This qualitative study explores the potential ways that a traditional Yeshiva education (TYE) helps prepare students for entering and succeeding in law school. The researcher interviewed five rabbi-law professors for their take on this phenomenon and compared the results of those findings with the scholarly literature on the topic to date. Much of that existing scholarly literature focuses on how a Yeshiva education might help students who later switch to law school because of the Yeshiva's focus on Talmud study, as well as the Yeshiva's use of the Socratic Method and dyadic Chavrusa study models. To that end, this study sheds light on the various aspects of traditional Yeshiva education that could be beneficial for those pursuing a legal career. The findings demonstrate that there is a broad consensus that Yeshiva education fosters critical thinking and analytical skills through its emphasis on Talmud study, which can be advantageous in comprehending complex legal concepts and arguments. Moreover, exposure to aspects of the law school culture and methodology during Yeshiva education can arguably prepare students for its use by law teachers in law school, contributing to their ability to productively engage in thoughtful and probing discussions. [ABSTRACT FROM AUTHOR]
Yadav, Pratibha, Rachamin, Reuven, Konheiser, Jörg, and Baier, Silvio
Subjects
*MONTE Carlo method, *RADIATION shielding, *NUCLEAR engineering
Abstract
In nuclear engineering, Monte Carlo (MC) methods are commonly used for reactor analysis and radiation shielding problems. These methods are capable of dealing with both simple and complex system models with accuracy. The application of MC methods experiences challenges when dealing with the deep penetration problems that are typically encountered in radiation shielding cases. It is difficult to produce statistically reliable results due to poor particle sampling in the region of interest. Therefore, such calculations are performed by the Monte Carlo N-Particle Transport (MCNP) code in association with the weight window (WW) variance reduction technique, which increases the particle statistics in the desired tally region. However, for large problems, MCNP's built-in weight window generator (WWG) produces zero WW parameters for tally regions located far from the source. To address this issue, the recursive Monte Carlo (RMC) method was proposed. This paper focuses on the RMC methodology and its implementation in the Helmholtz-Zentrum Dresden-Rossendorf's (HZDR's) in-house code TRAWEI, which is responsible for producing optimal zone weight parameters used for optimizing deep penetration MC calculations. In addition, this paper discusses the verification of the TRAWEI weight generator program to that of an existing MCNP WWG. The performance of TRAWEI-generated weight values is assessed using a handful of test cases involving two shield materials. Globally, the TRAWEI-generated weight values improved not only the statistical variance and computational efficiency of the MC run compared to the analog MCNP simulation but also those of the simulation with WW values generated by the standard MCNP WWG. [ABSTRACT FROM AUTHOR]
Tian, Hongzhen, Cohen, Reuven Zev, Zhang, Chuck, and Mei, Yajun
Subjects
*GALLSTONES, *DECISION making, *CHILD patients
Abstract
Multistage sequential decision-making occurs in many real-world applications such as healthcare diagnosis and treatment. One concrete example is when the doctors need to decide to collect which kind of information from subjects so as to make the good medical decision cost-effectively. In this paper, an active learning-based method is developed to model the doctors' decision-making process that actively collects necessary information from each subject in a sequential manner. The effectiveness of the proposed model, especially its two-stage version, is validated on both simulation studies and a case study of common bile duct stone evaluation for pediatric patients. [ABSTRACT FROM AUTHOR]
This paper focuses on two elements of the Passover Seder ritual and their connection to Piagetian education theory. After outlining Piaget's theory of genetic epistemology and its implications for education theory, it focuses on Sigel's distancing theory, which touts question asking as a tool for presenting information to students. This paper argues that the Jewish ritual of the Passover Seder was formulated with such pedagogical methods in mind, especially as it concerns the role of questioning. This paper also discusses storytelling's importance as an effective tool in pedagogical instruction, and how the Passover Seder also takes advantage of that modality to make the ritual more impactful for educational purposes. [ABSTRACT FROM AUTHOR]
