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Chronic wasting disease (CWD) is a widely distributed prion disease of cervids with implications for wildlife conservation and also for human and livestock health. The structures of infectious prions that cause CWD and other natural prion diseases of mammalian hosts have been poorly understood. Here we report a 2.8 Å resolution cryogenic electron microscopy-based structure of CWD prion fibrils from the brain of a naturally infected white-tailed deer expressing the most common wild-type PrP sequence. Like recently solved rodent-adapted scrapie prion fibrils, our atomic model of CWD fibrils contains single stacks of PrP molecules forming parallel in-register intermolecular β-sheets and intervening loops comprising major N- and C-terminal lobes within the fibril cross-section. However, CWD fibrils from a natural cervid host differ markedly from the rodent structures in many other features, including a ~ 180° twist in the relative orientation of the lobes. This CWD structure suggests mechanisms underlying the apparent CWD transmission barrier to humans and should facilitate more rational approaches to the development of CWD vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Methanogenic archaea are chemolithotrophic prokaryotes that can reduce carbon dioxide with hydrogen gas to form methane. These microorganisms make a significant contribution to the global carbon cycle, with methanogenic archaea from anoxic environments estimated to contribute > 500 million tons of global methane annually. Archaeal methanogenesis is dependent on the methanofurans; aminomethylfuran containing coenzymes that act as the primary C1 acceptor molecule during carbon dioxide fixation. Although the biosynthetic pathway to the methanofurans has been elucidated, structural adaptations which confer thermotolerance to Mfn enzymes from extremophilic archaea are yet to be investigated. Here we focus on the methanofuran biosynthetic enzyme MfnB, which catalyses the condensation of two molecules of glyceralde-3-phosphate to form 4‑(hydroxymethyl)-2-furancarboxaldehyde-phosphate. In this study, MfnB enzymes from the hyperthermophile Methanocaldococcus jannaschii and the mesophile Methanococcus maripaludis have been recombinantly overexpressed and purified to homogeneity. Thermal unfolding studies, together with steady-state kinetic assays, demonstrate thermoadaptation in the M. jannaschii enzyme. Molecular dynamics simulations have been used to provide a structural explanation for the observed properties. These reveal a greater number of side chain interactions in the M. jannaschii enzyme, which may confer protection from heating effects by enforcing spatial residue constraints. [ABSTRACT FROM AUTHOR]

Exposure to misleading information after witnessing an event can impair future memory reports about the event. This pervasive form of memory distortion, termed the misinformation effect, can be significantly reduced if individuals are warned about the reliability of post-event information before exposure to misleading information. The present fMRI study investigated whether such prewarnings improve subsequent memory accuracy by influencing encoding-related neural activity during exposure to misinformation. We employed a repeated retrieval misinformation paradigm in which participants watched a crime video (Witnessed Event), completed an initial test of memory, listened to a post-event auditory narrative that contained consistent, neutral, and misleading details (Post-Event Information), and then completed a final test of memory. At the behavioral level, participants who were given a prewarning before the Post-Event Information were less susceptible to misinformation on the final memory test compared with participants who were not given a warning (Karanian et al., Proceedings of the National Academy of Sciences of the United States of America, 117, 22771–22779, 2020). This protection from misinformation was accompanied by greater activity in frontal regions associated with source encoding (lateral PFC) and conflict detection (ACC) during misleading trials as well as a more global reduction in activity in auditory cortex and semantic processing regions (left inferior frontal gyrus) across all trials (consistent, neutral, misleading) of the Post-Event Information narrative. Importantly, the strength of these warning-related activity modulations was associated with better protection from misinformation on the final memory test (improved memory accuracy on misleading trials). Together, these results suggest that warnings modulate encoding-related neural activity during exposure to misinformation to improve memory accuracy. [ABSTRACT FROM AUTHOR]

HTTP Adaptive Streaming (HAS), the most prominent technology for streaming video over the Internet, suffers from high end-to-end latency when compared to conventional broadcast methods. This latency is caused by the content being delivered as segments rather than as a continuous stream, requiring the client to buffer significant amounts of data to provide resilience to variations in network throughput and enable continuous playout of content without stalling. The client uses an Adaptive Bitrate (ABR) algorithm to select the quality at which to request each segment to trade-off video quality with the avoidance of stalling to improve the Quality of Experience (QoE). The speed at which the ABR algorithm responds to changes in network conditions influences the amount of data that needs to be buffered, and hence to achieve low latency the ABR needs to respond quickly. Llama (Lyko et al. 28) is a new low latency ABR algorithm that we have previously proposed and assessed against four on-demand ABR algorithms. In this article, we report an evaluation of Llama that demonstrates its suitability for low latency streaming and compares its performance against three state-of-the-art low latency ABR algorithms across multiple QoE metrics and in various network scenarios. Additionally, we report an extensive subjective test to assess the impact of variations in video quality on QoE, where the variations are derived from ABR behaviour observed in the evaluation, using short segments and scenarios. We publish our subjective testing results in full and make our throughput traces available to the research community. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for abdominal wall hernia development and hernia recurrence. The management of these two pathologies is complex and often entwined. Bariatric and ventral hernia surgery require careful consideration of physiologic and technical components for optimal outcomes. In this review, a multidisciplinary group of Society of American Gastrointestinal and Endoscopic Surgeons' bariatric and hernia surgeons present the various weight loss modalities available for the pre-operative optimization of patients with severe obesity and concurrent hernias. The group also details the technical aspects of managing abdominal wall defects during weight loss procedures and suggests the optimal timing of definitive hernia repair after bariatric surgery. Since level one evidence is not available on some of the topics covered by this review, expert opinion was implemented in some instances. Additional high-quality research in this area will allow for better recommendations and therefore treatment strategies for these complex patients. [ABSTRACT FROM AUTHOR]

