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"Shaw, C"
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Barriers to healthcare and self-reported adverse outcomes for autistic adults: a cross-sectional study
ObjectivesAutistic people experience poor physical and mental health along with reduced life expectancy compared with non-autistic people. Our aim was to identify self-reported barriers to primary care access by autistic adults compared with non-autistic adults and to link these barriers to self-reported adverse health consequences.DesignFollowing consultation with the autistic community at an autistic conference, Autscape, we developed a self-report survey, which we administered online through social media platforms.SettingA 52-item, international, online survey.Participants507 autistic adults and 157 non-autistic adults.Primary and secondary outcome measuresSelf-reported barriers to accessing healthcare and associated adverse health outcomes.ResultsEighty per cent of autistic adults and 37% of non-autistic respondents reported difficulty visiting a general practitioner (GP). The highest-rated barriers by autistic adults were deciding if symptoms warrant a GP visit (72%), difficulty making appointments by telephone (62%), not feeling understood (56%), difficulty communicating with their doctor (53%) and the waiting room environment (51%). Autistic adults reported a preference for online or text-based appointment booking, facility to email in advance the reason for consultation, the first or last clinic appointment and a quiet place to wait. Self-reported adverse health outcomes experienced by autistic adults were associated with barriers to accessing healthcare. Adverse outcomes included untreated physical and mental health conditions, not attending specialist referral or screening programmes, requiring more extensive treatment or surgery due to late presentations and untreated potentially life-threatening conditions. There were no significant differences in difficulty attending, barriers experienced or adverse outcomes between formally diagnosed and self-identified autistic respondents.ConclusionsReduction of healthcare inequalities for autistic people requires that healthcare providers understand autistic perspectives, communication needs and sensory sensitivities. Adjustments for autism-specific needs are as necessary as ramps for wheelchair users.
Journal Article
Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity
We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer’s and has been linked to this disease and to the Guamanian variant, ALS–PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.
Journal Article
Cognitive test batteries in animal cognition research: evaluating the past, present and future of comparative psychometrics
For the past two decades, behavioural ecologists have documented consistent individual differences in behavioural traits within species and found evidence for animal “personality”. It is only relatively recently, however, that increasing numbers of researchers have begun to investigate individual differences in cognitive ability within species. It has been suggested that cognitive test batteries may provide an ideal tool for this growing research endeavour. In fact, cognitive test batteries have now been used to examine the causes, consequences and underlying structure of cognitive performance within and between many species. In this review, we document the existing attempts to develop cognitive test batteries for non-human animals and review the claims that these studies have made in terms of the structure and evolution of cognition. We argue that our current test battery methods could be improved on multiple fronts, from the design of tasks, to the domains targeted and the species tested. Refining and optimising test battery design will provide many benefits. In future, we envisage that well-designed cognitive test batteries may provide answers to a range of exciting questions, including giving us greater insight into the evolution and structure of cognition.
Journal Article
The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease
•Impaired brain glucose metabolism and amyloid β plaques are associated with Alzheimer's disease pathology.•Ketones provide an alternative metabolic precursor to glucose in the brain.•Ketogenic diets likely reduce amyloid plaques and may reverse their neurotoxicity.•Modern diets high in carbohydrates may contribute to increasing Alzheimer's incidence.•The ketogenic diet (including carbohydrate restriction) might be useful in the management of Alzheimer's disease.
The prevalence of Alzheimer's disease, a chronic neurodegenerative condition, is increasing as is the need for effective treatments and preventions. The underlying pathology of Alzheimer's is not yet fully understood, so existing research has focused on understanding the prominent features of the disease. These include amyloid plaques, which accumulate in the brains of those with Alzheimer's disease; impaired glucose metabolism; and neuronal cell death. Emerging evidence suggests that a low-carbohydrate, high-fat ketogenic diet may help to mitigate the damage associated with these pathologies. The ketogenic diet could alleviate the effects of impaired glucose metabolism by providing ketones as a supplementary energy source. In addition, this diet may help to reduce the accumulation of amyloid plaques while reversing amyloid β toxicity. Research has begun to identify early underlying mechanisms in Alzheimer's disease that could be targeted by new prevention strategies. Glycation of the ApoE protein leads to impaired transportation of important lipids, including cholesterol, to the brain, resulting in lipid deficiencies that could explain progression to the later pathologies of the disease. In this review, we hypothesize that the ketogenic diet could be an effective treatment and prevention for Alzheimer's disease, but both ketone production and carbohydrate restriction may be needed to achieve this.
