Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: Two-Year Results from a Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt (Santen Inc) versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: Prospective, randomized, multicenter trial conducted in the United States and Europe. PARTICIPANTS: Adult patients (aged 40-85 years) with mild to severe POAG inadequately controlled on maximum tolerated medical therapy and intraocular pressure (IOP) ≥ 15 mmHg and ≤ 40 mmHg. METHODS: Patients were randomized 3:1 to stand-alone MicroShunt implantation (n = 395) or trabeculectomy (n = 132), both augmented with mitomycin C (MMC) 0.2 mg/ml for 2 minutes. MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥ 20% reduction in mean diurnal IOP from baseline with no increase in glaucoma medications. Secondary end points included changes in mean IOP and medication use from baseline and the need for postoperative interventions. RESULTS: At 2 years, the rate of surgical success was lower in the MicroShunt group than in the trabeculectomy group (50.6% vs. 64.4%, P = 0.005). Mean diurnal IOP was reduced from 21.1 ± 4.9 mmHg at baseline to 13.9 ± 3.9 mmHg at 24 months in the MicroShunt group and from 21.1 ± 5.0 mmHg at baseline to 10.7 ± 3.7 mmHg at 24 months in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Mean medication use decreased from 3.1 to 0.9 in the MicroShunt group and from 2.9 to 0.4 in the trabeculectomy group (P < 0.001 compared with baseline in both groups). Adverse events at 2 years were generally similar in the 2 groups, except that hypotony was more common in eyes undergoing trabeculectomy (51.1% vs. 30.9%, P < 0.001). Repositioning or explantation of the implant occurred in 6.8% of MicroShunt patients. The majority of these patients had device removal at the time of subsequent glaucoma surgery. Vision-threatening complications were uncommon in both groups. CONCLUSION: At 2 years, both the MicroShunt and trabeculectomy provided significant reductions in IOP and medication use, with trabeculectomy continuing to have greater surgical success. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Association between Glucagon-like Peptide-1 Receptor Agonists and the Risk of Glaucoma in Individuals with Type 2 Diabetes.

PURPOSE: To examine the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the development of glaucoma in individuals with type 2 diabetes. DESIGN: Nationwide, nested case-control study. PARTICIPANTS: From a nationwide cohort of 264 708 individuals, we identified 1737 incident glaucoma cases and matched them to 8685 glaucoma-free controls, all aged more than 21 years and treated with metformin and a second-line antihyperglycemic drug formulation, with no history of glaucoma, eye trauma, or eye surgery. METHODS: Cases were incidence-density-matched to 5 controls by birth year, sex, and date of second-line treatment initiation. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for glaucoma, defined by first-time diagnosis, first-time use of glaucoma-specific medication, or first-time glaucoma-specific surgical intervention. RESULTS: Compared with the reference group, who received treatments other than GLP-1RA, individuals who were exposed to GLP-1RA treatment exhibited a lower risk of incident glaucoma (HR, 0.81; CI, 0.70-0.94; P = 0.006). Prolonged treatment extending beyond 3 years lowered the risk even further (HR, 0.71; CI, 0.55-0.91; P = 0.007). Treatment with GLP-1RA for 0 to 1 year (HR, 0.89; CI, 0.70-1.14; P = 0.35) and 1 to 3 years (HR, 0.85; CI, 0.67-1.06; P = 0.15) was not significant. CONCLUSIONS: Exposure to GLP-1RA was associated with a lower risk of developing glaucoma compared with receiving other second-line antihyperglycemic medication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Accountable care organization reform: past challenges and future opportunities for public health.

