculinity and male sexuality in a rural highland area of PNG. It explores one aspect of male sexuality: men's narratives of sexual violence. Most striking from the data is that the collective enactment of sexual violence against women and girls is reported as an everyday and accepted practice amongst young men. However, not all women and girls were described as equally at risk, with those who transgress gender roles and roles inscribed and reinforced by patriarchal structures, at greater risk. To address this situation, efforts to reduce sexual violence against women and girls require an increased focus on male-centred intervention to critically engage with the forms of patriarchal authority that give license to sexual violence. Understanding the perceptions and experiences of men as perpetrators of sexual violence is a critical first step in the process of changing normative perceptions of gender, a task crucial to reducing sexual violence in countries such as PNG.

Factors associated with antiretroviral treatment uptake and adherence: a review. Perspectives from Australia, Canada, and the United Kingdom.

International focus on reducing onward HIV transmission emphasizes the need for routine HIV testing and early uptake of antiretroviral treatment (ART). Strategic targets have been set for 2020 to achieve the goal of 90% of people infected with HIV diagnosed, 90% of identified cases on treatment, and 90% of persons on treatment virally suppressed (90-90-90). It is vital to understand the complexity of factors influencing a person's treatment decisions over time and the context which may enable better adherence. In this paper we present findings from the review of published and gray literature (2003-2013) on the documented factors associated with treatment initiation and adherence in the general adult population of Australia, Canada, and the UK. A framework developed by Begley, McLaws, Ross, and Gold [2008. Cognitive and behavioural correlates of non-adherence to HIV anti-retroviral therapy: Theoretical and practical insight for clinical psychology and health psychology. Clinical Psychologist, 12(1), 9-17] in Australia was adapted to summarize the findings. A systematic database search using keywords and a set of inclusion criteria yielded 17 studies (Australia = 6; Canada = 8; UK = 3). In addition 11 reports were included in the review. We found that a person's abilities and motivations (intrapersonal factors, reported in 7 studies) to start and continue ART are influenced by a host of interconnected factors spanning relationship (interpersonal, 3 studies) and broader structural (extrapersonal, 15 studies) factors that are situated within social determinants of health. People therefore evaluate various costs and benefits of starting and staying on treatment, in which biomedical concerns play an important yet often subsidiary role. In this review the economic barriers to care were found to be significant and under-reported, highlighting the persistent health inequities in terms of access to services. Our understanding of the context around people's use of ART remains poor. Qualitative social research within HIV-positive communities is urgently needed to capture people's lived experiences and may address some of this deficit in understanding.

Factors impacting HIV testing: a review--perspectives from Australia, Canada, and the UK.

With the current global focus on strengthening HIV prevention through greater testing and treatment uptake, it is increasingly salient to identify and address barriers to testing. A review of the published, peer-reviewed literature and national reports from Australia, Canada, and the UK (2003-2013) on barriers to HIV testing was conducted to provide new information relevant to Australia and to complement earlier reviews from Canada and the UK. A systematic database search using keywords and a set of inclusion criteria yielded 36 studies (Australia = 13; Canada = 6; and the UK = 17). In addition 17 unpublished reports were included in the review. Our study uses a novel, comprehensive framework to describe barriers to HIV testing, and thus contributes to moving beyond the traditional patient-provider-system categorization. Within that framework, barriers are categorized as either intrapersonal (reported in 15 studies), interpersonal (21), or extrapersonal (16) and conceptualized within wider sociocultural and structural contexts. People's abilities and motivations to test (intrapersonal factors) are influenced by a host of interconnected factors spanning relationship (interpersonal) and broader socioeconomic, political and cultural (extrapersonal) factors. We suggest that the relative effects of interventions targeting barriers to HIV testing at the intrapersonal and interpersonal levels are limited by the extent to which the social determinants of health are addressed. The framework may also lend itself to thinking about the enabling factors for HIV testing, and future research may investigate the application of that framework for strategizing the most effective response. Future studies should also capture the lived experiences of barriers to HIV testing experienced by patients, especially in populations which are hard to reach based on social and geographic distance. Context-specific studies to evaluate the feasibility and effectiveness of various interventions proposed in the literature to address barriers to HIV testing are needed.

