Short-range translocation by a restriction enzyme motor triggers diffusion along DNA.

Cleavage of bacteriophage DNA by the Type III restriction-modification enzymes requires long-range interaction between DNA sites. This is facilitated by one-dimensional diffusion ('DNA sliding') initiated by ATP hydrolysis catalyzed by a superfamily 2 helicase-like ATPase. Here we combined ultrafast twist measurements based on plasmonic DNA origami nano-rotors with stopped-flow fluorescence and gel-based assays to examine the role(s) of ATP hydrolysis. Our data show that the helicase-like domain has multiple roles. First, this domain stabilizes initial DNA interactions alongside the methyltransferase subunits. Second, it causes environmental changes in the flipped adenine base following hydrolysis of the first ATP. Finally, it remodels nucleoprotein interactions via constrained translocation of a ∼ 5 to 22-bp double stranded DNA loop. Initiation of DNA sliding requires 8-15 bp of DNA downstream of the motor, corresponding to the site of nuclease domain binding. Our data unify previous contradictory communication models for Type III enzymes.

Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Nonlinear Stiffness and Nonlinear Damping in Atomically Thin MoS2 Nanomechanical Resonators.

We report on experimental measurements and quantitative analyses of nonlinear dynamic characteristics in ultimately thin nanomechanical resonators built upon single-layer, bilayer, and trilayer (1L, 2L, and 3L) molybdenum disulfide (MoS2) vibrating drumhead membranes. This synergistic study with calibrated measurements and analytical modeling on observed nonlinear responses has led to the determination of nonlinear damping and stiffness coefficients at cubic and quintic orders for these two-dimensional (2D) resonators operating in the very high frequency (VHF) band (up to ∼90 MHz). We find that the quintic force can be ∼20% of the Duffing force at larger amplitudes, and thus, it generally cannot be ignored in a nonlinear dynamics analysis. This study provides the first quantification of nonlinear damping and frequency detuning characteristics in 2D semiconductor nanomechanical resonators and elucidates their origins and dependency on engineerable parameters, setting a foundation for future exploration and utilization of the rich nonlinear dynamics in 2D nanomechanical systems.

Evaluation of Escherichia coli Inactivation at High Altitudes Using Solar Water Disinfection.

INTRODUCTION: Solar disinfection (SODIS) is an effective method for microbiologic inactivation of contaminated water using ultraviolet rays at low elevations. The aim of this study was to determine the effectiveness of SODIS at higher elevations. METHODS: The ability of SODIS to inactivate Escherichia coli bacteria was evaluated at an altitude of ≥1600 m using Nalgene bottles, disposable plastic water bottles, and Ziploc plastic bags. Bacterial viability was determined through measurement of colony forming units (CFUs). Decreases in CFUs were determined at each time point relative to those at the baseline, and a multivariable regression analysis was used to assess significant changes in CFUs. RESULTS: Bacterial CFUs in exposed containers decreased by >5 log after 6 h of exposure to sunlight. In contrast, the CFUs remained nearly unchanged in unexposed containers, showing a mean decrease of 0.3 log. By 2 h, bacterial inactivation at high altitudes was 1.7-fold greater than that at lower altitudes (P<0.05). By 6 h, nearly all bacteria were inactivated at high or low altitudes. At 6 h, no statistical difference was observed in the efficiency of inactivation between elevations. Compared with Nalgene bottles, plastic bottles had a 1.4-fold greater decrease in CFUs (P<0.05). No statistical difference in bacterial inactivation was found between plastic bottles and plastic bags. CONCLUSIONS: At high altitudes, SODIS is an effective method for inactivating E coli. Further research investigating other microorganisms is warranted to determine whether SODIS is suitable for disinfecting contaminated water at high altitudes.

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study.

BACKGROUND: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019. METHODS: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. RESULTS: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. CONCLUSION: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Human amniotic fluid stem cells can improve cerebral vascular remodelling and neurological function after focal cerebral ischaemia in diabetic rats.