OBJECTIVES: This study aimed to analyze the regulatory landscape that governs accountable care organizations (ACOs) in the United States and the effects on organizational participation. STUDY DESIGN: This was a descriptive study of existing and prior regulations that govern ACOs in the United States. In addition, we analyze data on ACO participation over time. METHODS: We used content analysis methods to the regulatory framework governing ACOs. Authors read and analyzed all regulations since 2012. RESULTS: ACO participation has been undermined by a shifting regulatory landscape. Under the Trump administration, ACOs have had to take on additional risk earlier and that has contributed to the lowest number of participating organizations in the program's history. CONCLUSIONS: The Biden administration has the opportunity to remake regulations governing ACO development and support.

Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma: One-Year Results from a 2-Year Randomized, Multicenter Study.

PURPOSE: To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG). DESIGN: One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe. PARTICIPANTS: Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy. METHODS: Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use and adverse events. RESULTS: Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation, -12.34 decibels [dB]). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% vs. 72.7%, respectively; P < 0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1 ± 4.9 mmHg at baseline to 14.3 ± 4.3 mmHg (-29.1%; P < 0.01) at year 1, with a mean of 0.6 ± 1.1 glaucoma medications (baseline 3.1 ± 1.0; P < 0.01). In the trabeculectomy group, mean IOP decreased from 21.1 ± 5.0 mmHg to 11.1 ± 4.3 mmHg (-45.4%; P < 0.01), with a mean of 0.3 ± 0.9 glaucoma medications (baseline 3.0 ± 0.9; P < 0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P < 0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% vs. 28.9%; P < 0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients. CONCLUSIONS: Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.

Pre-frailty factors in community-dwelling 40-75 year olds: opportunities for successful ageing.

BACKGROUND: There is little known about pre-frailty attributes or when changes which contribute to frailty might be detectable and amenable to change. This study explores pre-frailty and frailty in independent community-dwelling adults aged 40-75 years. METHODS: Participants were recruited through local council networks, a national bank and one university in Adelaide, Australia. Fried frailty phenotype scores were calculated from measures of unintentional weight loss, exhaustion, low physical activity levels, poor hand grip strength and slow walking speed. Participants were identified as not frail (no phenotypes), pre-frail (one or two phenotypes) or frail (three or more phenotypes). Factor analysis was applied to binary forms of 25 published frailty measures Differences were tested in mean factor scores between the three Fried frailty phenotypes and ROC curves estimated predictive capacity of factors. RESULTS: Of 656 participants (67% female; mean age 59.9 years, SD 10.6) 59.2% were classified as not frail, 39.0% pre-frail and 1.8% frail. There were no gender or age differences. Seven frailty factors were identified, incorporating all 25 frailty measures. Factors 1 and 7 significantly predicted progression from not-frail to pre-frail (Factor 1 AUC 0.64 (95%CI 0.60-0.68, combined dynamic trunk stability and lower limb functional strength, balance, foot sensation, hearing, lean muscle mass and low BMI; Factor 7 AUC 0.55 (95%CI 0.52-0.59) comprising continence and nutrition. Factors 3 and 4 significantly predicted progression from pre-frail to frail (Factor 3 AUC 0.65 (95% CI 0.59-0.70)), combining living alone, sleep quality, depression and anxiety, and lung function; Factor 4 AUC 0.60 (95%CI 0.54-0.66) comprising perceived exertion on exercise, and falls history. CONCLUSIONS: This research identified pre-frailty and frailty states in people aged in their 40s and 50s. Pre-frailty in body systems performance can be detected by a range of mutable measures, and interventions to prevent progression to frailty could be commenced from the fourth decade of life.

Health assessments and screening tools for adults experiencing homelessness: a systematic review.

