Capacity shortfalls hinder the performance of marine protected areas globally.

Marine protected areas (MPAs) are increasingly being used globally to conserve marine resources. However, whether many MPAs are being effectively and equitably managed, and how MPA management influences substantive outcomes remain unknown. We developed a global database of management and fish population data (433 and 218 MPAs, respectively) to assess: MPA management processes; the effects of MPAs on fish populations; and relationships between management processes and ecological effects. Here we report that many MPAs failed to meet thresholds for effective and equitable management processes, with widespread shortfalls in staff and financial resources. Although 71% of MPAs positively influenced fish populations, these conservation impacts were highly variable. Staff and budget capacity were the strongest predictors of conservation impact: MPAs with adequate staff capacity had ecological effects 2.9 times greater than MPAs with inadequate capacity. Thus, continued global expansion of MPAs without adequate investment in human and financial capacity is likely to lead to sub-optimal conservation outcomes.

Trade-offs across values in cesspool management highlight challenges to policy making.

On-site Sewage Disposal Systems (OSDS) are globally common, and in Hawai'i they present a risk of contamination to drinking water sources and nearshore waters. State legislation has commanded that all cesspools are to be banned by 2050, thus requiring tens of thousands of systems to be converted in the coming decades. This project followed a participatory structured decision-making (SDM) approach to collaboratively design cost-effective and equitable solutions for thousands of cesspools in the high elevation areas of north Maui, Hawai'i. Participatory workshops with a diverse group of stakeholders set ten objectives and brainstormed 33 alternatives, for which the technical team then modeled groundwater nutrients, costs, and equity. All alternatives posed trade-offs, though composting toilets performed best across most objectives, albeit with high maintenance burden. Discounting innovative toilets, the multi-objective analysis suggests that the state should invest in cluster sewering of high-density communities, followed by incentivizing septic tank solutions in properties with the highest effluent flow first, then expanding across the area. The total project cost (installation and operation/maintenance) would be $183-258 million, depending upon the sewer-septic combination. An efficiency frontier reveals sub-par combinations, including aerobic treatment units and passive absorption systems, which cost much more and deliver lower mass flux reduction than more cost-effective alternatives. This study contributes a novel case of rural sanitation to the literature in which decision support tools are used to facilitate evidence-based, collaborative decision-making for sanitation planning. The state could use a similar participatory SDM process when approaching other communities to discuss their cesspool upgrade strategies. Broadening the use of decision analytic techniques can have wider ecological, economic, and social benefits for the state and contexts beyond Hawai'i, as SDM provides a transparent and rigorous, evidence-based decision-theoretic framework to explore multiple values and strategies to address difficult resource management problems.

A decision framework for estimating the cost of marine plastic pollution interventions.

Marine plastic pollution has emerged as one of the most pressing environmental challenges of our time. Although there has been a surge in global investment for implementing interventions to mitigate plastic pollution, there has been little attention given to the cost of these interventions. We developed a decision support framework to identify the economic, social, and ecological costs and benefits of plastic pollution interventions for different sectors and stakeholders. We calculated net cost as a function of six cost and benefit categories with the following equation: cost of implementing an intervention (direct, indirect, and nonmonetary costs) minus recovered costs and benefits (monetary and nonmonetary) produced by the interventions. We applied our framework to two quantitative case studies (a solid waste management plan and a trash interceptor) and four comparative case studies, evaluating the costs of beach cleanups and waste-to-energy plants in various contexts, to identify factors that influence the costs of plastic pollution interventions. The socioeconomic context of implementation, the spatial scale of implementation, and the time scale of evaluation all influence costs and the distribution of costs across stakeholders. Our framework provides an approach to estimate and compare the costs of a range of interventions across sociopolitical and economic contexts.

