Characterization of tumour-infiltrating lymphocytes and apoptosis in colitis-associated neoplasia: comparison with sporadic colorectal cancer

The development of colorectal cancer is a major complication for patients with chronic idiopathic colitis. Colitis-associated tumours tend to occur at a younger age and be more aggressive than sporadic colorectal cancers. While we have previously associated the presence of tumour-infiltrating lymphocytes (TILs) and increased apoptosis in sporadic colorectal cancer with high-level microsatellite instability and improved prognosis, little is known of the relationship between these variables in colitis-associated colorectal cancer. The aim of this study was to correlate TILs and tumour cell apoptosis in colitis-associated neoplasms stratified according to microsatellite instability. Twenty tumour and 11 dysplastic samples resected from 21 patients with long-standing colitis were analysed for microsatellite instability at 10 microsatellite markers. TIL distribution (CD3, CD8) and function (granzyme B) were quantified by immunohistochemistry. Neoplastic cell apoptosis was assessed using the M30 CytoDEATH antibody. These findings were compared with 40 microsatellite stable (MSS) sporadic colorectal cancers previously evaluated for TILs and neoplastic apoptosis. Low-level microsatellite instability was found in 1/20 colitis-associated tumours. All other colitis-associated lesions were designated MSS. CD3(+) and CD8(+) TIL counts were significantly higher in colitis-associated lesions compared with NISS sporadic colorectal cancer (p < 0.0001, p = 0.001 respectively). Despite their higher TIL density, colitis-associated tumours were more likely to present late (Dukes' stage C or D) (P = 0.02). Functionally, colitis-associated TILs demonstrated significantly less granzyme B expression compared to sporadic cancers (p = 0.002). The level of tumour cell apoptosis was similar between the two groups (sporadic, 1.53%; colitis cancers, 1.45%). In conclusion, NISS colitis-associated tumours have a higher prevalence of CD3(+)/CD8(+) TILs but no associated increase in tumour cell killing by apoptosis. Unlike cytotoxic T cells in sporadic colorectal cancer, TILs do not appear to enhance the prognosis of colitis-associated colorectal cancer. This may be related to an impairment of granzyme B expression within these lesions. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

A comparative study of hospital management in Great Britain and Brazil : cost information use

In Great Britain and Brazil healthcare is free at the point of delivery and based study only on citizenship. However, the British NHS is fifty-five years old and has undergone extensive reforms. The Brazilian SUS is barely fifteen years old. This research investigated the middle management mediation role within hospitals comparing managerial planning and control using cost information in Great Britain and Brazil. This investigation was conducted in two stages entailing quantitative and qualitative techniques. The first stage was a survey involving managers of 26 NHS Trusts in Great Britain and 22 public hospitals in Brazil. The second stage consisted of interviews, 10 in Great Britain and 22 in Brazil, conducted in four selected hospitals, two in each country. This research builds on the literature by investigating the interaction of contingency theory and modes of governance in a cross-national study in terms of public hospitals. It further builds on the existing literature by measuring managerial dimensions related to cost information usefulness. The project unveils the practice involved in planning and control processes. It highlights important elements such as the use of predictive models and uncertainty reduction when planning. It uncovers the different mechanisms employed on control processes. It also depicts that planning and control within British hospitals are structured procedures and guided by overall goals. In contrast, planning and control processes in Brazilian hospitals are accidental, involving more ad hoc actions and a profusion of goals. The clinicians in British hospitals have been integrated into the management hierarchy. Their use of cost information in planning and control processes reflects this integration. However, in Brazil, clinicians have been shown to operate more independently and make little use of cost information but the potential signalled for cost information use is seen to be even greater than that of their British counterparts.

An analysis of fatal accidents in agriculture in Great Britain

The number of fatal accidents in the agricultural, horticultural and forestry industry in Great Britain has declined from an annual rate of about 135 in the 1960's to its current level of about 50. Changes to the size and makeup of the population at risk mean that there has been no real improvement in fatal injury incidence rates for farmers. The Health and Safety Executives' (HSE) current system of accident investigation, recording, and analysis is directed primarily at identifying fault, allocating blame, and punishing wrongdoers. Relatively little information is recorded about the personal and organisational factors that contributed to, or failed to prevent accidents. To develop effective preventive strategies, it is important to establish whether errors by the victims and others, occur at the skills, rules, or knowledge level of functioning: are violations of some rule or procedure; or stem from failures to correctly appraise, or control a hazard. A modified version of the Hale and Glendon accident causation model was used to study 230 fatal accidents. Inspectors' original reports were examined and expert judgement applied to identify and categorise the errors committed by each of the parties involved. The highest proportion of errors that led directly to accidents occurred whilst the victims were operating at the knowledge level. The mix and proportion of errors varied considerably between different classes of victim and kind of accident. Different preventive strategies will be needed to address the problem areas identified.

