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Calabash chalk (CaC) is an aluminium silicate hydroxide compound with heavy metal constituents, making it a potential neurotoxicant. Pregnant women often consume CaC as an antiemetic, which may interfere with the normal development of the foetal brain. Here, we evaluated the effects of CaC administration in pregnant rats on the brain of the offspring. Wistar rat dams were assigned to one of three groups: control, 200 mg/kg and 800 mg/kg of a CaC suspension. Administrations lasted 14 days (gestation days 7–20). On day 14, 5-bromo-2′-deoxyuridine (BrdU) was administered and dams were allowed to term. Behavioural tests were performed on different days as the pups matured, and they were sacrificed on post-natal days 30 and 60. Brains were processed for histology and Western blotting. Results showed no significant differences in surface righting reflex, cliff avoidance, negative geotaxis and open-field activity. No hippocampal and somatosensory cortical cytoarchitectonic alterations and no significant signs of glial fibrillary acidic protein (GFAP) activation were observed. Neuronal nuclei counts showed variability in the somatosensory cortex and hippocampus of the CaC group. BrdU-positive cells were significantly lower in the 200 mg/kg group and higher in the 800 mg/kg group. Doublecortin-X-positive cells were not different in all the CaC groups. Astrocytes and microglia Western blotting quantification confirmed no significant increase in pup glial cells in adulthood. Prenatal consumption of CaC at indicated dosages may not be deleterious to the developing brain, especially after cessation of exposure and during maturation of the animal. However, the differences in neuronal and glial populations may be due to their ability to cope with CaC.

Abstract Notch development at the base of sea cliffs is an important control on cliff recession rates, but a detailed mechanistic understanding of notch formation by swash abrasion is lacking. We conducted physical experiments, using homogeneous erodible rock simulants, to study notch‐forming mechanisms under periodic sediment‐laden bore impacts. Our findings reveal shifts in the temporal dynamics of notch development. Initially, swash uprush and vortex formation contribute to a positive feedback loop that creates a shallow and wide notch. Subsequently, upward erosion ceases, and notch backwear and downwear are dominated by the vortex. Eventually, sediment deposition armors the notch floor; this negative feedback loop reduces erosion. The sediment size determines the amount of erosion, with a range of grain sizes generating maximum erosion. This indicates a dependence on the momentum of the sediment particles entrained within the bore. This research reveals fundamental notch formation mechanisms driven by swash abrasion.

Abstract It is often assumed that future coastal cliff retreat rates will accelerate as global sea level rises, but few studies have investigated how SLR (sea level rise) might change cliff-front wave dynamics. Using a new simple numerical model, this study simulates the number and type (breaking, broken, or unbroken) of cliff-front waves under future SLR scenarios. Previous research shows breaking waves deliver more energy to cliffs than broken waves, and unbroken waves generate minimal impact. Here, we investigated six cliff-platform profiles from three regions (USA, New Zealand, and UK) with varied tidal ranges and wave climates. Model inputs included 2013–2100 hindcast/forecast incident wave height and tidal water level, and three future SLR scenarios. Results show the number of both cliff-front breaking and broken waves generally increase for a high-elevation (relative to tide) cliff-platform junction. In contrast, breaking/broken wave occurrence decrease by 38–92% for a near-horizontal shore platform with a low-elevation cliff-platform junction under a high SRL scenario, leading to high (96–97%) unbroken wave occurrence. Overall, results suggest the response of cliff-front waves to future SLR is complex and depends on shore platform geometries and SLR scenarios, indicating that future cliff retreat rates may not homogeneously accelerate under SLR.

Abstract Sustainable drainage systems (SuDS) are nature-based methods of managing urban stormwater runoff. Although they are widely used, some SuDS, such as highway filter drains (HFDs), are understudied with respect to sizing and performance. For the first time, we developed an analytical probabilistic model (APM) that can be used to design and estimate the hydrologic performance of HFDs. Unlike the conventionally used design-storm based or continuous simulation approaches, our APM can directly calculate the runoff capture ratios of HFDs using closed-form analytical equations. Validation of the APM presented here shows that it is robust and reliable. The relative differences between the APM-estimated and continuous simulation-determined runoff capture ratios for all the simulated design cases are less than 8.5%.