Global surges in industrialization and human development have resulted in environmental contamination. Streambed sediment contamination threatens ecological and human health due to groundwater leaching and downstream contaminant mobilization. This is especially true in the wider Caribbean region, where streambed sediment contamination is understudied. In the current study, we assessed human impact on intermittent streams by measuring heavy metals and volatile organic compounds (VOCs) in streambed sediment on St. Croix in the United States Virgin Islands (USVI), where intermittent streams receive limited conservation and research attention. In contrast to our hypothesis that streambed sediment pollutant concentrations would be higher in developed, compared to undeveloped areas, contaminant concentrations did not vary significantly according to land cover. Elevated lead, mercury, and zinc concentrations were correlated with commercial building density, suggesting an unnatural origin of these elements in streambed sediment. At some sites, levels of arsenic, cadmium, chromium, nickel, lead, thallium, or zinc exceeded regulatory limits. The most prevalent VOCs at both developed and undeveloped sites were benzene and toluene. Sub-groups of heavy metals identified by principal component analysis indicated potential pollution sources, including fuel combustion (chromium, nickel, arsenic, selenium), vehicle exhaust, oil refining, and gasoline leaks (2-butanone and xylenes), and plastics (acetone and styrene). Our results suggest USVI intermittent streams require further research attention and intervention strategies for pollution reduction. [ABSTRACT FROM AUTHOR]

The ever-growing volume of network traffic and widening adoption of Internet protocols to underpin common communication processes augments the importance of network security. In order to enforce network security policies, network managers adopt a widening set of middleboxes and network appliances to improve traffic monitoring and processing capabilities. The resource requirements to support network security appliances are constantly increasing, making efficiency of these systems an essential aspect. The move toward Software-Defined Networking and programmable data planes offers a mean to offload traffic processing functionalities to within the network itself. To this end, we present the 4MIDable framework: a platform that facilitates the integration of existing middleboxes and monitoring appliances with an SDN (P4) network infrastructure. We also present P4Protect, a 4MIDable agent that protects the network from control plane DoS attacks with negligible impact on control plane latency, and P4ID (P4-Enhanced Intrusion Detection), a 4MIDable agent that offers stateful processing and feedback to unmodified Intrusion Detection System middleboxes and reduces traffic processing by over 80% without affecting threat detection rates. [ABSTRACT FROM AUTHOR]

Understanding corrosion mechanisms is of importance for reducing the global cost of corrosion. While the properties of engineering components are considered at a macroscopic scale, corrosion occurs at micro or nano scale and is influenced by local microstructural variations inherent to engineering alloys. However, studying such complex microstructures that involve multiple length scales requires a multitude of advanced experimental procedures. Here, we present a method using correlated electron microscopy techniques over a range of length scales, combined with crystallographic modelling, to provide understanding of the competing mechanisms that control the waterside corrosion of zirconium alloys. We present evidence for a competition between epitaxial strain and growth stress, which depends on the orientation of the substrate leading to local variations in oxide microstructure and thus protectiveness. This leads to the possibility of tailoring substrate crystallographic textures to promote stress driven, well-oriented protective oxides, and so to improving corrosion performance. The corrosion properties of engineering alloys are strongly influenced by local variations seen at the micro level. Here, the authors demonstrate how the metal grain orientation can influence the protectiveness of the oxide, which provides a possible route for improving corrosion performance. [ABSTRACT FROM AUTHOR]

This work investigates a statistical approach analysing data from monitoring activities on marine-coastal areas for environmental quality determination and surveillance. Analyses were performed on a database of the Environmental Protection and Prevention Agency of the Puglia Region. As, Cr, Ni, and Pb concentration values in marine sediments and biota from 2013 to 2015 and 2017 were processed to investigate different contaminant characteristics. Hierarchical cluster analysis identified three contaminant distribution classes with (1) highest Cr, Ni, and Pb concentrations, (2) highest As concentration, and (3) lowest contaminants concentration. The Kruskal-Wallis and Friedman tests showed that contaminant distributions were statistically different when considering the monitoring years and classes. However, statistical similarities resulted during the 2013–2017 and 2014–2015 periods. Spearman's coefficients displayed positive correlations among the pollutants in each matrix and mainly negative correlations for matrices comparison. This methodology aims to provide a practical support for monitoring to identify potential environmental deterioration over time and correlations with specific contamination sources. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Asian scores developed to predict unresponsiveness to intravenous immunoglobulin (IVIG) or development of coronary artery aneurysms (CAA) in patients with Kawasaki disease (KD) are not appropriate in Western populations. The purpose of this study is to develop 2 scores, to predict unresponsiveness to IVIG and development of CAA, appropriate for Spanish population. Method: Data of 625 Spanish children with KD collected retrospectively (2011–2016) were used to identify variables to develop the 2 scores of interest: unresponsiveness to IVIG and development of CAA. A statistical model selected best variables to create the scores, and scores were validated with data from 98 patients collected prospectively. Results: From 625 patients of the retrospective cohort, final analysis was performed in 439 subjects: 37 developed CAA, and 212 were unresponsive to IVIG. For the score to predict CAA, a cutoff ≥ 8 was considered for high risk, considering a score system with a different weight for each of the eight variables. External validation showed a sensitivity of 22% and a specificity of 75%. The score to predict unresponsiveness to IVIG established a cutoff ≥ 8 for high risk, considering a score system with a different weight for each of the nine variables. External validation showed a sensitivity of 78% and a specificity of 50%. Conclusions: Two risk scores for KD were developed from Spanish population, to predict development of CAA and unresponsiveness to IVIG; validation in other cohorts could help to implement these tools in the management of KD in other Western populations. Key Points • Two risk scores for KD were developed from Spanish population, to predict development of CAA and unresponsiveness to IVIG. • External validation of the score to predict development of CAA showed a sensitivity of 22% and a specificity of 75%. • External validation of the score to predict unresponsiveness to IVIG showed a sensitivity of 78% and a specificity of 50%. [ABSTRACT FROM AUTHOR]

