Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease

The injecting ‘event’: harm reduction beyond the human

Since the 1980s, the primary public health response to injecting drug use in the UK has been one of harm reduction. That is, reducing the harms associated with drug use without necessarily reducing consumption itself. Rooted in a post-Enlightenment idea of rationalism, interventions are premised on the rational individual who, given the right means, will choose to avoid harm. This lies in stark contrast to dominant addiction models that pervade popular images of the ‘out of control’ drug user, or worse, ‘junkie’. Whilst harm reduction has undoubtedly had vast successes, including challenging the otherwise pathologising and often stigmatising model of addiction, I argue that it has not gone far enough in addressing aspects of drug use that go beyond ‘rational’ and ‘human’ control. Drawing on my doctoral research with people who inject drugs, conducted in London, UK, this paper highlights the role of the injecting ‘event’, which far from being directed or controlled by a pre-defined individual or ‘body’ was composed by a fragile assemblage of bodies, human and nonhuman. Furthermore, in line with the ‘event’s’ heterogeneous and precarious make-up, multiple ways of ‘becoming’ through these events were possible. I look here at these ‘becomings’ as both stabilising and destabilising ways of being in the world, and argue that we need to pay closer attention to these events and what people are actually in the process of becoming in order to enact more accountable and ‘response-able’ harm reduction

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Social factors influencing child health in Ghana

Objectives Social factors have profound effects on health. Children are especially vulnerable to social influences, particularly in their early years. Adverse social exposures in childhood can lead to chronic disorders later in life. Here, we sought to identify and evaluate the impact of social factors on child health in Ghana. As Ghana is unlikely to achieve the Millennium Development Goals’ target of reducing child mortality by two-thirds between 1990 and 2015, we deemed it necessary to identify social determinants that might have contributed to the non-realisation of this goal. Methods ScienceDirect, PubMed, MEDLINE via EBSCO and Google Scholar were searched for published articles reporting on the influence of social factors on child health in Ghana. After screening the 98 articles identified, 34 of them that met our inclusion criteria were selected for qualitative review. Results Major social factors influencing child health in the country include maternal education, rural-urban disparities (place of residence), family income (wealth/poverty) and high dependency (multiparousity). These factors are associated with child mortality, nutritional status of children, completion of immunisation programmes, health-seeking behaviour and hygiene practices. Conclusions Several social factors influence child health outcomes in Ghana. Developing more effective responses to these social determinants would require sustainable efforts from all stakeholders including the Government, healthcare providers and families. We recommend the development of interventions that would support families through direct social support initiatives aimed at alleviating poverty and inequality, and indirect approaches targeted at eliminating the dependence of poor health outcomes on social factors. Importantly, the expansion of quality free education interventions to improve would-be-mother’s health knowledge is emphasised

Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14

Abstract The KIF14 locus is gained and overexpressed in various malignancies, with prognostic relevance. Its protein product, a mitotic kinesin, accelerates growth of normal mammary epithelial cells in vitro and retinoblastoma tumours in a mouse model, while KIF14 knockdown blocks growth of brain, liver, ovarian, breast, prostate, and other tumour cells and xenografts. However, the tumour-initiating effects of Kif14 overexpression have not been studied. We aged a cohort of Kif14-overexpressing transgenic mice and wild-type littermates and documented survival, cause of death, and tumour burden. The Kif14 transgene was expressed in all tissues examined, and was associated with increased proliferation marker expression. Neither mouse weights nor overall survival differed between genotypes. However, Kif14 transgenic mice showed a higher incidence of fatal lymphomas (73 vs. 50%, p = 0.03, Fisher’s exact test), primarily follicular and diffuse B-cell lymphomas. Non-tumour findings included a bilateral ballooning degeneration of lens in 12% of Kif14 transgenic mice but no wild-type mice (p = 0.02). Overall, this work reveals a novel association of Kif14 overexpression with lymphoma but suggests that Kif14 does not have as prominent a role in initiating cancer in other cell types as it does in accelerating tumour development in response to other oncogenic insults

Transforming Industrial Manipulators via Kinesthetic Guidance for Automated Inspection of Complex Geometries

The increased demand for cost-efficient manufacturing and metrology inspection solutions for complex-shaped components in High-Value Manufacturing (HVM) sectors requires increased production throughput and precision. This drives the integration of automated robotic solutions. However, the current manipulators utilizing traditional programming approaches demand specialized robotic programming knowledge and make it challenging to generate complex paths and adapt easily to unique specifications per component, resulting in an inflexible and cumbersome teaching process. Therefore, this body of work proposes a novel software system to realize kinesthetic guidance for path planning in real-time intervals at 250 Hz, utilizing an external off-the-shelf force–torque (FT) sensor. The proposed work is demonstrated on a 500 mm2 near-net-shaped Wire–Arc Additive Manufacturing (WAAM) complex component with embedded defects by teaching the inspection path for defect detection with a standard industrial robotic manipulator in a collaborative fashion and adaptively generating the kinematics resulting in the uniform coupling of ultrasound inspection. The utilized method proves superior in performance and speed, accelerating the programming time using online and offline approaches by an estimate of 88% to 98%. The proposed work is a unique development, retrofitting current industrial manipulators into collaborative entities, securing human job resources, and achieving flexible production