Abstract Brain transcriptional variation is a heritable trait that mediates complex behaviors, including addiction. Expression quantitative trait locus (eQTL) mapping reveals genomic regions harboring genetic variants that influence transcript abundance. In this study, we profiled transcript abundance in the striatum of 386 Diversity Outbred (J:DO) mice of both sexes using RNA-Seq. All mice were characterized using a behavioral battery of widely-used exploratory and risk-taking assays prior to transcriptional profiling. We performed eQTL mapping, incorporated the results into a browser-based eQTL viewer, and deposited co-expression network members in GeneWeaver. The eQTL viewer allows researchers to query specific genes to obtain allelic effect plots, analyze SNP associations, assess gene expression correlations, and apply mediation analysis to evaluate whether the regulatory variant is acting through the expression of another gene. GeneWeaver allows multi-species comparison of gene sets using statistical and combinatorial tools. This data resource allows users to find genetic variants that regulate differentially expressed transcripts and place them in the context of other studies of striatal gene expression and function in addiction-related behavior.

Abstract Sensory stimuli are natural rewards in mice and humans. Consequently, preference for a drug reward relative to a sensory reward may be an endophenotype of addiction vulnerability. In this study, we developed a novel behavioral assay to quantify the preference for intravenous drug self-administration relative to sensory stimulus self-administration. We used founder strains of the BXD recombinant inbred mouse panel (C57BL/6J, DBA/2J) and a model of stress (isolation vs enriched housing) to assess genetic and epigenetic effects. Following 10 weeks of differential housing, all mice were tested under three reward conditions: sensory rewards available, cocaine rewards available, both rewards available. When a single reward was available (sensory stimuli or cocaine; delivered using distinct levers), DBA/2J mice self-administered significantly more rewards than C57BL/6J mice. When both rewards were available, DBA/2J mice exhibited a significant preference for cocaine relative to sensory stimuli; in contrast, C57BL/6J mice exhibited no preference. Housing condition influenced sensory stimulus self-administration and strain-dependently influenced inactive lever pressing when both rewards were available. Collectively, these data reveal strain effects, housing effects, or both on reward self-administration and preference. Most importantly, this study reveals that genetic mechanisms underlying preference for a drug reward relative to a nondrug reward can be dissected using the full BXD panel.

This study establishes that the magnitude of observed physical changes in coral reef islands over the period of recent global warming is not unprecedented, and islands have continually adjusted to environmental change over the past millennia.

Abstract The genetic mechanisms underlying fentanyl addiction, a highly heritable disease, are unknown. Identifying these mechanisms will lead to better risk assessment, early diagnosis, and improved intervention. To this end, we used intravenous fentanyl self-administration to quantify classical self-administration phenotypes and addiction-like fentanyl seeking in male and female mice from the two founder strains of the BXD recombinant inbred mouse panel (C57BL/6J and DBA/2J). We reached three primary conclusions from these experiments. First, mice from all groups rapidly acquired intravenous fentanyl self-administration and exhibited a dose–response curve, extinction burst, and extinction of the learned self-administration response. Second, fentanyl intake (during acquisition and dose response) and fentanyl seeking (during extinction) were equivalent among groups. Third, strain effects, sex effects, or both were identified for several addiction-like behaviors (cue-induced reinstatement, stress-induced reinstatement, escalation of intravenous fentanyl self-administration). Collectively, these data indicate that C57BL/6J and DBA/2J mice of both sexes were able to acquire, regulate, and extinguish intravenous fentanyl self-administration. Moreover, these data reveal novel strain and sex effects on addiction-like behaviors in the context of intravenous fentanyl self-administration in mice and indicate that the full BXD panel can be used to identify and dissect the genetic mechanisms underlying these effects.

Abstract Interbasin water transfers (IBTs) can have a significant impact on the environment, water availability, and economies within the basins importing and exporting water, as well as basins downstream of these water transfers. The lack of comprehensive data identifying and describing IBTs inhibits understanding of the role IBTs play in supplying water for society, as well as their collective hydrologic impact. We develop three connected datasets inventorying IBTs in the United States and Canada, including their features, geospatial details, and water transfer volumes. We surveyed the academic and gray literature, as well as local, state, and federal water agencies, to collect, process, and verify IBTs in Canada and the United States. Our comprehensive IBT datasets represent all known transfers of untreated water that cross subregion (US) or subdrainage area (CA) boundaries, characterizing a total of 641 IBT projects. The infrastructure-level data made available by these data products can be used to close water budgets, connect water supplies to water use, and better represent human impacts within hydrologic and ecosystem models.