The electrical characteristics of graphene have reinvigorated research into inorganic, two-dimensional materials for use in various fields such as optoelectronics, renewable energy, and energy storage. However, graphene has limited use in the aforementioned fields given that it lacks an inherent energy bandgap. To circumvent this one exception in an otherwise groundbreaking electronic material, researchers have increasingly focused attention on transition metal dichalcogenides (TMDCs). The TMDCs we shall discuss are layered materials that with recent developments can be synthesized as monolayers. These layered TMDCs consist of three different atomic layers that make up a single monolayer TMDC. As TMDCs move from bulk form to monolayer form, they also transition from an indirect bandgap to a direct bandgap. These monolayer TMDCs, among other electronically useful properties, exhibit a direct bandgap of 1.8 eV which, in turn, allows them to be used in various applications such as photodetectors, energy storage, and transistors, to name a few. Within these applications, the deposition or growth of monolayer or few-layer TMDCs continues to be a challenge. The more common deposition methods such as chemical vapor deposition (CVD) and electrophoretic deposition (EPD) have pros and cons, and each are better suited for different applications. Raman spectroscopy is a useful tool in determining whether a deposition has produced monolayer TMDCs and the quality of the deposition. [ABSTRACT FROM AUTHOR]

Background: Potential complications after inguinal hernia repair include uncontrolled post-operative pain and post-operative urinary retention (POUR). Enhanced Recovery After Surgery (ERAS) protocols aim to mitigate post-operative morbidity. We study the impact of ERAS measures alongside discharge without a narcotic prescription on post-operative pain and POUR after minimally invasive inguinal hernia repair.Methods: A retrospective review of a prospectively maintained database identified patients that underwent minimally invasive inguinal hernia repair at a single institution. Intra-operative data included operative time, narcotic usage, non-narcotic adjunct medication, and fluid administration. Primary outcomes included rates of POUR and uncontrolled post-operative pain. Operations performed after 2018 were included in the ERAS cohort. Uncontrolled post-operative pain was defined as needing additional narcotic prescriptions, admission, or ER visits for post-operative pain. POUR was defined as requiring an indwelling urethral catheter at discharge, admission for retention, or returning to the ER for urinary retention.Results: Between January 2008 and March 2021, 1097 patients who underwent minimally invasive inguinal hernia repair were identified. 91.3% of these procedures were laparoscopic and 8.7% were robotic. Average patient age was 57.4 years, 93% were male. Patients receiving care after initiation of the ERAS protocol were significantly less likely to experience POUR when compared to their prior counterparts (1.4% vs. 4.2% p = 0.01); there was no difference in post-operative pain complications (1.4% vs. 2.9% p = 0.15). Patients who were discharged without a narcotic prescription had 0% incidence of POUR. Significant differences were found between the ERAS and non-ERAS cohort regarding narcotic usage and fluid administration. Age, higher fluid volume, and higher narcotic usage were found to be risk factors for POUR while ERAS, sugammadex, and dexamethasone were found to be protective.Conclusion: Implementation of an ambulatory ERAS protocol can significantly decrease urinary retention and narcotic usage rates after minimally invasive inguinal hernia repair. [ABSTRACT FROM AUTHOR]

While nanoscale quantum emitters are effective tags for measuring biomolecular interactions, their utilities for applications that demand single-unit observations are limited by the requirements for large numerical aperture (NA) objectives, fluorescence intermittency, and poor photon collection efficiency resulted from omnidirectional emission. Here, we report a nearly 3000-fold signal enhancement achieved through multiplicative effects of enhanced excitation, highly directional extraction, quantum efficiency improvement, and blinking suppression through a photonic crystal (PC) surface. The approach achieves single quantum dot (QD) sensitivity with high signal-to-noise ratio, even when using a low-NA lens and an inexpensive optical setup. The blinking suppression capability of the PC improves the QDs on-time from 15% to 85% ameliorating signal intermittency. We developed an assay for cancer-associated miRNA biomarkers with single-molecule resolution, single-base mutation selectivity, and 10-attomolar detection limit. Additionally, we observed differential surface motion trajectories of QDs when their surface attachment stringency is altered by changing a single base in a cancer-specific miRNA sequence. Nanoscale emitters are useful for measuring biomolecular interactions, but are limited by weak signals. Here, the authors use a photonic crystal surface for 3000-fold signal enhancement, achieving single emitter sensitivity with extended on-time, and demonstrate its application in miRNA biomarker sensing. [ABSTRACT FROM AUTHOR]

Purpose: Pollution from oil operations; exploration, drilling, transfer, transport, refinery and distribution reduce soil quality, and results in the removal of a large amount of soil from annual utilization cycles. Soil quality is an essential asset of sustainable development and is negatively affected by erosion and anthropogenic activity. Co-composting is a biological technique used in the bioremediation of soils, which was investigated in this study. Materials and methods: This study focused on the remediation of 1200 m3 of saline contaminated soil from an oil-polluted operational area in Iran. The initial total petroleum hydrocarbon (TPH) content of the soil was between 6.9 and 17.1 g kg−1 and was contaminated with heavy oil. Initial water repellency of the soil was between 1500 and 12,500 S. The remediation procedure commenced with trials in which organic waste of a local sugarcane sugar factory, mixed urea, sugar, and compost mixtures was added to contaminated soils. Results: After irrigation and aeration of piles of organic materials and soil over 3 months of operation, the TPH reduced from 4.86, 6.52, and 9.89 to 0.068, 0.080, and 0.109 g kg−1, in the moderately, highly, and very highly polluted soil piles respectively. At the end of the remediation project, following gas chromatography analysis of contaminant content, and in accordance with governmental authorities, recovered soils were added to the surrounding environment to the support growth of the natural ecosystem. Conclusion: Soil recovery and remediation utilizing valorization and complimentary local industries have a transferable quality that may be adapted to additional vulnerable sites in droughted and variable edaphic and climatic conditions. [ABSTRACT FROM AUTHOR]

Little is known about the structural basis of prion strains. Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. However, detailed comparisons reveal variations in these shared structural topologies and other features. Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. This work demonstrates both common and divergent structural features of prion strains at the near-atomic level. The authors report the near-atomic structure of the ex vivo aRML prion fibril. The comparison between this structure and the previously solved 263K prion fibril shows that both common and divergent features characterize these prion strains and their respective conformational replication templates. [ABSTRACT FROM AUTHOR]