Sebia Capillarys 2 versus the Helena Biosciences V8 capillary electrophoresis analyser for carbohydrate-deficient transferrin measurement: comparison and analytical evaluation.

This study compares two automated capillary electrophoresis (CE) systems, the Capillarys 2 (Sebia, Surrey, UK) and V8 (Helena Biosciences, Tyne and Wear, UK) for the measurement of carbohydrate-deficient transferrin (CDT). Analytical imprecision was calculated for both platforms using internal quality control material from Sebia and Helena Biosciences, while a patient comparison was performed on 150 patient samples with CDT% levels ranging from 0.3% to 23.7%. Inter- and intra-assay imprecision between the two platforms were comparable. The correlation between platforms using patient samples was r2 = 0.985. However, there was a significant proportional bias at higher CDT concentration ranges, with the Helena system showing negative bias but good correlation over the clinically significant range. Analytical performances from both CE systems have been proven as suitable for routine laboratory use. The V8 CDT results were comparable to the Capillarys 2 in human sera over the clinical range of interest.

Evolution of Carotid Surgical Practice in the last Decade.

Stroke units provide immediate care and appropriate intervention in the evolving stroke. The aims of this study were to review the practice of carotid endarterectomy (CEA) before and after the establishment of a Stroke Unit in St. James's Hospital. Prior to the introduction of the Stroke Unit, 263 CEA's were performed over a five-year period. 139/263 (53%) of these were for symptomatic disease. 229 were performed in the five years since. 179/229 (78%) of these were for symptomatic disease. The 30-day stroke and death rates were < 2% before the introduction of the Stroke Unit, and have remained unchanged. Since the introduction of the Stroke Unit, there has been a slight decrease in the overall number of CEA's performed with a 25% increase in the proportion of endarterectomies performed for symptomatic disease. Despite the reduction in surgery for asymptomatic disease the overall 30-day stroke and death rate remains excellent at 2/229 (2%).

Dissecting Arabidopsis Gß signal transduction on the protein surface.

The heterotrimeric G-protein complex provides signal amplification and target specificity. The Arabidopsis (Arabidopsis thaliana) Gß-subunit of this complex (AGB1) interacts with and modulates the activity of target cytoplasmic proteins. This specificity resides in the structure of the interface between AGB1 and its targets. Important surface residues of AGB1, which were deduced from a comparative evolutionary approach, were mutated to dissect AGB1-dependent physiological functions. Analysis of the capacity of these mutants to complement well-established phenotypes of Gß-null mutants revealed AGB1 residues critical for specific AGB1-mediated biological processes, including growth architecture, pathogen resistance, stomata-mediated leaf-air gas exchange, and possibly photosynthesis. These findings provide promising new avenues to direct the finely tuned engineering of crop yield and traits.

Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders.

PURPOSE: Tumour genomic profiling is of increasing importance in early phase trials to match patients to targeted therapeutics. Mutations vary by demographic group; however, regional differences are not characterised. This was investigated by comparing mutation prevalence for common cancers presenting to Newcastle Experimental Cancer Medicine Centre (ECMC) to The Cancer Genome Atlas (TCGA) and utility of trial matching modalities. METHODS: Detailed clinicogenomic data were obtained for patients presenting September 2017-December 2020. Prevalence of mutations in lung, colorectal, breast and prostate cancer was compared to TCGA GDC Data Portal. Experimental Cancer (EC) Trial Finder utility in matching trials was compared to a Molecular Tumour Board (MTB) and commercial sequencing reports. RESULTS: Of 311 patients with advanced cancer, this consisted of lung (n = 131, 42.1%), colorectal (n = 44, 14.1%), breast (n = 36, 11.6%) and prostate (n = 18, 5.6%). More than one mutation was identified in the majority (n = 260, 84%). Significant prevalence differences compared to TCGA were identified, including a high prevalence of EGFR in lung (P = 0.001); RB1 in breast (P = 0.0002); and multiple mutations in prostate cancer. EC Trial Finder demonstrated significantly different utility than sequencing reports in identifying trials (P = 0.007). CONCLUSIONS: Regional differences in mutations may exist with advanced stage accounting for prevalence of specific mutations. A national Trial Finder shows utility in finding targeted trials whilst commercial sequencing reports may over-report 'actionable' mutations. Understanding local prevalence and trial availability could increase enrolment onto matched early phase trials.

Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer.

BACKGROUND: Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH). METHODS: Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. RESULTS: Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10(-11)). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10(-5) and 10(-29)), and identified breast and pancreatic cell lines with BRCA defects. CONCLUSION: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.

Re-evaluating the role of ascorbic acid and phenolic glycosides in ozone scavenging in the leaf apoplast of Arabidopsis thaliana L.

Phenolic glycosides are effective reactive oxygen scavengers and peroxidase substrates, suggesting that compounds in addition to ascorbate may have functional importance in defence responses against ozone (O(3)), especially in the leaf apoplast. The apoplastic concentrations of ascorbic acid (AA) and phenolic glycosides in Arabidopsis thaliana L. Col-0 wild-type plants were determined following exposure to a range of O(3) concentrations (5, 125 or 175 nL L(-1)) in controlled environment chambers. AA in leaf apoplast extracts was almost entirely oxidized in all treatments, suggesting that O(3) scavenging by direct reactions with reduced AA was very limited. In regard to phenolics, O(3) stimulated transcription of numerous phenylpropanoid pathway genes and increased the apoplastic concentration of sinapoyl malate. However, modelling of O(3) scavenging in the apoplast indicated that sinapoyl malate concentrations were too low to be effective protectants. Furthermore, null mutants for sinapoyl esters (fah1-7), kaempferol glycosides (tt4-1) and the double mutant (tt4-1/fah1-7) were equally sensitive to chronic O(3) as Ler-0 wild-type plants. These results indicate that current understanding of O(3) defence schemes deserves reassessment as mechanisms other than direct scavenging of O(3) by extracellular AA and antioxidant activity of some phenolics may predominate in some plant species.

Influence of atmospheric vapour pressure deficit on ozone responses of snap bean (Phaseolus vulgaris L.) genotypes.

Environmental conditions influence plant responses to ozone (O(3)), but few studies have evaluated individual factors directly. In this study, the effect of O(3) at high and low atmospheric vapour pressure deficit (VPD) was evaluated in two genotypes of snap bean (Phaseolus vulgaris L.) (R123 and S156) used as O(3) bioindicator plants. Plants were grown in outdoor controlled-environment chambers in charcoal-filtered air containing 0 or 60 nl l(-1) O(3) (12 h average) at two VPDs (1.26 and 1.96 kPa) and sampled for biomass, leaf area, daily water loss, and seed yield. VPD clearly influenced O(3) effects. At low VPD, O(3) reduced biomass, leaf area, and seed yield substantially in both genotypes, while at high VPD, O(3) had no significant effect on these components. In clean air, high VPD reduced biomass and yield by similar fractions in both genotypes compared with low VPD. Data suggest that a stomatal response to VPD per se may be lacking in both genotypes and it is hypothesized that the high VPD resulted in unsustainable transpiration and water deficits that resulted in reduced growth and yield. High VPD- and water-stress-induced stomatal responses may have reduced the O(3) flux into the leaves, which contributed to a higher yield compared to the low VPD treatment in both genotypes. At low VPD, transpiration increased in the O(3) treatment relative to the clean air treatment, suggesting that whole-plant conductance was increased by O(3) exposure. Ozone-related biomass reductions at low VPD were proportionally higher in S156 than in R123, indicating that differential O(3) sensitivity of these bioindicator plants remained evident when environmental conditions were conducive for O(3) effects. Assessments of potential O(3) impacts on vegetation should incorporate interacting factors such as VPD.

A systemic lupus erythematosus gene expression array in disease diagnosis and classification: a preliminary report.

