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Intracranial aneurysm (IA) is an expansion of the weakened arterial wall that is often asymptomatic until rupture, resulting in subarachnoid hemorrhage. Here we describe the high prevalence of familial IA in a cohort of Newfoundland ancestry. We began to investigate the genetic etiology of IA in affected family members, as the inheritance of this disease is poorly understood.
Whole exome sequencing was completed for a cohort of 12 affected individuals from two multiplex families with a strong family history of IA. A filtering strategy was implemented to identify rare, shared variants. Filtered variants were prioritized based on validation by Sanger sequencing and segregation within the families.
In family R1352, six variants passed filtering; while in family R1256, 68 variants remained, so further filtering was pursued. Following validation by Sanger sequencing, top candidates were investigated in a set of population controls, namely, C4orf6 c.A1G (p.M1V) and SPDYE4c.C103T (p.P35S). Neither was detected in 100 Newfoundland control samples.
Rare and potentially deleterious variants were identified in both families, though incomplete segregation was identified for all filtered variants. Alternate methods of variant prioritization and broader considerations regarding the interplay of genetic and environmental factors are necessary in future studies of this disease.
Selective solar absorbers comprised of plasmonic materials offer great flexibility in design along with a highly promising optical performance. However, the nanopattern generation, typically done with electron beam writing, is a very time-intensive process. In this work, we present a fast, scalable, and flexible method for the fabrication of plasmonic materials by the combination of a deposition mask prepared by nanoimprint lithography and thin film deposition by magnetron sputtering. The fabrication process was first performed on silicon wafer substrates using AFM and SEM measurements to calibrate the deposition time, determine maximal deposition height, and characterize samples. Afterwards, the process was transferred to polished Inconel NiCr-alloy substrates used in high temperature solar absorbers. To investigate the adhesion properties of the nanostructure on the substrate, two different deposition methods were investigated: DC magnetron sputtering and High Power Impulse Magnetron Sputtering (HiPIMS).
The phenomenon of buying-shopping disorder (BSD) was described over 100 years ago. Definitions of BSD refer to extreme preoccupation with shopping and buying, to impulses to purchase that are experienced as irresistible, and to recurrent maladaptive buying excesses that lead to distress and impairments. Efforts to stop BSD episodes are unsuccessful, despite the awareness of repeated break-downs in self-regulation, experiences of post-purchase guilt and regret, comorbid psychiatric disorders, reduced quality of life, familial discord, work impairment, financial problems, and other negative consequences. A recent meta-analysis indicated an estimated point prevalence of BSD of 5%. In this narrative review, the authors offer a perspective to consider BSD as a mental health condition and to classify this disorder as a behavioral addiction, based on both research data and on long-standing clinical experience.
A bioeconomic model is used to estimate how managing glyphosate resistance to horseweed affects short- and long-run profits in corn, soybean, and corn-soybean rotation systems. Model results found that resistance management reduces profits in the first year of implementation, but increases profits in the second and subsequent 18 yr. In all three systems, long run gains begin to outweigh short-run costs (and resistance management “pays for itself”) by the second year. Over a 20-yr horizon, the estimated annual average profit advantage from managing resistance exceeded $158 ha–1 ($64/acre) for corn, $137 ha–1 ($55/acre) for corn-soybean, and $55 ha–1 ($22/acre) for soybean. Seed immigration from a neighbor's field can reduce these gains, but this reduction is negligible if the neighbor also practices resistance management. If the neighbor did not manage resistance, however, the grower's estimated annual profit advantage fell to roughly $123 ha–1 ($50/acre) for corn, $60 ha–1 ($24/acre) for the corn-soybean rotation, and virtually zero for soybean. Methods applied in this study identify corn and corn-soybean rotations as cases where resistance management “pays for itself' quickly and significantly, even if the neighbor does not manage resistance. Continuous soybean presents a more challenging case that may require additional programs and incentives to encourage collective resistance management among growers. Even for continuous soybean, however, joint grower–neighbor resistance management can pay for itself within 2 yr.