Diabetes causes vascular injury and carries a high risk of ischaemic stroke. Human amniotic fluid stem cells (hAFSCs) can enhance cerebral vascular remodelling and have the potential to improve neurological function after stroke in diabetic rats. Five groups of female rats were examined: (1) normal control, (2) type 1 diabetic (T1DM) rats induced by streptozotocin injection (DM), (3) non-DM rats receiving 60-minute middle cerebral artery occlusion (MCAO), (4) T1DM rats receiving 60-minute MCAO (DM + MCAO) and (5) T1DM rats receiving 60-minute MCAO and injection with 5 × 106  hAFSCs at 3 h after MCAO (DM + MCAO + hAFSCs). Neurological function was examined before, and at 1, 7, 14, 21 and 28 days, and cerebral infarction volume and haemorrhage, cerebral vascular density, angiogenesis and inflammatory were examined at 7 and 28 days after MCAO. hAFSCs treatment caused a significant improvement of neurological dysfunction, infarction volume, blood-brain barrier leakage, cerebral arterial density, vascular density and angiogenesis and a reduction of brain haemorrhage and inflammation compared with non-treatment. Our results showed that the effect of hAFSCs treatment against focal cerebral ischaemia may act through the recovery of vascular remodelling and angiogenesis and the reduction of inflammation in ischaemic brain.

IGF-1 infusion to fetal sheep increases organ growth but not by stimulating nutrient transfer to the fetus.

Insulin-like growth factor-1 (IGF-1) is an important fetal growth factor. However, the role of fetal IGF-1 in increasing placental blood flow, nutrient transfer, and nutrient availability to support fetal growth and protein accretion is not well understood. Catheterized fetuses from late gestation pregnant sheep received an intravenous infusion of LR3 IGF-1 (LR3 IGF-1; n = 8) or saline (SAL; n = 8) for 1 wk. Sheep then underwent a metabolic study to measure uterine and umbilical blood flow, nutrient uptake rates, and fetal protein kinetic rates. By the end of the infusion, fetal weights were not statistically different between groups (SAL: 3.260 ± 0.211 kg, LR3 IGF-1: 3.682 ± 0.183; P = 0.15). Fetal heart, adrenal gland, and spleen weights were higher (P < 0.05), and insulin was lower in LR3 IGF-1 (P < 0.05). Uterine and umbilical blood flow and umbilical uptake rates of glucose, lactate, and oxygen were similar between groups. Umbilical amino acid uptake rates were lower in LR3 IGF-1 (P < 0.05) as were fetal concentrations of multiple amino acids. Fetal protein kinetic rates were similar. LR3 IGF-1 skeletal muscle had higher myoblast proliferation (P < 0.05). In summary, LR3 IGF-1 infusion for 1 wk into late gestation fetal sheep increased the weight of some fetal organs. However, because umbilical amino acid uptake rates and fetal plasma amino acid concentrations were lower in the LR3 IGF-1 group, we speculate that animals treated with LR3 IGF-1 can efficiently utilize available nutrients to support organ-specific growth in the fetus rather than by stimulating placental blood flow or nutrient transfer to the fetus.NEW & NOTEWORTHY After a 1-wk infusion of LR3 IGF-1, late gestation fetal sheep had lower umbilical uptake rates of amino acids, lower fetal arterial amino acid and insulin concentrations, and lower fetal oxygen content; however, LR-3 IGF-1-treated fetuses were still able to effectively utilize the available nutrients and oxygen to support organ growth and myoblast proliferation.

Current update of first trimester preeclampsia screening in Asia.

