bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between Aromatase Gene Polymorphism Cyp19 Val 80 and Endometriosis Risk
Authors: Alkaf Syifa , Ziske Maritska  , Venny Patricia
Published: February 2021

A B S T R A C TIntroduction: Endometriosis implant has been known to express aromataseenzyme, Cytochrome p450 that catalyzes androgen into estrogen. It causes localestrogen production, leading to increased estrogen level, and subsequently triggersendometriosis lesion. CYP19 gene resided at chromosome 15q21.1 is the biggestcomponent of aromatase coding cytochrome p450 enzyme. Objective: To identifyrelationship between aromatase gene polymorphism CYP19 Val 80 and the risk ofendometriosis. Methods: This is an observational case-control study using frozenDNA sample from women with endometriosis and/ or adenomyosis who hadundergone laparotomy/ laparoscopy at Obstetrics and Gynecology Department Dr.Mohammad Hoesin General Hospital Palembang January-November 2013. Sampleswere amplified and cut by PCR-FRLP using Rsa1 restriction enzyme. Results weredivided into A/A genotype (homozygote mutant), G/A (heterozygote mutant), andG/G (homozygote wild type). Data were analyzed by SPSS 21.0 version. Results:PCR-RFLP results for A/A genotype were 20 (21.3%) in endometriosis group and 8(8.5%) in control group. G/A genotype were 18 (19.1%) in endometriosis group and22 (23.4%) in control group. G/G genotype were 9 (9.6%) and 17 (18.1%) inendometriosis group and control group, respectively. There was significant increaserisk of endometriosis in women carrying genotype A/A to those with genotype G/Gwith OR 4.722 (p<0.05). Conclusion: Polymorphism on aromatase gene CYP19 Val80 A/A increases risk of endometriosis.
Preclinical Test Methods with Animal Mouse and Rats Biomedical Research: Technical Guideline
Authors: Hidayat Rachmat , Patricia Wulandari
Published: February 2021

A B S T R A C TTrials in pre-clinical trials are very complex multidisciplinary studies. Extrapolatingdata from animals to humans requires information from many fields of science. Frompre-clinical trials, more detailed information and data on efficacy and safety wereobtained, especially at doses equivalent to doses in humans, and the presence orabsence of cumulative effects and whether these effects could return to normal(reversible) after the administration of the test material was stopped. This test canbe used to predict the negative impact on humans if he is exposed to the materialfor a long time.
CORRELATIVE STUDY OF HISTOPATHOLOGICAL DIAGNOSIS WITH CLINICAL & ENDOSCOPIC DIAGNOSIS IN UPPER GASTROINTESTINAL ENDOSCOPIC BIOPSY AT TERTIARY CARE CENTER
Authors: Khan Shana Nikhat , Narang Sanjeev
Published: February 2021

Lesions of Upper gastrointestinal tract (GIT) is commonly seen in surgical department patients. These patients are subjected to endoscopic examination and biopsy is taken for further histopathological diagnosis.  A clinical, endoscopic and histopathological diagnosis is made. This study was done to compare and correlate the results of histopathological diagnosis with endoscopic and clinical findings.

Study Designed: A total 50 Upper Gastrointestinal tract biopsy cases received in histopathology lab were analyzed. 

Material and Method: All endoscopic biopsies from upper GIT were received and processed. Paraffin blocks were made and sections were cut at 4 microns thickness and stained with routine hematoxylin and eosin stain. Their clinical and endoscopic reports were collected and compared with histopathological diagnosis.

Result: After analyzing statistically the data, we found that endoscopy results were better than clinical diagnosis and more closer to histopathological diagnosis.

Conclusion: Relation of histopathological diagnosis with endoscopic findings & clinical diagnosis was done in our study. We conclude that endoscopy is incomplete without histopathological examination of biopsy & so, the combinations of both plays an important role in diagnosis & management of upper gastrointestinal tract disorders. Histopathological examination remains the gold standard.

Keywords: Histopathology, endoscopy, gastrointestinal lesions.
Structural and Electrical Properties of Nano [Ni 0.6 Zn 0.4 Fe2 O4] Spinel Ferrite
Authors: N. Taikar Ramesh , Sarve Sadanand R. , Yele Disha T. , Taikar Deepak R. , Nagde Kalpana R.
Published: February 2021

Nano Ni-Zn ferrite with composition Ni 0.6 Zn 0.4 Fe2O4 is prepared by using sol-gel auto-combustion method with citric acid as a fuel. The structural properties of synthesized nano-ferrite is characterized by powder X-ray diffraction (XRD) technique while the electrical properties have been studied using two probe method. The X-ray diffraction study confirms that, there is a formation of single-phase cubic spinel with most intense peak at [311] having lattice constant of 8.3585 A0 and the average particle size is found to be 45.63 nm. In addition to this, the electrical resistivity of Ni-Zn Ferrite decreases with increase in temperature which exhibits semiconductor nature.
İyonize Radyasyonun Karaciğer ve Böbrek Dokusu Üzerine Etkisi
Authors: BARAN Münevver , ÖNDER Gözde Özge , GÖKTEPE Özge , BALCIOĞLU Esra , YILDIZ Oğuz Galip , YAY Arzu
Published: February 2021

