Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.

Background: Despite efforts toward gender equality in clinical trial enrollment, females are frequently underrepresented and gender-specific data analysis is often unavailable. The purpose of this study was to determine if gender equality exists in the management of degenerative lumbar disease. Methods: Part 1: A systematic scoping review was conducted according to PRISMA guidelines, in order to synthesize the adult surgical literature regarding gender differences in pre- and post-operative clinical assessment scores for patients diagnosed with degenerative lumbar disease.

Part 2: An ambispective cohort analysis (multi-variate logistic regression) of the Canadian Spine Outcomes Research Network registry was performed to address knowledge gaps identified in “Part 1”. Results: Part 1: Thirty articles were identified, accounting for 32,951 patients. Female patients have worse absolute pre-operative pain, disability and health-related quality-of-life (HRQoL). Following surgery, females have worse absolute pain, disability, and HRQoL, but demonstrate an equal or greater interval change compared to males.

Part 2: Data was analyzed for 5,039 patients. Significant gender differences in pre-operative utilization of healthcare resources (medication use, diagnostic testing, medical and allied healthcare professional visits) were identified. Conclusions: Significant gender disparities in clinical assessment scores and the pre-operative utilization of healthcare resources were identified for patients undergoing surgery for degenerative lumbar disease.

We present the most sensitive and detailed view of the neutral hydrogen ( ${\rm H\small I}$ ) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ( $1.6\,\mathrm{mJy\ beam}^{-1}$ ) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ ( ${\sim}10\,\mathrm{pc}$ ). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.

Background: Despite efforts toward gender equality in clinical trial enrollment, females are frequently underrepresented and gender-specific data analysis is often unavailable. The purpose of this study was to determine if gender equality exists in the management of degenerative lumbar disease. Methods: Part 1: A systematic scoping review was conducted according to PRISMA guidelines, in order to synthesize the adult surgical literature regarding gender differences in pre- and post-operative clinical assessment scores for patients diagnosed with degenerative lumbar disease.

Part 2: An ambispective cohort analysis (multi-variate logistic regression) of the Canadian Spine Outcomes Research Network registry was performed to address knowledge gaps identified in “Part 1”. Results: Part 1: Thirty articles were identified, accounting for 32,951 patients. Female patients have worse absolute pre-operative pain, disability and health-related quality-of-life (HRQoL). Following surgery, females have worse absolute pain, disability, and HRQoL, but demonstrate an equal or greater interval change compared to males.

Part 2: Data was analyzed for 5,039 patients. Significant gender differences in pre-operative utilization of healthcare resources (medication use, diagnostic testing, medical and allied healthcare professional visits) were identified. Conclusions: Significant gender disparities in clinical assessment scores and the pre-operative utilization of healthcare resources were identified for patients undergoing surgery for degenerative lumbar disease.

Background: Decisions to treat large-vessel occlusion with endovascular therapy(EVT) or intravenous alteplase depend on how physicians weigh benefits against risks when considering patients’ pre-stroke comorbidities. Methods: In an international survey, experts chose treatment approaches under current resources and under assumed ideal conditions for 10 of 22 randomly assigned case-scenarios. Five included comorbidities(metastatic/non-metastatic cancer, cardiac/respiratory/renal disease, non-disabling/mild cognitive impairment[MCI], physical dependence). We examined scenario/respondent characteristics associated with EVT/alteplase decisions using multivariable logistic regressions. Results: Among 607 physicians(38 countries), EVT was favoured in 1,097/1,379(79.6%) responses for comorbidity-related scenarios under current resources versus 1,510/1,657(91.1%,OR:0.38, 95%CI.0.31-0.47) for six “level-1A” scenarios (assuming ideal conditions:82.7% vs 95.1%,OR:0.25,0.19-0.33). However, this was reversed on including all other scenarios(e.g. under current resources:3,489/4,691[74.4%], OR:1.34,1.17-1.54). Responses favouring alteplase for comorbidity-related(e.g.75.0% under current resources) scenarios were comparable to level-1A scenarios(72.2%) and higher than all others(60.4%). No comorbidity-related factor independently diminished EVT-odds. MCI and dependence carried higher alteplase-odds; cancer and cardiac/respiratory/renal disease had lower odds. Relevant respondent characteristics included performing more EVT cases/year (higher EVT, lower alteplase-odds), practicing in East-Asia (higher EVT-odds), and in interventional neuroradiology(lower alteplase-odds vs neurology). Conclusions: Moderate-to-severe comorbidities did not consistently deter experts from EVT, suggesting equipoise about withholding EVT based on comorbidities. However, alteplase was often foregone when respondents chose EVT.