Two field experiments were conducted to evaluate six Salicornia species (Salicornia bigelovii Torr., S. europaea L., S. persica Gorgan ecotype, S. persica Urmia ecotype, S. sinus persica Bushehr ecotype, and S. persica Central Plateau ecotype) at different planting dates and densities under irrigation with Persian Gulf water. Evaluated planting dates were 14 November and 18 December 2016 and 16 January, 8 February, 8 March, and 28 March 2017. Examined planting densities included 13, 20, and 40 plant m−2. Only S. bigelovii and S. europaea produced measurable yield in all planting dates. The highest dry weight (651.1 gm−2) was obtained in S. sinus persica (Bu) planted on 8 February. Dry weight of S. bigelovii, S. europaea, S. sinus persica Bushehr, S. persica Central Plateau, S. persica Gorgan, and S. persica Urmia planted on 8 March were 174.2, 220.7, 542.5, 240.9, 158.0, and 147.5 g m−2, respectively. The ash contents of S. bigelovii, S. europaea, S. sinus persica Bushehr, S. persica Central Plateau, S. persica Gorgan, and S. persica Urmia were 46.3%, 45.0%, 49.6%, 49.6%, 50.0%, and 53.1%, respectively. Sodium and chloride contents of different Salicornia species varied from 13–15% and 16–17%, respectively. The oilseed content of S. bigelovii and S. sinus persica Bushehr was about 24.0% for both species. The highest and lowest dry weight, from the second experiment, were for S. sinus persica Bushehr and S. persica Central Plateau, respectively, in all planting density. The highest dry weight equal to 1336.2 gm−2 was obtained for S. sinus persica Bushehr in 40 plant m−2 density. Under such conditions, forage production potential of Salicornia is more achievable rather than seed production. Nevertheless, high ash content is a serious constraint to direct consumption by livestock; therefore, determining the nutritional value of Salicornia fodder requires further evaluations. [ABSTRACT FROM AUTHOR]

Forecasting nitrate concentration in rivers is essential for environmental protection and careful treatment of drinking water. This study shows that nonlinear autoregressive with exogenous inputs neural networks can provide accurate models to predict nitrate plus nitrite concentrations in waterways. The Susquehanna River and the Raccoon River, USA, were chosen as case studies. Water discharge, water temperature, dissolved oxygen, and specific conductance were considered exogenous inputs. The forecasting sensitivity to changes in the exogenous input parameters and time series length was also assessed. For Kreutz Creek at Strickler station (Pennsylvania), the prediction accuracy increased with the number of exogenous input variables, with the best performance achieved considering all the variables (R2 = 0.77). The predictions were accurate also for the Raccoon River (Iowa), although only the water discharge was considered exogenous input (South Raccoon River at Redfield—R2 = 0.94). Both short- and long-term predictions were satisfactory. [ABSTRACT FROM AUTHOR]

This study was done to evaluate the appropriateness, diagnostic yield, and quality of paediatric gastrointestinal endoscopy in a large DGH with tertiary paediatric gastroenterology services. It was a retrospective cohort study of children who had at least one gastrointestinal endoscopy during 31 months (May 2018-Dec 2020) in a district general hospital in Southeast England. The participants were children (2–17 years). Two hundred ninety-three procedures were performed in total, 80% were diagnostic and 20% for surveillance. The median age was 12 years and 52.5% were males. Oesophago-gastro-duodenoscopy (OGD) corresponded to 79.5% of procedures, ileo-colonoscopy (IC) to 7.2% and the remaining had both procedures. The main diagnostic indication was persistent abdominal pain in 33.5% of cases, followed by suspected GORD (14.8%), recurrent vomiting (14.3%), dysphagia (9.1%) and blood loss per rectum (8.6%). A total of 64.7% showed abnormal macroscopic findings, and 69.2% showed histopathological signs of disease. The most common histological diagnosis was gastritis in 23% followed by coeliac disease in 13%, reflux oesophagitis in 12.2% and inflammatory bowel disease in 9.6%. Procedures were performed with utmost safety with two reported cases of complications, which were appropriately managed. The completion rate of diagnostic IC was 87%. A waiting time of 6 weeks was achieved in 50.4% of cases. Conclusion: Paediatric endoscopy can be safely performed in a district general hospital with the right setup and can aid in the management of gastrointestinal disease in the paediatric patient. It is important to monitor and regularly audit such practices to improve the quality of specialist services. What is Known: • Paediatric endoscopy is predominantly performed in large tertiary centres and included in the diagnostic algorithm for many paediatric gastrointestinal conditions. • There are recommendations on clinical indication endorsed by ESPGHAN and key quality indicators published jointly by JAG and BSPGHAN. What is New: • Paediatric endoscopy can be appropriately and safely performed in district general hospital by trained professionals, decreasing the workload in larger tertiary paediatric centres. • Adoption of regular audit practices is essential to ensure and improve quality and appropriateness of this specialist service. [ABSTRACT FROM AUTHOR]

Efforts to contain the spread of chronic wasting disease (CWD), a fatal, contagious prion disease of cervids, would be aided by the availability of additional diagnostic tools. RT-QuIC assays allow ultrasensitive detection of prion seeds in a wide variety of cervid tissues, fluids and excreta. The best documented antemortem diagnostic test involving RT-QuIC analysis targets lymphoid tissue in rectal biopsies. Here we have tested a more easily accessed specimen, ear pinna punches, using an improved RT-QuIC assay involving iron oxide magnetic extraction to detect CWD infections in asymptomatic mule and white-tailed deer. Comparison of multiple parts of the ear pinna indicated that a central punch spanning the auricular nerve provided the most consistent detection of CWD infection. When compared to results obtained from gold-standard retropharyngeal lymph node specimens, our RT-QuIC analyses of ear samples provided apparent diagnostic sensitivity (81%) and specificity (91%) that rivaled, or improved upon, those observed in previous analyses of rectal biopsies using RT-QuIC. These results provide evidence that RT-QuIC analysis of ear pinna punches may be a useful approach to detecting CWD infections in cervids. [ABSTRACT FROM AUTHOR]

