How animal agriculture stakeholders define, perceive, and are impacted by antimicrobial resistance: challenging the Wellcome Trust’s Reframing Resistance principles

Humans, animals, and the environment face a universal crisis: antimicrobial resistance (AR). Addressing AR and its multidisciplinary causes across many sectors including in human and veterinary medicine remains underdeveloped. One barrier to AR efforts is an inconsistent process to incorporate the plenitude of stakeholders about what AR is and how to stifle its development and spread—especially stakeholders from the animal agriculture sector, one of the largest purchasers of antimicrobial drugs. In 2019, The Wellcome Trust released Reframing Resistance: How to communicate about antimicrobial resistance effectively (Reframing Resistance), which proposed the need to establish a consistent and harmonized messaging effort that describes the AR crisis and its global implications for health and wellbeing across all stakeholders. Yet, Reframing Resistance does not specifically engage the animal agriculture community. This study investigates the gap between two principles recommended by Reframing Resistance and animal agriculture stakeholders. For this analysis, the research group conducted 31 semi-structured interviews with a diverse group of United States animal agriculture stakeholders. Participants reported attitudes, beliefs, and practices about a variety of issues, including how they defined AR and what entities the AR crisis impacts most. Exploration of Reframing Resistance’s Principle 2, “explain the fundamentals succinctly” and Principle 3, “emphasis that this is universal issue; it can affect anyone, including you” reveals disagreement in both the fundamentals of AR and consensus of “who” the AR crisis impacts. Principle 2 may do better to acknowledge that animal agriculture stakeholders espouse a complex array of perspectives that cannot be summed up in a single perspective or principle. As a primary tool to combat AR, behavior change must be accomplished first through outreach to stakeholder groups and understanding their perspectives

An Experimental Field Study of Delayed Density Dependence in Natural Populations of Aedes albopictus

Aedes albopictus, a species known to transmit dengue and chikungunya viruses, is primarily a container-inhabiting mosquito. The potential for pathogen transmission by Ae. albopictus has increased our need to understand its ecology and population dynamics. Two parameters that we know little about are the impact of direct density-dependence and delayed density-dependence in the larval stage. The present study uses a manipulative experimental design, under field conditions, to understand the impact of delayed density dependence in a natural population of Ae. albopictus in Raleigh, North Carolina. Twenty liter buckets, divided in half prior to experimentation, placed in the field accumulated rainwater and detritus, providing oviposition and larval production sites for natural populations of Ae. albopictus. Two treatments, a larvae present and larvae absent treatment, were produced in each bucket. After five weeks all larvae were removed from both treatments and the buckets were covered with fine mesh cloth. Equal numbers of first instars were added to both treatments in every bucket. Pupae were collected daily and adults were frozen as they emerged. We found a significant impact of delayed density-dependence on larval survival, development time and adult body size in containers with high larval densities. Our results indicate that delayed density-dependence will have negative impacts on the mosquito population when larval densities are high enough to deplete accessible nutrients faster than the rate of natural food accumulation

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Climate Change Projected To Increase Costs of U.S. Vibrio Infections

Vibrio are bacteria that thrive in brackish and marine waters. In the United States, Vibrio are found in coastal areas and are most prevalent in the summer, when waters are warm. Many Vibrio species can cause human illness through foodborne and waterborne exposure. Foodborne exposure typically occurs from eating raw or undercooked seafood. Vibrio exposure may cause mild vomiting, diarrhea, swimmer’s ear, or skin infections. However, it can also result in rare but more serious outcomes like sepsis, amputations, and death. Climate change is expected to expand the range and season of Vibrio infections as sea surface temperatures become warmer. There is evidence this already may be happening

Projecting the Suicide Burden of Climate Change in the United States

Abstract We quantify and monetize changes in suicide incidence across the conterminous United States (U.S.) in response to increasing levels of warming. We develop an integrated health impact assessment model using binned and linear specifications of temperature‐suicide relationship estimates from Mullins and White (2019), in combination with monthly age‐ and sex‐specific baseline suicide incidence rates, projections of six climate models, and population projections at the conterminous U.S. county scale. We evaluate the difference in the annual number of suicides in the U.S. corresponding to 1–6°C of warming compared to 1986–2005 average temperatures (mean U.S. temperatures) and compute 2015 population attributable fractions (PAFs). We use the U.S. Environmental Protection Agency’s Value of a Statistical Life to estimate the economic value of avoiding these mortality impacts. Assuming the 2015 population size, warming of 1–6°C could result in an annual increase of 283–1,660 additional suicide cases, corresponding to a PAF of 0.7%–4.1%. The annual economic value of avoiding these impacts is $2 billion–$3 billion (2015 U.S. dollars, 3% discount rate, and 2015 income level). Estimates based on linear temperature‐suicide relationship specifications are 7% larger than those based on binned temperature specifications. Accounting for displacement decreases estimates by 17%, while accounting for precipitation decreases estimates by 7%. Population growth between 2015 and the future warming degree arrival year increases estimates by 15%–38%. Further research is needed to quantify and monetize other climate‐related mental health outcomes (e.g., anxiety and depression) and to characterize these risks in socially vulnerable populations

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the “connectivity” framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics. A large compendium of cellular responses to drugs as profiled through proteomic assays of phosphosignaling and histone modifications reveals cellular responses that transcend lineage, discovers unexpected associations between drugs, and recognizes therapeutic hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. Keywords: mass spectrometry; proteomics; drug discovery; signaling; epigenetics; mechanism of action; LINCS project; GCP; P100; L1000NIH Common Fund's Library of Integrated Network-based Cellular Signatures (LINCS) program (Grant U54HG008097)NIH Common Fund's Library of Integrated Network-based Cellular Signatures (LINCS) program (Grant U54HG008699