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Search Results: 1 - 10 of 299762 matches for " Nick J. Spencer "
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Localization of the Sensory Neurons and Mechanoreceptors Required for Stretch-Evoked Colonic Migrating Motor Complexes in Mouse Colon
Vladimir P. Zagorodnyuk,Nick J. Spencer
Frontiers in Physiology , 2011, DOI: 10.3389/fphys.2011.00098
Abstract: The pacemaker and pattern generator that underlies the cyclical generation of spontaneous colonic migrating motor complexes (CMMCs) has recently been identified to lie within the myenteric plexus and/or muscularis externa. Neither the mucosa, nor the release of substances from the mucosa were found to be required for the spontaneous generation of CMMCs. However, it is known that stretch applied to the colonic wall can also evoke CMMCs and since stretch of the gut wall is known to stimulate the mucosa, it is not clear whether release of substances from the mucosa and/or submucosal plexus are required for stretch-evoked CMMCs. Therefore, the aim of this study was to determine whether circumferential stretch-evoked CMMCs require the presence of the mucosa and/or submucosal plexus in isolated mouse colon. Spontaneous CMMCs were recorded from full length sheet preparations of colon in vitro. Graded circumferential stretch (at a rate of 100 μm/s) applied to a 15-mm segment of mid–distal colon reliably evoked a CMMC, which propagated to the oral recording site. Sharp dissection to remove the mucosa and submucosal plexus from the entire colon did not prevent spontaneous CMMCs and circumferential stretch-evoked CMMCs were still reliably evoked by circumferential stretch, even at significantly lower thresholds. In contrast, in intact preparations, direct stimulation of the mucosa (without accompanying stretch) proved highly inconsistent and rarely evoked a CMMC. These observations lead to the inescapable conclusion that the sensory neurons activated by colonic stretch to initiate CMMCs lie in the myenteric plexus, while the mechanoreceptors activated by stretch, lie in the myenteric ganglia and/or muscularis externa. Stretch activation of these mechanoreceptors does not require release of any substance(s) from the mucosa, or neural inputs arising from submucosal ganglia.
Identification of the Visceral Pain Pathway Activated by Noxious Colorectal Distension in Mice
Vladimir P. Zagorodnyuk,Simon J. Brookes,Nick J. Spencer
Frontiers in Neuroscience , 2011, DOI: 10.3389/fnins.2011.00016
Abstract: In patients with irritable bowel syndrome, visceral pain is evoked more readily following distension of the colorectum. However, the identity of extrinsic afferent nerve pathway that detects and transmits visceral pain from the colorectum to the spinal cord is unclear. In this study, we identified which extrinsic nerve pathway(s) underlies nociception from the colorectum to the spinal cord of rodents. Electromyogram recordings were made from the transverse oblique abdominal muscles in anesthetized wild type (C57BL/6) mice and acute noxious intraluminal distension stimuli (100–120 mmHg) were applied to the terminal 15 mm of colorectum to activate visceromotor responses (VMRs). Lesioning the lumbar colonic nerves in vivo had no detectable effect on the VMRs evoked by colorectal distension. Also, lesions applied to the right or left hypogastric nerves failed to reduce VMRs. However, lesions applied to both left and right branches of the rectal nerves abolished VMRs, regardless of whether the lumbar colonic or hypogastric nerves were severed. Electrical stimulation applied to either the lumbar colonic or hypogastric nerves in vivo, failed to elicit a VMR. In contrast, electrical stimulation (2–5 Hz, 0.4 ms, 60 V) applied to the rectum reliably elicited VMRs, which were abolished by selective lesioning of the rectal nerves. DiI retrograde labeling from the colorectum (injection sites 9–15 mm from the anus, measured in unstretched preparations) labeled sensory neurons primarily in dorsal root ganglia (DRG) of the lumbosacral region of the spinal cord (L6-S1). In contrast, injection of DiI into the mid to proximal colon (injection sites 30–75 mm from the anus, measured in unstretched preparations) labeled sensory neurons in DRG primarily of the lower thoracic level (T6-L2) of the spinal cord. The visceral pain pathway activated by acute noxious distension of the terminal 15 mm of mouse colorectum is transmitted predominantly, if not solely, through rectal/pelvic afferent nerve fibers to the spinal cord. The sensory neurons of this spinal afferent pathway lie primarily in the lumbosacral region of the spinal cord, between L6 and S1.
