Trace

The pots in the exhibition Trace speak both to my desire to belong, to connect to my beginnings, and yet to still trace my own path forward; they are about making connections and missing connections. Through these pots I ask questions of myself and the world around me in an attempt to negotiate the edges of my life. How do I feel connected and present in my own life and relationships? How do I feel connected to my family and my roots, while still finding my own path? What does it mean to belong in a family that is divided by great physical distance? What is the cure for loneliness? My work is intended to convey a sense of life lived, and life still to be lived. Each pot is a snapshot of the journey, a tether that connects me to me, and me to you—a memory frozen in mud-made-stone for years to come

Identification of functional variants in the Alzheimer’s disease candidate gene ABCA7

Late onset Alzheimer’s disease (LOAD) is the commonest form of dementia, affecting approximately 850,000 patients in the UK alone, predicted to exceed one million by 2025. The cause of LOAD is complex, but several large Genome Wide Association Studies have highlighted 21 genetic loci associated with this devastating disease and the ATP-Binding Cassette Protein, family A, member 7 (ABCA7) is one of these genetic loci. However, the exact reasons behind this association are still unknown, focusing work on identifying functional, pathogenic mutations within this locus. A total of 240 exonic variations within ABCA7 were therefore annotated in order to identify ones potentially altering the functionality of ABCA7. A total of five variants were predicted to be damaging by in silico annotation tools: rs3752233; rs59851484; rs3752237; rs114782266 and a novel mutation at genomic position 19:1056958. These were genotyped in the ARUK DNA Bank resource and three (rs59851484, rs3752239 and 19:1056958) showed tentative association with LOAD. However, lack of power in this study prevented any definitive associations from being formed. A further two variants were examined within functional cell assays. rs881768 had been predicted to affect the splicing of the ABCA7 protein and appeared to do so within minigene cellular assays. However, this did not appear to be the case when RNA from brain tissue harbouring this variation was examined. rs2020000 was examined through the dual luciferase assays, with the minor allele seeming to down regulate the reporter protein by approximately 30% (p<0.02) in these in vitro assays. Functional variations within the ABCA7 locus do play a role in LOAD risk and improvements within functional databases and annotation programmes will assist in identifying these causative mutations, in order to put a halt to LOAD, as well as other destructive complex disorders

Identification of functional variants in the Alzheimer’s disease candidate gene ABCA7

Late onset Alzheimer’s disease (LOAD) is the commonest form of dementia, affecting approximately 850,000 patients in the UK alone, predicted to exceed one million by 2025. The cause of LOAD is complex, but several large Genome Wide Association Studies have highlighted 21 genetic loci associated with this devastating disease and the ATP-Binding Cassette Protein, family A, member 7 (ABCA7) is one of these genetic loci. However, the exact reasons behind this association are still unknown, focusing work on identifying functional, pathogenic mutations within this locus. A total of 240 exonic variations within ABCA7 were therefore annotated in order to identify ones potentially altering the functionality of ABCA7. A total of five variants were predicted to be damaging by in silico annotation tools: rs3752233; rs59851484; rs3752237; rs114782266 and a novel mutation at genomic position 19:1056958. These were genotyped in the ARUK DNA Bank resource and three (rs59851484, rs3752239 and 19:1056958) showed tentative association with LOAD. However, lack of power in this study prevented any definitive associations from being formed. A further two variants were examined within functional cell assays. rs881768 had been predicted to affect the splicing of the ABCA7 protein and appeared to do so within minigene cellular assays. However, this did not appear to be the case when RNA from brain tissue harbouring this variation was examined. rs2020000 was examined through the dual luciferase assays, with the minor allele seeming to down regulate the reporter protein by approximately 30% (p<0.02) in these in vitro assays. Functional variations within the ABCA7 locus do play a role in LOAD risk and improvements within functional databases and annotation programmes will assist in identifying these causative mutations, in order to put a halt to LOAD, as well as other destructive complex disorders

New approaches to the restoration of shallow marginal peatlands

ArticleGlobally, the historic and recent exploitation of peatlands through management practices such as agricultural reclamation, peat harvesting or forestry, have caused extensive damage to these ecosystems. Their value is now increasingly recognised, and restoration and rehabilitation programmes are underway to improve some of the ecosystem services provided by peatlands: blocking drainage ditches in deep peat has been shown to improve the storage of water, decrease carbon losses in the long-term, and improve biodiversity. However, whilst the restoration process has benefitted from experience and technical advice gained from restoration of deep peatlands, shallow peatlands have received less attention in the literature, despite being extensive in both uplands and lowlands. Using the experience gained from the restoration of the shallow peatlands of Exmoor National Park (UK), and two test catchments in particular, this paper provides technical guidance which can be applied to the restoration of other shallow peatlands worldwide. Experience showed that integrating knowledge of the historical environment at the planning stage of restoration was essential, as it enabled the effective mitigation of any threat to archaeological features and sites. The use of bales, commonly employed in other upland ecosystems, was found to be problematic. Instead, ‘leaky dams’ or wood and peat combination dams were used, which are both more efficient at reducing and diverting the flow, and longer lasting than bale dams. Finally, an average restoration cost (£306 ha-1) for Exmoor, below the median national value across the whole of the UK, demonstrates the cost-effectiveness of these techniques. However, local differences in peat depth and ditch characteristics (i.e. length, depth and width) between sites affect both the feasibility and the cost of restoration. Overall, the restoration of shallow peatlands is shown to be technically viable; this paper provides a template for such process over analogous landscapes.South West WaterUniversity of ExeterTechnology Strategy BoardNERCKnowledge Transfer Partnership programm

Continuity of care for people with psychotic illness: its relationship to clinical and social functioning.