BACKGROUND: Homelessness is increasing globally. It results in poorer physical and mental health than age matched people living in permanent housing. Better information on the health needs of people experiencing homelessness is needed to inform effective resourcing, planning and service delivery by government and care organisations. The aim of this review was to identify assessment tools that are valid, reliable and appropriate to measure the health status of people who are homeless. METHODS: Data sources: A systematic literature search was conducted in PubMed (and Medline), PsychInfo, Scopus, CINAHL and ERIC from database inception until September 2018. Key words used were homeless, homelessness, homeless persons, vagrancy, health status, health, health issues, health assessment and health screening. The protocol was registered with PROSPERO. The National Health and Medical Research Council of Australia (NHMRC) hierarchy of evidence was applied; methodological quality of included articles was assessed using the McMaster critical appraisal tools and psychometric properties of the tools were appraised using the International Centre for Allied Health Evidence Ready Reckoner. RESULTS: Diverse tools and measures (N = 71) were administered within, and across the reviewed studies (N = 37), with the main focus being on general health, oral health and nutrition. Eleven assessment tools in 13 studies had evidence of appropriate psychometric testing for the target population in domains of quality of life and health status, injury, substance use, mental health, psychological and cognitive function. Methodological quality of articles and tools were assessed as moderate to good. No validated tools were identified to assess oral health, chronic conditions, anthropometry, demography, nutrition, continence, functional decline and frailty, or vision and hearing. However, assessments of physical constructs (such as oral health, anthropometry, vision and hearing) could be applied to homeless people on a presumption of validity, because the constructs would be measured with clinical indicators in the same manner as people living in permanent dwellings. CONCLUSIONS: This review highlighted the need to develop consistent and comprehensive health assessment tools validated with, and tailored for, adults experiencing homelessness.

Comparison of hyperspectral classification methods for the analysis of cerium oxide nanoparticles in histological and aqueous samples.

Hyperspectral imaging (HSI) and classification are established methods that are being applied in new ways to the analysis of nanoscale materials in a variety of matrices. Typically, enhanced darkfield microscopy (EDFM)-based HSI data (also known as image datacubes) are collected in the wavelength range of 400-1000 nm for each pixel in a datacube. Utilising different spectral library (SL) creation methods, spectra from pixels in the datacube corresponding to known materials can be collected into reference spectral libraries (RSLs), which can be used to classify materials in datacubes of experimental samples using existing classification algorithms. In this study, EDFM-HSI was used to visualise and analyse industrial cerium oxide (CeO2 ; ceria) nanoparticles (NPs) in rat lung tissues and in aqueous suspension. Rats were exposed to ceria NPs via inhalation, mimicking potential real-world occupational exposures. The lung tissues were histologically prepared: some tissues were stained with hematoxylin and eosin (H&E) and some were left unstained. The goal of this study was to determine how HSI and classification results for ceria NPs were influenced by (1) the use of different RSL creation and classification methods and (2) the application of those methods to samples in different matrices (stained tissue, unstained tissue, or aqueous solution). Three different RSL creation methods - particle filtering (PF), manual selection, and spectral hourglass wizard (SHW) - were utilised to create the RSLs of known materials in unstained and stained tissue, and aqueous suspensions, which were then used to classify the NPs in the different matrices. Two classification algorithms - spectral angle mapper (SAM) and spectral feature fitting (SFF) - were utilised to determine the presence or absence of ceria NPs in each sample. The results from the classification algorithms were compared to determine how each influenced the classification results for samples in different matrices. The results showed that sample matrix and sample preparation significantly influenced the NP classification thresholds in the complex matrices. Moreover, considerable differences were observed in the classification results when utilising each RSL creation and classification method for each type of sample. Results from this study illustrate the importance of appropriately selecting HSI algorithms based on specific material and matrix characteristics in order to obtain optimal classification results. As HSI is increasingly utilised for NP characterisation for clinical, environmental and health and safety applications, this investigation is important for further refining HSI protocols while ensuring appropriate data collection and analysis.

Smoking in pregnancy is a key factor for sudden infant death among Maori.

