A core outcome set for evaluating the effectiveness of mixed-diagnosis falls prevention interventions for people with Multiple Sclerosis, Parkinson's Disease and stroke.

INTRODUCTION: Clinical trials evaluating the effectiveness of falls prevention interventions for people with Multiple Sclerosis (MS), Parkinson's Disease (PD) and stroke measure heterogeneous outcomes, often omitting those meaningful to patients. A core outcome set (COS) is a standardised set of outcomes that should be assessed in all trials within a research area. The aim of this study was to develop a COS for evaluating mixed-diagnosis falls prevention interventions for people with MS, PD and stroke in non-acute and community settings, with input from relevant stakeholder groups. METHODS: Previously published research undertaken by the team, including a qualitative study with 20 patients and a review of the literature, were used to derive a longlist of potential outcomes. Outcomes were prioritised for inclusion in the COS using a three-round online Delphi survey. A multi-stakeholder, consensus meeting was conducted to agree upon the final COS and to provide a recommendation for a single outcome measure for each outcome in the COS. RESULTS: Forty-eight participants were recruited across four stakeholder groups (researchers, patients, clinicians, and service-planners/policymakers). A total of 42 participants (87.5%) completed all three rounds of the surveys. Sixty-two outcomes were considered for inclusion in the COS throughout the Delphi process. A total of 15 participants attended the consensus meeting where they agreed upon the final COS and accompanying measurement instruments: fall incidence, injurious fall incidence, quality of life, falls self-efficacy, fear of falling, activity curtailment due to fear of falling, and cost-effectiveness. Attendees at the consensus meeting recommended that the proposed mechanism of impact of an intervention is considered when selecting additional outcomes outside of those in the COS to assess. CONCLUSIONS: This study identified a COS for evaluating the effectiveness of mixed-diagnosis falls prevention interventions for people with MS, PD and stroke. It is recommended that this COS and accompanying measurement instruments be used in all future trials in this research area so that findings can be combined and compared.

Variation in the practice of wide local excision for melanoma in Ireland and the UK: a questionnaire survey.

BACKGROUND: Wide local excision (WLE) is standard practice in the management of melanoma, but no national or international guidelines exist regarding its technique. OBJECTIVES: To assess variation in the practice of WLE and to explore the effect of clinicians' specialty and grade on such variation. METHODS: This was an international, anonymized, cross-sectional study. An online questionnaire was distributed to the Irish Association of Dermatologists, British Association of Dermatologists, British Association of Plastic and Reconstructive and Aesthetic Surgeons, Melanoma Focus and BioGenoMEL members. RESULTS: Of 128 respondents, 57% were dermatologists and 38% plastic surgeons. Most (80%) were consultants. Almost all clinicians learned their technique from colleagues (99%) 'on the job', although 21% also used textbooks or other media as part of WLE training. There was significant variation in planning and performing WLE: 59% considered margins already achieved, 71% marked margins with the skin relaxed. For 1 cm WLE, 84% delineated 1 cm from the edge of the scar; with a greater proportion of plastic surgeons than dermatologists marking from the centre of the scar (P < 0.05). Most followed a longitudinal/oblique axis on the limbs for WLE (81%). Only 40% sent 'dog ears' for histology. Most (70%) incised through the marked line, 27% incised outside it. Most (79%) excised to deep fascia, 18% to the next biological margin. CONCLUSIONS: This study demonstrates significant variation among clinicians performing WLE, an essential component of melanoma management. We postulate that this could have an impact on patient outcomes. A consensus statement should be developed, to achieve more consistency in the practice of WLE.

HepCare Plus: Enhancing Primary Care Identification and Treatment of Hepatitis C Virus in High-Risk Individuals.