The core of this article is the search for an 'organizing principle' for the State of Israel in the present era. To approach this core goal, it conducted 40 interviews with well-known and influential Israeli individuals and attempted to identify common grounds of Israeli society. Analysis of the interviews finds a broad common denominator among those with a wide variety of opinions, which is closely linked with the major principles of the Declaration of Independence of the State of Israel. [ABSTRACT FROM AUTHOR]
Background: No current data exists regarding the occurrence of pathological results when using Whole Exome Sequencing (WES) analysis in a subgroup of fetuses with minor abnormalities and normal Chromosomal Microarray Analysis (CMA) results. Objective: Our study aimed to report our experience with in-utero WES abnormal results, found in fetuses with minor anomalies after a normal CMA result. Methods: A retrospective study conducted in a single tertiary center, during four years, included collating data regarding fetuses with minor structural abnormalities, normal CMA results, and abnormal triple WES test results. Results: Eleven fetuses were included in the study. Eight were with cardiovascular and lymphatic drainage alterations. Two fetuses developed late third-trimester macrocephaly (head circumference ≥ +2 standard deviations), and one fetus had unilateral mildly short and bowed femur bone. In seven cases (63.6%) the parents opted to terminate the pregnancy as a result of the WES analysis results. Conclusion: Our case series raises the possibility that fetuses with even minor structural alterations and normal CMA results can have genetic variants revealable only by WES analysis which can provide critical information regarding pregnancy management. [ABSTRACT FROM AUTHOR]
Objective: The aim of this study was to describe the prenatal diagnosis of Major Aortopulmonary Collateral Arteries (MAPCAs), and to present a systematic ultrasound method for evaluating lung vascularity in fetuses with pulmonary atresia with ventricular septal defect (PAVSD) and agenesis of ductus arteriosus (DA). Method: This retrospective study evaluated fetuses diagnosed with PAVSD with agenesis of DA, for the presence of the MAPCAs anomaly. Fetal pulmonary vasculature was investigated by 2D and 4D Spatio Temporal Image Correlation (STIC) technology using High Definition Color Doppler. Results: Over a 10 year period, six fetuses were diagnosed with MAPCAs. Prenatal diagnosis was made between 17 w 6 d and 28 w 4 d in five fetuses, with the sixth diagnosed at 37 w 6 d. All six had PAVSD with agenesis DA, four exhibited pulmonic atresia without any arterial outflow, while two fetuses presented with absent left pulmonary artery, and a miniscule right pulmonary artery. In five cases, the parents elected to terminate the pregnancy and the last, although born alive, did not survive an attempt at restorative surgery and died at the age of 5 months. Postnatal CT angiography imaging of this case revealed the subclavian origin of the MAPCAs. Chromosomal micro array analysis of the amniotic fluid revealed that five of the six fetuses were normal and one was lost to follow up. Conclusion: MAPCAs should be investigated in cases of PAVSD with agenesis DA. A meticulous ultrasound evaluation using 2D and 4D STIC can permit the prenatal diagnosis of this anomaly and provide the parents with the opportunity for prenatal consultation. [ABSTRACT FROM AUTHOR]
We present the herpetofauna from Raqefet Cave, a Natufian (terminal Pleistocene) cemetery site in Mount Carmel, Israel. We provide a systematic description of the findings. By using intra-site comparisons of diversity and bone fragmentation, we identify possible agents of deposition and modification. To reconstruct the paleoenvironment, we conducted a habitat-weighting analysis and compared our results to the herpetofauna assemblages of a contemporaneous residential site in Mount Carmel, to modern herpetofauna sightings from Mount Carmel and to the micro-mammal assemblages of Raqefet Cave. Furthermore, we attempted to reconstruct the paleoclimate according to the modern presence of the identified herpetofauna species in different geographic zones in Israel with regard to their mean annual precipitation and temperature. Our analysis shows that all the Raqefet faunal assemblages originated from a mosaic of open and wooded Mediterranean habitats, similar to present-day Mount Carmel, albeit in slightly different proportions, which may be indicative of different depositional histories and possibly different accumulation agents. Paleoclimate reconstruction also indicates similarities to present-day Mount Carmel. Our analysis joins others in suggesting that the postulated climatic fluctuations of the latest Pleistocene did not have a considerable impact on the environments surrounding Raqefet Cave during the Natufian use of the site. [ABSTRACT FROM AUTHOR]