AIM: To examine the sudden unexpected death in infancy (SUDI) disparity between Maori and non-Maori in New Zealand. METHODS: A nationwide prospective case-control study ran from March 2012 to February 2015. Exposure to established SUDI risk factors was analysed to investigate the disparity experienced by Maori. Infant ethnicity was based on mother's ethnicity. Maori ethnicity was prioritised. Non-Maori includes Pacific, Asian, NZ European and Other. RESULTS: There were 137 cases and 649 controls. The Maori SUDI rate was 1.41/1000 live births compared to 0.53/1000 for non-Maori. Parents/caregivers of 132 cases (96%) and 258 controls (40%) were interviewed. Smoking in pregnancy was associated with an equally increased SUDI risk for Maori (adjusted OR = 8.11, 95% CI = 2.64, 24.93) and non-Maori (aOR = 5.09, 95% CI = 1.79, 14.47), as was bed-sharing (aOR = 3.66, 95% CI = 1.49, 9.00 vs aOR = 11.20, 95% CI = 3.46, 36.29). Bed-sharing prevalence was similar; however, more Maori controls smoked during pregnancy (46.7%) than non-Maori (22.8%). The main contributor relating to increased SUDI risk for Maori/non-Maori infants is the combination of smoking in pregnancy and bed sharing. CONCLUSION: The association between known SUDI risk factors, including bed sharing and/or smoking in pregnancy and SUDI risk, is the same regardless of ethnicity. Maori infants are exposed more frequently to both behaviours because of the higher Maori smoking rate.

Launching the dialogue: Safety and innovation as partners for success in advanced manufacturing.

Emerging and novel technologies, materials, and information integrated into increasingly automated and networked manufacturing processes or into traditional manufacturing settings are enhancing the efficiency and productivity of manufacturing. Globally, there is a move toward a new era in manufacturing that is characterized by: (1) the ability to create and deliver more complex designs of products; (2) the creation and use of materials with new properties that meet a design need; (3) the employment of new technologies, such as additive and digital techniques that improve on conventional manufacturing processes; and (4) a compression of the time from initial design concept to the creation of a final product. Globally, this movement has many names, but "advanced manufacturing" has become the shorthand for this complex integration of material and technology elements that enable new ways to manufacture existing products, as well as new products emerging from new technologies and new design methods. As the breadth of activities associated with advanced manufacturing suggests, there is no single advanced manufacturing industry. Instead, aspects of advanced manufacturing can be identified across a diverse set of business sectors that use manufacturing technologies, ranging from the semiconductors and electronics to the automotive and pharmaceutical industries. The breadth and diversity of advanced manufacturing may change the occupational and environmental risk profile, challenge the basic elements of comprehensive health and safety (material, process, worker, environment, product, and general public health and safety), and provide an opportunity for development and dissemination of occupational and environmental health and safety (OEHS) guidance and best practices. It is unknown how much the risk profile of different elements of OEHS will change, thus requiring an evolution of health and safety practices. These changes may be accomplished most effectively through multi-disciplinary, multi-sector, public-private dialogue that identifies issues and offers solutions.

A multivariate examination of 'artificial mussels' in conjunction with spot water tests in freshwater ecosystems.

Metal pollution in aquatic systems is considered a serious environmental issue globally due to their ability to accumulate in aquatic environments. Wetlands are vulnerable to this pollution as they are known to trap toxins, removing them from the water. Artificial mussel technology, originally developed for marine environments, was applied to this freshwater system and spot water samples were collected. The Nyl River floodplain (Ramsar classified) is one of the largest and most ecologically significant wetlands in South Africa. The aims of this study were to determine metal contamination along the Nyl River system by means of artificial mussels (AM) and water ICP-MS analysis and to determine whether the use of AMs in conjunction with spot water testing could give more insight into the pollution in freshwater wetlands. The concentrations of Al, Cd, Cr, Co, Cu, Fe, Mn, Ni, Pb and Zn were determined at seven sites. It was determined that the levels accumulated by the AMs differed in spatial and temporal trends when compared to spot water samples. It was determined that there were high levels of some metals found in the spot water tests that were not corroborated by the AMs results, which could indicate isolated pollution events. The use of AMs in conjunction with spot water testing was determined to be beneficial in gaining deeper insight into water metal conditions in dynamic freshwater systems.