Seasonal wetlands and exuberant crop growth present challenges to systematic archaeological survey in alluvial settings, particularly in the tropical lowlands. Lidar can reduce the time and cost required to survey such areas by allowing targeting of elevated features not buried under recent alluvium, but demographic interpretation requires estimating post-abandonment alluvial depths. The broad alluvial plain between the Papaloapan delta and the Tuxtla Mountains in southern Veracruz, Mexico, offers a valuable case study, featuring seasonally inundated marshes, lakes, and vast fields of sugar cane, a crop infamously obstructive to lidar mapping. Undertaken to reconstruct demographic and organizational change in the Tres Zapotes polity, this study evaluates the benefits and limitations of lidar for archaeological survey in tropical alluvial settings based on overlap between lidar and systematic pedestrian survey and estimates of alluvial depth obtained by auger testing and underscores the importance of timing for lidar mapping in sugar cane.
Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.
Archaeologists studying shell assemblages from prehistoric sites along the Pacific coast of North America have been interested in the influences of collecting intensity and environmental variability on California mussel (Mytilus californianus) size. To determine the variation in mussel size within a shell assemblage, researchers have developed a variety of proxies of mussel valve length based on measurements of morphological features occurring at or near the valve’s umbo. We propose four additional measurements that can serve as proxies and evaluate their correlation with valve length using regression analysis. Of the four, anterior adductor scar length has the strongest correlation, and we present two examples of its application. We also evaluate a popular visual technique based on a set of outline drawings of valves of varying lengths, and we found that it systematically underestimated valve length but could be useful under certain circumstances. We conclude that the selection of a particular proxy of mussel valve length depends on the nature of the mussel shell assemblage being studied and the research context.
Appropriate use of antimicrobials for surgical prophylaxis is an important patient safety issue. Antimicrobial levels should be present during the duration of the surgical procedure until incision site closure. For prolonged surgical procedures in which the tissue concentration of the prophylactic antimicrobial may decrease to below the necessary minimum inhibitory concentration, intraoperative redosing of antimicrobials may be crucial
To evaluate compliance of appropriate intraoperative antimicrobial surgical prophylaxis using real-time intraoperative antimicrobial dosing reminders at a large teaching hospital.
A retrospective review of electronic records (March 2009–October 2012) was performed. Patients were included if they were at least 18 years of age and underwent a procedure requiring antimicrobial surgical prophylaxis. Compliance was determined by comparing 3 time intervals: baseline (March 2009–March 2010); intervention period 1 (IP-1; April 1, 2010–April 30, 2012), and intervention period 2 (IP-2; May 1, 2012–October 31, 2012). Interventions included a hospital-wide standardized protocol comprising an automated intraoperative paging system to notify when antimicrobials should be redosed.
A total of 7,461 of 75,230 surgical procedures required intraoperative redosing of antimicrobials and were analyzed. Patient mean age (± standard deviation) was 45 ± 19 years, and 62.6% were female. The most common procedures that required prophylaxis were solid organ transplantation, neurosurgical procedures, and orthopedic procedures. Baseline compliance (n = 2,183) was 15.8%; compliance significantly improved to 65.3% during IP-1 (n = 4,486; P < .001). The compliance rate improved to 76.7% during IP-2 (P > .001 compared with no reminder).
Compliance with redosing of intraoperative antimicrobials was improved with the combined approach of guidelines, education to healthcare providers, and real-time automated paging system.