Kanser tedavisinde kullanılan radyasyon uygulamalarının önemli komplikasyonları arasında radyasyona bağlı karaciğer ve böbrek toksisitesi bulunur. Doku ve/veya organlarda şekillenen radyasyon hasarı, alınan radyasyon dozu-na bağlıdır. Bu çalışma ile farklı dozlarda verilen iyonize radyasyonun (IR) sıçan karaciğer ve böbrek dokusu üzerine olası toksik etkilerinin değerlendirilmesi amaçlandı. Çalışmada, 40 adet dişi Wistar albino cinsi sıçan rastgele 4 gruba ayrıldı. Gruplar; kontrol grubu, 1Gy radyasyon grubu, 5Gy radyasyon grubu ve 10Gy radyasyon grubu şeklinde belir-lendi. Radyasyon uygulamaları gama ışını kullanılarak tek doz total vücut ışınlaması şeklinde yapıldı. Gruplara ait kara-ciğer ve böbrek dokuları Hematoksilen-Eozin (H&E), Masson trikrom ve Periyodik asit Schiff (PAS) boyama ile histopa-tolojik olarak değerlendirildi. Ayrıca, kaspaz-3 immünboyama ile apopitotik hücre sayısı belirlendi. IR uygulanan karaci-ğer dokuları histolojik olarak incelendiğinde, radyasyon uygulanan karaciğer dokularında başta vasküler ve interstisyel hemoraji alanları olmak üzere çeşitli hücresel hasarlar gözlenmiş olup hasar dereceleri radyasyon dozu ile doğru oran-tılıydı. Kontrol grubu ile kıyaslandığında en belirgin fibrozisin 10 Gy radyasyon uygulanan grupta olduğu gözlendi. Ayrı-ca, 5 Gy ve 10 Gy gruplarında hepatositlerin glikojen içeriğinde tükenme olduğu görüldü. Uygulanan IR, böbrek tübülle-rinde ve interstisyel dokuda değişikliklere ve hücresel hasara neden oldu. Özellikle 5 Gy ve 10 Gy IR uygulanan grup-larda kollajen liflerin miktarının arttığı ve proksimal tübül epitel hücrelerinde belirgin mikrovillus kaybı ile epitel bazal membranlarında kalınlaşma olduğu görüldü. Kaspaz-3 + hücre sayısı IR’nin hem karaciğer hem de böbrek dokuları üzerinde apopitozu arttırıcı etkiye sahip olduğunu gösterdi. Sonuç olarak, çalışma bulguları karaciğer ve böbrekte olu-şan doku hasarının ve apopitotik hücre sayısının IR’da uygulanan doza bağlı olduğunu ortaya koymuştur.
Kantitatif RT-PCR (RT-qPCR) ile MikroRNA (miRNA) Ekspresyon Profillemesi
Authors: SİDEKLİ Özge , KORKMAZ AĞAOĞLU Özgecan
Published: February 2021

Gen ekspresyonunun post-transkripsiyonel düzenleyicisi olarak bilinen miRNA’lar ökaryotik canlılarda çeşitli fizyolojik ve patolojik süreçlerde rol oynamaktadır. miRNA'ların rollerinin ortaya konulması ile birlikte miRNA’lar üzerine yapılan çalışmaların sayısı da gün geçtikçe artmaktadır. Yapılan çalışmalar ile birlikte miRNA'ların bütün hücre ve doku tiplerinde eksprese olduğu ortaya konmuştur. miRNA ekspresyon profilinin ortaya konması için çeşitli yöntemler öneril-mesine rağmen, yüksek duyarlılığı ve özgüllüğü nedeniyle RT-qPCR altın standart olarak kabul edilmektedir. Bu derle-mede; RT-qPCR ile miRNA ekspresyon profillemesi sürecindeki adımlar detaylı olarak özetlenmiş ve konu ile ilgili lite-ratür bilgisine yer verilmiştir.
O Perfil do professor de Sociologia da Coordenadoria Regional de Educação de Canoinhas/SC
Authors: Wieczorkievicz Alessandra Krauss , Santos Adelcio Machado dos , Baade Joel Haroldo
Published: February 2021

