Features of cancer in teenagers and young adults in primary care: a population-based nested case-control study

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Teenagers and young adults (TYA, 15-24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers. METHODS: Population-based, case-control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13,206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated. RESULTS: In the 3 months before diagnosis, 397 (42.9%) cases consulted > or =4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included - LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015%; LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024%; and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%. CONCLUSION: Teenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.RMD is funded by the National Institute for Health Research (NIHR). WH was, in part, funded by an NIHR postdoctoral fellowship. This study is based on data from the Full Feature Clinical Practice Research Datalink (CPRD) obtained under licence from the UK Medicines and Healthcare Products Regulatory Agency (MHRA). Access to the CPRD was funded through the Medical Research Council (MRC) licence agreement with the UK Medicines and Healthcare Products Regulatory Agency. The conduct of this study was approved by the Independent Scientific Advisory Committee (ISAC) of the MHRS (Protocol 10_056A) and the University of Bristol (reference: 35515

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

Role of the reversible electrochemical deprotonation of phosphate species in anaerobic biocorrosion of steels

Sulphate reducing bacteria are known to play a major role in anaerobic microbiological influenced corrosion of steels, but mechanisms behind their influence are still source of debates as certain phenomena remain unexplained. Some experiments have shown that hydrogen consumption by SRB or hydrogenase increased the corrosion rate of mild steel. This was observed only in the presence of phosphate species. Here the cathodic behaviour of phosphate species on steel was studied to elucidate the role of phosphate in anaerobic corrosion of steel. Results showed: a linear correlation between reduction waves in linear voltammetry and phosphate concentration at a constant pH value; that phosphate ions induced considerable anaerobic corrosion of mild steel, which was sensitive to hydrogen concentration in the solution; and that the corrosion potential of stainless steel in presence of phosphate was shifted to more negative values as molecular hydrogen was added to the atmosphere in the reaction vessel. Phosphate species, and possibly other weak acids present in biofilms, are suggested to play an important role in the anaerobic corrosion of steels via a reversible mechanism of electrochemical deprotonation that may be accelerated by hydrogen removal

Evolutionary instability of Zero Determinant strategies demonstrates that winning isn't everything

Zero Determinant (ZD) strategies are a new class of probabilistic and conditional strategies that are able to unilaterally set the expected payoff of an opponent in iterated plays of the Prisoner's Dilemma irrespective of the opponent's strategy, or else to set the ratio between a ZD player's and their opponent's expected payoff. Here we show that while ZD strategies are weakly dominant, they are not evolutionarily stable and will instead evolve into less coercive strategies. We show that ZD strategies with an informational advantage over other players that allows them to recognize other ZD strategies can be evolutionarily stable (and able to exploit other players). However, such an advantage is bound to be short-lived as opposing strategies evolve to counteract the recognition.Comment: 14 pages, 4 figures. Change in title (again!) to comply with Nature Communications requirements. To appear in Nature Communication

The information needs of people living with ankylosing spondylitis: a questionnaire survey

<p>BACKGROUND:Today, health care is patient-centred with patients more involved in medical decision making and taking an active role in managing their disease. It is important that patients are appropriately informed about their condition and that their health care needs are met. We examine the information utilisation, sources and needs of people with ankylosing spondylitis (AS).</p> <p>METHODS: Participants in an existing AS cohort study were asked to complete a postal or online questionnaire containing closed and open-ended questions, regarding their information access and needs. Participants were stratified by age and descriptive statistics were performed using STATA 11, while thematic analysis was performed on open-ended question narratives. Qualitative data was handled in Microsoft Access and explored for emerging themes and patterns of experiences.</p> <p>RESULTS: Despite 73% of respondents having internet access, only 49% used the internet to access information regarding AS. Even then, this was only infrequently. Only 50% of respondents reported accessing written information about AS, which was obtained mainly in specialist clinics. Women were more likely than men to access information (63% (women) 46% (men)) regardless of the source, while younger patients were more likely to use online sources. The main source of non-written information was the rheumatologist. Overall, the respondents felt there was sufficient information available, but there was a perception that the tone was often too negative. The majority (95%) of people would like to receive a regular newsletter about AS, containing positive practical and local information. Suggestions were also made for more information about AS to be made available to non-specialist medical professionals and the general public.</p> <p>CONCLUSIONS: There appears to be sufficient information available for people with AS in the UK and this is mostly accessed by younger AS patients. Many patients, particularly men, choose not to access AS information and concerns were raised about its negative tone. Patients still rely on written and verbal information from their specialists. Future initiatives should focus on the delivery of more positive information, targeting younger participants in particular and increasing the awareness in the general population and wider non-specialist medical community.</p&gt

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA