A theory-based framework for understanding the establishment, persistence, and diffusion of community-based conservation

Over decades, biodiversity conservation researchers and practitioners have developed theories and conceptual frameworks to inform the planning, implementation, and evaluation of community-based conservation (CBC). While a diversity of mechanisms for understanding and supporting CBC has helped tailor approaches to local needs and conditions, the absence of a unified lens to understand CBC has limited the capacity for integrating foundational theory into practice more systemically, and for learning across different projects, stakeholders, and institutions. We introduce a theory-based framework called “the CBC framework” that draws upon three foundational theories from sociology, economics, and political science to understand the establishment, persistence, and diffusion of CBC. Experience applying aspects of the framework within different conservation organizations demonstrates how this integrative approach can provide a gateway for practitioners to engage with social science theory to understand the status and context of CBC interventions and efforts. For practitioners, scientists, evaluators, and strategists, the framework can guide the design of CBC interventions and monitoring and evaluation systems to facilitate theory-based learning and enable evidence-informed decision-making. Approaches like the CBC framework that facilitate collaborative planning, evaluation, and research can help better integrate social science theory in conservation practice while increasing the capacity for conservation scientists, practitioners, and stakeholders to learn together and adaptively manage CBC to deliver positive results for both people and nature

West Nile Virus–associated Flaccid Paralysis

The causes and frequency of acute paralysis and respiratory failure with West Nile virus (WNV) infection are incompletely understood. During the summer and fall of 2003, we conducted a prospective, population-based study among residents of a 3-county area in Colorado, United States, with developing WNV-associated paralysis. Thirty-two patients with developing paralysis and acute WNV infection were identified. Causes included a poliomyelitislike syndrome in 27 (84%) patients and a Guillain-Barré–like syndrome in 4 (13%); 1 had brachial plexus involvement alone. The incidence of poliomyelitislike syndrome was 3.7/100,000. Twelve patients (38%), including 1 with Guillain-Barré–like syndrome, had acute respiratory failure that required endotracheal intubation. At 4 months, 3 patients with respiratory failure died, 2 remained intubated, 25 showed various degrees of improvement, and 2 were lost to followup. A poliomyelitislike syndrome likely involving spinal anterior horn cells is the most common mechanism of WNV-associated paralysis and is associated with significant short- and long-term illness and death

Inequitable Gains and Losses from Conservation in a Global Biodiversity Hotspot

A billion rural people live near tropical forests. Urban populations need them for water, energy and timber. Global society benefits from climate regulation and knowledge embodied in tropical biodiversity. Ecosystem service valuations can incentivise conservation, but determining costs and benefits across multiple stakeholders and interacting services is complex and rarely attempted. We report on a 10-year study, unprecedented in detail and scope, to determine the monetary value implications of conserving forests and woodlands in Tanzania’s Eastern Arc Mountains. Across plausible ranges of carbon price, agricultural yield and discount rate, conservation delivers net global benefits (+US$8.2B present value, 20-year central estimate). Crucially, however, net outcomes diverge widely across stakeholder groups. International stakeholders gain most from conservation (+US$10.1B), while local-rural communities bear substantial net costs (-US$1.9B), with greater inequities for more biologically important forests. Other Tanzanian stakeholders experience conflicting incentives: tourism, drinking water and climate regulation encourage conservation (+US$72M); logging, fuelwood and management costs encourage depletion (-US$148M). Substantial global investment in disaggregating and mitigating local costs (e.g., through boosting smallholder yields) is essential to equitably balance conservation and development objectives

Rationale, design, and methods of a randomized, controlled, open-label clinical trial with open-label extension to investigate the safety of vosoritide in infants, and young children with achondroplasia at risk of requiring cervicomedullary decompression surgery