A Sociologia enquanto componente escolar, tem atributos fundamentais para a construção de uma sociedade melhor, por intermédio da formação de seus alunos. Sua contribuição na sociedade é tema de debates e discussões em diversos contextos sociais. Partindo desse pressuposto, para que a contribuição sociológica aconteça de forma plena na formação dos alunos, a figura do professor de Sociologia entra em destaque. Sendo protagonista na formação de seus alunos. Diante disso, este estudo possui como objeto de pesquisa analisar o perfil dos professores de Sociologia da Coordenadoria Regional de Educação de Canoinhas/SC. Nessa direção, a pesquisa de natureza quantitativa, com questionários fechados foram utilizados para a aplicação de entrevista aos 16 professores de Sociologia. Com o intuito, em compreender o perfil desse professor que está lecionando a disciplina de Sociologia na Coordenadoria. Concluiu-se com esta pesquisa, que o professor da disciplina de Sociologia, leciona além da Sociologia, outras disciplinas para complementar sua carga horária, não se dedicando exclusivamente a preparar e lecionar aulas de Sociologia, desloca-se para os demais municípios da Coordenadoria e não está há muito tempo atuando em sala de aula. A partir dessa análise, é possível entender quem é esse professor e se enfrenta dificuldades no processo de ensino da Sociologia no Ensino Médio.
PELANGGARAN DAN PENCABULAN KONTRAK PSIKOLOGI SERTA KESANNYA TERHADAP TINGKAH LAKU DEVIAN DI TEMPAT KERJA (Breach and Violation of Psychological Contract and its Effect on Workplace Deviance)
Authors: Arshad Rasidah , Nurmaya Ema
Published: February 2021

Tingkah laku devian di tempat kerja didapati memberi kesan negatif bukan sahaja kepada pekerja tetapi juga kepada organisasi secara keseluruhan. Dapatan kajian lepas menunjukkan anteseden atau punca yang mempengaruhi tingkah laku devian di tempat kerja terdiri daripada faktor individu iaitu faktor diri pekerja, dan faktor situasi yang berkaitan dengan organisasi. Kajian ini dijalankan untuk mengkaji hubungan antara pelanggaran dengan pencabulan kontrak psikologi (sebagai faktor peramal) dengan tingkah laku devian di tempat kerja. Secara khususnya, kajian ini menghipotesiskan wujudnya hubungan langsung antara pelanggaran kontrak psikologi dengan tingkah laku devian serta hubungan tidak langsung menerusi pencabulan kontrak psikologi. Kesahan model pengukuran dan hipotesis diuji menggunakan teknik statistik Model Persamaan Berstruktur (SEM) dengan menggunakan data yang dikumpulkan daripada 477 orang jururawat di Indonesia. Selaras dengan kerangka kerja Morrison dan Robinson (1997), dapatan kajian ini menunjukkan wujudnya hubungan tidak langsung yang signifikan antara pelanggaran kontrak psikologi dengan tingkah laku devian menerusi pencabulan kontrak psikologi sebagai pemboleh ubah pengantara. Secara teorinya, kajian ini dapat menyumbang kepada literatur menerusi penggunaan teori kontrak psikologi dalam menerangkan tingkah laku devian di tempat kerja. Abstract Workplace deviance behaviour was found to not only harm employees but also the organisation as a whole. Findings from past research have shown that individual and situational or organisational factors act as antecedents of deviant behaviour. The purpose of this paper is to examine the relationship between psychological contract breach, violation and workplace deviance. Specifically, this study hypothesised both direct relationship between psychological contract breach and workplace deviance, and indirect relationship between the two variables via psychological contract violation. To test the validity of the measurement model and to test the hypotheses, Structural Equation Modelling (SEM) statistical technique was employed to analyse the survey data collected from 477 nurses in Indonesia. Consistent with Morrison and Robinson’s (1997) framework, the results showed that psychological contract violation mediates the relation between psychological contract breach and workplace deviance. Theoretically, this study contributes to the existing literature by expanding the utility of psychological contract theory in explaining workplace deviant behaviours. Keywords: Psychological contract, breach, violation, workplace deviance, social exchange theory.
CAN THE “TAX THE RICH, SUBSIDISE THE POOR” POLICY IMPROVE FINANCIAL SATISFACTION AMONG MALAYSIANS?
Authors: Chan Ling-Meng , Keh Chia-Guan , Tang Siu-Eng , Tan Yan-Teng , Koay Ying-Yin
Published: February 2021

“Tax the rich, subsidise the poor” is deemed one of the typical finance characteristics of democracy and a solution in reducing income inequality. The Malaysian government has also adopted this strategy in its income redistribution policy. Evidently, this strategy can minimise the income gaps at the country level. However, it is doubtful if it can be effectively done at the individual level. The rich have to pay more while the poor can enjoy the ‘free’ income. Would that lead to financial satisfaction? Hence, the main objective of this study was to investigate the impact of individual perceptions on the government’s democratic act in implementing "tax the rich, subsidise the poor" policy for financial satisfaction among Malaysians. For an empirical analysis, this paper discusses the study conducted which used the sixth wave of the World Value Survey (WVS) data with 1290 respondents and is regressed by the ordered logit and ordered probit modelling. The results indicated that the democratic act of ‘taxing the rich and subsidising the poor’ in reality reduces financial satisfaction among Malaysians. In contrast, these same Malaysians wish for a larger income difference as an incentive for individual efforts. In view of this, the government and policy makers should make revisions to the current progressive taxation system or look for other alternative taxation systems which may be seen as fairer and can improve financial satisfaction among Malaysians at each income level.
JOB SEEKERS’ ACCEPTANCE TOWARDS PRODUCING VIDEO RESUMES FOR COMPANY’S RECRUITMENT
Authors: Tong David Yoon Kin , Tong Xue Fa , Balakrishnan Kavitha , Luo Shiwen
Published: February 2021

