Vampire Bats and Rabies: Toward an Ecological Solution to a Public Health Problem

In the first half of 2011, 21 school-age children and two adults died of rabies transmitted by the common vampire bat (Desmodus rotundus) in and around the small rural village of Yupicusa in the Peruvian Amazon (Figure 1) [1]. This is only one of many such outbreaks occurring throughout the greater Amazon Basin (Figure 2), which, despite efforts at increasing education, vaccination, and bat population control, seem to have escalated over the last three decades—a timeline concurrent with major social and ecological changes in the area [2]. The remote and impoverished nature of communities affected by these outbreaks and the unique niche of vampire bats in a changing socioecological landscape create challenges beyond those faced in previous rabies control efforts and require new strategies to address this public health menace through ecosystem-level intervention. Here we examine this complex system and offer perspectives from a field expedition to Imaza following the 2011 outbreak

College Women: Documenting the Student Experience at the Seven Sisters Colleges

White Paper prepared for the National Endowment for the Humanities Division of Preservation and Access, Humanities Collections and Reference Resources as part of a grant for the College Women: Documenting the Student Experience at the Seven Sisters College

College Women: Documenting the Student Experience at the Seven Sisters Colleges

White Paper prepared for the National Endowment for the Humanities Division of Preservation and Access, Humanities Collections and Reference Resources as part of a grant for the College Women: Documenting the Student Experience at the Seven Sisters College

Waiting times between orders and trades in double-auction markets

In this paper, the survival function of waiting times between orders and the corresponding trades in a double-auction market is studied both by means of experiments and of empirical data. It turns out that, already at the level of order durations, the survival function cannot be represented by a single exponential, thus ruling out the hypothesis of constant activity during trading. This fact has direct consequences for market microstructural models. They must include such a non-exponential behaviour to be realistic.Comment: 19 pages, 3 figures, paper presented at the WEHIA 2005, Colchester, U

Immunochemotherapy and Maintenance With Obinutuzumab or Rituximab in Patients With Previously Untreated Marginal Zone Lymphoma in the Randomized GALLIUM Trial

The aim of this study was to explore the efficacy and safety of obinutuzumab (G)- versus rituximab (R)-chemotherapy in a subgroup of patients with previously untreated marginal zone lymphoma (MZL) in the phase III GALLIUM trial (NCT01332968). Patients had stage III/IV (or stage II with bulky disease), splenic, nodal, or extranodal MZL requiring treatment. Patients were randomized 1:1 to receive G- or R-chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; cyclophosphamide, vincristine, and prednisone; or bendamustine, allocated at patient level). Patients with complete/partial response at the end of induction (EOI) received G/R maintenance. Investigator-assessed progression-free survival (PFS), other time-to-event endpoints, response, and safety were assessed. Overall, 195 patients with MZL were included in this analysis: G-chemotherapy (n = 99), R-chemotherapy (n = 96). Median observation time: 59.3 months. No meaningful difference was observed between arms for PFS (4-y PFS rates: G-chemotherapy, 72.6%; R-chemotherapy, 64.1%), other time-to-event endpoints, or EOI response rates (by computed tomography [CT; G-chemotherapy, 81.8%; R-chemotherapy, 81.3%] and positron emission tomography CT [G-chemotherapy, 79.2%; R-chemotherapy, 87.5%]). All patients experienced ≥1 adverse event (AE). G-chemotherapy was associated with a higher incidence of grade 3–5 (86.1% versus 77.4%), grade 5 (14.9% versus 9.7%), and serious (66.3% versus 51.6%) AEs versus R-chemotherapy. Both arms had a higher incidence of grade 3–5 and serious AEs than patients with follicular lymphoma (GALLIUM), with G-chemotherapy being less tolerable than R-chemotherapy. Based on the observed tolerability of G-chemotherapy versus R-chemotherapy, and the comparable efficacy of G-chemotherapy and R-chemotherapy in this analysis, G-chemotherapy cannot be recommended as first-line treatment for MZL

