Now showing items 1-20 of 5769

    • Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells

      Sheard, Jonathan J.; Southam, Andrew D.; MacKay, Hannah L.; Ellington, Max A.; Snow, Martyn D.; Khanim, Farhat L.; Bunce, Christopher M.; Johnson, William E.; orcid: 0000-0002-7247-9087 (Portland Press Ltd., 2021-01-05)
      Abstract Drug repurposing is a cost-effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts.
    • Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study

      Ruiz-Casas, Leonardo; O’Hara, Sonia; orcid: 0000-0002-9119-8336; Mighiu, Claudia; Finnegan, Alan; Taylor, Alison; Ventura, Emily; Dhawan, Anil; Murray, Karen F; Schattenberg, Jorn; orcid: 0000-0002-4224-4703; Willemse, Jose; et al. (Informa UK Limited, 2021-01-07)
    • Real-world evidence on Kovaltry (81-8973) in children with moderate or severe hemophilia A in Europe: a nested cohort analysis

      O’Hara, Jamie; Hirst, Ceri; orcid: 0000-0001-9094-2437; email: ceri.hirst@bayer.com; Cabre Marquez, Jose Francisco; Burke, Tom (BioMed Central, 2021-01-15)
      Abstract: Background: Untreated hemophilia A patients may experience recurrent bleeding events leading to debilitating joint damages. While RCT and pharmacokinetic data support the value of Kovaltry [an unmodified full-length recombinant factor VIII (FVIII) product], real world evidence in children is lacking. This report describes a descriptive and multivariate analysis of the effectiveness of Kovaltry in children with hemophilia A in the real-world setting, using data from medical chart abstraction and cross-sectional surveys of physicians, patients, and caregivers. Results: Male patients aged < 18 years with moderate or severe hemophilia A, residing in five European countries and treated with FVIII were studied. The co-primary endpoints were the annualized bleeding rate (ABR) and the annual FVIII utilization rate. Twenty nine patients treated with Kovaltry were included, of whom 93% had severe disease and 75% were on continuous prophylactic treatment. The mean ABR was 2.66 ± 2.06, with rates decreasing with age. The children received on average 2.45 infusions per week, consistent across age groups (median 3; range 1–3). There were no reports of inhibitor development or adverse events in the study (AEs), and all patients were satisfied or very satisfied with the treatment. An exploratory multivariate analysis suggests no significant difference in ABR or units utilized between Kovaltry and some extended half life products in children with severe hemophilia A, though characteristics of these patient cohorts were markedly different. Conclusion: This analysis demonstrates the effectiveness and safety of Kovaltry in a pan-European pediatric population with severe hemophilia A.
    • COVID-19 presenting as intussusception in infants: A case report with literature review

      Athamnah, Mohammad N.; Masade, Salim; Hamdallah, Hanady; orcid: 0000-0001-6314-0236; Banikhaled, Nasser; Shatnawi, Wafa; Elmughrabi, Marwa; Al Azzam, Hussein S.O. (Elsevier, 2021-01-12)
      The novel Corona virus disease 2019 (COVID-19) first presented in Wuhan, China. The virus was able to spread throughout the world, causing a global health crisis. The virus spread widely in Jordan after a wedding party held in northern Jordan. In most cases of COVID-19 infection, respiratory symptoms are predominant. However, in rare cases the disease may present with non-respiratory symptoms. The presentation of COVID-19 as a case of intussusception in children is a strange and rare phenomenon. We present here a case of a two-and-a-half month old male baby who was brought to hospital due to fever, frequent vomiting, dehydration and blood in stool. He was diagnosed as intussusception. The child was tested for corona due to the large societal spread of the virus and because he was near his mother, who was suffering from symptoms similar to corona or seasonal flu (she did not conduct a corona test). Patient was treated without surgery and recovered quickly. The COVID-19 infection was without respiratory symptoms, and there was no need for the child to remain in hospital after treatment of intussusception. The relationship between viruses, mesenteric lymphoid hyperplasia, and intussusception is a confirmed relation. ACE2 is the key receptor required for SARA-COV-2 to enter the host cells. ACE2 has been also found in the brush border of the intestinal mucosa, as well as it is a key inflammatory regulator in the intestine. This may suggest that SARSA-COV-2 could invade the respiratory tract as well as gastrointestinal tract or both. Few case reports documented the presentation of COVID-19 as intussusception in children. In the light of the wide-spread of corona virus, performing COVID-19 tests for children with intussusception can help linking the two entities. Development of gastrointestinal symptoms in COVID-19 positive children should raise concern about the development of intussusception.
    • Are Prisoners More Psychopathic than Non-forensic Populations? Profiling Psychopathic Traits among Prisoners, Community Adults, University Students, and Adolescents