Hepatitis C Virus (HCV) disproportionately affects people who inject drugs, migrants, prisoners and the homeless. An integrated, peer-led model of care involving primary and secondary care is required to enhance the identification and treatment of HCV in these marginalised groups. HepCare Plus builds on the network and achievements of HepCare Europe (a co-funded Third Health Programme of the European Union/Health Service Executive project). It further identifies those not accessing care and facilitates prompt assessment and treatment of those diagnosed with HCV, with the aid of a peer support worker (PSW) and a community HCV nurse specialist. Of 109 individuals identified and assessed for HCV treatment, 100 commenced HCV treatment. Despite interruptions to treatment (COVID-19 pandemic and national health service cyberattack) there was a high-level of treatment completion with PSW engagement (98%, n = 98). Eighty (73%) individuals were previously aware of a positive HCV status, highlighting the ongoing need to address barriers preventing marginalised groups from engaging with care. HepCare Plus reiterates the defining role of peer-led community interventions in HCV treatment engagement and the need for continuous open-ended HCV care. It provides a sustainable framework to meaningfully combat HCV and achieve the United Nations Sustainable Development Goal of HCV elimination by 2030.

Integrating Hepatitis C Care for Opioid Substitution Treatment Patients Attending General Practice: Feasibility, Clinical, and Cost-Effectiveness Analysis.

BACKGROUND: Hepatitis C virus (HCV) infection is common among people who inject drugs, yet well-described barriers mean that only a minority have accessed HCV treatment. Recent developments in HCV diagnosis and treatment facilitate innovative approaches to HCV care that improve access to, and uptake of, care by people who inject drugs. OBJECTIVE: This study aims to examine feasibility, acceptability, likely clinical effectiveness, and cost-effectiveness of an integrated model of HCV care for patients receiving opioid substitution treatment in general practice. METHODS: A pre- and postintervention design with an embedded economic analysis was used to establish the feasibility, acceptability, and clinical and cost-effectiveness of a complex intervention to optimize HCV identification and linkage to HCV treatment among patients prescribed methadone in primary care. The "complex intervention" comprised general practitioner (GP)/practice staff education, nurse-led clinical support, and enhanced community-based HCV assessment of patients. General practices in North Dublin were recruited from the professional networks of the research team and from GPs who attended educational sessions. RESULTS: A total of 135 patients from 14 practices participated. Follow-up data were collected 6 months after intervention from 131 (97.0%) patients. With regard to likely clinical effectiveness, among patients with HCV antibody positivity, there was a significant increase in the proportions of patients who had a liver FibroScan (17/101, 16.8% vs 52/100, 52.0%; P<.001), had attended hepatology/infectious diseases services (51/101, 50.5% vs 61/100 61.0%; P=.002), and initiated treatment (20/101, 19.8% vs 30/100, 30.0%; P=.004). The mean incremental cost-effectiveness ratio of the intervention was €13,255 (US $13,965.14) per quality-adjusted life-year gained at current full drug list price (€39,729 [US $41,857.48] per course), which would be cost saving if these costs are reduced by 88%. CONCLUSIONS: The complex intervention involving clinical support, access to assessment, and practitioner education has the potential to enhance patient care, improving access to assessment and treatment in a cost-effective manner.

Mixed methods protocol to examine the acceptability and clinical characteristics of a remote monitoring programme for delivery of COVID-19 care, among healthcare staff and patients.

INTRODUCTION: The use of remote monitoring technology to manage the care of patients with COVID-19 has been implemented to help reduce the burden placed on healthcare systems during the pandemic and protect the well-being of both staff and patients. Remote monitoring allows patients to record their signs and symptoms remotely (eg, while self-isolating at home) rather than requiring hospitalisation. Healthcare staff can, therefore, continually monitor their symptoms and be notified when the patient is showing signs of clinical deterioration. However, given the recency of the COVID-19 outbreak, there is a lack of research regarding the acceptance of remote monitoring interventions to manage COVID-19. This study will aim to evaluate the use of remote monitoring for managing COVID-19 cases from the perspective of both the patient and healthcare staff. METHODS AND ANALYSIS: Discharged patients from a large urban teaching hospital in Ireland, who have undergone remote monitoring for COVID-19, will be recruited to take part in a cross-sectional study consisting of a quantitative survey and a qualitative interview. A mixed methods design will be used to understand the experiences of remote monitoring from the perspective of the patient. Healthcare staff who have been involved in the provision of remote monitoring of patients with COVID-19 will be recruited to take part in a qualitative interview to understand their experiences with the process. Structural equation modelling will be used to examine the acceptance of the remote monitoring technology. Latent class analysis will be used to identify COVID-19 symptom profiles. Interview data will be examined using thematic analysis. ETHICS AND DISSEMINATION: Ethical approval has been granted by the ethical review boards at University College Dublin and the National Research Ethics Committee for COVID-19-related Research. Findings will be disseminated via publications in scientific journals, policy briefs, short reports and social media.

