Autocrine Production of IGF‐I Increases Stem Cell‐Mediated Neuroprotection

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A‐SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin‐like growth factor‐I (IGF‐I) production contributes to cellular therapy neuroprotection. IGF‐I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF‐I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF‐I, we demonstrate that IGF‐I production augments the production of glial‐derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF‐I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS. Stem Cells 2015;33:1480–1489Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111155/1/stem1933.pd

“The embodiment of pure thought”? Digital fabrication, disability and new possibilities for auto/biography

This essay draws on findings from a UK Arts and Humanities Research Council project: “In the Making” (AH/M006026/1) to argue that the digital turn in art therapy – particularly 3D printing – makes possible new forms of disability agency, engaging post-humanist theory to suggest re-conceptualizations of embodied person-hood. Keywords: digital fabrication; disability; auto/biography; embodimen

Radiocarbon chronology and environmental context of Last Glacial Maximum human occupation in Switzerland

Central Europe during the Last Glacial Maximum (LGM) was dominated by polar desert and steppe-tundra biomes. Despite this, a human presence during this time period is evident at several locations across the region, including in Switzerland, less than 50 km from the Alpine ice sheet margin. It has been hypothesised that such human activity may have been restricted to brief periods of climatic warming within the LGM, but chronological information from many of these sites are currently too poorly resolved to corroborate this. Here we present a revised chronology of LGM human occupation in Switzerland. AMS radiocarbon dating of cut-marked reindeer (Rangifer tarandus) bones from the sites of Kastelhöhle-Nord and Y-Höhle indicates human occupation of Switzerland was most likely restricted to between 23,400 and 22,800 cal. BP. This timeframe corresponds to Greenland Interstadial 2, a brief warming phase, supporting the hypothesis that human presence was facilitated by favourable climatic episodes. Carbon, nitrogen and sulphur stable isotope analysis of the fauna provides palaeoenvironmental information for this time period. These findings contribute to our understanding of human activity in ice-marginal environments and have implications for understanding cultural connections across central Europe during the LGM

Reducing risk with e-based support for adherence to lifestyle change in hypertension (REACH): Protocol for a multicentred randomised controlled trial

Introduction: Web-based lifestyle counselling designed to improve adherence to self-management behaviours for diet, exercise and medication has been shown to reduce blood pressure (BP). However, the long-term clinical outcome of these interventions is not established. Our aim was to establish whether an e-counselling program is independently associated with improved clinical outcomes over a 12-month period, as defined by the following criteria: (1) reduction of systolic BP, diastolic BP, pulse pressure and associated risk factors for cardiovascular events; and (2) adherence to self-management behaviour (diet, exercise, smoke-free living and prescribed medication). Methods and analysis: Reducing risk with e-based support for adherence to lifestyle change in hypertension is a two-parallel group, double-blind randomised controlled trial that will utilise a two (Groups: e-counselling vs control) by three (assessment intervals: baseline, 4-month and 12-month outcome) design. BP, lipoprotein cholesterol, physical activity and dietary behaviours and psychological distress will be measured at each assessment. We plan to recruit 528 participants (35-74 years of age) diagnosed with stage 1 or 2 hypertension (systolic BP, 140-180 mm Hg; diastolic BP 90-110 mm Hg) from three major cities (Toronto, London, Vancouver) and one rural area (Grey Bruce region) across Canada between February 2012 and July 2015. Controls will receive general educational e-messages on heart healthy living and the e-counselling group will receive tailored e-messages that are matched to their stage of readiness for change. For both groups, e-messages will be sent proactively on a weekly basis during months 1-4, then bi-weekly during months 5-8 and then monthly during months 9-12. Ethics and dissemination: Ethical approval has been obtained from all recruitment sites. This will be one of the first studies to evaluate the long-term efficacy of preventive e-counselling strategies for cardiovascular disease prevention in patients with hypertension. Findings from this study will be used to guide the ongoing development of e-counselling services

Nitrogen palaeo-isoscapes: changing spatial gradients of faunal δ15N in late Pleistocene and early Holocene Europe

Nitrogen isotope ratio analysis (δ15N) of animal tissue is widely used in archaeology and palaeoecology to investigate diet and ecological niche. Data interpretations require an understanding of nitrogen isotope compositions at the base of the food web (baseline δ15N). Significant variation in animal δ15N has been recognised at various spatiotemporal scales and related to changes both in baseline δ15N, linked to environmental and climatic influence on the terrestrial nitrogen cycle, and animal ecology. Isoscapes (models of isotope spatial variation) have proved a useful tool for investigating spatial variability in biogeochemical cycles in present-day marine and terrestrial ecosystems, but so far, their application to palaeo-data has been more limited. Here, we present time-sliced nitrogen isoscapes for late Pleistocene and early Holocene Europe (c. 50,000 to 10,000 years BP) using herbivore collagen δ15N data. This period covers the Last Glacial-Interglacial Transition, during which significant variation in the terrestrial nitrogen cycle occurred. We use generalized linear mixed modelling approaches for interpolation and test models which both include and exclude climate covariate data. Our results show clear changes in spatial gradients of δ15N through time. Prediction of the lowest faunal δ15N values in northern latitudes after, rather than during, the Last Glacial Maximum is consistent with the Late Glacial Nitrogen Excursion (LGNE). We find that including climatic covariate data does not significantly improve model performance. These findings have implications for investigating the drivers of the LGNE, which has been linked to increased landscape moisture and permafrost thaw, and for understanding changing isotopic baselines, which are fundamental for studies investigating diets, niche partitioning, and migration of higher trophic level animals

Sustainable development and African local government: can electronic training help build capacities?