Enhancing food security in Latin America with forage legumes

Forage legumes could enhance ruminant production in Latin America far more than they currently do. With a few instructive exceptions, decades invested in domesticating, testing and divulgating pasture and rangeland species have had limited impact. Reasons include lack of end-user involvement in research and development, inadequate commercial seed sources, low persistence under grazing, and substitution with industrial nitrogen fertilizer. Current efforts to improve legume adoption include research on domestication of new species especially natives, grass-legume mixtures, silvopasture, protein banks, and mitigating anti-nutritive components. Future challenges might include a greater focus on economical seed production, establishment in multi-species plantings, persistence under grazing, sustainable intensification, domesticating local germplasm, ecosystems services, multiple uses, harnessing condensed tannins, and greater crop-livestock integration of legumes. We believe that these and other innovations make the future of forage legumes very promising in Latin America.Forage legumes could enhance ruminant production in Latin America far more than they currently do. With a few instructive exceptions, decades invested in domesticating, testing and divulgating pasture and rangeland species have had limited impact. Reasons include lack of end-user involvement in research and development, inadequate commercial seed sources, low persistence under grazing, and substitution with industrial nitrogen fertilizer. Current efforts to improve legume adoption include research on domestication of new species especially natives, grass-legume mixtures, silvopasture, protein banks, and mitigating anti-nutritive components. Future challenges might include a greater focus on economical seed production, establishment in multi-species plantings, persistence under grazing, sustainable intensification, domesticating local germplasm, ecosystem services, multiple uses, harnessing condensed tannins, and greater crop-livestock integration of legumes. We believe that these and other innovations make the future of forage legumes very promising in Latin America

Evaluation of the 3-Minute Diagnostic Confusion Assessment Method for identification of postoperative delirium in older patients

Importance: Delirium is a common postoperative complication in older patients that often goes undetected and might lead to worse outcomes. The 3-Minute Diagnostic Confusion Assessment Method (3D-CAM) might be a practical tool for routine clinical diagnosis of delirium. Objective: To assess the 3D-CAM for detecting postoperative delirium compared with the long-form CAM used for research purposes. Design, Setting, and Participants: This cohort study of older patients enrolled in ongoing clinical trials between 2015 and 2018 was conducted at a single tertiary US hospital. Included participants were aged 60 years or older undergoing major elective surgical procedures that required at least a 2-day hospital stay. Data were analyzed between February and April 2019. Exposures: Surgical procedures of at least 2 hours in length requiring general anesthesia with planned extubation. Main Outcomes and Measures: Patients were concurrently assessed for delirium using the 3D-CAM assessment and the long-form CAM, scored based on a standardized cognitive assessment. Agreement between these 2 methods was tested using Cohen κ with repeated measures, a generalized linear mixed-effects model, and Bland-Altman analysis. Results: Sixteen raters conducted 471 concurrent CAM and 3D-CAM interviews including 299 patients (mean [SD] age, 69 [6.5] years), the majority of whom were men (152 [50.8%]), were White (263 [88.0%]), and had noncardiac operations (211 [70.6%]). Both instruments had good intraclass correlation (0.84 for the CAM and 0.98 for the 3D-CAM). Cohen κ demonstrated good overall agreement between the CAM and 3D-CAM (κ = 0.71; 95% CI, 0.58 to 0.83). According to the mixed-effects model, there was statistically significant disagreement between the 3D-CAM and CAM (estimated difference in fixed effect, -0.68; 95% CI, -1.32 to -0.05; P = .04). Bland-Altman analysis showed the probability of a delirium diagnosis with the 3D-CAM was more than twice the probability of a delirium diagnosis with the CAM (probability ratio, 2.78; 95% CI, 2.44 to 3.23). Conclusions and Relevance: The 3D-CAM instrument demonstrated agreement with the long-form CAM and might provide a pragmatic and sensitive clinical tool for detecting postoperative delirium, with the caveat that the 3D-CAM might overdiagnose delirium

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen