Oxford, United Kingdom

Time filter

Source Type

Haywood K.L.,University of Warwick | Staniszewska S.,University of Warwick | Chapman S.,Oxford Business Park
Quality of Life Research | Year: 2012

Purpose To review the quality and acceptability of condition-specific, domain-specific and generic multi-item patient-reported outcome measures (PROMs) used in the assessment of adults with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Methods Systematic literature searches were made to identify PROMs. Quality and acceptability was assessed against an appraisal framework, which captured evidence of both the thoroughness and results of evaluations: evidence of measurement (reliability, validity, responsiveness, interpretability, data quality/precision) and practical properties (feasibility, patient acceptability), and the extent of active patient involvement was sought. Results A total of 11 CFS/ME-specific, 55 domain-specific and 11 generic measures were reviewed. With the exception of the generic SF-36, all measures had mostly limited evidence of measurement and/or practical properties. Patient involvement was poorly reported and often cursory. Conclusions The quality and acceptability of reviewed PROMs is limited, and recommendations for patient-reported assessment are difficult. Significant methodological and quality issues in PROM development/evaluation were identified by the appraisal framework, which must be addressed in future research. Clear discrepancies exist between what is measured in research and how patients define their experience of CFS/ME. Future PROM development/ evaluation must seek to involve patients more collaboratively to measure outcomes of importance using relevant and credible methods of assessment. © Springer Science+Business Media B.V. 2011.


Fragouli E.,Oxford Business Park | Wells D.,Oxford Business Park | Delhanty J.D.A.,University College London
Cytogenetic and Genome Research | Year: 2011

Aneuploidy is the most commonly occurring type of chromosome abnormality and the most significant clinically. It arises mostly due to segregation errors taking place during female meiosis and is also closely associated with advancing maternal age. Two main aneuploidy-causing mechanisms have been described: the first involves the non-disjunction of entire chromosomes and can take place during both meiotic divisions, whereas the second involves the premature division of a chromosome into its 2 sister chromatids, followed by their random segregation, upon completion of meiosis I. To elucidate the causal mechanisms of maternally derived aneuploidy and the manner with which they affect the 2 meiotic divisions, a large number of oocytes and their corresponding polar bodies have been examined. Various classical and molecular cytogenetic methods have been employed for this purpose, and valuable data have been obtained. Moreover, research into the gene expression patterns of oocytes according to maturity, maternal age, and chromosome status has provided a unique insight into the complex nature of the biological processes and genetic pathways regulating female meiosis. Findings obtained from the cytogenetic and molecular analysis of oocytes will be reviewed in this article. Copyright © 2011 S. Karger AG, Basel.


Alfarawati S.,University of Oxford | Alfarawati S.,Oxford Business Park | Fragouli E.,University of Oxford | Fragouli E.,Oxford Business Park | And 2 more authors.
Human Reproduction | Year: 2011

BACKGROUND: Balanced chromosomal rearrangements represent one of the most frequent indications for preimplantation genetic diagnosis (PGD). Although fluorescence in situ hybridization (FISH) has been successfully employed for diagnosis in such cases, this approach usually restricts assessment of the chromosomes involved in the rearrangement. Furthermore, with FISH-based strategies, it is sometimes necessary to create patient-specific protocols, increasing the waiting time and costs. In the current study, we explored the use of two comprehensive chromosome screening methods, conventional metaphase comparative genomic hybridization (CGH) and microarray-CGH (aCGH), as alternatives for PGD of chromosome rearrangements. Methods The study included 16 patients who underwent 20 cycles of PGD for a variety of chromosome rearrangements (reciprocal or Robertsonian translocations or inversions). Testing was performed at various embryonic stages using CGH (9 cases) or aCGH (11 cases). Results Results were obtained for 121 out of 132 samples (91.7%). Of the diagnosed samples, 48.8% were found to carry abnormalities associated with the rearrangement, either alone or in combination with other chromosomal abnormalities. A further 28.9% of samples were normal/balanced for the rearranged chromosomes, but affected by aneuploidy for other chromosomes. Only 22.3% of samples were chromosomally normal. Of the 15 patients who completed their treatment cycles, 5 became pregnant after one or two cycles resulting in four healthy births. The delivery rate per cycle was 21% (27% per embryo transfer). CONCLUSIONS This is the first study to describe the clinical application of comprehensive chromosome screening applied to polar bodies, blastomeres or trophectoderm cells from patients carrying inversions and translocations. Using these techniques, most patients requesting PGD for a chromosome rearrangement can be treated using a single protocol. Additionally, the detection of abnormalities affecting chromosomes unrelated to the rearrangement may assist in the selection of viable embryos for transfer. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Enciso M.,University of Oxford | Enciso M.,Oxford Business Park | Alfarawati S.,University of Oxford | Alfarawati S.,Oxford Business Park | And 2 more authors.
Human Reproduction | Year: 2013