The purpose of this study is to explore the job seekers’ acceptance towards producing video resumes for the company’s video-based recruitment. The study aims to analyse the moderating effect of self-video resumes by experienced and non-experienced applicants’ in terms of their perceived stress and coping strategies in creating the videos when applying for jobs. The quota sampling method was used to collect data from four faculties in a private university. The conceptual model was developed with constructs consisting of perceived stress, problem-focused coping, self-efficacy, self-presentation and acceptance of video resumes. The model was validated by two-level confirmatory factor analysis (CFA). Subsequently, the moderation effects between the two groups of applicants were computed to uncover different group behaviours. The perceived stress and problem-focused coping responses were found to be significantly related to self-presentations for video resumes. A direct positive relationship was also found between the applicants’ self-efficacy and their acceptance of video resumes. The results of the moderation analysis indicate a significant difference in perceived stress between groups but not in the problem-focused coping strategies.
THE MEDIATING EFFECT OF LEADERS’ IDEALISED INFLUENCE ON THE RELATIONSHIP BETWEEN LEADERS’ EMOTIONAL INTELLIGENCE AND JOB PERFORMANCE AMONG ACADEMICS IN MALAYSIAN PUBLIC RESEARCH UNIVERSITIES
Authors: Raman Gopalan , Peng Ng Lee , Chi Chen I
Published: February 2021

Academics exert themselves tremendously to advance in higher education institutions, and their leadersâ€™ emotional intelligence and idealised influence are fundamental to responsiveness regarding performance. The effects of transformational leadership on job performance have been established, but a single component, idealised influence, has been neglected. Hence, this study aims to investigate the potential mediating effects of academic leadersâ€™ idealised influence between academic leadersâ€™ emotional intelligence and subordinatesâ€™ job performance. Approximately 386 questionnaires from five Malaysian public research universities were obtained. The partial least squares structural equation model was utilised in dichotomising the measurements. Drawing from attribution theory and social exchange theory, it was predicted that academic leadersâ€™ idealised influence will mediate the relationship between academic leadersâ€™ emotional intelligence and their subordinatesâ€™ job performance. However, the study reveals that the relationship between academic leadersâ€™ emotional intelligence and their subordinatesâ€™ job performance was not mediated by academic leadersâ€™ idealised influence. This study is useful for government and higher institutions in planning, developing, and implementing programs or policies in producing highly talented academic leaders in Malaysian research universities.
THE INFLUENCE OF ASYMMETRIC INFORMATION ON FOREIGN CAPITAL INFLOWS IN ASEAN PLUS THREE COUNTRIES
Authors: Yaacob Mohd Hasimi , Mohd Nor Raihan Ashikin , Janor Hawati , Hashim Noor Azuan
Published: February 2021

This paper examines the influence of asymmetric information on foreign capital inflows in ASEAN PLUS THREE (ASEAN+3) countries. Linking capital flows to stock market setting, it substantiates other efforts concerning the debatable issues of the effect of asymmetric information on foreign direct investment (FDI) and foreign portfolio investment (FPI). The asymmetric information is captured through the stock market microstructure perspective on the width and depth dimensions using highly frequency cross sectional data from year 2000 to 2015. Roll and Amivest models are employed to quantify the width and depth aspects of the asymmetric information. Employing the panel data technique, the results demonstrate the significant effect of market transparency on foreign capital inflows specifically the FDI as compared to the FPI. An increase in the width and depth analysis based on the Amivest model signifies a high informational transparency, thus shows a lower asymmetric information which consequently leads to the high foreign capital inflows. The results of the study provide information to the policymakers in monitoring capital inflows on the aspect of market transparency and highlight the importance of the stock market microstructure in assessing the asymmetric information for ASEAN+3 countries.
MEASURING HUMAN RESOURCE ATTITUDE USING ORGANISATIONAL THEORY OF RELATIONSHIP: THE WAY FORWARD
Authors: Hussain Munir , Mubarak Shujaat
Published: February 2021

This paper argues that classical socialisation theories generally discuss the organisational structures rather than the newcomerâ€™s psychology of relationships in any organisation and contributes to the socialisation stage model. In doing so, this research proposes an Organisational Theory of Relationship (OTR) for understanding the relationships of human resources in any organisation in four stages, namely fascination, contention, adaptation and adoration. The four stages have been examined in an empirical setting based on the data collected from 270 participants. Using the structural equation modelling, the measurement model validity was ascertained and several hypotheses were tested. The findings reveal that all employees in any organisation, intentionally or unintentionally, undergo some or all of the four stages. This model can provide a better insight into the organisational socialisation and individualism of its human resource. It also recommends the organisations to adopt the best possible strategies for uplifting employeesâ€™ psychological engagement to utilise their full potentials. The findings of the study can help to understand socialisation in relation to interpersonal relationships and provide a foundation for making socialisation in the organisation better.
Voluntary Sex, Rape and Incest among Unmarried Pregnant Female Adolescents in Malaysia (Seks Sukarela, Rogol dan Sumbang Mahram dalam kalangan Remaja Perempuan Hamil tanpa Nikah di Malaysia)
Authors: Sekh Bidin‬ Mohamad Shahbani , Shaffie‬ Fauziah
Published: February 2021

