Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues

Date of Acceptance: 28/07/2015 The authors thank Scott McMenemy for carrying out preliminary, early studies looking at effects of Gu compounds upon chicken embryology, as well as Charles D. Crowe, Jeffrey E. Roth, and Adam C. Rolt for critical comments on the article. fli1:EGFP zebrafish were obtained from the Zebrafish International Research Center (27). mpo:GFP zebrafish [also termed Tg(MPO:GFP)114] zebrafish were obtained from Dr. Stephen Renshaw, University of Sheffield (Sheffield, South Yorkshire, UK; ref. 29).

Anticancer Properties of a Novel Class of Tetrafluorinated Thalidomide Analogues

Date of Acceptance: 28/07/2015 The authors thank Scott McMenemy for carrying out preliminary, early studies looking at effects of Gu compounds upon chicken embryology, as well as Charles D. Crowe, Jeffrey E. Roth, and Adam C. Rolt for critical comments on the article. fli1:EGFP zebrafish were obtained from the Zebrafish International Research Center (27). mpo:GFP zebrafish [also termed Tg(MPO:GFP)114] zebrafish were obtained from Dr. Stephen Renshaw, University of Sheffield (Sheffield, South Yorkshire, UK; ref. 29).

Managing the multiplicities of graduate level education! Are Master’s students’ expectations matched by their experiences?

With rapid increases in student fees reflecting moves towards a QUASI Market model of Higher Education in the UK and across much of the Western World[1], many universities find themselves having to meet progressively higher levels of student expectations[2]. This is particularly the case at undergraduate level, where increases in fees over the past decade have far exceeded inflation. Yet with so much attention on ‘consumer savvy’ undergraduates, the question of whether Master’s level students’ expectations are matched by their experiences is one which remains largely unanswered. Grounded in an empirically grounded approach to learning and teaching developed by the paper authors[3], this paper sets out to being to answer this question. In doing so it makes a distinctive contribution to debates about graduate level engineering education and concludes with a number of recommendations. Discussion: The ‘MSc: Managing Expectations’ Project analyses the expectations and experiences of Graduate level Engineering Management Students over a two year period. Focusingon the ‘student experience’, three main concepts are identified as being particular relevant to enhancing learning [3]: Relationships: Variety: Synergy. Relationships: Based on empirical research, the significance of Relationships within the academic environment is discussed with particular attention being paid to the value of students’ social and academic support networks, including academic tutoring. Variety: Grounded in a statistical analysis of ‘engagement data’ together with survey and interview findings, the concept of variety critically examines students’ perspectives and experiencesof different approaches to learning and teaching. Synergy: Possibly the most important concept discussed within this paper, the need for constructively aligned curriculum is extended to reflect the students’ apriori knowledge and experienceas well as employer and societal demands and expectations. The conclusion brings the different concepts within the discussion together, providing a set of practical recommendations for colleagues working both at graduate and undergraduate level. References 1.Gibbs, P. (2001) "Higher education as a market: a problem or solution?." Studies in Higher Education 26. 1. pp. 85-94. 2.Tricker, T., (2005) Student Expectations-How do we measure up. University of Sheffield. Available from: http://www.persons.org.uk/tricker%20paper.pdf Accessed 9/10/14 3.Clark, R. & Andrews, J. (2014). Relationships, Variety & Synergy [RVS]: The Vital Ingredients for Scholarship in Engineering Education? A Case-Study. European Journal of Engineering Education. 39.6. pp. 585-600.

Democracy Matters: Lessons from the 2015 Citizens' Assemblies on English Devolution

The Citizens’ Assembly pilots on local democracy and devolution were the first of their kind in the United Kingdom. Organised by Democracy Matters — an alliance of university researchers and civil society organisations led by Professor Matthew Flinders — and funded by the UK’s Economic and Social Research Council, the Assemblies took place in Southampton and Sheffield towards the end of 2015.

Sacrificio y ejemplaridad. Comprendiendo los fenómenos de Leonel Messi y Diego A Maradona

Leo Messi y Diego Maradona, son dos grandes deportistas que han alcanzado fama mundial. En parte, si bien esa fama les da a los argentinos cierta posición de privilegio respecto al futbol, no menos cierto es que se los estima de diversas maneras. El arquetipo del padre de la fe y del héroe trágico acuñados por Kierkegaard da una ruta conceptual clara y pertinente al estudio de los ídolos contemporáneos como así también esboza una crítica al deporte moderno como revitalizador ideológico de las fallas o frustraciones que se ha multiplicado por acción del capitalismo.