A recent study carried out by European and African organizations into the potential for electronic distance training (EDT) on sustainability in African local governments concluded that EDT was both 'useful and feasible'. This article reflects on some of the theoretical and practical implications of that study. It focuses on the connection between learning and sustainability and how EDT programmes might be designed and promoted. The paper argues that, while resource issues and poor access to Information and Communication Technologies (ICTs) create considerable constraints and point to the need for policies to improve access, in general the most important factors for successful capacity building relate to the design of learning programmes that take account of the work contexts and skill and capability requirements of those targeted as learners. 'Useful' and 'feasible' depend on (i) how work-based and work-related learning processes are understood and (ii) the conditions to promote learning within African local government. Keywords: Africa; Electronic distance training; Local government; Sustainability; Workplace learnin

Heterogeneity in reporting on urinary outcome and cure after surgical interventions for stress urinary incontinence in adult neuro-urological patients: A systematic review

Aims: To describe all outcome parameters and definitions of cure used to report on outcome of surgical interventions for stress urinary incontinence (SUI) in neuro-urological (NU) patients. Methods: This systematic review was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The study protocol was registered and published (CRD42016033303; http://www.crd.york.ac.uk/PROSPERO). Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov were systematically searched for relevant publications until February 2017. Result

Responsive Operations for Key Services (ROKS): A Modular, Low SWaP Quantum Communications Payload

Quantum key distribution (QKD) is a theoretically proven future-proof secure encryption method that inherits its security from fundamental physical principles. With a proof-of-concept QKD payload having flown on the Micius satellite since 2016, efforts have intensified globally. Craft Prospect, working with a number of UK organisations, has been focused on miniaturising the technologies that enable QKD so that they may be used in smaller platforms including nanosatellites. The significant reduction of size, and therefore the cost of launching quantum communication technologies either on a dedicated platform or hosted as part of a larger optical communications will improve potential access to quantum encryption on a relatively quick timescale. The Responsive Operations for Key Services (ROKS) mission seeks to be among the first to send a QKD payload on a CubeSat into low Earth orbit, demonstrating the capabilities of newly developed modular quantum technologies. The ROKS payload comprises a quantum source module that supplies photons randomly in any of four linear polarisation states fed from a quantum random number generator; an acquisition, pointing, and tracking system to fine-tune alignment of the quantum source beam with an optical ground station; an imager that will detect cloud cover autonomously; and an onboard computer that controls and monitors the other modules, which manages the payload and assures the overall performance and security of the system. Each of these modules have been developed with low Size, Weight and Power (SWaP) for CubeSats, but with interoperability in mind for other satellite form factors. We present each of the listed components, together with the initial test results from our test bench and the performance of our protoflight models prior to initial integration with the 6U CubeSat platform systems. The completed ROKS payload will be ready for flight at the end of 2022, with various modular components already being baselined for flight and integrated into third party communication missions

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study):study protocol for a cluster randomised controlled trial

BACKGROUND: People with severe mental illnesses die up to 20 years earlier than the general population, with cardiovascular disease being the leading cause of death. National guidelines recommend that the physical care of people with severe mental illnesses should be the responsibility of primary care; however, little is known about effective interventions to lower cardiovascular disease risk in this population and setting. Following extensive peer review, funding was secured from the United Kingdom National Institute for Health Research (NIHR) to deliver the proposed study. The aim of the trial is to test the effectiveness of a behavioural intervention to lower cardiovascular disease risk in people with severe mental illnesses in United Kingdom General Practices. METHODS/DESIGN: The study is a cluster randomised controlled trial in 70 GP practices for people with severe mental illnesses, aged 30 to 75 years old, with elevated cardiovascular disease risk factors. The trial will compare the effectiveness of a behavioural intervention designed to lower cardiovascular disease risk and delivered by a practice nurse or healthcare assistant, with standard care offered in General Practice. A total of 350 people will be recruited and followed up at 6 and 12 months. The primary outcome is total cholesterol level at the 12-month follow-up and secondary outcomes include blood pressure, body mass index, waist circumference, smoking status, quality of life, adherence to treatments and services and behavioural measures for diet, physical activity and alcohol use. An economic evaluation will be carried out to determine the cost effectiveness of the intervention compared with standard care. DISCUSSION: The results of this pragmatic trial will provide evidence on the clinical and cost effectiveness of the intervention on lowering total cholesterol and addressing multiple cardiovascular disease risk factors in people with severe mental illnesses in GP Practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13762819 . Date of Registration: 25 February 2013. Date and Version Number: 27 August 2014 Version 5