Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

The long-distance stable transport of relativistic electron beams (REBs) in plasmas is studied by full three-dimensional particle-in-cell simulations. Theoretical analysis shows that the beam transport is mainly influenced by three transverse instabilities, where the excitation of self-modulation instability, and the suppression of the filamentation instability and the hosing instability are important to realize the beam stable transport. By modulating the transport parameters such as the electron density ratio, the relativistic Lorentz factor, the beam envelopes and the density profiles, the relativistic bunches having a smooth density profile and a length of several plasma wave periods can suppress the beam-plasma instabilities and propagate in plasmas for long distances with small energy losses. The results provide a reference for the research of long-distance and stable transport of REBs, and would be helpful for new particle beam diagnosis technology and space active experiments.

The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009–2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009–2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.

The butterfly plastic zone theory based on Mohr Coulomb criterion has been widely used in coal mine production. In order to verify the universality of the theory, it is necessary to compare the distribution of plastic zone under different strength criteria. Based on the elastic-plastic mechanics, the principal stress distribution function around the circular tunnel is deduced in the paper, and the boundary and radius of the plastic zone under different strength criteria are calculated. The results show that the change laws of the plastic zone around the circular tunnel under different strength criteria has the following commonness: firstly, with the increase of the lateral pressure coefficient, the shape of the plastic zone presents the change laws of “circle ellipse butterfly”; Secondly, with the increase of the lateral pressure coefficient, the radius of the plastic zone is exponential distribution, while the characteristic value is different when the radius of the plastic zone is infinite. At same time, it shows that the butterfly plastic zone has a low sensitivity dependence on the strength criterion, no matter which strength criterion is adopted, and the butterfly plastic zone will inevitably appear in the surrounding rock mass of circular tunnel in the high deviator stress environment; The plastic zone with butterfly shape is highly sensitive to the stress change, and the small stress change may promote the expansion of the plastic zone. This result is significant for us to understand and prevent rock engineering disasters and accidents.

To improve the endurance performance of long-endurance Unmanned Aerial Vehicles (UAVs), a smart morphing method to adjust the UAV and flight mode continuously during flight is proposed. Using this method as a starting point, a smart morphing long-endurance UAV design is conducted and the resulting improvement in the endurance performance studied. Firstly, the initial overall design of the smart morphing long-endurance UAV is carried out, then the morphing form is designed and various control parameters are selected. Secondly, based on multi-agent theory, an architecture for the smart morphing control system is built and the workflow of the smart morphing control system is planned. The morphing decision method is designed in detail based on the particle swarm optimisation algorithm. Finally, a simulation of the smart morphing approach in the climb and cruise stages is carried out to quantitatively verify the improvement in the endurance performance. The simulation results show that the smart morphing method can improve the cruise time by 4.1% with the same fuel consumption.

Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.

Introduction: Despite the visibility of the homeless population, there is limited data on the information of this patient population. Point-in-time counts and survey data from selected samples (such as those admitted to emergency shelter) have primarily been used. This literature suggests that this hard-to-reach population has high rates of presentation at emergency departments (EDs), and as such, EDs often become their main point of contact for health and social services. Leveraging this fact and administrative data we construct a crude census of homeless persons within Ontario. We further examine demographic characteristics of patients experiencing homelessness, and compare this data to findings from previous literature. Methods: All routinely collected administrative health data from EDs located within Ontario, Canada from 2010-2017 were analyzed to examine patient characteristics. Individuals experiencing homelessness were identified by a marker that was adopted in 2009 replacing their recorded postal code with an XX designation. s. Aggregating by LHIN, date and week of year, we examine the overall number of patients experiencing homelessness and number by LHIN location and seasonality. Demographic outcomes examined include age and sex. Results: 640,897 visits to the ED over 7 years were made by 39,525 unique individuals experiencing homelessness. Number of ED visits has steadily increased over 10 years in all of Ontario, despite decline in shelter use for individuals. Presentations were concentrated in large urban centres like Toronto, Ottawa and Hamilton. Fewer presentations occur in the spring and summer months and rise in the winter. Male patients presented older and in greater numbers than female patients. The modal female age of presentation is in the 20-24 age category. The modal male age of presentation is in the 25-29 age category. Older male patients were more likely to have multiple presentations. Conclusion: The utilization of administrative health data offers a novel, cost-effective method to measure demographic characteristics of people experiencing homelessness. Identifying characteristics of homeless patients through this method allows for a more complete understanding of the characteristics of a hard-to-reach population, which will allow policy makers to develop appropriate services for this sub-group. Furthermore, through analysis of trends of demographics over time, changes in the homeless population can be tracked in real-time to allow for coordination and implementation of services in a time-sensitive manner.