Un Marco de Decisión para Estimar el Costo de Intervenciones en la Contaminación Marina por Plástico Resumen La contaminación marina por plásticos ha emergido como uno de los retos ambientales más prioritarios de nuestro tiempo. Mientras ha habido un aumento en la inversión global para implementar intervenciones para mitigar la contaminación por plásticos, se ha dado poca atención al costo de estas intervenciones. Desarrollamos un marco de soporte a las decisiones para identificar los costos y beneficios económicos, sociales y ecológicos de las intervenciones en la contaminación por plástico para diferentes sectores y partes interesadas. Calculamos el costo neto como una función de 6 categorías de costo y beneficio con la siguiente ecuación: costo de la implementación de una intervención (costos directos, indirectos y no monetarios) menos los costos y beneficios recuperados (monetarios y no monetarios) producidos por las intervenciones. Aplicamos nuestro marco a 2 estudios de caso cuantitativos (un plan de manejo de residuos sólidos y un interceptor de basura) y 4 casos de estudio comparativos evaluando los costos de limpieza de playas y plantas de transformación de desechos a energía en varios contextos para identificar los factores que influyen en los costos de las intervenciones de la contaminación por plástico. El contexto socioeconómico de la implementación, la escala espacial de la implementación y la escala de tiempo de evaluación influyen en los costos y distribución de costos entre las partes interesadas. Nuestro marco proporciona una aproximación para estimar y comparar los costos de una gama de intervenciones en contextos sociopolíticos y económicos.

A Randomized, Placebo-Controlled, Split-Neck Trial of Hyaluronic Acid Filler for Static Horizontal Neck Rhytides Using Either a Cannula or Needle.

BACKGROUND: Hyaluronic acid (HA) fillers have been studied extensively on the face; however, their safety and efficacy on the neck has not yet been evaluated in a prospective trial in the United States. OBJECTIVE: Analyze the efficacy and safety of a HA filler for static horizontal neck rhytides using either a cannula or needle. MATERIALS AND METHODS: Twenty-six subjects were randomized to receive up to 1 mL of the HA filler Restylane Refyne (HARR, n = 20) or saline (n = 6) using a cannula on one side and a needle on the other with optional repeat treatment. Subjects were graded using the Transverse Neck Line Scale, Canfield photography, and the Global Aesthetic Improvement Scale. RESULTS: A significant improvement 30 days after the last treatment was achieved on the Transverse Neck Line Scale when comparing HARR with saline according to the blind evaluator, subjects, and investigator without any significant side effects. In addition, the blind evaluator, subjects, and investigator rated the side of the neck injected with a needle as having significantly greater improvement than the cannula. CONCLUSION: The hyaluronic acid filler, Restylane Refyne, achieved significant improvement in static horizontal neck rhytides using either a cannula or needle without any serious side effects, although the needle was more effective.

Barriers and facilitators to participation in breast, bowel and cervical cancer screening in rural Victoria: A qualitative study.

ISSUE ADDRESSED: Population cancer screening rates are around 50% for the general population and even lower in rural areas. This study aimed to explore knowledge, attitudes, behaviours, motivators and barriers to breast, bowel and cervical screening participation in under-screened men and women. METHODS: We used a qualitative research design. Focus groups were segmented by age, sex and screening participation. Participants were under-screened in at least one of the cancer screening programs, with separate groups for each of the programs. The discussion guides were designed around the Health Belief Model and group discussions were coded using a thematic content analysis approach. RESULTS: Fourteen focus groups were held with 80 participants. Key themes were that the concept of cancer screening was not well understood, a low priority for preventive health behaviours, issues relating to local general practitioners (GP) and screening was unpleasant, embarrassing and/or inconvenient. A key determinant of participation in cancer screening was exposure to prompts to action, and it was evident that participants often required multiple prompts before they took action. CONCLUSIONS: Opportunities that develop attitudes to health that place disease prevention as a high priority; improve understanding of the benefit of screening in terms of early detection and treatment; improve GP availability and the patient-practitioner relationship; and the development of messages for each of the screening programs should be further explored as factors that may influence rural population screening rates. SO WHAT?: Addressing health attitudes, beliefs, knowledge, health practitioner and test-related barriers and improving messaging may increase cancer screening participation in under-screened rural populations.

Mismatch between bird species sensitivity and the protection of intact habitats across the Americas.