Creutzfeldt–Jakob Disease (CJD) is a fatal, currently incurable, neurodegenerative disease. The search for candidate treatments would be greatly facilitated by the availability of human cell-based models of prion disease. Recently, an induced pluripotent stem cell derived human cerebral organoid model was shown to take up and propagate human CJD prions. This model offers new opportunities to screen drug candidates for the treatment of human prion diseases in an entirely human genetic background. Here we provide the first evidence that human cerebral organoids can be a viable model for CJD drug screening by using an established anti-prion compound, pentosan polysulfate (PPS). PPS delayed prion propagation in a prophylactic-like treatment paradigm and also alleviated propagation when applied following establishment of infection in a therapeutic-like treatment paradigm. This study demonstrates the utility of cerebral organoids as the first human 3D cell culture system for screening therapeutic drug candidates for human prion diseases. [ABSTRACT FROM AUTHOR]

Purpose: The naturally-occurring omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and inexpensive, making it an attractive anti-cancer intervention. However, EPA has only modest anti-colorectal cancer (CRC) activity, when used alone. Both cyclooxygenase (COX) isoforms metabolise EPA and are over-expressed in CRC cells. We investigated whether COX inhibition increases the sensitivity of CRC cells to growth inhibition by EPA. Methods: A panel of 18 human and mouse CRC cell lines was used to characterize the differential sensitivity of CRC cells to the growth inhibitory effects of EPA. The effect of CRISPR-Cas9 genetic deletion and pharmacological inhibition of COX-1 and COX-2 on the anti-cancer activity of EPA was determined using in vitro and in vivo models. Results: Genetic ablation of both COX isoforms increased sensitivity of CT26 mouse CRC cells to growth inhibition by EPA in vitro and in vivo. The non-selective COX inhibitor aspirin and the selective COX-2 inhibitor celecoxib increased sensitivity of several human and mouse CRC cell lines to EPA in vitro. However, in a MC38 mouse CRC cell tumour model, with dosing that mirrored low-dose aspirin use in humans, thereby producing significant platelet COX-1 inhibition, there was ineffective intra-tumoral COX-2 inhibition by aspirin and no effect on EPA sensitivity of MC38 cell tumours. Conclusion: Cyclooxygenase inhibition by non-steroidal anti-inflammatory drugs represents a therapeutic opportunity to augment the modest anti-CRC activity of EPA. However, intra-tumoral COX inhibition is likely to be critical for this drug-nutrient interaction and careful tissue pharmacodynamic profiling is required in subsequent pre-clinical and human studies. [ABSTRACT FROM AUTHOR]

Time-to-event data often violate the proportional hazards assumption inherent in the popular Cox regression model. Such violations are especially common in the sphere of biological and medical data where latent heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed in the literature which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the First Hitting Time (FHT) paradigm which assumes that a subject's event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of the FHT model have also been proposed which allow for better modeling of data with unmeasured covariates. While often appropriate, these methods often display limited flexibility due to their inability to model a wide range of heterogeneities. To address this issue, we propose a Bayesian model which loosens assumptions on the mixing distribution inherent in the random effects FHT models currently in use. We demonstrate via simulation study that the proposed model greatly improves both survival and parameter estimation in the presence of latent heterogeneity. We also apply the proposed methodology to data from a toxicology/carcinogenicity study which exhibits nonproportional hazards and contrast the results with both the Cox model and two popular FHT models. [ABSTRACT FROM AUTHOR]

This study proposes a comparison of different ex situ technologies aimed at the removal of polycyclic aromatic hydrocarbons from marine sediments in terms of performances, costs and energy balance. In accordance with the principles of water-energy nexus, anaerobic bioremediation, soil washing and thermal desorption were investigated under low liquid phase and temperature conditions using phenanthrene (PHE) as model compound. After 42 days of anaerobic bioremediation, the highest PHE biodegradation of 68 and 64% was observed under denitrifying and methanogenic conditions, respectively, accompanied by N2 and CH4 production and volatile fatty acid accumulation. During soil washing, more than 97% of PHE was removed after 60 min using a solid-to-liquid ratio of 1:3. Along the same treatment time, low-temperature thermal desorption (LTTD) allowed a PHE removal of 88% at 200 °C. The economic analysis indicated that LTTD resulted in a higher cost (i.e. 1782 € m−3) than bioremediation and soil washing (228 and 371 € m−3, respectively). The energy balance also suggested that bioremediation and soil washing are more sustainable technologies as a lower required energy (i.e. 16 and 14 kWh m−3, respectively) than LTTD (i.e. 417 kWh m−3) is needed. [ABSTRACT FROM AUTHOR]

Microglia act as the protective immune cell of the brain. By surveying the tissue to identify and rectify problems, they function to maintain the health of brain cells. The prion protein N-terminal cleavage fragment, N1, has demonstrated neuroprotective activities in vitro and in vivo. This study aimed to elucidate whether N1 could modulate microglial function and, if so, determine the consequences for the surrounding tissue. Using a mixed neuronal lineage and microglia co-culture system, we showed that N1 stimulation changed overall morphology and metabolism, suggesting enhanced cellular viability. Furthermore, N1 induced an increase in Cxcl10 secretion in the co-cultures. Recombinant Cxcl10, administered exogenously, mediated the changes in the mixed neuronal lineage culture morphology and metabolism in the absence of microglia, but no effect of Cxcl10 was observed on microglia cultured on their own. Direct cell-to-cell contact was required for N1 to influence microglia in the co-cultures, and this was linked with restructuring of microglial membrane composition to include a higher GM1 content at interaction sites with surrounding cells. Our findings show that N1 can play a regulatory role in microglial function in the context of an inter-connected network of cells by changing both cellular interaction sites and cytokine secretion. [ABSTRACT FROM AUTHOR]

