Oligonucleotide therapies in the treatment of arthritis:a narrative review

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common chronic inflammatory joint diseases, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. The pathology of both OA and RA involves multiple tissues within the joint, including the synovial joint lining and the bone, as well as the articular cartilage in OA. In this review, we discuss the potential for the development of oligonucleotide therapies for these disorders by examining the evidence that oligonucleotides can modulate the key cellular pathways that drive the pathology of the inflammatory diseased joint pathology, as well as evidence in preclinical in vivo models that oligonucleotides can modify disease progression

Domestic factors in Italian intervention in the First World War.

This thesis attempts to explain Italian intervention in World War I as essentially a product of various domestic economic and political issues. It begins with a discussion of the growing economic difficulties in the years before 1914, problems which lead to greater organisation amongst both employers and labour and the collapse of Giovanni Giolitti's former political dominance. The emergence of Italian imperial aspirations in North and East Africa, the Balkans and Asia Minor is then followed. This is seen as a further symptom of Italy's economic malaise, and as the ground for cooperation between agrarian and industrial interests. Italy's demands in 1915 are linked to this imperialist programme developed over the previous decade. Salandra's decision to pull Italy out of the Triple Alliance and join the Entente powers is also caused in part by the constant clash of economic interests between Italy and the Central Powers in both the Balkans and Asia Minor: above all in their diametrically opposed railway plans which are of such great importance to both Rome and Berlin. Further pressure for intervention comes through the economic crisis of neutrality, bringing with it the threat of a repetition of the insurrection in June 1914. Neutrality also demonstrates Italy's dependence on Britain for vital raw materials and security on the seas, and brings a growing demand for intervention from industrialists. This demand also springs from a desire for lucrative state contracts, and a mounting distrust of the Banca Commerciale -which is attacked as a vehicle of German domination over economic and political life in Italy. Salandra is shown to use the campaign against this bank to strengthen his position in the political struggle against Giolitti: while intervention in the war also serves as a means to set Italian politics on a new course. The final chapter discusses the appearance and significance of the nationalist movement; in particular, its influence throughout the Italian press and on members of Salandra's Cabinet. The similar short-term goals of the government and the nationalists leads to much tacit cooperation in the campaign for intervention

Scholarly insight Autumn 2017:a Data wrangler perspective

As the OU is going through several fundamental changes, it is important that strategic decisions made by Faculties and senior management are informed by evidence-based research and insights. One way how Data Wranglers provide insights of longitudinal development and performance of OU modules is the Key Metric Report 2017. A particular new element is that data can now also be unpacked and visualised on a Nation-level. As evidenced by the Nation-level reporting, there are substantial variations of success across the four Nations, and we hope that our interactive dashboards allow OU staff to unpack the underlying data. The second way Data Wranglers provide insight to Faculties and Units is through the Scholarly insight report series. Building on the previous two reports whereby we reported on substantial variation and inconsistencies in learning designs and assessment practices within qualifications across the OU, in this Scholarly insight Autumn 2017 report we address four big pedagogical questions that were framed and co-constructed together with the Faculties and LTI units. Many Faculties and colleagues have reacted positively on our Scholarly insight Spring 2017 report, whereby for the first time we were able to show empirically that students experienced substantial variations in success within 12 large OU qualifications. As evidenced in our previous report, 55% of variation in students’ success over time was explained by OU institutional factors (i.e., how students were assessed within their respective module; how students were able to effectively transition from one learning design of one module to the next one), rather than students’ characteristics, engagement and behaviour. We have received several queries and questions from Faculties and Units about how to better understand these students’ journeys, and how qualifications and module designs could be better aligned within their respective qualification(s). As these are complex conceptual and Big Pedagogy questions, in Chapter 1 we continued these complex analyses by looking at the transitional processes of the first two modules that OU students take, and how well aligned these modules and qualification paths are. In Chapter 2, we explored the more fine-grained, qualitative, and lived experiences of 19 students across a range of qualifications to understand how OU grading practices and (in)consistencies of assessment and feedback influenced their affect, behaviour, and cognition. In addition to building on previous topics, we introduced two new Scholarly insights in Chapter 3 and Chapter 4. As the OU is increasingly using learning analytics to support our staff and students, in Chapter 3 we analysed the impact of giving Predictive Learning Analytics to over 500 Associate Lecturers across 31 modules on student retention. Finally, in Chapter 4 we explored the impact of first presentations of new modules on pass rates and satisfaction, whereby we were able to bust another myth that may have profound implications for Student First Transformation. Working organically in various Faculty sub-group meetings and LTI Units and in a google doc with various key stakeholders in the Faculties , we hope that our Scholarly insights can help to inform our staff, but also spark some ideas how to further improve our module designs and qualification pathways. Of course we are keen to hear what other topics require Scholarly insight

Active PinScreen: Exploring Spatio-Temporal Tactile Feedbackfor Multi-Finger Interaction