General practice attendances among patients attending a post-COVID-19 clinic: a pilot study.

BACKGROUND: About 10-35% of people with COVID-19 need medical care within 3 weeks of infection. However, the prevalence of ongoing care needs among those experiencing severe COVID-19 illness is unclear. AIM: This pilot study aimed to address this knowledge gap by examining GP attendance trends among patients attending a post-COVID-19 hospital follow-up clinic, 3-6 months after an initial clinic visit. DESIGN & SETTING: Data were collected from adult patients attending a post-COVID-19 follow-up clinic at the Mater Misericordiae University Hospital (MMUH), Dublin, Ireland. METHOD: Participants completed questionnaires outlining their demographics; medical histories; emergency hospital admissions and readmissions where applicable; and, where relevant, GP attendances following hospital discharge. Analyses were conducted using descriptive and inferential statistics. RESULTS: Participants' (n = 153) median age was 43.5 years (interquartile range [IQR] = 30.9-52.1 years). There were 105 females (68.6%, 95% confidence interval [CI] = 61.3% to 75.9%). Various medical histories were reported among participants. Sixty-seven (43.2%, 95% CI = 35.9% to 51.6%) received emergency COVID-19 hospital care. Older adults, males, intensive care unit [ICU] admissions, and readmissions were common among hospital attendees. Of the hospital attendees, 16 (24%, 95% CI = 13.7% to 34.2%) attended GPs within 7 days of hospital discharge, and 26 (39%, 95% CI = 27.3% to 50.7%) within 30 days. Older adults, people with pre-existing medical conditions, and individuals admitted to ICU and/or readmitted to hospital were common among general practice attendees. CONCLUSION: Persistent health issues appear to be common among patients with severe COVID-19, particularly those who are older adults, have pre-existing health problems, and who had been in ICU and/or readmission care. Larger scale studies of ongoing COVID-19 care needs in primary care and general practice are required.

HepCare Ireland-a service innovation project.

Hepatitis C virus (HCV) remains a major cause of morbidity and death worldwide, with prevalence highest among people who inject drugs (PWID), homeless populations and prisoners. The World Health Organization has published targets to be achieved by 2030 as part of its global health sector strategy to eliminate viral hepatitis. Recent innovations in testing and treatment of HCV mean such goals are achievable with effective infrastructure, political will and funding. 'HepCare Europe' was a 3-year, EU-funded project involving four member states. It sought to develop, implement and evaluate interventions to improve HCV outcomes through multiple-level interventions, running between 2016 and 2019. This paper aims to summarize the methods and present the aggregate cascade of care figures for the Irish components of HepCare. 'HepCare Ireland' contained five integrated work packages: HepCheck, HepLink, HepFriend, HepEd and HepCost. Interventions included intensified screening, community-based assessment, linkage to specialist care, peer training and support, multidisciplinary educational resources and cost-effectiveness analysis. A total of 812 participants were recruited across the three clinical work packages in Ireland. Two hundred and fifty-seven (31.7%) of the tested participants had an HCV antibody-positive result, with 162 (63.0%) testing positive for HCV RNA. At the time of writing (6th of November 2019), 57 (54.8%) of participants put on treatment had achieved SVR12, with 44 (42.3%) still undergoing treatment. In HepCheck, HepLink. HepEd and HepFriend, we demonstrate a series of interventions to improve Irish HCV outcomes. Our findings highlight the benefits of multilevel interventions in HCV care.

Integrating hepatitis C care for at-risk groups (HepLink): baseline data from a multicentre feasibility study in primary and community care.