In consideration of high prevalence of preeclampsia, enormous studies attempted to look for strategies in early gestation. Hence, a powerful screening should be built up in first trimester. Then, Aspirin could be administrated for proper prevention. The objective of this article is reviewing the screening for preeclampsia in first trimester recently. To identify the high-risk group precisely, an effective model should be recommended to Asian population. Articles related to first trimester screening of PE in Asia from databases of PubMed, ScienceDirect and Scopus were searched for this narrative review. The criteria included randomized clinical trials, observational prospective and retrospective cohort studies, case-control studies, systematic review and meta-analysis and professional review articles. Screening models combining maternal factors, biophysical factors, ultrasound studies and biochemical factors achieved high predictive performance of preeclampsia. In Asia, the detection rate of the Fetal Medicine Foundation is superior to those of the American College of Obstetricians and Gynecologists and the National Institute for Health and Care Excellence. Consequently, this effective model from the Fetal Medicine Foundation should be continuously used for screening in first trimester for the Asian.

Two-year outcome after implantation of a full magnetically levitated left ventricular assist device: results from the ELEVATE Registry.

AIMS: The ELEVATE Registry was designed to study long-term outcomes with the Heartmate 3 (HM3), a fully magnetically levitated centrifugal ventricular assist device, in a real-world population following CE-mark approval. METHODS AND RESULTS: A total of 540 patients, implanted in Europe and the Middle East were followed in ELEVATE. The registry included 463 patients receiving the HM3 as primary implant (Primary Implant Cohort), 19 patients underwent a pump upgrade from another device (Pump Exchange Cohort) and 58 patients who had experienced an outcome before having the possibility to sign the Informed Consent, for which only outcome data were collected (Anonymized Cohort). Data collection included demographics, survival, adverse events, EQ-5D Visual Analog Score quality of life (EQ-5D VAS QOL) questionnaire, and 6-min walk distance (6MWD). Mean age was 55.6 ± 11.7 years (89% male, 48% ischaemic cardiomyopathy). Seventy per cent of patients were in INTERMACS Profile 1-3 and 12.7% were on temporary mechanical circulatory support. Primary Implant Cohort survival was 83% after 2 years. In the Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Primary Implant Cohort, strokes were observed in 10.2%, gastrointestinal bleedings in 9.7%, pump thrombosis in 1.5%, and outflow graft twists in 3.5%. Heartmate 3 implantation resulted in a significant and sustained improvement of functional capacity and QOL. CONCLUSION: In a real-world population, cohort implanted with the HM3 left ventricular assist device we demonstrate good long-term survival, sustained improvement of functional capacity, and low rates of adverse events (including pump thrombosis). CLINICALTRIALS.GOV IDENTIFIER: NCT02497950.

A Taiwan's experience: A case report and review of literature of successful early intrauterine treatment with radiofrequency ablation in twin reversed arterial perfusion (TRAP) sequence.

Acardiac twin or twin reversed arterial perfusion (TRAP) sequence is a rare medical complication of Monozygotic twins. Taiwanese Obstetricians usually treat TRAP sequence conservatively. Occasionally, repeated amnio-reduction is performed to decompress the polyhydramnios caused by the TRAP sequence, even though there was no correction of the pathophysiologic mechanism. Radiofrequency ablation is a minimally invasive, percutaneous technique that can effectively obliterate blood supply to an acardiac twin to preserve and protect the pump twin. This recent technique has never been used before for the treatment of the TRAP sequence in Taiwan. This article reported the first-hand experience of acardiac twin management with RFA in Taipei Chang Gung Memorial Hospital.

Taiwanese Clinical Experience with Noninvasive Prenatal Testing for DiGeorge Syndrome.

OBJECTIVE: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. METHODS: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. RESULTS: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57-100.00%) and 99.92% (95% CI 99.83-99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14-76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. DISCUSSION/CONCLUSION: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention.

Predictors of Physical Capacity 6 Months After Implantation of a Full Magnetically Levitated Left Ventricular Assist Device: An Analysis From the ELEVATE Registry.