Protected areas are highly heterogeneous in their effectiveness at buffering human pressure, which may hamper their ability to conserve species highly sensitive to human activities. Here, we use 60 million bird observations from eBird to estimate the sensitivity to human pressure of each bird species breeding in the Americas. Concerningly, we find that ecoregions hosting large proportions of high-sensitivity species, concentrated in tropical biomes, do not have more intact protected habitat. Moreover, 266 high-sensitivity species have little or no intact protected habitat within their distributions. Finally, we show that protected area intactness is decreasing faster where high-sensitivity species concentrate. Our results highlight a major mismatch between species conservation needs and the coverage of intact protected habitats, which likely hampers the long-term effectiveness of protected areas at retaining species. We highlight ecoregions where protection and management of intact habitats, complemented by restoration, is urgently needed.

Statistical matching for conservation science.

The awareness of the need for robust impact evaluations in conservation is growing and statistical matching techniques are increasingly being used to assess the impacts of conservation interventions. Used appropriately matching approaches are powerful tools, but they also pose potential pitfalls. We outlined important considerations and best practice when using matching in conservation science. We identified 3 steps in a matching analysis. First, develop a clear theory of change to inform selection of treatment and controls and that accounts for real-world complexities and potential spillover effects. Second, select the appropriate covariates and matching approach. Third, assess the quality of the matching by carrying out a series of checks. The second and third steps can be repeated and should be finalized before outcomes are explored. Future conservation impact evaluations could be improved by increased planning of evaluations alongside the intervention, better integration of qualitative methods, considering spillover effects at larger spatial scales, and more publication of preanalysis plans. Implementing these improvements will require more serious engagement of conservation scientists, practitioners, and funders to mainstream robust impact evaluations into conservation. We hope this article will improve the quality of evaluations and help direct future research to continue to improve the approaches on offer.

Emparejamiento Estadístico para la Ciencia de la Conservación Resumen Hay más conciencia sobre la necesidad de evaluaciones de impacto más rigurosas y las técnicas de emparejamiento estadístico se están usan con más frecuencia para evaluar los impactos de intervenciones de conservación. Las técnicas de emparejamiento pueden ser herramientas poderosas si son utilizadas correctamente, pero también pueden llevar a conclusiones erróneas. En este artículo describimos consideraciones importantes para realizar estudios de conservación que utilizan técnicas de emparejamiento estadístico. Identificamos tres pasos dentro de un análisis de emparejamiento. Primero, es importante desarrollar una teoría del cambio que considere las complejidades del mundo real y las posibles consecuencias indirectas para poder seleccionar unidades de tratamiento y controles. Segundo, es clave seleccionar las covarianzas y la estrategia de emparejamiento apropiadas. Tercero, evaluar la calidad del emparejamiento a través de una serie de revisiones. El segundo y el tercer paso pueden ser repetidos y deben concluirse antes de que se exploren los resultados. Evaluaciones de impacto de intervenciones de conservación podrían mejorarse con una mejor planeación de las evaluaciones junto con la intervención, una mejor integración de los métodos cualitativos, mejor consideración de consecuencias indirectas a grandes escalas espaciales y un incremento en la publicación de planes pre-analíticos. La implementación de estas mejoras requerirá de un compromiso más serio por parte de científicos de la conservación, y de practicantes y financiadores. Esperamos que este artículo mejore la calidad de evaluaciones y ayude a guiar futuras investigaciones e intervenciones de conservación.

Potent and selective NOP receptor activation reduces cocaine self-administration in rats by lowering hedonic set point.