The antiplasmodial effects of Senna alata and Dennettia tripetalla on chloroquine-sensitive Plasmodium berghei berghei (NK65) were analysed. P. berghei was obtained from National Institute for Medical Research, Lagos, Nigeria, and maintained in the laboratory by serial passage in mice. Chemosuppressive, prophylactic, and curative procedures were used to evaluate the antiplasmodial potentials of the extracts against established infection. A total of 320 albino mice were used for this study. Twenty-five albino mice were divided into 5 groups and used for D. tripetalla acute toxicity study. Eighty-five albino mice were divided into 15 groups of five albino mice each and used for chemosuppressive tests while two hundred and ten mice were used for prophylactic and curative tests. The infected mice were orally treated daily with 5mg/kg chloroquine 500 mg/kg, 1000 mg/kg, 1500 mg/kg, and 2000 mg/kg body weight of S. alata, D. tripetalla, and S. alata + D. tripetalla respectively. The in vivo antiplasmodial effect of the extracts against P. berghei infection showed a significant (p?0.05) dose-dependent schizontocidal activity for the chemosuppressive, and prophylactic test. Results of the curative study showed that the combination of both S. alata and D. tripetalla exhibited a strong curative effect on malaria parasitaemia. There was a significant clearance (p?0.05) in parasiteamia level from day 1 to day 5 of treatment in a dose-dependent manner with a corresponding significant (p?0.05) percentage suppression. It was therefore concluded that the leaf extracts of S. alata and D. tripetalla possess antimalarial potencies which could be exploited for antimalarial therapy.

IMPORTANCE:. Outcomes for critically ill COVID-19 are well described; however, the impact of the pandemic on critically ill patients without COVID-19 infection is less clear. OBJECTIVES:. To demonstrate the characteristics and outcomes of non-COVID patients admitted to an ICU during the pandemic, compared with the previous year. DESIGN:. A population-based study conducted using linked health administrative data comparing a cohort from March 1, 2020, to June 30, 2020 (pandemic) to a cohort from March 1, 2019, to June 30, 2019 (nonpandemic). SETTING AND PARTICIPANTS:. Adult patients (18 yr old) admitted to an ICU in Ontario, Canada, without a diagnosis of COVID-19 during the pandemic and nonpandemic periods. MAIN OUTCOMES AND MEASURES:. The primary outcome was all-cause in-hospital mortality. Secondary outcomes included hospital and ICU length of stay, discharge disposition, and receipt of resource intensive procedures (e.g., extracorporeal membrane oxygenation, mechanical ventilation, renal replacement therapy, bronchoscopy, feeding tube insertion, and cardiac device insertion). We identified 32,486 patients in the pandemic cohort and 41,128 in the nonpandemic cohort. Age, sex, and markers of disease severity were similar. Fewer patients in the pandemic cohort were from long-term care facilities and had fewer cardiovascular comorbidities. There was an increase in all-cause in-hospital mortality among the pandemic cohort (13.5% vs 12.5%; p < 0.001) representing a relative increase of 7.9% (adjusted odds ratio, 1.10; 95% CI, 1.05–1.56). Patients in the pandemic cohort admitted with chronic obstructive pulmonary disease exacerbation had an increase in all-cause mortality (17.0% vs 13.2%; p = 0.013), a relative increase of 29%. Mortality among recent immigrants was higher in the pandemic cohort compared with the nonpandemic cohort (13.0% vs 11.4%; p = 0.038), a relative increase of 14%. Length of stay and receipt of intensive procedures were similar. CONCLUSIONS AND RELEVANCE:. We found a modest increase in mortality among non-COVID ICU patients during the pandemic compared with a nonpandemic cohort. Future pandemic responses should consider the impact of the pandemic on all patients to preserve quality of care.