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease diagnosed on the presence of a constellation of clinical and laboratory findings. At the pathogenetic level, multiple factors using diverse biochemical and molecular pathways have been recognized. Succinct recognition and classification of clinical disease subsets, as well as the availability of disease biomarkers, remains largely unsolved. Based on information produced by the present authors' and other laboratories, a lupus gene expression array consisting of 30 genes, previously claimed to contribute to aberrant function of T cells, was developed. An additional eight genes were included as controls. Peripheral blood was obtained from 10 patients (19 samples) with SLE and six patients with rheumatoid arthritis (RA) as well as 19 healthy controls. T cell mRNA was subjected to reverse transcription and PCR, and the gene expression levels were measured. Conventional statistical analysis was performed along with principal component analysis (PCA) to capture the contribution of all genes to disease diagnosis and clinical parameters. The lupus gene expression array faithfully informed on the expression levels of genes. The recorded changes in expression reflect those reported in the literature by using a relatively small (5 ml) amount of peripheral blood. PCA of gene expression levels placed SLE samples apart from normal and RA samples regardless of disease activity. Individual principal components tended to define specific disease manifestations such as arthritis and proteinuria. Thus, a lupus gene expression array based on genes previously claimed to contribute to immune pathogenesis of SLE may define the disease, and principal components of the expression of 30 genes may define patients with specific disease manifestations.

Adhesive properties of the beta 3 integrins: comparison of GP IIb-IIIa and the vitronectin receptor individually expressed in human melanoma cells.

Glycoprotein IIb-IIIa (alpha IIb beta 3) and the vitronectin receptor (alpha v beta 3), two integrins that share the common beta 3 subunit, have been reported to function as promiscuous receptors for the RGD-containing adhesive proteins fibrinogen, vitronectin, fibronectin, von Willebrand factor, and thrombospondin. The present study was designed to establish a cell system for the expression of either GP IIb-IIIa or the vitronectin receptor in an otherwise identical cellular environment and to compare the adhesive properties of these two integrins with those of native GP IIb-IIIa and the vitronectin receptor constitutively expressed in HEL cells or platelets. M21 human melanoma cells lack GP IIb-IIIa and use the vitronectin receptor to attach to vitronectin, fibrinogen, fibronectin, and von Willebrand factor. To study the functional properties of GP IIb-IIIa in these cells, we transfected GP IIb into M21-L cells, a variant of M21 cells (Cheresh, D.A., and R.C. Spiro. 1987. J. Biol. Chem. 262:17703-17711), which lack the expression of functional alpha v and are therefore unable to attach to vitronectin, fibrinogen, and von Willebrand factor. Transfectants expressing GP IIb were isolated by immunomagnetic beads and surface expression of the GP IIb-IIIa complex was documented by FACS analysis and immunoprecipitation experiments performed with 125I-labeled M21-L/GP IIb cells. Comparative functional studies demonstrated that GP IIb-IIIa expressed in M21-L/GPIIb cells as well as native GP IIb-IIIa constitutively expressed in HEL-5J20 cells (an HEL variant lacking alpha v beta 3) mediated cell attachment to immobilized fibrinogen, but not to vitronectin or von Willebrand factor, whereas the vitronectin receptor expressed in M21 cells and HEL-AD1 cells (an HEL variant expressing alpha v beta 3) mediated cell attachment to fibrinogen, vitronectin, and von Willebrand factor. Similarly, PGl2-treated resting platelets attached to immobilized fibrinogen but not to vitronectin or von Willebrand factor, and this attachment could be inhibited by mAb A2A9 (directed against a functional site on the GP IIb-IIIa complex). However, in contrast to platelets, which adhered to vitronectin and von Willebrand factor after stimulation by thrombin or PMA, activation of the protein kinase C pathway in M21-L/GP IIb or HEL cells did not induce cell adhesion to vitronectin or von Willebrand factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii.

The complete 1.66-megabase pair genome sequence of an autotrophic archaeon, Methanococcus jannaschii, and its 58- and 16-kilobase pair extrachromosomal elements have been determined by whole-genome random sequencing. A total of 1738 predicted protein-coding genes were identified; however, only a minority of these (38 percent) could be assigned a putative cellular role with high confidence. Although the majority of genes related to energy production, cell division, and metabolism in M. jannaschii are most similar to those found in Bacteria, most of the genes involved in transcription, translation, and replication in M. jannaschii are more similar to those found in Eukaryotes.