Journal Article
Epidemiology of Sarcopenia: Determinants Throughout the Lifecourse
Sarcopenia is an age-related syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength; it is a major contributor to the risk of physical frailty, functional impairment in older people, poor health-related quality of life and premature death. Many different definitions have been used to describe sarcopenia and have resulted in varying estimates of prevalence of the condition. The most recent attempts of definitions have tried to integrate information on muscle mass, strength and physical function and provide a definition that is useful in both research and clinical settings. This review focuses on the epidemiology of the three distinct physiological components of sarcopenia, and highlights the similarities and differences between their patterns of variation with age, gender, geography and time and the individual risk factors that cluster selectively with muscle mass, strength and physical function. Methods used to measure muscle mass, strength and physical functioning and how differences in these approaches can contribute to the varying prevalence rates will also be described. The evidence for this review was gathered by undertaking a systematic search of the literature. The descriptive characteristics of muscle mass, strength and function described in this review point to the urgent need for a consensual definition of sarcopenia incorporating these parameters.
Journal Article
Reasonable adjustments for autistic clinicians: A qualitative study
Autistic people experience barriers to accessing healthcare. Autistic clinical professionals may be able to help improve this situation. Previous research, however, has shown that Autistic clinical professionals experience numerous challenges in the workplace. If there is a ‘substantial’ and ‘long-term’ negative effect on the person’s ability to do normal daily activities, then Autism may be considered a disability under The Equality Act 2010; the jurisdiction of which covers Great Britain. Autistic clinical professionals working in healthcare settings across England, Wales, and Scotland are therefore entitled to reasonable adjustments to aid them in their clinical practice. This is a qualitative study. We recruited 82 Autistic clinical professionals via social media to complete an online survey. Questions broadly explored: 1) the challenges they faced in their clinical workplaces; and 2) the reasonable adjustments that they needed, had, or needed but did not have. Data were analysed quasi-thematically, also drawing on the principles of content analysis. Respondents reported multiple challenges from our analysis, from which we developed 8 themes: gaining and attending employment, reasonable adjustments under the radar, connecting and integrating (specifically, the communication mismatches between Autistic professionals and non-autistic colleagues, and fitting in socially and professionally), executive functioning, change, working environment, working practices/cultures, and the consequences and effects on Autistic clinical professionals). We recommend that Autistic clinical professionals and their employers individually discuss and iteratively revisit the unique combination of reasonable adjustments suitable for each person. In this way, employers may provide equitable workplaces for their staff which will benefit not only them, but their patients, and healthcare as a whole.
Journal Article
CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy
The immunosuppressive tumor microenvironment (TME) represents a major barrier for effective immunotherapy. Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic cell components of the TME which can either promote tumor progression (M2-like) or boost antitumor immunity (M1-like). Here, we demonstrate that a subset of TAMs that express folate receptor β (FRβ) possess an immunosuppressive M2-like profile. In syngeneic tumor mouse models, chimeric antigen receptor (CAR)-T cell-mediated selective elimination of FRβ
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TAMs in the TME results in an enrichment of pro-inflammatory monocytes, an influx of endogenous tumor-specific CD8
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T cells, delayed tumor progression, and prolonged survival. Preconditioning of the TME with FRβ-specific CAR-T cells also improves the effectiveness of tumor-directed anti-mesothelin CAR-T cells, while simultaneous co-administration of both CAR products does not. These results highlight the pro-tumor role of FRβ
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TAMs in the TME and the therapeutic implications of TAM-depleting agents as preparative adjuncts to conventional immunotherapies that directly target tumor antigens.
Several strategies have been attempted to target immune suppressive populations in the tumor microenvironment. Here the authors show that folate receptor β-targeted CAR-T cells eliminate immunosuppressive tumor associated macrophages, promoting endogenous antitumor immune responses and adoptive T-cell therapy in pre-clinical models.
Journal Article