The COVID-19 outbreak caused persons to be reluctant to seek medical care due to fear of contracting the infection. To evaluate the effect of the COVID-19 pandemic on admission rates to the delivery room and the feto-maternal unit, and to assess the effect on the nature of presenting obstetrical complaints to the emergency department. A retrospective cohort study in one medical center. The population was women > 20 weeks pregnant who presented to the obstetrical emergency department with self-complaints during 29 days at the peak of the pandemic outbreak, and a matched group during the exact period in the previous year. We compared between the groups: clinical, obstetrical, and demographic data, including age, area of residence, gravidity, parity, previous cesarean deliveries, high-risk pregnancy follow-up, the last 30 days admissions to the obstetrical emergency department, gestational age, chief complaints, cervical dilatation, cervical effacement, admissions to the delivery room or feto-maternal unit, time from admissions to the delivery room to birth, if applicable, and acute obstetrical complications diagnosed at the emergency department. During the pandemic outbreak, 398 women met study inclusion criteria, compared to 544 women in the matched period of the previous year. During the COVID-19 period, women visited the obstetrical emergency department at a more advanced mean gestational age (37.6 ± 3.7 vs. 36.7 ± 4.6, p =.001). Higher proportions of women in the COVID-19 cohort presented in active labor, defined by cervical dilation of at least 5 cm on admission to the labor ward [37 (9.3%) vs 28 (5.1%), p =.013)] and with premature rupture of membranes [82 (20.6%) vs 60 (11.0%), p <.001)], and consequently with more admissions to the delivery room [198 (49.7%) vs 189 (34.7%), p <.001)]. We also recorded a significant increase in urgent obstetrical events in the emergency department during the recorded COVID-19 pandemic [23 (5.8%) vs 12 (2.2%)), p =.004]. However, the rates of neonatal and maternal morbidity did not change. During the outbreak the proportion of visits during the night was higher than during the matched period of the previous year: [138 (34.7%) vs 145 (26.6%)), p =.008]. In a multivariate logistic regression, the higher rates of admission to the delivery room during active labor and of urgent events during the pandemic outbreak compared to the matched period in the previous year remained statistically significant. The pandemic outbreak of COVID-19 caused a behavioral change among women who presented to the obstetrical emergency department. This was characterized by delayed arrival to the obstetrical emergency department and the delivery room, which led to a significant increase in urgent and acute interventions. The change in behavior did not affect the rates of maternal and neonatal morbidity. [ABSTRACT FROM AUTHOR]
Placenta accreta spectrum constitutes one of the most complicated challenges in modern obstetrics. Given the conflicting data regarding the added value of MRI in the diagnosis of invasive placentation, we aim to assess individual and combined ability of multiple sonographic and MRI signs to diagnose placenta accreta spectrum in suspected cases. We assessed 28 cases of suspected placenta accreta spectrum in the third trimester. All cases underwent ultrasound assessment as well as MRI scan. Diagnosis was confirmed during surgery. The value of sonographic and MRI signs in the detection of placenta accreta spectrum was assessed. A total of 23 cases were diagnosed with placenta accreta spectrum during cesarean delivery. Overall, ultrasound was found to be more sensitive and specific compared to MRI (sensitivity of 0.96 and specificity of 0.6 in ultrasound vs. sensitivity of 0.83 and specificity of 0.4 in MRI). However, the use of a post-hoc structured model improved MRI performance to a similar level of ultrasound (sensitivity of 0.96 and specificity of 0.6). Ultrasound is superior to MRI in the detection of placenta accreta spectrum. However, MRI performance can be greatly improved by the use of a structured scoring system. [ABSTRACT FROM AUTHOR]
CORPUS callosum, CEREBRAL hemispheres, AGENESIS of corpus callosum, PRENATAL diagnosis, DYSGENESIS, NOMOGRAPHY (Mathematics)
Abstract
The corpus callosum (CC) is the largest commissure connecting the cerebral hemispheres. Its components are recognized sonographically at 18–20 GW and from that point forward, its growth can be assessed using nomograms for CC length and thickness according to gestational week. Prenatal diagnosis of agenesis of the CC has been reported comprehensively. On the contrary, information regarding findings as short or thick CC is very rare. Is short CC an expression of callosal dysgenesis or could it be a variant of the normal development when all its parts exist? We discuss this issue through this case report. [ABSTRACT FROM AUTHOR]