Developing new medications for the treatment of cocaine dependence continues to be a research priority. Compelling evidence indicates that mixed opioid receptor agonists, particularly bifunctional compounds that target nociceptin/orphanin FQ peptide (NOP) and mu opioid receptors, may be useful for the treatment of cocaine addiction. Here, we verify that potent and selective pharmacological activation of NOP receptors is sufficient to reduce relevant facets of cocaine addiction in animal models. Accordingly, we determined whether systemic injections of the small molecule AT-312 (0, 1, 3 mg/kg) could reduce operant cocaine self-administration, motivation for cocaine, and vulnerability to cocaine relapse in rats. Results indicate that a potent and selective NOP receptor agonist was equally efficacious in reducing the number of cocaine infusions in short (1-hour), as well as long (6-hour) access sessions. When tested on an economic-demand reinforcement schedule, AT-312 reduced Q0 , the parameter that describes the amount of drug consumed at zero price, while leaving the parameter α, a measure of motivation for drug consumption, unaltered. Furthermore, AT-312 successfully reduced conditioned reinstatement of cocaine seeking. In contrast, the NOP receptor agonist did not modify food self-administration. Blockade of the NOP receptor with the antagonist SB-612111 prevented the effect of AT-312 in decreasing cocaine-reinforced responding under a 2-hour fixed ratio 1 schedule, suggesting a NOP receptor-mediated mechanism. This work demonstrates that potent and selective activation of NOP receptors is sufficient to decrease cocaine taking and seeking behaviors in rats.

NOP Receptor Antagonists Decrease Alcohol Drinking in the Dark in C57BL/6J Mice.

BACKGROUND: The nociceptin/orphanin FQ opioid peptide (NOP) receptor and its endogenous ligand N/OFQ have been implicated in the regulation of drug and alcohol use disorders (AUD). In particular, evidence demonstrated that NOP receptor activation blocks reinforcing and motivating effects of alcohol across a range of behavioral measures, including alcohol intake, conditioned place preference, and vulnerability to relapse. METHODS: Here, we show the effects of pharmacological activation and inhibition of NOP receptors on binge-like alcohol consumption, as measured by the "drinking in the dark" (DID) model in C57BL/6J mice. RESULTS: We found that 2 potent and selective NOP agonists AT-202 (0, 0.3, 1, 3 mg/kg) and AT-312 (0, 0.3, 1 mg/kg) did not affect binge alcohol drinking at doses that do not affect locomotor activity. AT-202 also failed to alter DID behavior when administered to mice previously exposed to chronic alcohol treatment with an alcohol-containing liquid diet. Conversely, treatment with either the high affinity NOP receptor antagonist SB-612111 (0, 3, 10, 30 mg/kg) or the selective antagonist LY2817412 (0, 3, 10, 30 mg/kg) decreased binge drinking. SB-612111 was effective at all doses examined, and LY2817412 was effective at 30 mg/kg. Consistently, NOP receptor knockout mice consumed less alcohol compared to wild type. SB-612111 reduced DID and increased sucrose consumption at doses that do not appear to affect locomotor activity. However, the high dose of SB-612111 (30 mg/kg) reduced alcohol intake but failed to inhibit preference in a 2-bottle choice DID model that can assess moderate alcohol intake. CONCLUSIONS: The present results suggest that NOP receptor inhibition rather than activation may represent a valuable approach for treatment of AUD characterized by excessive alcohol consumption such as binge drinking.

Bolder science needed now for protected areas.

Recognizing that protected areas (PAs) are essential for effective biodiversity conservation action, the Convention on Biological Diversity established ambitious PA targets as part of the 2020 Strategic Plan for Biodiversity. Under the strategic goal to "improve the status of biodiversity by safeguarding ecosystems, species, and genetic diversity," Target 11 aims to put 17% of terrestrial and 10% of marine regions under PA status by 2020. Additionally and crucially, these areas are required to be of particular importance for biodiversity and ecosystem services, effectively and equitably managed, ecologically representative, and well-connected and to include "other effective area-based conservation measures" (OECMs). Whereas the area-based targets are explicit and measurable, the lack of guidance for what constitutes important and representative; effective; and OECMs is affecting how nations are implementing the target. There is a real risk that Target 11 may be achieved in terms of area while failing the overall strategic goal for which it is established because the areas are poorly located, inadequately managed, or based on unjustifiable inclusion of OECMs. We argue that the conservation science community can help establish ecologically sensible PA targets to help prioritize important biodiversity areas and achieve ecological representation; identify clear, comparable performance metrics of ecological effectiveness so progress toward these targets can be assessed; and identify metrics and report on the contribution OECMs make toward the target. By providing ecologically sensible targets and new performance metrics for measuring the effectiveness of both PAs and OECMs, the science community can actively ensure that the achievement of the required area in Target 11 is not simply an end in itself but generates genuine benefits for biodiversity.