Biomethane is the most energy-efficient biofuel and it is also environmentally advantageous because it can be utilized as a partial alternative to fossil fuels for heat and electricity generation when an adequate biogas upgradation strategy is followed. Several recent studies have been conducted to identify the renewable sources of biohydrogen, such as biohydrogen production from unused glycerol from biodiesel production, oil palm waste hydrolysate, second-generation biomass, forestry biomass and kitchen waste. [Extracted from the article]

The present work aims to provide a comprehensive review of the experimental studies focusing on municipal solid waste incineration fly-ash (FA) treatments that are required before the application of advanced processes aimed at their final reuse or safe disposal. The investigated pre-treatments are divided into three categories: (1) water washing/chemical leaching; (2) electrodialysis; and (3) thermal separation. Analysed aspects include: (1) process efficiency; (2) effect on FA physical–chemical characteristics; and (3) process applicability as a function of secondary FA treatment steps which are generally required for final disposal or reuse of the remediated waste. Investigations related to these elements allows a determination of the efficacy and the operational convenience of a specific pre-treatment to achieve a proper FA remediation level. A comparison of studies in the literature provides a thorough source and a useful basis for correctly addressing future experimental activities and research efforts. The discussion of the results provides the basis for the development of a suitable methodology to optimize the environmentally sustainable reuse or safer disposal of treated FA. [ABSTRACT FROM AUTHOR]

Two-dimensional transition metal dichalcogenides (TMDCs) are attracting a broad range of research interest. MoS2 is one of the most common TMDCs. Here, studies on the atomic scale characterization of MoS2 with particular emphasis on Raman spectroscopy and atomic force microscopy are reviewed. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 64-year-old man who was diagnosed with spinal onset probable amyotrophic lateral sclerosis (ALS) in which 38 (G4C2) repeats in the C9orf72 gene shows TDP-43 and sparse dipeptide repeat protein pathology.

Screening for fragile X syndrome (FXS) is essential in children with developmental delay or intellectual disability (ID). In addition, using clinical screening checklists remains of high interest in resource-limited settings. We aimed to gain insight into the prevalence of FXS and the distribution of CGG alleles and to evaluate the usefulness of three checklists in specialized institutions in Kinshasa, DR Congo. We recruited 80 males and 25 females from six specialized institutions in Kinshasa and administered a questionnaire comprising items from the following FXS checklists: Hagerman, Maes, and Guruju. FMR1 CGG repeats were assessed for every patient. About 37% of patients were referable for FX testing based on Hagerman's checklist, 35% for Maes', and 43.80% for Guruju's, but none of them was molecularly confirmed to have FXS. Thus, specificities were 62.86, 64.76, and 56.5%, respectively, for Hagerman, Maes, and Guruju, respectively. The mean CGG allele size was 28.55 ± 2.83 (ranges, 17-48). The 29 CGG was the most frequent allele (24.61%). Thus, existing checklists should not be automatically applied to Congolese patients without adjustments. The distribution of CGG repeats and the number of CGG alleles are similar to other African studies. [ABSTRACT FROM AUTHOR]

A facile, cost-effective, voltage-controlled, “single-step” method for spray deposition of surfactant-assisted dispersed carbon nanotube (CNT) thin films on semiconducting and insulating substrates has been developed. The fabrication strategy enables direct deposition and adhesion of CNT films on target samples, eliminating the need for substrate surface functionalization with organosilane binder agents or metal layer coatings. Spray coating experiments on four types of sample [bare silicon (Si), microscopy-grade glass samples, silicon dioxide (SiO2), and polymethyl methacrylate (PMMA)] under optimized control parameters produced films with thickness ranging from 40 nm to 6 μm with substantial surface coverage and packing density. These unique deposition results on both semiconducting and insulator target samples suggest potential applications of this technique in CNT thin-film transistors with different gate dielectrics, bendable electronics, and novel CNT-based sensing devices, and bodes well for further investigation into thin-film coatings of various inorganic, organic, and hybrid nanomaterials on different types of substrate. [ABSTRACT FROM AUTHOR]

The research was designed to answer how households and local communities in rural Nepal are responding to the impacts of climate change. Using four villages as case study units, a mixed method approach was adopted in a multi-scaled process carried out at community, district and national levels. The research found that adaptation practices being adopted differ according to household well-being and are largely governed by access to education, information and resources within the community. Responses such as livelihood and income diversification, internal migration, share cropping, taking consumption loans, use of alternative energy and use of bio-pesticides were found to mostly vary according to well-being status of the interviewees. Development of adaptation plans, strategies and support mechanisms should take account of the different adaptation practices and needs of households. If such individual situations are not considered, adaptation responses may be ineffective or even be maladaptive and increase vulnerability. The research also found that the autonomous, unplanned and reactive nature of adaptation practices chosen by rural communities can contribute to further inequity and unequal power relations. The knowledge generated from this research contributes to understanding of how climate change contributes to vulnerability, but also how local practices and lack of an effective climate policy or response measures may magnify the effects of many existing drivers of vulnerability in terms of maladaptation and increasing social inequalities. [ABSTRACT FROM AUTHOR]

Objectives: Bariatric surgery is an effective treatment for youth with severe obesity. However, outcomes are variable and there remains sparse understanding of predictors of weight loss following surgery. The current study examines the role of adolescent-reported pre-operative social support around exercise, binge eating, and exercise to predict excess body mass index (EBMI) loss from 3 to 12 months post-surgery. Method: Participants were 101 adolescents ages 12-21 ( M age = 16.6, SD = 1.8). Pre-operative body mass index (BMI) ranged from 35 to 87 ( M = 50.3, SD = 8.6). Structural equation modeling (SEM) was used to evaluate a model of the association of adolescent report of perceived social support for exercise with less binge eating (items from the Eating Disorder Diagnostic Scale) and more self-reported exercise (items from the Youth Risk Behavior Surveillance System). The model was used to predict EBMI loss at 3, 6, 9, and 12 months post-surgery. Results: Social support significantly predicted exercise and demonstrated a trend for predicting binge eating, such that more social support was associated with more exercise and a trend for less binge eating. Binge eating was associated with less EBMI loss. However, there was no association of exercise with EBMI loss. Conclusions: Pre-operative binge eating should be a target for identification and treatment prior to sleeve gastrectomy in adolescents. Although not directly or indirectly associated with EBMI loss, perceived social support around exercise was associated with increased exercise, which may make it a consideration for a target for intervention as well. [ABSTRACT FROM AUTHOR]