OBJECTIVES: To examine HCV prevalence and management among people who inject drugs (PWID) attending primary care and community-based health services at four European sites using baseline data from a multicentre feasibility study of a complex intervention (HepLink). METHODS: Primary care and community-based health services in Dublin, London, Bucharest and Seville were recruited from the professional networks of the HepLink consortium. Patients were eligible to participate if aged ≥18 years, on opioid substitution treatment or at risk of HCV (i.e. injecting drug use, homeless or incarcerated), and attended the service. Data on patient demographics and prior HCV management were collected on participants at baseline. RESULTS: Twenty-nine primary care and community-based health services and 530 patients were recruited. Baseline data were collected on all participants. Participants' mean age ranged from 35 (Bucharest) to 51 years (London), with 71%-89% male. Prior lifetime HCV antibody testing ranged from 65% (Bucharest) to 95% (Dublin) and HCV antibody positivity among those who had been tested ranged from 78% (Dublin) to 95% (Bucharest). Prior lifetime HCV RNA testing among HCV antibody-positive participants ranged from 17% (Bucharest) to 84% (London). Among HCV antibody- or RNA-positive participants, prior lifetime attendance at a hepatology/infectious disease service ranged from 6% (London) to 50% (Dublin) and prior lifetime HCV treatment initiation from 3% (London) to 33% (Seville). CONCLUSIONS: Baseline assessment of the HCV cascade of care among PWID attending primary care and community-based health services at four European sites identified key aspects of the care cascade at each site that need to be improved.

Evaluating peer-supported screening as a hepatitis C case-finding model in prisoners.

BACKGROUND: Hepatitis C Virus (HCV) infection is endemic in prison populations, and HCV management in prisons is suboptimal. Incarceration is a public health opportunity to target this cohort. Community peer support increases HCV screening and treatment uptake. Prison peer workers have the potential to support the engagement of prisoners with health services and reduce stigma. This study's primary aim is to evaluate peer-supported screening as a model of active HCV case finding with a secondary aim to describe the HCV cascade among those infected including linkage to care and treatment outcomes. METHODS: An observational study was conducted in a medium-security Irish male prison housing 538 inmates, using a risk-based questionnaire, medical records, peer-supported screening, laboratory-based HCV serology tests and mobile elastography. RESULTS: A prison peer-supported screening initiative engaged large numbers of prisoners in HCV screening (n = 419). The mean age of participants was 32.8 years, 92% were Irish and 33% had a history of injecting drug use. Multiple risk factors for HCV acquisition were identified including needle sharing (16%). On serological testing, 87 (21%) were HCV Ab +ve and 50 (12%) were HCV RNA +ve of whom 80% were fibroscaned (25% showing evidence of liver disease). Eighty-six percent of those with active infection were linked with HCV care, with 33% undergoing or completing treatment. There was a high concordance with HCV disclosure at committal and serological testing (96% for HCV Ab +ve and 89% for HCV Ab -ve). CONCLUSION: Peer-supported screening is an effective active HCV case-finding model to find and link prisoners with untreated active HCV infection to HCV care.

Hepatitis C Prevalence and Management Among Patients Receiving Opioid Substitution Treatment in General Practice in Ireland: Baseline Data from a Feasibility Study.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and death. Injection drug use is now one of the main routes of transmission of HCV in Ireland and globally with an estimated 80% new infections occurring among people who inject drugs (PWID). OBJECTIVE: We aimed to examine whether patients receiving opioid substitution therapy in primary care practices in Ireland were receiving guideline-adherent care regarding HCV screening. Ireland has developed a model of care for delivering opioid substitution treatment in the primary care setting. We conducted this study given the shift of providing care for PWID from secondary to primary care settings, in light of current guidelines aimed at scaling up interventions to reduce chronic HCV infection and associated mortality. METHODS: We included baseline data from the Dublin site of the Heplink study, a feasibility study focusing on developing complex interventions to enhance community-based HCV treatment and improve the HCV care pathway between primary and secondary care. We recruited 14 opioid substitution treatment-prescribing general practices that employed the administration of opioid substitution therapy from the professional networks and databases of members of the research consortium. A standardized nonprobability sampling framework was used to identify 10 patients from each practice to participate in the study. Patients were eligible if aged ≥18 years, on opioid substitution treatment, and attending the practice for any reason during the recruitment period. The baseline data were collected from the clinical records of participating patients. We collected and analyzed data on demographic characteristics, care processes and outcomes regarding HCV and other blood-borne viruses, urinalysis test results, alcohol use disorders, chronic illness, and health service utilization. We examined whether patients received care concordant with guidelines related to HCV screening and care. RESULTS: The baseline data were collected from clinical records of 134 patients; 72.2% (96/134) were males; (mean age 43, SD 7.6; range 27-71 years); 94.8% (127/134) of patients had been tested for anti-HCV antibody in their lifetime; of those, 77.9% (99/127) tested positive. Then, 83.6% (112/134) of patients had received an HIV antibody test in their lifetime; of those, 6.3% (7/112) tested HIV positive. Moreover, 66.4% (89/134) of patients had been tested for hepatitis B virus in their lifetime and 8% (7/89) of those were positive. In the 12 months before the study, 30.6% (41/134) of patients were asked about their alcohol use by their general practitioner, 6.0% (8/134) received a brief intervention, and 2.2% (3/134) were referred to a specialist addiction or alcohol treatment service. CONCLUSIONS: With general practice and primary care playing an increased role in HCV care, this study highlights the importance of prioritizing the development and evaluation of real-world clinical solutions that support patients from diagnosis to treatment completion.