      Boduszek, Daniel; orcid: 0000-0001-5863-2906; Debowska, Agata; Sherretts, Nicole; Willmott, Dominic; Boulton, Mike; Kielkiewicz, Krzysztof; Popiolek, Katarzyna; Hyland, Philip (Informa UK Limited, 2019-09-12)
    • Refining the blank line‐up procedure: How should we instruct eyewitnesses?

      Kucina, Talira; Sauer, James D.; Holt, Glenys A.; Brewer, Neil; Palmer, Matthew A.; orcid: 0000-0002-3467-3364 (Wiley, 2020-08-19)
    • Universal credit, Lone mothers and poverty: Some context and challenges for social work with children and families

      Carey, Malcolm; University of Chester
      Universal Credit is a streamlined benefits delivery system initially introduced in the United Kingdom (UK) in 2008. Conditionality-based welfare policies are increasingly international in scale, and are now widely adopted by neoliberal governments on the basis that paid employment offers the most efficacious route out of poverty for citizen-subjects. Numerous studies suggest otherwise, and highlight their negative impact upon the social rights, lived experiences, and attempts to alleviate poverty for service users. This article analyses the reformed benefit system and wider workfare policies effect upon lone mothers, including as a consequence of engagement with an ever more stigmatizing benefit system, and associated risks posed by sanctions or precarious low-paid employment. It highlights some of the consequences for social work with children and families of Universal Credit: including ongoing tensions and challenges created for the profession by the punitive policies of the workfare-orientated centaur state.
    • Leading brand products and their supermarket economy line equivalents, is there a difference in nutritional content?

      Mushtaq, Sohail; Jackson, Emma; University of Chester
      Since the introduction of supermarket economy lines (SELs) in the early 1990s, their popularity has been established nationwide(1).However, these economical alternatives are commonly perceived to be of lower nutritional quality than their leading brand (LB)equivalents(2,3,4). The present study aimed to determine if there is a significant difference in nutritional content between the UKtop-selling LBs and their SEL equivalents. Additionally, the study aimed to investigate if on average, LBs or SELs provide better‘value for money’.The LBs of 38 most popular food categories were identified from UK market research, and equivalent SEL products were identifiedfrom each of the retailers with the top-five majority UK market share: Tesco, Sainsbury’s, Asda, Morrisons and Aldi. In each foodcategory, differences between LBs and SELs in: energy, fat, saturated fatty acid, carbohydrate, sugar,fibre, protein and salt content,per 100 g of food product were determined using a one-sample T-test. The nutritional quality of each product was also determined bya nutrient profiling system. Cost was analysed in relation to shopping baskets containing 33 equivalent products. Six shopping basketswere analysed, one containing LB products and one from each SEL retailer. The cost of each shopping basket was calculated usingpack price and price per 100 g or 100mL of food product.Data was collected for 219 products; 38 LBs and 181 SELs. 86 significant differences were identified in specific nutrients across thefood categories, but the direction of the differences was inconsistent. Based on pack price, the total LB shopping basket cost was£61·91 whereas average SEL basket cost £28·62, a difference of £33·29 or 54 % (P = 0·001). However, there was no difference betweenthe nutrient profile of LBs and SELs.Although significant differences were identified between nutrients in some food categories, overall, there appeared to be no differ-ence in nutritional content between LBs and SEL equivalents. This association is consistent with previous studies and is contrary tothe common perception that SELs are of lower nutritional quality than LBs(2,3,4,5,6). Pertinent to public health, the present studyfound that SEL breakfast cereals contained a significantly higher amount of salt than the LB (P = 0·035)(4,6). Additionally, althoughthe majority of food categories did not show a significant difference in energy content per 100 g of food product (29 of 38) LB pastahad significantly higher energy content per 100 g of food product than SEL equivalents (P = 0·017)(6).In conclusion, there appears to be no difference in nutritional content between the LB and SEL equivalents in 38 popular foodcategories, however, there appears to be twofold difference in price The cost analysis demonstrates that consumers can purchasethe same quantity of foodstuff for significantly less when opting for SEL products. Low income households may therefore be encour-aged to purchase SEL products to reduce weekly household expenditure and enable a greater proportion of the budget to be availablefor the purchase fresh produce such as fruit, vegetables and meat
    • Estimates of fibre intake and percentage of the population with intake below the dietary reference values (DRVs) in England (1991–2015)

