Evaluating the importance of a core competency and capability framework for advanced practice physiotherapy: A cross-sectional survey.

INTRODUCTION: The need for a global core competency and capability framework for advanced practice physiotherapy is important due to the rapidly changing nature of health care delivery internationally and the need to standardize advanced practice physiotherapy. OBJECTIVE: To determine the importance of a proposed international core competency and capability framework for advanced practice physiotherapy. METHODS: We conducted a cross-sectional online survey of advanced practice physiotherapists across seven countries. The importance of each competency and capability was rated on a five-point agreement Likert scale. Participants were from the United Kingdom, Ireland, Australia, New Zealand, Canada, Switzerland and Argentina. RESULTS: A total of 99 participants completed the survey, comprising 63% (57/90) females and 33% (30/90) males. Sixty percent, 60% (54/90), had over 20 years of experience. The survey participants represented a diverse geographic distribution, with 25% (23/90) from Australia, 25% (23/90) from Canada, 18% (6/90) from New Zealand, and 18% (6/90) from the United Kingdom. Four percent 4% (4/90) from Ireland, and 4% (4/90) from other countries (Switzerland and Argentina). The survey revealed a strong consensus among participants, with all competencies and capabilities ranked as high and considered important to advanced practice. CONCLUSION: This study demonstrates a consensus among advanced practice physiotherapists across seven countries on the importance of a proposed competency and capability framework. The findings highlight the need for a global standard in advanced practice physiotherapy, particularly in light of the rapidly changing healthcare landscape.

Exploration of the polymorphic solid-state landscape of an amide-linked organic cage using computation and automation.

Organic cages can possess complex, functionalised cavities that make them promising candidates for synthetic enzyme mimics. Conformationally flexible, chemically robust structures are needed for adaptable guest binding and catalysis, but rapidly exchanging systems are difficult to resolve in solution. Here, we use low-cost calculations and high-throughput crystallisation to identify accessible conformers of a recently reported organic cage by 'locking' them in the solid state. The conformers exhibit varying distances between the internal carboxylic acid groups, suggesting adaptability for binding a wide array of target guest molecules.

Developing an international competency and capability framework for advanced practice physiotherapy: a scoping review with narrative synthesis.

INTRODUCTION: The need to address increasing numbers of people seeking care, insufficient numbers of physicians, and providing high-value and sustainable care has contributed to changing physiotherapy practice across the world, often referred to as advanced practice physiotherapy. Currently, there is no internationally standardized competency and capability framework to support advanced practice physiotherapy. OBJECTIVES: This scoping review has two aims; 1) To identify and map out the competencies of advanced practice physiotherapy available in the literature. 2) To develop a competency and capability framework by mapping the competencies identified from the review. DESIGN: The Arksey and O'Malley framework and the PRISMA Scoping review methodology were used. Databases searched included CINAHL Plus, MEDLINE Ovid, PubMed, and Scopus. The competency and capability framework was developed through a narrative synthesis approach. RESULTS: Nineteen documents were included in the final review, with 13 grey literature (government reports, policy documents, thesis) and six research papers. Included publications came from the United Kingdom, Ireland, Australia, New Zealand, and Canada. The included documents covered predominantly musculoskeletal practice (n = 17). The others focused on cardiorespiratory care, incontinence and pelvic health. Through narrative synthesis, 27 competencies and capabilities were identified and grouped under seven domains. CONCLUSION: The synthesis of this scoping review provides the first competency and capability framework for advanced practice physiotherapy that integrates competencies and capabilities from five different countries. With the expansion of advanced practice physiotherapy, the framework developed from this review is the first step towards international recognition, standardization and consistency of education and training of practitioners. CONTRIBUTION OF THE PAPER.

Assessing the feasibility of a clinical trial to evaluate an advanced practice physiotherapy model of care in chronic pain management: a feasibility study.

