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Abstract Background Falls are common in a range of clinical cohorts, where routine risk assessment often comprises subjective visual observation only. Typically, observational assessment involves evaluation of an individual’s gait during scripted walking protocols within a lab to identify deficits that potentially increase fall risk, but subtle deficits may not be (readily) observable. Therefore, objective approaches (e.g., inertial measurement units, IMUs) are useful for quantifying high resolution gait characteristics, enabling more informed fall risk assessment by capturing subtle deficits. However, IMU-based gait instrumentation alone is limited, failing to consider participant behaviour and details within the environment (e.g., obstacles). Video-based eye-tracking glasses may provide additional insight to fall risk, clarifying how people traverse environments based on head and eye movements. Recording head and eye movements can provide insights into how the allocation of visual attention to environmental stimuli influences successful navigation around obstacles. Yet, manual review of video data to evaluate head and eye movements is time-consuming and subjective. An automated approach is needed but none currently exists. This paper proposes a deep learning-based object detection algorithm (VARFA) to instrument vision and video data during walks, complementing instrumented gait. Method The approach automatically labels video data captured in a gait lab to assess visual attention and details of the environment. The proposed algorithm uses a YoloV8 model trained on with a novel lab-based dataset. Results VARFA achieved excellent evaluation metrics (0.93 mAP50), identifying, and localizing static objects (e.g., obstacles in the walking path) with an average accuracy of 93%. Similarly, a U-NET based track/path segmentation model achieved good metrics (IoU 0.82), suggesting that the predicted tracks (i.e., walking paths) align closely with the actual track, with an overlap of 82%. Notably, both models achieved these metrics while processing at real-time speeds, demonstrating efficiency and effectiveness for pragmatic applications. Conclusion The instrumented approach improves the efficiency and accuracy of fall risk assessment by evaluating the visual allocation of attention (i.e., information about when and where a person is attending) during navigation, improving the breadth of instrumentation in this area. Use of VARFA to instrument vision could be used to better inform fall risk assessment by providing behaviour and context data to complement instrumented e.g., IMU data during gait tasks. That may have notable (e.g., personalized) rehabilitation implications across a wide range of clinical cohorts where poor gait and increased fall risk are common.

Abstract A wide-field microscope with epi-fluorescence and selective plane illumination was combined with a single-photon avalanche diode (SPAD) array camera to enable live-cell fluorescence lifetime imaging (FLIM) using time-correlated single-photon counting (TCSPC). The camera sensor comprised of $$\text {192}\times \text {128}$$ 192 × 128 pixels, each integrating a single SPAD and a time-to-digital converter. Jointly, they produced a stream of single-photon images of photon arrival times with $$\approx \text {38 ps}$$ ≈ 38 ps accuracy. The photon arrival times were subject to systematic delays and nonlinearities, which were corrected by a Monte-Carlo algorithm. The SPAD camera was then applied to FLIM where histogramming the resulting photon arrival times in each pixel resulted in decays compatible with common data processing pipelines for fluorescence lifetime analysis. The capabilities of the TCSPC camera-based FLIM microscope were demonstrated by imaging living unicellular photosynthetic algae and artificial lipid vesicles. Epi-fluorescence illumination enabled rapid fluorescence lifetime imaging of living cells and selective-plane illumination enabled 3-dimensional FLIM of stationary samples.

Abstract Wearable inertial measurement units (IMUs) are being used to quantify gait characteristics that are associated with increased fall risk, but the current limitation is the lack of contextual information that would clarify IMU data. Use of wearable video-based cameras would provide a comprehensive understanding of an individual’s habitual fall risk, adding context to clarify abnormal IMU data. Generally, there is taboo when suggesting the use of wearable cameras to capture real-world video, clinical and patient apprehension due to ethical and privacy concerns. This perspective proposes that routine use of wearable cameras could be realized within digital medicine through AI-based computer vision models to obfuscate/blur/shade sensitive information while preserving helpful contextual information for a comprehensive patient assessment. Specifically, no person sees the raw video data to understand context, rather AI interprets the raw video data first to blur sensitive objects and uphold privacy. That may be more routinely achieved than one imagines as contemporary resources exist. Here, to showcase/display the potential an exemplar model is suggested via off-the-shelf methods to detect and blur sensitive objects (e.g., people) with an accuracy of 88%. Here, the benefit of the proposed approach includes a more comprehensive understanding of an individual’s free-living fall risk (from free-living IMU-based gait) without compromising privacy. More generally, the video and AI approach could be used beyond fall risk to better inform habitual experiences and challenges across a range of clinical cohorts. Medicine is becoming more receptive to wearables as a helpful toolbox, camera-based devices should be plausible instruments.

Abstract How long-term changes in surface topography relate to coseismic uplift is key to understanding the creation of high elevations along active mountain fronts, and remains hotly debated. Here we investigate this link by modeling the development of growth strata and the folding of river terraces above the Pishan duplex system in the southern Tarim Basin. We show that synchronous duplex thrusting of two neighboring faults with varying slip rates, associated with in-sequence propagation of the Pishan thrust system, is required to explain the presence of opposite-dipping panels of growth strata on the duplex front, and basinward migration of terrace fold crests. Importantly, this process of synchronous thrusting within the duplex reconciles the discrepancy between the deformation of terrace folds at the 10−1–100 million-year timescale and the maximum coseismic uplift of the 2015 Mw 6.4 Pishan earthquake on the frontal thrust. These results suggest that topography mismatch at different time scales can reflect the long-term kinematic evolution of fault systems. Thus, our study highlights the importance of characterizing complex subsurface fault kinematics for studying topographic growth, and motivates rethinking of the mountain building process in worldwide active fold-and-thrust belts, from short-term to long-term timescales.

The water quality risk assessment is the foundation for every drinking Water Safety Plan. The need to conform with a ‘Corporate’ risk assessment model commonly dominated by asset management frequency data can cause misjudgement of microbial risk. Well-performed risk assessments should identify potential risks. Risk assessments which place too much emphasis on historical evidence to demonstrate ‘likelihood’ of microbial contamination are unsuitable for drinking water quality because they fail to recognise ‘latent’ risks associated with absent or underperforming barriers to contamination. Most outbreaks occur when these ‘latent’ factors align to create a failure. Good risk assessments need to provide foresight. This is achieved if drinking water quality risk assessments are based on a ‘barrier’ approach. Where adequate and reliable multiple barriers to contamination are present the likelihood of a hazardous event should then be categorised as rare. Where barriers are absent, inadequate, or unreliable, then a higher likelihood is appropriate, depending on the nature and extent of the barrier shortfall. Practical examples show how the ‘barrier’ approach can be applied. The barrier risk assessment directly informs the operational monitoring programme, enabling regular confirmation that the challenge and barrier performance are consistent with the predictions of the risk assessment. HIGHLIGHTS Explains why commonly used risk assessment methods can lead to water quality risks being misjudged.; Provides a ‘barrier’ risk assessment method to account for ‘latent’ risks.; Demonstrates that the greater the gap between barriers required and those existing, the higher the likelihood of contamination.; Explains how operational monitoring should be used to continuously validate the risk assessment;

Falls are a major concern for people with Parkinson’s disease (PwPD), but accurately assessing real-world fall risk beyond the clinic is challenging. Contemporary technologies could enable the capture of objective and high-resolution data to better inform fall risk through measurement of everyday factors (e.g., obstacles) that contribute to falls. Wearable inertial measurement units (IMUs) capture objective high-resolution walking/gait data in all environments but are limited by not providing absolute clarity on contextual information (i.e., obstacles) that could greatly influence how gait is interpreted. Video-based data could compliment IMU-based data for a comprehensive free-living fall risk assessment. The objective of this study was twofold. First, pilot work was conducted to propose a novel artificial intelligence (AI) algorithm for use with wearable video-based eye-tracking glasses to compliment IMU gait data in order to better inform free-living fall risk in PwPD. The suggested approach (based on a fine-tuned You Only Look Once version 8 (YOLOv8) object detection algorithm) can accurately detect and contextualize objects (mAP50 = 0.81) in the environment while also providing insights into where the PwPD is looking, which could better inform fall risk. Second, we investigated the perceptions of PwPD via a focus group discussion regarding the adoption of video technologies and AI during their everyday lives to better inform their own fall risk. This second aspect of the study is important as, traditionally, there may be clinical and patient apprehension due to ethical and privacy concerns on the use of wearable cameras to capture real-world video. Thematic content analysis was used to analyse transcripts and develop core themes and categories. Here, PwPD agreed on ergonomically designed wearable video-based glasses as an optimal mode of video data capture, ensuring discreteness and negating any public stigma on the use of research-style equipment. PwPD also emphasized the need for control in AI-assisted data processing to uphold privacy, which could overcome concerns with the adoption of video to better inform IMU-based gait and free-living fall risk. Contemporary technologies (wearable video glasses and AI) can provide a holistic approach to fall risk that PwPD recognise as helpful and safe to use.

