Features of childhood cancer in primary care: a population-based nested case-control study.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: This study investigated the risk of cancer in children with alert symptoms identified in current UK guidance, or with increased consultation frequency in primary care. METHODS: A population-based, nested case-control study used data from the General Practice Research Database. In all, 1267 children age 0-14 years diagnosed with childhood cancer were matched to 15,318 controls. Likelihood ratios and positive predictive values (PPVs) were calculated to assess risk. RESULTS: Alert symptoms recorded in the 12 and 3 months before diagnosis were present in 33.7% and 27.0% of cases vs 5.4% and 1.4% of controls, respectively. The PPV of having cancer for any alert symptom in the 3 months before diagnosis was 0.55 per 1000 children. Cases consulted more frequently particularly in the 3 months before diagnosis (86% cases vs 41% controls). Of these, 36% of cases and 9% of controls had consulted 4 times or more. The PPV for cancer in a child consulting 4 times or more in 3 months was 0.13 per 1000 children. CONCLUSION: Alert symptoms and frequent consultations are associated with childhood cancer. However, individual symptoms and consultation patterns have very low PPVs for cancer in primary care (e.g., of 10,000 children with a recorded alert symptom, approximately 6 would be diagnosed with cancer within 3 months).RMD is funded by the National Institute for Health Research (NIHR). WH was part funded by a NIHR postdoctoral fellowship. This study is based on data from the Full Feature General Practice Research Database (GPRD) obtained under licence from the UK Medicines and Healthcare Products Regulatory Agency (MHRA). However, the interpretation and conclusions contained in this study are those of the author/s alone. Access to the GPRD was funded through the Medical Research Council (MRC) licence agreement with the UK Medicines and Healthcare Products Regulatory Agency

Fathers of adults who have a learning disability : roles, needs and concerns

Background: There is little research that specifically relates to fathers of adults with a learning disability despite the social expectation that fathers will provide a supportive role over the lifespan. Methods: Semi-structured interviews were carried out with seven fathers of adults with a learning disability to explore their roles, needs and concerns. Data was analysed using a framework associated with Interpretative Phenomenological Analysis (IPA). Results: Themes arising demonstrate that fathers were shocked at the diagnosis of learning disability but usually reported adaptation over time. The impact of learning disability upon men’s lives, their perception of their adult child and the roles they assumed were varied. Fathers valued support from wives and grandparents; having knowledge and interests and work type roles. All fathers were concerned about the future yet comprehensive futures planning was lacking. Some fathers reported difficulties in being emotionally open, and referred to societal stereotypes. Fathers valued positive support from service providers; however this relationship was often in conflict. Conclusion: Although mothers are often the main carers for adults with a learning disability, fathers can make a significant contribution. The findings presented here support the results of previous studies regarding paternal response to learning disability and varied impact upon men’s lives. Identified support strategies include leisure interests, volunteer/ work roles, having information and support from wives and grandparents. Ongoing concerns incorporate the future and ambivalent relationships with service providers, which could have a negative impact upon the individual who has a learning disability

Species-specific cuticular hydrocarbon stability within European Myrmica Ants

Recognition is a fundamental process on which all subsequent behaviors are based at every organizational level, from the gene up to the super-organism. At the whole organism level visual recognition is the best understood. However, chemical communication is far more widespread than visual communication, but despite its importance is much less understood. Ants provide an excellent model system for chemical ecology studies as it is well established that compounds known as cuticular hydrocarbons (CHCs) are used as recognition cues in ants. Therefore, stable species-specific odors should exist, irrespective of geographic locality. We tested this hypothesis by comparing the CHC profiles of workers of twelve species of Myrmica ants from four countries across Europe, from Iberia to the Balkans and from the Mediterranean to Fennoscandia. CHCs remained qualitatively stable within each species, right down to the isomer level. Despite the morphological similarity that occurs within the genus Myrmica, their CHCs were highly diverse but remarkably species-specific and stable across wide geographical areas. This indicates a genetic mechanism under strong selection that produces these species-specific chemical profiles, despite each species encountering different environmental conditions across its range

Adaptability of great cormorants Phalacrocorax carbo in a coastal environment demonstrated by their exploitation of introduced prey species and use of artificial breeding sites