BACKGROUND: Chronic pain management is challenging for health systems worldwide. Clinical practice guidelines recommend interprofessional chronic pain management, but chronic pain clinics often have lengthy wait-lists. Advanced practice physiotherapists (APP) in orthopedic clinics and emergency departments have provided effective care and reduced wait times. The purpose of this study is to determine the feasibility of a clinical trial to evaluate the effects of integrating an APP into a chronic pain clinic setting. The primary objectives are as follows: (1) determine the feasibility of implementing trial methods by evaluating participant recruitment rates, retention, and assessment completion; (2) determine the feasibility of implementing the APP model of care by monitoring care provided and treatment fidelity; and (3) assess contextual factors that may influence implementation of the APP model of care by exploring the perspectives of patient participants and healthcare providers related to the model of care. METHODS: This will be a single-arm feasibility study with embedded qualitative interviews to assess contextual factors influencing implementation by exploring participant and provider perspectives. Approximately 40 adults with chronic musculoskeletal pain referred for care at an interprofessional chronic pain clinic will be invited to participate in the feasibility study. Approximately 10-12 patient participants and 5-10 health professionals from the interprofessional team will be interviewed using an interpretive description approach. The APP model of care will involve participants seeing a physiotherapist as the first point of contact within the interprofessional team. The APP will complete an initial assessment and make care recommendations. Outcome measures planned for the full trial will be reported descriptively, including pain severity, pain interference, health-related quality of life, psychosocial risk factors for chronic pain, treatment satisfaction, perceived change, healthcare utilization, and healthcare costs over one year. DISCUSSION: This study will inform plans to implement a full-scale study to evaluate the impact of an APP model of care in an interprofessional chronic pain management program. The results of the full study are intended to inform stakeholders considering this model to improve patient-centered and health system outcomes in interprofessional pain management program settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05336903 (Registered April 5, 2022).

Medicated-related burden and adherence in patients with co-morbid type 2 diabetes mellitus and hypertension.

Background: Medication adherence is an integral component in the management of patients with co-morbid type 2 diabetes mellitus (T2DM) and hypertension. However due to their combined conditions, there is likelihood of polypharmacy and medication-related burden, which could negatively impact adherence to therapy. This study aimed to assess the perceived medication-related burden among patients with co-morbid T2DM and hypertension and to evaluate the association between the perceived burden and adherence to medication therapy. Methods: A cross-sectional study was conducted among adult patients with co-morbid T2DM and hypertension attending a primary health facility. The living with medicines questionnaire and the medication adherence report scale were used to assess extent of medication-related burden and adherence respectively. Binary logistic regression model was used to estimate the adjusted odds and their corresponding 95% confidence interval for medication-related burden and adherence outcomes. All observed categorical variables were considered for the multivariable binary logistic regression model. Results: The total number of participants was 329 with a median age of 57.5 ± 13.2 years. The median score for the overall burden was 99 (IQR: 93-113), and this significantly varied by sex (p = 0.012), monthly income (p = 0.025), monthly expenditure on medications (p = 0.012), frequency of daily dose of medications (p = 0.020) and family history of T2DM (p < 0.001). About 30.7% and 36.8% of participants reported moderate/high burden and medication adherence respectively. Uncontrolled diastolic blood pressure (AOR: 2.46, 95% CI: 1.20-5.05, p = 0.014), high glucose (AOR: 4.24, 95% CI: 2.13-8.46, p < 0.001) and no family history of T2DM (AOR: 2.14, 95% CI: 1.14-4.02, p = 0.026) were associated with moderate/high medication burden. Uncontrolled diastolic blood pressure (AOR: 0.48, 95% CI: 0.25-0.94, p = 0.031), at least 5 years since hypertension diagnosis (AOR: 0.55, 95% CI: 0.30-0.99, p = 0.045) and moderate/high medication-related burden (AOR: 0.33, 95% CI: 0.16-0.69, p = 0.003) were associated with lower odds of medication adherence. Conclusion: These findings suggest that to improve the preventive and optimal care of patients with T2DM and hypertension, interventions that aim to reduce medication-related burden and morbidity are recommended. The study proposes that health stakeholders such as clinicians, pharmacists, and policy makers, develop multidisciplinary clinical and pharmaceutical care interventions to include provision of counselling to patients on adherence. In addition, developing policies and sensitization activities on deprescribing and fixed-dose drug combinations aimed at reducing medication-related burden, while promoting better adherence, blood pressure and blood glucose outcomes are recommended.

Developing a core competency and capability framework for advanced practice physiotherapy: A qualitative study.

INTRODUCTION: There is an urgent need to develop an international competency and capability framework to support standardization of education and roles in advanced practice physiotherapy (APP). This need arose due to the rapid growth of the APP model of care, implemented out of necessity in the absence of agreement as to the competencies and capabilities or formal education required for the roles. This study explores the views and perceptions of practitioners and key stakeholders on a draft competency and capability framework for advanced practice physiotherapists. OBJECTIVES: The purpose of this study was to: 1) gather feedback from key stakeholders (advanced practice physiotherapists, researchers, and leaders) on a draft competency and capability framework and 2) use that feedback to revise and improve the draft framework. DESIGN: Qualitative study using a series of four multi-national online focus groups. Thematic analysis was conducted according to Braun and Clarke. RESULTS: Sixteen participants from the United Kingdom, Ireland, Canada, Australia, and New Zealand participated in the study. Five themes were generated after data analysis: clinical expert, experienced communicator, strong leader, collaborator, and knowledge creator). A modified competency and capability framework was developed based on feedback from the focus groups and input from subject matter experts (SMEs). CONCLUSION: This study provides a modified core competency and capability framework comprising 24 competencies grouped under six domains. This study is a step toward international standardization of advanced practice physiotherapy based on a commonly agreed framework for the education and training of advanced practice physiotherapists.

The Family-Check-Up® Autism Implementation Research (FAIR) Study: protocol for a study evaluating the effectiveness and implementation of a family-centered intervention within a Canadian autism service setting.

Introduction: Prevalence rates of emotional and behavior problems (EBP) in autistic children and youth are high (40-70%), and often cause severe and chronic impairment. Furthermore, autistic children are also more likely to experience family "social-ecological" adversity compared to neurotypically developing peers, including social isolation, child maltreatment, caregiver mental illness, and socioeconomic risk. These family stressors increase the risk of co-occurring EBP among autistic children and can often impede access to evidence-based care, thus amplifying long-term health inequities for autistic children and their caregivers. In the current autism services landscape, there are few scalable, evidence-based programs that adequately address these needs. The Family Check-Up (FCU®) is a brief, strength-based, and tailored family-centered intervention that supports positive parenting and explicitly assesses the social determinants of child and family mental health within an ecological framework. Studies have demonstrated long-term positive child and caregiver outcomes in other populations, but the FCU® has not been evaluated in families of autistic children and youth. Therefore, we aimed to evaluate FCU® implementation within an established, publicly funded Autism Program in Ontario, Canada, with delivery by autism therapists, to demonstrate sustainable effectiveness within real-world settings. Methods: In this study, we outline the protocol for a hybrid implementation-effectiveness approach with two key components: (1) A parallel-arm randomized controlled trial of N = 80 autistic children/youth (ages 6-17 years) and high levels of EBP and their caregivers. Primary and secondary outcomes include child EBP, and caregiver well-being and parenting. (2) A mixed methods implementation study, to describe facilitators and barriers to implementation of the FCU® within an autism service setting. Discussion: Scalable, ecologically focused family-centered interventions offer promise as key components of a public health framework aimed at reducing mental health inequities among autistic children, youth, and their caregivers. Results of this study will inform further program refinement and scale-up.