Abstract Background Between 40 and 50% of patients with Parkinson’s disease (PD) experience anxiety and depression, associated with impaired physical function, high care dependency and mortality. Recently, the United States National Institutes of Health has urged the implementation of mindfulness practices in chronic illness care. Most research to date has examined the effects on chronically ill patients of complex interventions using a combination of mindfulness techniques. In PD patients, however, such complex modalities appear to hinder the technique mastery. Hence, the aim of this trial is to investigate the effects and underlying mechanism of individual mindfulness techniques among PD patients, as well as exploring participants’ experience in using individual mindfulness techniques as a lifestyle intervention for stress and symptom management. Methods We will conduct an assessor-blind three-arm randomized waitlist-controlled trial with a descriptive qualitative evaluation. Up to 168 PD patients will be recruited from community settings and out-patient clinics, and randomized to meditation, yoga, or usual care group. Meditation and yoga sessions of 90-minute are held weekly for 8 weeks. Primary outcomes include anxiety and depression. Secondary outcomes include PD-related motor and non-motor symptoms and quality-of-life; and level of mindfulness and biomarkers of stress and inflammatory responses will be measured as mediating variables. All outcome evaluations will be assessed at baseline, 8 weeks, and 24 weeks. Following the intention-to-treat principle, generalized estimating equation models and path analysis will be used to identify the treatment effects and the mediating mechanisms. A subsample of 30 participants from each intervention group will be invited for qualitative interviews. Discussion The study would also generate important insights to enhance the patients’ adaptation to debilitating disease. More specifically, symptom management and stress adaptation are highly prioritized healthcare agenda in managing PD. The research evidence will further inform the development of community-based, nurse-led compassionate care models for neurodegenerative conditions, which is complementary to existing health services. Trial registration WHO Primary Registry – Chinese Clinical Trials Registry number: ChiCTR2100045939; registered on 2021/04/29 ( https://www.chictr.org.cn/showproj.html?proj=125878 ).

Background The global population is ageing rapidly, with low- and middle-income countries (LMICs) undergoing a fast demographic transition. As the number of older adults in LMICs increases, services able to effectively address their physical and mental health needs will be increasingly important. Objective We review the health and socioeconomic resources currently available for older people in South Asian countries, Bangladesh, India, Nepal, Pakistan and Sri Lanka, to identify gaps in available resources and assess areas for improvement. Methods We conducted a search of grey and published literature via Google Search, Compendex, EBSCO, JSTOR, Medline, Ovid, ProQuest databases, Scopus and Web of Science. Data on population demographics, human resources, health funding and social protection for older people were extracted. Local informants were consulted to supplement and verify the data. Results In the study countries, the number of health professionals with expertise in elderly care was largely unknown, with minimal postgraduate training programmes available in elderly medicine or psychiatry. Older adults are therefore cared for by general physicians, nurses and community health workers, all of whom are present in insufficient numbers per capita. Total average healthcare expenditure was 2.5–5.5% of GDP, with 48.1–72.0% of healthcare costs covered by out-of-pocket payments. Pakistan did not have a social pension; only India and Nepal offered financial assistance to people with dementia; and all countries had disproportionately low numbers of care elderly homes. Conclusions Inadequate healthcare funding, a shortage of healthcare professionals and insufficient government pension and social security schemes are significant barriers to achieving universal health coverage in LMICs. Governing bodies must expand training programmes for healthcare providers for older adults, alongside increasing social protection to improve access to those in need and to prevent catastrophic health expenditure.

Objective:. To conduct a systematic review, critical appraisal, and external validation of survival prediction tools for patients undergoing intrahepatic cholangiocarcinoma (iCCA) resection. Summary background data:. Despite the development of several survival prediction tools in recent years for patients undergoing iCCA resections, there is a lack of critical appraisal and external validation of these models. Methods:. We conducted a systematic review and critical appraisal of survival and recurrence prediction models for patients undergoing curative-intent iCCA resections. Studies were evaluated based on their model design, risk of bias, reporting, performance, and validation results. We identified the best model and externally validated it using our institution’s data. Results:. This review included a total of 31 studies, consisting of 26 studies with original prediction tools and 5 studies that only conducted external validations. Among the 26, 54% of the studies conducted internal validations, 46% conducted external validations, and only 1 study scored a low risk of bias. Harrell’s C-statistics ranged from 0.67 to 0.76 for internal validation and from 0.64 to 0.75 for external validation. Only 81% of the studies reported model calibration. Our external validation of the best model (Intrahepatic Cholangiocarcinoma [ICC]-Metroticket) estimated Harrell’s and Uno’s C-statistics of 0.67 (95% CI: 0.56–0.77) and Uno’s time-dependent area under the receiver operating characteristic curve (AUC) of 0.71 (95% CI: 0.53–0.88), with a Brier score of 0.20 (95% CI: 0.15–0.26) and good calibration plots. Conclusions:. Many prediction models have been published in recent years, but their quality remains poor, and minimal methodological quality improvement has been observed. The ICC-Metroticket was selected as the best model (Uno’s time-dependent AUC of 0.71) for 5-year overall survival prediction in patients undergoing curative-intent iCCA resection.

Plain English summary The population in sub-Saharan Africa is ageing. The majority of people living with HIV infection also live in Africa, and they are ageing now that treatment is widely available. Current research on the chronic complications of ageing with and without HIV in sub-Saharan Africa is very limited, meaning that little is known on how to improve symptoms. In this pilot study, researchers from Tanzania and the UK worked with older people living with HIV, and community elders in Tanzania in a health research priority-setting exercise. Thirty older people living with HIV and thirty community elders attended workshops where they listed issues important to them, and then voted for each item as a group. Priorities were ranked in order of importance by adding up the number of votes. We also asked how interested and motivated older people were to work jointly with academic researchers and what might help and support them to do this. Both groups reported that they felt very motivated to participate in, conduct and oversee future research studies. A key finding was that basic needs, such as being able to see a doctor regularly and buying medications, were prioritised much higher than specific HIV-complications or chronic disease. Stigma and social isolation were important issues for older people with HIV. Our pilot findings suggest that meeting basic needs should be a key part of future work on living and ageing with chronic disease in Tanzania. The importance of working with patients and communities is also highlighted.

Abstract Objectives This paper aims to describe the prevalence and socio-economic associations with multimorbidity, by both self-report and clinical assessment/screening methods in community-dwelling older people living in rural Tanzania. Methods A randomised frailty-weighted sample of non-institutionalised adults aged ≥ 60 years underwent comprehensive geriatric assessment and in-depth assessment. The comprehensive geriatric assessment consisted of a history and focused clinical examination. The in-depth assessment included standardised questionnaires, screening tools and blood pressure measurement. The prevalence of multimorbidity was calculated for self-report and non-self-reported methods (clinician diagnosis, screening tools and direct measurement). Multimorbidity was defined as having two or more conditions. The socio-demographic associations with multimorbidity were investigated by multiple logistic regression. Results A sample of 235 adults participated in the study, selected from a screened sample of 1207. The median age was 74 years (range 60 to 110 inter-quartile range (IQR) 19) and 136 (57.8%) were women. Adjusting for frailty-weighting, the prevalence of self-reported multimorbidity was 26.1% (95% CI 16.7–35.4), and by clinical assessment/screening was 67.3% (95% CI 57.0–77.5). Adjusting for age, sex, education and frailty status, multimorbidity by self-report increased the odds of being financially dependent on others threefold (OR 3.3 [95% CI 1.4–7.8]), and of a household member reducing their paid employment nearly fourfold (OR 3.8. [95% CI 1.5–9.2]). Conclusions Multimorbidity is prevalent in this rural lower-income African setting and is associated with evidence of household financial strain. Multimorbidity prevalence is higher when not reliant on self-reported methods, revealing that many conditions are underdiagnosed and undertreated.