Integrated Hepatitis C Care for People Who Inject Drugs (Heplink): Protocol for a Feasibility Study in Primary Care.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and death. Drug use remains the significant cause of new infections in the European Union, with estimates of HCV antibody prevalence among people who inject drugs ranging from 5% to 90% in 29 European countries. In Ireland and the European Union, primary care is a key area to focus efforts to enhance HCV diagnosis and treatment among people who inject drugs. OBJECTIVE: The Heplink study aims to improve HCV care outcomes among opiate substitution therapy (OST) patients in general practice by developing an integrated model of HCV care and evaluating its feasibility, acceptability, and likely efficacy. METHODS: The integrated model of care comprises education of community practitioners, outreach of an HCV-trained nurse into general practitioner (GP) practices, and enhanced access of patients to community-based evaluation of their HCV disease (including a novel approach to diagnosis, that is, Echosens FibroScan Mini 430). A total of 24 OST-prescribing GP practices were recruited from the professional networks and databases of members of the research consortium. Patients were eligible if they are aged ≥18 years, on OST, and attend the practice for any reason during the recruitment period. Baseline data on HCV care processes and outcomes were extracted from the clinical records of participating patients. RESULTS: This study is ongoing and has the potential to make an important impact on patient care and provide high-quality evidence to help GPs make important decisions on HCV testing and onward referral. CONCLUSIONS: A substantial proportion of HCV-positive patients on OST in general practice are not engaged with specialist hospital services but qualify for direct-acting antiviral drugs treatment. The Heplink model has the potential to reduce HCV-related morbidity and mortality. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9043.

Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of Healthy Young Adults.

In a laboratory exercise for undergraduate biology majors, students plated bacteria from swabs of their facial skin under conditions that selected for coagulase-negative Staphylococcus; added disks containing the antibiotics penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of inhibition. Students also recorded demographic and lifestyle variables and merged this information with similar data collected from 9,000 other students who had contributed to the database from 2003 to 2011. Minimum inhibitory concentration (MIC) testing performed at the Harborview Medical Center Microbiology Laboratory (Seattle, WA) indicated a high degree of accuracy for student-generated data; species identification with a matrix-assisted laser desorption ionization (MALDI) Biotyper revealed that over 88% of the cells analyzed by students were S. epidermidis or S. capitus. The overall frequency of resistant cells was high, ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant to penicillin. Stepwise logistic regressions suggested that recent antibiotic use was strongly associated with resistance to three of the four antibiotics tested (p = 0.0003 for penicillin, p << 0.0001 for erythromycin and tetracycline), and that age, gender, use of acne medication, use of antibacterial soaps, or makeup use were associated with resistance to at least one of the four antibiotics. Furthermore, drug resistance to one antibiotic was closely linked to resistance to the other three antibiotics in every case (all p values << 0.0001), suggesting the involvement of multidrug-resistant strains. The data reported here suggest that citizen science could not only provide an important educational experience for undergraduates, but potentially play a role in efforts to expand antibiotic resistance (ABR) surveillance.

Increased platelet reactivity in HIV-1-infected patients receiving abacavir-containing antiretroviral therapy.

