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A higher intake of foods rich in flavonoids such as quercetin can reduce the risk of cardiovascular disease. Enzymatically modified isoquercitrin (EMIQ®) has a bioavailability 17-fold higher than quercetin aglycone and has shown potential cardiovascular disease moderating effects in animal studies. The present study aimed to determine if acute ingestion of EMIQ® improves endothelial function, blood pressure, and cognitive function in human volunteers at risk of cardiovascular disease. Twenty-five participants (12 males, 13 females) with at least one cardiovascular disease risk factor completed this randomized, controlled, crossover study. In a random order, participants were given EMIQ® (2 mg aglycone equivalent)/kg body weight or placebo alongside a standard breakfast meal. Endothelial function, assessed by flow mediated dilatation (FMD) of the brachial artery was measured before and 1.5 hrs after intervention. Blood pressure (BP), arterial stiffness, cognitive function, BP during cognitive stress and measures of quercetin metabolites, oxidative stress and markers of nitric oxide (NO) production were assessed post-intervention. After adjustment for pre-treatment measurements and treatment order, EMIQ® treatment resulted in a significantly higher FMD response compared to the placebo [0.60%, 95% CI: 0.03, 1.17 (p=0.04)]. Plasma concentrations of quercetin metabolites were significantly higher (p<0.001) after EMIQ® treatment compared to the placebo. No changes in blood pressure, arterial stiffness, cognitive function, or biochemical parameters were observed. In this human intervention study, the acute administration of EMIQ® significantly increased circulating quercetin metabolites and improved endothelial function. Further clinical trials are required to assess whether health benefits are associated with long-term EMIQ® consumption.
First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.
We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.
In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.
The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
Recent studies have highlighted that illegal activities occurring within protected areas, including the poaching of fauna and flora, cannot be addressed with increased law enforcement alone. Moreover, research on the increasingly militarized nature of front-line conservation efforts has pointed to potentially detrimental aspects of such approaches. This has led to a shift in focus to identifying ways to further engage local communities in the prevention and reduction of wildlife crimes. However, few studies have examined the potential for changing the responsibilities of front-line conservation personnel or their views on such changes. Such insight is vital in forecasting the successful adoption of, or possible resistance towards, a more community-oriented policy. We examined rangers’ perceptions in Uganda to assess their attitudes towards traditional enforcement strategies and alternative, non-enforcement approaches for reducing illegal activities in protected areas. Our findings suggest that although respondents believed that traditional enforcement strategies (e.g. foot patrols) are important and effective in reducing wildlife crime, these strategies on their own were insufficient to address illegal activities. Study participants emphasized the importance of expanding the role of front-line rangers, in line with approaches suggested in the policing literature. We discuss the implications of our findings for transdisciplinary conservation science research and front-line conservation policy and practice.
Despite the global significance of the Leach’s Storm-petrel Hydrobates leucorhous colony on Baccalieu Island, Newfoundland and Labrador, Canada, the estimate of 3.36 million breeding pairs reported for 1984 by Sklepkovych and Montevecchi stands as the single published population estimate for the world’s largest colony. This study increases knowledge of this population by analysing data from additional independent surveys conducted in 1984 and 1985, and by updating the population status with a survey conducted in 2013. Population estimates were derived by extrapolating occupied burrow densities to the estimated occupied area of four main habitat types (heath, forest, grass and fern), which in turn were based on proportions of habitats observed in plots (1984 and 1985) or by using a Geographic Information System approach (2013). Based on these surveys, the Leach’s Storm-petrel breeding population size on Baccalieu Island was estimated at 5.12 ± 0.73 (SE) and 4.60 ± 0.42 (SE) million pairs in 1984 and 1985 respectively, representing estimates 37–51% greater than the original 1984 survey. While discrepancies among these estimates were largely driven by the way occupied areas were estimated, our study confirms that Baccalieu Island hosts the largest Leach’s Storm-petrel colony in the world. Results from the 2013 survey estimate the current breeding Leach’s Storm-petrel population at 1.95 ± 0.14 (SE) million pairs, representing a 42% decline over 29 years (-1.4% per year), relative to the original published estimate of 3.36 ± 0.12 (SE) million pairs. The most prominent change has occurred in the density of storm-petrel burrows found in forest habitat which dropped by 70% despite forest remaining the second most abundant habitat available to nesting storm-petrels on Baccalieu Island. The cause of this decline remains unknown and is likely multi-faceted. Future research focusing on demographic studies is required to understand what is driving the population decline of this internationally important colony.