During the early afternoon of June 29, 2012, a line of destructive thunderstorms producing straight line winds known as a derecho developed near Chicago (Illinois, USA). The storm moved southeast with wind speeds recorded from 100 to 160 kilometers per hour (kph, 60 to 100 miles per hour [mph]). The storm swept across much of West Virginia (USA) later that evening. Power outage was substantial as an estimated 1,300,000 West Virginians (more than half) were without power in the aftermath of the storm and approximately 600,000 citizens were still without power a week later. This was one of the worst storms to strike this area and occurred as residents were enduring a prolonged heat wave. The wind damage left much of the community without electricity and the crippling effect compromised or destroyed critical infrastructure including communications, air conditioning, refrigeration, and water and sewer pumps. This report describes utilization of Emergency Medical Services (EMS) and hospital resources in West Virginia in response to the storm. Also reported is a review of the weather phenomena and the findings and discussion of the disaster and implications.
KearnsRD, WigalMS, FernandezA, TuckerMAJr, ZuidgeestGR, MillsMR, CairnsBA, CairnsCB. The 2012 Derecho: Emergency Medical Services and Hospital Response. Prehosp Disaster Med. 2014;29(5):1-4.
We present radiocarbon dates, stable isotope data, and osteological analysis of the remains of a minimum of 17 individuals deposited in the western part of the burial chamber at Coldrum, Kent. This is one of the Medway group of megalithic monuments – sites with shared architectural motifs and no very close parallels elsewhere in Britain – whose location has been seen as important in terms of the origins of Neolithic material culture and practices in Britain. The osteological analysis identified the largest assemblage of cut-marked human bone yet reported from a British early Neolithic chambered tomb; these modifications were probably undertaken as part of burial practices. The stable isotope dataset shows very enriched δ15N values, the causes of which are not entirely clear, but could include consumption of freshwater fish resources. Bayesian statistical modelling of the radiocarbon dates demonstrates that Coldrum is an early example of a British Neolithic burial monument, though the tomb was perhaps not part of the earliest Neolithic evidence in the Greater Thames Estuary. The site was probably initiated after the first appearance of other early Neolithic regional phenomena including an inhumation burial, early Neolithic pottery and a characteristic early Neolithic post-and-slot structure, and perhaps of Neolithic flint extraction in the Sussex mines. Coldrum is the only site in the Medway monument group to have samples which have been radiocarbon dated, and is important both for regional studies of the early Neolithic and wider narratives of the processes, timing, and tempo of Neolithisation across Britain
The emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In this article, we intend to analyse how efficacy models are used to discover new antimalarial drugs. Our analysis indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development. In light of this analysis, we propose new ways to accelerate drug discovery using efficacy models.
Nanoporous metal-organic framework (MOF) materials are strong candidates for energy efficient carbon capture and storage (CCS) technologies. A total of ∼20,000 hypothetical MOFs were ab initio screened for CO2 adsorption using grand canonical Monte-Carlo (GCMC) simulations. Novel radial distribution function (RDF) scores were modified for periodic systems to predict the CO2 adsorption of MOFs using chemoinformatic models. The test set predictions yielded accuracies of 0.76 and 0.85 at 0.1 bar and 1 bar, respectively. The models were used to screen a large database for high performing MOFs and the top 100 structures were successfully validated by GCMC simulations. The chemoinformatic predictors of the CO2 adsorption of MOFs are available online at http://titan.chem.uottawa.ca/woolab/MOFIA/#carbondioxide.
Food-based dietary guidelines (FBDG) aim to address the nutritional requirements at population level in order to prevent diseases and promote a healthy lifestyle. Diet quality indices can be used to assess the compliance with these FBDG. The present study aimed to investigate whether the newly developed Diet Quality Index for Adolescents (DQI-A) is a good surrogate measure for adherence to FBDG, and whether adherence to these FBDG effectively leads to better nutrient intakes and nutritional biomarkers in adolescents. Participants included 1804 European adolescents who were recruited in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study. Dietary intake was assessed by two, non-consecutive 24 h recalls. A DQI-A score, considering the components' dietary quality, diversity and equilibrium, was calculated. Associations between the DQI-A and food and nutrient intakes and blood concentration biomarkers were investigated using multilevel regression analysis corrected for centre, age and sex. DQI-A scores were associated with food intake in the expected direction: positive associations with nutrient-dense food items, such as fruits and vegetables, and inverse associations with energy-dense and low-nutritious foods. On the nutrient level, the DQI-A was positively related to the intake of water, fibre and most minerals and vitamins. No association was found between the DQI-A and total fat intake. Furthermore, a positive association was observed with 25-hydroxyvitamin D, holo-transcobalamin and n-3 fatty acid serum levels. The present study has shown good validity of the DQI-A by confirming the expected associations with food and nutrient intakes and some biomarkers in blood.
