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Abstract Complex reef structure, built via calcium carbonate production by stony corals and other calcifying taxa, supports key ecosystem services. However, the decline in coral cover on reefs of the Florida Reef Tract (US), caused by ocean warming, disease, and other stressors, has led to erosion exceeding accretion, causing net loss of reef framework. Active coral restoration, aimed at rapidly increasing coral cover, is essential for recovering reef structure and function. Traditionally, restoration success focused on the survivorship and growth of transplanted corals. This is the first empirical study to examine the role of high-density outplants of the endangered staghorn coral, Acropora cervicornis, in restoring positive carbonate accretion on Florida reefs. Successful transplantation of staghorn corals contributed to positive net carbonate production. Restored plots yielded a mean net carbonate production rate of 3.06 kg CaCO3 m− 2 yr− 1, whereas control plots exhibited net erosive states. Staghorn restoration plots sustained positive net carbonate production at a threshold of ~ 2.96% coral cover. However, bleaching, storms, and disease challenge these reefs, highlighting the need for restoration strategies that enhance resilience to environmental stressors. Establishing Acroporid aggregations through outplanting, alongside climate adaptation strategies, could foster reef habitat growth and enhance the recovery of ecosystem services.

ABSTRACT: The global food animal industry faces a growing concern regarding antimicrobial resistance (AMR), primarily driven by the use of antimicrobials (AM) for the treatment, control, and prevention of diseases. Addressing this challenge requires promoting responsible antimicrobial use (AMU) practices. In 2019, the province of Québec, Canada, took a significant step by implementing a regulation that limits the use of AM of very high importance for human medicine (category I AM as defined by Health Canada) in the food animal industry. However, the implementation of such regulation can significantly influence behavioral shifts among producers, contributing to the wider effort against AMR. Therefore, the objective of this observational study was to describe the perceived changes in dairy producers' knowledge and on-farm practices following the implementation of this regulation, using a cohort design. Data collection involved administering questionnaires to 87 dairy producers from 3 regions of the province of Québec (Estrie, Montérégie, Centre-Du-Québec) before (2017–2018) and after (2020–2021) the implementation of the regulation. The questionnaires explored the descriptive characteristics of farms, the knowledge of producers about the categorization of AM, the on-farm treatment practices, and the perceived effects of the regulation. Statistical analysis included t-tests and McNemar tests to compare the paired data obtained using the 2 questionnaires. The results indicated an increase in the knowledge score (the number of AM correctly categorized by the producers by their importance for human medicine) after the implementation of the regulation, suggesting an improved understanding of the categorization of AM based on their importance for human medicine. Trends in AMU practices for treating clinical mastitis and reproductive diseases suggested that category I AM were less likely to be reported as the primary treatment after the regulation, whereas category II AM were more often reported as primary treatment. Adoption of the selective dry cow therapy method significantly increased, whereas the use of teat sealants remained unchanged. Moreover, producers had divergent perceptions regarding the effect of the regulation on the cure rates and disease frequencies. This disparity emphasizes the need for comprehensive data collection to discern the risks associated with such regulatory shifts. The study acknowledges several limitations, including the potential for recall bias, confirmation bias, and desirability bias. Despite these limitations, this study shows that implementing regulations to encourage responsible AMU drives positive transformations in producers' knowledge and on-farm practices. This underscores the pivotal effect of proactive interventions in combating the escalating threat of AMR within the global food animal industry.

Abstract Background A range of strategies are available that can improve the outcomes of older persons particularly in relation to basic activities of daily living during and after an acute care (AC) episode. This paper outlines the original development of outcome-oriented quality indicators (QIs) in relation to common geriatric syndromes and function for the care of the frail aged hospitalized in acute general medical wards. Methods Design QIs were developed using evidence from literature, expert opinion, field study data and a formal voting process. A systematic literature review of literature identified existing QIs (there were no outcome QIs) and evidence of interventions that improve older persons’ outcomes in AC. Preliminary indicators were developed by two expert panels following consideration of the evidence. After analysis of the data from field testing (indicator prevalence, variability across sites), panel meetings refined the QIs prior to a formal voting process. Setting Data was collected in nine Australian general medical wards. Participants Patients aged 70 years and over, consented within 24 h of admission to the AC ward. Measurements The interRAI Acute Care – Comprehensive Geriatric Assessment (interRAI AC-CGA) was administered at admission and discharge; a daily risk assessment in hospital; 28-day phone follow-up and chart audit. Results Ten outcome QIs were established which focused on common geriatric syndromes and function for the care of the frail aged hospitalized in acute general medical wards. Conclusion Ten outcome QIs were developed. These QIs can be used to identify areas where specific action will lead to improvements in the quality of care delivered to older persons in hospital.