Unmarried pregnancy among adolescents is a concern for all. This problem is misunderstood and is often associated solely with free sex or voluntary sex outside of marriage. However, the prevalence of unmarried pregnancy among female adolescents also resulted from rape and incest. Understanding the causes of adolescent pregnancy is crucial because it will give a different perspective. In addition, the way how to tackle this problem and the effects on female adolescents involved are also different. Hence, this article attempts to discuss the issues of voluntary sex, rape, and incest among unmarried pregnant female adolescents in Malaysia. This article is also hopefully can enhance the understanding between voluntary sex, rape, and incest that contributes to unmarried pregnancies among female adolescents in Malaysia. Abstrak Hamil tanpa nikah dalam kalangan remaja amat membimbangkan semua pihak. Permasalahan ini disalahertikan dan sering dikaitkan semata-mata dengan perlakuan seks secara rambang atau seks sukarela di luar pernikahan. Namun demikian, kejadian hamil tanpa nikah dalam kalangan remaja juga turut disebabkan oleh kes rogol dan sumbang mahram. Pemahaman mengenai punca kehamilan remaja amat penting kerana akan memberikan pandangan yang berbeza. Selain daripada itu, cara mengatasi masalah ini dan kesan yang dihadapi oleh para remaja yang terlibat juga berbeza. Oleh hal yang demikian, artikel ini akan cuba membincangkan isu mengenai seks sukarela, rogol dan sumbang mahram yang berlaku dalam kalangan remaja hamil tanpa nikah di Malaysia. Artikel ini juga diharapkan dapat meningkatkan pemahaman dan perbezaan antara seks sukarela, rogol dan sumbang mahram yang menyumbang kepada kehamilan tanpa nikah dalam kalangan remaja wanita di Malaysia. Kata kunci: Seks sukarela, rogol, sumbang mahram, remaja, hamil tanpa nikah.
EXTERNAL AUDIT(OR) QUALITY AND ACCRUAL EARNINGS MANAGEMENT: FURTHER EVIDENCE FROM NIGERIA
Authors: Soyemi Kenny Adedapo , Olufemi Olubukonla Abosede , Adeyemie Semiu Babatunde
Published: February 2021

Hinged on the quest for quality financial information, this study examined the influence of audit quality on restricting the incidence of accrual-based earnings management among 30 quoted non-financial firms in Nigeria, an emerging country which provides a rich institutional background and cultural setting different from developed nations. Secondary data were gathered from annual reports and audited financial statements for 11 years from 2008-2018. These firms were selected using stratified sampling technique. Thereafter, panel ordinary least square technique was used to estimate specified model for the study. While the descriptive statistics revealed the absence of accrualbased manipulation of earnings among quoted non-financial firms in Nigeria, the multivariate fixed effects ordinary least square depicted that audit quality variables adopted are mutually and statistically significant in explaining 49 percent changes in earnings management. Further, audit tenure and auditor independence exhibited positive and significant relationship, while total assets as the control variable, displayed a negative and significant influence on earnings management. Surprisingly, the size of audit firm appeared positive but statistically insignificant. Consequently, the relevant authorities and policy makers should not only sustain but improve on the current practice of audit engagement partner and/or auditor switch after certain years of continuous engagement to enhance their independence and reduce client-auditor engagement periods to avoid familiarity threat.
THE RELATIONSHIP BETWEEN ORGANIZATIONAL CLIMATE FOR INNOVATION AND INNOVATIVE WORK BEHAVIOR: MEDIATING ROLE OF EMPLOYEE ENGAGEMENT IN PAKISTAN
Authors: Ali Asif , Farooq Waqas , Khalid Muhammad Ahsan
Published: February 2021