Visual problems are common in people who have neurological injury or disease, with deficits linked to postural control and gait impairment. Vision therapy could be a useful intervention for visual impairment in various neurological conditions such as stroke, head injury, or Parkinson's disease. Stroboscopic visual training (SVT) has been shown to improve aspects of visuomotor and cognitive performance in healthy populations, but approaches vary with respect to testing protocols, populations, and outcomes. The purpose of this structured review was to examine the use of strobe glasses as a training intervention to inform the development of robust protocols for use in clinical practice. Within this review, any studies using strobe glasses as a training intervention with visual or motor performance-related outcomes was considered. PubMed, Scopus, and ProQuest databases were searched in January 2023. Two independent reviewers (JD and RM) screened articles that used strobe glasses as a training tool. A total of 33 full text articles were screened, and 15 met inclusion/exclusion criteria. Reported outcomes of SVT included improvements in short-term memory, attention, and visual response times, with emerging evidence for training effects translating to balance and physical performance. However, the lack of standardisation across studies for SVT protocols, variation in intervention settings, duration and outcomes, and the limited evidence within clinical populations demonstrates that further work is required to determine optimal strobe dosage and delivery. This review highlights the potential benefits, and existing research gaps regarding the use of SVT in clinical practice, with recommendations for clinicians considering adopting this technology as part of future studies in this emerging field.

Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of cueing through prescribed auditory, visual, and/or tactile cues. Each has shown use to rectify abnormal gait patterns, improving mobility. Yet, a limitation remains, i.e., long-term engagement with cueing modalities. A paradigm shift towards personalised cueing approaches, considering an individual’s unique physiological condition, may bring a contemporary approach to ensure longitudinal and continuous engagement. Sonification could be a useful auditory cueing technique when integrated within personalised approaches to gait rehabilitation systems. Previously, sonification demonstrated encouraging results, notably in reducing freezing-of-gait, mitigating spatial variability, and bolstering gait consistency in people with Parkinson’s disease (PD). Specifically, sonification through the manipulation of acoustic features paired with the application of advanced audio processing techniques (e.g., time-stretching) enable auditory cueing interventions to be tailored and enhanced. These methods used in conjunction optimize gait characteristics and subsequently improve mobility, enhancing the effectiveness of the intervention. The aim of this narrative review is to further understand and unlock the potential of sonification as a pivotal tool in auditory cueing for gait rehabilitation, while highlighting that continued clinical research is needed to ensure comfort and desirability of use.

Background Cognitive stimulation therapy (CST) is the only non-pharmacological, treatment for dementia recommended by the UK National Institute for Health and Care Excellence, following multiple international trials demonstrating beneficial cognitive outcomes in people with mild-to-moderate dementia. However, there is limited understanding of whether treatment prognosis is influenced by sociodemographic and clinical variables (such as dementia subtype and gender), information which could inform clinical decision-making. Aim We describe the protocol for a systematic review and individual patient data meta-analysis assessing the prognostic factors related to CST. In publishing this protocol, we hope to increase the transparency of our work, and keep healthcare professionals aware of the latest evidence for effective CST. Method A systematic review will be conducted with searches of the bibliographic databases Medline, EMBASE and PsycINFO, from inception to 7 February 2023. Studies will be included if they are clinical trials of CST, use the Alzheimer's Disease Assessment Scale – Cognitive Subscale (gold-standard measure of cognition in dementia in clinical trials) and include participants with mild-to-moderate dementia. Following harmonisation of the data-set, mixed-effect models will be constructed to explore the relationship between the prognostic indicators and change scores post-treatment. Conclusions This is the first individual patient data meta-analyses on CST, and has the potential to significantly optimise patient care. Previous analyses suggest people with advanced dementia could benefit more from CST treatment. Given that CST is currently used post-diagnosis in people with mild-to-moderate dementia, the implications of confirming this finding, among identifying other prognostic indicators, are profound.

Summary: Background: Identification of convulsive epilepsy in sub-Saharan Africa relies on access to resources that are often unavailable. Infrastructure and resource requirements can further complicate case verification. Using machine-learning techniques, we have developed and tested a region-specific questionnaire panel and predictive model to identify people who have had a convulsive seizure. These findings have been implemented into a free app for health-care workers in Kenya, Uganda, Ghana, Tanzania, and South Africa. Methods: In this retrospective case-control study, we used data from the Studies of the Epidemiology of Epilepsy in Demographic Sites in Kenya, Uganda, Ghana, Tanzania, and South Africa. We randomly split these individuals using a 7:3 ratio into a training dataset and a validation dataset. We used information gain and correlation-based feature selection to identify eight binary features to predict convulsive seizures. We then assessed several machine-learning algorithms to create a multivariate prediction model. We validated the best-performing model with the internal dataset and a prospectively collected external-validation dataset. We additionally evaluated a leave-one-site-out model (LOSO), in which the model was trained on data from all sites except one that, in turn, formed the validation dataset. We used these features to develop a questionnaire-based predictive panel that we implemented into a multilingual app (the Epilepsy Diagnostic Companion) for health-care workers in each geographical region. Findings: We analysed epilepsy-specific data from 4097 people, of whom 1985 (48·5%) had convulsive epilepsy, and 2112 were controls. From 170 clinical variables, we initially identified 20 candidate predictor features. Eight features were removed, six because of negligible information gain and two following review by a panel of qualified neurologists. Correlation-based feature selection identified eight variables that demonstrated predictive value; all were associated with an increased risk of an epileptic convulsion except one. The logistic regression, support vector, and naive Bayes models performed similarly, outperforming the decision-tree model. We chose the logistic regression model for its interpretability and implementability. The area under the receiver operator curve (AUC) was 0·92 (95% CI 0·91–0·94, sensitivity 85·0%, specificity 93·7%) in the internal-validation dataset and 0·95 (0·92–0·98, sensitivity 97·5%, specificity 82·4%) in the external-validation dataset. Similar results were observed for the LOSO model (AUC 0·94, 0·93–0·96, sensitivity 88·2%, specificity 95·3%). Interpretation: On the basis of these findings, we developed the Epilepsy Diagnostic Companion as a predictive model and app offering a validated culture-specific and region-specific solution to confirm the diagnosis of a convulsive epileptic seizure in people with suspected epilepsy. The questionnaire panel is simple and accessible for health-care workers without specialist knowledge to administer. This tool can be iteratively updated and could lead to earlier, more accurate diagnosis of seizures and improve care for people with epilepsy. Funding: The Wellcome Trust, the UK National Institute of Health Research, and the Oxford NIHR Biomedical Research Centre.

Abstract Globally, 43 million people are living with HIV, 90% in developing countries. Increasing life expectancy with combination antiretroviral therapy (cART) results in chronic complications, including HIV-associated neurocognitive disorders (HAND) and eye diseases. HAND screening is currently challenging. Our aim was to evaluate clinical utility of retinopathy as a screening measure of HAND in older cART-treated individuals in Tanzania and feasibility of smartphone-based retinal screening in this low-resource setting. A cross-sectional systematic sample aged ≥ 50-years attending routine HIV follow-up in Tanzania were comprehensively assessed for HAND by American Academy of Neurology criteria and received ophthalmic assessment including smartphone-based retinal imaging. HAND and ophthalmic assessments were independent and blinded. Diagnostic accuracy was evaluated by AUROC curves. Of 129 individuals assessed, 69.8% were visually impaired. Thirteen had retinopathy. HAND prevalence was 66.7%. Retinopathy was significantly associated with HAND but HIV-disease factors (CD4, viral load) were not. Diagnostic accuracy of retinopathy for HAND was poor (AUROC 0.545-0.617) but specificity and positive predictive value were high. We conclude that ocular pathology and HAND appear highly prevalent in this low-resource setting. Although retinal screening cannot be used alone identify HAND, prioritization of individuals with abnormal retinal screening is a potential strategy in low-resource settings.

