Enumeration in Alzheimer's disease and other late life psychiatric syndromes

Previous studies suggest that visual enumeration is spared in normal aging but impaired in abnormal aging (late stage Alzheimer's disease, AD), raising the task's potential as a marker of dementia. Experiment 1 compared speeded enumeration of 1–9 random dots in early stage AD, vascular dementia (VAD), depression, and age-matched controls. Previous deficits were replicated but they were not specific to AD, with the rate of counting larger numerosities similarly slowed relative to controls by both AD and VAD. Determination of subitizing span was complicated by the surprisingly slower enumeration of one than of two items, especially in AD patients. Experiment 2 showed that AD patients’ relative difficulty with one item persisted with further practice and extended to the enumeration of targets among distractors. However, it was abolished when pattern recognition was possible (enumerating dots on a die). Although an enumeration test is unlikely to help differentiate early AD from other common dementias, the unexpected pattern of patients’ performance challenges current models of enumeration and requires further investigation

Epidemiology of imported cutaneous leishmaniasis at the Hospital for Tropical Diseases, London, United Kingdom: use of polymerase chain reaction to identify the species.

This study reviewed all patients diagnosed with imported cutaneous leishmaniasis (CL) at the Hospital for Tropical Diseases in London, United Kingdom, over an 11-year period. Diagnostic and epidemiologic information was collected prospectively for all patients with imported CL to this hospital during 1998-2009. A total of 223 patients were given a diagnosis of CL. Ninety patients were diagnosed with Old World CL, which was caused most commonly by Leishmania donovani complex (n = 20). A total of 71% were tourists to the Mediterranean region, 36% were migrants or visiting friends and relatives, and 17% were soldiers. One hundred thirty-three patients were given a diagnosis of New World CL. The Leishmania subgenus Viannia caused 97 of these cases; 44% of these were in backpackers and 29% were in soldiers. Polymerase chain reaction was more sensitive and faster for detecting Leishmania DNA (86% for Old World CL and 96% for New World CL) than culture. This is the largest study of imported leishmaniasis, and demonstrates that tourists to the Mediterranean and backpackers in Central and South America are at risk for this disease

London Schools Excellence Fund: Final Report: Enhancing the teaching of STEM through Design and Technology

London Schools Excellence Fund: Final Report: Enhancing the teaching of STEM through Design and Technolog

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

Twelve weeks of supervised exercise improves self-reported symptom burden and fatigue in chronic kidney disease : a secondary analysis of the ‘ExTra CKD’ trial

Background Chronic kidney disease (CKD) patients experience a high symptom burden including fatigue, sleep difficulties, muscle weakness and pain. These symptoms reduce levels of physical function (PF) and activity, and contribute to poor health-related quality of life (HRQoL). Despite the gathering evidence of positive physiological changes following exercise in CKD, there is limited evidence on its effect on self-reported symptom burden, fatigue, HRQoL and physical activity. Methods Thirty-six patients [mean ± SD 61.6 ± 11.8 years, 22 (61%) females, estimated glomerular filtration rate: 25.5 ± 7.8 mL/min/1.73 m2] not requiring renal replacement therapy underwent 12 weeks (3 times/week) of supervised aerobic exercise (AE), or a combination (CE) of AE plus resistance training. Outcomes included self-reported symptom burden, fatigue, HRQoL and physical activity. Results Exercise reduced the total number of symptoms reported by 17% and had favourable effects on fatigue in both groups. AE reduced the frequency of ‘itching’, ‘impotence’ and ‘shortness of breath’ symptoms, and the intrusiveness for symptoms of ‘sleep disturbance’, ‘loss of muscular strength/power’, ‘muscle spasm/stiffness’ and ‘restless legs’. The addition of resistance exercise in the CE group saw a reduction in ‘loss of muscular strength/power’. No changes were seen in subjective PF or physical activity levels. AE increased self-efficacy for physical activity. Conclusions Supervised exercise had favourable effects on symptom frequency and intrusiveness, including substantial improvements in fatigue. Although the intervention did not improve self-reported physical activity levels, AE increased patients’ self-efficacy for physical activity. These favourable changes in self-reported outcomes support the important role of exercise in CKD