The purpose of this study is to empirically investigate the mediating result of employee engagement between organisational climate for innovation and innovative work behaviour. This study will have positive contribution towards theory. The tool used for data collection was closed-ended questionnaire. Results indicated that organisational climate for innovation and innovative work behaviour has a direct and indirect impact on innovative work behaviours. In this study, employee engagement has partial mediation impact between the organisational climate for innovation and innovative work behaviour. Approximately, 210 respondents participated in this study. The unit of analysis used in this study was employees. For practical implication, it will be useful for HR specialists who are concerned in increasing successful intercession that encourage employees to engage in innovative work behaviour. This paper offers contribution to the understanding of the relationship between the innovative work behaviour and organisational climate and mediating role of employee engagement.
The use of paclitaxel in the management of early stage breast cancer
Authors: Griffin S , Dunn G , Palmer S , Macfarlane K , Brent S , Dyker A , Erhorn S , Humphries C , White S , Horsley W , Ferrie L , Thomas S
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of paclitaxel in the management of early stage breast cancer based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The scope was not clearly defined in the manufacturer’s submission. Two of the three clinical trials included in the submission report showed that the addition of four cycles of paclitaxel to four cycles of doxorubicin and cyclophosphamide (AC-P) resulted in modest improvements in the two end points of disease-free survival (DFS) and overall survival (OS). The third unpublished study evaluating four cycles of AC followed by paclitaxel or docetaxel in breast cancer did not show any statistically significant differences in DFS or OS between any group. The economic evaluation of paclitaxel for adjuvant therapy in early breast cancer was based on two of the three trials submitted as clinical evidence and used a probabilistic Markov state-transition model. The measure of health benefit was quality-adjusted life-years (QALYs) and the model included direct costs using a UK NHS perspective. The primary analysis compared AC-P with four cycles of AC. The reported incremental cost-effectiveness ratio (ICER) for this comparison was £4726 per additional QALY for AC-P compared with four cycles of AC. The submission did not include a systematic review for clinical or cost-effectiveness evidence. As a result, potentially relevant trials and previously published studies were omitted. The main comparator used did not represent standard care in the UK NHS and a large number of relevant comparators were omitted, including docetaxel. The manufacturer did not consider potentially important patient subgroups defined by baseline risk, and the cost-effectiveness result in the average overall patient population may conceal important variation between subgroups. Overall, although the economic model may have indicated that the addition of four cycles of paclitaxel to four cycles of AC may be cost-effective compared with providing four cycles of AC only, this comparison is not informative to current clinical practice in the UK NHS. In the context of this review it is not possible for the ERG to predict the cost-effectiveness of paclitaxel compared with more appropriate, and potentially more effective, relevant comparators. The guidance issued by NICE in July 2006 as a result of the STA states that paclitaxel is not recommended as an option for the adjuvant treatment of women with early node-positive breast cancer.
Rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma
Authors: Dundar Y , Bagust A , Hounsome J , McLeod C , Boland A , Davis H , Walley T , Dickson R
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of rituximab for the first-line treatment of stage III/IV follicular non-Hodgkin’s lymphoma (FNHL) based upon the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The manufacturer’s scope restricts the intervention to rituximab in combination with CVP (cyclophosphamide, vincristine and prednisolone) (R-CVP); the only comparator used was CVP alone. The evidence from the one included randomised controlled trial (RCT) suggests that the addition of rituximab to a CVP chemotherapy regimen has a positive effect on the outcomes of time to treatment failure, disease progression, overall tumour response, duration of response and time to new lymphoma treatment in patients with stage III/IV FNHL compared with CVP alone. Adverse events were comparable between the two arms. This study was confirmed as the only relevant RCT. The economic analyses provided by the manufacturer were modelled using a three-state Markov model with with the health states being defined as progression-free survival (PFS), progressed (in which patients have relapsed) and death (which is an absorbing state). The model generated results for a cohort of patients with an initial age of 53 and makes no distinction between men and women. The model is basic in design, with several serious design flaws and key parameter values that are probably incompatible. Attempting to rectify the identified errors and limitations of the model did not increase the incremental cost-effectiveness ratio (ICER) above £30,000. Although the cost-effectiveness results obtained appear to be compelling in support of R-CVP compared with CVP for the trial population the results may not be so convincing for a more representative population. The results of the ERG analysis on the impact of age suggest that ICERs increase steadily with age, as the proportion of PFS that can be converted to overall survival (OS) is diminished by rising mortality rates in the general population. For the most extreme scenario (no OS gain) the ICER appears to remain below £30,000 per QALY gained. On balance the evidence indicates that R-CVP is more cost-effective than CVP. The guidance issued by NICE in July 2006 as a result of the STA states that rituximab within its licensed indication (in combination with cyclophosphamide, vincristine and prednisolone) is recommended as an option for the treatment of symptomatic stage III/IV follicular non-Hodgkin’s lymphoma in previously untreated patients.
Fludarabine phosphate for the first-line treatment of chronic lymphocytic leukaemia
Authors: Walker S , Palmer S , Erhorn S , Brent S , Dyker A , Ferrie L , Horsley W , Macfarlane K , White S , Thomas S