Multiple fingers are often used for efficient interaction with handheld computing devices. Currently, any tactile feedback provided is felt on the finger pad or the palm with coarse granularity. In contrast, we present a new tactile feedback technique, Active PinScreen, that applies localised stimuli on multiple fingers with fine spatial and temporal resolution. The tactile screen uses an array of solenoid-actuated magnetic pins with millimetre scale form-factor which could be deployed for back-of-device handheld use without instrumenting the user. As well as presenting a detailed description of the prototype, we provide the potential design configurations and the applications of the Active PinScreen and evaluate the human factors of tactile interaction with multiple fingers in a controlled user evaluation. The results of our study show a high recognition rate for directional and patterned stimulation across different grip orientations as well as within- and between- fingers. We end the paper with a discussion of our main findings, limitations in the current design and directions for future work

Plant and soil communities are associated with the response of soil water repellency to environmental stress

A warming climate and expected changes in average and extreme rainfall emphasise the importance of understanding how the land surface routes and stores surface water. The availability and movement of water within an ecosystem is a fundamental control on biological and geophysical activity, and influences many climatic feedbacks. A key phenomenon influencing water infiltration into the land surface is soil hydrophobicity, or water repellency. Despite repellency dictating the speed, volume and pattern of water infiltration, there is still major uncertainty over whether this critical hydrological process is biologically or physicochemically controlled. Here we show that soil water repellency is likely driven by changes in the plant and soil microbial communities in response to environmental stressors. We carried out a field survey in the summers of 2013 to 2016 in a variety of temperate habitats ranging across arable, grassland, forest and bog sites. We found that moderate to extreme repellency occurs in 68% of soils at a national scale in temperate ecosystems, with 92% showing some repellency. Taking a systems approach, we show that a wetter climate and low nutrient availability alter plant, bacterial and fungal community structure, which in turn are associated with increased soil water repellency across a large-scale gradient of soil, vegetation and land-use. The stress tolerance of the plant community and associated changes in soil microbial communities were more closely linked to changes in repellency than soil physicochemical properties. Our results indicate that there are consistent responses to diverse ecosystem stresses that will impact plant and microbial community composition, soil properties, and hydrological behaviour. We suggest that the ability of a biological community to induce such hydrological responses will influence the resilience of the whole ecosystem to environmental stress. This highlights the crucial role of above-belowground interactions in mediating climatic feedbacks and dictating ecosystem health

Dietary interventions for adult cancer survivors.

BACKGROUND: International dietary recommendations include guidance on healthy eating and weight management for people who have survived cancer; however dietary interventions are not provided routinely for people living beyond cancer. OBJECTIVES: To assess the effects of dietary interventions for adult cancer survivors on morbidity and mortality, changes in dietary behaviour, body composition, health-related quality of life, and clinical measurements. SEARCH METHODS: We ran searches on 18 September 2019 and searched the Cochrane Central Register of Controlled trials (CENTRAL), in the Cochrane Library; MEDLINE via Ovid; Embase via Ovid; the Allied and Complementary Medicine Database (AMED); the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and the Database of Abstracts of Reviews of Effects (DARE). We searched other resources including reference lists of retrieved articles, other reviews on the topic, the International Trials Registry for ongoing trials, metaRegister, Physicians Data Query, and appropriate websites for ongoing trials. We searched conference abstracts and WorldCat for dissertations. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited people following a cancer diagnosis. The intervention was any dietary advice provided by any method including group sessions, telephone instruction, written materials, or a web-based approach. We included comparisons that could be usual care or written information, and outcomes measured included overall survival, morbidities, secondary malignancies, dietary changes, anthropometry, quality of life (QoL), and biochemistry. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Two people independently assessed titles and full-text articles, extracted data, and assessed risk of bias. For analysis, we used a random-effects statistical model for all meta-analyses, and the GRADE approach to rate the certainty of evidence, considering limitations, indirectness, inconsistencies, imprecision, and bias. MAIN RESULTS: We included 25 RCTs involving 7259 participants including 977 (13.5%) men and 6282 (86.5%) women. Mean age reported ranged from 52.6 to 71 years, and range of age of included participants was 23 to 85 years. The trials reported 27 comparisons and included participants who had survived breast cancer (17 trials), colorectal cancer (2 trials), gynaecological cancer (1 trial), and cancer at mixed sites (5 trials). For overall survival, dietary intervention and control groups showed little or no difference in risk of mortality (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.77 to 1.23; 1 study; 3107 participants; low-certainty evidence). For secondary malignancies, dietary interventions versus control trials reported little or no difference (risk ratio (RR) 0.99, 95% CI 0.84 to 1.15; 1 study; 3107 participants; low-certainty evidence). Co-morbidities were not measured in any included trials. Subsequent outcomes reported after 12 months found that dietary interventions versus control probably make little or no difference in energy intake at 12 months (mean difference (MD) -59.13 kcal, 95% CI -159.05 to 37.79; 5 studies; 3283 participants; moderate-certainty evidence). Dietary interventions versus control probably led to slight increases in fruit and vegetable servings (MD 0.41 servings, 95% CI 0.10 to 0.71; 5 studies; 834 participants; moderate-certainty evidence); mixed results for fibre intake overall (MD 5.12 g, 95% CI 0.66 to 10.9; 2 studies; 3127 participants; very low-certainty evidence); and likely improvement in Diet Quality Index (MD 3.46, 95% CI 1.54 to 5.38; 747 participants; moderate-certainty evidence). For anthropometry, dietary intervention versus control probably led to a slightly decreased body mass index (BMI) (MD -0.79 kg/m², 95% CI -1.50 to -0.07; 4 studies; 777 participants; moderate-certainty evidence). Dietary interventions versus control probably had little or no effect on waist-to-hip ratio (MD -0.01, 95% CI -0.04 to 0.02; 2 studies; 106 participants; low-certainty evidence). For QoL, there were mixed results; several different quality assessment tools were used and evidence was of low to very low-certainty. No adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS: Evidence demonstrated little effects of dietary interventions on overall mortality and secondary cancers. For comorbidities, no evidence was identified. For nutritional outcomes, there was probably little or no effect on energy intake, although probably a slight increase in fruit and vegetable intake and Diet Quality Index. Results were mixed for fibre. For anthropometry, there was probably a slight decrease in body mass index (BMI) but probably little or no effect on waist-to-hip ratio. For QoL, results were highly varied. Additional high-quality research is needed to examine the effects of dietary interventions for different cancer sites, and to evaluate important outcomes including comorbidities and body composition. Evidence on new technologies used to deliver dietary interventions was limited