      Mushtaq, Sohail; Farzad, Amirabdollahian; Buczkowski, Bartek; Davies, Ian; University of Chester
      In 1991, the Committee on Medical Aspects of Foods (COMA) defined dietary fibre as non-starch polysaccharides (NSP) and set the DRV as the population average intake of 18 g/day 1 , determined using the Englyst method of analysis 2 . The latest publication of the Scientific Advisory Committee on Nutrition (SACN) 3 broadened the definition of dietary fibre beyond NSP to broader definition of Association of Analytical Communities (AOAC) fibre, recommending the DRV to be 30 g/day based on AOAC method. The COMA 1991, DRV of 18 g/day of NSP corresponds to around 24 g/day of AOAC fibre 3 and therefore the new DRV of fibre would represent a higher recommendation (around 22·5 g fibre as per the Englyst method) for the average population. The purpose of this study was to investigate variation in fibre intake of English population by age and gender, in comparison with the COMA and SACN DRVs. Data on the core sample of the National Diet and Nutrition Survey rolling programme from 2008–2012 was reanalysed. Children aged below 16 years were excluded in consideration of their different DRVs. The data on dietary fibre was extracted from fully productive individuals (i.e. participants who completed three/four diary days), as an average daily intake based on the NSP/Englyst fibre. Inferential statistics included the analysis of variance to discover if there were any significant variations in fibre intake of males and females in relation to their age groups. The statistical significance was set at 0·05. For all age groups, the average fibre intake is below the DRVs. The average daily fibre intake slightly increased with age for both genders until 64 years. When differences in energy intake were taken into account, the average daily fibre density (g/1000 kcal) still increased with the age of participants. Overall, less than a third of populations had an intake above the COMA DRV 1 . More than 90 % of the population had intake below the SACN DRV 3 , demonstrating a challenge for future policies to meet the nutritional guidelines, particularly amongst females and younger adults. The findings should be treated with caution considering the definition of AOAC fibre used as the basis for the SACN DRV includes non-digestible oligosaccharides, resistant starch and polydextrose, going beyond NSP/Englyst variables analysed.
    • Full fat cheese intake and cardiovascular health: a randomised control trial