Background: The relationship between continuity of care and user characteristics or outcomes has rarely been explored. The ECHO study operationalized and tested a multi-axial definition of continuity of care, producing a seven-factor model used here. Aims: To assess the relationship between user characteristics and established components of continuity of care, and the impact of continuity on clinical and social functioning. Methods: The sample comprised 180 community mental health team users with psychotic disorders who were interviewed at three annual time-points, to assess their experiences of continuity of care and clinical and social functioning. Scores on seven continuity factors were tested for association with user-level variables. Results: Improvement in quality of life was associated with better Experience & Relationship continuity scores (better user-rated continuity and therapeutic relationship) and with lower Meeting Needs continuity factor scores. Higher Meeting Needs scores were associated with a decrease in symptoms. Conclusion: Continuity is a dynamic process, influenced significantly by care structures and organizational change

Freedom of expression, accountability and development in the Arab region

Mechanisms for ensuring government transparency and accountability have yet to become established in the Arab region, where oil rents and security rents have traditionally enabled governments to provide jobs and services without having to rely heavily, if at all, on raising revenue through personal income tax on citizens. Yet various forms of resource mobilisation, which will be needed in future, are likely to require a greater degree of accountability from those responsible for such mobilisation. This paper considers whether a move in this direction is under way. It reviews government approaches to freedom of expression in the media and among non-governmental organisations. It notes changes that have taken place in this sphere since the start of the 1990s, not all of them positive, and concludes that many more steps remain to be taken if media organisations and NGOs are to exert pressure for accountability on behalf of citizens, and especially the disadvantaged

Air-sea interaction and the seasonal cycle of the subtropical anticyclones

The causes of the seasonal cycles of the subtropical anticyclones, and the associated zonal asymmetries of sea surface temperature (SST) across the subtropical oceans, are examined. In all basins the cool waters in the east and warm waters in the west are sustained by a mix of atmosphere and ocean processes. When the anticyclones are best developed, during local summer, subsidence and equatorward advection on the eastern flanks of the anticyclones cool SSTs, while poleward flow on the western flanks warms SSTs. During local winter the SST asymmetry across the subtropical North Atlantic and North Pacific is maintained by warm water advection in the western boundary currents that offsets the large extraction of heat by advection of cold, dry air of the continents and by transient eddies. In the Southern Hemisphere ocean processes are equally important in cooling the eastern oceans by upwelling and advection during local winter. Ocean dynamics are important in amplifying the SST asymmetry, as experiments with general circulation models show. This amplification has little impact on the seasonal cycle of the anticyclones in the Northern Hemisphere, strengthens the anticyclones in the Southern Hemisphere, and helps position the anticyclones over the eastern basins in both hemispheres. Experiments with an idealized model are used to suggest that the subtropical anticyclones arise fundamentally as a response to monsoonal heating over land but need further amplification to bring them up to observed strength. The amplification is provided by local air–sea interaction. The SST asymmetry, generated through local air–sea interaction by the weak anticyclones forced by heating over land, stabilizes the atmosphere to deep convection in the east and destabilizes it in the west. Convection spreads from the land regions to the adjacent regions of the western subtropical oceans, and the enhanced zonal asymmetry of atmospheric heating strengthens the subtropical anticyclones

Metformin for endometrial hyperplasia (Review)

Background Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain. Objectives To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia. Search methods We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar,OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015. Selection criteria We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type. Data collection and analysis Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment. Main results We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision. We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59)provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others. Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37,one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea. Authors’ conclusions At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question

The evaluation of an e-learning prescribing course for general practice

Prescribed medication may lead to significant morbidity or mortality as a result of these medications causing adverse events, or because of a prescribing error. E-learning is a common tool used in supporting training in prescribing. This paper describes the development of an e-learning course and the subsequent evaluation undertaken by the users with the aim of obtaining an effective e-learning course for prescribing. The e-learning course was developed by general practitioners and pharmacists and focussed on the principles of good prescribing, examined the common reasons for prescribing errors, and was evaluated using self-reported quantitative and qualitative measures. Scores significantly increased on an assessment given before and after the course. The majority of respondents reported that the e-learning course had a positive impact on prescribing knowledge, skills and attitudes, with medication reviews the top area where a change in prescribing practice was reported. Over 90% of the respondents agreed that the e-learning course was easy to use and a useful part of their continuing professional education. This study shows that clinicians recognise the on-going need for training in prescribing, but the lack of training is one of the factors contributing to errors, which suggests that more education is needed, not just for GPs in training, but for qualified GPs as well