Ecological risk assessment of trace elements in sediment: A case study from Limpopo, South Africa.

This study aimed to determine the ecological risk posed by metals, in sediments from the Nyl River system in Limpopo, South Africa. Metals were extracted from sediment samples by aqua regia microwave digestion and were analysed using standard ICP-OES techniques. The ecological risk indices applied to the data included Contamination Factor, Pollution Load Index, Geo-accumulation Index and Enrichment Factor. The results showed that the levels of Ni at STW and NYL in the HF period exceeded the Canadian Sediment Quality Guidelines by a factor of 1.36 and 1.83 respectively whereas NYL and MDD had 2.57 and 1.32 times the allowed limit of Ni in the LF period. During the HF period, the GC site exceeded the allowed limit of Zn by a factor of 1.04 and NYL had 1.21 times the allowed Zn in the LF period. The levels of metals are generally low near the origin of the river and increase moving downstream. The levels of metals in the Nyl River floodplain, a Ramsar accredited wetland, were high with CF scores ranging between 0.905 and 5.82, Igeo values with a range of -0.541 to 2.441 and EF scores ranging from 0.959 to 6.171. and posed a greater risk than the other sites. This indicated that the wetland is performing its ecological function by trapping and removing toxins from the water body. The Pollution Load Index determined that the Golf Course (PLI=4.586) and STW (PLI=2.617) sites were polluted only in the low flow period whereas the Nyl River floodplain (HF PLI=79.845; LF PLI=30378.768) and Moorddrift Dam (HF PLI=1.903; LF PLI=9.256) sites were polluted in high flow and low flow periods.

CONSTRUCTING SURROGATE MODELS OF COMPLEX SYSTEMS WITH ENHANCED SPARSITY: QUANTIFYING THE INFLUENCE OF CONFORMATIONAL UNCERTAINTY IN BIOMOLECULAR SOLVATION.

Biomolecules exhibit conformational fluctuations near equilibrium states, inducing uncertainty in various biological properties in a dynamic way. We have developed a general method to quantify the uncertainty of target properties induced by conformational fluctuations. Using a generalized polynomial chaos (gPC) expansion, we construct a surrogate model of the target property with respect to varying conformational states. To alleviate the high-dimensionality of the corresponding stochastic space, we propose a method to increase the sparsity of the gPC expansion by defining a set of conformational "active space" random variables. With the increased sparsity, we employ the compressive sensing method to accurately construct the surrogate model. We demonstrate the performance of the surrogate model by evaluating fluctuation-induced uncertainty in solvent-accessible surface area for the bovine trypsin inhibitor protein system and show that the new approach offers more accurate statistical information than standard Monte Carlo approaches. Furthermore, the constructed surrogate model also enables us to directly evaluate the target property under various conformational states, yielding a more accurate response surface than standard sparse grid collocation methods. In particular, the new method provides higher accuracy in high-dimensional systems, such as biomolecules, where sparse grid performance is limited by the accuracy of the computed quantity of interest. Our new framework is generalizable and can be used to investigate the uncertainty of a wide variety of target properties in biomolecular systems.

A novel system for spatial and temporal imaging of intrinsic plant water use efficiency.

Instrumentation and methods for rapid screening and selection of plants with improved water use efficiency are essential to address current issues of global food and fuel security. A new imaging system that combines chlorophyll fluorescence and thermal imaging has been developed to generate images of assimilation rate (A), stomatal conductance (gs), and intrinsic water use efficiency (WUEi) from whole plants or leaves under controlled environmental conditions. This is the first demonstration of the production of images of WUEi and the first to determine images of g s from themography at the whole-plant scale. Data are presented illustrating the use of this system for rapidly and non-destructively screening plants for alterations in WUEi by comparing Arabidopsis thaliana mutants (OST1-1) that have altered WUEi driven by open stomata, with wild-type plants. This novel instrument not only provides the potential to monitor multiple plants simultaneously, but enables intra- and interspecies variation to be taken into account both spatially and temporally. The ability to measure A, gs, and WUEi progressively was developed to facilitate and encourage the development of new dynamic protocols. Images illustrating the instrument's dynamic capabilities are demonstrated by analysing plant responses to changing photosynthetic photon flux density (PPFD). Applications of this system will augment the research community's need for novel screening methods to identify rapidly novel lines, cultivars, or species with improved A and WUEi in order to meet the current demands on modern agriculture and food production.