BACKGROUND: Current or recent use of abacavir for treating human immunodeficiency virus type 1 (HIV-1) infection has been associated with increased rates of myocardial infarction (MI). Given the role of platelet aggregation in thrombus formation in MI and the reversible nature of the abacavir association, we hypothesized that patients treated with abacavir would have increased platelet reactivity. METHODS: In a prospective study in adult HIV-infected patients, we determined associations between antiretrovirals (ARVs), and in particular the nucleoside reverse transcriptase inhibitor abacavir, and platelet reactivity by measuring time-dependent platelet aggregation in response to agonists: adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), collagen, and epinephrine. RESULTS: Of 120 subjects, 40 were ARV-naive and 80 ARV-treated, 40 of whom were receiving abacavir. No consistent differences in platelet reactivity were observed between the ARV-naive and ARV-treated groups. In contrast, within the ARV-treated group, abacavir-treated subjects had consistently higher percentages of platelet aggregation upon exposure to ADP, collagen, and epinephrine (P = .037, P = .022, and P = .032, respectively) and had platelets that were more sensitive to aggregation upon exposure to TRAP (P = .025). CONCLUSIONS: The consistent increases in platelet reactivity observed in response to a range of agonists provides a plausible underlying mechanism to explain the reversible increased rates of MI observed in abacavir-treated patients.

Platelet function and HIV: a case-control study.

OBJECTIVE: Cardiovascular disease and myocardial infarction are of increasing concern in HIV-infected populations. Although platelets mediate arterial thrombosis, central to myocardial infarction, data on platelet function in HIV infection are lacking. We hypothesized that HIV-infected patients would have altered platelet reactivity. DESIGN: A case-control study of platelet reactivity in 20 HIV-infected (HIVpos) and 20 age and sex-matched HIV-negative (HIVneg) individuals. METHODS: Time-dependent platelet aggregation was measured in response to increasing concentrations of platelet agonists: epinephrine, collagen, thrombin receptor-activating peptide and ADP using light absorbance. RESULTS: In both groups, mean age was 34 years, and 65% were men. Sixteen out of 20 (80%) of the HIVpos patients were on antiretroviral therapy with 12 out of 20 (60%) patients having HIV RNA less than 50 copies/ml. There were significant between-group differences in platelet reactivity across all four agonists. Platelets from HIVpos patients were more reactive to epinephrine [mean (SD) log concentration required to induce 50% maximal aggregation, 1.9 (1.2) versus 3.0 (1.7) mumol/l in HIVneg individuals, P = 0.028], whereas less platelet aggregation was observed in response to submaximal concentrations of the other agonists [thrombin receptor-activating peptide 72.5 (14.5)% versus 82.2 (7.6)% at 10 mumol/l, P = 0.011; ADP 67.3 (12.1)% versus 75.2 (8.8)% at 10 mumol/l, P = 0.035; collagen 16.6 (25.1)% versus 35.4 (31.5)% at 71.25 microg/ml, P = 0.007]. CONCLUSION: Between-group differences in platelet responses to all agonists suggest multiple underlying defects in platelet function in HIV infection. Further research is required to determine the contribution of antiretroviral therapy and relationships between platelet function and the increased cardiovascular disease observed in HIV-infected populations.

If schools are closed, who will watch our kids? Family caregiving and other sources of role conflict among nurses during large-scale outbreaks.

OBJECTIVES: The global impact of severe acute respiratory syndrome (SARS) brought attention to the role of healthcare professionals as "first receivers" during infectious disease outbreaks, a collateral aspect to their role as responders. This article records and reports concerns expressed by Canadian emergency and critical care nurses in terms of organizational and social supports required during infectious disease outbreaks. The nature of work-family and family-work conflict perceived and experienced by nurses during infectious disease outbreaks, as well as the supports needed to enable them to balance their social roles during this type of heightened stress, are explored. METHODS: Five focus groups consisting of 100 nurses were conducted using a Structured Interview Matrix facilitation technique. RESULTS: Four emergent themes included: (1) substantial personal/professional dilemmas; (2) assistance with child, elder, and/or pet care; (3) adequate resources and vaccinations to protect families; and (4) appropriate mechanisms to enable two-way communication between employees and their families under conditions of quarantine or long work hours. CONCLUSIONS: Social and organizational supports are critical to help buffer the effects of stress for nurses and assist them in managing difficult role conflicts during infectious disease outbreaks. These supports are necessary to improve response capacity for bio-disasters.

