Comparing primary and secondary health-care use between diagnostic routes before a colorectal cancer diagnosis: Cohort study using linked data

BACKGROUND: Survival in cancer patients diagnosed following emergency presentations is poorer than those diagnosed through other routes. To identify points for intervention to improve survival, a better understanding of patients' primary and secondary health-care use before diagnosis is needed. Our aim was to compare colorectal cancer patients' health-care use by diagnostic route. METHODS: Cohort study of colorectal cancers using linked primary and secondary care and cancer registry data (2009-2011) from four London boroughs. The prevalence of all and relevant GP consultations and rates of primary and secondary care use up to 21 months before diagnosis were compared across diagnostic routes (emergency, GP-referred and consultant/other). RESULTS: The data set comprised 943 colorectal cancers with 24% diagnosed through emergency routes. Most (84%) emergency patients saw their GP 6 months before diagnosis but their symptom profile was distinct; fewer had symptoms meeting urgent referral criteria than GP-referred patients. Compared with GP-referred, emergency patients used primary care less (IRR: 0.85 (95% CI 0.78-0.93)) and urgent care more frequently (IRR: 1.56 (95% CI 1.12; 2.17)). CONCLUSIONS: Distinct patterns of health-care use in patients diagnosed through emergency routes were identified in this cohort. Such analyses using linked data can inform strategies for improving early diagnosis of colorectal cancer

Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care

The field of acquired CNS neuroimmune demyelination in children is transforming. Progress in assay development, refinement of diagnostic criteria, increased biological insights provided by advanced neuroimaging techniques, and high-level evidence for the therapeutic efficacy of biological agents are redefining diagnosis and care. Three distinct neuroimmune conditions-multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (AQP4-NMOSD)-can now be distinguished, with evidence from humans and animal models supporting distinct pathobiological disease mechanisms. The development of highly effective therapies for adult-onset multiple sclerosis and AQP4-NMOSD that suppress relapse rate by more than 90% has motivated advocacy for trials in children. However, doing clinical trials is challenging because of the rarity of these conditions in the paediatric age group, necessitating new approaches to trial design, including age-based trajectory modelling based on phase 3 studies in adults. Despite these limitations, the future for children and adolescents living with multiple sclerosis, MOGAD, or AQP4-NMOSD is far brighter than in years past, and will be brighter still if successful therapies to promote remyelination, enhance neuroprotection, and remediate cognitive deficits can be further accelerated

Multi-frequency, Multi-Epoch Study of Mrk 501: Hints for a two-component nature of the emission

Since the detection of very high energy (VHE) $\gamma$-rays from Mrk 501, its broad band emission of radiation was mostly and quite effectively modeled using one zone emission scenario. However, broadband spectral and flux variability studies enabled by the multiwavelength campaigns carried out during the recent years have revealed rather complex behavior of Mrk 501. The observed emission from Mrk 501 could be due to a complex superposition of multiple emission zones. Moreover new evidences of detection of very hard intrinsic $\gamma$-ray spectra obtained from {\it Fermi}--LAT observations have challenged the theories about origin of VHE $\gamma$-rays. Our studies based on {\it Fermi}--LAT data indicate the existence of two separate components in the spectrum, one for low energy $\gamma$-rays and the other for high energy $\gamma$-rays. Using multiwaveband data from several ground and space based instruments, in addition to HAGAR data, the spectral energy distribution of Mrk~501 is obtained for various flux states observed during 2011. In the present work, this observed broadband spectral energy distribution is reproduced with a leptonic, multi-zone Synchrotron Self-Compton model.Comment: Published in Astrophysical Journal (ApJ

Evaluation of different deployment strategies for larviciding to control malaria: a simulation study

BACKGROUND: Larviciding against malaria vectors in Africa has been limited to indoor residual spraying and insecticide-treated nets, but is increasingly being considered by some countries as a complementary strategy. However, despite progress towards improved larvicides and new tools for mapping or treating mosquito-breeding sites, little is known about the optimal deployment strategies for larviciding in different transmission and seasonality settings. METHODS: A malaria transmission model, OpenMalaria, was used to simulate varying larviciding strategies and their impact on host-seeking mosquito densities, entomological inoculation rate (EIR) and malaria prevalence. Variations in coverage, duration, frequency, and timing of larviciding were simulated for three transmission intensities and four transmission seasonality profiles. Malaria transmission was assumed to follow rainfall with a lag of one month. Theoretical sub-Saharan African settings with Anopheles gambiae as the dominant vector were chosen to explore impact. Relative reduction compared to no larviciding was predicted for each indicator during the simulated larviciding period. RESULTS: Larviciding immediately reduced the predicted host-seeking mosquito densities and EIRs to a maximum that approached or exceeded the simulated coverage. Reduction in prevalence was delayed by approximately one month. The relative reduction in prevalence was up to four times higher at low than high transmission. Reducing larviciding frequency (i.e., from every 5 to 10 days) resulted in substantial loss in effectiveness (54, 45 and 53% loss of impact for host-seeking mosquito densities, EIR and prevalence, respectively). In seasonal settings the most effective timing of larviciding was during or at the beginning of the rainy season and least impactful during the dry season, assuming larviciding deployment for four months. CONCLUSION: The results highlight the critical role of deployment strategies on the impact of larviciding. Overall, larviciding would be more effective in settings with low and seasonal transmission, and at the beginning and during the peak densities of the target species populations. For maximum impact, implementers should consider the practical ranges of coverage, duration, frequency, and timing of larviciding in their respective contexts. More operational data and improved calibration would enable models to become a practical tool to support malaria control programmes in developing larviciding strategies that account for the diversity of contexts

Multiwavelength study of TeV Blazar Mrk421 during giant flare

Context: The nearby (z=0.031) TeV blazar Mrk421 was reported to be in a high state of flux activity since November, 2009. Aims: To investigate possible changes in the physical parameters of Mrk421 during its high state of activity using multiwavelength data. Methods: We have observed this source in bright state using High Altitude GAmma Ray (HAGAR) telescope array at energies above 250 GeV during February 13 - 19, 2010. Optical, X-ray and gamma-ray archival data are also used to obtain the SEDs and light curves. Results: Mrk421 was found to undergo one of its brightest flaring episodes on February 17, 2010 by various observations in X-rays and gamma-rays. HAGAR observations during February 13 - 19, 2010 at the energies above 250 GeV show an enhancement in the flux level, with a maximum flux of ~ 7 Crab units being detected on February 17, 2010. We present the spectral energy distributions during this flaring episode and investigate the correlation of the variability in X-ray and gamma-ray bands. Conclusions: Our multiwavelength study suggests that the flare detected during February 16 and 17, 2010 could arise due to a passing shock in the jet.Comment: 9 pages, 10 figures, Accepted for publication in Astronomy and Astrophysics (A & A

A Monte Carlo Simulation Approach to the Reliability Modeling of the Beam Permit System of the Relativistic Heavy Ion Collider (RHIC) at BNL

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