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of fludarabine phosphate or fludarabine plus cyclophosphamide for the first-line treatment of chronic lymphocytic leukaemia, based upon the evidence submission from Schering Health Care (SHC) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission was of good quality with no major errors or omissions in the clinical evidence. Two published studies and seven abstracts were included in the company submission, which showed improvements in overall response and progression-free survival (PFS) and a higher complete response rate in the fludarabinecontaining arms; however, until the complete data are made available for evaluation these results must be interpreted with caution. The manufacturer’s decision-analytic Markov model to estimate the cost-effectiveness of treatment with fludarabine monotherapy, fludarabine plus cyclophosphamide and chlorambucil was considered to be the most relevant source for informing this STA; it was appropriate for the decision problem and the data sources used to inform the model were appropriate from a UK NHS perspective. The incremental cost-effectiveness ratio of fludarabine plus cyclophosphamide compared with chlorambucil from the revised model presented in the manufacturer’s addendum was £3244 per additional quality-adjusted life-year. The results were robust to a range of subgroup and sensitivity analyses. Additional sensitivity and survival analyses were carried by the ERG to investigate possible bias in the results. This brought into question the validity of the assumptions underpinning the extrapolation of data over a lifetime time horizon and showed that the ICER estimates submitted by the manufacturer were not calculated correctly and uncertainty surrounding the decision problems was not expressed fully. Based on these analyses the ERG suggests that further evidence is needed to enable an accurate assessment to be made of the clinical and cost-effectiveness of fludarabine as first-line treatment for chronic lymphocytic leukaemia. The guidance issued by NICE in December 2006 as a result of the STA states that fludarabine monotherapy, within its licensed indication, is not recommended for the first-line treatment of chronic lymphocytic leukaemia; no recommendations have been made with respect to fludarabine plus cyclophosphamide combination therapy because the current marketing authorisation does not specifically provide a recommendation that fludarabine should be used concurrently with other drugs for the treatment of chronic lymphocytic leukaemia.
Adalimumab for the treatment of psoriasis
Authors: Turner D , Picot J , Cooper K , Loveman E
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of adalimumab for the treatment of moderate to severe plaque psoriasis based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission’s clinical evidence came from three randomised controlled trials comparing adalimumab with placebo, two extension studies and one ongoing open-label extension study. The studies were of reasonable quality and measured a range of clinically relevant outcomes. A higher proportion of patients on 40 mg adalimumab every other week achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) compared with placebo groups after 12 or 16 weeks of treatment, and there was a statistically significant difference in favour of adalimumab for the proportion of patients achieving a PASI 50 and a PASI 90. In a mixed treatment comparison, for each PASI outcome the probability of a response was greater for infliximab than for adalimumab, but the probability of response with adalimumab was greater than that with etanercept, efalizumab and non-biological systemic therapies. Adverse event rates were similar in the treatment and placebo arms and discontinuations because of adverse events were low and comparable between groups. The submission’s economic model presents treatment effectiveness for adalimumab versus other biological therapies based upon utility values obtained from two clinical trials. The model is generally internally consistent and appropriate to psoriasis in terms of structural assumptions and the methods used are appropriate. The base-case incremental cost-effectiveness ratio for adalimumab compared with supportive care for patients with severe psoriasis was £30,538 per quality-adjusted life-year. Scenario analysis shows that the model was most sensitive to the utility values used. Weaknesses of the clinical evidence included not undertaking a systematic review of the comparator trials, providing very little in the way of a narrative synthesis of outcome data from the key trials and not performing a meta-analysis so that the overall treatment effect of adalimumab achieved across the trials is unknown. Weaknesses of the economic model included that the assumptions made to estimate the cost-effectiveness of intermittent etanercept used inconsistent methodology for costs and benefits and there were no clear data on the amount of inpatient care required under supportive care. The NICE guidance issued as a result of the STA states that adalimumab is recommended as a treatment option for adults with plaque psoriasis in whom anti-tumour necrosis factor treatment is being considered and when the disease is severe and when the psoriasis has not responded to standard systemic therapies or the person is intolerant to or has a contraindication to these treatments.
Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal
Authors: Stevenson M , Pandor A
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of febuxostat for the management of hyperuricaemia in patients with gout based upon a review of the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission’s evidence came from two randomised controlled trials comparing the efficacy and safety of febuxostat with allopurinol. The trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. A pooled clinical efficacy analysis showed that a daily dose of 80 mg or 120 mg of febuxostat was significantly more effective than fixed-dose allopurinol (300/100 mg/day) at lowering serum uric acid (sUA) levels to therapeutic targets (< 6 mg/dl); however, a large percentage of febuxostat patients did not achieve the primary end point and the fixed-dose allopurinol regimen may have introduced bias. There were no differences between treatments in more clinically important outcomes such as gout flares and tophi resolution after 52 weeks of treatment. No subgroup analyses were conducted for patients with renal impairment, non-responders to allopurinol or patients with severe disease. Supplementary data from a 2-year open-label extension study were also provided, but were difficult to interpret and poorly reported. The incidence of adverse events was similar between treatments, although more febuxostat recipients discontinued treatment prematurely. A decision tree model was developed to determine the cost-effectiveness of febuxostat. The scope was limited to the comparison of continual febuxostat treatment with continual allopurinol treatment. Switching between treatments or withdrawing treatment in patients whose sUA levels had not decreased was not permitted. The model predicted a cost-effectiveness of £16,324 [95% confidence interval (CI) £6281 to £239,928] per quality-adjusted life-year (QALY) gained for febuxostat compared with allopurinol after 2 years of treatment. The incremental cost per QALY was below £20,000 in 63% of the simulations undertaken. Changes in the time horizon did not materially affect the results. The ERG believes that the modelling structure employed was not appropriate to estimate the cost-effectiveness of febuxostat within a treatment algorithm. In addition, there were concerns about the methodology used for collecting data on key model inputs. Given these reservations the cost-effectiveness of febuxostat could not be determined. The guidance issued by NICE in August 2008 as a result of the STA states that febuxostat is recommended as an option for the management of chronic hyperuricaemia in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated.
Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia
Authors: Dretzke J , Barton P , Kaambwa B , Connock M , Uthman O , Bayliss S , Meads C
Published: February 2021