Introduction: Administrative data can aid in study and intervention design, incorporating hard-to-reach individuals who may otherwise be poorly represented. We aim to use administrative health data to examine emergency department visits by people experiencing homelessness and explore the application of this data for planning interventions. Methods: We conducted a serial cross-sectional study examining emergency department use by people experiencing homelessness and non-homeless individuals in the Niagara region of Ontario, Canada. The study period included administrative health data from April 1st, 2010 to March 31st, 2018. Outcomes included number of visits, number of unique patients; group proportions of Canadian Triage and Acuity Scale (CTAS) scores; time spent in emergency; and time to see an MD. Descriptive statistics were generated, and t-tests were performed for point estimates and a Mann-Whitney U test for distributional measures. Results: Our data included 1,486,699 emergency department visits. The number of unique people experiencing homelessness ranged from 91 in 2010 to 344 in 2017, trending higher over the study period compared to non-homeless patients. The rate of visits increased from 1.7 to 2.8 per person. People experiencing homelessness tend to present later in the day and with higher overall acuity as compared to the general population. Time in emergency department and time to see an MD were greater among people experiencing homelessness. Conclusion: Administrative health data allows researchers to enhance interventions and models of care to improve services for vulnerable populations. Given the challenging fiscal realities of research, our study provides insights to more effectively target interventions for vulnerable populations.

Introduction: People experiencing homelessness have complex psychiatric and medical presentations, and have poor access to primary care. Thus, emergency departments (EDs) often become their main point of healthcare contact. Using routinely collected administrative data from EDs, we examine the ED utilization, health and reasons for presentations of people experiencing homelessness.. Methods: All routinely collected administrative health data from EDs located within Ontario, Canada from 2010-2017 were analyzed. Individuals experiencing homelessness were identified by a marker that was adopted in 2009 replacing their recorded postal code with an XX designation. Outcomes include number of unique patients, number of visits and repeat visits, CTAS scores, ambulance utilization, and type of ICD-10 presentation. Results: 640,897 visits to the ED over 10 years were made by 39,525 unique individuals experiencing homelessness. A visit to an ED by a homeless patient resulted in repeat presentation on the same day 5% of the time. The median repeat presentation to an ED was 14 days. In people experiencing homelessness, the most prevalent category of presentations were primary mental health diagnoses, accounting for 34.8% of visits (n = 223,392). Under mental health conditions, psychoactive substance use presentations made up more than 54% of the presentations (n = 121,112). Alcohol was by far the most common cause of substance use/induced disorders (n = 84,805). Conclusion: Applications of administrative data presents a novel method of measuring health and healthcare outcomes for marginalized populations. We found people experiencing homelessness are presenting to ED more frequently in Ontario, with significant mental health and addiction problems. Our study identifies several important health vulnerabilities within the population, which may serve as potential targets for future interventions.

Introduction: Understanding how homeless patients interact with healthcare systems can be challenging. The nature of the population is such that identifying and following these persons can be severely limited by data. Previous studies have used survey data which relies on self-reporting and selected samples such as those persons admitted to homeless shelters (Gray et al. 2011). Other studies have been able to leverage administrative data but only for selected local geographic areas (Somers et al. 2016, Tompkins et al 2003). It is possible that the current literature has not examined a large proportion of homeless persons and their healthcare use. This is concerning because this population can have higher associated medical costs and greater medical resource utilization especially with regards to psychiatric and emergency department (ED) resources (Tulloch et al. 2012, Forchuk et al, 2015). Methods: Administrative health data (2010 to 2017) is used to analyze ambulatory care records for homeless individuals in Ontario, Canada. Uniquely, we are able to use ED contacts as a way of identifying homeless migrations from region to region within Ontario. Using a network analysis we identify high impact ED nodes and discrete hospital networks where homeless patients congregate. We are also able to more fully characterize this population's demographics, health issues, and disposition from the ED. Results: We provide a more complete understanding of migration patterns for homeless individuals, across Ontario and their concomitant ED use and hospitalizations. The three most frequented regions in Ontario (n = 640,897) were Toronto Central (35.96%), Hamilton Niagara Halimand Brant (8.9%) and Champlain (7.84%). In subsequent visits, the majority of patients presented to different EDs, however a subgroup who always presented to the same site was present. Over the 7 year period, migration between visits occurred most often between urban areas, and increased as a whole. Conclusion: The results of the study allow for the enhancement care coordination for vulnerable populations and enhance the availability and delivery of services for sub-groups of homelessness whose care needs may differ based on migration patterns. Services can be coordinated between jurisdictions for homeless individuals, and appropriate referrals can be made across the health care system. Further evidence is provided for a novel method of mapping migration among the homeless and its associations and effects on ED use.

This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.