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Differential Evolution (DE) algorithms are widely recognized as effective metaheuristic techniques used to solve continuous optimization problems. However, DE algorithms encounter limitations in exploration and exploitation due to their sensitivity to parameter settings and reliance on mutation strategies. To overcome these drawbacks, we introduced a self-adaptive mutation and population improvement strategy in differential evolution, SAMPIDE. The algorithm adjusts the mutation operator automatically according to the successful mutation operator value from the previous generation. Additionally, to enhance the algorithm’s convergence, we adopted a random learning mechanism to update the population. SAMPIDE was compared with nine state-of-the-art DE variants and four other metaheuristic algorithms across thirty-two benchmark functions. SAMPIDE consistently outperformed others on unimodal, step and noisy functions, while maintaining competitive performance on multimodal functions. Additionally, when tested on five real-world problems, SAMPIDE outperformed other metaheuristic algorithms. Thus, the self-adaptive mutation and population improvement strategy incorporated into SAMPIDE positioned it as a promising solution for a wide range of optimization problems.

Zero-valent copper and silver metals (Ms) nanoparticles (NPs) supported on carboxymethylcellulose (CMC) were synthesized for treating Enterotoxigenic Escherichia coli fimbriae 4 (ETEC:F4), a major cause of diarrhea in post-weaned pigs. The antibacterial properties of Cu0/CMC and Ag0/CMC were assessed on infected porcine intestinal enterocyte IPEC-J2, an in vitro model mimicking the small intestine. The lower average particle size (218 nm) and polydispersity index [PDI]: 0.25) for Ag0/CMC, when compared with those of Cu0/CMC (367 nm and PDI 0.96), were explained by stronger Ag0/CMC interactions. The minimal inhibitory concentration (MIC) and half inhibitory concentration (IC50) of Ag0/CMC were lower in both bacteria and IPEC-J2 cells than those of Cu0/CMC, confirming that silver nanoparticles are more bactericidal than copper counterparts. IPEC-J2, less sensitive in MNP/CMC treatment, was used to further investigate the infective process by ETEC:F4. The IC50 of MNP/CMC increased significantly when infected IPEC-J2 cells and ETEC were co-treated, showing an inhibition of the cytotoxicity effect of ETEC:F4 infection and protection of treated IPEC-J2. Thus, it appears that metal insertion in CMC induces an inhibiting effect on ETEC:F4 growth and that MNP/CMC dispersion governs the enhancement of this effect. These results open promising prospects for metal-loaded biopolymers for preventing and treating swine diarrhea.

Summary: Background: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. Methods: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. Findings: We found both tau metrics significantly elevated across increasing disease stages (p

This study aimed to identify contamination sources in raw milk and cheese on small farms in Brazil by isolating Escherichia coli at various stages of milk production and cheese manufacturing. The study targeted EAEC, EIEC, ETEC, EPEC, STEC, and ExPEC pathotypes, characterizing isolates for the presence of virulence genes, phylogroups, antimicrobial susceptibility, and phylogenetic relationships using PFGE and MLST. The presence of antimicrobial resistance genes and serogroups was also determined. Three categories of E. coli were identified: pathogenic, commensal, and ceftriaxone-resistant (ESBL) strains. Pathogenic EPEC, STEC, and ExPEC isolates were detected in milk and cheese samples. Most isolates belonged to phylogroups A and B1 and were resistant to antimicrobials such as nalidixic acid, ampicillin, kanamycin, streptomycin, sulfisoxazole, and tetracycline. Genetic analysis revealed that E. coli with identical virulence genes were present at different stages within the same farm. The most frequently identified serogroup was O18, and MLST identified ST131 associated with pathogenic isolates. The study concluded that E. coli was present at multiple points in milk collection and cheese production, with significant phylogroups and high antimicrobial resistance. These findings highlight the public health risk posed by contamination in raw milk and fresh cheese, emphasizing the need to adopt hygienic practices to control these microorganisms.