BackgroundMobile applications and technology (e.g., stroboscopic glasses) are increasingly being used to deliver combined visual and cognitive (termed visuo-cognitive) training that replaces standard pen and paper-based interventions. These 'technological visuo-cognitive training' (TVT) interventions could help address the complex problems associated with visuo-cognitive dysfunction in people with long term neurological conditions such as Parkinson's disease. As data emerges to support the effectiveness of these technologies, patient perspectives offer an insight into how novel TVT is received by people living with long term neurological conditions.ObjectiveTo explore experiences of people with Parkinson's in using technology as part of a home-based visuo-cognitive training programme compared to traditional approaches to rehabilitation.MethodsEight people with Parkinson's who took part in a pilot randomised cross-over trial, investigating the efficacy and feasibility of TVT compared to standard care, were interviewed to explore their experiences of each arm of the training they received. Integration of Normalisation Process Theory (NPT) into the analysis enabled examination of the potential to embed novel TVT into a home-based rehabilitation intervention for people with Parkinson's disease.ResultsThree key themes emerged from the thematic analysis as factors influencing the implementation potential of TVT for people with Parkinson's disease: perceived value of technology, perceived ease of use and support mechanisms. Further examination of the data through the lens of NPT revealed that the implantation and embedding of novel technology was dependent on positive user experience, individual disease manifestation and engagement with a professional.ConclusionsOur findings provide insights into the challenges of engaging with technology-based interventions while living with a progressive and fluctuating disease. When implementing technology-based interventions for people with Parkinson's, we recommend that patients and clinicians collaborate to determine whether the technology fits the capacity, preference, and treatment needs of the individual patient.

Drooling is a common symptom of Parkinson's Disease (PD) experienced in up to 70% of people with PD (PwP). Drooling can be a major problem in PwP leading to adverse physical and psychosocial issues. Current medical treatments decrease the production of saliva, whereas the problem is due to decreased swallowing frequency, not over production of saliva. Such treatments are problematic as saliva is essential for good oral health. Therefore, non-invasive treatments options such as behavioural cueing methods are recommended. A wrist-worn device delivering haptic cueing has been demonstrated to be an effective treatment method to increase swallowing frequency and a socially acceptable solution for PwP. However, the device had limited functionality and was tested on a small sample size over a short period of usage. Further work is required to understand the real-world behaviours and usage of the intervention to understand the longer-term effects with a larger sample size. This research will deploy CueBand, a discrete and comfortable wrist-worn device designed to work with a smartphone application to support the real-world evaluation of haptic cueing for the management of drooling. We will recruit 3,000 PwP to wear the device day and night for the intervention period to gain a greater understanding of the effectiveness and acceptability of the technology within real-world use. Additionally, 300 PwP who self-identity as having an issue with drooling will be recruited into an intervention study to evaluate the effectiveness of the wrist-worn CueBand to deliver haptic cueing (3-weeks) compared with smartphone cueing methods (3-weeks). PwP will use our smartphone application to self-assess their drooling frequency, severity, and duration using visual analogue scales and through the completion of daily diaries. Semi-structured interviews to gain feedback about utility of CueBand will be conducted following participants completion of the intervention.

Inferences about sheet intrusion emplacement mechanisms have been built largely on field observations of intrusion tip zones: magmatic systems that did not grow beyond their observed state. Here we use finite element simulation of elliptical to superelliptical crack tips, representing observed natural sill segments, to show the effect of sill tip shape in controlling local stress concentrations, and the potential propagation pathways. Stress concentration magnitude and distribution is strongly affected by the position and magnitude of maximum tip curvature κmax. Elliptical tips concentrate stress in-plane with the sill, promoting coplanar growth. Superelliptical tips concentrate maximum tensile stress (σmax) and shear stress out-of-plane of the sill, which may promote non-coplanar growth, vertical thickening, or coplanar viscous indentation. We find that σmax = Pe(1+ 2(√[aκmax]), where Pe is magma excess pressure and a is sill half length. At short length-scales, blunted tips locally generate large tensile stresses; at longer length-scales, elliptical-tipped sills become more efficient at concentrating stress than blunt sills.

Igneous sheet intrusions are segmented across several orders of magnitude, with segment tip geometry commonly considered indicative of the propagation mechanism (brittle or non-brittle). Proposed propagation mechanisms are inferred to represent host rock mechanical properties during initial magma emplacement; typically, these models do not account for segment sets that show a range of tip geometries within the same lithology. We present a detailed structural characterization of basaltic sill segments and their associated host rock deformation from the Little Minch Sill Complex, Isle of Skye, UK, and a broader comparison with segment geometries in three additional intrusive suites (Utah, USA; and Mull and Orkney, UK). Each separate host lithology shows multiple tip geometries and styles of host rock deformation, from elastic-brittle fracture, to viscous indentation and fluidisation. We attribute this range of host rock deformations to evolving conditions that occur at the tips both during sheet growth and arrest.

ABSTRACT In sub-Saharan Africa (SSA),cognitive screening is complicated by both cultural and educational factors, and the existing normative values may not be applicable. The Identification of Dementia in Elderly Africans (IDEA) cognitive screen is a low-literacy measure with good diagnostic accuracy for dementia. Objective: The aim of this study is to report normative values for IDEA and other simple measures [i.e., categorical verbal fluency, the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) 10-word list] in representative community-dwelling older adults in SSA. Methods: Individuals aged ≥60 years resident in 12 representative villages in Kilimanjaro, Tanzania and individuals aged ≥65 years resident within three communities in Akinyele Local Government Area, Oyo State, Nigeria underwent cognitive screening. The normative data were generated by the categories of age, sex, and education. Results: A total of 3,011 people in Tanzania (i.e., 57.3% females and 26.4% uneducated) and 1,117 in Nigeria (i.e., 60.3% females and 64.5% uneducated) were screened. Individuals with higher age, lower education, and female gender obtained lower scores. The 50th decile values for IDEA were 13 (60–64 years) vs. 8/9 (above 85 years), 10–11 uneducated vs. 13 primary educated, and 11/12 in females vs. 13 in males. The normative values for 10-word list delayed recall and categorical verbal fluency varied with education [i.e., delayed recall mean 2.8 [standard deviation (SD) 1.7] uneducated vs. 4.2 (SD 1.2) secondary educated; verbal fluency mean 9.2 (SD 4.8) uneducated vs. 12.2 (SD 4.3) secondary educated], substantially lower than published high-income country values. Conclusions: The cut-off values for commonly used cognitive screening items should be adjusted to suit local normative values, particularly where there are lower levels of education.

BackgroundStroke in adults is a critical clinical condition and a leading cause of death and disability globally. Epidemiological data on stroke in sub-Saharan Africa are limited. This study describes incidence rates, stroke types and antecedent factors among patients hospitalized with stroke in Zanzibar.MethodsThis was a prospective, observational study of stroke patients at hospitals in Unguja, Zanzibar. Socioeconomic and demographic data were recorded alongside relevant past medical history, medicine use and risk factors. The modified National Institute of Health Stroke Scale (mNIHSS) was used to assess admission stroke severity and, when possible, stroke was confirmed by neuroimaging.ResultsA total of 869 stroke admissions were observed from 1st October 2019 through 30th September 2020. Age-standardized to the World Health Organization global population, the yearly incidence was 286.8 per 100,000 adult population (95%CI: 272.4–301.9). Among these patients, 720 (82.9%) gave consent to participate in the study. Median age of participants was 62 years (53–70), 377 (52.2%) were women, and 463 (64.3%) had a first-ever stroke. Known stroke risk factors included hypertension in 503 (72.3%) patients, of whom 279 (55.5%) reported regularly using antihypertensive medication, of whom 161 (57.7%) had used this medication within the last week before stroke onset. A total of 460 (63.9%) participants had neuroimaging performed; among these there was evidence of intracerebral hemorrhage (ICH) in 140 (30.4%). Median stroke severity score using mNIHSS was 19 (10–27).ConclusionZanzibar has high incidence of hospitalization for stroke, indicating a very high population incidence of stroke. The proportion of strokes due to ICH is substantially higher than in high-income countries. Most stroke patients had been in contact with health care providers prior to stroke onset and been diagnosed with hypertension. However, few were using antihypertensive medication at the time of stroke onset.www.ClinicalTrial.gov registration NCT04095806.