BACKGROUND: In patients with a continuous-flow left ventricular assist device, preimplant predictors of poor physical performance are not well-described. We aimed to identify predictors of inability to walk more than 300 m on 6-minute walk test (6MWT) 6 months after HeartMate 3 implantation. METHODS AND RESULTS: Using data from the European Registry of Patients Implanted With a Full Magnetically Levitated LVAD, patients with available 6MWT at 6 months after implantation were included (N = 194) and grouped according to 6MWT distance (6MWD) of >300 m (n = 150) or 6MWD of <300 m (n = 44). Patients walking <300 m were older (60 ± 10 vs 52 ± 12 years; P < .001), more often New York Heart Association functional class IV (63% vs 42%; P = .03), and more often had type 2 diabetes (43% vs 17%; P < .001) at implantation. Atrial fibrillation was seen in 57% in those with a 6MWT of <300 m vs 31% in those walking longer (P < .002). Further, hemoglobin and estimated glomerular filtration rate was lower in those walking <300 m (both P < .01). In multivariable regression analysis, independent predictors of a 6MWD of <300 m were: atrial fibrillation (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.12-8.67), older age (OR for 10-year increment, 2.81; 95% CI, 1.55-5.07), New York Heart Association functional class IV (OR, 3.37; 95% CI, 1.27-8.98), and Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (OR, 6.53; 95% CI, 1.92-22.19). CONCLUSIONS: Six months after HeartMate 3 implantation, 77% of patients walked >300 meters in 6 minutes. Apart from age and measures of heart failure severity, atrial fibrillation at implantation is an independent predictor of low 6MWD at 6 months after implantation.

Pulmonary Alveolar Microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive disorder that is caused by mutations in SCL34A2 that encodes for the type IIb sodium-dependent phosphate cotransporter (Npt2b). The loss of Npt2b transporter function from alveolar epithelial cells results in failure to export inorganic phosphate from the alveolar lining fluid, which then accumulates, binds to calcium, and forms hydroxyapatite microliths. Radiographs and computed tomography of the chest demonstrate hyperdense infiltrates that are often quite dramatic and distinctive, and in many cases, the diagnosis can be made without invasive measures. The most common presenting symptom of PAM is dyspnea on exertion, but the disease is frequently first noted as an incidental finding in asymptomatic patients who have chest films performed for unrelated reasons. Pulmonary fibrosis, pulmonary hypertension, and respiratory failure can develop as the disease progresses, and treatment remains supportive. Lung transplantation is an option for those with end stage disease.

Fetal surgery and stem cell therapy for meningomyelocele.

PURPOSE OF REVIEW: To review the advance of maternal--fetal surgery, the research of stem cell transplantation and tissue engineering in prenatal management of fetal meningomyelocele (fMMC). RECENT FINDINGS: Advance in the imaging study provides more accurate assessment of fMMC in utero. Prenatal maternal--fetal surgery in fMMC demonstrates favourable postnatal outcome. Minimally invasive fetal surgery minimizes uterine wall disruption. Endoscopic fetal surgery is performed via laparotomy-assisted or entirely percutaneous approach. The postnatal outcome for open and endoscopic fetal surgery shares no difference. Single layer closure during repair of fMMC is preferred to reduce postnatal surgical intervention. All maternal--fetal surgeries impose anesthetic and obstetric risk to pregnant woman. Ruptured of membrane and preterm delivery are common complications. Trans-amniotic stem cell therapy (TRASCET) showed potential tissue regeneration in animal models. Fetal tissue engineering with growth factors and dura substitutes with biosynthetic materials promote spinal cord regeneration. This will overcome the challenge of closure in large fMMC. Planning of the maternal--fetal surgery should adhere to ethical framework to minimize morbidity to both fetus and mother. SUMMARY: Combination of endoscopic fetal surgery with TRASCET or tissue engineering will be a new vision to achieve to improve the outcome of prenatal intervention in fMMC.

Prospective evaluation of screening performance of first-trimester prediction models for preterm preeclampsia in an Asian population.