Prevalence of childhood disability and the characteristics and circumstances of disabled children in the UK: secondary analysis of the Family Resources Survey
Clare M Blackburn, Nick J Spencer, Janet M Read
BMC Pediatrics , 2010, DOI: 10.1186/1471-2431-10-21
Abstract: Data were generated from secondary analysis of the Family Resources Survey, a national UK cross-sectional survey, (2004/5) which had data on 16,012 children aged 0-18 years. Children were defined as disabled if they met the Disability Discrimination Act (DDA) definition (1995 and 2005). Frequency distributions and cross-tabulations were run to establish prevalence estimates, and describe the circumstances of disabled children. To establish the association between individual social and material factors and childhood disability when other factors were controlled for, logistic regression models were fitted on the dependent variable 'DDA defined disability'.7.3% (CI 6.9, 7.7) of UK children were reported by as disabled according to the DDA definition. Patterns of disability differed between sexes with boys having a higher rate overall and more likely than girls to experience difficulties with physical coordination; memory, concentration and learning; communication. Disabled children lived in different personal situations from their non-disabled counterparts, and were more likely to live with low-income, deprivation, debt and poor housing. This was particularly the case for disabled children from black/minority ethnic/mixed parentage groups and lone-parent households. Childhood disability was associated with lone parenthood and parental disability and these associations persisted when social disadvantage was controlled for.These analyses suggest that UK disabled children experience higher levels of poverty and personal and social disadvantage than other children. Further research is required to establish accurate prevalence estimates of childhood disability among different black and minority ethnic groups and to understand the associations between childhood disability and lone parenthood and the higher rates of sibling and parental disability in households with disabled children.There is considerable global concern to reduce the prevalence of childhood disability and to
Regulatory barriers to equity in a health system in transition: a qualitative study in Bulgaria
Boika Rechel, Clare M Blackburn, Nick J Spencer, Bernd Rechel
BMC Health Services Research , 2011, DOI: 10.1186/1472-6963-11-219
Abstract: 50 qualitative in-depth interviews with users, providers and policy-makers concerned with child health services in Bulgaria, conducted in two villages, one town of 70,000 inhabitants, and the capital Sofia.The participants in our study reported a variety of regulatory barriers which undermined the principles of equity and, as far as the health insurance system is concerned, solidarity. These included non-participation in the compulsory health insurance system, informal payments, and charging user fees to exempted patients. The participants also reported seemingly unnecessary treatments in the growing private sector. These regulatory failures were associated with the fast pace of reforms, lack of consultation, inadequate public financing of the health system, a perceived "commercialization" of medicine, and weak enforcement of legislation. A recurrent theme from the interviews was the need for better information about patient rights and services covered by the health insurance system.Regulatory barriers to equity and compliance in daily practice deserve more attention from policy-makers when embarking on health reforms. New financing sources and an increasing role of the private sector need to be accompanied by an appropriate and enforceable regulatory framework to control the behavior of health care providers and ensure equity in access to health services.Bulgaria, a post-communist country with a population of 7.50 million people in 2010 [1] situated in South-East Europe, joined the European Union (EU) in January 2007. In the late 1990s, Bulgaria began embarking on major reforms of its health system. These included introducing general practice, establishing a health insurance system, reorganizing hospital services, and setting up new payment mechanisms for providers [2]. Up to 1998, Bulgaria's health system had been mainly financed through general taxation and was characterized by a number of weaknesses, including underfunding, a focus on curative and hospital servi
Access to health care for Roma children in Central and Eastern Europe: findings from a qualitative study in Bulgaria
Boika Rechel, Clare M Blackburn, Nick J Spencer, Bernd Rechel
International Journal for Equity in Health , 2009, DOI: 10.1186/1475-9276-8-24
Abstract: 50 qualitative in-depth interviews with users, providers and policy-makers concerned with child health services in Bulgaria, conducted in two villages, one town of 70,000 inhabitants, and the capital Sofia.Our findings provide important empirical evidence on the range of barriers Roma children face when accessing health services. Among the most important barriers are poverty, administrative and geographical obstacles, low levels of parental education, and lack of ways to accommodate the cultural, linguistic and religious specifics of this population group.Our research illustrates the complexity of the problems the Roma face. Access to health care cannot be discussed in isolation from other problems this population group experiences, such as poverty, restricted access to education, and social exclusion.Our paper reports findings on access to health services for Roma children that emerged from a wider qualitative study on access to child health services in Bulgaria in the context of the health care reforms that were implemented since the late 1990s. Similarly to other countries of Central and Eastern Europe, Bulgaria undertook substantial reforms of the financing, organization and delivery of its health services. These included introducing social health insurance and general practice, and reforming hospital services [1]. The impact of these changes on access to health services for children, particularly for disadvantaged groups such as ethnic minority children, has received hardly any attention so far [2].Of the estimated 7–9 million Roma in Europe, most are living in Central and Eastern Europe, where they are estimated to account for over 8% of the population in Bulgaria, Macedonia, Slovakia and Romania (see Table 1) [3-5]. With a long history of discrimination and social exclusion, many Roma are reluctant to identify as such in censuses or other surveys that elucidate ethnic origin. Estimates of the number of Roma in different countries vary significantly, which is
A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity
Matthew D. J. Dicks, Alexandra J. Spencer, Nick J. Edwards, G?ran Wadell, Kalifa Bojang, Sarah C. Gilbert, Adrian V. S. Hill, Matthew G. Cottingham
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040385
Abstract: Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent pre-existing anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunological comparison of multiple adenoviral vectors, we optimised a method for accurate determination of infectious titre, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estimation. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clinical trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titre >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clinical use.
