Ambient pH and the response to chemical alarm cues in juvenile Atlantic salmon (Salmo salar): mechanisms of reduced behavioral responses.

Even at sublethal concentrations, various anthropogenic pollutants may disrupt the transfer of chemosensory information, often inducing maladaptive behavioral responses. Recent studies of freshwater prey fishes have shown impaired abilities to respond to damage-released chemical alarm cues from conspecifics under weakly acidic conditions (pH ; 6.0). Several factors acting individually or collectively may account for such chemosensory impairment. By itself, acidification may chemically disrupt the alarm cues and affect fish olfactory functions. Alternatively, differences in local environmental conditions may affect biochemical composition, quantity of chemical alarm cues produced by epidermal tissue, or both, leading to variations in alarm response. Our goal was to assess whether the ability to produce and detect onspecific chemical alarm cues is similar in individuals reared under neutral versus acidic conditions. We conducted two experiments in which we measured the behavioral response of wild juvenile Atlantic salmon Salmo salar exposed to chemical alarm cues. In particular, we looked for differences in the ability of individual fish to (1) produce alarm cues capable of eliciting consistent antipredator behavior in conspecifics and (2) detect alarm cues upon the fish’s introduction into a stream with a pH differing from that of the stream of origin; the latter experiment involved reciprocal transplant of fish between neutral (pH range ; 7.0–7.3) and acidic (pH range ; 5.9–6.3) sites. Our results demonstrate that the ability to produce and respond to chemical alarm cues is maintained in Atlantic salmon reared under acidic conditions and did not differ from that of fish reared under neutral conditions. Overall, these data suggest that no permanent olfactory damage occurred under reduced pH and, likewise, no significant difference in functional alarm cue production existed between Atlantic salmon reared under neutral and acidic conditions. Short-term reduction in olfactory sensitivity and degradation of the chemical alarm cues under acidic conditions are the likely mechanisms affecting detection of these important chemicals by prey fish

Selectivity, efficacy and toxicity studies of UCCB01-144, a dimeric neuroprotective PSD-95 inhibitor

Inhibition of postsynaptic density protein-95 (PSD-95) decouples N-methyl-d-aspartate (NMDA) receptor downstream signaling and results in neuroprotection after focal cerebral ischemia. We have previously developed UCCB01-144, a dimeric PSD-95 inhibitor, which binds PSD-95 with high affinity and is neuroprotective in experimental stroke. Here, we investigate the selectivity, efficacy and toxicity of UCCB01-144 and compare with the monomeric drug candidate Tat-NR2B9c. Fluorescence polarization using purified proteins and pull-downs of mouse brain lysates showed that UCCB01-144 potently binds all four PSD-95-like membrane-associated guanylate kinases (MAGUKs). In addition, UCCB01-144 affected NMDA receptor signaling pathways in ischemic brain tissue. UCCB01-144 reduced infarct size in young and aged male mice at various doses when administered 30 min after permanent middle cerebral artery occlusion, but UCCB01-144 was not effective in young male mice when administered 1 h post-ischemia or in female mice. Furthermore, UCCB01-144 was neuroprotective in a transient stroke model in rats, and in contrast to Tat-NR2B9c, high dose of UCCB01-144 did not lead to significant changes in mean arterial blood pressure or heart rate. Overall, UCCB01-144 is a potent MAGUK inhibitor that reduces neurotoxic PSD-95-mediated signaling and improves neuronal survival following focal brain ischemia in rodents under various conditions and without causing cardiovascular side effects, which encourages further studies towards clinical stroke trials

Participation in collaborative fisheries research improves the perceptions of recreational anglers towards marine protected areas

Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes

The San Francisco Health Systems Collaborative: Public Health and Health Care Delivery Systems Response to the Covid-19 Pandemic.

The Covid-19 pandemic challenged health care delivery systems worldwide. Many acute care hospitals in communities that experienced surges in cases and hospitalizations had to make decisions such as rationing scarce resources. Hospitals serving low-income communities, communities of color, and those in other historically marginalized or vulnerable groups reported the greatest operational impacts of surges. However, cross-institutional collaborations within jurisdictions offer unique opportunities to prevent or mitigate health disparities in resource utilization and access to care. In January 2020, in response to the emerging coronavirus epidemic, the San Francisco Department of Public Health (SFDPH) and local hospital and health systems partners convened to align and coordinate medical surge planning and response. Adopting a governance structure of mutual accountability and transparency, the San Francisco Health Systems Collaborative guided local medical and public health response in the areas of medical surge, vaccination administration, testing, and therapeutics. Four principles guided the collaborative response: (1) shared priorities, (2) clear governance and accountability, (3) data transparency, and (4) operational coordination. High-level priorities established included protecting vulnerable people, protecting health care workers, and maintaining health system capacity. The governance structure consisted of three layers: local hospital and health systems CEOs coordinating with SFDPH executives; hospital chief medical and nursing officers coordinating high-level surge capacity assessments and mitigation plans; and local clinical operational managers working with public health response operational leaders to coordinate scarce resource utilization. Fluctuating with the tempo of the disease indicators and medical surge, governance and coordination were maintained through a tiered meeting and reporting system. Data visibility and transparency were key principles facilitating operational decision-making and executive-level coordination of resources, including identifying additional surge bed capacity for use systemwide, as well as ensuring efficient and equitable vaccine distribution through implementation of five mass-vaccination sites with prioritized access for vulnerable communities. Applying these four principles of shared priorities, accountability, transparency, and operational coordination and pragmatism helped the public health and individual hospital systems make contributions to the overall response that were aligned with their unique strengths and resources. Publication here represents the first official public use of the name San Francisco Health Systems Collaborative (which had served as the term used internally to refer to the group) and the first time codifying this structure. Through this coordination, San Francisco achieved one of the lowest Covid-19 death rates and had one of the highest vaccination and booster rates, compared with rates across California or the United States. Similar principles and implementation methods can be adopted by other health jurisdictions for future emergency outbreak response

Measurement challenge : protocol for international case–control comparison of mammographic measures that predict breast cancer risk

Introduction: For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk. Methods and analysis: The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk. Ethics and dissemination: Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3)

Meeting report:International soil virus conference 2024

The research field of soil viral ecology continues to advance rapidly as the roles of viruses in the functioning of soil ecosystems are increasingly recognized. To address recent developments in the field, the second International Soil Virus Conference was held in Livermore, California, USA, from June 25 to 27th, 2024, providing soil viral ecologists the opportunity to share new findings and suggest guidelines for future research, while encouraging international scientific discussion and collaboration. The meeting was held in person with sessions simultaneously streamed online. Fifty researchers attended from ten different countries and spanned a wide range of subfields and career stages. A total of 21 oral presentations were presented, followed by discussions covering key themes in soil viral research. This report summarizes the main takeaways and recommendations from the talks and discussions.</p

Participation in collaborative fisheries research improves the perceptions of recreational anglers towards marine protected areas

Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common