Disasters and major incidents, while uncommon in each country, occur sufficiently frequently worldwide and have such societal impacts that they make headlines on most days. Perhaps, paradoxically, emergencies are so common as to be almost ordinary, if only in purely statistical terms, if it were not for the human impact, worry and suffering that is involved. This chapter shows how disasters are integral to and, thus, present a microcosm of our worlds. Our intention is to use them, in common with each of the topics in Section 3 of this book, to explore social influences on how people, communities and societies respond to and cope with the physical and psychosocial impacts of major events. This chapter links John Drury et al.’s exploration of the contribution of social psychology to crowd science in Chapter 15 with Drury and Alfadhli’s Chapter 17, on disasters. We intend that Chapters 15, 16 and 17 provide another window on the human condition, the importance of social relationships and the powerful influences of social identity.
There is a long history of exploitation of the South American river turtle Podocnemis expansa. Conservation efforts for this species started in the 1960s but best practices were not established, and population trends and the number of nesting females protected remained unknown. In 2014 we formed a working group to discuss conservation strategies and to compile population data across the species’ range. We analysed the spatial pattern of its abundance in relation to human and natural factors using multiple regression analyses. We found that > 85 conservation programmes are protecting 147,000 nesting females, primarily in Brazil. The top six sites harbour > 100,000 females and should be prioritized for conservation action. Abundance declines with latitude and we found no evidence of human pressure on current turtle abundance patterns. It is presently not possible to estimate the global population trend because the species is not monitored continuously across the Amazon basin. The number of females is increasing at some localities and decreasing at others. However, the current size of the protected population is well below the historical population size estimated from past levels of human consumption, which demonstrates the need for concerted global conservation action. The data and management recommendations compiled here provide the basis for a regional monitoring programme among South American countries.
Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Crystallization is one of the main separation and purification processes in the pharmaceutical, biotechnology, food, microelectronics, fine and bulk chemicals industries. The production of more than 70 percent of all solid products involves at least one crystallization as a key processing step, which can have a significant effect on the overall performance of the entire production process and the properties of the final product. The control of crystallization processes is challenging because of the highly nonlinear dynamics, large variations in length and time scales at which the various simultaneous mechanisms occur, variations in crystallization rates over time owing to variations in the impurity profiles of chemical feedstocks, unexpected polymorphic transformations, and nonideal mixing conditions.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Background: Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disease due to mutation of the VPS13A gene encoding the protein chorein. ChAc is a slowly progressive disorder that typically presents in early adulthood, and whose clinical features include chorea and dystonia with involuntary lip, cheek and tongue biting. Some patients also have seizures. Treatment for ChAc is symptomatic. A small number of ChAc patients have been treated with bilateral deep brain stimulation (DBS) of the globus pallidus interna (GPi), and we now present an additional case. Methods: Patient chart, functional measures, and laboratory findings were reviewed from the time of ChAc diagnosis until 6 months after deep brain stimulation (DBS) surgery. Results: Here we present a case of ChAc in a 31 year old male positive for VPS13A gene muations who presented with chorea, tongue biting, dysarthria, weight loss, and mild cognitive dysfunction. GPi-DBS using monopolar stimulation was associated with significant improvement in chorea and dysarthria. Conclusions: This case adds to the current state of knowledge regarding the efficacy and safety of bilateral GPi-DBS for symptomatic control of drug-resistant hyperkinetic movements seen in ChAc. Controlled trials are needed to better assess the impact of DBS in ChAc.
The Bristol Radiocarbon Accelerator Mass Spectrometry (BRAMS) Facility was established at the University of Bristol after the commissioning of our dedicated sample preparation laboratories and the installation and acceptance of the BrisMICADAS AMS in 2016. Routine measurements commenced in mid-2016, once validation was completed for each sample type. Herein, we give an overview of the standard pretreatment methods currently employed in the Facility and the results of radiocarbon (14C) determinations on a wide range of standards, blank materials, and intercomparison samples which have been measured during our extensive pretreatment method validation program and during our routine 14C analyses.
Exposure to threat increases the risk for internalizing problems in adolescence. Deficits in integrating bodily cues into representations of emotion are thought to contribute to internalizing problems. Given the role of the medial prefrontal cortex in regulating bodily responses and integrating them into representations of emotional states, coordination between activity in the medial prefrontal cortex and autonomic nervous system responses may be influenced by past threat exposure with consequences for the emergence of internalizing problems. A sample of 179 Mexican-origin adolescents (88 female) reported on neighborhood and school crime, peer victimization, and discrimination when they were 10–16 years old. At age 17, participants underwent a functional neuroimaging scan during which they viewed pictures of emotional faces while respiratory sinus arrhythmia (RSA) and skin conductance responses were measured. Adolescents also reported symptoms of internalizing problems. Greater exposure to threats across adolescence was associated with more internalizing problems. Threat exposure was also associated with stronger negative coupling between the ventromedial prefrontal cortex and RSA. Stronger negative ventromedial prefrontal cortex–RSA coupling was associated with fewer internalizing problems. These results suggest the degree of coordinated activity between the brain and parasympathetic nervous system is both enhanced by threat experiences and decreased in adolescents with more internalizing problems.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.