The Parasitic Plant Genome Project has sequenced transcripts from three parasitic species and a nonparasitic relative in the Orobanchaceae with the goal of understanding genetic changes associated with parasitism. The species studied span the trophic spectrum from free-living nonparasite to obligate holoparasite. Parasitic species used were Triphysaria versicolor, a photosynthetically competent species that opportunistically parasitizes roots of neighboring plants; Striga hermonthica, a hemiparasite that has an obligate need for a host; and Orobanche aegyptiaca, a holoparasite with absolute nutritional dependence on a host. Lindenbergia philippensis represents the closest nonparasite sister group to the parasitic Orobanchaceae and was included for comparative purposes. Tissues for transcriptome sequencing from each plant were gathered to identify expressed genes for key life stages from seed conditioning through anthesis. Two of the species studied, S. hermonthica and O. aegyptiaca, are economically important weeds and the data generated by this project are expected to aid in research and control of these species and their relatives. The sequences generated through this project will provide an abundant resource of molecular markers for understanding population dynamics, as well as provide insight into the biology of parasitism and advance progress toward understanding parasite virulence and host resistance mechanisms. In addition, the sequences provide important information on target sites for herbicide action or other novel control strategies such as trans-specific gene silencing.
Self-assembly is a promising technique to overcome fundamental limitations with integrating, packaging, and generally handling individual electronic-related components with characteristic lengths significantly smaller than 1 mm. Here we briefly summarize the use of capillary and magnetic forces to realize two example microscale systems. In the first example, we use capillary forces from a low melting point solder alloy to integrate 500 μm square, 100 μm thick silicon chips with thermally and chemically sensitive metal-polymer hinge actuators, for potential medical applications. The second example demonstrates a path towards self-assembling 3-D silicon circuits formed out of 280 μm sized building blocks, utilizing both capillary forces from a low melting point solder alloy and magnetic forces from integrated, permanent magnets. In the latter example, the utilization of magnetic forces combined with capillary forces improved the assembly yield to 7.8% over 0.1% achieved previously with capillary forces alone.
Numerical simulations were performed to see the effect of geometrical misalignment in pressure driven flows. Geometric misalignment effects on flow characteristics arising in three types of interconnection methods a) end-to-end interconnection, b) channel overlap when chips are stacked on top of each other, and c) the misalignment occurring due to the offset between the external tubing and the reservoir were investigated. For the case of end-to-end interconnection, the effect of misalignment was investigated for 0, 13, 50, 58, and 75% reduction in the available flow area at the location of geometrical misalignment. In the interconnection through channel overlap, various possible misalignment configurations were simulated by maintaining the same amount of misalignment (75% flow area reduction) for all the configurations. The effect of misalignment in a Tube-in-Reservoir interconnection was investigated by positioning the tube at an offset of 164μm from the reservoir center. All the results were evaluated in terms of the equivalent length of a straight pipe. The effect of reynolds number (Re) was also taken into account by performing additional simulations of aforementioned cases at reynolds numbers ranging from 0.075 to 75. The results are interpreted in terms of equivalent length (Le) as a function of Re and misalignment area ratio (A1:A2), where A1 is the original cross-sectional area of the channel and A2 is the available flow area at mismatch location. Equivalent length calculations revealed that the effect of misalignment in tube-in-reservoir interconnection method was the most insignificant when compared to the other two methods of interconnection