• Investigating the role of heatshock on diabetic wound healing

      Contractor, Taha (University of Chester, 2017-05)
      The increasing occurrence of diabetes in the general population as a result of over nutrition and increasingly inactive lifestyle has led to an obesity epidemic which is set to grow over time. With an ever increasing obese population type 2 diabetes and cardiovascular complications are set to become the major causes of human mortality. Chronic non healing wounds are a major cause of mortality and morbidity in patients with type 2 diabetes. They are predominantly caused by macrophage dysfunction and a lack of migration of fibroblasts into the wound. This study aimed to investigate diabetic wound healing through development of an artificial scratch assay. An in vitro scratch assay developed in WS1 cells. The effect of heat shock treatments from 39°C to 45° was tested to determine if cell migration increased; however, no significant difference was seen. Mitomycin C was used to determine if wound closure occurred as a result of cell proliferation and migration or migration alone. 10μg/ml of mitomycin C inhibited cell division by 79.9% without exhibiting cytotoxicity over a 12h period. The effect of hyperglycaemia and heat shock was also tested and showed no significant difference when compared to control conditions, suggesting that fibroblast migration in vivo is hindered through other factors such as debridement or macrophage dysfunction in the wound. GLUT4 is present in insulin sensitive organs (liver, adipose and muscle) and is the major glucose transporter responsible for the clearance of glucose from the blood after a meal, thus playing a central role in glucose homeostasis. Monocytes are precursors to macrophages and can easily be isolated from whole blood. They have also been shown to express GLUT4 in response to insulin and could be used as model to assess inflammation in diabetes. A glucose uptake assay was developed in U937 cells using a fluorescent glucose analogue, 2NBDG. 2NBDG fluorescence was shown to be competitively inhibited by increasing concentrations of glucose suggesting that 2NBDG enters the cell through glucose transporters. 2NBDG uptake was also assessed at different pH and in presence of membrane fluidizers (DMSO, benzyl alcohol and phenethyl alcohol). Extremes of pH significantly reduced cell viability and only at pH 4 was 2NBDG fluorescence significantly reduced. Treatment with DMSO showed that at high concentrations (≤ 1.56%) cell viability was reduced with a concurrent reduction in 2NBDG fluorescence. The effect of benzyl alcohol and phenethyl alcohol was foundto be insignificant at the concentrations and time points tested. The presence of GLUT4 was also determined by flow cytometry and Western blotting and found to be situated in the cytoplasmic region of the cell. This study indicates that monocytes and macrophages could be a potential therapeutic target to improve diabetic wound healing as they are a source of growth factors and cytokines that can bring about resolution of inflammation and it is their dysfunction in diabetic wounds that causes poor clinical outcomes.
    • An investigation into the numerical determinants of secondary sex ratio

      Lewis, Stephen J.; Glenn, Janine; Chester College of Higher Education (2000)
      Data from the North Wales parishes of Hawarden and Northop were found previously to show seasonality for birth rate. In keeping with values reported in other studies, the annual secondary sex ratio of 105.3% was found. This sex ratio was also found to vary throughout the year in a cyclical way with a peak occuring in late summer. When male and female birth rates were investigated separately, it was found that females showed a more pronounced cyclicity than males with the peaks for both sexes occuring in the spring. A significant negative correlation between sex ratio at birth and mean day lenght (hours between sunrise and sunset) of the putative month of conception was observed. Sex ratio is a useful but derived parameter and has no independant existence upon which natural selection can be said to exert a direct influence. Therefore, the behaviour of the determinants of sex ratio should not be overlooked.
    • An investigation of canine mesenchymal stem cells and their secretome in the context of spinal cord injury