STUDY QUESTION Is there a relationship between DNA damage and numerical chromosome abnormalities in the sperm of infertile patients? SUMMARY ANSWER A strong link between DNA fragmentation and the presence of numerical chromosome abnormalities was detected in human sperm. Chromosomally abnormal spermatozoa were more likely to be affected by DNA fragmentation than those that were chromosomally normal. WHAT IS KNOWN ALREADY Several studies have described the presence of elevated levels of DNA damage or chromosome defects in the sperm of infertile or subfertile men. However, the nature of the relationship between sperm DNA damage and chromosome abnormalities is poorly understood. The fact that some assisted reproductive techniques have the potential to allow abnormal spermatozoa to achieve oocyte fertilization has led to concerns that pregnancies achieved using such methods may be at elevated risk of genetic anomalies. STUDY DESIGN, SIZE, DURATION For this prospective study, semen samples were collected from 45 infertile men. PARTICIPANTS, SETTING, METHODSSamples were assessed for DNA fragmentation using the Sperm Chromatin Dispersion Test (SCDt) and for chromosome abnormalities using multi-colour fluorescence in situ hybridization (FISH) with probes specific to chromosomes 13, 16, 18, 21, 22, X and Y. Additionally, both parameters were assessed simultaneously in 10 of the samples using a protocol combining SCDt and FISH. MAIN RESULTS AND THE ROLE OF CHANCE A significant correlation between the proportion of sperm with a numerical chromosome abnormality and the level of DNA fragmentation was observed (P < 0.05). Data from individual spermatozoa subjected to combined chromosome and DNA fragmentation analysis indicated that chromosomally abnormal sperm cells were more likely to display DNA damage than those that were normal for the chromosomes tested (P < 0.05). Not only was this association detected in samples with elevated levels of numerical chromosome abnormalities, but it was also evident in samples with chromosome abnormality rates in the normal range. LIMITATIONS, REASONS FOR CAUTION The inability to assess the entire chromosome complement is the main limitation of all studies aimed at assessing numerical chromosome abnormalities in sperm samples. As a result, some of the sperm classified as 'chromosomally normal' may be aneuploid for chromosomes that were not tested. WIDER IMPLICATIONS OF THE FINDINGS During spermatogenesis, apoptosis (a process that involves active DNA degradation) acts to eliminate abnormal sperm. Failure to complete apoptosis may explain the coincident detection of aneuploidy and DNA fragmentation in some spermatozoa. In addition to shedding light on the biological mechanisms involved in the processing of defective sperm, this finding may also be of clinical relevance for the identification of patients at increased risk of miscarriage or chromosomally abnormal pregnancy. In some instances, detection of elevated sperm DNA fragmentation may indicate the presence of chromosomal abnormalities. It may be worth considering preimplantation genetic screening (PGS) of embryos produced using such samples in order to minimize the risk of aneuploidy.STUDY FUNDING AND COMPETING INTERESTSThis work was supported by funding from Oxford NIHR Biomedical Research Centre programme, the Spanish Ministerio de Educación Cultura y Deporte and a Grant for Fertility Innovation (Merck Serono). The views expressed are those of the authors. © 2013 The Author. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Murchison A.G.,Oxford Business Park
Medical Hypotheses | Year: 2015

Hiccups are an unexplained phenomenon and a subject of medical curiosity. They arise through a reflex arc with central control at the level of the medulla, and their primary physiological effect is the generation of negative intra-thoracic pressure. This paper presents the hypothesis that hiccups serve a purpose during the first half of gestation, when they are most prevalent; namely, that they promote amniotic fluid influx to the primitive gut, allowing fluid to be transferred to the foetal and then maternal vasculature. Furthermore, hiccups could be provoked by increasing amniotic fluid volume and pressure, and act in a regulatory capacity. This hypothesis could be tested by studying foetal movements in the first half of gestation, and assessing whether there is correlation with amniotic fluid flux in the developing gut. Ascertaining whether hiccups increase in frequency with increasing amniotic fluid volume would provide evidence for or against a regulatory function. © 2015 Elsevier Ltd.


Fragouli E.,Oxford Business Park | Wells D.,Oxford Business Park
Cytogenetic and Genome Research | Year: 2011

Studies of human cleavage stage embryos, 3 days after fertilization of the oocyte, have revealed remarkably high levels of chromosome abnormality. In addition to meiotic errors derived from the gametes, principally the oocyte, mitotic errors occurring after fertilization are also common, leading to widespread chromosomal mosaicism. The prevalence of chromosome anomalies in embryos may explain the relatively poor fertility and fecundity in humans and the low success rates of assisted reproductive treatments (e.g., IVF). While much is known concerning the incidence of aneuploidy during the first 3 days following fertilization, it is only in the last couple of years that large numbers of embryos at the final stage of preimplantation development, the blastocyst stage, 5 days after fertilization, have been subjected to detailed analysis. Here we discuss the latest data from the comprehensive cytogenetic analysis of blastocysts. These findings indicate that the majority of selection against chromosome abnormalities does not occur until the time of implantation or shortly after, with aneuploidy typically affecting more than 50% of blastocysts. Additionally, clinical results presented suggest that screening of blastocyst stage embryos for chromosome abnormality, with preferential transfer to the uterus of those found to be euploid, may help to improve the success rates of assisted reproductive treatments. Copyright © 2011 S. Karger AG, Basel.


