Project description:In Quebec (Canada), the roll-out of the vaccination started slowly in December 2020 due to limited vaccine supply. While the first and second doses were well-accepted among adults and vaccine uptake was above 90%, in late 2021 and 2022, vaccine acceptance decreased for children vaccination and receipt of a 3rd or a 4th dose. In the autumn of 2022, four focus groups were conducted with vaccine-hesitant parents of children aged 0-4 and adults who expressed little intention to receive a booster dose. The objective of this study was to gather participants' perspectives on vaccination in general, on the COVID-19 vaccination campaign and the information available, and to gain insights into the underlying reasons for their low intention of either having their child(ren) vaccinated, or receiving an additional dose of vaccine. A total of 35 participants took part in the focus groups. While participants expressed a certain level of trust and confidence in public health and government authorities regarding pandemic management and the vaccination campaign, they were also concerned that transparent information was lacking to support an informed decision on booster doses and children's vaccination. Many participants felt adequately protected against the infection during the focus groups, citing a lack of perceived benefits as the primary reason for refusing a booster dose. Parents who refused to administer the COVID-19 vaccine to their young children felt that the vaccine was not useful for children and were concerned about potential side effects. The majority reported that their opinions regarding other recommended vaccines had not changed since the beginning of the pandemic. While these results are reassuring, our findings highlight the importance of transparency in public health communications about vaccines to increase confidence and to develop strategies to address vaccine fatigue and complacency toward COVID-19 vaccines.
Project description:In the central nervous system, immunologic surveillance and response are carried out, in large part, by microglia. These resident macrophages derive from myeloid precursors in the embryonic yolk sac, migrating to the brain and eventually populating local tissue prior to blood-brain barrier formation. Preserved for the duration of lifespan, microglia serve the host as more than just a central arm of innate immunity, also contributing significantly to the development and maintenance of neurons and neural networks, as well as neuroregeneration. The critical nature of these varied functions makes the characterization of key roles played by microglia in neurodegenerative disorders, especially Alzheimer's disease, of paramount importance. While genetic models and rudimentary pharmacologic approaches for microglial manipulation have greatly improved our understanding of central nervous system health and disease, significant advances in the selective and near complete in vitro and in vivo depletion of microglia for neuroscience application continue to push the boundaries of research. Here we discuss the research efficacy and utility of various microglial depletion strategies, including the highly effective CSF1R inhibitor models, noteworthy insights into the relationship between microglia and neurodegeneration, and the potential for therapeutic repurposing of microglial depletion and repopulation.
Project description:Social support for goals can be beneficial for goal pursuit, but often has unintended negative consequences for the recipient. We propose that action crisis-the state in which an individual is considering disengaging from a goal they are currently pursuing-may result in people experiencing more ambivalent reactions to goal support. Drawing on both experimental and longitudinal methods, we show that action crisis increases negative consequences of goal support, but does not reduce positive consequences of goal support. In Study 1, we experimentally manipulated goal phase (action crisis, deliberative, or implemental) and had participants imagine support or neutral interactions. In Study 2, we measured experiences of action crisis and receipt of goal support in first-year pre-health students over the course of the academic year. Action crisis predicted more negative appraisals of support, but did not impact positive appraisals of support. Similarly, action crisis predicted more negative emotions and depressive symptoms among people who received goal support, but did not impact positive emotions. These results suggest that action crisis increases the extent to which support is received as a "mixed blessing".Supplementary informationThe online version contains supplementary material available at 10.1007/s11031-022-09977-8.
Project description:The mid-Proterozoic, spanning 1.8 to 0.8 billion years ago, is recognized as a phase of marine anoxia, low marine primary productivity (MPP), and constrained eukaryotic biodiversity. However, emerging evidence suggesting intermittent environmental disturbances and concurrent eukaryotic evolution challenges the notion of a stagnant Earth during this era. We present a study detailing volcanic activity and its consequential impact on terrestrial weathering and MPP, elucidated through the examination of 1.4-billion-year-old tropical offshore sediments. Our investigation, leveraging precise mercury (Hg) and lithium (Li) isotopic analyses, reveals the introduction of fresh rock substrates by local volcanism. This geological event initiated a transformative process, shifting the initial regolith-dominated condition in tropical lowland to a regime of enhanced chemical weathering and denudation efficiency. Notably, the heightened influx of nutrient-rich volcanic derivatives, especially phosphorus, spurred MPP rates and heightened organic carbon burial. These factors emerge as potential drivers in breaking the long-term static state of the mid-Proterozoic.