      Johnson, Eustace; Wood, Chelsea R (University of Chester, 2020-05-26)
      Spinal cord injury (SCI) is a condition that has devastating effects on both humans and animals alike. Damage inflicted causes loss of neural tissue and secondary inflammatory mechanisms produce an inhibitory environment that results in partial or complete loss of motor and sensory functions. Additionally, SCI can cause multisystem issues such as organ failures, infections, muscle atrophy and decrease in mental health. Coupled with emotional and financial burdens, these effects can reduce quality of life. Mesenchymal Stem Cells (MSC) are known to have immunomodulatory, angiogenic and paracrine activity, all of which are beneficial to wound healing following SCI. Pre-clinical studies have shown encouraging results of MSC therapy for SCI, however replication of results has been difficult to achieve in the clinic. Dogs also suffer from SCI and show the same heterogenous nature and pathophysiology of SCI as humans. This provides a good potential clinical model for MSC therapies for SCI, as well as providing benefit in the veterinary clinic. Therefore, the overall aim of this study was to assess if canine MSC (cMSC) and cMSC secretome (conditioned medium; CM) could potentially be used for treatment of SCI in veterinary clinics, simultaneously providing model data that could be translated into the human clinic. It was first required to confirm efficacy of cMSC when used to treat other conditions in dogs, such as arthritis, along with safety of autologous transplantation. Characterisation of both cMSC phenotype and paracrine (angiogenic and neurogenic) activity was confirmed using ISCT criteria and the established cell lines EA.hy926 and SH-SY5Y. Further examination showed that exposure to certain elements of the injured spinal cord, such as CSPG which are found within the inhibitory glial scar, exerted some effects on cMSC and cMSC angiogenic and neurogenic paracrine activity. To finish, the study aimed to assess the effect of cMSC CM on an ex vivo model of the spinal cord, a multicellular environment and it was found that cMSC CM increased astrocyte reactivity but reduced neuronal maturation and growth, suggesting that cMSC paracrine activity depends in part on the spinal cord microenvironment. Overall, this study has shown that cMSC, in particular cMSC CM, could be used as complete or partial treatment for SCI in dogs.
    • An investigation of the test-retest reliability of an ultrasound densitometer

      Lamb, Kevin L.; Owen, David G. (University of Liverpool (Chester College of Higher Education), 18/10/1998)
      Army recruits undertake a rapidly increasing amount of exercise in their initial basic training period. Injuries due physical training forces many recruits out of the Army and costs the Ministry of Defence millions of pounds. Stress fractures are one of the most commonly diagnosed injuries amongst Army recruits. Low bone mineral density has been identified as a risk factor for stress fractures. A technique which can measure bone mineral density is Ultrasound Densitometry (US). This study will address a gap in the research by assessing the inter-observer and intra-observer reliability of the two US measurements, broadband ultrasound attenuation (BUA) and the velocity of sound (VOS). Ninety eight white male recruits, median aged 18 (I.Q. range 1yr) were measured at the calcanea of the non-dominant foot. A repeated measures design was used, BUA and VOS were measured in 55 subjects by both researcher 'A1 and 'B' for inter-observer (inter-BUA & inter-VOS), and 43 subjects were measured for BUA and VOS twice by researcher 'A' for the intra-observer analysis (intra-BUA & intra-VOS). The results from this study found that a coefficient of variation (CV) analysis was not appropriate for assessing measurement error, this was due to the homoscedasity of the data. An alternative method the '95% limits of agreement' found that only VOS was reliable. The '95% limits of agreement1 results (bias ±1.96 x s) were 0.74 ±22.77 m/s for intra-VOS and 4.85 ±23.44 m/s for inter-VOS, the variance in scores were judged to be acceptable, f-test confirmed this with a non-significant difference between measurements (t=0.83, p=0.477; t=0.42, p=0.677, respectively). The '95% limits of agreement1 results for BUA were -0.22±11.56 dB/MHz (inter-BUA) and -1.39 ±11.11 dB/MHz (intra-BUA). These results represent an unacceptable variability in the range of scores obtained. This is highlighted when expressed as a proportion of the mean measurement: inter-BUA ±11.41% and intra-BUA ± 11.91%. However, the West's for inter- and intra-BUA indicate no significant difference (t = -0.07, p = 0.091; t = 1.60, p = 0.116). This insignificance may be the result of the inappropriateness of a statistical method that reliance on a comparison of means. The CV results for BUA indicate that both inter- and intra-BUA are reliable (4.08% & 4.38%, respectively), even though as already stated that the BUA measurements are not deemed reliable when analysed by the '95% limits of agreement'. The results of this study suggest that VOS measurements are reliable and that BUA measurements are non-reliable. As both BUA and VOS would have been used to assess those at risk of suffering stress fractures it was essential that both were found to be reliable. Thus US's appropriateness in individual diagnosis is questioned. This study has also highlighted how the use of an inappropriate statistical method, in this case the CV, can effect the interpretation of data and cause false claims over e.g. reliability.
    • An investigation to determine the nutritional adequacy and individuals experience of a very low fat diet used to treat type V hypertriglyceridaemia