Constructing medical social authority on dress in Victorian Canada.

During the late-Victorian period, campaigns to "reform" middle-class women's dress were grounded in discourses on health, eugenics, declining birth rates, comfort, and aesthetics. In Britain, the United States and Germany, organized "dress reform" movements emerged in the latter half of the 19th century, while in Canada the campaign was led primarily by physicians through public health education. This article explores the discussion on women's dress in public health literature in Canadian circulation between 1860-1900 and interprets findings within a feminist poststructuralist framework that posits the understanding of women's bodies and gender regulation to be central to knowledge construction on women's dress.

Prescribed active learning increases performance in introductory biology.

We tested five course designs that varied in the structure of daily and weekly active-learning exercises in an attempt to lower the traditionally high failure rate in a gateway course for biology majors. Students were given daily multiple-choice questions and answered with electronic response devices (clickers) or cards. Card responses were ungraded; clicker responses were graded for right/wrong answers or participation. Weekly practice exams were done as an individual or as part of a study group. Compared with previous versions of the same course taught by the same instructor, students in the new course designs performed better: There were significantly lower failure rates, higher total exam points, and higher scores on an identical midterm. Attendance was higher in the clicker versus cards section; attendance and course grade were positively correlated. Students did better on clicker questions if they were graded for right/wrong answers versus participation, although this improvement did not translate into increased scores on exams. In this course, achievement increases when students get regular practice via prescribed (graded) active-learning exercises.

Evolving therapies for multiple sclerosis.

The introduction of immunomodulatory and immunosuppressive agents for treatment of multiple sclerosis (MS) has forever altered the natural course of this incurable and disabling neurodegenerative disorder. Despite early diagnosis of relapsing-remitting MS and early initiation of therapy, patients still experience breakthrough relapses and progression of their underlying MS pathology. The imperfect effectiveness, side effects, and toxicity of these agents, emphasize the necessity for development of more effective medications with less adverse events. This chapter presents readers with the most current information on the nature, mechanism(s) of action, and side effects of the most promising experimental agents currently under clinical trials. Some of the agents now at different stages of clinical trial have emerged as both safe and promising. The understanding of MS etiology will lead to the development of increasingly specific, safer, and effective treatments for MS by neuroscientists and neurologists.

Relatedness between the two-component lantibiotics lacticin 3147 and staphylococcin C55 based on structure, genetics and biological activity.

BACKGROUND: Two component lantibiotics, such as the plasmid-encoded lacticin 3147 produced by Lactococcus lactis DPC3147 and staphylococcin C55 produced by Staphylococcus aureus C55, represent an emerging subgroup of bacteriocins. These two bacteriocins are particularly closely related, exhibiting 86% (LtnA1 and C55alpha) and 55% (LtnA2 and C55beta) identity in their component peptides. The aim of this study was to investigate, for the first time for any two component bacteriocins, the significance of the relatedness between these two systems. RESULTS: So close is this relatedness that the hybrid peptide pairs LtnA1:C55beta and C55alpha:LtnA2 were found to have activities in the single nanomolar range, comparing well with the native pairings. To determine whether this flexibility extended to the associated post-translational modification/processing machinery, the staphylococcin C55 structural genes were directly substituted for their lacticin 3147 counterparts in the ltn operon on the large conjugative lactococcal plasmid pMRC01. It was established that the lacticin LtnA1 post-translational and processing machinery could produce functionally active C55alpha, but not C55beta. In order to investigate in closer detail the significance of the differences between LtnA1 and C55alpha, three residues in LtnA1 were replaced with the equivalent residues in C55alpha. Surprisingly, one such mutant LtnA1-Leu21Ala was not produced. This may be significant given the positioning of this residue in a putative lipid II binding loop. CONCLUSION: It is apparent, despite sharing striking similarities in terms of structure and activity, that these two complex bacteriocins display some highly dedicated features particular to either system.