Project description:BackgroundEnsuring patient rights is an extension of applying human rights principles to health care. A critical examination of how the notion of patient rights is perceived and enacted by various actors through critical discourse analysis (CDA) can help understand the impediments to its realization in practice.MethodsWe studied the discourses and discursive practices on patient rights in subnational policies and in ten health facilities in southern Karnataka, India. We conducted interviews (78), focus group discussions (3) with care-seeking individuals, care-providers, health care administrators and public health officials. We also conducted participant observation in selected health facilities and examined subnational policy documents of Karnataka pertaining to patient rights. We analyzed the qualitative data for major and minor themes.ResultsPatient rights discourses were not based upon human rights notions. In the context of neoliberalism, they were predominantly embedded within the logic of quality of care, economic, and consumerist perspectives. Relatively powerful actors such as care-providers and health facility administrators used a panoply of discursive strategies such as emphasizing alternate discourses and controlling discursive resources to suppress the promotion of patient rights among care-seeking individuals in health facilities. As a result, the capacity of care-seeking individuals to know and claim patient rights was restricted. With neoliberal health policies promoting austerity measures on public health care system and weak implementation of health care regulations, patient rights discourses remained subdued in health facilities in Karnataka, India.ConclusionsThe empirical findings on the local expression of patient rights in the discourses allowed for theoretical insights on the translation of conceptual understandings of patient rights to practice in the everyday lives of health system actors and care-seeking individuals. The CDA approach was helpful to identify the problematic aspects of discourses and discursive practices on patient rights where health facility administrators and care-providers wielded power to oppress care-seeking individuals. From the practical point of view, the study demonstrated the limitations of care-seeking individuals in the discursive realms to assert their agency as practitioners of (patient) rights in health facilities.
Project description:BackgroundWidespread antibiotic prescribing contributes to globally emerging antimicrobial resistance (AMR). Despite stewardship recommendations by the Infectious Diseases Society of America, there is a lack of literature identifying barriers and facilitators to antimicrobial stewardship programs (ASPs) in United States (U.S.) carceral settings.MethodsGuided by the Theoretic Domains Framework, we performed in-depth interviews with 68 key stakeholders in Massachusetts carceral settings to contextualize barriers and facilitators to ASP implementation. We recruited 32 people incarcerated in Massachusetts jails and 36 carceral clinicians, correctional officers/administrators in Massachusetts and other U.S. states, and Massachusetts community clinicians for interviews.ResultsFrom the completed semi-structured in-depth interviews, we identified seven salient themes-four barriers and three facilitators-both specific to and across stakeholder groups. Barriers included the following: (1) jail being viewed as a "dirty place" that increases the risk of infections; (2) variable awareness and knowledge of AMR and ASPs; (3) clinicians' opposition to change and oversight of their antibiotic prescribing; (4) competing priorities taking precedence over ASP implementation. Facilitators included (5) interest in changing the narrative about carceral healthcare through ASP implementation; (6) opportunities for education about ASP and AMR; and (7) the development of systems, policies, and regulations to improve antibiotic prescribing.ConclusionsTo our knowledge, this is the first qualitative study to leverage broad criminal-legal stakeholder groups to inform the next steps in developing and implementing ASPs in carceral settings in the U.S.
Project description:The present experiment assessed implicit alcohol motivations and explicit alcohol expectancies following the interaction between alcohol-congruent (i.e. social drinking) versus incongruent (i.e. driving safety) goal primes and recent drinking habits among college students (n = 176). Heavy drinkers exhibited greater implicit alcohol approach and explicit tension reduction expectancies following social goal primes, while displaying greater implicit alcohol avoidance and explicit cognitive and behavioural impairment expectancies after driving safety goal primes. These findings indicate recent drinking habits interact with goal salience to influence explicit and implicit responses to alcohol, which has implications for the development of interventions to reduce college drinking.