      Whitfield-Brown, Louisa M.; Hamer, O.; Ellahi, Basma; Burden, Sorrel; Durrington, Paul; University of Chester ; Manchester Royal Infirmary ; University of Chester ; Manchester Royal Infirmary ; University of Manchester (Wiley, 2009-05-15)
      This article discusses a study of eight patients with type V hypertriglyceridaemia on a low fat diet. The nutritional adequact of the diet and the barriers and enablers to adherence were analysed.
    • Involvement and detachment in researching sexuality: Reflections on the process of semistructured interviewing

      Perry, Catherine; Thurston, Miranda; Green, Ken; University College Chester (SAGE, 2004-01-01)
      This article discusses the utility of the concept of involvement-detachment for involved in the study of the lifeworlds of gay, lesbian, and bisexual young people where one of the researchers was a lesbian. The processes of semistructured interviewing and the benefits of teamwork in research are discussed.
    • Involvement of recreational anglers in the eradication of alien brook trout from high altitude lakes

      Tiberti, Rocco; Ottino, Michelle; Brighenti, Stefano; Iacobuzio, Rocco; Rolla, Matteo; von Hardenberg, Achaz; Bassano, Bruno; Gran Paradiso National Park, University of Pavia, Università degli studi di Trento, Fondazione E. Mach, Università degli Studi di Milano, Swansea University, University of Chester (Gran Paradiso National Park Agency, 2017)
      Stocking programmes for recreational angling are primarily responsible for the spread and ecological impact of introduced sh in high-altitude, originally shless lakes. In 2013, the Gran Paradiso National Park started an eradication campaign of brook trout by intensive gill-netting. Local anglers were invited to attend two angling sessions to start the eradication before gill-netting in an experimental lake, as part of an education action devoted to these critical stakeholders. The angling sessions turned out to be a valuable help for the eradication campaign and the aim of this study is to report on the outcomes of these angling sessions. Angling techniques were highly size-selective, removing a substantial part of the adult population and of the sh biomass, but their contribution to the eradication of small sh (<15cm) was irrelevant. Therefore, angling cannot completely eradicate age-structured populations. However, there is scope to use angling sessions as a support for eradication campaigns and as an emergency measure for recent sh introduc- tions. Similar actions should be considered whenever a sh eradication programme is planned. These ndings, however, do not imply a general endorsement for angling within protected areas.
    • Is cortisol a reliable indicator of primate well-being?

      Skyner, Lindsay J.; Smith, Tessa E.; University of Chester (Primate Society of Great Britain, 2006-06)
    • Is Wounding Aggression in Zoo-housed Chimpanzees and Ring-tailed Lemurs related to Zoo Visitor Numbers?

      Hosey, Geoff; Melfi, Vicky; Formella, Isabel; Ward, Samantha J.; Tokarski, Marina; Brunger, Dave; Brice, Sara; Hill, Sonya P.; University of Bolton; Taronga Zoo; South Lakes Wild Animal Park; Nottingham Trent University; Chester Zoo; University of Chester (Wiley, 2016-02-29)
      Chimpanzees in laboratory colonies experience more wounds on week days than on weekends, which has been attributed to the increased number of people present during the week; thus the presence of more people was interpreted as stressful. If this were also true for primates in zoos, where high human presence is a regular feature, this would clearly be of concern. Here we examine wounding rates in two primate species (chimpanzees Pan troglodytes and ring-tailed lemurs Lemur catta) at three different zoos, to determine whether they correlate with mean number of visitors to the zoo. Wounding data were obtained from zoo electronic record keeping system (ZIMS™). The pattern of wounds did not correlate with mean gate numbers for those days for either species in any group. We conclude that there is no evidence that high visitor numbers result in increased woundings in these two species when housed in zoos.
    • Isn’t it good, Norwegian wood? Lifestyle and adventure sports participation among Norwegian youth