Abstract Working memory and pattern separation are fundamental cognitive abilities which, when impaired, significantly diminish quality of life. Discovering genetic mechanisms underlying innate and disease-induced variation in these cognitive abilities is a critical step towards treatments for common and devastating neurodegenerative conditions such as Alzheimer's disease. In this regard, the trial-unique nonmatching-to-location assay (TUNL) is a touchscreen operant conditioning procedure allowing simultaneous quantification of working memory and pattern separation in mice and rats. In the present study, we used the TUNL assay to quantify these cognitive abilities in C57BL/6J and DBA/2J mice. These strains are the founders of the BXD recombinant inbred mouse panel which enables discovery of genetic mechanisms underlying phenotypic variation. TUNL testing revealed that pattern separation was significantly influenced by mouse strain, whereas working memory was not. Moreover, horizontal distance and vertical distance between choice-phase stimuli had dissociable effects on TUNL performance. These findings provide novel data on mouse strain differences in pattern separation and support previous findings of equivalent working memory performance in C57BL/6J and DBA/2J mice. Although working memory of the BXD founder strains was equivalent in this study, working memory of BXD strains may be divergent because of transgressive segregation. Collectively, data presented here indicate that pattern separation is heritable in the mouse and that the BXD panel can be used to identify mechanisms underlying variation in pattern separation.

Abstract Sensation seeking is a multidimensional phenotype that predicts the development of drug addiction in humans and addiction-like drug seeking in rodents. Several lines of evidence suggest that chronic stress increases sensation seeking and addiction-like drug seeking through common genetic mechanisms. Discovery and characterization of these mechanisms would reveal how chronic stress interacts with the genome to influence sensation seeking and how drugs of abuse hijack these fundamental reward mechanisms to drive addiction. To this end, we tested the hypothesis that chronic isolation housing stress (relative to environmental enrichment) influences operant sensation seeking as a function of strain, sex, or their interaction. To determine if the BXD recombinant inbred panel could be used to identify genetic and epigenetic mechanisms underlying any identified gene-by-environment interactions, we used mice from the two BXD founder strains. Following 10 weeks of differential housing, we assessed operant sensation seeking using several reinforcement schedules. The primary finding from this study was that DBA/2J but not C57BL/6J mice were significantly vulnerable to an isolation-induced increase (relative to environmental enrichment) in sensation seeking during extinction when the sensory reward was no longer available; this effect was significantly more robust in females. These data reveal a previously unknown isolation-induced effect on extinction of operant sensation seeking that is sex-dependent, addiction-relevant, and that can be dissected using the BXD recombinant inbred panel.

Abstract Environmental factors such as stress drive the development of drug addiction in genetically vulnerable individuals; the genes underlying this vulnerability are unknown. One strategy for uncovering these genes is to study the impact of environmental manipulation on high-throughput phenotypes that predict drug use and addiction-like behaviors. In the present study, we assessed the viability of this approach by evaluating the relative effects of environmental enrichment and isolation housing on three high-throughput phenotypes known to predict variation on distinct aspects of intravenous drug self-administration. Prior to behavioral testing, male and female C57BL/6J and DBA/2J mice (BXD founders) were housed in enrichment or isolation for ten weeks beginning at weaning. Enrichment significantly reduced novelty reactivity; this effect was significantly more robust in C57BL/6J mice relative to DBA/2J mice. Enrichment significantly reduced novelty preference; this effect was significantly dependent on novel environment characteristics and was significantly more robust in DBA/2J mice relative to C57BL/6J mice. Enrichment significantly increased anxiety; this effect was not strain-dependent. Collectively, these data indicate that (1) environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in mice, and (2) the BXD panel can be used to discover the genetic and epigenetic mechanisms underlying this phenomenon.