Determinants of blood pressure and blood glucose control in patients with co-morbid hypertension and type 2 diabetes mellitus in Ghana: A hospital-based cross-sectional study.

Hypertension and diabetes are major risk factors for cardiovascular diseases and optimal control of blood pressure (BP) and blood glucose are associated with reduced cardiovascular disease events. This study, therefore, sought to estimate the prevalence and associated factors of controlled BP and blood glucose levels among patients diagnosed with both hypertension and Type 2- diabetes mellitus (T2DM). A quantitative cross-sectional study was conducted in a primary health setting in Ghana among patients 18 years and older diagnosed with both hypertension and T2DM. Pearson's chi-square was used to assess the association between BP and blood glucose levels and the independent variables. The multivariable binary logistic regression model was used to assess the adjusted odds of controlled BP and blood glucose levels. Among the 329 participants diagnosed with both hypertension and T2DM, 41.3% (95% CI: 36.1-46.8%) had controlled BP, 57.1% (95% CI: 51.7-62.4%) had controlled blood glucose whilst 21.8% (95% CI: 17.7-26.7%) had both controlled BP and blood glucose levels. Increased age, non-formal education, non-married, employed, single-dose anti-hypertensives or anti-diabetic medications, and hyperlipidaemia or stroke co-morbidities were positively associated with controlled BP levels. Being female, married, taking 2 or more anti-hypertensive medications, and moderate to high medication-related burden were positively associated with controlled blood glucose levels. In terms of both controlled BP and blood glucose levels, being employed, reduced income level, being registered with national health insurance, single anti-diabetes or anti-hypertensive medications, hyperlipidaemia or stroke co-morbidities, and moderate to high medication-related burden were positively associated with having both controlled BP and blood glucose levels. One in five patients with hypertension and T2DM had both BP and blood glucose levels under control. The benefits and risks of blood pressure and blood glucose targets should thus be factored into the management of patients with hypertension and T2DM.

Worldwide prevalence, genotype distribution and management of hepatitis C.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma, resulting in major global public health concerns. The HCV infection is unevenly distributed worldwide, with variations in prevalence across and within countries. The studies on molecular epidemiology conducted in several countries provide an essential supplement for a comprehensive knowledge of HCV epidemiology, genotypes, and subtypes, along with providing information on the impact of current and earlier migratory flows. HCV is phylogenetically classified into 8 major genotypes and 57 subtypes. HCV genotype and subtype distribution differ according to geographic origin and transmission risk category. Unless people with HCV infection are detected and treated appropriately, the number of deaths due to the disease will continue to increase. In 2015, 1.75 million new viral infections were mostly due to unsafe healthcare procedures and drug use injections. In the same year, access to direct-acting antivirals was challenging and varied in developing and developed countries, affecting HCV cure rates based on their availability. The World Health Assembly, in 2016, approved a global strategy to achieve the elimination of the HCV public health threat by 2030 (by reducing new infections by 90% and deaths by 65%). Globally, countries are implementing policies and measures to eliminate HCV risk based on their distribution of genotypes and prevalence.

Advanced practice in physiotherapy: a global survey.