Peer-led group learning is a variation of collaborative learning and is based on ‘small groups of students meeting regularly with a peer – one who has additional expertise in the subject matter – to work on problems collaboratively’ (Pazos, Micari, and Light 2010). In this study, we explored how a Slack team environment could be used in a blended course design to support students working remotely on individual research projects, helping them in collaborative trouble-shooting and problem-solving activities with their ‘near peer’. We drew on lessons learned from an initial trial (2017–2018 cohort) to inform a revised peer-led research design (2018–2019 cohort).Our findings demonstrate the potential of collaborative platforms such as Slack to support near-peer learning, providing distinct channels for questioning, ideas sharing and agile problem-solving support in response to individual queries. The peer-led support contributed to high levels of engagement with the project work and deeper learning, helping less confident students to learn from group members and achieve positive outcomes in their own project work. We discuss the necessary conditions for effective peer-led learning to take place within a virtual space – identifying the clear communication of instructional roles, socialisation of students and responsiveness of near peers as factors influencing the adoption of the targeted learning methods – which we addressed in our revised peer-led design.

Although the multifactorial nature of falls in Parkinson’s disease (PD) is well described, optimal assessment for the identification of fallers remains unclear. Thus, we aimed to identify clinical and objective gait measures that best discriminate fallers from non-fallers in PD, with suggestions of optimal cutoff scores. METHODS: Individuals with mild-to-moderate PD were classified as fallers (n = 31) or non-fallers (n = 96) based on the previous 12 months’ falls. Clinical measures (demographic, motor, cognitive and patient-reported outcomes) were assessed with standard scales/tests, and gait parameters were derived from wearable inertial sensors (Mobility Lab v2); participants walked overground, at a self-selected speed, for 2 min under single and dual-task walking conditions (maximum forward digit span). Receiver operating characteristic curve analysis identified measures (separately and in combination) that best discriminate fallers from non-fallers; we calculated the area under the curve (AUC) and identified optimal cutoff scores (i.e., point closest-to-(0,1) corner). RESULTS: Single gait and clinical measures that best classified fallers were foot strike angle (AUC = 0.728; cutoff = 14.07°) and the Falls Efficacy Scale International (FES-I; AUC = 0.716, cutoff = 25.5), respectively. Combinations of clinical + gait measures had higher AUCs than combinations of clinical-only or gait-only measures. The best performing combination included the FES-I score, New Freezing of Gait Questionnaire score, foot strike angle and trunk transverse range of motion (AUC = 0.85). CONCLUSION: Multiple clinical and gait aspects must be considered for the classification of fallers and non-fallers in PD.

Double-mutant heat-labile toxin (dmLT, LTR192G/L211A) of enterotoxigenic Escherichia coli (ETEC) is an effective mucosal adjuvant. Recent studies have shown that dmLT also exhibits adjuvanticity for antigens administered parenterally. In this study, we subcutaneously (SC) immunized mice with the ETEC adhesin-based vaccine, CFA/I/II/IV MEFA (multiepitope fusion antigen), adjuvanted with dmLT and examined the impact of dmLT on antibody responses specific to the seven adhesins in the vaccine construction [CFA/I, CFA/II (CS1, CS2, CS3) and CFA/IV (CS4, CS5, CS6)]. Mice were immunized with a fixed dose of CFA/I/II/IV MEFA and ascending doses of dmLT adjuvant (0, 0.05, 0.1, 0.5 or 1.0 µg) to assess the potential dmLT dose response relationship. Data showed that dmLT enhanced systemic antibody responses to all seven antigens (CFA/I, CS1-CS6) targeted by MEFA in a dose-dependent way. The adjuvant effect of dmLT on the MEFA construct plateaued at a dose of 0.1 µg. Results also indicated that dmLT is an effective parenteral adjuvant when given by the SC route with the ETEC adhesin MEFA vaccine and that antibody enhancement was achieved with relatively low doses. These observations suggest the potential usefulness of dmLT for parenteral ETEC vaccine candidates and also perhaps for vaccines against other pathogens.

Visual and cognitive dysfunction are common in Parkinson's disease and relate to balance and gait impairment, as well as increased falls risk and reduced quality of life. Vision and cognition are interrelated (termed visuo-cognition) which makes intervention complex in people with Parkinson's (PwP). Non-pharmacological interventions for visuo-cognitive deficits are possible with modern technology, such as combined mobile applications and stroboscopic glasses, but evidence for their effectiveness in PwP is lacking. We aim to investigate whether technological visuo-cognitive training (TVT) can improve visuo-cognitive function in PwP. We will use a parallel group randomised controlled trial to evaluate the feasibility and acceptability of TVT versus standard care in PwP. Forty PwP who meet our inclusion criteria will be randomly assigned to one of two visuo-cognitive training interventions. Both interventions will be carried out by a qualified physiotherapist in participants own homes (1-hour sessions, twice a week, for 4 weeks). Outcome measures will be assessed on anti-parkinsonian medication at baseline and at the end of the 4-week intervention. Feasibility of the TVT intervention will be assessed in relation to safety and acceptability of the technological intervention, compliance and adherence to the intervention and usability of equipment in participants homes. Additionally, semi structured interviews will be conducted to explore participants' experience of the technology. Exploratory efficacy outcomes will include change in visual attention measured using the Trail Making Test as well as changes in balance, gait, quality of life, fear of falling and levels of activity. This pilot study will focus on the feasibility and acceptability of TVT in PwP and provide preliminary data to support the design of a larger, multi-centre randomised controlled trial. This trial is registered at isrctn.com (ISRCTN46164906).

Fall risk assessment needs contemporary approaches based on habitual data. Currently, inertial measurement unit (IMU)-based wearables are used to inform free-living spatio-temporal gait characteristics to inform mobility assessment. Typically, a fluctuation of those characteristics will infer an increased fall risk. However, current approaches with IMUs alone remain limited, as there are no contextual data to comprehensively determine if underlying mechanistic (intrinsic) or environmental (extrinsic) factors impact mobility and, therefore, fall risk. Here, a case study is used to explore and discuss how contemporary video-based wearables could be used to supplement arising mobility-based IMU gait data to better inform habitual fall risk assessment. A single stroke survivor was recruited, and he conducted a series of mobility tasks in a lab and beyond while wearing video-based glasses and a single IMU. The latter generated topical gait characteristics that were discussed according to current research practices. Although current IMU-based approaches are beginning to provide habitual data, they remain limited. Given the plethora of extrinsic factors that may influence mobility-based gait, there is a need to corroborate IMUs with video data to comprehensively inform fall risk assessment. Use of artificial intelligence (AI)-based computer vision approaches could drastically aid the processing of video data in a timely and ethical manner. Many off-the-shelf AI tools exist to aid this current need and provide a means to automate contextual analysis to better inform mobility from IMU gait data for an individualized and contemporary approach to habitual fall risk assessment.

Abstract Major faults of the Tien Shan, Central Asia, have long repeat times, but fail in large (Mw 7+) earthquakes. In addition, there may be smaller, buried faults off the major faults which are not properly characterized or even recognized as active. These all pose hazard to cities along the mountain range front such as Almaty, Kazakhstan. Here, we explore the seismic hazard and risk for Almaty from specific earthquake scenarios. We run three historical‐based earthquake scenarios (1887 Verny Mw 7.3, 1889 Chilik Mw 8.0 and 1911 Chon‐Kemin Mw 8.0) on the current population and four hypothetical scenarios for near‐field faulting. By making high‐resolution Digital Elevation Models (DEMs) from SPOT and Pleiades stereo optical satellite imagery, we identify fault splays near and under Almaty. We assess the feasibility of using DEMs to estimate city building heights, aiming to better constrain future exposure datasets. Both Pleiades and SPOT‐derived DEMs find accurate building heights of the majority of sampled buildings within error; Pleiades tri‐stereo estimates 80% of 15 building heights within one sigma and has the smallest average percentage difference to field‐measured heights (14%). A moderately sized Mw 6.5 earthquake rupture occurring on a blind thrust fault, under folding north of Almaty is the most damaging scenario explored here due to the modeled fault stretching under Almaty, with estimated 12,300±5,000 completely damaged buildings, 4,100 ± 3,500 fatalities and an economic cost of 4,700 ± 2,700 Million US dollars (one sigma uncertainty). This highlights the importance of characterizing location, extent, geometry, and activity of small faults beneath cities.