Intersectionality and identity were the focus of a qualitative study that took place from 2017–19 in the dance undergraduate major at a religious college in Israel. The objective was to analyze the ongoing process of dialogue between secular faculty and orthodox female students, as this constitutes an intersection of two different cultures. A model called 'Mutual Creative Space' developed by Ben Ezer and Bar Lev, was utilized to understand the intercultural encounters that took place in the classroom and studio and also to identify ways in which there could be a bridge between religious and secular cultures. This model contains seven categories, which can be used to analyze the encounter process, and these were used in analyzing the narratives recorded and then transcribed from both faculty and students. In this article, we see how tensions and contradictions exist between dance and religion. We also recognize that a positive process can be developed, allowing students to live a life of faith and gain new dimensions of expressiveness and female empowerment through involvement in dance. [ABSTRACT FROM AUTHOR]
CAR-T cells were not detectable in the blood sample for Patient 1, but for Patients 2 and 3, they were present at 30 days post-infusion, after treatment which included anakinra as well as corticosteroids. Chimeric antigen receptor-T (CAR-T) therapy has demonstrated impressive efficacy in B-cell malignancies, but its therapeutic index has been impaired by unique immune-mediated toxicities not seen with traditional cytotoxic chemotherapy.[1],[2] These toxicities include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH)-like syndrome.[2] Although IL-6 blockade with tocilizumab has become standard treatment for CRS, patients refractory to tocilizumab or those with ICANS often require corticosteroids. She was treated with bridging chemotherapy including cyclophosphamide, etoposide, vincristine, and dexamethasone, and then lymphodepleting therapy with fludarabine (30 mg/m SP 2 sp , 4 doses) and cyclophosphamide (500 mg/m SP 2 sp , 2 doses) prior to the CAR-T cell infusion. HT
The core feature of parliamentary democracy is government responsibility to the legislature. The most important instrument by which parliament can express its lack of support for the government is the vote of no confidence. This mechanism remains significantly under-studied, and research on votes of no confidence calls out for systematic attention. It is also timely because parliamentary democracies are making it procedurally harder for parliament to terminate the government. Through developing and conceptualising a series of indicators that affect the relative ease with which parliament can challenge and terminate government, this study proposes the first ever framework for analysing votes of no confidence. It then empirically locates countries in the framework and discusses those that have shifted over time. The goal of this study is to begin to fill an academic lacuna concerning, arguably, the defining feature of parliamentary democracy. [ABSTRACT FROM AUTHOR]
The core feature of a parliamentary system is not that governments tend to emerge from the legislatures in some way or another, but their political responsibility to this body. While in only some parliamentary systems the government needs formal support of parliament in order to take office, in all parliamentary systems no government can survive against the will of parliament. The academic literature related to the rules for how governments form is vast. Strikingly, scholars have paid far less attention to unpacking the core institution of parliamentary systems of government – the confidence relationship and the various no confidence procedures. Placing the focus on how the parliament can hold the government accountable, this special issue assesses the larger influences legislative confidence has on executive–legislative relations, and improves our understanding of the ways in which the executive may be challenged or dismissed. [ABSTRACT FROM AUTHOR]
DRUG efficacy, ASTHMA, QUALITY of life, ASTHMATICS, MONOCLONAL antibodies
Abstract
The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathway. Clinical trials showed efficacy of Mepolizumab in patients with severe eosinophilic asthma. However, reports on experience with treatment in a real-world cohort are limited. Evaluation of the efficacy and safety of Mepolizumab for treatment of severe eosinophilic asthma in a real-world cohort of patients. A clinical prospective observational trial included all patients >18 years treated with Mepolizumab between March 2016 to March 2019 at Rabin Medical Center. The composite primary outcome measures evaluated: increase in FEV1 by≥ 200 ml and/or decrease in exacerbation rate of ≥50% and/or cessation of oral corticosteroids (OCS) treatment or ≥50% decrease in dosage. Also evaluated: blood eosinophil count, adverse events and quality of life. Of 61 patients, 50 (82.0%) achieved the primary outcome. The number of patients who suffered from frequent exacerbations decreased from 52 (85.2%) to 8 (13.1%) (p < 0.001). Twenty-two patients (68%) stopped OCS treatment or received >50% reduced dosage (p < 0.001). Mean FEV1 increased from 1.72 ± 0.78 liters to 1.87 ± 0.85 liters (p = 0.043). Response to therapy was seen within six months. Forty-nine patients (80%) reported an improvement in quality of life (p < 0.001). Only minor adverse events were reported. Treatment with mepolizumab was well tolerated and significantly lowered the exacerbation rate and OCS dependence in a real-world cohort of severe eosinophilic asthma patients. Response to therapy was within six months and treatment effect was sustained over time. [ABSTRACT FROM AUTHOR]