N6-Methyladenosine (m6A) regulates oocyte-to-embryo transition and the reprogramming of somatic cells into induced pluripotent stem cells. However, the role of m6A methylation in porcine early embryonic development and its reprogramming characteristics in somatic cell nuclear transfer (SCNT) embryos are yet to be known. Here, we showed that m6A methylation was essential for normal early embryonic development and its aberrant reprogramming in SCNT embryos. We identified a persistent occurrence of m6A methylation in embryos between 1-cell to blastocyst stages and m6A levels abruptly increased during the morula-to-blastocyst transition. Cycloleucine (methylation inhibitor, 20 mM) treatment efficiently reduced m6A levels, significantly decreased the rates of 4-cell embryos and blastocysts, and disrupted normal lineage allocation. Moreover, cycloleucine treatment also led to higher levels in both apoptosis and autophagy in blastocysts. Furthermore, m6A levels in SCNT embryos at the 4-cell and 8-cell stages were significantly lower than that in parthenogenetic activation (PA) embryos, suggesting an abnormal reprogramming of m6A methylation in SCNT embryos. Correspondingly, expression levels of m6A writers (METTL3 and METTL14) and eraser (FTO) were apparently higher in SCNT 8-cell embryos compared with their PA counterparts. Taken together, these results indicated that aberrant nuclear transfer-mediated reprogramming of m6A methylation was involved in regulating porcine early embryonic development.

This paper provides a solution to the active vibration control of a microsatellite with two solar panels. At first, the microsatellite is processed as a finite element model containing a rigid body and two flexible bodies, according to the principles of mechanics, and that the dynamic characteristics are solved by modal analysis. Secondly, the equation involving vibration control is established according to the finite element calculation results. There are several actuators composed of macro fibre composite on the two solar panels for outputting control force. Furthermore, the control voltage for driving actuator is calculated by using fuzzy algorithm. It is clear that the smart structure consists of the flexible bodies and actuators. Finally, the closed-loop control simulation for suppressing harmful vibration is established. The simulation results illustrate that the responses to the external excitation are decreased significantly after adopting fuzzy control.

In the American continent, the sugarcane borer Diatraea saccharalis (F.) is the main pest in sugarcane producing areas. The objective of this study was to assess the effect of crop residue management on damage by D. saccharalis, its egg parasitoids and the ants associated with sugarcane. The study was carried out during 2011–2012, 2012–2013 and 2013–2014 crop cycles, in three commercial fields located in different regions of Tucumán state, Argentina. Two types of crop residue management (= treatments) were compared: conservation of trash at the soil surface (CT) and trash burning (TB). In ‘trash conservation’ treatment, crop residue was allowed to remain over the soil surface during the whole sugarcane growing season, while the second treatment consisted of complete burning of trash blanket approximately 2 weeks after harvest. The injury level was measured by recording the number of stalks bored and internodes bored. Parasitism was estimated by counting the total number of eggs and number of black eggs (which indicates the occurrence of egg parasitoids). Ants (Formicidae) richness was calculated by two estimators; abundance-based coverage estimator and incidence-based coverage estimator, using the non-parametric richness estimators: Chao 2 and Jackknife. Finally, the indicator value was estimated through the measurement of specificity and fidelity. In all the parameters studied no significant difference was found between TB and CT treatments.

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.

Raw milk cheeses are commonly consumed in France and are also a common source of foodborne outbreaks (FBOs). Both an FBO surveillance system and a laboratory-based surveillance system aim to detect Salmonella outbreaks. In early August 2018, five familial FBOs due to Salmonella spp. were reported to a regional health authority. Investigation identified common exposure to a raw goats' milk cheese, from which Salmonella spp. were also isolated, leading to an international product recall. Three weeks later, on 22 August, a national increase in Salmonella Newport ST118 was detected through laboratory surveillance. Concomitantly isolates from the earlier familial clusters were confirmed as S. Newport ST118. Interviews with a selection of the laboratory-identified cases revealed exposure to the same cheese, including exposure to batches not included in the previous recall, leading to an expansion of the recall. The outbreak affected 153 cases, including six cases in Scotland. S. Newport was detected in the cheese and in the milk of one of the producer's goats. The difference in the two alerts generated by this outbreak highlight the timeliness of the FBO system and the precision of the laboratory-based surveillance system. It is also a reminder of the risks associated with raw milk cheeses.

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.