Abstract Background In Ontario, Canada, Indigenous communities experience some of the province’s worst drinking water, with issues ranging from deteriorating water quality to regulatory problems and lack of support. When water is known, or suspected, to be unsafe for human consumption, communities are placed under a Drinking Water Advisory. Between 2004 and 2013, approximately 70% of all on-reserve communities in Ontario were under at least one Drinking Water Advisory. Despite the widespread impact of Drinking Water Advisories on health and wellbeing, little is known about First Nation individuals’ perceptions and experiences living with a Drinking Water Advisory. This study presents information shared by members of a community who have lived with Boil Water Advisories on and off for many years, and a long-term Boil Water Advisory since 2017. The goal of this paper is to unpack and explore the Boil Water Advisories from the perspective of community members and provide considerations for current and future Boil Water Advisory management. Methods Methodological choices were driven by the principles of community-based participatory research. Two data collection methodologies were employed: hard copy surveys and interviews. Results Forty-four individuals (19.5%) completed a survey. Eight Elders and 16 key informants participated in 20 interviews. Respondents expressed varying degrees of uncertainty regarding protective actions to take while under a Boil Water Advisory. Further, 79% of men but only 46% of women indicated they always adhere to the Boil Water Advisory. Knowledge gaps that could lead to risky behaviours were also identified. Finally, Boil Water Advisories were demonstrated to have physical, financial, and time impacts on the majority of respondents. Conclusions A direct outcome was the identification of a critical need to reinforce best practices for health protection through community education and outreach. More broadly, Chief and Council were able to use the findings to successfully advocate for improved drinking water for the community. Additionally, benefits of participatory research and community ownership include enhanced local research capacity, and increased awareness of, and desire for, research to inform decisions.

Abstract A scientific storytelling approach is used to communicate results from a transdisciplinary model of human‐environment estuarine systems for the purpose of developing system understanding and improving transdisciplinary communication. Questionnaires and a media analysis are used to collate public perceptions of observed environmental change in estuarine systems, with an agent‐based model developed to investigate the effects of these environmental changes and the complex network of interactions that lead to them. Five scenarios that correspond to the main public interests identified during questionnaire analyses are presented and described using a narrative textual approach; flow diagrams are used to explain model processes and interactions. We test whether the earth science storytelling approach of Phillips (2012), https://doi.org/10.1016/j.earscirev.2012.09.005 can be applied more broadly to transdisciplinary models of complex human‐environment systems. Results indicate that all eight storytelling plots of Phillips (2012), https://doi.org/10.1016/j.earscirev.2012.09.005 are applicable to describing pathways within human‐environment systems and are useful in succinctly explaining complex interactions within such systems; the crucial initial step is determining what needs to be communicated and subsequently deciding on appropriate plot or plots to convey the story.

Substance use disorders are prevalent and present a tremendous societal cost but the mechanisms underlying addiction behavior are poorly understood and few biological treatments exist. One strategy to identify novel molecular mechanisms of addiction is through functional genomic experimentation. However, results from individual experiments are often noisy. To address this problem, the convergent analysis of multiple genomic experiments can discern signal from these studies. In the present study, we examine genetic loci that modulate the locomotor response to cocaine identified in the recombinant inbred (BXD RI) genetic reference population. We then applied the GeneWeaver software system for heterogeneous functional genomic analysis to integrate and aggregate multiple studies of addiction genomics, resulting in the identification of Rab3b as a functional correlate of the locomotor response to cocaine in rodents. This gene encodes a member of the RAB family of Ras-like GTPases known to be involved in trafficking of secretory and endocytic vesicles in eukaryotic cells. The convergent evidence for a role of Rab3b includes co-occurrence in previously published genetic mapping studies of cocaine related behaviors; methamphetamine response and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) transcript abundance; evidence related to other addictive substances; density of polymorphisms; and its expression pattern in reward pathways. To evaluate this finding, we examined the effect of RAB3 complex perturbation in cocaine response. B6;129-Rab3btm1Sud Rab3ctm1sud Rab3dtm1sud triple null mice (Rab3bcd–/–) exhibited significant deficits in habituation, and increased acute and repeated cocaine responses. This previously unidentified mechanism of the behavioral predisposition and response to cocaine is an example of many that can be identified and validated using aggregate genomic studies.

