Acidic Drug Concentrations in Postmortem Vitreous Humor and Peripheral Blood.

Vitreous humor is a potential alternative matrix for postmortem toxicology drug screens when peripheral blood is unavailable. It is easily and reliably collected and may not suffer from the same postmortem redistribution as seen in blood. Here, we compared the concentrations of 7 acidic drugs (acetaminophen, ibuprofen, naproxen, salicylic acid, carbamazepine, phenobarbital and phenytoin) in peripheral blood and vitreous fluid collected in 89 autopsy cases. Analysis was done by high-performance liquid chromatography with diode-array detection. Overall, we found that vitreous drug concentrations were significantly lower than peripheral blood with median vitreous to peripheral blood (V/PB) ratios ranging from 0.0 to 0.6 (mean, 0.1-0.6). The correlations between the concentrations of over-the-counter analgesics in peripheral blood versus vitreous fluid were poor, with acetaminophen exhibiting the best linearity (R2 = 0.72). The antiepileptic drugs (carbamazepine, phenytoin and phenobarbital) exhibited good correlations between peripheral blood and vitreous humor, with all exhibiting an R2 ≥ 0.95. Overall, we have demonstrated the potential of vitreous fluid as an alternative matrix for the detection of select acidic drugs

Strategies for simulating the drift of marine debris

Modelling the drift of marine debris in quasi-real time can be of societal relevance. One pertinent example is Malaysia Airlines flight MH370. The aircraft is assumed to have crashed in the Indian Ocean, leaving floating wreckage to drift on the surface. Some of these items were recovered around the western Indian Ocean. We use ocean currents simulated by an operational ocean model in conjunction with surface Stokes drift to determine the possible paths taken by the debris. We consider: (1) How important is the influence of surface waves on the drift? (2) What are the relative benefits of forward- and backward-tracking in time? (3) Does including information from more items refine the most probable crash-site region? Our results highlight a critical contribution of Stokes drift and emphasise the need to know precisely the buoyancy characteristics of the items. The differences between the tracking approaches provide a measure of uncertainty which can be minimised by simulating a sufficiently large number of virtual debris. Given the uncertainties associated with the timings of the debris sightings, we show that at least 5 items are required to achieve an optimal most probable crash-site region. The results have implications for other drift simulation applications

Strategies for simulating the drift of marine debris

Modelling the drift of marine debris in quasi-real time can be of societal relevance. One pertinent example is Malaysia Airlines flight MH370. The aircraft is assumed to have crashed in the Indian Ocean, leaving floating wreckage to drift on the surface. Some of these items were recovered around the western Indian Ocean. We use ocean currents simulated by an operational ocean model in conjunction with surface Stokes drift to determine the possible paths taken by the debris. We consider: (1) How important is the influence of surface waves on the drift? (2) What are the relative benefits of forward- and backward-tracking in time? (3) Does including information from more items refine the most probable crash-site region? Our results highlight a critical contribution of Stokes drift and emphasise the need to know precisely the buoyancy characteristics of the items. The differences between the tracking approaches provide a measure of uncertainty which can be minimised by simulating a sufficiently large number of virtual debris. Given the uncertainties associated with the timings of the debris sightings, we show that at least 5 items are required to achieve an optimal most probable crash-site region. The results have implications for other drift simulation applications

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Correspondence with Louis Rosenhead (Department of Applied Mathematics, University of Liverpool)

May 1946, January 1949, November 1955. 7 letters and notes

Correspondence with Lancelot Hogben (London School of Economics and Political Science, Queen Elizabeth Hospital, Birmingham)

December 1930 - June 1953. 43 letters and notes, some with attachments

Correspondence with Sir Lionel Whitby (University of Cambridge)

November 1948 – January 1956. 9 letters and notes

Correspondence with E.L. LeClerg (Agricultural Research Service, United States Department of Agriculture)

October 1936 - September 1945, March-April 1954. 18 letters and notes

Correspondence with L.F. Richardson

December 1927 - September 1953. 27 letters