Overwintering Locations, Migrations, and Fidelity of Radio-Tagged Dolly Varden in the Hulahula River, Arctic National Wildlife Refuge, 2007–09

Essential overwintering habitats for anadromous Dolly Varden Salvelinus malma on Alaska’s North Slope appear to be limited to a small number of perennial springs, primarily in eastern Brooks Range drainages. Because future petrochemical development in the region continues to be a possibility, and development would require large quantities of freshwater, we sought to identify and document the overwintering areas used by Dolly Varden in the Hulahula River, eastern Brooks Range. In August 2007, we implanted 52 Dolly Varden with multi-year radio transmitters at a known overwintering area in the lower Hulahula River. Other wintering areas were located during 11 aerial surveys conducted over the next 2.5 years. A stationary receiver located in the lower Hulahula River provided migration timing information. Radio-tagged Dolly Varden used four discrete areas with perennial springs for overwintering in the Hulahula River drainage. The springs, totaling approximately 12 km in stream length, were located between river km 40 and 105. Radio-tagged Dolly Varden migrated downstream on their way to the Beaufort Sea in early June. Most tagged fish known to have survived the summer at sea returned to the Hulahula River during late July and August, but seven fish overwintered in other North Slope drainages. Within the Hulahula River drainage, 15 fish overwintered in more than one area during the three winters of the project, but only the four identified perennial spring areas were used. These data clearly indicate that the perennial springs in the Hulahula River are essential overwintering habitats for Dolly Varden.Les aires de concentration hivernales essentielles du Dolly Varden Salvelinus malma anadrome sur la North Slope de l’Alaska semblent limitées à un petit nombre de sources pérennes, principalement dans les bassins hydrographiques de l’est de la chaîne de Brooks. Puisqu’il est toujours possible qu’il y ait des aménagements pétrochimiques dans la région et que ceux-ci demanderaient de grandes quantités d’eau douce, nous avons tâché de déterminer les aires de concentration hivernales du Dolly Varden dans la rivière Hulahula faisant partie de l’est de la chaîne de Brooks, et nous les avons répertoriées. En août 2007, nous avons installé des émetteurs radio pluriannuels sur 52 poissons Dolly Varden dans une aire de concentration hivernale connue faisant partie de la rivière Hulahula inférieure. D’autres aires de concentration hivernales ont été repérées grâce à 11 levés aériens effectués au cours des 2,5 années qui ont suivi. Un récepteur fixe situé dans la rivière Hulahula inférieure nous a permis de relever des données sur le moment de la migration. Les Dolly Varden dotés d’émetteurs radio ont utilisé quatre sources discrètes où se trouvent des sources pérennes pour passer l’hiver, dans le bassin versant de la rivière Hulahula. Les sources, qui s’étendent sur une douzaine de kilomètres de longueur, étaient situées entre les kilomètres 40 et 105 de la rivière. Les Dolly Varden munis d’émetteurs radio ont migré en aval, en route vers la mer de Beaufort au début juin. La plupart des poissons avec émetteur ont survécu l’été à la mer et ont regagné la rivière Hulahula vers la fin de juillet et en août, mais sept poissons ont passé l’hiver dans d’autres bassins versants de la North Slope. Dans le bassin versant de la rivière Hulahula, 15 poissons ont passé l’hiver dans plus d’une aire au cours des trois hivers visés par le projet, mais seules les quatre sources pérennes déterminées ont été utilisées. Ces données indiquent clairement que les sources pérennes de la rivière Hulahula sont des aires de concentration hivernales essentielles pour le Dolly Varden

Text Mining the History of Medicine

Historical text archives constitute a rich and diverse source of information, which is becoming increasingly readily accessible, due to large-scale digitisation efforts. However, it can be difficult for researchers to explore and search such large volumes of data in an efficient manner. Text mining (TM) methods can help, through their ability to recognise various types of semantic information automatically, e.g., instances of concepts (places, medical conditions, drugs, etc.), synonyms/variant forms of concepts, and relationships holding between concepts (which drugs are used to treat which medical conditions, etc.). TM analysis allows search systems to incorporate functionality such as automatic suggestions of synonyms of user-entered query terms, exploration of different concepts mentioned within search results or isolation of documents in which concepts are related in specific ways. However, applying TM methods to historical text can be challenging, according to differences and evolutions in vocabulary, terminology, language structure and style, compared to more modern text. In this article, we present our efforts to overcome the various challenges faced in the semantic analysis of published historical medical text dating back to the mid 19th century. Firstly, we used evidence from diverse historical medical documents from different periods to develop new resources that provide accounts of the multiple, evolving ways in which concepts, their variants and relationships amongst them may be expressed. These resources were employed to support the development of a modular processing pipeline of TM tools for the robust detection of semantic information in historical medical documents with varying characteristics. We applied the pipeline to two large-scale medical document archives covering wide temporal ranges as the basis for the development of a publicly accessible semantically-oriented search system. The novel resources are available for research purposes, while the processing pipeline and its modules may be used and configured within the Argo TM platform

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D’Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease

OBJECTIVE: To determine if future studies of coenzyme Q10 and GPI-1485 in Parkinson disease (PD) may be warranted. METHODS: We conducted a randomized, double-blind, calibrated futility clinical trial of coenzyme Q10 and GPI-1485 in early untreated PD using placebo data from the DATATOP study to establish the futility threshold. RESULTS: The primary outcome measure (change in total Unified Parkinson\u27s Disease Rating Scale scores over 1 year) did not meet the prespecified criteria for futility for either agent. Secondary analyses using calibration controls and other more recent placebo data question the appropriateness of the predetermined definition of futility, and suggest that a more restrictive threshold may be needed. CONCLUSIONS: Coenzyme Q10 and GPI-1485 may warrant further study in Parkinson disease, although the data are inconsistent. Additional factors (cost, availability of other agents, more recent data on placebo outcomes, other ongoing trials) should also be considered in the selection of agents for Phase III studies. ©2007 AAN Enterprises, Inc