This article considers literary representations of the body in female mysticism from a transdisciplinary and comparative perspective. It is one of the first studies to provide a comparative reading of three female authors of the Middle Ages: Mechthild of Magdeburg's Das Fließende Licht der Gottheit (c. 1250), Elsbeth of Oye's Leben und Offenbarungen (c. 1340) and The Book of Margery Kempe (c. 1440). The literary depiction of bodily urges ranges from erotic encounters as a representation of mystical union, to longing, suffering and despair in order to be a living example of imitatio Christi. Through analysing relevant excerpts of the three mystical texts, which illustrate the yearning for physical pain (the vita of Elsbeth of Oye) and differing accentuations of sexuality ( The Book of Margery Kempe, Das Fließende Licht der Gottheit), the instrumentalisation of the female body for salvific purposes becomes clear. These carnal manifestations of divine love can be viewed as major motifs structuring the texts rather than giving unmediated and 'documentary' evidence of their authors' experience. [ABSTRACT FROM AUTHOR]

Contaminated soil has become a growing issue in recent years. The most common technique used to remove contaminants (such as metals) from the soil is the soil washing process. However, this process produces a final effluent containing chelating agents (i.e., ethylenediaminedisuccinic acid, also known as EDDS) and extracted metals (i.e., Cu, Fe, and Zn) at concentrations higher than discharge limits allowed by the Italian and Brazilian environmental law. Therefore, it is necessary to develop further treatments before its proper disposal or reuse. In the present study, soil washing tests were carried out through two sequential paths. Moreover, different artificial sunlight-driven photocatalytic treatments were used to remove Cu, Zn, Fe, and EDDS from soil washing effluents. Metal concentrations after the additional treatment were within the Brazilian and Italian regulatory limits for discharging in public sewers. The combined TiO-photocatalytic processes applied were enough to decontaminate the effluents, allowing their reuse in soil washing treatment. Ecotoxicological assessment using different living organisms was carried out to assess the impact of the proposed two-step photocatalytic process on the effluent ecotoxicity. [ABSTRACT FROM AUTHOR]

This research explored the effectiveness of a manualized contemplative intervention among children receiving intensive residential psychiatric care. Ten children with severe psychiatric disabilities received 12 sessions (30-45 min) of 'Mindful Life: Schools' (MLS) over the course of a month. Facility-reported data on the use of physical intervention (i.e., seclusions and restraints) were analyzed. Acceptability questionnaires and broad-band behavioral questionnaire data were also collected from children and their primary clinicians. Robust logistic regression analyses were conducted on person-period data for the 10 children to explore the timing of incidents resulting in the use of physical intervention. Incidents within each person-period were regressed on indicators of days of contemplative practice and days without contemplative practice. Results indicated that during the 24-h period following MLS class, relative to a comparison 24-h period, children had significantly reduced odds of receiving a physical intervention (OR = 0.3; 95 % CI 0.2, 0.5; p < 0.001). Behavioral questionnaires did not indicate significant contemplative intervention effects ( ps >0.05), and MLS was found to be generally acceptable in this population and setting. These data indicate that contemplative practices acutely reduced the utilization of physical interventions. Clinicians seeking to implement preventative strategies to reduce the necessity of physical intervention in response to dangerous behavior should consider contemplative practices. Those wishing to empirically evaluate the effectiveness of contemplative practices should consider evaluating objective measures, such as utilization of physical intervention strategies, as oppose to subjective reports. [ABSTRACT FROM AUTHOR]

Climate change is predicted to lead to warmer temperatures and more intense storms within the century in central and northern Australia. The ensuing impacts are anticipated to present immense challenges for remote communities, in terms of maintaining housing comfort, family health and wellbeing, engagement in education and employment, and community services and businesses. About 50 % of the Australian landmass is considered remote and it is home to a highly dispersed population of about half a million people (with 30 % being Indigenous people). Much of the population in remote Australia is considered highly vulnerable to the effects of climate change as they are highly exposed and sensitive to the impacts, with many having a low adaptive capacity. The lives of Aboriginal Australians living in remote communities are strongly influenced and governed by traditional customs, knowledge and practices. Even when living in large towns, people who are strongly connected to their country are able to blend knowledge from traditional and modern sources to adapt to the current climate. This article explores the extent of adaptive capacity of people to climate change in a small remote community and large service town in the Northern Territory of Australia and provides insights about their capacities and vulnerabilities. Results indicate that the social and cultural capital are of greater importance than commonly assessed and provide scope to enhance effective community-based climate adaptation. [ABSTRACT FROM AUTHOR]

This study assessed the psychometric properties of a questionnaire designed to measure consumer satisfaction with inpatient psychiatric care. To this end, 37 inpatient psychiatric units from across the United States agreed to participate. The questionnaire was completed by 1,351 individuals, or a responsible party, for an average response rate of 53%. The factor analysis identified six scales: Nonclinical Services, Psychiatric Care, Staff, Medical Outcome, Patient Education, and Program Components/Activities. The internal reliability of the scales was high to moderate (.88 to .74). Results of a stepwise regression model showed good criterion-related validity, explaining 58% of the variance in overall quality ratings. Little shrinkage in this variance occurred when the model was cross-validated. Also, differences in satisfaction levels were noted for select facility and consumer characteristics. Results are interpreted as providing support for the reliability and validity of a newly developed consumer satisfaction survey for use in evaluating inpatient psychiatric care. [ABSTRACT FROM AUTHOR]