Policy for sustainable entrepreneurship: a crowdsourced framework

Sustainable entrepreneurship—entrepreneurship with social and ecological gains as well as economic ones—has the potential to play a significant role in addressing societal and environmental challenges. However, sustainability and entrepreneurship have hitherto been addressed through separate policy regimes, and it is not clear how policymakers can encourage sustainable entrepreneurship specifically. The authors develop a policy framework for sustainable entrepreneurship, using an open innovation approach with policymakers, business executives, academics, entrepreneurs and other relevant actors, including an online crowdsourcing event with 150 participants. The framework incorporates five policy domains: creating awareness and skills; building networks; funding and investing; measuring impact and performance; and innovating government. The article proposes a modified version of the multi-level perspective (MLP) on how socio-technical transitions occur, since the findings suggest that policy can catalyze the facilitation and aggregation of innovations coming from the niche level, thereby evolving the socio-technical regime, in addition to the role of policy described in earlier work in stabilizing the socio-technical regime. Contributions to entrepreneurship policy literature include the policy domain of measuring impact and performance, as appropriate success measures are non-trivial in a triple bottom line environment, and the potential for open policy innovation in entrepreneurship policy. Contributions to sustainability policy literature include the requirements for support mechanisms and capacity building to empower individuals to contribute as innovators and entrepreneurs and not just consumers. The sustainable entrepreneurship framework can be applied by policymakers to develop context-specific policies: this is illustrated with a worked example of EU policy recommendations. The paper also outlines a method for crowdsourcing policy innovations

The association of physical function and physical activity with all-cause mortality and adverse clinical outcomes in non-dialysis chronic kidney disease : a systematic review

Objective: People with nondialysis-dependent chronic kidney disease (CKD) and renal transplant recipients (RTRs) have compromised physical function and reduced physical activity (PA) levels. Whilst established in healthy older adults and other chronic diseases, this association remains underexplored in CKD. We aimed to review the existing research investigating poor physical function and PA with clinical outcome in nondialysis CKD. Data sources: Electronic databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials) were searched until December 2017 for cohort studies reporting objective or subjective measures of PA and physical function and the associations with adverse clinical outcomes and all-cause mortality in patients with nondialysis CKD stages 1–5 and RTRs. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42016039060). Review methods: Study quality was assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare and Research Quality (AHRQ) standards. Results: A total of 29 studies were included; 12 reporting on physical function and 17 on PA. Only eight studies were conducted with RTRs. The majority were classified as ‘good’ according to the AHRQ standards. Although not appropriate for meta-analysis due to variance in the outcome measures reported, a coherent pattern was seen with higher mortality rates or prevalence of adverse clinical events associated with lower PA and physical function levels, irrespective of the measurement tool used. Sources of bias included incomplete description of participant flow through the study and over reliance on self-report measures. Conclusions: In nondialysis CKD, survival rates correlate with greater PA and physical function levels. Further trials are required to investigate causality and the effectiveness of physical function and PA interventions in improving outcomes. Future work should identify standard assessment protocols for PA and physical function

Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium.

Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells.This study was supported by the Medical Research Council (G0900424 to E.R.), European Union grant EuroSyStem (200720; FP7/2008), the Newton Trust (to E.R.), the Wellcome Trust (098357/Z/12/Z to B.D.S.). Core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2015.06.01

Identification of a novel class of autotaxin inhibitors through cross-screening

Three novel series were generated in order to mimic the pharmacophoric features displayed by lead compound AM095, a Lysophosphatidic acid (LPA1) receptor antagonist. Biological evaluation of this array of putative LPA1 antagonists led us to the discovery of three novel series of inhibitors of the ecto-enzyme Autotaxin (ATX), responsible for LPA production in blood, with potencies in the range 1 – 4 μM accompanied with good (> 100 μg/mL) solubility