BACKGROUND: The administration of aspirin <16 weeks gestation to women who are at high risk for preeclampsia has been shown to reduce the rate of preterm preeclampsia by 65%. The traditional approach to identify such women who are at risk is based on risk factors from maternal characteristics, obstetrics, and medical history as recommended by the American College of Obstetricians and Gynecologists and the National Institute for Health and Care Excellence. An alternative approach to screening for preeclampsia has been developed by the Fetal Medicine Foundation. This approach allows the estimation of patient-specific risks of preeclampsia that requires delivery before a specified gestational age with the use of Bayes theorem-based model. OBJECTIVE: The purpose of this study was to examine the diagnostic accuracy of the Fetal Medicine Foundation Bayes theorem-based model, the American College of Obstetricians and Gynecologists, and the National Institute for Health and Care Excellence recommendations for the prediction of preterm preeclampsia at 11-13+6 weeks gestation in a large Asian population STUDY DESIGN: This was a prospective, nonintervention, multicenter study in 10,935 singleton pregnancies at 11-13+6 weeks gestation in 11 recruiting centers across 7 regions in Asia between December 2016 and June 2018. Maternal characteristics and medical, obstetric, and drug history were recorded. Mean arterial pressure and uterine artery pulsatility indices were measured according to standardized protocols. Maternal serum placental growth factor concentrations were measured by automated analyzers. The measured values of mean arterial pressure, uterine artery pulsatility index, and placental growth factor were converted into multiples of the median. The Fetal Medicine Foundation Bayes theorem-based model was used for the calculation of patient-specific risk of preeclampsia at <37 weeks gestation (preterm preeclampsia) and at any gestation (all preeclampsia) in each participant. The performance of screening for preterm preeclampsia and all preeclampsia by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, and placental growth factor (triple test) was evaluated with the adjustment of aspirin use. We examined the predictive performance of the model by the use of receiver operating characteristic curve and calibration by measurements of calibration slope and calibration in the large. The detection rate of screening by the Fetal Medicine Foundation Bayes theorem-based model was compared with the model that was derived from the application of American College of Obstetricians and Gynecologists and National Institute for Health and Care Excellence recommendations. RESULTS: There were 224 women (2.05%) who experienced preeclampsia, which included 73 cases (0.67%) of preterm preeclampsia. In pregnancies with preterm preeclampsia, the mean multiples of the median values of mean arterial pressure and uterine artery pulsatility index were significantly higher (mean arterial pressure, 1.099 vs 1.008 [P<.001]; uterine artery pulsatility index, 1.188 vs 1.063[P=.006]), and the mean placental growth factor multiples of the median was significantly lower (0.760 vs 1.100 [P<.001]) than in women without preeclampsia. The Fetal Medicine Foundation triple test achieved detection rates of 48.2%, 64.0%, 71.8%, and 75.8% at 5%, 10%, 15%, and 20% fixed false-positive rates, respectively, for the prediction of preterm preeclampsia. These were comparable with those of previously published data from the Fetal Medicine Foundation study. Screening that used the American College of Obstetricians and Gynecologists recommendations achieved detection rate of 54.6% at 20.4% false-positive rate. The detection rate with the use of National Institute for Health and Care Excellence guideline was 26.3% at 5.5% false-positive rate. CONCLUSION: Based on a large number of women, this study has demonstrated that the Fetal Medicine Foundation Bayes theorem-based model is effective in the prediction of preterm preeclampsia in an Asian population and that this method of screening is superior to the approach recommended by American College of Obstetricians and Gynecologists and the National Institute for Health and Care Excellence. We have also shown that the Fetal Medicine Foundation prediction model can be implemented as part of routine prenatal care through the use of the existing infrastructure of routine prenatal care.

Six-month outcomes after treatment of advanced heart failure with a full magnetically levitated continuous flow left ventricular assist device: report from the ELEVATE registry.