Turning is a common impairment of mobility in people with Parkinson’s disease (PD), which increases freezing of gait (FoG) episodes and has implications for falls risk. Visual cues have been shown to improve general gait characteristics in PD. However, the effects of visual cues on turning deficits in PD remains unclear. We aimed to (i) compare the response of turning performance while walking (180° and 360° turns) to visual cues in people with PD with and without FoG; and (ii) examine the relationship between FoG severity and response to visual cues during turning. This exploratory interventional study measured turning while walking in 43 participants with PD (22 with self-reported FoG) and 20 controls using an inertial sensor placed at the fifth lumbar vertebrae region. Participants walked straight and performed 180° and 360° turns midway through a 10 m walk, which was done with and without visual cues (starred pattern). The turn duration and velocity response to visual cues were assessed using linear mixed effects models. People with FoG turned slower and longer than people with PD without FoG and controls (group effect: p < 0.001). Visual cues reduced the velocity of turning 180° across all groups and reduced the velocity of turning 360° in people with PD without FoG and controls. FoG severity was not significantly associated with response to visual cues during turning. Findings suggest that visual cueing can modify turning during walking in PD, with response influenced by FoG status and turn amplitude. Slower turning in response to visual cueing may indicate a more cautious and/or attention-driven turning pattern. This study contributes to our understanding of the influence that cues can have on turning performance in PD, particularly in freezers, and will aid in their therapeutic application.

Introduction: Several reports highlight the importance of global health education (GHE) for training tomorrow’s doctors. In 2006, Newcastle University Medical School developed a Student Selected Component (SSC) in Global Health. We followed up students who completed the SSC to assess the impact on their experience as practising clinicians and postgraduate career development. Methods: We developed an electronic survey including questions about speciality choice, postgraduate qualifications, extracurricular activity and international work. Surveys were sent to 72 SSC participants identified between 2006-2017 through the Newcastle University Alumni and Supporters network and social media. Results: Surveys were returned by 37 (51%) SSC participants; 25 (71%) and 16 (46%) believed the SSC had influenced their clinical practice and career choice, respectively. Twenty-two (59%) obtained an intercalated degree programme, of whom nine (24%) did a Masters programme specifically in Global Health and four (11%), and two (5%) completed a Masters degree in Epidemiology and Control of Infectious Diseases respectively, both key themes within GHE. Four (11%) undertook, and 10 (29%) were considering postgraduate study related to global health, of whom three (9%) specified undertaking a Diploma in Tropical Medicine and Hygiene (DTM&H) and one (3%) studying a Masters degree in Public Health. Five (14%) had, and 19 (54%) were planning to work abroad, most referring to work in humanitarian or low resource settings and GHE programmes. Discussion and Conclusion: Participation in an SSC in Global Health may affect positive change in students’ clinical practice and help inform academic and clinical career choice. Whilst a causative relationship cannot be inferred, the experience may support or increase the pursuit of additional global health-related qualifications, research and international health work. Medical schools that endeavour to produce graduates motivated to tackle our society’s global health challenges should champion comprehensive global health modules for students.

Objectives: To determine the sociodemographic characteristics, clinical findings and outcome by HIV status in a series of adult patients presenting with neurological disorders (NDs) and admitted to a consultant hospital in Northern Tanzania. Methods: A cohort study took place over a 6-month period from Oct 2007 to March 2008 and included all adult patients with a neurological disorder admitted to the medical wards. Results: A total of 1790 patients were admitted during this period, of whom 337 (18.8%) were diagnosed with a neurological disorder and formed the study group. Of these 337, 69 (20.5%) were HIV-positive. Among the 69 HIV positives, 25% were previously known to be HIV seropositive of whom 82% were on antiretroviral (ARV) medication. Seropositive patients were more likely than seronegative patients to be younger, better educated, have a business occupation, present clinically with confusion, headache and aphasia and have meningitis/CNS infection or a space occupying lesion. Seropositive patients were more likely to present with a Glasgow Coma Score (GCS) of 9–12/15 (33.3% v 17.2%). Seropositive patients had a median CD4 T-lymphocyte count of 47cells/L and were more likely to be anaemic and have an elevated ESR. CT of the head was carried out on 132/337 (39%) patients. The overall findings were infarction 37%, hemorrhage 19%, tumors 15% and abscesses 9%. Brain abscess was more likely in seropositive patients and hemorrhage in seronegatives. The outcome at discharge for all patients was: death 27.6%, disability 54% and no disability 18.4% with death (39.1%) being more likely in seropositive patients. Patients presenting with coma (GCS

Demographic models of human cultural evolution have high explanatory potential but weak empirical support. Here we use a global dataset of rock art sites and climate and genetics-based estimates of ancient population densities to test a new model based on epidemiological principles. The model focuses on the process whereby a cultural innovation becomes endemic in a population, predicting that this cannot occur unless population density exceeds a critical threshold. Analysis of the data, using a Bayesian statistical framework, shows that the model has stronger empirical support than a proportional model, where detection is directly proportional to population density, or a null model, where rock art detection ratios and population density are independent. Results for different geographical areas and periods are compatible with the predictions of the model and confirm its superiority with respect to the null model. Re-analysis of the rock art data, using a second set of independent population estimates, again supports the superiority of the model. Although the available data is sparse and the analysis cannot exclude all possible sources of bias, this is evidence that population density above a critical threshold may be a necessary condition for the maintenance of rock art as a stable part of a population's cultural repertoire. Methods similar to those described can be used to test the model for other classes of archaeological artifact and to compare it against other models.

Abstract Background The frailty phenotype is defined by the presence of three from the following five clinical features: weakness, slow walking speed, unintentional weight loss, exhaustion, and low physical activity. It has been widely applied in different research and clinical contexts, including across many low and middle-income countries. However, there is evidence that the operationalisation of each component of the frailty phenotype significantly alters its characteristics and predictive validity, and care is needed when applying the phenotype across settings. The study’s objective was to operationalise the frailty phenotype in a rural Tanzanian population of older community-dwelling adults. Methods Consenting adults aged ≥60 years, and resident in five randomly selected villages of Hai district Demographic Surveillance Site, were eligible to participate in this cross-sectional study. From a screened sample of 1207 older adults, 235 were randomised and consented to an assessment of their frailty status by the frailty phenotype. Trained research fieldworkers (Tanzanian medical doctors and nurses) carried out measurements and questionnaires at local village centres or at participants’ homes. Results The prevalence of the frailty phenotype, calculated from complete data for 196 participants, was 9.25% (95% CI 4.39–14.12) When missing data were counted as meeting frailty criterion (i.e. missing due to inability to perform an assessment), the prevalence increased to 11.22% (95% CI 7.11–15.32). Frailty by phenotype criteria was more common in older age groups, and was associated with self-assessed poor health and depression symptoms. Conclusions Frailty can be successfully estimated using the frailty phenotype, however there are challenges in its operationalisation cross-culturally. Further work is needed to explore the potential clinical application of the frailty phenotype in such settings.