The continued emergence of hantaviruses: isolation of a Seoul virus implicated in human disease, United Kingdom, October 2012.

Following a suspected case of hantavirus in a patientsuffering from acute kidney injury, rodents fromthe patient's property in Yorkshire and the Humber,United Kingdom (UK) were screened for hantaviruses.Hantavirus RNA was detected via RT-PCR in two Rattusnorvegicus. Complete sequencing and phylogeneticanalysis established the virus as a Seoul hantavirus,which we have provisionally designated as strainHumber. This is the first hantavirus isolated from wildrodents in the UK and confirms the presence of a pathogenicSeoul virus in Europe.

Method for assessing IFN-γ responses in guinea pigs during TB vaccine trials.

AIMS: We sought to develop a new method that enables the assessment of the immune response of guinea pigs during TB vaccine evaluation studies, without the need to cull or anaesthetize animals. METHOD AND RESULTS: Guinea pigs were vaccinated with five different formulations of oral BCG. One week prior to challenge with Mycobacterium bovis, blood (50-200 µl) was taken from the ears of vaccinated subjects. Host RNA was isolated and amplified following antigenic restimulation of PBMCs for 24 h with 30 µg of bovine PPD. The up- or down-regulation of γ-interferon (IFN-γ), a key cytokine involved in protection against tuberculosis, was assessed using real-time PCR. The relative expression of prechallenge IFN-γ mRNA in the vaccinated groups (n=5) correlated (P<0·001) with protection against M. bovis challenge. CONCLUSION: We have demonstrated that it is possible to take blood samples and track IFN-γ responses in guinea pigs that then go on to be exposed to M. bovis, thus providing prechallenge vaccine uptake information. SIGNIFICANCE AND IMPACT OF THE STUDY: This methodology will also be applicable for tracking the immune responses of vaccinated guinea pigs over time that then go on to be challenged with M. tuberculosis during human TB vaccine evaluation studies.

Nanoinformatics: developing new computing applications for nanomedicine.

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended "nanotype" to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others.

Adapted cardiac rehabilitation for people with sub-acute, mild-to-moderate stroke: a mixed methods feasibility study.

OBJECTIVE: To determine the recruitment strategy, acceptability, adherence, outcome measures, and adverse events for a definitive study that will explore adapted cardiac rehabilitation (CR) for people post-stroke with mild-to-moderate severity stroke in the sub-acute stage of recovery. DESIGN: Mixed methods feasibility study. SETTING: Acute hospital setting, neurology outpatients and community hospitals. PARTICIPANTS: 32 participants with stroke (mean age: 64.4 years) of median National Institutes of Health Stroke Scale (NIHSS) score 2 (range: 0 to 6) within six months of stroke. INTERVENTION: All participants attended six weeks, adapted CR within one to six months after a stroke. A combined class with people post cardiac event. MAIN OUTCOME MEASURES: Incremental shuttle walk test (ISWT), blood pressure, heart rate, weight, body mass index, quality of life, fatigue, anxiety and depression, tone, falls, stroke attitude and knowledge, physical activity (accelerometry) and functional ability. QUALITATIVE: Interviews with participants, non-participants and people post-cardiac event. Focus groups with Stroke and CR teams. RESULTS: 32 participants were recruited. The programme was acceptable to people with mild stroke (NIHSS<3) and people post cardiac events; 80% of classes attended, a mean of 9.6 classes, with six drop-outs. The ISWT was an acceptable outcome measure (for NIHSS<3) and most measures showed positive changes. There was one adverse event. CONCLUSION: A definitive study to determine the effect of six weeks of adapted CR on cardiorespiratory fitness (CRf) in people who have had a mild severity stroke (NIHSS<3) in the sub-acute phase of recovery, is feasible. Teams need specialist education and support. A more specialist service may be needed for people with a stroke severity defined by NIHSS>2. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN14861846.