Antimicrobial resistance can be effectively limited by improving the judicious use of antimicrobials in food production. However, its effect on the spread of AMR genes in animal populations is not well described. In the province of Québec, Canada, a new legislation implemented in 2019 has led to an unprecedented reduction in the use of critical antimicrobials in dairy production. We aimed to investigate the potential link between ESBL/AmpC E. coli isolated before and after legislation and to determine the presence of plasmids carrying genes responsible for critical AMR. We collected fecal samples from calves, cows, and manure pit from 87 Québec dairy farms approximately 2 years before and 2 years after the legislation came into effect. The whole genomes of 183 presumptive ESBL/AmpC E. coli isolated after cefotaxime enrichment were sequenced. Their phylogenetic characteristics (MLST, serogroup, cgMLST) and the presence of virulence and resistance genes and replicons were examined. A maximum likelihood phylogenetic tree was constructed based on single nucleotide polymorphism (SNPs). We identified 10 clonal lineages (same cgMLST) and 7 clones (SNPs ≤ 52). Isolates belonging to these clones could be found on different farms before and after the legislation, strongly suggesting a clonal spread of AMR genes in the population during this 4-year period. All isolates were multidrug resistant (MDR), with clone 2 being notable for the presence of macrolide, fluoroquinolone, and third-generation cephalosporin resistance genes. We also identified clinically relevant ExPEC (ST10) and APEC-like lineages (ST117, ST58, ST88) associated with the presence of ExPEC and APEC virulence genes, respectively. Our data also suggests the presence of one epidemic plasmid belonging to the IncY incompatibility group and carrying qnrs1 and blaCTX–M–15. We demonstrated that AMR genes spread through farms and can persist over a 4-year period in the dairy cattle population through both plasmids and E. coli clones, despite the restriction of critical antimicrobial use. MDR ExPEC and APEC-like STs are present in the normal microbiota of cattle (more frequently in calves). These data increase our knowledge on gene dissemination dynamics and highlight the fact that biosecurity measures should be enhanced in this industry to limit such dissemination.

AbstractPyrolysis of waste biomass to produce usable energy has the potential to, in part, alleviate the consumption of limited fossil fuel resources. We describe bio-oil production via fast pyrolysis of cassava residues, a mostly wasted byproduct of cassava crops. The waste biomass was combined with two readily available additives—volcanic rock and ethanol—in a free fall reactor to generate bio-oil, char and syngas. Using cassava stems as the raw feed-stock we tested pyrolysis reaction temperatures in the range 450–500 °C in a free fall reactor using a N2 flow. Analysis of the pyrolysis products should little variation in this range, so analyses for the effects of ethanol and volcanic rock as additives were tested at 500 °C. The bio-oil yield ranged between 58 and 60%, char represented 17–19% and gas 21–24%. With volcanic rock, the higher heating value was significantly higher at 23.6 MJ/kg compared to ~19 MJ/kg for cassava alone or added ethanol. Readily available, inexpensive, naturally occuring zeolites in the volcanic rock led to significant extra degradation of the biomass, under the same experimental conditions, leading to this improvement.

Antimicrobials serve as crucial treatments in both veterinary and human medicine, aiding in the control and prevention of infectious diseases. However, their misuse or overuse has led to the emergence of antimicrobial resistance, posing a significant threat to public health. This review focuses on extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in animals and their associated food products, which contribute to the proliferation of antimicrobial-resistant strains. Recent research has highlighted the presence of ESBL-producing E. coli in animals and animal-derived foods, with some studies indicating genetic similarities between these isolates and those found in human infections. This underscores the urgent need to address antimicrobial resistance as a pressing public health issue. More comprehensive studies are required to understand the evolving landscape of ESBLs and to develop strategic public health policies grounded in the One Health approach, aiming to control and mitigate their prevalence effectively.

Objective: Long-term care (LTC) homes (“nursing homes”) were challenged during the first year of the COVID-19 pandemic in Canada. The objective of this study was to measure the impact of the COVID-19 pandemic on resident admission and discharge rates, resident health attributes, treatments, and quality of care. Design: Synthesis analysis of “Quick Stats” standardized data table reports published yearly by the Canadian Institute for Health Information. These reports are a pan-Canadian scorecard of LTC services rendered, resident health characteristics, and quality indicator performance. Setting and participants: LTC home residents in Alberta, British Columbia, Manitoba, and Ontario, Canada that were assessed with the interRAI Minimum Data Set 2.0 comprehensive health assessment in fiscal years 2018/2019, 2019/2020 (pre-pandemic period), and 2020/2021 (pandemic period). Methods: Risk ratio statistics were calculated to compare admission and discharge rates, validated interRAI clinical summary scale scores, medication, therapy and treatment provision, and seventeen risk-adjusted quality indicator rates from the pandemic period relative to prior fiscal years. Results: Risk of dying in the LTC home was greater in all provinces (risk ratio [RR] range 1.10 to 1.29) during the pandemic. Quality of care worsened substantially on 6 of 17 quality indicators in British Columbia and Ontario, and 2 quality indicators in Manitoba and Alberta. The only quality indicator where performance worsened during the pandemic in all provinces was the percentage of residents that received antipsychotic medications without a diagnosis of psychosis (RR range 1.02 - 1.16). Conclusions and implications: The COVID-19 pandemic has unveiled numerous areas to strengthen LTC and ensure that resident’s physical, social, and psychological needs are addressed during public health emergencies. Except an increase in potentially inappropriate antipsychotic use, this provincial-level analysis indicates that most aspects of resident care were maintained during the first year of the COVID-19 pandemic.

