Forecasting GOES 15 >2 MeV Electron Fluxes From Solar Wind Data and Geomagnetic Indices

The flux of > 2 MeV electrons at geosynchronous orbit is used by space weather forecasters as a key indicator of enhanced risk of damage to spacecraft in low, medium or geosynchronous Earth orbits. We present a methodology that uses the amount of time a single input dataset (solar wind data or geomagnetic indices) exceeds a given threshold to produce deterministic and probabilistic forecasts of the > 2 MeV flux at GEO exceeding 1000 or 10000 cm ‐2 s ‐1 sr ‐1 within up to 10 days. By comparing our forecasts with measured fluxes from GOES 15 between 2014 and 2016, we determine the optimum forecast thresholds for deterministic and probabilistic forecasts by maximising the ROC and Brier Skill Scores respectively. The training dataset gives peak ROC scores of 0.71 to 0.87 and peak Brier Skill Scores of ‐0.03 to 0.32. Forecasts from AL give the highest skill scores for forecasts of up to 6‐days. AL, solar wind pressure or SYM‐H give the highest skill scores over 7‐10 days. Hit rates range over 56‐89% with false alarm rates of 11‐53%. Applied to 2012, 2013 and 2017, our best forecasts have hit rates of 56‐83% and false alarm rates of 10‐20%. Further tuning of the forecasts may improve these. Our hit rates are comparable to those from operational fluence forecasts, that incorporate fluence measurements, but our false alarm rates are higher. This proof‐of‐concept shows that the geosynchronous electron flux can be forecast with a degree of success without incorporating a persistence element into the forecasts

Molecular evidence for the presence of malaria vector species a of the Anopheles annularis complex in Sri Lanka

<p>Abstract</p> <p>Background</p> <p><it>Anopheles annularis s.l</it>. is a wide spread malaria vector in South and Southeast Asia, including Sri Lanka. The taxon <it>An. annularis </it>is a complex of two sibling species viz. A and B, that are differentiated by chromosome banding patterns and ribosomal gene sequences in India. Only species A is reported to be a malaria vector in India while the occurrence of sibling species in Sri Lanka has not been documented previously.</p> <p>Findings</p> <p>Anopheline larvae were collected at a site in the Jaffna district, which lies within the dry zone of Sri Lanka, and reared in the laboratory. Emerged adults were identified using standard keys. DNA sequences of the D3 domain of 28S ribosomal DNA (rDNA) and the internal transcribed spacer-2 (ITS-2) of the morphologically identified <it>An. annularis </it>were determined. BLASTn searches against corresponding <it>An. annularis </it>sequences in GenBank and construction of phylogenetic trees from D3 and ITS-2 rDNA sequences showed that the Sri Lankan specimens, and <it>An. annularis s.l</it>. specimens from several Southeast Asian countries were closely related to species A of the Indian <it>An. annularis </it>complex.</p> <p>Conclusions</p> <p>The results show the presence of the malaria vector <it>An. annularis </it>species A in Sri Lanka and Southeast Asia. Because <it>An. annularis </it>vectors have been long associated with malaria transmission in irrigated agricultural areas in the Sri Lankan dry zone, continued monitoring of <it>An. annularis </it>populations, and their sibling species status, in these areas need to be integral to malaria control and eradication efforts in the island.</p

Movements of Wolves at the Northern Extreme of the Species' Range, Including during Four Months of Darkness

Information about wolf (Canis lupus) movements anywhere near the northern extreme of the species' range in the High Arctic (>75°N latitude) are lacking. There, wolves prey primarily on muskoxen (Ovibos moschatus) and must survive 4 months of 24 hr/day winter darkness and temperatures reaching −53 C. The extent to which wolves remain active and prey on muskoxen during the dark period are unknown, for the closest area where information is available about winter wolf movements is >2,250 km south. We studied a pack of ≥20 wolves on Ellesmere Island, Nunavut, Canada (80°N latitude) from July 2009 through mid-April 2010 by collaring a lead wolf with a Global Positioning System (GPS)/Argos radio collar. The collar recorded the wolf's precise locations at 6:00 a.m. and 6:00 p.m. daily and transmitted the locations by satellite to our email. Straight-line distances between consecutive 12-hr locations varied between 0 and 76 km. Mean (SE) linear distance between consecutive locations (n = 554) was 11 (0.5) km. Total minimum distance traveled was 5,979 km, and total area covered was 6,640 km2, the largest wolf range reported. The wolf and presumably his pack once made a 263-km (straight-line distance) foray to the southeast during 19–28 January 2010, returning 29 January to 1 February at an average of 41 km/day straight-line distances between 12-hr locations. This study produced the first detailed movement information about any large mammal in the High Arctic, and the average movements during the dark period did not differ from those afterwards. Wolf movements during the dark period in the highest latitudes match those of the other seasons and generally those of wolves in lower latitudes, and, at least with the gross movements measurable by our methods, the 4-month period without direct sunlight produced little change in movements

Priority setting in primary health care - dilemmas and opportunities: a focus group study

<p>Abstract</p> <p>Background</p> <p>Swedish health care authorities use three key criteria to produce national guidelines for local priority setting: severity of the health condition, expected patient benefit, and cost-effectiveness of medical intervention. Priority setting in primary health care (PHC) has significant implications for health costs and outcomes in the health care system. Nevertheless, these guidelines have been implemented to a very limited degree in PHC. The objective of the study was to qualitatively assess how general practitioners (GPs) and nurses perceive the application of the three key priority-setting criteria.</p> <p>Methods</p> <p>Focus groups were held with GPs and nurses at primary health care centres, where the staff had a short period of experience in using the criteria for prioritising in their daily work.</p> <p>Results</p> <p>The staff found the three key priority-setting criteria (severity, patient benefit, and cost-effectiveness) to be valuable for priority setting in PHC. However, when the criteria were applied in PHC, three additional dimensions were identified: 1) viewpoint (medical or patient's), 2) timeframe (now or later), and 3) evidence level (group or individual).</p> <p>Conclusions</p> <p>The three key priority-setting criteria were useful. Considering the three additional dimensions might enhance implementation of national guidelines in PHC and is probably a prerequisite for the criteria to be useful in priority setting for individual patients.</p

The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy

Workflow in Clinical Trial Sites & Its Association with Near Miss Events for Data Quality: Ethnographic, Workflow & Systems Simulation

10.1371/journal.pone.0039671PLoS ONE76

Antibodies for Assessing Circadian Clock Proteins in the Rodent Suprachiasmatic Nucleus

Research on the mechanisms underlying circadian rhythmicity and the response of brain and body clocks to environmental and physiological challenges requires assessing levels of circadian clock proteins. Too often, however, it is difficult to acquire antibodies that specifically and reliably label these proteins. Many of these antibodies also lack appropriate validation. The goal of this project was to generate and characterize antibodies against several circadian clock proteins. We examined mice and hamsters at peak and trough times of clock protein expression in the suprachiasmatic nucleus (SCN). In addition, we confirmed specificity by testing the antibodies on mice with targeted disruption of the relevant genes. Our results identify antibodies against PER1, PER2, BMAL1 and CLOCK that are useful for assessing circadian clock proteins in the SCN by immunocytochemistry