An analysis of the contents of regurgitations of great cormorant Phalacrocorax carbo chicks at two coastal colonies in South Africa, one on an offhore island (St Croix) and the other at a saltworks in an estuary (Swartkops), revealed that the diet was dominated by introduced freshwater and estuarine fish. Most other prey species were indigenous euryhaline fish, and from the size ranges of the estuary-dependent species it was clear that they had been obtained in estuaries. Great cormorants in this coastal environment have learned to exploit introduced fish species, but use offshore islands as safe breeding sites, unless suitably safe artificial sites are created near their preferred foraging areas.Keywords: chick regurgitations, diet, St Croix Island, Swartkops RiverAfrican Journal of Marine Science 2002, 24: 317–32

X-ray diffraction from bone employing annular and semi-annular beams

This is the final version of the article. Available from the publisher via the DOI in this record.There is a compelling need for accurate, low cost diagnostics to identify osteo-tissues that are associated with a high risk of fracture within an individual. To satisfy this requirement the quantification of bone characteristics such as 'bone quality' need to exceed that provided currently by densitometry. Bone mineral chemistry and microstructure can be determined from coherent x-ray scatter signatures of bone specimens. Therefore, if these signatures can be measured, in vivo, to an appropriate accuracy it should be possible by extending terms within a fracture risk model to improve fracture risk prediction.In this preliminary study we present an examination of a new x-ray diffraction technique that employs hollow annular and semi-annular beams to measure aspects of 'bone quality'. We present diffractograms obtained with our approach from ex vivo bone specimens at Mo Kα and W Kα energies. Primary data is parameterized to provide estimates of bone characteristics and to indicate the precision with which these can be determined.We acknowledge gratefully the funding provided by the UK Engineering and Physical Sciences Research Council (EPSRC) grant number EP/K020196/

Life inside and out: making and breaking protein disulfide bonds in Chlamydia

© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Disulphide bonds are widely used among all domains of life to provide structural stability to proteins and to regulate enzyme activity. Chlamydia spp. are obligate intracellular bacteria that are especially dependent on the formation and degradation of protein disulphide bonds. Members of the genus Chlamydia have a unique biphasic developmental cycle alternating between two distinct cell types; the extracellular infectious elementary body (EB) and the intracellular replicating reticulate body. The proteins in the envelope of the EB are heavily cross-linked with disulphides and this is known to be critical for this infectious phase. In this review, we provide a comprehensive summary of what is known about the redox state of chlamydial envelope proteins throughout the developmental cycle. We focus especially on the factors responsible for degradation and formation of disulphide bonds in Chlamydia and how this system compares with redox regulation in other organisms. Focussing on the unique biology of Chlamydia enables us to provide important insights into how specialized suites of disulphide bond (Dsb) proteins cater for specific bacterial environments and lifecycles

First-principles modeling of strain in perovskite ferroelectric thin films

We review the role that first-principles calculations have played in understanding the effects of substrate-imposed misfit strain on epitaxially grown perovskite ferroelectric films. We do so by analyzing the case of BaTiO$_3$, complementing our previous publications on this subject with unpublished data to help explain in detail how these calculations are done. We also review similar studies in the literature for other perovskite ferroelectric-film materials.Comment: 14 pages, submitted to Phase Transition

Energy's and amplitudes' positivity

In QFT, the null energy condition (NEC) for a classical field configuration is usually associated with that configuration's stability against small perturbations, and with the sub-luminality of these. Here, we exhibit an effective field theory that allows for stable NEC-violating solutions with exactly luminal excitations only. The model is the recently introduced `galileon', or more precisely its conformally invariant version. We show that the theory's low-energy S-matrix obeys standard positivity as implied by dispersion relations. However we also show that if the relevant NEC-violating solution is inside the effective theory, then other (generic) solutions allow for superluminal signal propagation. While the usual association between sub-luminality and positivity is not obeyed by our example, that between NEC and sub-luminality is, albeit in a less direct way than usual.Comment: 21 pages. v2: Typos in eq. (2.41) and (2.41) corrected; discussion of section 2.3 modified accordingly. Other sections and conclusions unchanged. Matches the Erratum published in JHE

Achieving highly efficient gene transfer to the bladder by increasing the molecular weight of polymer-based nanoparticles

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1.35 ng/g luciferase protein expression in the urothelium and lamina propria regions. The relatively higher molecular weight polymer (83 kDa) did not induce morphologic changes or inflammatory responses in the bladder. This approach of altering polymer molecular weight for prolonging gene transfer residence time and deeper penetration through the BPB could be the basis for the design of future gene therapies for bladder diseases