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Significance Statement Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.0% of them. We detected no significant differences in the overall diagnostic yield among COU subphenotypes, with characteristic variable expressivity of several mutant genes. Our findings therefore may legitimize a genetic first diagnostic approach for COU, especially when burdening clinical and imaging characterization is not complete or available. Background Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. Methods We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction (n=321), ureterovesical junction obstruction/congenital megaureter (n=178), and COU not otherwise specified (COU-NOS ; n=234). Results We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders (GDs) in 23 (3.1%) cases. We detected no significant differences in the overall diagnostic yield between COU sub-phenotypes, and pathogenic SNVs in several genes were associated to any of the three categories. Hence, although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. On the other hand, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and GDs suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU. Conclusions We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis.

Background: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. Methods: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. Results: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73–0.97]; P =0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76–0.95]; P =0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS P interaction =0.033, MCS P interaction =0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55–5.30]; P =0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction ( P interaction =0.002). Conclusions: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. Registration: URL: https://www.clinicaltrials.gov ; SYNTAXES Unique identifier: NCT03417050. URL: https://www.clinicaltrials.gov ; SYNTAX Unique identifier: NCT00114972.

BACKGROUND: In the TWILIGHT trial, ticagrelor monotherapy after a short course of dual antiplatelet therapy (DAPT) was shown to be a safe bleeding avoidance strategy in high-risk patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES). AIMS: The aim of this study was to evaluate the effects of ticagrelor monotherapy after three-month DAPT in patients undergoing PCI, according to DES type. METHODS: In the current sub-analysis from TWILIGHT, patients were stratified into three groups based on DES type: durable polymer everolimus-eluting stents (DP-EES), durable polymer zotarolimus-eluting stents (DP-ZES), and biodegradable polymer DES (BP-DES). Bleeding and ischaemic outcomes were assessed at one year after randomisation. RESULTS: Out of 5,769 patients, 3,014 (52.2%) had DP-EES, 1,350 (23.4%) had DP-ZES and 1,405 (24.4%) had BP-DES. Compared with ticagrelor plus aspirin, ticagrelor monotherapy had significantly lower BARC type 2, 3 or 5 bleeding compared with DAPT; DP-EES (3.8% vs 6.7%; HR 0.56, 95% CI: 0.41-0.78), DP-ZES (4.6% vs 6.9%; HR 0.66, 95% CI: 0.42-1.04) and BP-DES (4.2% vs 7.9%; HR 0.52, 95% CI: 0.33-0.81; p(interaction)=0.76). Ticagrelor monotherapy resulted in similar rates of death, MI, or stroke: DP-EES (4.2% vs 4.3%; HR 0.97; 95% CI: 0.68-1.37); DP-ZES (4.1% vs 3.1%; HR 1.32; 95% CI: 0.75-2.33); BP-DES (3.9% vs 4.2%; HR 0.92; 95% CI: 0.54-1.55; p(interaction)=0.60). In both unadjusted and covariate-adjusted analyses, DES type was not associated with any differences in ischaemic or bleeding complications. CONCLUSIONS: As compared with ticagrelor plus aspirin, ticagrelor monotherapy after a short DAPT duration lowered bleeding complications without increasing the ischaemic risk, irrespective of DES type. We observed no significant differences among DES types.

Near-infrared spectroscopy (NIRS) can measure tissue blood content and oxygenation; however, its use for adult neuromonitoring is challenging due to significant contamination from their thick extracerebral layers (ECL; primarily scalp and skull). This report presents a fast method for accurate estimation of adult cerebral blood content and oxygenation from hyperspectral time resolved NIRS (trNIRS) data. A two-phase fitting method, based on a two-layer head model (ECL and brain), was developed. Phase 1 uses spectral constraints to accurately estimate the baseline blood content and oxygenation in both layers, which are then used by Phase 2 to correct for the ECL contamination of the late-arriving photons. The method was validated with in silico data from Monte-Carlo simulations of hyperspectral trNIRS in a realistic model of the adult head obtained from a high-resolution MRI. Phase 1 recovered cerebral blood oxygenation and total hemoglobin with an accuracy of 2.7 ± 2.5 and 2.8 ± 1.8%, respectively, with unknown ECL thickness, and 1.5 ± 1.4 and 1.7 ± 1.1% when the ECL thickness was known. Phase 2 recovered these parameters with an accuracy of 1.5 ± 1.5 and 3.1 ± 0.9%, respectively. Future work will include further validation in tissue-mimicking phantoms with various top layer thicknesses and in a pig model of the adult head before human applications.