CRANIOMETRY, CESAREAN section, LOGISTIC regression analysis, FIRST stage of labor (Obstetrics)
Abstract
Objectives: To assess if measurement of the head progression distance (PD) during the first stage of labor in nulliparous women can predict the delivery method. Methods: A prospective study was conducted on consecutive nulliparous women beyond 37 week's gestation during the first stage of labor. Transperineal ultrasound was performed to assess the PD. Analysis was performed on the relationships between PD during rest and during voluntary pushing and the fetal and maternal characteristics, delivery mode, and immediate postnatal outcomes. Results: Eighty seven suitable nulliparous women were suitable for analysis. PD was found to be significantly longer in women who delivered vaginally (VD) compared to those who underwent a cesarean section (CS) for obstructed labor: PD at rest was 2.51 ± 1.71 cm in women who delivered vaginally compared to 1.48 ± 1.9 cm in women who delivered by CS (p =.01). The PD during pushing was 3.43 ± 1.8 cm for a VD compared to 1.5 ± 2.1 cm for CS (p =.015). Logistic regression and receiver-operating characteristics curve analysis demonstrated a moderate predictive value of PD with respect to the mode of delivery (area under the curve was 0.67 during both resting and pushing period). Conclusion: PD measurements during the first stage of labor among nulliparous women differ significantly both in rest and during pushing between patients who delivered vaginally compared to CS and can therefore assist in predicting the mode of delivery. [ABSTRACT FROM AUTHOR]
Introduction: Despite meticulous investigation of polyhydramnios cases, in many of these cases, congenital anomalies are detected only after birth. The aim of our study was to explore the contribution of fetal brain MRI to the detection of CNS anomalies in cases of polyhydramnios. Materials and methods: This was retrospective cohort study on fetuses referred for the investigation of polyhydramnios at a single tertiary center. All fetuses underwent a detailed sonographic anatomical scan and a fetal brain MRI. Isolated and nonisolated polyhydramnios were differentiated according to associated anomalies. MRI findings were compared between the groups. Results: A total of 46 fetuses were included in the study. Brain anomalies were detected in ultrasound in 12 (26%) cases while MRI detected brain anomalies in 23 (50%) cases. MRI detected more anomalies in fetuses with nonisolated compared to isolated polyhydramnios (62.9% and 31.6%, respectively, p = .019). Conclusions: Fetal brain MRI may contribute to the evaluation of fetuses with polyhydramnios. The clinical value and cost-effectiveness of MRI use in the routine work-up of polyhydramnios should be assessed in future studies. [ABSTRACT FROM AUTHOR]
Tsur, Abraham, Weisz, Boaz, Rosenblat, Orgad, Shai, Daniel, Derazne, Estela, Stevenson, David K., Achiron, Reuven, and Katorza, Eldad
Subjects
CORPUS callosum, FETAL ultrasonic imaging, LENGTH measurement, GESTATIONAL age, FETUS
Abstract
Objective: To personally customize the antenatal ultrasound charts for the fetal corpus callosum (CC) length. Methods: A retrospective analysis of fetal neuro-sonography scans. Cases were grouped as normal neuro-sonographic evaluation (normal) or as high risk and suspected brain anomaly (abnormal). The normal group was subcategorized according to Cignini's CC length charts. Data of fetuses with a CC length between the 5th-95th percentile served for creating new charts, describing the ratio of the CC length to the major biometric parameters as a function of gestational age (GA). Results: A total of 410 measurements were included. Of them 255 were normal and 155 abnormal. The CC length/estimated fetal weight (EFW) ratio had the strongest linear association with GA (R2 = 0.929). Applying charts using this ratio to the normal group, significantly increased the percent of CC length measurements defined as normal from 84.7 to 94.5% (p < .001). Conversely, applying these charts to the abnormal group nonsignificantly decreased the number of measurement defined as normal from 89 to 83.2% (p = .137) Conclusions: The CC length/EFW ratio is strongly and linearly associated with GA. Using this personalized ratio may improve the diagnostic accuracy of CC evaluation by adjusting the CC length to the fetus natural proportions. [ABSTRACT FROM AUTHOR]