Background & Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn’s disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10-9, Holm P = .002) and EFNA3 (P = 4.9 × 10-8, Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2–2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19, SBNO2 = 1.2 × 10-11) and regions (TXK [false discovery rate, P = 3.6 × 10-14], WRAP73 [false discovery rate, P = 1.9 × 10-9], VMP1 [false discovery rate, P = 1.7 × 10-7], and ITGB2 [false discovery rate, P = 1.4 × 10-7]). Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

Polylactide stereocomplex (ST) of poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) (PLLA:PDLA 50:50) was blended with poly(methyl methacrylate) (PMMA) 10 – 50 wt.%. The materials were dissolved in chloroform at room temperature and the films were then cast. Differential scanning calorimetry showed a stereocomplex melting peak at 208 °C – 50 °C higher than that for neat PLLA or PDLA - confirming the polylactide stereocomplex crystallites. The PMMA content ratio of 10 – 50 wt.% in the stereocomplex showed almost complete stereocomplex crystallites. A peak at about 908 cm-1 in Fourier transform infrared spectra further confirmed the stereocomplex crystallites which indicated that PMMA could blend and efficiently bond with the stereocomplex. The X-ray diffraction analysis showed that the stereocomplex crystallinity became smaller when PMMA was added. Morphology from scanning electron microscopy revealed that phases separated in the ST/PMMA blend when the amount of PMMA was increased. Adding PMMA to stereocomplex films led to an increased elongation at break which peaked at 30 % added PMMA. Increased PMMA also led to the improved thermal stability of the stereocomplex. These properties and higher toughness are also needed in common applications, in particular films for packaging and protection of manufactured products.

Enterotoxigenic Clostridium perfringens is one of the main causes of foodborne illness in Canada. The use of a conventional bacterial culture approach to isolate enterotoxigenic C. perfringens from poultry meat is common. This approach is based on the phenotype attributable to a double hemolysis phenomenon, whereas few enterotoxigenic strains of C. perfringens produce it, which further complicates the study of the reservoirs of this important pathogen. The objectives of the current study were to validate the ability of a digoxigenin-labeled probe to detect the C. perfringens cpe gene and to validate the use of either a filtration or a direct plating approach, combined with colony hybridization to detect enterotoxigenic C. perfringens. Pure DNA and pure colonies of enterotoxigenic C. perfringens and broiler chicken carcass rinsate samples were subjected to colony hybridization. The results showed that the synthesized DNA probe can detect the cpe gene from both DNA and pure colonies of enterotoxigenic C. perfringens, and from colonies grown from carcass rinsates artificially contaminated with enterotoxigenic C. perfringens. Our study suggests that this isolation method is a promising tool for a better understanding of the epidemiology of this zoonotic pathogen.

Abstract Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10–12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs.

With the emergence of antimicrobial resistance (AMR), many countries are implementing restrictive regulations to reduce antimicrobial use (AMU) in animal production. Although these measures are effective at the national level, their implementation may generate challenges for producers and veterinarians. The objective of this study was to explore the barriers and facilitators of implementing a new regulation restricting the use of antimicrobials of very high importance for human health in the dairy production sector in the province of Québec, Canada. Individual interviews were conducted with fifteen veterinarians and twenty-seven dairy producers. Thematic analysis was performed based on the COM-B model of behavior change (capability-opportunity-motivation-behavior). Our results indicated that the lack of availability of alternative treatments, the long delays related to diagnostic tests and the fear of economic consequences were major barriers to the implementation of the regulation. A small number of producers also perceived that the regulation negatively impacted the health and wellbeing of their animals. Additionally, participants acknowledged the importance of early education and training to better understand the purpose of the regulation and increase its acceptability. Lastly, most participants reported that they had not only reduced their use of antimicrobials of very high importance for human health following the regulation, but they had also increased preventive practices on their farm. This study reveals that the implementation of restrictive regulations to reduce AMU in animal production can lead to multiple challenges in practice. Our results highlight the need for better communication and training of producers and veterinarians before and during the implementation of similar regulations in the future and underline the importance of measuring the direct and indirect impacts of those regulations on productivity and on animal health and wellbeing.