We construct a positivity-preserving Lie--Trotter splitting scheme with finite difference discretization in space for approximating the solutions to a class of nonlinear stochastic heat equations with multiplicative space-time white noise. We prove that this explicit numerical scheme converges in the mean-square sense, with rate $1/4$ in time and rate $1/2$ in space, under appropriate CFL conditions. Numerical experiments illustrate the superiority of the proposed numerical scheme compared with standard numerical methods which do not preserve positivity.

We introduce a positivity-preserving numerical scheme for a class of nonlinear stochastic heat equations driven by a purely time-dependent Brownian motion. The construction is inspired by a recent preprint by the authors where one-dimensional equations driven by space-time white noise are considered. The objective of this paper is to illustrate the properties of the proposed integrators in a different framework, by numerical experiments and by giving convergence results.

Background Persistence to P2Y12 inhibitors after myocardial infarction (MI) remains low. Out-of-pocket cost is cited as a factor affecting medication compliance. We examined whether a copayment intervention affected 1-year persistence to P2Y12 inhibitors and clinical outcomes. Methods and Results In an analysis of ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study), patients with MI discharged on a P2Y12 inhibitor were stratified by baseline out-of-pocket medication burden: low ($0-$49 per month), intermediate ($50-$149 per month), and high (≥$150 per month). The impact of the voucher intervention on 1-year P2Y12 inhibitor persistence was examined using a logistic regression model with generalized estimating equations. We assessed the rates of major adverse cardiovascular events among the groups using a Kaplan-Meier estimator. Among 7351 MI-treated patients at 282 hospitals, 54.2% patients were in the low copay group, 32.0% in the middle copay group, and 13.8% in the high copay group. Patients in higher copay groups were more likely to have a history of prior MI, heart failure, and diabetes compared with the low copay group (all P

The workhorse in the diagnosis of aortic stenosis (AS) has been transthoracic echocardiography (TTE) with clear-cut validated threshold values for grading it mild, moderate, or severe. However, up to one-third of patients may present with discordant findings on echo sonogram and may need further evaluation with other imaging modalities such as computed tomography (CT). CT is useful in determining aortic valve area (AVA) by planimetry and outperforms TTE in identifying severe AS in bicuspid aortic valve (BAV), but it is not routinely ordered for those purposes. It has been widely used in helping, determining, and grading the severity of AS by calculating aortic valve calcium (AVC) load with a scoring system. AVC scores of 2000 AU or more for men and 1300 AU for women are highly indicative of severe AS and have been associated with the poor outcomes. AVC score will underestimate AS in a minority of circumstances where the process is driven more by fibrosis than calcification. CT use is limited by its recent adoption into medical practice and, therefore, is still not universally available in every center. It requires additional training for providers and low-dose radiation exposure may be a concern for some patients.

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

database of computerized handwriting samples of BHK texts written by French children from 1st- to 5th-grade, with or without handwriting deficits

Systematic review of psychotropic drug RCTs (2000-2017) to examine uses of, and justifications for, drug discontinuation, and awareness of withdrawal symptoms.

Online supplementary material, source data, and other project-related files.

Supplementary Material 1: Table S1: Distribution of psychiatric Adverse Events during the quarterly follow-up

Additional file 1: Additional Table 1. Distribution of diagnosis categories at T1 and T2 in our study compared to that of the Rondeau et al. meta-analysis. Additional Table 2. Ratio of change of diagnosis category between T1 and T2 in our study compared to that of Rondeau et al. meta-analysis. Additional Figure. CARS evolution in our study compared to that of the Baghdadli French cohort study.

Additional file 2: Figure S1. Schematic structure of the microsimulation model. Figure S2. Model of internal validation. Internal validation of our microsimulation model shows agreement with the 4.5-year period of in-trial data across first stroke rates.

For her capstone project, Alexandra sought to interrogate the U.S. foreign policy approaches to Southeast Asia and ASEAN countries in particular with the result being a final published piece. The final product was published in the diplomacy section of The Diplomat as a feature article. Against the backdrop of the Biden administration’s current efforts to re-engage with ASEAN, Alexandra assessed the impact of the Ukraine conflict on US strategic commitments and presence in Southeast Asia. She analyzed how the US significantly increased its commitment to NATO amidst a major reorientation in the Indo-Pacific that has already begun, and how ASEAN states remain preoccupied with whether the US has the will to commit over the long term the necessary resources to support the Southeast Asian region and reflect its priorities in the region within its global security strategy. She argues that as doubt permeates the region, US success will rely on a policy approach that doesn’t succumb to reactionary pivots, but rather acknowledges the need for sustained US engagement in Southeast Asia that will be recognized as such by the different ASEAN Member States from each of their national perspectives as well as from the ASEAN point of view.