Developing the public health function of locum pharmacists under the auspices of the new pharmacy contract

Focal Point - There are reduced opportunities for locum pharmacists to access training and education that meets their needs and enables them to play a full role under the new pharmacy contract - Eighty-six per cent of locums consider themselves to be more health professional than business person, compared to just 48% of pharmacy owners - Forty per cent of locums believe that a lack of access to training is a major barrier to the development of their public health function - While locum pharmacists are arguably more likely to embrace 'professionalising', patient-care-based roles, they are also the group least likely to be able to access the necessary training to fulfill such roles Introduction It has been suggested that locum pharmacists do not want the business-based responsibilities (e.g. staff management, meeting targets, etc) that come with pharmacy management.1 Research also suggests that locums derive great satisfaction from the health-professional aspects of the pharmacists’ role (e.g. patient contact, the provision of advice, etc).1 However, upon the introduction of the new pharmacy contract (April 2005), concerns were expressed that it was becoming increasingly difficult for locum pharmacists to access training and education that would meet their needs and enable them to play a full role under the new framework.2,3 Method After piloting, in August 2006 a self-completion postal questionnaire was sent to a random sample of practising community pharmacists, stratified for country and sex, within Great Britain (n = 1998), with a follow-up to non-responders 4 weeks later. Data were analysed using SPSS (v12.0). A final response rate of 51% (n = 1023/1998) was achieved. Respondents were asked ‘indicate how you view yourself as a pharmacist’ – in terms of their relative focus on the health-professional and business aspects of their role. Respondents were also asked ‘do you consider a lack of training opportunities to be a barrier to the development of the public health role of community pharmacists?’. Results Locums were significantly more likely than owners or employees to consider each factor a major barrier. Discussion Four in 10 locums consider a lack of training opportunities to constitute a major barrier to the development of their public health function. Pharmacy may not be able to provide the services required of it by the policy agenda if pharmacists are unable to be involved in extended role activities through a lack of training opportunities. Therefore, the paradox that needs to be addressed is that while locum pharmacists are arguably more likely to embrace ‘professionalising’, patient-care-based roles, they are also the group least likely to be able to access training to fulfil such roles. The training needs of this large subset of the pharmacist population need to be assessed and met if the whole community pharmacy workforce is going to maximise its contribution to public health under the new contractual framework. References 1 Shann P, Hassell K. An exploration of the diversity and complexity of the pharmacy locum workforce. London: Royal Pharmaceutical Society of Great Britain; 2004. 2 Almond M. Locums – key players in workforce – cast adrift as contract launched. Pharm J 2005;274:420. 3 Bishop DH. A lack of appreciation of what really happens. Pharm J 2005;274:451.

The implications of internet auctions for small to medium sized enterprises (SMEs) in Great Britain

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Blastocyst environment and its influence on offspring cardiovascular health:the heart of the matter

The development of adult-onset diseases such as type II diabetes, obesity and cardiovascular disease is traditionally attributed to adult lifestyle characteristics such as a lack of physical exercise, poor diet and smoking. However, evidence from both human and animal model studies has demonstrated that environmental factors such as an imbalance or reduction in maternal nutrition during gestation can have adverse effects on offspring metabolism and cardiovascular health. The severity and nature of the phenotypic changes induced in offspring is influenced by the period of gestation manipulated. In particular, the mammalian preimplantation embryo in different animal models displays particular sensitivity to environmental factors, either in vivo (maternal diet) or in vitro (embryo culture) that is associated with the onset of cardiovascular dysfunction in adult life. The detailed mechanisms by which environmental conditions can alter postnatal cardiovascular physiology are poorly understood. However, various factors including endothelial function, vascular responsiveness, the renin-angiotensin system, kidney structure and early postnatal growth dynamics have all been recognize as potential contributors. Here, we review the relationship between preimplantation embryo environment and postnatal cardiovascular disease risk, and consider biochemical, molecular, genetic and physiological pathways implicated in this association. © 2009 The Authors Journal compilation © 2009 Anatomical Society of Great Britain and Ireland.