The genetic prehistory of central America has not been well explored. Here, the authors find evidence from ancient DNA from twenty individuals who lived in Belize 9,600 to 3,700 years ago of a migration from the south that coincided with the first evidence for forest clearing and the spread of maize horticulture.

“Brain-predicted age” quantifies apparent brain age compared to normative neuroimaging trajectories. Advanced brain-predicted age has been well established in symptomatic Alzheimer disease (AD), but is underexplored in preclinical AD. Prior brain-predicted age studies have typically used structural MRI, but resting-state functional connectivity (FC) remains underexplored. Our model predicted age from FC in 391 cognitively normal, amyloid-negative controls (ages 18–89). We applied the trained model to 145 amyloid-negative, 151 preclinical AD, and 156 symptomatic AD participants to test group differences. The model accurately predicted age in the training set. FC-predicted brain age gaps (FC-BAG) were significantly older in symptomatic AD and significantly younger in preclinical AD compared to controls. There was minimal correspondence between networks predictive of age and AD. Elevated FC-BAG may reflect network disruption during symptomatic AD. Reduced FC-BAG in preclinical AD was opposite to the expected direction, and may reflect a biphasic response to preclinical AD pathology or may be driven by inconsistency between age-related vs. AD-related networks. Overall, FC-predicted brain age may be a sensitive AD biomarker.

Abstract Deep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ± 10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ± 1.9 points (χ 2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ± 3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no serious psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS in the region of the BNST for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.

The high cost, low heat resistance, and brittleness of poly(L-lactide) (PLLA) is a significant drawback that inhibits its diffusion into many industrial applications. These weaknesses were solved by forming a polylactide stereocomplex (ST) and blending it with thermoplastic starch (TPS). We blended poly (L-lactide)(PLLA), up to 30% thermoplastic starch, and a chain extender (2%) in an internal mixer, which was then hand-mixed with poly (D-lactide)(PDLA) and injection molded to form specimens, in order to study mechanical, thermal, and crystallization behavior. Differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (XRD) demonstrated that the stereocomplex structures were still formed despite the added TPS and showed melting points ~55 °C higher than neat PLLA. Furthermore, stereocomplex crystallinity decreased with the increased TPS content. Dynamic mechanical analysis revealed that ST improved PLLA heat resistance, and tensile testing suggested that the TPS improved the elongation-at-break of ST. Moreover, the chain extender reduced the degradation of ST/TPS blends and generally improved ST/TPS composites’ mechanical properties.

Low-cost sensors (LCS) have been increasingly deployed to monitor PM2.5 concentrations. More than 1500 LCS have been installed in Thailand to increase public awareness of air quality. However, performance of these sensors has not been systematically investigated. In this study, PM2.5 LCS were co-located next to a PM2.5 federal equivalent method (FEM) reference instrument at three Thai locations—in the north, center and northeast. We evaluated the performance of a PM2.5 LCS (PMS7003, Plantower) to understand the key factors affecting performance, including emission sources, relative humidity, temperature and PM2.5 concentration. Low PM concentration and high humidity levels had a significant impact on performance. Sensors in a high traffic emission area showed low correlation. The unadjusted PM2.5 LCS performance varied with locations. Errors were mainly observed at low concentrations. They significantly underestimated concentrations in congested urban environments. After calibration, accuracy was improved with multiple regression models. The performance of sensors only at Chiang Mai (CM) during the dry season and Ubon Ratchathani (URT) during the dry and wet seasons were acceptable with coefficient of variation: 5.8 ± 4.7–6.8 ± 5.0%, slope: 0.829–0.945, intercept: 1.12–5.49 µg/m3, R2: 0.880–0.934 and RMSE: 4.3–5.1 µg/m3. In the congested area in Bangkok (BKK), they underestimated concentrations of small particles.

Introduction Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs—to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.Methods and analysis In this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care.Ethics and dissemination This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS.

PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.

WAGR syndrome is a rare genetic disorder characterized by Wilms tumor, Aniridia, Genitourinary anomalies, and Range of developmental delays. In addition to the classic features, patients affected by WAGR syndrome can develop obesity and kidney failure, and a wide variety of non-classical manifestations have also been described. This suggests that a broader phenotypic spectrum beyond the classic syndrome exists and here we demonstrate that spectrum using data from the WAGR Syndrome Patient Registry. In the present study, we collected information from 91 individuals enrolled in the registry to explore self-reported health issues in this patient population. A wide variety of common clinical issues not classically associated with the disorder were found, prompting the redefinition from WAGR syndrome to WAGR spectrum disorder to incorporate the phenotypic variations that occur. A comprehensive care management approach is needed to address the wide range of clinical issues and we propose a care model for patients affected by WAGR spectrum disorder. Further research is needed to solidify the breath of the phenotype and confirm the observations in this study to advance individualized patient care in this population.