INTRODUCTION: Advanced practice in physiotherapy represents a development in the practice of physiotherapy and has developed in different ways around the world. There is growing evidence to support advanced physiotherapy practice. In May 2019, the member organisations adopted the first World Physiotherapy policy on advanced practice in physiotherapy. However, to date, there is no evidence on the nature and extent of this practice globally. OBJECTIVES: To investigate the extent to which advanced practice is present within the global physiotherapy community, to document the titles used, to describe the pathway to become an advanced physiotherapy practitioner and to investigate the barriers and facilitators to the development of the roles. DESIGN: An online cross-sectional survey was sent to the various national associations of the World Physiotherapy. PARTICIPANTS: Participants were the member organisations of World Physiotherapy. INSTRUMENT: The survey comprised 14 questions. The questions were developed based on a review of the evidence around advanced practice and in-depth discussions with the expert group set up by World Physiotherapy. RESULTS: A total of 82/112 MOs responded to the survey representing a 73% response rate. Fourteen respondents (14/82, 17%) indicated that they had formal roles in their country/territory. The terms specialist and advanced physiotherapy practitioner were often used interchangeably and were a source of confusion. Seventy-nine (11/14, 79%) percent stated that most advanced physiotherapy practitioners have a combination of clinical practice and a Master's or Doctoral degree. The major facilitators to the development and sustainability of the role were the research evidence, advocacy by the professional organisation, the need to reduce cost and the support received by the advanced physiotherapy practitioners from their employers. CONCLUSION: The outcomes of this study provide a clearer understanding of how member organisations of World Physiotherapy defined advanced practice in physiotherapy and what titles are used. It provides insights into the barriers and facilitators to the development of advanced practice in physiotherapy.

Antiplasmodial activity of the natural product compounds alstonine and himbeline.

Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue. Despite a decline in malaria related deaths over the last decade, overall progress has plateaued. Key challenges to malaria prevention and control include the lack of a broadly effective vaccine and parasite drug resistance, including to the current gold standard artemisinin combination therapies (ACTs). New drugs with unique modes of action are therefore a priority for both the treatment and prevention of malaria. Unlike treatment drugs which need to kill parasites quickly to reduce or prevent clinical symptoms, compounds that kill parasites more slowly may be an option for malaria prevention. Natural products and natural product derived compounds have historically been an excellent source of antimalarial drugs, including the artemisinin component of ACTs. In this study, 424 natural product derived compounds were screened for in vitro activity against P. falciparum in assays designed to detect slow action activity, with 46 hit compounds identified as having >50% inhibition at 10 µM. Dose response assays revealed nine compounds with submicromolar activity, with slow action activity confirmed for two compounds, alstonine and himbeline (50% inhibitory concentration (IC50) 0.17 and 0.58 µM, respectively). Both compounds displayed >140-fold better activity against P. falciparum versus two human cell lines (Selectivity Index (SI) >1,111 and > 144, respectively). Importantly, P. falciparum multi-drug resistant lines showed no cross-resistance to alstonine or himbeline, with some resistant lines being more sensitive to these two compounds compared to the drug sensitive line. In addition, alstonine displayed cross-species activity against the zoonotic species, P. knowelsi (IC50 ~1 µM). Outcomes of this study provide a starting point for further investigations into these compounds as antiplasmodial drug candidates and the investigation of their molecular targets.

Clinical outcomes of combined surgical treatment of medial epicondylitis and cubital tunnel syndrome.

Surgical results for treatment of medial epicondylitis and cubital tunnel syndrome are generally satisfactory when performed alone. However, our experience suggests a combined procedure is associated with inferior outcomes. A retrospective review was conducted of consecutive surgical cases of medial epicondylectomy/debridement and ulnar nerve decompression during a single operation at our institution from March 2008 to February 2017 using CPT codes. Thirty combined procedures were identified in 29 patients. Fourteen patients and 15 elbows returned to clinic for evaluation at average 4.3 years after surgery (8 men, 6 women, mean age 45.1 years). A Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analogue pain scale (VAS), and physical examination were performed. The data was stratified by type of ulnar nerve procedure and analyzed. Three of fifteen elbows underwent in situ ulnar nerve decompression, and twelve of 15 had transposition, five subcutaneous and seven submuscular. The mean DASH score for in situ decompression was significantly higher than that of transposition (68.2 vs. 13.1). The average visual pain score for patients whom underwent in situ decompression was significantly higher than that of those with ulnar nerve transposition (8.0 vs. 1.2). All other physical exam measures demonstrated no significant difference between the two groups. In situ ulnar nerve decompression in the setting of medial epicondylectomy/debridement may be associated with inferior clinical outcomes in comparison to ulnar nerve transposition. Further studies are needed to validate the results of our study and inform management.