Role of phosphodiesterase-5 inhibitors in heart failure: emerging data and concepts.

Novel treatment of congestive heart failure (HF) involves utilizing unique pathways to improve upon contemporary therapies. Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Preclinical studies suggest a favorable myocardial effect of PDE5 inhibitors by blocking adrenergic, hypertrophic and pro-apoptotic signaling, thereby supporting their use in HF. The clinical benefits of acute and chronic PDE5 inhibition on lung diffusion capacity, exercise performance and ejection fraction in humans are emerging and appear promising. Larger, controlled trials are now on-going to assess the safety, efficacy and tolerability of PDE5 inhibitors on morbidity and mortality in patients with both systolic and diastolic heart failure. If the results of these trials are positive, a new avenue for the treatment of HF will open, which will help curtail the societal effects of this costly and morbid disease.

Circulating extracellular vesicles in healthy and pathological pregnancies: A scoping review of methodology, rigour and results.

Extracellular vesicles (EVs) play a crucial role in pregnancy, revealed by the presence of placental-derived EVs in maternal blood, their in vitro functionality, and their altered cargo in pregnancy pathologies. These EVs are thought to be involved in the development of pregnancy pathologies, such as pre-eclampsia, pre-term birth, and fetal growth restriction, and have been suggested as a source of biomarkers for gestational diseases. However, to accurately interpret their function and biomarker potential, it is necessary to critically evaluate the EV isolation and characterization methodologies used in pregnant cohorts. In this systematic scoping review, we collated the results from 152 studies that have investigated EVs in the blood of pregnant women, and provide a detailed analysis of the EV isolation and characterization methodologies used. Our findings indicate an overall increase in EV concentrations in pregnant compared to non-pregnant individuals, an increased EV count as gestation progresses, and an increased EV count in some pregnancy pathologies. We highlight the need for improved standardization of methodology, greater focus on gestational changes in EV concentrations, and further investigations into the functionality of EVs. Our review suggests that EVs hold great promise as diagnostic and translational tools for gestational diseases. However, to fully realize their potential, it is crucial to improve the standardization and reliability of EV isolation and characterization methodologies, and to gain a better understanding of their functional roles in pregnancy pathologies.

Human infection challenge in the pandemic era and beyond, HIC-Vac annual meeting report, 2022.

HIC-Vac is an international network of researchers dedicated to developing human infection challenge studies to accelerate vaccine development against pathogens of high global impact. The HIC-Vac Annual Meeting (3rd and 4th November 2022) brought together stakeholders including researchers, ethicists, volunteers, policymakers, industry partners, and funders with a strong representation from low- and middle-income countries. The network enables sharing of research findings, especially in endemic regions. Discussions included pandemic preparedness and the role of human challenge to accelerate vaccine development during outbreak, with industry speakers emphasising the great utility of human challenge in vaccine development. Public consent, engagement, and participation in human challenge studies were addressed, along with the role of embedded social science and empirical studies to uncover social, ethical, and regulatory issues around human infection challenge studies. Study volunteers shared their experiences and motivations for participating in studies. This report summarises completed and ongoing human challenge studies across a variety of pathogens and demographics, and addresses other key issues discussed at the meeting.

Mucosal Immune Responses to Respiratory Syncytial Virus.

Despite over half a century of research, respiratory syncytial virus (RSV)-induced bronchiolitis remains a major cause of hospitalisation in infancy, while vaccines and specific therapies still await development. Our understanding of mucosal immune responses to RSV continues to evolve, but recent studies again highlight the role of Type-2 immune responses in RSV disease and hint at the possibility that it dampens Type-1 antiviral immunity. Other immunoregulatory pathways implicated in RSV disease highlight the importance of focussing on localised mucosal responses in the respiratory mucosa, as befits a virus that is essentially confined to the ciliated respiratory epithelium. In this review, we discuss studies of mucosal immune cell infiltration and production of inflammatory mediators in RSV bronchiolitis and relate these studies to observations from peripheral blood. We also discuss the advantages and limitations of studying the nasal mucosa in a disease that is most severe in the lower airway. A fresh focus on studies of RSV pathogenesis in the airway mucosa is set to revolutionise our understanding of this common and important infection.