The burden of hypertension in Sub-Saharan African countries is rising. Low-cost and effective interventions are needed to mitigate these alarming trends. No evidence is available on the use of dietary nitrate for treating hypertension in African populations. The objectives of this study are to assess the feasibility and efficacy of using beetroot and folate as a combined dietary intervention to treat Tanzanian adults with pre- and mild to moderate hypertension. This was a three-arm double-blind, placebo-controlled, parallel randomised clinical trial conducted within the Hai Demographic Surveillance Site in the Kilimanjaro region in Tanzania. 48 participants were randomised to one of three groups for a 60-day intervention period. Group 1: Combined dietary intervention (beetroot juice and folate), Group 2: Single dietary intervention (beetroot juice and placebo capsule), and Group 3: Control group (placebo beetroot juice and placebo capsule). The primary outcome of the trial was to evaluate the feasibility of the study in a low-income setting. Trial assessments included resting clinic and ambulatory 24-hr blood pressure measurements, lifestyle and dietary questionnaires and collection of biological samples. Our cohort included 8 (16.7%) males and 40 (83.3%) females with mean age 60.7 years (SD 6.5). The mean (SD) BMI, clinic systolic blood pressure and ambulatory systolic blood pressure at baseline were 27.6 kg/m2 (5.4), 151.0 (19.4), and 140.4 (15.0) mmHg, respectively. Eight (16.7%) participants were classified as pre-hypertensive, 20 (41.7%) as stage-1 hypertensive, and 20 (41.7%) as stage-2 hypertensive. Overall, the results support the feasibility of a study of this nature within a hypertensive African population. Trial registration number: ISRCTN67978523. Keywords: Dietary nitrate, Folate supplementation, Hypertension, Sub Saharan Africa

A low prevalence of Parkinson’s disease (PD) has been reported in the Sub-Saharan Africa (SSA) region. The genetic causes and clinical features of PD in this region have been poorly described. Very few reports have examined the availability and access to evidence-based quality care for people living with PD in this region. We reviewed all publications focusing on idiopathic PD from SSA published up to May 2016 and observed a prevalence of PD ranging from 7/100,000 in Ethiopia to 67/100,000 in Nigeria. The most recent community-based study reported a mean age at onset of 69.4 years. The infrequent occurrence of mutations in established PD genes was also observed in the region. Treatments were non-existent or at best irregular. Additionally, there is a lack of well-trained medical personnel and multidisciplinary teams in most countries in this region. Drugs for treating PD are either not available or unaffordable. Large-scale genetic and epidemiological studies are therefore needed in SSA to provide further insights into the roles of genetics and other etiological factors in the pathogenesis of PD. The quality of care also requires urgent improvement to meet the basic level of care required by PD patients.

Personal exposure to volatile organic compounds (VOCs) from indoor sources including consumer products is an understudied public health concern. To develop and evaluate methods for monitoring personal VOC exposures, we performed a pilot study and examined time-resolved sensor-based measurements of geocoded total VOC (TVOC) exposures across individuals and microenvironments (MEs). We integrated continuous (1 min) data from a personal TVOC sensor and a global positioning system (GPS) logger, with a GPS-based ME classification model, to determine TVOC exposures in four MEs, including indoors at home (Home-In), indoors at other buildings (Other-In), inside vehicles (In-Vehicle), and outdoors (Out), across 45 participant-days for five participants. To help identify places with large emission sources, we identified high-exposure events (HEEs; TVOC > 500 ppb) using geocoded TVOC time-course data overlaid on Google Earth maps. Across the 45 participant-days, the MEs ranked from highest to lowest median TVOC were: Home-In (165 ppb), Other-In (86 ppb), In-Vehicle (52 ppb), and Out (46 ppb). For the two participants living in single-family houses with attached garages, the median exposures for Home-In were substantially higher (209, 416 ppb) than the three participant homes without attached garages: one living in a single-family house (129 ppb), and two living in apartments (38, 60 ppb). The daily average Home-In exposures exceeded the estimated Leadership in Energy and Environmental Design (LEED) building guideline of 108 ppb for 60% of the participant-days. We identified 94 HEEs across all participant-days, and 67% of the corresponding peak levels exceeded 1000 ppb. The MEs ranked from the highest to the lowest number of HEEs were: Home-In (60), Other-In (13), In-Vehicle (12), and Out (9). For Other-In and Out, most HEEs occurred indoors at fast food restaurants and retail stores, and outdoors in parking lots, respectively. For Home-In HEEs, the median TVOC emission and removal rates were 5.4 g h−1 and 1.1 h−1, respectively. Our study demonstrates the ability to determine individual sensor-based time-resolved TVOC exposures in different MEs, in support of identifying potential sources and exposure factors that can inform exposure mitigation strategies.

The global diarrheal disease burden for Shigella, enterotoxigenic Escherichia coli (ETEC), and Campylobacter is estimated to be 88M, 75M, and 75M cases annually, respectively. A vaccine against this target trio of enteric pathogens could address about one-third of diarrhea cases in children. All three of these pathogens contribute to growth stunting and have demonstrated increasing resistance to antimicrobial agents. Several combinations of antigens are now recognized that could be effective for inducing protective immunity against each of the three target pathogens in a single vaccine for oral administration or parenteral injection. The vaccine combinations proposed here would result in a final product consistent with the World Health Organization’s (WHO) preferred product characteristics for ETEC and Shigella vaccines, and improve the vaccine prospects for support from Gavi, the Vaccine Alliance, and widespread uptake by low- and middle-income countries’ (LMIC) public health stakeholders. Broadly protective antigens will enable multi-pathogen vaccines to be efficiently developed and cost-effective. This review describes how emerging discoveries for each pathogen component of the target trio could be used to make vaccines, which could help reduce a major cause of poor health, reduced cognitive development, lost economic productivity, and poverty in many parts of the world.

Photonic lanterns are made by merging several single-mode cores into one multimode core. Here, the authors show this type of structure can both perform wavelength-to-time mapping of multimode states of light and couple such light to an array of single-photon avalanche detectors.

The issues influencing student engagement with high-stakes computer-based exams were investigated, drawing on feedback from two cohorts of international MA Education students encountering this assessment method for the first time. Qualitative data from surveys and focus groups on the students’ examination experience were analysed, leading to the identification of engagement issues in the delivery of high-stakes computer-based assessments.The exam combined short-answer open-response questions with multiple-choice-style items to assess knowledge and understanding of research methods. The findings suggest that engagement with computer-based testing depends, to a lesser extent, on students’ general levels of digital literacy and, to a greater extent, on their information technology (IT) proficiency for assessment and their ability to adapt their test-taking strategies, including organisational and cognitive strategies, to the online assessment environment. The socialisation and preparation of students for computer-based testing therefore emerge as key responsibilities for instructors to address, with students requesting increased opportunities for practice and training to develop the IT skills and test-taking strategies necessary to succeed in computer-based examinations. These findings and their implications in terms of instructional responsibilities form the basis of a proposal for a framework for Learner Engagement with e-Assessment Practices.

Introduction In low/middle-income countries (LMICs), the prevalence of people diagnosed with dementia is expected to increase substantially and treatment options are limited, with acetylcholinesterase inhibitors not used as frequently as in high-income countries (HICs). Cognitive stimulation therapy (CST) is a group-based, brief, non-pharmacological intervention for people with dementia that significantly improves cognition and quality of life in clinical trials and is cost-effective in HIC. However, its implementation in other countries is less researched. This protocol describes CST-International; an implementation research study of CST. The aim of this research is to develop, test, refine and disseminate implementation strategies for CST for people with mild to moderate dementia in three LMICs: Brazil (upper middle-income), India (lower middle-income) and Tanzania (low-income).Methods and analysis Four overlapping phases: (1) exploration of barriers to implementation in each country using meetings with stakeholders, including clinicians, policymakers, people with dementia and their families; (2) development of implementation plans for each country; (3) evaluation of implementation plans using a study of CST in each country (n=50, total n=150). Outcomes will include adherence, attendance, acceptability and attrition, agreed parameters of success, outcomes (cognition, quality of life, activities of daily living) and cost/affordability; (4) refinement and dissemination of implementation strategies, enabling ongoing pathways to practice which address barriers and facilitators to implementation.Ethics and dissemination Ethical approval has been granted for each country. There are no documented adverse effects associated with CST and data held will be in accordance with relevant legislation. Train the trainer models will be developed to increase CST provision in each country and policymakers/governmental bodies will be continually engaged with to aid successful implementation. Findings will be disseminated at conferences, in peer-reviewed articles and newsletters, in collaboration with Alzheimer’s Disease International, and via ongoing engagement with key policymakers.