Discriminative validity of the EQ-5D-5 L and SF-12 in older adults with arthritis.

BACKGROUND: The EQ-5D-5 L and the SF-12 are the most commonly used generic measures of health-related quality of life among people with arthritis. However, there is little evidence on the extent to which the individual dimensions and domains of these instruments perform among this population. The objective was to examine the discriminative validity of the EQ-5D-5 L and the SF-12 version 2 (and SF-6D) in capturing the burden of arthritis on health-related quality of life in older adults. METHODS: Cross-sectional data from the Alberta Retired Teachers Association survey were used. A known-groups approach, with a-priori hypotheses, was used to examine the discriminative validity of the domain and summary scores of the EQ-5D-5 L and the SF-12 version 2 (and SF-6D). Groups were defined based on self-reported of arthritis, chronic pain level, presence and number of comorbidities, and self-reported health status. RESULTS: Mean age of respondents (N = 2844) was 68.6 (standard deviation [SD] 5.9) years; 54.8% were female, with mean body mass index (BMI) of 27.2 kg/m2 (SD 4.8), and 36.6% reported having arthritis. The overall mean EQ-5D-5 L index score was 0.86 (SD 0.11) and that of SF-6D was 0.79 (SD 0.13). Participants with arthritis had lower EQ-5D-5 L index score (0.83, SD 0.13) and SF-6D index score (0.75, SD 0.13) compared to those without arthritis (0.88, SD 0.09 and 0.81, SD 0.12, respectively). EQ-5D-5 L and SF-6D index scores demonstrated moderate discriminative validity with a moderate effect size (0.5). Related dimensions and domains between the EQ-5D-5 L and SF-12 (e.g., mobility with physical functioning score, pain/discomfort with bodily pain and anxiety/depression with mental health) were moderately to strongly correlated (r = 0.6-0.7). Both instruments could not adequately discriminate between participants with moderate and severe chronic pain of 6-month duration. CONCLUSION: Overall, the EQ-5D-5 L pain/discomfort and mobility dimensions, and the SF-12 bodily pain scale had moderate discriminative ability among older adults with arthritis. However, both instruments had limited discriminative ability for chronic pain. The importance and nature of chronic pain assessment in a given application need to be considered when choosing any of these instruments for measuring health-related quality of life in this patient population.

Seasonality and trends in incidence of human ehrlichiosis in two Missouri ecoregions.

Ehrlichiosis is a zoonotic illness caused by Ehrlichia pathogens transmitted by ticks. Case data from 1999 to 2015, provided by the Missouri Department of Health and Senior Services (DHSS), were used to compare the seasonality and the change in incidence over time of ehrlichiosis infection in two Missouri ecoregions, Eastern Temperate Forest (ETF) and Great Plains (GP). Although the number of cases has increased over time in both ecoregions, the rate of change was significantly faster in ETF region. There was no significant difference in seasonality of ehrlichiosis between ecoregions. In Missouri, the estimated ehrlichiosis season begins, on average, in mid-March, peaks in June, and concludes in mid-October. Our results show that the exposure and risk season for ehrlichiosis in Missouri is at least 7 months long.

Associations of physical activity with anxiety symptoms and status: results from The Irish longitudinal study on ageing.

AIMS: Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland. METHODS: Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009-2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017. RESULTS: Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78-1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76-1.10) and 18.8% (OR = 0.81, 0.67-0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63-1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89-2.32) increased, and 4.3% (OR = 0.96, 0.56-1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80-2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41-3.11) increase in odds of incident anxiety. CONCLUSION: High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose-response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.

Interactions of organic acids with vancomycin-resistant Enterococcus faecium isolated from community wastewater in Texas.