Martin A.,Oxford Business Park
Procedia Engineering | Year: 2015

This paper describes how the TRIZ concept of Ideality was used to inform the development and deployment of a 'free-touse' TRIZ database of scientific and physical effects. The TRIZ 'Time and Scale' framework (also known as Nine Boxes, Nine Windows or System Operator) is used to structure the narrative based on three phases: Pre- Development, Development and Post-Development. In the Pre-Development phase it was recognized that most comprehensive effects databases tend to be commercial products providing excellent content but at a price presenting a potential barrier to their use, especially by those new to TRIZ. The few 'free-to-use' effects databases that were available tended to be less comprehensive than the best of their commercial rivals. This led to an Ideal Outcome (or Ideal Final Result) for the effects database: "delivery of complete and perfect results to any user without restriction or cost". This highlighted a contradiction between the performance of the system (primarily represented by the quality and quantity of the results it produces) and the cost of delivery (primarily represented by the cost of developing the database infrastructure and collecting and collating the database content). As the project moved into the Development Phase this contradiction was tackled using a three-pronged Ideality-based strategy of: focus on delivering only the essential Benefits, reduction of Harms that detract from the essential Benefits and finally reduction of Costs by using existing and/or low-cost resources. Focusing on essential Benefits resulted in the selection of a simple database design that minimised the data required to populate the database. The principle Harm (where Harm is an output that is not useful) considered was that of an inaccuracy in the results delivered to the User. A taxonomy of database inaccuracies was compiled and each identified inaccuracy type considered in terms of its influence on the Ideality of the database system. This revealed, somewhat surprisingly, that inaccuracies were not only inevitable but were also not critical to the overall usefulness of the system. The principle resources used for cost reduction were: open-source database development tools, available internet resources and people. The Post-Development Phase was triggered in October 2011 with the deployment of the database on the Oxford Creativity website (www.triz.co.UK). The principle activity since that time has been a series of content updates. In addition consideration has been given (somewhat belatedly) to other aspects of the Post-Development column of the Nine Box model. The User's perception of Ideality has shifted from "Can I have more results" to "There are a lot of suggestions here - can they be filtered in some way?" This is a useful reminder that (in common with most systems) the database falls short of delivering the Ideal Outcome of complete and perfect results. Some candidate routes towards the realization of this Ideal are suggested. © 2015 The Authors. Published by Elsevier Ltd.


Rayner S.,Oxford Business Park
Energy Policy | Year: 2010

The author looks at diverse concepts and roles of trust in the challenge of decarbonising energy systems, drawing on 25 years of personal experience in the fields of energy and environmental policy research. The paper focuses on three issues-public trust in science, institutional trust in making technology choices, and the idea that high-trust societies are more sustainable than those exhibiting low-trust. While trust is a key concept in understanding the public acceptability of technology choices, it is only one of a suite of interrelated concepts that must be addressed, which also includes liability, consent, and fairness. Furthermore, rational distrust among competing institutional world views may be critical in understanding the role of social capital in socioeconomic and technological development. Thus the concept of trust has become a portmanteau, carrying a diverse range of ideas and conditions for sustainable energy systems. The paper concludes with three emphases for decision makers. First, the issue is the energy system, not particular generating technologies. Second, the energy system must be recognized to be as much a social system as it is a technical one. Third, the system requires incorporation of the minimum level of diversity of engineering technologies and social actors to be sustainable. © 2009.


Swanton A.,Royal Berkshire Hospital | Storey L.,Oxford Business Park | McVeigh E.,Oxford Business Park | Child T.,Oxford Business Park
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2010

Objective: To examine the outcome of IVF in women who have normal ovaries, ovulatory PCO or PCOS. Study design: Analysis of a prospectively collected database in an assisted conception unit in a university teaching hospital including 290 women <37 years of age undergoing their first IVF cycle. The main outcome measure was severe OHSS requiring hospitalization. Results: Severe OHSS rates were significantly higher in women with PCO (12.6%) and PCOS (15.4%) compared to those with normal ovaries (2.7%). Coasting was used significantly more often. Live birth rates per cycle started are similar among women with PCO (38%), PCOS (37%) and normal ovaries (40%). Conclusion: Women with ovaries of polycystic morphology are at increased risk of developing severe OHSS and of requiring avoidance techniques such as coasting, regardless of ovulatory status. However, live birth rates per cycle are similar to women with normal ovaries. © 2009 Elsevier Ireland Ltd. All rights reserved.


Loading Oxford Business Park collaborators
Loading Oxford Business Park collaborators