      Green, Ken; Thurston, Miranda; Vaage, Odd; University of Chester; Hedmark University College; Norsk Statistisk Sentralbyra (Taylor & Francis, 2014-08-19)
      Based primarily on quantitative data from the Norwegian Statistisk Sentralbyrå (Statistics Norway) study of Mosjon, Friluftsliv og Kulturaktiviteter (Vaage, 2009) supplemented by a little qualitative data, this paper explores Norwegian youngsters’ (and, to a lesser extent, adults’) engagement with conventional and lifestyle sports via an examination of recent trends. Norway boasts particularly high levels of sports participation as well as sports club membership among young people and young Norwegians are the quintessential sporting omnivores. Nevertheless, among the age group where regular participation peaks in Norway (16-19-year-olds) the popularity of games declined over the decade 1997-2007 while participation in lifestyle sports continued to increase (Vaage, 2009). It seems that the particular mix of conventional and lifestyle sports that Norwegian youngsters favour has shifted within a generation, with lifestyle activities more prominent in 2007 than they had been even a decade earlier. The changes in participation in a particular area of sporting participation strongly associated with Norwegian culture – friluftsliv (outdoor life) – may well represent a shift among Norwegian youth towards sports and physical activities that offer alternative forms, as well as types, of participation to conventional sports. They may also represent alternative motivations to those traditionally associated with sport and, for that matter, friluftsliv. The paper draws upon these findings in order to tentatively hypothesize developments in youth leisure-sport in Norway.
    • Isoform-specific Ras signaling is growth factor dependent

      Hood, Fiona E.; Klinger, Bertram; Newlaczyl, Anna U.; Sieber, Anja; Dorel, Mathurin; Oliver, Simon P.; Coulson, Judy M.; Bluthgen, Nils; Prior, Ian A.; University of Liverpool; Universitätsmedizin Berlin; University of Chester (ASCB, 2019-04-11)
      HRAS, NRAS and KRAS isoforms are almost identical proteins that are ubiquitously expressed and activate a common set of effectors. In vivo studies have revealed that they are not biologically redundant; however, the isoform-specificity of Ras signaling remains poorly understood. Using a novel panel of isogenic SW48 cell lines endogenously expressing wild type or G12V mutated activated Ras isoforms we have performed a detailed characterization of endogenous isoform-specific mutant Ras signaling. We find that despite displaying significant Ras activation, the downstream outputs of oncogenic Ras mutants are minimal in the absence of growth factor inputs. The lack of mutant KRAS-induced effector activation observed in SW48 cells appears to be representative of a broad panel of colon cancer cell lines harboring mutant KRAS. For MAP kinase pathway activation in KRAS mutant cells, the requirement for co-incident growth factor stimulation occurs at an early point in the Raf activation cycle. Finally, we find that Ras isoform-specific signaling was highly context dependent and did not conform to the dogma derived from ectopic expression studies.
    • “It is always going to change” – examining the experiences of managing top-down changes by sport development officers working in national governing bodies of sport in England

      Thompson, Anne; Bloyce, Daniel; Mackintosh, Chris; Manchester Metropolitan University; University of Chester
      Research question: This article examines how sport development officers (SDOs) employed within national governing bodies of sport (NGB) managed Sport England’s top-down policy changes from 2008 to 2015. The main research question examines the experiences of SDOs as they responded to, and managed these changes at the community level. Research methods: In-depth, semi-structured interviews gathered qualitative data from 18 employees from four NGBs, including 6 SDOs, Chief Executive Officers (CEOs), senior managers and a representative from Sport England, with responsibility for policy formulation. Results and Findings: SDOs felt increasingly constrained in how they worked due to the intensification of a top-down and cyclical process of change, a result-orientated approach and the sporting habitus of SDOs. These factors combined to create resistance among some SDOs as the power differentials within the interdependencies formed, which contributed to the unintentional outcome of elongating the time taken to implement policy on the ground. Implications: This article has developed more object-adequate insights into how SDOs have responded to, and managed top-down policy implementation. The article suggests recommendations for policy-makers, Sport England and NGBs, to consider the dynamic interdependencies in which employees are bound and a more rounded and processual view to policy formulation and implementation
    • ‘It’s alpha omega for succeeding and thriving’: Parents, children and sporting cultivation in Norway

      Johansen, Patrick F.; Green, Ken; Innland University Norway; University of Chester (Taylor & Francis, 2017-11-13)
      It has become increasingly apparent, internationally, that childhood is a crucial life-stage in the formation of predispositions towards sports participation and that parents are increasingly investing in the sporting capital of their children via a process of ‘concerted cultivation’. It is surprising, therefore, that parents’ involvement in the development of their children’s sporting interests has received so little attention in Norway, given that sport is a significant pastime for Norwegians and participation has been steadily increasing – among youngsters, in particular – over the past several decades. Through a qualitative case study of a combined primary and secondary school in a small Norwegian city, this study sought to add to recent explorations of the role of parents in children’s sporting involvement in Norway. As expected, it was evident that sport becomes taken for granted and internalized very early on in Norwegian children’s lives. Less expected was the recognition that children’s nascent sporting interests were often generated by sports clubs via early years schooling and, therefore, that parents played only one (albeit very important) part in the formation of their youngsters’ early sporting habits. Thus, parents, sports clubs and early years schooling appeared to form something akin to a ‘sporting trinity’ in youngsters’ nascent sporting careers. These findings may have implications for policy-makers looking towards Norway for the ‘recipe’ for sports participation.
    • John Moores and the ‘professional’ baseball leagues in 1930s England