Scholarly insight Spring 2018: a Data wrangler perspective

In the movie classic Back to the Future a young Michael J. Fox is able to explore the past by a time machine developed by the slightly bizarre but exquisite Dr Brown. Unexpectedly by some small intervention the course of history was changed a bit along Fox’s adventures. In this fourth Scholarly Insight Report we have explored two innovative approaches to learn from OU data of the past, which hopefully in the future will make a large difference in how we support our students and design and implement our teaching and learning practices. In Chapter 1, we provide an in-depth analysis of 50 thousands comments expressed by students through the Student Experience on a Module (SEAM) questionnaire. By analysing over 2.5 million words using big data approaches, our Scholarly insights indicate that not all student voices are heard. Furthermore, our big data analysis indicate useful potential insights to explore how student voices change over time, and for which particular modules emergent themes might arise. In Chapter 2 we provide our second innovative approach of a proof-of-concept of qualification path way using graph approaches. By exploring existing data of one qualification (i.e., Psychology), we show that students make a range of pathway choices during their qualification, some of which are more successful than others. As highlighted in our previous Scholarly Insight Reports, getting data from a qualification perspective within the OU is a difficult and challenging process, and the proof-of-concept provided in Chapter 2 might provide a way forward to better understand and support the complex choices our students make. In Chapter 3, we provide a slightly more practically-oriented and perhaps down to earth approach focussing on the lessons-learned with Analytics4Action. Over the last four years nearly a hundred modules have worked with more active use of data and insights into module presentation to support their students. In Chapter 3 several good-practices are described by the LTI/TEL learning design team, as well as three innovative case-studies which we hope will inspire you to try something new as well. Working organically in various Faculty sub-group meetings and LTI Units and in a google doc with various key stakeholders in the Faculties, we hope that our Scholarly insights can help to inform our staff, but also spark some ideas how to further improve our module designs and qualification pathways. Of course we are keen to hear what other topics require Scholarly insight. We hope that you see some potential in the two innovative approaches, and perhaps you might want to try some new ideas in your module. While a time machine has not really been invented yet, with the increasing rich and fine-grained data about our students and our learning practices we are getting closer to understand what really drives our students

Incorporating sedimentological data in UK flood frequency estimation

This study presents a new analytical framework for combining historical flood data derived from sedimentological records with instrumental river flow data to increase the reliability of flood risk assessments. Historical flood records were established for two catchments through re-analysis of sedimentological records; the Nant Cwm-du, a small, steep upland catchment in the Cambrian Mountains of Wales, and a piedmont reach of the River Severn in mid Wales. The proposed framework is based on maximum likelihood and least-square estimation methods in combination with a Generalised Logistic distribution; this enables the sedimentological data to be combined effectively with existing instrumental river flow data. The results from this study are compared to results obtained using existing industry standard methods based solely on instrumental data. The comparison shows that inclusion of sedimentological data can have an important impact on flood risk estimates, and that the methods are sensitive to assumptions made in the conversion of the sedimentological records into flood flow data. As current industry standard methods for flood risk analysis are known to be highly uncertain, the ability to include additional evidence of past flood events derived from sedimentological records as demonstrated in this study can have a significant impact on flood risk assessments