Impact of electric vehicles on GB electricity demand and associated benefits for system control

This paper investigates the impact that electric vehicle uptake will have on the national electricity demand of Great Britain. Data from the National Travel Survey, and the Coventry and Birmingham Low Emissions Demonstration (CABLED) are used to model an electrical demand profile in a future scenario of significant electric vehicle market penetration. These two methods allow comparison of how conventional cars are currently used, and the resulting electrical demand with simple substitution of energy source, with data showing how electric vehicles are actually being used at present. The report finds that electric vehicles are unlikely to significantly impact electricity demand in GB. The paper also aims to determine whether electric vehicles have the potential to provide ancillary services to the grid operator, and if so, the capacity for such services that would be available. Demand side management, frequency response and Short term Operating Reserve (STOR) are the services considered. The report finds that electric cars are unlikely to provide enough moveable demand peak shedding to be worthwhile. However, it is found that controlling vehicle charging would provide sufficient power control to viably act as frequency response for dispatch by the transmission system operator. This paper concludes that electric vehicles have technical potential to aid management of the transmission network without adding a significant demand burden. © 2013 IEEE.

In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2- methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom

Objectives Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a 'snakebite antidote'. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom. Methods The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice. Key findings The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene] -succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 μg/ml venom, was reversed by 2-16 μg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group. Conclusions The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source. © 2010 Royal Pharmaceutical Society of Great Britain.

Comparative physical, mechanical and crystallographic properties of a series of gemfibrozil salts

Objectives Understanding the impact of the counterion on the properties of an acidic or basic drug may influence the choice of salt form, especially for less potent drugs with a high drug load per unit dose. The aim of this work was to determine the influence of the hydrogen bonding potential of the counterion on the crystal structure of salts of the poorly soluble, poorly compressible, acidic drug gemfibrozil and to correlate these with mechanical properties. Methods Compacts of the parent drug and the salts were used to determine Young's modulus of elasticity using beam bending tests. Crystal structures were determined previously from X-ray powder diffraction data. Key findings The free acid, tert-butylamine, 2-amino-2-methylpropan-1-ol and 2-amino-2-methylpropan-1, 3-diol salts had a common crystal packing motif of infinite hydrogen-bonded chains with cross-linking between pairs of adjacent chains. The tromethamine (trsi) salt, with different mechanical properties, had a two-dimensional sheet-like network of hydrogen bonds, with slip planes, forming a stiffer compact. Conclusions The type of counter ion is important in determining mechanical properties and could be selected to afford slip and plastic deformation. © 2010 Royal Pharmaceutical Society of Great Britain.

Great Britain's Olympians with generalised joint hypermobility have a higher prevalence of knee osteoarthritis.

Purpose: Individuals with generalized joint hypermobility (GJH) are reported, in the clinical setting, to be at greater risk of developing musculoskeletal related joint pain, joint dislocations and tendinopathies. It is hypothesized that impaired static and dynamic neuromuscular movement control in those with GJH is responsible for contributing to an increased risk of injury and subsequent knee osteoarthritis (OA). Yet, to date, it remains unproven if there is an association between GJH and knee OA.

“Something radically wrong somewhere”: the kindred of the Kibbo Kift, 1920-1932

This thesis examines the Kindred of the Kibbo Kift, a co-educational outdoors organisation that claimed to be a youth organisation and a cultural movement active from August 1920 to January 1932. Originally part of the Boy Scouts and Girl Guides, the Kibbo Kift offers rich insight into the interwar period in Britain specifically because it carried forward late Victorian and Edwardian ideology in how it envisioned Britain. Members constructed their own historical narrative, which endeavoured to place the organisation at the heart of British life. The organisation’s internal life revolved around the unique mythology members developed, and the movement aspired to regenerate Britain after the First World War physically and spiritually. This thesis argues Kibbo Kift was a distinctive movement that drew upon its members’ intellectual preoccupations and ideals and inspired its members to create unique cultural artefacts. While the Kibbo Kift was ultimately too politically ambiguous to have lasting political impact on a national scale, examining the organisation offers important insight into intellectual thought and cultural production during the British interwar period. This thesis charts the changes the organisation underwent through its membership and the different trends of intellectual thought brought in by individual members, such as its leader, John Hargrave, brought to the group. It examines the cultural production of the organisation’s unique mythology, which created a distinctive historical narrative. It surveys gender issues within the organisation through the “roof tree”, an experimental family unit, and the group’s increasing anti-feminism. Finally, it considers how Clifford H. Douglas’ economic theory of social credit caused the Kibbo Kift to transform into the Green Shirts Movement for Social Credit and later into the Social Credit Party of Great Britain and Northern Ireland.