This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators’ data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer’s model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer’s base-case incremental cost-effectiveness ratio (ICER) changed from £15,593 to between £40,000 and £42,000 per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at £20,000/QALY (£30,000/QALY) if a reduction in survival advantage relative to the manufacturer’s base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.
CAREER IN THE LIGHT OF EDUCATIONAL ATTAINMENT AND CAREER MANAGEMENT SKILLS
Authors: Lovšin Miha
Published: February 2021

The career usually refers to individuals’ working life, education and training and to life in general. The studies and reports evaluating the relations between these components mainly justify the power of educational attainment level in gaining employment or higher socio-economic status. In contrast to Bourdieu’s concept of cultural capital providing the theoretical background of these reports and studies, the concept of career management paradigm shift, elaborated by Jarvis, justifies the power of career management skills over the educational attainment level in gaining employment or higher socio-economic status.
Such approach towards the evaluation of someone’s career entirely overlooks the individuals’ notion of what would be relevant for their working life, education and training or life in general. Secondly, neither the concept of career relevance from the individuals’ point of view nor the career management skills were included when the relation between different career components was evaluated. The survey addressing these two problems was based on quantitative empirical methodology, conducted in 2016 in Slovenia. The non-random sample of 150 men and 468 women, born between 1940 and 1998, was collected through an online questionnaire.
Four different variables were set: career relevance, career management skills, social, cultural and economic capital. The indicators of career relevance were built upon various definitions of career. Career management skills were conceptualised according to Law’s and Krumboltz’s theoretical discourse of social learning and career learning. Their forms of capital were conceptualised according to the Bourdieu’s conception of social, cultural and economic capital which is in direct relation to the OECD concept of socio-economic status.
Bivariate analysis proved a statistically significant correlation between career relevance from individuals’ perspective and career management skills, educational attainment level, social, cultural and economic capital. However, the multivariate linear regression model confirms that only career management skills and economic capital, as independent variables, influence the dependent variable career relevance from individual’s perspective. One-way ANOVA proved that employed and unemployed differ statistically significant in the level of career management skills, career relevance, social and economic capital. In this respect, the results imply more systemic approach to career management skills learning in formal education.
Key words: career guidance, career management skills, policy making, career relevance, socio – economic status
Sequence-specific 2'-O-methoxyethyl antisense oligonucleotides activate human platelets through glycoprotein VI, triggering formation of platelet-leukocyte aggregates
Authors: Slingsby Martina H. Lundberg , Vijey Prakrith , Tsai I-Ting , Roweth Harvey , Couldwell Genevieve , Wilkie Adrian R. , Gaus Hans , Goolsby Jazana M. , Okazaki Ross , Terkovich Brooke E. , Semple John W. , Thon Jonathan N. , Henry Scott P. , Narayanan Padmakumar , Italiano Jr. Joseph E.
Published: February 2021

Antisense oligonucleotides (ASO) are DNA-based, disease-modifying drugs. Clinical trials with 2'-O-methoxyethyl (2’MOE) ASO have shown dose- and sequence-specific lowering of platelet counts according to two phenotypes. Phenotype 1 is a moderate (but not clinically severe) drop in platelet count. Phenotype 2 is rare, severe thrombocytopenia. This article focuses on the underlying cause of the more common phenotype 1, investigating the effects of ASO on platelet production and platelet function. Five phosphorothioate ASO were studied: three 2’MOE sequences; 487660 (no effects on platelet count), 104838 (associated with phenotype 1), and 501861 (effects unknown) and two CpG sequences; 120704 and ODN 2395 (known to activate platelets). Human cord bloodderived megakaryocytes were treated with these ASO to study their effects on proplatelet production. Platelet activation (determined by surface Pselectin) and platelet-leukocyte aggregates were analyzed in ASO-treated blood from healthy human volunteers. None of the ASO inhibited proplatelet production by human megakaryocytes. All the ASO were shown to bind to the platelet receptor glycoprotein VI (KD ~0.2-1.5 mM). CpG ASO had the highest affinity to glycoprotein VI, the most potent platelet-activating effects and led to the greatest formation of platelet-leukocyte aggregates. 2’MOE ASO 487660 had no detectable platelet effects, while 2’MOE ASOs 104838 and 501861 triggered moderate platelet activation and SYKdependent formation of platelet-leukocyte aggregates. Donors with higher platelet glycoprotein VI levels had greater ASO-induced platelet activation. Sequence-dependent ASO-induced platelet activation and platelet-leukocyte aggregates may explain phenotype 1 (moderate drops in platelet count). Platelet glycoprotein VI levels could be useful as a screening tool to identify patients at higher risk of ASO-induced platelet side effects.