Project description:In two experiments, we provided support for the hypothesis that stimuli with preexisting memory representations (e.g., famous faces) are easier to associate to their encoding context than are stimuli that lack long-term memory representations (e.g., unknown faces). Subjects viewed faces superimposed on different backgrounds (e.g., the Eiffel Tower). Face recognition on a surprise memory test was better when the encoding background was reinstated than when it was swapped with a different background; however, the reinstatement advantage was modulated by how many faces had been seen with a given background, and reinstatement did not improve recognition for unknown faces. The follow-up experiment added a drug intervention that inhibited the ability to form new associations. Context reinstatement did not improve recognition for famous or unknown faces under the influence of the drug. The results suggest that it is easier to associate context to faces that have a preexisting long-term memory representation than to faces that do not.
Project description:Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 are enzymes which post-translationally modify proteins through poly(ADP-ribosyl)ation (PARylation)-the transfer of ADP-ribose chains onto amino acid residues-with a resultant modulation of protein function. Many targets of PARP-1/2-dependent PARylation are involved in the DNA damage response and hence, the loss of these proteins disrupts a wide range of biological processes, from DNA repair and epigenetics to telomere and centromere regulation. The central role of these PARPs in DNA metabolism in cancer cells has led to the development of PARP inhibitors as new cancer therapeutics, both as adjuvant treatment potentiating chemo-, radio-, and immuno-therapies and as monotherapy exploiting cancer-specific defects in DNA repair. However, a cancer is not just made up of cancer cells and the tumor microenvironment also includes multiple other cell types, particularly stromal and immune cells. Interactions between these cells-cancerous and non-cancerous-are known to either favor or limit tumorigenesis. In recent years, an important role of PARP-1 and PARP-2 has been demonstrated in different aspects of the immune response, modulating both the innate and adaptive immune system. It is now emerging that PARP-1 and PARP-2 may not only impact cancer cell biology, but also modulate the anti-tumor immune response. Understanding the immunomodulatory roles of PARP-1 and PARP-2 may provide invaluable clues to the rational development of more selective PARP-centered therapies which target both the cancer and its microenvironment.
Project description:PurposeLymphocyte activation gene 3 (LAG3) is thought to contribute to T cell exhaustion within the tumor microenvironment of solid tumors. This study aimed to analyze the spatial distribution of LAG3 + cells in relation to clinicopathological and survival data in a large set of 580 primary resected and neoadjuvantly treated gastric cancers (GC).MethodsLAG3 expression was evaluated in tumor center and invasive margin using immunohistochemistry and whole-slide digital image analysis. Cases were divided into LAG3-low and LAG3-high expression groups based on (1) median LAG3 + cell density, (2) cut-off values adapted to cancer-specific survival using Cutoff Finder application.ResultsSignificant differences in spatial distribution of LAG3 + cells were observed in primarily resected GC, but not in neoadjuvantly treated GC. LAG3 + cell density showed evident prognostic value at following cut-offs: in primarily resected GC, 21.45 cells/mm2 in tumor center (17.9 vs. 10.1 months, p = 0.008) and 208.50 cells/mm2 in invasive margin (33.8 vs. 14.7 months, p = 0.006); and in neoadjuvantly treated GC, 12.62 cells/mm2 (27.3 vs. 13.2 months, p = 0.003) and 123.00 cells/mm2 (28.0 vs. 22.4 months, p = 0.136), respectively. Significant associations were found between LAG3 + cell distribution patterns and various clinicopathological factors in both cohorts. In neoadjuvantly treated GC, LAG3 + immune cell density was found to be an independent prognostic factor of survival (HR = 0.312, 95% CI 0.162-0.599, p < 0.001).ConclusionIn this study, a higher density of LAG3 + cells was associated with favorable prognosis. Current results support the need for extended analysis of LAG3. Differences in the distribution of LAG3 + cells should be considered, as they could influence clinical outcomes and treatment responses.