Aims: The ELEVATE registry was planned to study post-approval outcomes with HeartMate 3™ (HM3), a fully magnetically levitated continuous flow left ventricular assist device (LVAD). Methods and results: A total of 482 patients provided consent to participate in ELEVATE (enrolled cohort). Data collection included baseline demographics, survival, adverse events, quality of life (QOL) [EuroQoL-5 Dimensions visual analogue scale (VAS), and 6-minute walk distance (6MWD)]. An additional 58 patients were implanted with HM3 during the same period but expired or were explanted prior to consent, and only survival data were collected (anonymized cohort). We report the 6-month outcomes of the patients who received HM3 as their primary implant (n = 463) and the survival of the 540 patients in the full cohort (enrolled + anonymized). Baseline characteristics included a mean age of 55.6 ± 11.7 years, 89% male, 48% ischaemic aetiology, and 70% on inotropes. The majority of patients (66%) were bridge-to-transplantation (BTT) and 32% were INTERMACS profile 1-2. Full cohort survival at 6 months was 82 ± 2%. In the enrolled primary implant patients, there was no incidence of pump thrombosis, major bleeding was 25%, major infection 35%, and any stroke type 5%. Functional capacity improved significantly (Δ6MWD 230 ± 191 m) as did QOL (ΔVAS 31 ± 23). Freedom from unplanned rehospitalizations at 6 months was 68 ± 2%. Conclusion: The 6-month outcomes of the HM3 LVAD demonstrate a highly reliable, thrombosis free, device with low incidence of stroke and improved functional capacity, and QOL. ClinicalTrials. gov Identifier: NCT02497950.

Recommended practices to organize and deliver school-based services for children with disabilities: A scoping review.

BACKGROUND: Inclusive educational environments can have a positive effect on the general health and well-being of children with disabilities. However, their level of academic success and participation remains limited. Considering scarce resources and high needs, identifying efficient methods for providing interdisciplinary services is critical. This scoping review, therefore, aims to (a) synthesize current evidence about principles for organizing and delivering interdisciplinary school-based support services for students with disabilities and (b) ascertain useful strategies for implementation of principles in the school setting. METHODS: Scholarly and grey literature in rehabilitation and education were reviewed collaboratively with school-based stakeholders. A search of five databases identified 13,141 references and resulted in 56 relevant articles published from 1998 to 2017. Information (e.g., principles to organize services and strategies for implementation) was extracted, and thematic analysis was used to summarize findings. RESULTS: Within the documents retained, 65% were scientific and 35% were grey. Services primarily targeted students with behavioral issues, followed by those with cognitive and learning disabilities with a focus on improving social-emotional functioning and academic performance. Thematic analysis revealed 10 common principles to guide service organization (e.g., collaborative interventions and support for teachers) and seven implementation strategies (e.g., training and coordination) for employing these principles. CONCLUSIONS: Findings can guide rehabilitation professionals, educators, and policy makers in restructuring well-coordinated collaborative services involving training and capacity-building of school-based service providers. Such knowledge can contribute to the improved provision of care and, consequently, promote children's school participation and inclusion.

Bifurcation Generated Mechanical Frequency Comb.

We demonstrate a novel response of a nonlinear micromechanical resonator when operated in a region of strong, nonlinear mode coupling. The system is excited with a single drive signal and its response is characterized by periodic amplitude modulations that occur at timescales based on system parameters. The periodic amplitude modulations of the resonator are a consequence of nonlinear mode coupling and are responsible for the emergence of a "frequency-comb" regime in the spectral response. By considering a generic model for a 1∶3 internal resonance, we demonstrate that the novel behavior results from a saddle node on an invariant circle (SNIC) bifurcation. The ability to control the operating parameters of the micromechanical structures reported here makes the simple micromechanical resonator an ideal test bed to study the dynamic response of SNIC behavior demonstrated in mechanical, optical, and biological systems.