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Wearable sensors facilitate running kinematics analysis of joint kinematics in real running environments. The use of a few sensors or, ideally, a single inertial measurement unit (IMU) is preferable for accurate gait analysis. This study aimed to use a convolutional neural network (CNN) to predict level-ground running kinematics (measured by four IMUs on the lower extremities) by using treadmill running kinematics training data measured using a single IMU on the anteromedial side of the right tibia and to compare the performance of level-ground running kinematics predictions between raw accelerometer and gyroscope data. The CNN model performed regression for intraparticipant and interparticipant scenarios and predicted running kinematics. Ten recreational runners were recruited. Accelerometer and gyroscope data were collected. Intraparticipant and interparticipant R2 values of actual and predicted running kinematics ranged from 0.85 to 0.96 and from 0.7 to 0.92, respectively. Normalized root mean squared error values of actual and predicted running kinematics ranged from 3.6% to 10.8% and from 7.4% to 10.8% in intraparticipant and interparticipant tests, respectively. Kinematics predictions in the sagittal plane were found to be better for the knee joint than for the hip joint, and predictions using the gyroscope as the regressor were demonstrated to be significantly better than those using the accelerometer as the regressor.

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) premRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 copies of SMN2.SUNFISH (NCT02908685) is a two-part, randomised, placebocontrolled, double-blind study in a broad population of patients aged 2–25 years with Type 2/3 SMA. Part 2 assesses the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. Participants were treated with risdiplam or placebo for 12 months; all participants then received risdiplam until Month 24. At Month 24, patients were offered the opportunity to enter the openlabel extension.The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Gains observed with risdiplam at Month 12 were maintained or improved upon at Month 24. At Month 24, there were no treatment-related safety findings leading to withdrawal. Here we present efficacy and safety data of patients who have received risdiplam for 36 months.

Risdiplam (EVRYSDI®) is an oral survival of motor neuron 2 (SMN2) premRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months, with a clinical diagnosis of Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 copies of SMN2.SUNFISH (NCT02908685) is a two-part, randomised, placebo-controlled, double-blind study in a broad population of patients aged 2–25 years at enrolment, with Type 2/3 SMA. Part 2 assesses the efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and nonambulant Type 3 SMA. Participants were treated with risdiplam or placebo for 12 months; all participants then received risdiplam until Month 24, when patients were offered the opportunity to enter the open-label extension.The primary outcome of Part 2 – change from baseline to Month 12 in the 32-item Motor Function Measure total score in patients treated with risdiplam (n=120) versus placebo (n=60) – was met. Here we present analyses to compare 24-month data from the risdiplam arm with an external comparator dataset con- taining data from participants in the NatHis-SMA study (NCT02391831) and the placebo arm of a Phase 2 study of olesoxime in patients with SMA (NCT01302600).

Risdiplam (EVRYSDI®) is an oral survival of motor neuron (SMN2) pre-mRNA splicing modifier approved by the EMA and MHRA for the treatment of patients aged ≥2 months with Type 1, 2 or 3 spinal muscular atrophy (SMA) or 1–4 SMN2 copies.SUNFISH (NCT02908685) is a two-part, randomised, placebo-controlled, double-blind study in patients with Types 2/3 SMA aged 2–25 years at enrolment. Part 2 (N=180) assessed efficacy and safety of the Part 1-selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. Participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until Month 24, when they entered the open-label extension.The primary endpoint (Part 2) of change from baseline in the 32-item Motor Function Measure (MFM32) total score in patients receiving risdiplam (n=120) versus placebo (n=60) was met at Month 12. Motor function increases were sustained in the second and third year after risdiplam treatment (assessed by the MFM32, Hammersmith Functional Motor Scale – Expanded and Revised Upper Limb Module). At Month 36, no safety findings led to treatment withdrawal in SUNFISH Part 1 or 2.Here we present 4-year efficacy and safety data from SUNFISH.

The concentrations of polychlorinated dibenzo- p -dioxins/dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (PCBs), and polychlorinated naphthalenes (PCNs) were measured in two sediment cores collected from Jiaozhou Bay. The concentrations of PCDD/Fs, dioxin-like PCBs, and PCNs in the cores were in the range of 2.8–26.3, 7.1–82.4 and 3.9–56.4 pg/g dw, respectively. The depth profiles of total concentrations PCDD/Fs and dioxin-like PCBs were similar in the sediment core J37 inside Jiaozhou Bay, but different from those in the sediment core J94 outside the bay, suggesting the different sources. In both cores Tri-CNs and Tetra-CNs were dominant, similar to the PCNs composition of some Halowax technical products. The maximal PCNs contamination occurred in the mid-1970s (outside the Bay) and early-1990s (inside the Bay). An increase of the indicator CN congeners characteristic for thermal source in the top layers of the sediment core inside the bay indicated that the contribution from the municipal solid waste incineration has been more important in recent years.