Shigella is a highly prevalent bacterium causing acute diarrhea and dysentery in developing countries. Shigella infections are treated with antibiotics but Shigellae are increasingly resistant to these drugs. Vaccination can be a countermeasure against emerging antibiotic-resistant shigellosis. Because of the structural variability in Shigellae O-antigen polysaccharides (Oag), cross-protective Shigella vaccines cannot be derived from single serotype-specific Oag. We created an attenuated Shigella flexneri 2a strain with one rather than multiple Oag units by disrupting the Oag polymerase gene (Δwzy), which broadened protective immunogenicity by exposing conserved surface proteins. Inactivated Δwzy mutant cells combined with Escherichia coli double mutant LT(R192G/L211A) as adjuvant, induced potent antibody responses to outer membrane protein PSSP-1, and type III secretion system proteins IpaB and IpaC. Intranasal immunization with the vaccine preparation elicited cross-protective immunity against S. flexneri 2a, S. flexneri 3a, S. flexneri 6, and Shigella sonnei in a mouse pneumonia model. Thus, S. flexneri 2a Δwzy represents a promising candidate strain for a universal Shigella vaccine.

A reliable and effective human challenge model is needed to help down-select the most promising ETEC vaccines currently under development. Such a model would need to reliably induce diarrhea in a high proportion of volunteers using the lowest possible inoculum to maximize safety and sensitivity. Previously we validated a challenge model that utilized a dose of 2x107 CFU of ETEC strain H10407 (LT+, ST+, CFA/I+ and O78+) to induce attack rates for moderate to severe diarrhea (MSD) of ~60-70%. Here we detail efforts to further refine the model in an attempt to determine if a lower challenge dose of H10407 can be used. Thirty subjects were randomized 1:1 to receive an oral administration of H10407 at doses of 106 or 105 CFU in bicarbonate buffer. After challenge, subjects were monitored for signs and symptoms of enteric illness and stool samples were collected to detect shedding of the challenge strain. Systemic and mucosal immune responses were measured using serum, antibody in lymphocyte supernatant and fecal samples. The attack rate was 13.3% (2/15) and 26.7% (4/15) for MSD in the 105 and 106 groups, respectively. Four MSD cases met criteria for early antibiotic treatment. All subjects but one shed the challenge strain in fecal samples. The frequency and magnitude of anti-LT toxin, CFA/I and LPS O78 immune responses were antigen, dose, severity of diarrhea and shedding levels dependent. Notably, although of lower magnitude, there were considerable immune responses in the subjects with no diarrhea. This may indicate that immune responses to asymptomatic infections of ETEC in children in the endemic countries may contribute to protection. Based on this and our prior studies, we conclude that a dose of 2x107 H10407 remains the lowest practical dose for use in future volunteer studies evaluating candidate vaccines and other preventive or therapeutic ETEC interventions.ClinicalTrials.gov NCT00844493.

INTRODUCTION: In-service training of healthcare workers is essential for improving healthcare services and outcome. METHODS: the Millennium Development Goal (MDG) 6 Partnership for African Clinical Training (M-PACT) program was an innovative in-service training approach designed and implemented by the Royal College of Physicians (RCP) and West African College of Physicians (WACP) with funding from Eco Bank Foundation. The goal was to develop sustainable capacity to tackle MDG 6 targets in West Africa through better postgraduate medical education. Five training centres were establised: Nigeria (Abuja, Ibadan), Ghana (Accra), Senegal (Dakar) and Sierra Leone (Freetown) for training 681 physicians from across West Africa. A curriculum jointly designed by the RCP-WACP team was used to deliver biannual 5-day training courses over a 3-year period. RESULTS: of 602 trained in clinical medicine, 358 (59.5%) were males and 535 (88.9%) were from hosting countries. 472 (78.4%) of participants received travel bursaries to participate, while 318 (52.8%) were residents in Internal Medicine in the respective institutions. Accra had the highest number of participants (29.7%) followed by Ibadan, (28.7%), Dakar, (24.9%), Abuja, (11.0%) and Freetown, (5.6%). Pre-course clinical knowledge scores ranged from 35.1% in the Freetown Course to 63.8% in Accra Course 1; whereas post-course scores ranged from 50.5% in the Freetown course to 73.8% in Accra course 1. CONCLUSION: M-PACT made a positive impact to quality and outcome of healthcare services in the region and is a model for continued improvement for healthcare outcomes, e.g malaria, HIV and TB incidence and mortality in West Africa.

Large pre-historical earthquakes leave traces in the geological and geomorphological record, such as primary and secondary surface ruptures and mass movements, which are the only means to estimate their magnitudes. These environmental earthquake effects (EEEs) can be calibrated using recent seismic events and the Environmental Seismic Intensity Scale (ESI2007). We apply the ESI2007 scale to the 1992 MS7.3 Suusamyr Earthquake in the Kyrgyz Tien Shan, because similar studies are sparse in that area and geological setting, and because this earthquake was very peculiar in its primary surface rupture pattern. We analyze literature data on primary and secondary earthquake effects and add our own observations from fieldwork. We show that the ESI2007 distribution differs somewhat from traditional intensity assessments (MSK (Medvedev-Sponheuer-Karnik) and MM (Modified Mercalli)), because of the sparse population in the epicentral area and the spatial distribution of primary and secondary EEEs. However, the ESI2007 scale captures a similar overall pattern of the intensity distribution. We then explore how uncertainties in the identification of primary surface ruptures influence the results of the ESI2007 assignment. Our results highlight the applicability of the ESI2007 scale, even in earthquakes with complex and unusual primary surface rupture patterns.

Background: We have previously reported the prevalence of dementia in older adults living in the rural Hai district of Tanzania according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria. The aim of this study was to compare prevalence rates using the DSM-IV criteria with those obtained using the 10/66 diagnostic criteria, which is specifically designed for use in low- and middle-income countries. Methods: In phase I, 1,198 people aged 70 and older were screened for dementia. A stratified sample of 296 was then clinically assessed for dementia according to the DSM-IV criteria. In addition, data were collected according to the protocol of the 10/66 Dementia Research Group, which allowed a separate diagnosis of dementia according to these criteria to be established. Results: The age-standardised prevalence of clinical DSM-IV dementia was 6.4% (95% confidence interval [CI] 4.9–7.9%) and of ‘10/66 dementia’ was 21.6% (95% CI 17.5–25.7%). Education was a significant predictor of ‘10/66 dementia’, but not of DSM-IV dementia. Conclusions: There are large discrepancies in dementia prevalence rates depending on which diagnostic system is used. In rural sub-Saharan Africa, it is not clear whether the association between education and dementia using the 10/66 criteria is a genuine effect or the result of an educational bias within the diagnostic instrument. Despite its possible flaws, the DSM-IV criteria represent an international standard for dementia diagnosis. The 10/66 diagnostic criteria may be more appropriate when identification of early and mild cognitive impairment is required.

Assessments for acquired motor-speech disorders that look at movements of the articulators would appear at first glance to be universal. This may be true for the most basic non-speech aspects of movement. We argue that assessments for speech motor control must be attuned to language-specific variables to be fully valid. We describe the rationale for, and development of a motor-speech-disorder screening test for Swahili speakers which includes impairment measures as well as measures of intelligibility and speech-voice naturalness. We further describe its initial validation in terms of content validity, feasibility of administration and scoring without requirements for lengthy training and technical expertise and application to groups of people with and without Parkinson’s disease in Tanzania. Results indicate that the protocol is ready to use in so far as it is acceptable to users (clinicians, patients), is feasible to use, shows good interrater reliability, and is capable of differentiating performance in healthy speakers and those whose speech is disordered. We highlight needs for further development, including issues around training, development of local norms for healthy speakers and for speakers with a variety of neurological disturbances, and extension of the tool to cover culturally valid assessment of impact of communication disorders.

We have successfully demonstrated video-rate CMOS single-photon avalanche diode (SPAD)-based cameras for fluorescence lifetime imaging microscopy (FLIM) by applying innovative FLIM algorithms. We also review and compare several time-domain techniques and solid-state FLIM systems, and adapt the proposed algorithms for massive CMOS SPAD-based arrays and hardware implementations. The theoretical error equations are derived and their performances are demonstrated on the data obtained from 0.13 μm CMOS SPAD arrays and the multiple-decay data obtained from scanning PMT systems. In vivo two photon fluorescence lifetime imaging data of FITC-albumin labeled vasculature of a P22 rat carcinosarcoma (BD9 rat window chamber) are used to test how different algorithms perform on bi-decay data. The proposed techniques are capable of producing lifetime images with enough contrast.