      Bloyce, Daniel; University of Chester (Routledge, 2007-03)
      This article discusses an attempt, inspired and mainly financed by John Moores, to establish baseball in England in the 1930s. ‘Professional’ leagues were set up in 1936 in Lancashire, Yorkshire and London. However, the English press, particularly the national press, failed to support the development of baseball in England.
    • ‘Just stretch it out and try to dance’: Young Irish dancers’ views and experiences of pain and injury

      Pentith, Rebecca; McEvilly, Nollaig; University of Chester (Graduate Journal of Sport, Exercise & Physical Education Research, 2018-11-16)
      Dancers frequently experience pain and injury due to the physical demands of performance. Previous research primarily focuses on professional dancers over the age of 18 years, and Irish dance has been largely unexplored, with research from a sociological perspective particularly lacking. To address these gaps, the purpose of this study was to explore the influence of the culture of Irish dance on young female dancers’ views and experiences of pain and injury. Data were generated through semi-structured interviews with eight girls (aged 11-16 years) from an Irish dance academy in the North West of England. We analysed the data by engaging in thematic analysis, and drew on Bourdieu’s concepts (habitus and capital, in particular) to explain our findings. Key themes within the data were: the values of Irish dance; trust and teamwork; and strength and weakness. The findings show that Irish dancers make sacrifices to achieve success, and the culture of Irish dance encourages them to dance through pain and injury in order to appear strong. While dancers recognise the potential consequences of injury and believe it is beneficial to take time away from training to recover, they are often encouraged (and encourage each other) to persevere through pain and injury. The findings suggest that there are some potentially harmful consequences of the Irish dance culture, as pain and injury are normalised. We suggest that coaches (and parents/guardians) should encourage young dancers to engage with self-care, and ensure they are not risking their future health and wellbeing by dancing through pain and injury.
    • Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study

      Martin-McGill, KJ; Marson, Anthony; Tudur Smith, Catrin; Young, Bridget; Mills, Samantha; Cherry, M. Gemma; Jenkinson, Michael; University of Chester; University of Liverpool; The Walton Centre NHS Foundation Trust;
      Purpose We conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients’ quality of life and health; (iii) patients’ perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials. Methods A single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modifed ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n=15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo. Results KEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n=3; MKD n=1). Participants’ decisions were intuitive and emotional; caregivers supported diet implementation and infuenced the patients’ decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew. Conclusion Recruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregiver should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.
    • Ketogenic diets for drug-resistant epilepsy

      Martin-McGill, Kirsty J; Bresnahan, Rebecca; Levy, Robert G; Cooper, Paul N; University of Chester; University of Liverpool; The CroD ShiDa Health Centre, Rochdale; Salford Royal Hospitals NHS Trust
      Background Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018. Objectives To assess the effects of ketogenic diets for people with drug-resistant epilepsy. Search methods For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies. Selection criteria RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy. Data collection and analysis Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs). Main results We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction(RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD aDer three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction.Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD)and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate.The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD,whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate.Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported. Authors' conclusions The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associatedr isk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty.More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.
    • Kicking against tradition: A career in women's football

      Owen, Wendy (Tempus, 2005-06-01)
      This book is the autobiography of former English international footballer Wendy Owen. It discusses the rise of women's football in England after the success of the 1966 World Cup and how women's football was slowly accepted by the FA and society in general.
    • Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

      Saunders, Philippa M.; Pymm, Phillip; Pietra, Gabriella; Hughes, Victoria A.; Hitchen, Corinne; O'Connor, Geraldine M.; Loiacono, Fabrizio; Widjaja, Jacqueline M.; Price, David A.; Falco, Michela; et al. (Rockefeller University Press, 2016-04-04)
      NK cells play a key role in immunity, but how HLA-I and KIR3DL1 polymorphism impacts on disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognising the widest array of HLA-I ligands. These differences were further reflected in unctional studies utilising NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005 and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.