As online retail services proliferate and are pervasive in modern lives, applications for classifying fashion apparel features from image data are becoming more indispensable. Online retailers, from leading companies to start-ups, can leverage such applications in order to increase profit margin and enhance the consumer experience. Many notable schemes have been proposed to classify fashion items, however, the majority of such schemes have focused upon classifying basic-level categories, such as T-shirts, pants, skirts, shoes, bags, and so forth. In contrast to most prior efforts, this paper aims to enable an in-depth classification of fashion item attributes within the same category. Beginning with a single dress, we seek to classify the type of dress hem, the hem length, and the sleeve length. The proposed scheme is comprised of three major stages: (a) localization of a target item from an input image using semantic segmentation, (b) detection of human key points (e.g., point of shoulder) using a pre-trained CNN and a bounding box, and (c) three-phase classification of the attributes using a combination of algorithmic approaches and deep neural networks. The experimental results demonstrate that the proposed scheme is highly effective, with all categories having average precision of above 93.02%, and outperforms existing Convolutional Neural Networks (CNNs)-based schemes.

The application of scientific and technological approaches in education has been increasing year by year. We evaluated the effect of a TSCCK model based on the cognitive load theory on the cognitive load and learning achievement of vocational students: this model had six components: (1) analysis; (2) content development; (3) cloud development; (4) learning activity development; (5) model implementation; and (6) model revision. We used 62 students randomly selected from 115 students taking an “E-commerce data analysis and processing” course and used cluster random sampling. A total of 31 students were taught with instructions based on the TSCCK model, while 31 students were taught with a traditional method. The instruments used included lesson plans for the TSCCK group developed using the cognitive load theory and the workload profile self-rating scale (WP scale) used to measure the student cognitive load for both groups. The students who learned with TSCCK had significantly lower cognitive load (WP scale) scores than the students who learned with the traditional method, and their achievement scores were higher. The MANOVA confirmed that both the achievement scores and cognitive load measures for the two groups were significantly different at the 0.05 level.

We studied the properties of the bio-oil and char from fast pyrolysis of cassava rhizomes in a free-fall reactor, catalyzed by adding various soil conditioners (or improvers) as catalysts to the reactor at 500 °C and 200 g/h feed rate. Four conditioners were evaluated - granular TPI pH11 soil conditioner, volcanic rock, TPI pelletized organic fertilizer and super dolomite - and added at 50% (w/w) of the rhizomes. Bio-oil and gas yields decreased, whereas char yields increased, yielding bio-oil 57–59%, gas 14–20% and char 23–28%. With the catalysts, the bio-oil higher heating value increased, while that of char decreased: for cassava rhizomes with volcanic rock the bio-oil high heating value increased from 19.4 to 23.6 MJ/kg, whereas rhizomes with dolomite led to an increased viscosity from 27 to 34 × 10−3 mm2/s.

Abstract Background Antimicrobial resistance (AMR) in food-producing animals is a global public health issue. This study investigated AMR and virulence profiles of E. coli isolated from healthy chickens in Vietnam. E. coli were isolated from fecal samples collected in five chicken farms located in the provinces of Hoa Binh, Thai Nguyen and Bac Giang in the North of Vietnam. These isolates were examined by disk diffusion for their AMR, PCR for virulence and AMR genes, pulsed-field gel electrophoresis for relatedness between bla CMY-2 /bla CTX-M –positive isolates, electroporation for transferability of bla CMY-2 or bla CTX-M genes and sequencing for mutations responsible for ciprofloxacin resistance. Results Up to 99% of indicator isolates were multidrug resistant. Resistance to third-generation cephalosporins (3GC) was encoded by both bla CTX-M and bla CMY-2 genes; bla CTX-M genes being of genotypes bla CTX-M-1, − 14, − 15, − 17, − 57 and − 87 , whereas ciprofloxacin resistance was due to mutations in the gyrA and parC genes. Some isolates originating from farms located in different provinces of Vietnam were found to be closely related, suggesting they may have been disseminated from a same source of contamination. Plasmids may also have played a role in the diffusion of 3GC-resistance as the bla CMY-2 gene was located on plasmids A/C and I1, and the bla CTX-M gene variants were carried by I1, FIB, R and HI1. Plasmids carrying the bla CMY-2 /bla CTX-M genes also co-transferred resistance to other antimicrobials. In addition, isolates potentially capable of infecting humans, of which some produced bla CMY-2 /bla CTX-M , were identified in this study. Conclusions Both clones and plasmids could be involved in the dissemination of 3GC-resistant E. coli within and between chicken farms in Vietnam. These results demonstrate the necessity to monitor AMR and control antimicrobial use in poultry in Vietnam.