Achondroplasia causes narrowing of the foramen magnum and the spinal canal leading to increased mortality due to cervicomedullary compression in infants and significant morbidity due to spinal stenosis later in adulthood. Vosoritide is a C-natriuretic peptide analogue that has been shown to improve endochondral ossification in children with achondroplasia. The objective of this trial is to evaluate the safety of vosoritide and whether vosoritide can improve the growth of the foramen magnum and spinal canal in children that may require decompression surgery. An Achondroplasia Foramen Magnum Score will be used to identify infants at risk of requiring decompression surgery. This is a 2-year open label randomized controlled trial of vosoritide in infants with achondroplasia ages 0 to ≤12 months. Approximately 20 infants will be randomized 1:1 to either open label once daily subcutaneous vosoritide combined with standard of care or standard of care alone. The primary and secondary aims of the study are to evaluate the safety and efficacy of vosoritide in children with cervicomedullary compression at risk of requiring decompression surgery. The trial will be carried out in specialized skeletal dysplasia treatment centers with well established multidisciplinary care pathways and standardized approaches to the neurosurgical management of cervicomedually compression. After 2 years, infants randomized to standard of care alone will be eligible to switch to vosoritide plus standard of care for an additional 3 years. This pioneering trial hopes to address the important question as to whether treatment with vosoritide at an early age in infants at risk of requiring cervicomedullary decompression surgery is safe, and can improve growth at the foramen magnum and spinal canal alleviating stenosis. This in turn may reduce compression of surrounding structures including the neuraxis and spinal cord, which could alleviate future morbidity and mortality

Inequitable gains and losses from conservation in a global biodiversity hotspot

A billion rural people live near tropical forests. Urban populations need them for water, energy and timber. Global society benefits from climate regulation and knowledge embodied in tropical biodiversity. Ecosystem service valuations can incentivise conservation, but determining costs and benefits across multiple stakeholders and interacting services is complex and rarely attempted. We report on a 10-year study, unprecedented in detail and scope, to determine the monetary value implications of conserving forests and woodlands in Tanzania’s Eastern Arc Mountains. Across plausible ranges of carbon price, agricultural yield and discount rate, conservation delivers net global benefits (+US$8.2B present value, 20-year central estimate). Crucially, however, net outcomes diverge widely across stakeholder groups. International stakeholders gain most from conservation (+US$10.1B), while local-rural communities bear substantial net costs (-US$1.9B), with greater inequities for more biologically important forests. Other Tanzanian stakeholders experience conflicting incentives: tourism, drinking water and climate regulation encourage conservation (+US$72M); logging, fuelwood and management costs encourage depletion (-US$148M). Substantial global investment in disaggregating and mitigating local costs (e.g., through boosting smallholder yields) is essential to equitably balance conservation and development objectives

Effect of prior treatments on selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma

Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT. Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562

Virology, Pathology, and Clinical Manifestations of West Nile Virus Disease

Virologic characteristics of WNV likely interact with host factors in the pathogenesis of fever, meningitis, encephalitis, and flaccid paralysis

Once-weekly selinexor, bortezomib, and dexamethasone versus twice-weekly bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label phase 3 trial

Background Selinexor with dexamethasone has demonstrated activity in patients with heavily pretreated multiple myeloma (MM). In a phase 1b/2 study, the combination of oral selinexor with the proteasome inhibitor (PI) bortezomib, and dexamethasone (SVd) induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. The aim of this trial was to evaluate the clinical benefit of weekly SVd versus standard bortezomib and dexamethasone (Vd) in patients with previously treated MM. Methods This phase 3, randomised, open label trial was conducted at 123 sites in 21 countries. Patients who were previously treated with one to three lines of therapy, including PIs were randomised (1:1) to selinexor (100 mg once-weekly) plus bortezomib (1·3 mg/m2 once-weekly) and dexamethasone (20 mg twice-weekly) [SVd] or bortezomib (1·3 mg/m2 twice-weekly) and dexamethasone (20 mg 4 times per week) [Vd]. Randomisation was done using interactive response technology and stratified by previous PI therapy, lines of treatment, and MM stage. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. Findings Between June 2017 and February 2019, 402 patients were randomised: 195 to SVd and 207 to Vd. Median PFS was 13·93 (95% CI 11·73–NE) with SVd versus 9·46 months (8·11–10·78) with Vd; HR 0·70, [95% CI 0·53–0·93]; P=0.0075. Most frequent grade ≥3 adverse events (SVd vs Vd) were thrombocytopenia (77 [40%] vs 35 [17%]), fatigue (26 [13%] vs 2 [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy rates (overall, 32·3% vs 47·1%; OR 0·52, [95% CI 0·35-0·79]; P=0.0010 and grade ≥2, 21·0% vs 34·3%; OR 0·50, [95% CI 0·32-0·79]; P=0.0013) were lower with SVd. There were 47 (24%) deaths on SVd and 62 (30%) on Vd. Interpretation Once-weekly SVd is a novel, effective, and convenient treatment option for patients with MM who have received 1-3 prior therapies. Funding Karyopharm Therapeutics In