      Mushtaq, Sohail; Butler, Thomas; Davies, Ian; University of Chester
      Milk and milk products contribute approximately 22 % of the nation's saturated fat (SFA) intake. Recently, the role of dairy and its SFA composition and link to cardiovascular disease (CVD) has been analysed( 1 ), suggesting a beneficial action of this food group on reducing cardiovascular risk in high-risk groups( 2 , 3 ). The aim of this study was to examine the effects of 4 weeks full-fat cheese on circulating lipoprotein fractions, blood pressure and arterial stiffness in healthy adults. Participants were recruited in the city of Chester, UK. Those meeting entry criteria of: 18–65 years of age, not taking antihypercholesterolaemic or antihypertensive medication took part in the study. Participants were randomised to receive either 50 g of a full-fat Red Leicester (FFC) or placebo (virtually zero fat Cheddar cheese, ZFC) per day for 4 weeks. Anthropometry, blood pressure, brachial and aortic augmentation index (BAIX and AAIX, respectively), pulse-wave velocity (PWV) and a full lipid profile were determined at baseline and post-intervention. Participants were asked to keep a 3-day food diary prior to and for the last 3 days of the protocol. All procedures were approved by the Faculty of Medicine, Dentistry and Life Sciences Research Ethics Committee at the University of Chester. Eighty-six (86) individuals completed the study (43 per group). No significant changes were observed in any measured parameter (Table 1). Both ZFC and FFC groups showed a significant increase in calcium intake during the course of the study (1002·1 ± 639·1 mg to 1815·0 ± 1340·1 mg and 1219·6 ± 1169·1 mg 1845·8 ± 1463·2 mg, P < 0·001, respectively) showing good adherence to the protocol. In conclusion, these results suggest that inclusion of 50 g full fat cheese into the diet of a healthy population does not impact negatively on traditional CVD risk markers. Future strategies to reduce SFA intake should focus on – and acknowledge the importance of the source – of SFA in the diet.
    • Effect of a single serving of pecan nuts on blood lipids and weight: a single blind randomised control trial

      Mushtaq, Sohail; Butler, Thomas; Confue, Charlotte; Guild, Joanne; University of Chester
      Nuts are a common component of many traditional cardioprotective diets primarily due to their ability to lower blood lipids and reduce cardiovascular risk(1, 2). Studies consistently show nut intake is associated with favourable changes in energy balance(3). However there is a paucity of data examining the acute changes following nut consumption. We sought to examine the effect of a single serving of pecan nuts on plasma lipids and bodyweight. Participants were sampled from the University of Chester, UK. Individuals (n = 54) were screened for eligibility to participate. Those meeting entry criteria (n = 25) of being either male or female aged 30 years or more and with no previous history of CVD were randomised to either a control (CON) or pecan nut group (PECAN). Participants in the PECAN group received a single 50 g serving of pecan nuts. Capillary blood was taken for analysis of triacylglycerol, total-cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein-cholesterol and non-high density lipoprotein cholesterol (TAG, TC, LDL-C, HDL-C and non-HDL-C, respectively), and anthropometric measurements were performed. All measurements were repeated after 3 days. Participants were instructed to record all food and drink consumed, and not to change their habitual eating habits. Procedures were approved by the Faculty of Medicine, Dentistry and Clinical Sciences Research Ethics Committee, University of Chester. No significant effect on TC, HDL-C or TAG was observed during the study (Fig. 1A–C). LDL-C decreased by 0.09 ± 0.37 mmol/L and increased by 0.16 ± 0.40 mmol/L in CON and PECAN groups, respectively. Non-HDL-C showed a similar pattern with the CON group showing a decrease and PECAN group displaying an increase (−0.18 ± 0.36 mmol/L vs. 0.16 ± 0.40 mmol/L, respectively). Bodyweight significantly (P = 0.025) decreased in the PECAN group when compared to the CON group (−0.58 ± 0.56 kg vs. −0.05 ± 0.55 kg, respectively). In conclusion, a single serving of pecan nuts had no significant impact on lipid markers of cardiovascular risk. Bodyweight was significantly reduced consistent with recent literature showing a favourable relationship with nut intake and energy balance(3).
    • Acute and chronic effects of beetroot supplementation on blood pressure and arterial stiffness in humans

      Mushtaq, Sohail; Turner, Emma; University of Chester
      Dietary supplementation of beetroot juice, containing nitrate- a potent vasodilation agent, has been shown to be vasoprotective( 1 ), and dose dependent decreases in blood pressure (BP) have been previously demonstrated(2,3). To our knowledge there has been only one study investigating the effect of beetroot supplementation in humans on arterial stiffness, measured using pulsewave velocity (PWV) and, although there was no effect of supplementation on PWV, there was a significant reduction due to beetroot supplementation in acute diastolic BP (3hrs, P = 0·023)( 4 ). A double-blind, randomised, cross-over intervention trial was carried out in a cohort of 12 healthy male participants (mean age (SEM) = 43 (2·1) yrs, BMI = 27·8 (1·1) kg.m2) who underwent both beetroot juice and placebo supplementation for 14 days. The aim of the study was to assess the effect of 6·45 mmol of nitrate in a concentrated 70 ml beetroot drink (James White Ltd, Ipswich, UK) on systolic and diastolic BP, mean arterial pressure (MAP) and arterial stiffness (PWV, aortic augmentation index (Aix), brachial Aix) in humans. BP and arterial stiffness measurements weretaken using PWV (Arteriograph, TensioMed,Hungary). Measurements were taken intriplicate at baseline, 3 hours post-supplementation (either beetroot juice orplacebo) and post-intervention (day 15). This was followed by a 7-day washoutperiod before participants were transferred to the alternate supplement. Table 1 shows that there was no significant acute or short term effect of beetroot juice supplementation on the parameters measured when compared to placebo. However, there was a significant decrease in systolic BP (P = 0·009), diastolic BP (P = 0·035), MAP (P = 0·017), aortic and brachial AIX (P = 0·042 and 0·041 respectively), 3hours post beetroot supplementation. These results confirm previous findings( 4 ) that beetroot supplementation does not have an acute or short term effect on arterial stiffness measures. However, acute effects on arterial stiffness and BP within the beetroot juice supplementation group were observed. Further large scale studies on dietary nitrate supplementation and cardiovascular health are required to further assess efficacy.
    • Dietary supplementation with n-3 fatty acids (n-3 FA) for 4 weeks reduces post-exercise fatigue and delayed onset muscle soreness (DOMS) in trained male athletes

      Mushtaq, Sohail; Benson, Lindsay; University of Chester
      High intensity exercise in the form of eccentric contractions can lead to the formation of free radicals, stimulating an inflammatory response( 1 , 2 ). Consumption of n-3 FA may help modify inflammation and immune reactions beneficial to health by decreasing interleukin-6, tumour necrosis factor-alpha and C-reactive protein( 3 ). For trained athletes to improve athletic performance, recovery from training is important and DOMS is frequently experienced following eccentric exercise, impacting negatively on strength( 4 ). The Western diet is however, characterised by a high n-6 FA consumption relative to n-3 FA, formulating ratios often in excess of 16:1( 5 ). The use of non-steroidal anti-inflammatory drugs in the form of n-3 FA has been investigated by a number of clinical trials in untrained athletes, but whether this can be translated into attenuating exercise induced inflammation in trained athletes is still under investigation. A double-blind, randomised controlled trial was conducted in 22 trained male athletes who supplemented their diet with either 3000 mg/d of fish oil (gel capsules) consisting of 990 mg eicosapentaenoic acid (EPA) and 660 mg docosahexaenoic acid (DHA) (n = 11), or 3000 mg/d olive oil placebo (n = 11), for 28d. Participants underwent 3 sets of eccentric bicep curls in their dominant arm until failure and arm circumference, number of repetitions completed and DOMS/fatigue scores via visual analogue scale (VAS) were recorded at 0, 24 and 48 h after exercise, pre and post supplementation. No group performed better during the eccentric bicep test, pre and post supplementation, and at baseline, no differences were observed between groups for DOMS and fatigue. However, post supplementation, DOMS was significantly lower at 24 h (P = 0·005) and 48 h (P = 0·002) and fatigue was significantly lower at 24 h (P = 0·043) and 48 h post exercise (P < 0·001) in the n-3 FA group compared to the placebo group (Fig. 1). These findings indicate that n-3 FA supplementation has the potential to promote recovery and subsequently increase athletic performance in trained male athletes and may be a useful ergogenic aid. Possible anti-inflammatory mechanisms of n-3 FA should be further investigated using specific biomarkers of inflammation.
    • The neoliberal university, social work and personalised care for older adults

      Carey, Malcolm; University of Chester
      This article critically examines the impact of the neoliberal university upon social work education and practice relating to older people. It appraises market-led pedagogical reforms, including of the training of social workers who go on to work with older adults, such in support of policies including personalisation. Influence is drawn from the work of Nancy Fraser (2019): specifically, her understanding of ‘progressive neoliberalism’, or the improbable fusion of free market ideals with the politics of recognition to create a rejuvenated hegemonic bloc. This theoretical framework is utilized to analyse the prevalence of emancipatory constructs such as empowerment, participation, anti-oppression, equality, choice and independence within acutely underfunded, bureaucratic, and risk-averse fields of social care and social work. While benefiting some older ‘service users’, it is argued that personalisation policy regularly disadvantages or excludes older people within fragmented adult social care sectors. Progressive neoliberalism has helped to promote policies which envisage participative self-care whilst more often excluding or objectifying older adults, especially those with higher level needs.
    • Ultrafast Electric Field-induced Phase Transition in Bulk Bi0.5Na0.5TiO3 under High Intensity Terahertz Irradiation

      Yang, Bin; Zhang, Man; McKinnon, Ruth A.; Viola, Giuseppe; Zhang, Dou; Reece, Michael J.; Abrahams, Isaac; Yan, Haixue; University of Chester; Queen Mary University of London; Central South University
      Ultrafast polarization switching is being considered for the next generation of ferroelectric based devices. Recently, the dynamics of the field-induced transitions associated with this switching have been difficult to explore, due to technological limitations. The advent of terahertz (THz) technology has now allowed for the study of these dynamic processes on the picosecond (ps) scale. In this paper, intense terahertz (THz) pulses were used as a high-frequency electric field to investigate ultrafast switching in the relaxor ferroelectric, Bi0.5Na0.5TiO3. Transient atomic-scale responses, which were evident as changes in reflectivity, were captured by THz probing. The high energy THz pulses induce an increase in reflectivity, associated with an ultrafast field-induced phase transition from a weakly polar phase (Cc) to a strongly polar phase (R3c) within 20 ps at 200 K. This phase transition was confirmed using X-ray powder diffraction and by electrical measurements which showed a decrease in the frequency dispersion of relative permittivity at low frequencies.
    • The use of photo elicitation to explore the impact of social work student’s perceptions of placements on social work tutors and consider their role in practice learning

      Caffrey, Bridget; Fruin, Helen; Bailey-McHale, Julie; Ridgeway, Victoria; Bailey-McHale, Bex; University of Chester
      The importance of learning in practice is acknowledged across health and social care professions. Social work students’ experiences in practice settings has attracted some attention in academic literature, and the role and impact of the Practice Educator (PE) on student learning is increasingly recognised. However, there is a paucity of research examining the role of the social work tutor generally and particularly within practice learning settings. This paper presents a small-scale qualitative study exploring the impact of visual images produced by social work students reflecting their practice experiences on six social work tutors. Photo elicitation prompted discussion in a focus group setting which was subsequently thematically analysed, with four themes emerging. These were dichotomous relationships, difference and diversity, tutor brokerage skills, and student support. The images encouraged tutors to reflect upon the complexity of their relationship with social work students and question whether they were professionally equipped to support students in complex placement situations. In addition, the effectiveness of the curriculum in preparing social work students for practice was considered, particularly space afforded to students to reflect on practice learning in a safe environment. Opportunities to support SW tutors in their role and SW students in practice are deliberated.
    • Across the threshold: a somaesthetic approach to the design of extended realities

      Summers, Alan; McGuirk, Tom; University of Chester
      The prospect that extended realities (XR) will become a seamless part of our everyday environment comes ever closer with the development of mixed reality headsets. These devices allow a blending of digital objects with the user’s actual spatial environment. The user interacts with the virtual objects and these objects can, in turn, interact with the ‘real-world’ environment. We argue that the design and interpretation of these extended realities requires design thinking that questions the dominant standard model of cognition, which is indebted to Cartesian perspectivism. We suggest that situated and enactive models of cognition furnish a better understanding of how the body, mind and environment are essentially integrated, enabling us to apply such understanding advantageously to the design of these devices and environments.
    • Charlotte Brontë's Gothic Fragment: 'The Story of Willie Ellin'