The magical transformation contest in the ancient storytelling tradition

El concurso de transformación mágica, esquema narrativo difundido en la tradición popular, se presenta en dos variantes principales: los hechiceros que compiten pueden metamorfosearse en varios seres o crear esos seres por medios mágicos. En cualquier caso el concursante ganador da a luz criaturas más fuertes que superan las de su oponente. La segunda variante fue preferida en el antiguo Cercano Oriente (Sumeria, Egipto, Israel). La primera se puede encontrar en algunos mitos griegos sobre cambiadores de forma (por ejemplo, Zeus y Némesis). El mismo esquema narrativo puede haber influido en un episodio de la Novela de Alejandro (1.36-38), en el que Darío envía regalos simbólicos a Alejandro y los dos monarcas enemigos ofrecen contrastantes explicaciones de ellos. Esta historia griega racionaliza el concurso de cuento de hadas, transfiriendo las fantásticas hazañas de creaciones milagrosas a un plano secundario pero realista de metáfora lingüística.

За някои топоси, свързани с женските роли, в текста на книга Царства

Статията се занимава със славянския превод на няколко топоса, свързани с разбирането на женските роли, в Първа и Втора книга Царства. За целите на сравнението основният ръкопис (Архивският хро- нограф) е съпоставен с още седем славянски ръкописа, извлечението от Книги Царства в Славянската версия на Хрониката на Георги Синкел, Острожката библия, както и с текста на Септуагинта и Вулгата. Въз основа на събрания богат речников и изворов материал, статията анализира и търси при- чината за необичайните преводачески решения на старобългарския книжовник.

"Sub Tiberio quies"? Judaea’s Political Situation under the Prefects (6-41 c.e.), between Reality and Ideology

Deeply conflicting views on the political situation of Judaea under the Roman prefects (6-41 c.e.) have been offered. According to some scholars, this was a period of persistent political unrest and agitation, whilst according to a widespread view it was a quiescent period of political calm (reflected in Tacitus’ phrase sub Tiberio quies). The present article critically examines again the main available sources –particularly Josephus, the canonical Gospels and Tacitus– in order to offer a more reliable historical reconstruction. The conclusions drawn by this survey calls into question some widespread and insufficiently nuanced views on the period. This, in turn, allows a reflection on the non-epistemic factors which might contribute to explain the origin of such views.

El discernimiento de espíritus en las periferias cristianas: gozo, pactos y poderosos entre aborígenes evangélicos del Chaco Argentino

El discernimiento de espíritus ha sido a lo largo de la historia del cristianismo un mecanismo fundamental para el control del acceso al carisma. Su desarrollo ha estado profundamente ligado a los cambios en la estructura social de las iglesias. Por ello buscamos aportar nuevas miradas sobre este dispositivo, analizándolo en el contexto de las periferias cristianas. Específicamente centraremos nuestro análisis en las iglesias evangélicas aborígenes mocoví del suroeste de la provincia del Chaco en Argentina. Nos aproximaremos a estas cuestiones a partir del análisis a la estructura social de estas iglesias, sus concepciones sobre los vínculos con las potencias no-humanas, la gestión de salud y enfermedad y la experiencia del culto.

Deconstrucción de los relatos evangélicos de la pasión. Sobre el arraigo de la ficción en la Historia de las religiones

Las más elementales exigencias de rigor crítico e independencia siguen a menudo sin cumplirse hoy en día en la reconstrucción histórica de la figura del judío Yeshua ben Yosef (Jesús el galileo), en parte porque el carácter inconsistente de las fuentes evangélicas no es tomado en serio. El presente artículo analiza las incongruencias de los relatos de la pasión, muestra en ellos los indicios de un proceso de despolitización, y señala el carácter insostenible de varias afirmaciones clave de muchos historiadores contemporáneos sobre el predicador galileo.

Factors affecting transition to second year of an engineering degree

Much research has focused on students’ transition from secondary school to university. Less is known about the transition from first to second year of a university degree programme. Given the difficulties that many students face at this stage of their education, research into the relevant factors is required. Through questionnaires and focus groups, views of second- and third-year aerospace and mechanical engineering students in our university have been gathered. A large majority believed that both the volume and difficulty of work increased in second year. Many stated that first year was slightly too trivial and could have been made more challenging to prepare them better for second year. Different teaching and assessment styles in second year were considered to affect attendance and performance. The survey revealed that students were generally very well settled into university life by the end of first year and were happy with their choice of course and only 23% reported that financial responsibilities have had a negative effect on their academic performance. Differences were observed between male and female students. Male students believed that transition was helped by having regular assessments and by worked examples in lectures. Females found the teaching staff were the most helpful factor for a successful transition. The results indicate that males require more structure and guidance whereas females are more independent and settle in better.

Cabazitaxel for Hormone-Relapsed Metastatic Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and were instead taken from the company's UK early access programme. Evidence on resource use came from the TROPIC trial, supplemented by both expert clinical opinion and a UK clinical audit. List prices were used for mitoxantrone, abiraterone and enzalutamide as directed by NICE, although commercial in-confidence patient-access schemes (PASs) are in place for abiraterone and enzalutamide. The confidential PAS was used for cabazitaxel. Sequential use of the advanced hormonal therapies (abiraterone and enzalutamide) does not usually occur in clinical practice in the UK. Hence, cabazitaxel could be used within two pathways of care: either when an advanced hormonal therapy was used pre-docetaxel, or when one was used post-docetaxel. The company believed that the former pathway was more likely to represent standard National Health Service (NHS) practice, and so their main comparison was between cabazitaxel and mitoxantrone, with effectiveness data from the TROPIC trial. Results of the company's updated cost-effectiveness analysis estimated a probabilistic incremental cost-effectiveness ratio (ICER) of £45,982 per quality-adjusted life-year (QALY) gained, which the committee considered to be the most plausible value for this comparison. Cabazitaxel was estimated to be both cheaper and more effective than abiraterone. Cabazitaxel was estimated to be cheaper but less effective than enzalutamide, resulting in an ICER of £212,038 per QALY gained for enzalutamide compared with cabazitaxel. The ERG noted that radium-223 is a valid comparator (for the indicated sub-group), and that it may be used in either of the two care pathways. Hence, its exclusion leads to uncertainty in the cost-effectiveness results. In addition, the company assumed that there would be no drug wastage when cabazitaxel was used, with cost-effectiveness results being sensitive to this assumption: modelling drug wastage increased the ICER comparing cabazitaxel with mitoxantrone to over £55,000 per QALY gained. The ERG updated the company's NMA and used a random effects model to perform a fully incremental analysis between cabazitaxel, abiraterone, enzalutamide and best supportive care using PASs for abiraterone and enzalutamide. Results showed that both cabazitaxel and abiraterone were extendedly dominated by the combination of best supportive care and enzalutamide. Preliminary guidance from the committee, which included wastage of cabazitaxel, did not recommend its use. In response, the company provided both a further discount to the confidential PAS for cabazitaxel and confirmation from NHS England that it is appropriate to supply and purchase cabazitaxel in pre-prepared intravenous-infusion bags, which would remove the cost of drug wastage. As a result, the committee recommended use of cabazitaxel as a treatment option in people with an Eastern Cooperative Oncology Group performance status of 0 or 1 whose disease had progressed during or after treatment with at least 225 mg/m(2) of docetaxel, as long as it was provided at the discount agreed in the PAS and purchased in either pre-prepared intravenous-infusion bags or in vials at a reduced price to reflect the average per-patient drug wastage.

Development of an instrument measuring the quality of residential care facilities for older people

Aims. To validate the Swedish version of the Sheffield Care Environment Assessment Matrix (S-SCEAM). The instrument’s items measure environmental elements important for supporting the needs of older people, and conceptualized within eight domains. Methods. Item relevance was assessed by a group of experts and measured using content validity index (CVI). Test-retest and inter-rater reliability tests were performed.  The domain structure was assessed by the inter-rater agreement of a second group of experts, and measured using Fleiss kappa. Results. All items attained a CVI above 0.78, the suggested criteria for excellent content validity. Test-retest reliability showed high stability (96% and 95% for two independent raters respectively), and inter-rater reliability demonstrated high levels of agreement (95% and 94% on two separate rating occasions). Kappa values were very good for test-retest (κ = 0.903 and 0.869) and inter-rater reliability (κ = 0.851 and 0.832). Domain structure was good,  Fleiss’ kappa was 0.63 (range 0.45 to 0.75).    Conclusion. The S-SCEAM of 210 items and eight domains showed good content validity and construct validity. The instrument is suggested for use in measuring of the quality of the physical environment in residential care facilities for older persons.

Public Protection? The Implication of Grayling's 'Transforming Rehabilitation' Agenda on the Safety of Women and Children

Abstract The Coalition Government's new Transforming Rehabilitation (TR) agenda jeopardises the work undertaken with perpetrators of domestic abuse by highly skilled, qualified probation staff. Under new changes outlined by Grayling, Lord Chancellor and Secretary of State for Justice, probation clients who are assessed as posing a medium/low risk of causing harm will be assigned to private sector/voluntary organisations rather than come under the remit of the National Probation Service. This article argues that victims of domestic abuse, primarily women and children, will be placed at an increased risk of harm given this latest TR strategy. The majority of domestic abuse cases will be assessed as posing a medium risk of causing harm and will receive lower levels of intervention by a variety of disparate agencies and organisations. The Ministry of Justice states that the National Probation Service will directly manage offenders who pose a high risk of serious harm to the public, this article will argue that all perpetrators of domestic abuse should be considered as an important exception to this stance, and should remain under the auspices of Probation supervision, irrespective of statistical risk assessment, as has sex offender case management and sex offender treatment programme delivery.

Employability, Skills Development and Enterprise Creation (Momentum, University of Worcester)

Background to the Momentum project : PSS1 (Sept 2014 - July 2016): funded by HEFCE to promote Postgraduate Education and Employability. A discussion of group demographics, student experience, employer feedback, and enterprise creation through the establishment of the University of Worcester Business Incubator. The presentation concludes with a number of lessons learned from the project.