Oncology workforce issues: the challenge of the outpatient clinic.

It is well-recognized that cancer prevalence is increasing and will continue to do so over the coming years. Adaptation of cancer services to this reality, however, has been slow. The oncology workforce, already short-staffed, will be overburdened if change does not occur in a timely manner. The results of this study seek to highlight the current workings of oncology outpatient clinics at this hospital, and to identify areas of deficiencies that need to be addressed. By presenting a portrait of our outpatient clinics, it is hoped that a discussion surrounding workforce issues can be actively engaged, as this is crucial in order to succeed in providing quality care for our cancer patients, and simultaneously to support and mentor our invaluable medical and allied health staff.

Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival.

Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and for transmission between hosts, requiring stringent spatial and temporal regulation. Here, we apply kinome-wide gene deletion and gene tagging in Leishmania mexicana promastigotes to define protein kinases with life cycle transition roles. Whilst 162 are dispensable, 44 protein kinase genes are refractory to deletion in promastigotes and are likely core genes required for parasite replication. Phenotyping of pooled gene deletion mutants using bar-seq and projection pursuit clustering reveal functional phenotypic groups of protein kinases involved in differentiation from metacyclic promastigote to amastigote, growth and survival in macrophages and mice, colonisation of the sand fly and motility. This unbiased interrogation of protein kinase function in Leishmania allows targeted investigation of organelle-associated signalling pathways required for successful intracellular parasitism.

Campylobacter fetus translocation across Caco-2 cell monolayers.

Campylobacter fetus is a recognized pathogen of cattle and sheep, though human infection has also been reported. Ingestion of contaminated food or water is a proposed route of transmission for both humans and animals. The subsequent detection of the organism from extra-intestinal and systemic locations implies an ability to translocate across epithelial barriers. To determine how C. fetus disseminates from the intestine, Caco-2 cells cultured on porous membrane supports, were used as model intestinal epithelial cell monolayers. C. fetus was found to translocate equally well in both apical-to-basolateral and basolateral-to-apical directions for up to 24 h without altering Caco-2 cell monolayer permeability as assessed by transepithelial resistance and absence of paracellular diffusion of FITC-inulin. Using modified antibiotic protection assays, C. fetus was also observed to invade and subsequently egress from Caco-2 cells. Caco-2 cell invasion and translocation occurred independently of C. fetus S layer expression. Scanning and transmission electron microscopy revealed the presence of C. fetus associated with both apical and basal surfaces as well as in intracellular locations. C. fetus was, however, never observed in paracellular locations nor associated with Caco-2 cells junctions. Neither C. fetus invasion nor translocation across Caco-2 cell monolayers was impacted by latrunculin A, though translocation was enhanced in the presence of cytochalasin D which disrupted tight junctions. Tubulin cytoskeleton disrupting agents, colchicine and vinblastine, did inhibit C. fetus translocation though entry into Caco-2 cells remained unaffected. Together, translocation without disrupting monolayer integrity, invasion and egression from Caco-2 cells, electron microscopy observations and the requirement of a functional tubulin cytoskeleton for translocation, support a transcellular mechanism of C. fetus translocation across Caco-2 cell monolayers. The ability to invade and subsequently egress would contribute to establishment of an infecting C. fetus population in the host, while the demonstrated ability to translocate across model intestinal epithelial barriers accounts for the observed in vivo recovery of C. fetus from extra-intestinal locations.