In recent years, electrophoretic deposition (EPD) has been adopted as a cost-effective and reliable single-step solution-based room temperature coating method for carbon nanotubes (CNTs), predominantly on conducting surfaces. Contrary to this general pre-requisite of conductive target substrates, in this work we have explored a fabrication strategy for the scalable deposition of CNTs on insulating glass surfaces by the sequential combination of electrospraying and the EPD technique. This combined process flow has been referred to as 'electrospray-assisted EPD', where an initial CNT coating on glass substrates is obtained by electrospraying which, in turn, further assists CNT film growth by EPD. The successful integration of the electrospray technique in the EPD process flow also eliminates the need for surface functionalization of the insulator substrates prior to the deposition step. Electrospray-assisted EPD has resulted in the successful fabrication of uniform, homogenous, and thick CNT deposits (∼4.5 - 5 μm) with precise thickness control. A detailed investigation of the effect of the initial electrosprayed coating on the final CNT film growth and thickness is also presented in this report. This research endeavor presents a significant opportunity for the integration of this deposition model into a wider platform of materials research and technology, chemical sensing, and applications based upon printable and flexible electronics. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Governments in developed economies are making considerable investments in energy efficiency technologies and encouraging residential households to conserve energy. A major programme in Australia has invested A$280 million to encourage residential households to become more energy aware and make additional investment in energy efficiency measures. This paper examines the adoption of energy efficiency measures by residential households participating in this programme in a geographically remote Australian town. It uses data collected by the programme developers. It examines the financial return of the investment in terms of payback period and internal rate of return. It then discusses the financial return with respect to adoption of a range of products offered by the programme. Results show that adoption of energy efficiency measures by households was not solely guided by rational economic-maximising principles. For example, some frequently adopted measures had negative financial effectiveness. A range of important determining factors are discussed, and the consequent impact this has for analysis of the effectiveness of incentive programmes. Finally, this paper proposes considerations for future programmes to more effectively measure and target efficient adoption of energy efficient measures, both in remote and non-remote residential settings. [ABSTRACT FROM AUTHOR]

The study analyzes the presence and the origin of heavy metals in environmental compartments affected by anthropogenic activities. The paper presents the results of a field study performed on the sediments of two of the main small urban creeks of the city of Prague (Czech Republic). The aim of the survey was to verify the presence and bioavailability of heavy metals (Cu, Cr, Ni, Pb, Zn) in the aquatic environment (water as well as bottom sediments), and to assess the source of these pollutants. The results were processed to evaluate the enrichment factor and the partition coefficient, and were statistically analyzed through the analysis of variance and the principal component analysis. Comparison with relevant environmental quality standards showed that measured heavy metal concentrations were always lower than the probable effect concentration (PEC). On the contrary, the threshold effect concentration (TEC) was frequently exceeded. Sequential extraction analysis showed that the bioavailability of studied metals is quite high, suggesting that they could be easily released from the sediment to the aquatic environment. Overall, several sources of pollution, different for the different metals, were identified, all related with anthropogenic factors. [ABSTRACT FROM AUTHOR]

Viral neuroinvasion is a critical step in the pathogenesis of viral encephalitis. Multiple mechanisms of neuroinvasion have been identified, but their relative contribution to central nervous system (CNS) infection remains unclear for many viruses. In this study, we examined neuroinvasion of the mosquito-borne bunyavirus La Crosse (LACV), the leading cause of pediatric viral encephalitis in the USA. We found that the olfactory bulb (OB) and tract were the initial areas of CNS virus infection in mice. Removal of the OB reduced the incidence of LACV-induced disease demonstrating the importance of this area to neuroinvasion. However, we determined that infection of the OB was not due to axonal transport of virus from olfactory sensory neurons as ablation of these cells did not affect viral pathogenesis. Instead, we found that OB capillaries were compromised allowing leakage of virus-sized particles into the brain. Analysis of OB capillaries demonstrated specific alterations in cytoskeletal and Rho GTPase protein expression not observed in capillaries from other brain areas such as the cortex where leakage did not occur. Collectively, these findings indicate that LACV neuroinvasion occurs through hematogenous spread in specific brain regions where capillaries are prone to virus-induced activation such as the OB. Capillaries in these areas may be 'hot spots' that are more susceptible to neuroinvasion not only for LACV, but other neurovirulent viruses as well. [ABSTRACT FROM AUTHOR]

Detailed geotechnical investigations were performed at two sites within the state of Arkansas (Monticello and Turrell). The soil parameters, predicted axial capacity, and predicted load-movement response values varied depending on (1) which geotechnical investigation methods and/or (2) which predictive software programs (FB-Deep, SHAFT) were utilized. The uncertainty associated with the different soil properties and the discrepancies between the different software programs are discussed. Parametric and nonparametric statistical testing methods, including the: T-test, F-Test, and Wilcoxon test were utilized to evaluate the soil parameters (corrected blow count, total unit weight, and undrained shear strength) and the predicted axial capacity data. No statistical differences (95 % confidence interval) were observed for the respective undrained shear strength, total unit weight (clay), and correlated corrected blow count parameters as determined from University of Arkansas (UofA) method and from Missouri Department of Transportation (MODOT) method. However, differences were observed for the predicted axial capacity and load-movement values that were predicted using the aforementioned soil parameters (percent differences ranging from 0.5 to 29.2 % for load-movement values). Because an inverse relationship was observed between the percent difference in the load-movement values and the number of statistically similar soil properties, it was determined that the predicted axial capacity and predicted load-movement response were dependent upon the soil sampling and testing methods and the utilized software program. [ABSTRACT FROM AUTHOR]

The choice of colour scheme used to present data can have a dramatic effect on the perceived structure present within the data. This is of particular significance in mass spectrometry imaging (MSI), where ion images that provide 2D distributions of a wide range of analytes are used to draw conclusions about the observed system. Commonly employed colour schemes are generally suboptimal for providing an accurate representation of the maximum amount of data. Rainbow-based colour schemes are extremely popular within the community, but they introduce well-documented artefacts which can be actively misleading in the interpretation of the data. In this article, we consider the suitability of colour schemes and composite image formation found in MSI literature in the context of human colour perception. We also discuss recommendations of rules for colour scheme selection for ion composites and multivariate analysis techniques such as principal component analysis (PCA). [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]