AIMS: Investigate the interactions of organic acids (OAs), acetic, butyric, citric, formic, lactic and propionic acid against 50 Gram-positive vancomycin-resistant Enterococcus faecium (VRE) strains to determine whether pH, undissociated or dissociated acid forms correlate with bacterial inhibition. METHODS AND RESULTS: Concentrations of undissociated and dissociated OAs at the molar minimum inhibitory concentrations (MICM s) of the VRE were calculated using the Henderson-Hasselbalch equation. The pH at the MICM s of all VRE strains against acetic, butyric, formic and propionic acids was similar, 4·66 ± 0·07, but there was a 1·1 pH unit difference for all six OAs. Inhibition of VRE by all six OAs did not appear to be solely dependent on pH or on the undissociated OA species. The inhibition of VRE by all six dissociated acids was within Δ = 3·1 mmol l-1 . CONCLUSIONS: Vancomycin-resistant Enterococcus faecium inhibition correlated with the dissociated OA species. A small decrease in the concentration of the dissociated OAs from optimum may result in allowing VRE strains to escape disinfection. SIGNIFICANCE AND IMPACT OF THE STUDY: When an OA is used to disinfect VRE strains, the concentration of the dissociated OA should be carefully controlled. A concentration of at least 20 mmol l-1 dissociated OA should be maintained when disinfecting VRE.

WAND2-A versatile wide angle neutron powder/single crystal diffractometer.

Wide Angle Neutron Diffractometer Squared is a high-flux versatile diffractometer with a 2-Dimensional Position Sensitive Detector at the High Flux Isotope Reactor. The instrument has strengths in both powder and single crystal diffraction. It is a unique instrument in the neutron scattering landscape of North America, and its capabilities are at least equal to similar instruments in the world.

A retrospective analysis of in vivo eye irritation, skin irritation and skin sensitisation studies with agrochemical formulations: Setting the scene for development of alternative strategies.

Analysis of the prevalence of health effects in large scale databases is key in defining testing strategies within the context of Integrated Approaches on Testing and Assessment (IATA), and is relevant to drive policy changes in existing regulatory toxicology frameworks towards non-animal approaches. A retrospective analysis of existing results from in vivo skin irritation, eye irritation, and skin sensitisation studies on a database of 223 agrochemical formulations is herein published. For skin or eye effects, high prevalence of mild to non-irritant formulations (i.e. per GHS, CLP or EPA classification) would generally suggest a bottom-up approach. Severity of erythema or corneal opacity, for skinor eye effects respectively, were the key drivers for classification, consistent with existing literature. The reciprocal predictivity of skin versus eye irritation and the good negative predictivity of the GHS additivity calculation approach (>85%) provided valuable non-testing evidence for irritation endpoints. For dermal sensitisation, concordance on data from three different methods confirmed the high false negative rate for the Buehler method in this product class. These results have been reviewed together with existing literature on the use of in vitro alternatives for agrochemical formulations, to propose improvements to current regulatory strategies and to identify further research needs.

Synthesis, biological characterisation and structure activity relationships of aromatic bisamidines active against Plasmodium falciparum.

Malaria is one of the most significant tropical diseases and remains a major challenge due to the lack of a broadly effective vaccine and parasite resistance to current drugs. This means there is a need for new drug candidates with novel modes of action. Aromatic bisamidines, such as furamidine (DB75), were initially developed as anti-Trypanosoma agents however as clinical trials with furamidine highlighted potential side effects they were not pursued further in that setting. Despite apparent cytotoxicity liabilities the potency of furamidine against Plasmodium falciparum makes it a promising scaffold for the development of new anti-Plasmodium agents with improved selectivity. In this study a bisamidine compound series based on furamidine was synthesized by introducing modifications at the furan core structure and terminal amidine groups. The activity of the derived compounds was tested in vitro against drug sensitive and resistant P. falciparum lines and a human cell line (HEK293 cells) to generate anti-Plasmodium structure-activity relationships and to provide preliminary selectivity data.