Risdiplam is an oral, survival of motor neuron 2 ( SMN2 ) pre-mRNA splicing modifier approved for the treatment of spinal muscular atrophy (SMA). SUNFISH (NCT02908685) Part 2, a Phase 3, randomized, double-blind, placebo-controlled study, investigated the efficacy and safety of risdiplam in type 2 and non‑ambulant type 3 SMA. The primary endpoint was met: a significantly greater change from baseline in 32-item Motor Function Measure (MFM32) total score was observed with risdiplam compared with placebo at month 12. After 12 months, all participants received risdiplam while preserving initial treatment blinding. We report 24-month efficacy and safety results in this population. Month 24 exploratory endpoints included change from baseline in MFM32 and safety. MFM‑derived results were compared with an external comparator. At month 24 of risdiplam treatment, 32% of patients demonstrated improvement (a change of ≥ 3) from baseline in MFM32 total score; 58% showed stabilization (a change of ≥ 0). Compared with an external comparator, a treatment difference of 3.12 (95% confidence interval [CI] 1.67–4.57) in favor of risdiplam was observed in MFM-derived scores. Overall, gains in motor function at month 12 were maintained or improved upon at month 24. In patients initially receiving placebo, MFM32 remained stable compared with baseline (0.31 [95% CI – 0.65 to 1.28]) after 12 months of risdiplam; 16% of patients improved their score and 59% exhibited stabilization. The safety profile after 24 months was consistent with that observed after 12 months. Risdiplam over 24 months resulted in further improvement or stabilization in motor function, confirming the benefit of longer-term treatment.

The original version of this article unfortunately contained a mistake. The corrected details are given below for your reading. In figure 1, there is an error in the n numbers below the graph in Panel 1b for the placebo group. The n numbers underneath Panel 1b should be 58 58 50. There is an error within Fig. 4. The dashed lines at ~ − 1.4 should be at 0. They have been moved downwards and are no longer in the correct place. The corrected Figs. 1 and 4 are given in the following page. (Figure presented.) (Figure presented.) Change from baseline in MFM32 total score in patients treated with risdiplam for up to 24 months and those who previously received placebo until study month 12. aThirty-one percent (55/180) of the SUNFISH intent-to-treat population were 2–5 years old at baseline. b± 95% CI. cBaseline is the last measurement prior to the first dose of risdiplam or placebo. dData cut-off: 30 Sep 2020. eData cut-off: 6 Sep 2019. fPatients in the placebo arm received placebo for 12 months followed by risdiplam treatment for 12 months. gNumber of patients with valid results = number of patients with an available total score (result) at respective time points. Intent-to-treat patients. hPatients in the placebo arm received placebo for 12 months followed by risdiplam treatment for 12 months. Placebo period not shown in this graph. CI confidence interval, MFM32 32-item motor function measure Change in caregiver- and patient-reported SMAIS upper limb total score from baseline in patients receiving risdiplam for up to 24 months and those who previously received placebo up to study month 12. a± 95% CI. Baseline is the last measurement prior to the first dose of risdiplam or placebo. bData cut-off: 30 Sep 2020. cData cut-off: 6 Sep 2019. dPatients in the placebo arm received placebo for 12 months followed by risdiplam treatment for 12 months. Risdiplam period not shown in this graph. eNumber of patients with valid results = number of patients with an available total score (result) at respective time points. Intent-to-treat patients. SMAIS scores range from 0 to 44 following rescoring to a 0–2 response scale for each item. Higher scores indicate greater independence in completing daily activities. CI confidence interval, SMA spinal muscular atrophy, SMAIS SMA Independence Scale, SMAIS-ULM SMA Independence Scale-Upper Limb Module.

Randomization schemes for two-treatment clinical trials are studied. Theoretical expressions for the power are derived under both complete randomization and Efron’s biased coin design for normal and binary responses. The better the scheme is at balancing the numbers of patients across treatments, the higher the power is. Efron’s biased coin design is more powerful than complete randomization. Normal approximations to the powers are obtained. The power of the adjustable biased coin design is also investigated by simulation. Covariate-adaptive randomization schemes are analysed when either global or marginal balance across cells is sought. By considering a fixed-effects linear model for normal treatment responses with several covariates, an analysis of covariance t test is carried out. Its power is simulated for global and marginal balance, both in the absence and in the presence of interactions between the covariates. Global balancing covariate-adaptive schemes are more efficient when there are interactions between the covariates. Restricted randomization schemes for more than two treatments are then considered. Their asymptotic properties are provided. An adjustable biased coin design is introduced for which assignments are based on the imbalance across treatments. The finitesample properties of the imbalance under these randomization schemes are studied by simulation. Assuming normal treatment responses, the power of the test for treatment differences is also obtained and is highest for the new design. Imbalance properties of complete randomization and centre-stratified permuted block randomization for several treatments are investigated. It is assumed that the patient recruitment process follows a Poisson-gamma model. When the number of centres is large, the imbalance for both schemes is approximately multivariate normal. The power of a test for treatment differences is simulated for normal responses. The loss of power can be compensated for by a small increase in sample size.

Predictable stereoselective formation of supramolecular assembly is generally believed to be an important but complicated process. Here, we show that point chirality of a ligand decisively influences its supramolecular assembly behavior. We designed three closely related chiral ligands with different point chiralities, and observe their self-assembly into europium (Eu) tetrametallic tetrahedral cages. One ligand exhibits a highly diastereoselective assembly into homochiral (either ΔΔΔΔ or ΛΛΛΛ) Eu tetrahedral cages whereas the two other ligands, with two different approaches of loosened point chirality, lead to a significant breakdown of the diastereoselectivity to generate a mixture of (ΔΔΔΔ and ΛΛΛΛ) isomers. The cages are highly emissive (luminescence quantum yields of 16(1) to 18(1)%) and exhibit impressive circularly polarized luminescence properties (| g lum |: up to 0.16). With in-depth studies, we present an example that correlates the nonlinear enhancement of the chiroptical response to the nonlinearity dependence on point chirality. Controlling the chirality of self-assembled polyhedra is a synthetic challenge. Here, the authors stereoselectively form emissive lanthanide tetrahedral cages from a series of chiral ligands, and use their circularly polarized luminescence to explore the effect of ligand point chirality on supramolecular architecture.