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer’s disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

Cryopreservation is a key step for the effective delivery of many cell therapies and for the maintenance of biological materials for research. The preservation process must be carefully controlled to ensure maximum, post-thaw recovery using cooling rates slow enough to allow time for cells to cryodehydrate sufficiently to avoid lethal intracellular ice. This study focuses on determining the temperature necessary at the end of controlled slow cooling before transfer to cryogenic storage which ensures optimal recovery of the processed cell samples. Using nucleated, mammalian cell lines derived from liver (HepG2), ovary (CHO) and bone tissue (MG63) this study has shown that cooling must be controlled to -40°C before transfer to long term storage to ensure optimal cell recovery. No further advantage was seen by controlling cooling to lower temperatures. These results are consistent with collected differential scanning calorimetry data, that indicated the cells underwent an intracellular, colloidal glass transition between -49 and -59°C (Tg’i) in the presence of the cryoprotective agent dimethyl sulfoxide (DMSO). The glass forms at the point of maximum cryodehydration and no further cellular dehydration is possible. At this point the risk of lethal intracellular ice forming on transfer to ultra-low temperature storage is eliminated. In practice it may not be necessary to continue slow cooling to below this temperature as optimal recovery at -40°C indicates that the cells have become sufficiently dehydrated to avoid further, significant damage when transferred into ultra-low temperature storage.

As medical imaging enters its information era and presents rapidly increasing needs for big data analytics, robust pooling and harmonization of imaging data across diverse cohorts with varying acquisition protocols have become critical. We describe a comprehensive effort that merges and harmonizes a large-scale dataset of 10,477 structural brain MRI scans from participants without a known neurological or psychiatric disorder from 18 different studies that represent geographic diversity. We use this dataset and multi-atlas-based image processing methods to obtain a hierarchical partition of the brain from larger anatomical regions to individual cortical and deep structures and derive age trends of brain structure through the lifespan (3–96 years old). Critically, we present and validate a methodology for harmonizing this pooled dataset in the presence of nonlinear age trends. We provide a web-based visualization interface to generate and present the resulting age trends, enabling future studies of brain structure to compare their data with this reference of brain development and aging, and to examine deviations from ranges, potentially related to disease.

Abstract Camels (Camelus dromedarius) are known to harbor multidrug resistant Gram-negative bacteria and to be involved in the transmission of various microorganisms to humans. Data on the occurrence of colistin resistant Escherichia coli as well as mobilized colistin resistance (mcr) genes in camels are lacking. We investigated the presence of colistin resistance and mcr (1–2) genes in E. coli from the feces of camels in Tunisia. Presumptive E. coli isolates from camel-calves in southern Tunisia were qualitatively screened for growth on Mueller–Hinton agar supplemented with 2 mg/L of colistin. The minimal inhibitory concentration of colistin was determined for isolates growing on this medium. All isolates were screened for the presence of the mcr-1 and mcr-2 genes by polymerase chain reaction without detecting any of these genes. However, one isolate was confirmed resistant to colistin and further testing of this isolate revealed it to be Enterobacter cloacae. Our study demonstrated absence of colistin resistance and of the mcr-1 and mcr-2 genes in E. coli isolated from camel feces in southern Tunisia. Thus, there is no evidence that camels represent a major source of mcr genes contamination for the local population or for tourists visiting southern Tunisia.