      Wynne, Deborah; University of Chester
      Charlotte Brontë’s eighteen-page fragment, ‘The Story of Willie Ellin’, written shortly after the publication of Villette in 1853, combines the gothic and realism and uses multiple narrators to tell a disturbing story of cruelty towards a child. The generic instability and disordered temporal framework of this fragment make it unlike anything Brontë had previously written, yet it has attracted the attention of few scholars. Those who have discussed it have condemned it as a failure; the later fragment ‘Emma’, also left incomplete by the author’s premature death, has been seen as the more likely beginning of a successor to Villette. ‘The Story of Willie Ellin’ reveals Brontë at her most experimental as she explores the use of different narrative voices, including that of an unnamed genderless ‘ghost’, to tell a story from different perspectives. It also shows Brontë representing a child’s experience of extreme physical abuse which goes far beyond the depictions of chastisement in Jane Eyre (1847). This essay argues that ‘The Story of Willie Ellin’ affords rich insights into Brontë’s ideas and working practices in her final years, suggesting that it should be more widely acknowledged as a unique aspect of Brontë’s oeuvre, revealing the new directions she may have taken had she lived to complete another novel.
    • Design, Synthesis and Evaluation of New Bioactive Oxadiazole Derivatives as Anticancer Agents Targeting Bcl-2

      Hamdy, Rania; Elseginy, Samia; Ziedan, Noha; El-Sadek, Mohamed; Lashin, El-Said; Jones, Arwyn T; Westwell, Andrew D; University of Chester; Cardiff University; Zagazig University; Bristol University; University of Sharjah
      A series of 2-(1H-indol-3-yl)-5-substituted-1,3,4-oxadiazoles, 4a–m, were designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2 inhibitory anticancer agents based on our previously reported hit compounds. Synthesis of the target 1,3,4-oxadiazoles was readily accomplished through a cyclization reaction of indole carboxylic acid hydrazide 2 with substituted carboxylic acid derivatives 3a–m in the presence of phosphorus oxychloride. New compounds 4a–m showed a range of IC50 values concentrated in the low micromolar range selectively in Bcl-2 positive human cancer cell lines. The most potent candidate 4-trifluoromethyl substituted analogue 4j showed selective IC50 values of 0.52–0.88 μM against Bcl-2 expressing cell lines with no inhibitory effects in the Bcl-2 negative cell line. Moreover, 4j showed binding that was two-fold more potent than the positive control gossypol in the Bcl-2 ELISA binding affinity assay. Molecular modeling studies helped to further rationalize anti-apoptotic Bcl-2 binding and identified compound 4j as a candidate with drug-like properties for further investigation as a selective Bcl-2 inhibitory anticancer agent.
    • Charlotte Brontë: Legacies and Afterlives

      Wynne, Deborah; Regis, Amber K.; University of Chester; University of Sheffield
      This edited collection offers a timely reflection on Charlotte Brontë's life and work in the context of the bicentenary of her birth in 2016. Brontë's legacy continues to evolve and the new essays in this volume, covering the period from her first publication to the present day, explain why she has remained at the forefront of global literary cultures. Taking a fresh look at over 150 years of engagement with one of the best-loved novelists of the Victorian period, the volume examines areas such as genre, narrative style, national and regional identities, sexuality, literary tourism, adaptation theories, cultural studies, postcolonial and transnational readings. The contributors to this volume offer innovative interpretations of the rich variety of afterlives enjoyed by characters such as Jane Eyre and Rochester in neo-Victorian fiction, cinema and television, on the stage and on the web. Bringing the story of Charlotte's legacy up to date, the essays analyse obituaries, vlogs, stage and screen adaptations, fan fiction and erotic makeovers, showing that Charlotte Brontë's influence has been manifold and an enduring feature of the feminist movement.