Second International Confernece on Inertial Confinement Fusion Sciences and Applications, Kyoto, Japan. September 10, 2001.

Additional file 1: Cost estimates for the rest of the first year or in post-CVD phase. Table S1. Lifetime cost-effectiveness results for each subgroup. Table S2. Baseline characteristics of the study participants. Table S3. Unit prices of drugs. Table S4. Costs of each treatment procedure. Table S5. Hazard ratios and parameters for scale and shape of the subgroup analysis.

Background Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders which core symptoms are impairments in socio-communication and repetitive symptoms and stereotypies. Although not cardinal symptoms per se, motor impairments are fundamental aspects of ASD. These impairments are associated with postural and motor control disabilities that we investigated using computational modeling and developmental robotics through human-machine interaction paradigms. Method First, in a set of studies involving a human–robot posture imitation, we explored the impact of 3 different groups of partners (including a group of children with ASD) on robot learning by imitation. Second, using an ecological task, i.e. a real-time motor imitation with a tightrope walker (TW) avatar, we investigated interpersonal synchronization, motor coordination and motor control during the task in children with ASD (n = 29), TD children (n = 39) and children with developmental coordination disorder (n = 17, DCD). Results From the human–robot experiments, we evidenced that motor signature at both groups’ and individuals’ levels had a key influence on imitation learning, posture recognition and identity recognition. From the more dynamic motor imitation paradigm with a TW avatar, we found that interpersonal synchronization, motor coordination and motor control were more impaired in children with ASD compared to both TD children and children with DCD. Taken together these results confirm the motor peculiarities of children with ASD despite imitation tasks were adequately performed. Discussion Studies from human-machine interaction support the idea of a behavioral signature in children with ASD. However, several issues need to be addressed. Is this behavioral signature motoric in essence? Is it possible to ascertain that these peculiarities occur during all motor tasks (e.g. posture, voluntary movement)? Could this motor signature be considered as specific to autism, notably in comparison to DCD that also display poor motor coordination skills? We suggest that more work comparing the two conditions should be implemented, including analysis of kinematics and movement smoothness with sufficient measurement quality to allow spectral analysis.

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file 9:(pdf file) Validation of microarray results by RT-qPCR. The Log 2 ratios were obtained either by RT-qPCR (a, b: -ΔΔCt) or by array analysis (c, d: intensity ratio). We compared the expression patterns of 4 selected genes in mature leaves (a, c) and of 5 selected genes in root apices (b, d). Gene models are given in Additional file 8. -ΔΔCt was calculated with PP2A as the housekeeping gene. (PDF 104 KB)

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Authors’ original file for figure 1

Additional file 8:(pdf file) Primer sequences used for RT-qPCR validation. (PDF 113 KB)

Authors’ original file for figure 5

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file 9:(pdf file) Validation of microarray results by RT-qPCR. The Log 2 ratios were obtained either by RT-qPCR (a, b: -ΔΔCt) or by array analysis (c, d: intensity ratio). We compared the expression patterns of 4 selected genes in mature leaves (a, c) and of 5 selected genes in root apices (b, d). Gene models are given in Additional file 8. -ΔΔCt was calculated with PP2A as the housekeeping gene. (PDF 104 KB)

Additional file 8:(pdf file) Primer sequences used for RT-qPCR validation. (PDF 113 KB)

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Authors’ original file for figure 3

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Additional file of Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

Authors’ original file for figure 2

Additional file 7:(pdf file) ABA-mediated drought response in poplar. Based on the literature and sequence homology with arabidopsis, putative ABA-related genes involved in drought response were identified. These genes were assigned to ABA biosynthesis (A, G), ABA-mediated signalling pathway (B, D), and response to ABA stimulus (C) as well as to cell rescue/detoxification process settled in response to ABA-mediated ROS production (H). Putative interactions with ABA-independent signalling pathway are shown (E). Genes (The Populus genome v1.1) and source are given in a table. Supporting literature [23, 42–60, 68, 76–86, 88, 91, 92, 109–113]. (PDF 25 KB)

Authors’ original file for figure 4

Additional file 2:(pdf file) Functional category enrichment analysis (SEA) among differentially expressed genes. For clarity, only the most enriched GO terms and their P- values are given for each pair comparison (treated vs respective control). SEA were performed independently for up and down regulated genes (no Log 2 ratio cut-off, P < 0.05). (PDF 288 KB)

No abstract available.

