Changes over time in socioeconomic inequalities in breast and rectal cancer survival in England and Wales during a 32-year period (1973-2004): the potential role of health care.

BACKGROUND: Socioeconomic inequalities in cancer survival are well documented but they vary for different cancers and over time. Reasons for these differences are poorly understood. PATIENTS AND METHODS: For England and Wales, we examined trends in socioeconomic survival inequalities for breast cancer in women and rectal cancer in men during the 32-year period 1973-2004. We used a theoretical framework based on Victora's 'inverse equity' law, under which survival inequalities could change with the advent of successive new treatments, of varying effectiveness, which are disseminated with different speed among patients of different socioeconomic groups. We estimated 5-year relative survival for patients of different deprivation quintiles and examined trends in survival inequalities in light of major treatment innovations. RESULTS: Inequalities in breast cancer survival (921,611 cases) narrowed steadily during the study (from -10% to -6%). In contrast, inequalities in rectal cancer survival (187,104 cases) widened overall (form -5% to -11%) with fluctuating periods of narrowing inequality. CONCLUSIONS: Trends in socioeconomic differences in tumour or patient factors are unlikely explanations of observed changes over time in survival inequalities. The sequential introduction into clinical practice of new treatments of progressively smaller incremental benefit may partly explain the reduction in inequality in breast cancer survival

The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.

The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system

Major Modes of Variability

This chapter focused on major modes of variability which serve the key role in controlling the regional climate. In terms of tropospheric variability, it defined and discussed ENSO (El Niño Southern Oscillation), NAO (North Atlantic Oscillation), AO and AAO (Arctic Oscillation, Antarctic Oscillation), Indian Monsoon, Indian Ocean Dipole (IOD), PDO (Pacific Decadal Oscillation) and AMO (Atlantic Multidecadal Oscillation). Later it attended stratosphere variability; this constitutes QBO (quasi-biennial oscillation) and SSW (stratospheric sudden warming). Main characteristic features of each of these modes were elaborately discussed

Ultrasonic NDE of Green-State Ceramics by Focused Through-Transmission

Reliable NDE techniques for green-state (unfired) ceramics are needed (1) to evaluate ceramic powder processing and compaction methods and (2) to screen out defective ceramic components prior to the costly densification process. Past work in the application of ultrasonic NDE to green-state ceramics has been hampered by the lack of an efficient yet safe means to obtain ultrasonic coupling, since conventional coupling fluids (water, gels, oils, etc.) have a detrimental effect on fragile green-state materials. In early work, direct contact pressure was used to obtain dry coupling between transducer and specimen [1]. This approach was later improved upon by placing an elastomer membrane between the transducer and specimen; this method provided efficient coupling at significantly lower contact pressures [2]. In the study presented here, an acoustically transparent plastic membrane was held against the ceramic specimen by atmospheric pressure [3]. The advantage of this technique is that it allows the use of ultrasonic immersion techniques as well as contact transducers

Experiences of the ‘Nearest Relative’ provisions in the compulsory detention of people under the Mental Health Act: rapid systematic review

This is the final version. Available from NIHR Journals Library via the DOI in this record.Background Service users detained for assessment and/or treatment under the Mental Health Act 1983 are allocated a ‘Nearest Relative’. The Nearest Relative has access to confidential information about the service user, and can make decisions about their care and treatment. Tensions exist regarding the identification, displacement and powers of the Nearest Relative. Objectives To examine the experiences of service users, carers and relevant professionals of the Nearest Relative provisions of the Mental Health Act 1983, and the equivalent Named Person provisions in Scotland. Five research objectives were defined, understanding the experiences of and issues associated with i) identification of the Nearest Relative, ii) displacement of the Nearest Relative, iii) confidentiality and information sharing iv) access to support from carers and v) making decisions about treatment or care. Data sources Seven bibliographic databases: MEDLINE (via Ovid), MEDLINE In-Process & Other Non-Indexed Citations (via Ovid), PsycINFO (via Ovid), Social Policy and Practice (via Ovid), HMIC (via Ovid), CINAHL (via EBSCO) and ASSIA (via ProQuest). Citation searching, author contact and grey literature searches were conducted. Review methods A rapid systematic review was conducted in six weeks. Evidence published after 1998 was sought from the UK, pertaining to the experiences of those involved in compulsory detention under the Mental Health Act 1983 (or UK variants), including service users, carers, family members, Nearest Relatives, Named Persons, mental health professionals, policy makers and lawyers. Study selection, data extraction and critical appraisal were completed independently by two reviewers. We sought data about experiences obtained through qualitative means or surveys. Included studies containing several paragraphs of participant quotes and/or author interpretations were entered into a framework synthesis; the rest were summarised descriptively. The framework synthesis was based upon the five research objectives and refined using the findings of key studies from England and Scotland and inductive thematic analysis. Findings Twenty studies were included with 12 prioritised for framework synthesis. Four themes emerged i) issues regarding the identification of the Nearest Relative/Named Person, ii) confidentiality and information sharing, iii) enabling use of the Nearest Relative/Named Person role and iv) importance of maintaining relationships. The involvement of service users in choosing their representative and the role of services in supporting the Nearest Relative/Named Person was identified as important. Limitations There is little recent evidence to inform this important and complex discussion. The review was rigorously conducted despite the short timescale; however a more in-depth, iterative thematic analysis of all the included studies may have provided additional insights into the mechanisms underpinning the issues. Conclusions The Nearest Relative provisions of the Mental Health Act 1983 are complex and of significant importance to individuals detained under the Act and their carers. This rapid review provides specific examples of issues that individuals may experience. More research is needed to aid understanding of this complex topic. Future work Primary research specifically focussed on the perceived and actual use and impact of the Nearest Relative provisions in England and Scotland.This report was commissioned by the Department of Health and Social Care via the NIHR HS&DR programme as a review project within NIHR HS&DR programme project number 16/47/22

Rapid and specific biotin labelling of the erythrocyte surface antigens of both cultured and ex-vivo Plasmodium parasites

<p>Abstract</p> <p>Background</p> <p>Sensitive detection of parasite surface antigens expressed on erythrocyte membranes is necessary to further analyse the molecular pathology of malaria. This study describes a modified biotin labelling/osmotic lysis method which rapidly produces membrane extracts enriched for labelled surface antigens and also improves the efficiency of antigen recovery compared with traditional detergent extraction and surface radio-iodination. The method can also be used with <it>ex-vivo </it>parasites.</p> <p>Methods</p> <p>After surface labelling with biotin in the presence of the inhibitor furosemide, detergent extraction and osmotic lysis methods of enriching for the membrane fractions were compared to determine the efficiency of purification and recovery. Biotin-labelled proteins were identified on silver-stained SDS-polyacrylamide gels.</p> <p>Results</p> <p>Detergent extraction and osmotic lysis were compared for their capacity to purify biotin-labelled <it>Plasmodium falciparum </it>and <it>Plasmodium chabaudi </it>erythrocyte surface antigens. The pellet fraction formed after osmotic lysis of <it>P. falciparum-infected </it>erythrocytes is notably enriched in suface antigens, including PfEMP1, when compared to detergent extraction. There is also reduced co-extraction of host proteins such as spectrin and Band 3.</p> <p>Conclusion</p> <p>Biotinylation and osmotic lysis provides an improved method to label and purify parasitised erythrocyte surface antigen extracts from both <it>in vitro </it>and <it>ex vivo Plasmodium </it>parasite preparations.</p

Genetic algorithm learning as a robust approach to RNA editing site prediction

BACKGROUND: RNA editing is one of several post-transcriptional modifications that may contribute to organismal complexity in the face of limited gene complement in a genome. One form, known as C → U editing, appears to exist in a wide range of organisms, but most instances of this form of RNA editing have been discovered serendipitously. With the large amount of genomic and transcriptomic data now available, a computational analysis could provide a more rapid means of identifying novel sites of C → U RNA editing. Previous efforts have had some success but also some limitations. We present a computational method for identifying C → U RNA editing sites in genomic sequences that is both robust and generalizable. We evaluate its potential use on the best data set available for these purposes: C → U editing sites in plant mitochondrial genomes. RESULTS: Our method is derived from a machine learning approach known as a genetic algorithm. REGAL (RNA Editing site prediction by Genetic Algorithm Learning) is 87% accurate when tested on three mitochondrial genomes, with an overall sensitivity of 82% and an overall specificity of 91%. REGAL's performance significantly improves on other ab initio approaches to predicting RNA editing sites in this data set. REGAL has a comparable sensitivity and higher specificity than approaches which rely on sequence homology, and it has the advantage that strong sequence conservation is not required for reliable prediction of edit sites. CONCLUSION: Our results suggest that ab initio methods can generate robust classifiers of putative edit sites, and we highlight the value of combinatorial approaches as embodied by genetic algorithms. We present REGAL as one approach with the potential to be generalized to other organisms exhibiting C → U RNA editing

Enhanced seasonal forecast skill following stratospheric sudden warmings

Advances in seasonal forecasting have brought widespread socio-economic benefits. However, seasonal forecast skill in the extratropics is relatively modest, prompting the seasonal forecasting community to search for additional sources of predictability. For over a decade it has been suggested that knowledge of the state of the stratosphere can act as a source of enhanced seasonal predictability; long-lived circulation anomalies in the lower stratosphere that follow stratospheric sudden warmings are associated with circulation anomalies in the troposphere that can last up to two months. Here, we show by performing retrospective ensemble model forecasts that such enhanced predictability can be realized in a dynamical seasonal forecast system with a good representation of the stratosphere. When initialized at the onset date of stratospheric sudden warmings, the model forecasts faithfully reproduce the observed mean tropospheric conditions in the months following the stratospheric sudden warmings. Compared with an equivalent set of forecasts that are not initialized during stratospheric sudden warmings, we document enhanced forecast skill for atmospheric circulation patterns, surface temperatures over northern Russia and eastern Canada and North Atlantic precipitation. We suggest that seasonal forecast systems initialized during stratospheric sudden warmings are likely to yield significantly greater forecast skill in some regions