Abstract Post-weaning diarrhea (PWD) is one of the most serious threats for the swine industry worldwide. It is commonly associated with the proliferation of enterotoxigenic Escherichia coli in the pig intestine. Colistin, a cationic antibiotic, is widely used in swine for the oral treatment of intestinal infections caused by E. coli, and particularly of PWD. However, despite the effectiveness of this antibiotic in the treatment of PWD, several studies have reported high rates of colistin resistant E. coli in swine. Furthermore, this antibiotic is considered of very high importance in humans, being used for the treatment of infections due to multidrug-resistant (MDR) Gram-negative bacteria (GNB). Moreover, the recent discovery of the mcr-1 gene encoding for colistin resistance in Enterobacteriaceae on a conjugative stable plasmid has raised great concern about the possible loss of colistin effectiveness for the treatment of MDR-GNB in humans. Consequently, it has been proposed that the use of colistin in animal production should be considered as a last resort treatment only. Thus, to overcome the economic losses, which would result from the restriction of use of colistin, especially for prophylactic purposes in PWD control, we believe that an understanding of the factors contributing to the development of this disease and the putting in place of practical alternative strategies for the control of PWD in swine is crucial. Such alternatives should improve animal gut health and reduce economic losses in pigs without promoting bacterial resistance. The present review begins with an overview of risk factors of PWD and an update of colistin use in PWD control worldwide in terms of quantities and microbiological outcomes. Subsequently, alternative strategies to the use of colistin for the control of this disease are described and discussed. Finally, a practical approach for the control of PWD in its various phases is proposed.

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer’s disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4−T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T−); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4−T−). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4−T− group, the other three groups showed different alterations in the clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4−T− group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.

BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.

The ‘short’ neutral section is a feature of alternating current (AC) railway overhead line electrification that is often unreliable and a source of train delays. However hardly any dynamic analysis of its behaviour has been undertaken. This paper briefly describes the work undertaken investigating the possibility of modelling the behaviour using a novel approach. The potential for thus improving the performance of short neutral sections is evaluated, with particular reference to the UK situation. The analysis fundamentally used dynamic simulation of the pantograph and overhead contact line (OCL) interface, implemented using a proprietary finite element analysis tool. The neutral section model was constructed using physical characteristics and laboratory tests data, and was included in a validated pantograph/OCL simulation model. Simulation output of the neutral section behaviour has been validated satisfactorily against real line test data. Using this method the sensitivity of the neutral section performance in relation to particular parameters of its construction was examined. A limited number of parameter adjustments were studied, seeking potential improvements. One such improvement identified involved the additional inclusion of a lever arm at the trailing end of the neutral section. A novel application of pantograph/OCL dynamic simulation to modelling neutral section behaviour has been shown to be useful in assessing the modification of neutral section parameters.

The definition of a high risk clone for antibiotic resistance dissemination was initially established for human medicine. We propose a revised definition of a high risk clone adapted to the One Health context. Then, we applied our criteria to a cluster of enrofloxacin non susceptible ETEC:F4 isolates which emerged in 2013 in diseased pigs in Quebec. The whole genomes of 183 ETEC:F4 strains isolated in Quebec from 1990 to 2018 were sequenced. The presence of virulence and resistance genes and replicons was examined in 173 isolates. Maximum likelihood phylogenetic trees were constructed based on SNP data and clones were identified using a set of predefined criteria. The strains belonging to the clonal lineage ST100/O149:H10 isolated in Quebec in 2013 or later were compared to ETEC:F4 whole genome sequences available in GenBank. Prior to 2000, ETEC:F4 isolates from pigs in Quebec were mostly ST90 and belonged to several serotypes. After 2000, the isolates were mostly ST100/O149:H10. In this article, we demonstrated the presence of a ETEC:F4 high risk clone. This clone (1) emerged in 2013, (2) is multidrug resistant, (3) has a widespread distribution over North America and was able to persist several months on farms, and (4) possesses specific virulence genes. It is crucial to detect and characterize high risk clones in animal populations to increase our understanding of their emergence and their dissemination.

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.

For large and complex tissue engineered constructs to be available on demand, long term storage using methods, such as cryopreservation, are essential. This study optimised parameters such as excess media concentration and warming rates and used the findings to enable the successful cryopreservation of 2.3 litres of alginate encapsulated liver cell spheroids. This volume of biomass is typical of those required for successful treatment of Acute Liver Failure using our Bioartificial Liver Device. Adding a buffer of medium above the biomass, as well as slow (0.6°C/min) warming rates was found to give the best results, so long as the warming through the equilibrium melting temperature was rapid. After 72 h post thaw-culture, viable cell number, glucose consumption, lactate production, and alpha-fetoprotein production had recovered to pre-freeze values in the 2.3 litre biomass (1.00 ± 0.05, 1.19 ± 0.10, 1.23 ± 0.18, 2.03 ± 0.04 per ml biomass of the pre-cryopreservation values respectively). It was also shown that further improvements in warming rates of the biomass could reduce recovery time to < 48 h. This is the first example of a biomass of this volume being successfully cryopreserved in a single cassette and re-cultured. It demonstrates that a bioartificial liver device can be cryopreserved, and has wider applications to scale-up large volume cryopreservation.