On the Significance of Cryptography as a Service  [PDF]
Nick Rahimi, Jacob J. Reed, Bidyut Gupta
Journal of Information Security (JIS) , 2018, DOI: 10.4236/jis.2018.94017
Abstract: Cryptography as a service is becoming extremely popular. It eases the way companies deal with securing their information without having to worry about their customer’s information being accessed by someone who should not have access to it. In this overview, we will be taking a closer look at Cryptography as a Service. The ground we will be examining is the effectiveness of it for mobile/wireless and desktop computing. Since we will be looking at something that operates as a service, we will need to first cover the application program interface (API) basics [1] or standard software as a service (SaaS) [2]. Next, what exactly cryptography as a service means for each of the aforementioned platforms. Lastly, other possible solutions and how they compare to CaaS. For the purpose of this review, we will be looking at CaaS in a cloud environment since typical SaaS is used that way. Subsequently most cloud environments utilize a UNIX based operating system or similar solution, which will be the target environment for the purpose of this paper. Popular algorithms that are used in CaaS will be the final part that will be examined on the grounds of how they perform, level of security offered, and usability in CaaS. Upon reading this paper the reader will have a better understanding of how exactly CaaS operates and what it has to offer for mobile, desktop, and wireless users in the present and future.
P. J. Spencer
Journal of Venomous Animals and Toxins , 1996, DOI: 10.1590/s0104-79301996000200011
Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress
Sarah J. Spencer
Frontiers in Neuroscience , 2013, DOI: 10.3389/fnins.2013.00109
Abstract: Feeding behavior is closely regulated by neuroendocrine mechanisms that can be influenced by stressful life events. However, the feeding response to stress varies among individuals with some increasing and others decreasing food intake after stress. In addition to the impact of acute lifestyle and genetic backgrounds, the early life environment can have a life-long influence on neuroendocrine mechanisms connecting stress to feeding behavior and may partially explain these opposing feeding responses to stress. In this review I will discuss the perinatal programming of adult hypothalamic stress and feeding circuitry. Specifically I will address how early life (prenatal and postnatal) nutrition, early life stress, and the early life hormonal profile can program the hypothalamic-pituitary-adrenal (HPA) axis, the endocrine arm of the body's response to stress long-term and how these changes can, in turn, influence the hypothalamic circuitry responsible for regulating feeding behavior. Thus, over- or under-feeding and/or stressful events during critical windows of early development can alter glucocorticoid (GC) regulation of the HPA axis, leading to changes in the GC influence on energy storage and changes in GC negative feedback on HPA axis-derived satiety signals such as corticotropin-releasing-hormone. Furthermore, peripheral hormones controlling satiety, such as leptin and insulin are altered by early life events, and can be influenced, in early life and adulthood, by stress. Importantly, these neuroendocrine signals act as trophic factors during development to stimulate connectivity throughout the hypothalamus. The interplay between these neuroendocrine signals, the perinatal environment, and activation of the stress circuitry in adulthood thus strongly influences feeding behavior and may explain why individuals have unique feeding responses to similar stressors.
Physical activity, weight status and diet in adolescents: are children meeting the guidelines  [PDF]
Spencer E. Boyle, Georgina L. Jones, Stephen J. Walters
Health (Health) , 2010, DOI: 10.4236/health.2010.210167
Abstract: Childhood obesity is on the increase and maintaining regular physical activity and consuming a healthy diet have become essential tools to combat the condition. The United Kingdom government has recommended guidelines for optimal levels of diet and activity in children. The aim of this paper is to describe and compare self-reported physical activity levels, diet, and Body Mass Indices (BMI) amongst adolescent children, aged 11-15, in the South West (SW) and North West (NW) regions of England and to see if these children were meeting the current targets for optimal levels of: physical activity; fruit/vegetable consumption; fat consumption and BMI. We report the results of a cross-sectional survey of four secondary schools and 1,869 children using the self-reported Western Australian Child and Adolescent Physical Activity and Nutrition Survey (CAPANS) physical activity instrument and a food intake screener questionnaire, in summer and winter. We found that 25% (469/1869) 95% CI: 23% to 27%, of children engaged in 60 minutes of moderate to vigorous physical activity per day; 53% (995/1866) 95% CI: 51% to 56%, took 5 portions of fruit and vegetables per day; while 22% (407/1861) 95% CI: 20% to 24% consumed recommended amount of fats, and 23.7% (276/1164) 95% CI: 21% to 26%, of pupils were obese or overweight as classified by their BMI. Self reported physical activity in young people regardless of area is lower than previously reported and the lack of students engaging in 60 minutes moderate to vigorous activity could have serious public health consequences. If sustained, this could lead to more overweight adults, and more ill health.
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