Effects of Acute Yohimbine Hydrochloride Supplementation on Repeated Supramaximal Sprint Performance.

The purpose of this study was to examine the effects of a single acute dose of yohimbine hydrochloride on repeated anaerobic sprint ability. Physically active females (n = 18) completed two separate repeated supramaximal sprint trials each with a different single-dose treatment: placebo (PL; gluten-free corn starch) or yohimbine hydrochloride (YHM; 2.5 mg). For each trial, participants consumed their respective treatment 20 min before exercise. Following a warm-up, participants completed 3 × 15 s Wingate anaerobic tests (WAnTs) separated by 2 min of active recovery. A capillary blood sample was obtained pre- and immediately post-exercise to measure blood concentrations of lactate (LA), epinephrine (EPI), and norepinephrine (NE). Heart rate (HR) and rate of perceived exertion (RPE) were measured following each WAnT. Findings showed that mean power (p < 0.001; η2 = 0.024), total work (p < 0.001; η2 = 0.061), and HR (p < 0.001; η2 = 0.046), were significantly higher with YHM supplementation versus PL. Fatigue index (p < 0.001; η2 = 0.054) and post-exercise LA (p < 0.001; d = 1.26) were significantly lower with YHM compared to PL. YHM resulted in significantly higher EPI concentrations versus PL (p < 0.001; η2 = 0.225) pre- and post-exercise while NE only increased as a function of time (p < 0.001; η2 = 0.227) and was unaffected by treatment. While RPE increased after each WAnT, no differences between treatments were observed (p = 0.539; η2 < 0.001). Together, these results suggest that acute YHM ingestion imparts ergogenic benefits which may be mediated by lower blood LA and fatigue concomitantly occurring with blood EPI increases. Thus, YHM may improve sprint performance although more mechanistic study is warranted to accentuate underlying processes mediating performance enhancement.

INfrastructure for a PHAge REference Database: Identification of Large-Scale Biases in the Current Collection of Cultured Phage Genomes.

Background: With advances in sequencing technology and decreasing costs, the number of phage genomes that have been sequenced has increased markedly in the past decade. Materials and Methods: We developed an automated retrieval and analysis system for phage genomes (https://github.com/RyanCook94/inphared) to produce the INfrastructure for a PHAge REference Database (INPHARED) of phage genomes and associated metadata. Results: As of January 2021, 14,244 complete phage genomes have been sequenced. The INPHARED data set is dominated by phages that infect a small number of bacterial genera, with 75% of phages isolated on only 30 bacterial genera. There is further bias, with significantly more lytic phage genomes (∼70%) than temperate (∼30%) within our database. Collectively, this results in ∼54% of temperate phage genomes originating from just three host genera. With much debate on the carriage of antibiotic resistance genes and their potential safety in phage therapy, we searched for putative antibiotic resistance genes. Frequency of antibiotic resistance gene carriage was found to be higher in temperate phages than in lytic phages and again varied with host. Conclusions: Given the bias of currently sequenced phage genomes, we suggest to fully understand phage diversity, efforts should be made to isolate and sequence a larger number of phages, in particular temperate phages, from a greater diversity of hosts.

The mismeasure of conservation.

One of the basic purposes of protected areas and other effective area-based conservation interventions is to achieve conservation impact, the sum of avoided biodiversity loss and promoted recovery relative to outcomes without protection. In the context of the Convention on Biological Diversity's negotiations on the post-2020 Global Biodiversity Framework, we find that targets for area-based interventions are framed overwhelmingly with measures that fail to inform decision-makers about impact and that risk diverting limited resources away from achieving it. We show that predicting impact in space and time is feasible and can provide the basis for global guidance for jurisdictions to develop targets for conservation impact and shift investment priorities to areas where impact can be most effectively achieved.