Coronavirus disease 2019 (COVID-19) has become a pandemic since first being described in January 2020. Clinical manifestations in non-transplant patients range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome, multiorgan system failure, and death. Limited reports in kidney transplant recipients suggest similar characteristics in that population. We report here the first case series of COVID-19 infection occurring in pancreas transplant recipients.

Supplemental material, EULT_manuals_070220 for Evaluation of the enhanced upper limb therapy programme within the Robot-Assisted Training for the Upper Limb after Stroke trial: descriptive analysis of intervention fidelity, goal selection and goal achievement by Helen Bosomworth, Helen Rodgers, Lisa Shaw, Leanne Smith, Lydia Aird, Denise Howel, Nina Wilson, Natasha Alvarado, Sreeman Andole, David L Cohen, Jesse Dawson, Cristina Fernandez-Garcia, Tracy Finch, Gary A Ford, Richard Francis, Steven Hogg, Niall Hughes, Christopher I Price, Laura Ternent, Duncan L Turner, Luke Vale, Scott Wilkes, Hermano I Krebs and Frederike van Wijck in Clinical Rehabilitation

New long Chandra grating observations of the O supergiant $��$ Pup show not only a brightening of the x-ray emission line flux of 13 per cent in the 18 years since Chandra's first observing cycle, but also clear evidence - at more than four sigma significance - of increased wind absorption signatures in its Doppler-broadened x-ray emission line profiles. We demonstrate this with non-parametric analysis of the profiles as well as Gaussian fitting and then use the line-profile model fitting to derive a mass-loss rate of $2.47 \pm 0.09 \times 10^{-6}$ Msun/yr, which is a 40 per cent increase over the value obtained from the cycle 1 data. The increase in the individual emission line fluxes is greater for short-wavelength lines than long-wavelength lines, as would be expected if a uniform increase in line emission is accompanied by an increase in the wavelength-dependent absorption by the cold wind in which the shock-heated plasma is embedded., Accepted by MNRAS. No longer a letter, but rather a nine page paper with several multi-panel figures showing all the line profiles. We have now included an analysis of the entire cycle 19 data set and present two model-independent confirmations of the line profile changes

Additional file 1:. Description of variables.

Additional file 1. Supplementary material DS1-EI 24 Months BMC Pediatrics. Per protocol analysis of the DS1-EI randomized controlled trial at 24 months. Table S1. Comparison at baseline (per protocol population, N = 63). Clinical characteristics at baseline of the per-protocol population by group. Table S2. Variables at 18-month outcome (PP population, N = 63). Changes according to time for CARS, ADI-R and PEP-3, by group. Table S3. Variables at 12- and 24-month outcome (PP population, N = 63). Changes according to time for VABS and CGAS, by group. Figure S1. Variables at 18-month outcome (PP population, N = 63). Changes according to time for CARS and PEP-3, by group. Figure S2. Variables at 12- and 24-month outcome (PP population, N = 63). Changes according to time for VABS and CGAS, by group.

Additional file 1. Table S1. Matching characteristics of the TD subgroups for machine learning. Table S2. Emotion production in children with ASD as a function of age, gender, group, order, modality, elicitation task, emotion and sites: results from the GLMM model. Table S3. Durations of videos during emotion production in children with ASD and TD children. Table S4. Radom forest classifier accuracy recognition of the FE. Table S5. Radom forest classifier accuracy recognition of FE when learning on TD group 1 or 2. Table S6. Confusion matrix when learning and testing on TD. Table S7. Confusion matrix when learning on TSA and testing on TSA. Table S8. Confusion matrix when learning on TD and testing on TSA. Table S9. Confusion matrix when learning on TD1 and testing on TD1. Table S10. Confusion matrix when learning on TD2 and testing on TD2. Figure S1. Histogram of the videos’ duration. Figure S2 and S3. Facial landmarks contributing to classification of anger using random forest (training and testing) in children with typical development (left) and children with autism spectrum disorder (S2: Distance; S3: HOG). Figure S4 and S5. Facial landmarks contributing to classification of neutral facial expression using random forest (training and testing) in children with typical development (left) and children with autism spectrum disorder (S4: Distance; S5: HOG). Figure S6 and S7. Facial landmarks contributing to classification of sadness using random forest (training and testing) in children with typical development (left) and children with autism spectrum disorder (S6: Distance; S7: HOG).