Sensation seeking is a heritable trait that is genetically correlated with substance use; the shared genetic mechanisms underlying these traits are largely unknown. The relationship of sensation seeking and substance use has practical importance because discovering genes that drive sensation seeking can reveal genes driving substance use, and quantification of sensation seeking in mice is higher throughput and less technically challenging than quantification of volitional drug use. In order to fully understand the genetic mechanisms driving sensation seeking, it is critical to first understand the nongenetic factors driving sensation seeking. In the present study, we used the operant sensation seeking paradigm to assess the effects of stimulus complexity on sensation seeking in C57BL/6J and DBA/2J mice. These strains are the founders of the BXD recombinant inbred mouse panel which enables the discovery of genes driving phenotypic variation. This study led to four principal conclusions. First, all sensory stimuli used in the study, regardless of complexity or number of stimulus modalities, served as reinforcers for C57BL/6J and DBA/2J mice. Second, for both C57BL/6J and DBA/2J mice, sensation seeking for a high complexity sensory stimulus was significantly greater than sensation seeking for a low complexity sensory stimulus. Third, for both C57BL/6J and DBA/2J mice, sensation seeking escalated significantly within-session when a multimodal sensory stimulus of medium or high complexity was used but not when a unimodal sensory stimulus of low complexity was used. Finally, both the magnitude of sensation seeking and the magnitude of within-session escalation of sensation seeking were significantly greater in mice from the DBA/2J strain relative to mice from the C57BL/6J strain. Collectively, these findings indicate that stimulus complexity and genetic background drive escalation of operant sensation seeking within and across sessions, and that the BXD recombinant inbred mouse panel can be used to discover the genetic mechanisms underlying these phenomena.

Abstract Background Sexual initiation occurs early in Sierra Leone. This study aims to analyze the determinants of condom and/or contraceptive use among a representative sample of young persons (10 to 24 years) in Sierra Leone. Methods This is a secondary analysis of data from a study conducted to monitor the implementation of a UNFPA package of interventions directed to improve SRH in young people of Sierra Leone. This assessment was conducted in 2016 at the end of the Ebola outbreak. In consequence, determinants linked to healthy lifestyle behaviors and UNFPA interventions were explored in addition to the usual determinants: socio demographic and sexual lifestyle. This study is a household quantitative survey with open ended questions used to illustrate and complete the analysis. Results A total of 1409 young people were interviewed: of these, 216 boys and 381 girls were sexually active. Those who were pregnant or wished for pregnancy were excluded, leaving 194 boys and 268 girls for the analysis of determinants. The proportion of young people using neither condom nor other contraception at their last sexual intercourse in the whole sample was 40.5% and there was no statistically significant difference between boys and girls (42.3 vs 39.2; P = 0.504). Determinants were assessed and, after multivariable analysis, results differed between boys and girls and showed the importance of behavioral aspects. Four determinants were common to boys and girls: literacy, distance, negotiation capacity and hand washing. However, the distance factor for girls was to the health facility and for boys it was to school. Three more determinants remained in the boy’s model: sleeping under a bednet, number of sexual partners and knowledge of contraceptive methods. Opinions about condoms and contraception revealed important barriers; opposition to contraceptive use was the main reason for non-use for both boys and girls, while lack of access was an important reason for boys. Conclusion There is a need to reach out to the 40% of young people who are sexually active and neither pregnant nor with pregnancy desire, and are not using condom or contraception.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy and the most common neuromuscular disorder. In addition to neuromuscular consequences, some individuals with DMD experience global intellectual dysfunction and executive dysfunction of unknown mechanistic origin. The cognitive profile of the mdx mouse, the most commonly used mouse model of DMD, has been incompletely characterized and has never been assessed using the touchscreen operant conditioning paradigm. The touchscreen paradigm allows the use of protocols that are virtually identical to those used in human cognitive testing and may, therefore, provide the most translational paradigm for quantifying mouse cognitive function. In the present study, we used the touchscreen paradigm to assess the effects of the mdx mutation on visual discrimination learning, serial reversal learning, and extinction learning. To enable measuring task-dependent learning and memory processes while holding demands on sensory-driven information processing constant, we developed equally salient visual stimuli and used them on all experimental stages. Acquisition of the initial pairwise visual discrimination was facilitated in mdx mice relative to wildtype littermates; this effect was not explained by genotypic differences in impulsivity, motivation, or motor deficits. The mdx mutation had no effect on serial reversal or extinction learning. Together, findings from this study and previous studies suggest that mdx effects on cognitive function are task-specific and may be influenced by discrimination type (spatial, visual), reward type (food, escape from a non-preferred environment), sex, and genetic background.