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IntroductionLymphatic filariasis (LF) is a neglected tropical disease caused by parasitic worms, transmitted via mosquito bites. Significant global efforts have led to the interruption of LF transmission, with eight of the 16 previously endemic Pacific Island countries and territories (PICTs) validated by WHO as having eliminated the disease as a public health problem. Post-validation surveillance (PVS) is recommended to verify the absence of a resurgence in transmission; however, there are no guidelines on how to implement such surveillance effectively.AimThis protocol outlines a research study that aims to explore, synthesise, and prioritise the perspectives of LF program staff from LF-eliminated PICTs. The study will focus on identifying the challenges faced in implementing PVS in the PICT settings and determining corresponding context-relevant operational research priorities.MethodThe study will employ a nominal group technique (NGT) involving representatives from LF-eliminated PICTs. The NGT will adhere to a structured process for generating, ranking, and prioritising ideas, followed by group discussions, debates, and the collation of shared views.DiscussionThe research will provide insights into the most significant challenges faced in implementing PVS in the PICTs. It will also identify priority areas where operational research is required to inform policy and practice. To our knowledge, this study is the first to apply a rigorous consensus group method to distil challenges and research priorities for LF PVS in PICTs. We expect that this research will inform the development of national and regional LF guidelines.

Pharmaceuticals and their packaging have a significant negative impact on the environment providing a very strong argument for action on the part of pharmacists and pharmacy technicians to engage with pro-environmental behaviours (PEBs) in their workplaces. The aims of this research were therefore to investigate in hospital pharmacists and pharmacy technicians, 1) factors affecting engagement with workplace PEBs, and 2) determine if legislated carbon reduction targets in the UK influenced workplace PEBs in the UK compared with Australia which does not have legislated carbon reduction targets. The environmentally responsible disposal of pharmaceutical waste was the PEB of interest in this study. A mixed methods research design was utilised and a conceptual model (key variables: environmental attitude, concern, and knowledge, and organisational factors) was developed to identify factors influencing workplace PEBs. Participants were from five hospitals in Queensland, Australia and five NHS hospitals in England, UK. There was no statistically significant difference in environmental attitude or concern between the two groups-most had a mid-environmental attitude score and low levels of environmental concern. Participants lacked knowledge of the issue and the link between the environment and public health. Both Australian and UK participants reported recycling packaging waste was not a priority in the hospital pharmacy workplace (even in hospitals with recycling capability) as hospitals focused on compliance with clinical (contaminated) and confidential waste streams. Environmental attitude, knowledge, and concern therefore appeared to be weak influences on intention to perform workplace PEBs with workplace social norms (compliance due to audits) appearing to be a significant mediator of action. The key difference between the cohorts was that UK pharmacists felt waste was not in the scope of their role, and therefore not their responsibility. This study identified that legislated carbon reduction targets did not influence hospital pharmacy workplace PEBs-neither cohort reported engaging significantly in workplace PEBs. UK Government and NHS sustainability policy did not appear to have disseminated to pharmacy department level of UK public hospitals to any great extent.

Empirical data on contact patterns can inform dynamic models of infectious disease transmission. Such information has not been widely reported from Pacific islands, nor strongly multi-ethnic settings, and few attempts have been made to quantify contact patterns relevant for the spread of gastrointestinal infections. As part of enteric fever investigations, we conducted a cross-sectional survey of the general public in Fiji, finding that within the 9,650 mealtime contacts reported by 1,814 participants, there was strong like-with-like mixing by age and ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians. Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the overall data do not simply reflect household structures. Inter-ethnic mixing was most common amongst school-age children. Serological responses indicative of recent Salmonella Typhi infection were found to be associated, after adjusting for age, with increased contact rates between meal-sharing iTaukei, with no association observed for other contact groups. Animal ownership and travel within the geographical division were common. These are novel data that identify ethnicity as an important social mixing variable, and use retrospective mealtime contacts as a socially acceptable metric of relevance to enteric, contact and respiratory diseases that can be collected in a single visit to participants. Application of these data to other island settings will enable communicable disease models to incorporate locally relevant mixing patterns in parameterisation.

Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke.Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3-6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3-6 months after stroke.Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20-0.63) and stretching & toning physical exercise (0.37, 0.21-0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p

BACKGROUND:The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. METHODS:Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3-6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer's Disease (AD) pathology. RESULTS:50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. CONCLUSION:Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.

The survival effect in memory refers to the memory enhancement for materials encoded in reference to a survival scenario compared to those encoded in reference to a control scenario or with other encoding strategies. The current study examined whether this effect is well maintained in old age by testing young (ages 18-29) and older adults (ages 65-87) on the survival effect in memory for words encoded in ancestral and/or non-ancestral modern survival scenarios relative to a non-survival control scenario. A pilot study was conducted to select the best matched comparison scenarios based on potential confounding variables, such as valence and arousal. Experiment 1 assessed the survival effect with a well-matched negative control scenario in both young and older adults. The results showed an age-equivalent survival effect across an ancestral and a non-ancestral modern survival scenario. Experiment 2 replicated the survival effect in both age groups with a positive control scenario. Taken together, the data suggest a robust survival effect that is well preserved in old age across ancestral and non-ancestral survival scenarios.

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome.

Following exit from meiosis I, mammalian oocytes immediately enter meiosis II without an intervening interphase, accompanied by rapid reassembly of a bipolar spindle that maintains condensed chromosomes in a metaphase configuration (metaphase II arrest). Here we study the effect of nicotinamide (NAM), a non-competitive pan-sirtuin inhibitor, during meiotic maturation in mouse oocytes. Sirtuins are a family of seven NAD+-dependent deacetylases (Sirt1-7), which are involved in multiple cellular processes and are emerging as important regulators in oocytes and embryos. We found that NAM significantly delayed entry into meiosis I associated with delayed accumulation of the Cdk1 co-activator, cyclin B1. GVBD was also inhibited by the Sirt2-specific inhibitor, AGK2, and in a very similar pattern to NAM, supporting the notion that as in somatic cells, NAM inhibits sirtuins in oocytes. NAM did not affect subsequent spindle assembly, chromosome alignment or the timing of first polar body extrusion (PBE). Unexpectedly, however, in the majority of oocytes with a polar body, chromatin was decondensed and a nuclear structure was present. An identical phenotype was observed when flavopiridol was used to induce Cdk1 inactivation during late meiosis I prior to PBE, but not if Cdk1 was inactivated after PBE when metaphase II arrest was already established, altogether indicating that NAM impaired establishment rather than maintenance of metaphase II arrest. During meiosis I exit in NAM-treated medium, we found that cyclin B1 levels were lower and inhibitory Cdk1 phosphorylation was increased compared with controls. Although activation of the anaphase-promoting complex-Cdc20 (APC-Cdc20) occurred on-time in NAM-treated oocytes, Cdc20 levels were higher in very late meiosis I, pointing to exaggerated APC-Cdc20-mediated proteolysis as a reason for lower cyclin B1 levels. Collectively, therefore, our data indicate that by disrupting Cdk1 regulation, NAM impairs entry into meiosis I and the establishment of metaphase II arrest.

Background: Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches., Objective: We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers., Methods: Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis., Results: In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count., Conclusions: Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.