Background: Assessment of pelvic configuration is an important factor in the prediction of a successful vaginal birth. However, manual evaluation of the pelvis is practically a vanishing art, and imaging techniques are not available as a real-time bed-side tool. Unlike the obstetrical conjugate diameter (OC) and inter spinous diameter (ISD), the pubic arch angle (PAA) can be easily measured by transperineal ultrasound. Objectives: Three-dimensional computed tomography bone reconstructions were used to measure the three main birth canal diameters, evaluate the correlation between them, and establish the normal reference range for the inlet, mid-, and pelvic outlet. Study design: Measurements of the PAA, obstetric conjugate (OC), and ISD were performed offline using three-dimensional post processing reconstruction in bone algorithm application of the pelvis on examinations performed for suspected renal colic in nonpregnant reproductive age woman. The mean of two measurements was used for statistical analysis which included reproducibility of measurements, regression curve estimation between PAA, OC, and ISD, and calculation of the respective reference range centiles for each PAA degree. Results: Two hundred ninety-eight women comprised the study group. The mean ± SD of the PAA, ISD, and OC were 104.9° (±7.4), 103.8 mm (±7.3), and 129.9 mm (±8.3), respectively. The intra- and interobserver agreement defined by the intraclass correlation coefficient (ICC) was excellent for all parameters (range 0.905-0.993). A significant positive correlation was found between PAA and ISD and between PAA and OCD (Pearson's correlation = 0.373 (p < .001), and 0.163 (p = .022), respectively). The best regression formula was found with quadratic regression for inter spinous diameter (ISD): 34.122778 + (0.962182*PAA - 0.002830*PAA2), and linear regression for obstetric conjugate (OC): 110.638397 + 0.183156*PAA. Modeled mean, SD, and reference centiles of the ISD and OCD were calculated using the above regression models as function of the PAA. Conclusions: We report significant correlation between the three pelvic landmarks with greatest impact on the prediction of a successful vaginal delivery: the PAA which is easily measured sonographically and the ISD and OC which are not measurable by ultrasound. This correlation may serve as a basis for future studies to assess its utility and prognostic value for a safe vaginal delivery. [ABSTRACT FROM AUTHOR]
Objective: The objective of this study is to examine the frequency of abnormal Chromosomal Microarray (CMA) analyses among fetuses with isolated non-visualization of fetal gallbladder.Methods: Data from CMA analyses performed due to isolated non-visualization of fetal gallbladder between January 2013 and September 2016 were retrospectively acquired from a computerized database of the Israeli Ministry of Health. The results were compared with the rate for clinically significant CMA findings in general population, based on a large cohort of 5541 pregnancies undergoing CMA due to maternal request, and a systematic review of 9272 cases with normal ultrasound.Results: Of 45 pregnancies with isolated non-visualization of fetal gallbladder, CMA testing yielded one (2.22%) gain-of-copy-number variant at 16p11.2, categorized as "pathogenic". In addition, one finding of unknown significance was demonstrated. The risk for clinically meaningful CMA findings among pregnancies with isolated absent gallbladder was not significantly increased compared to control population.Conclusions: To the best of our knowledge, this study is the first report describing the rate of pathogenic CMA results in fetuses with isolated non-visualization of fetal gallbladder. The results, in conjunction with previous studies, show that the risk for abnormal CMA results in pregnancies diagnosed with non-visualized gallbladder is not significantly different from pregnancies with normal ultrasound. [ABSTRACT FROM AUTHOR]
Schore, Reuven J., Devidas, Meenakshi, Bleyer, Archie, Reaman, Gregory H., Winick, Naomi, Loh, Mignon L., Raetz, Elizabeth A., Carroll, William L., Hunger, Stephen P., and Angiolillo, Anne L.
The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05 and 0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02–0.049 versus 0.05–0.22 IU/mL (p =.25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95% CI for plasma asparagine depletion after a pegaspargase dose is 22–29 days. Clinical trial registration: identifier NCT00671034. [ABSTRACT FROM AUTHOR]
Sukenik-Halevy, Rivka, Katz, Adi, Regev, Rivka H., Markovitch, Ofer, Sharony, Reuven, Ganor Paz, Yael, and Biron-Shental, Tal
Subjects
PRENATAL care, FETAL growth retardation, FETAL abnormalities, ECHOCARDIOGRAPHY, SYMMETRY
Abstract
Objective: To evaluate the yield of work-up in intrauterine growth restriction (IUGR) pregnancies and their outcomes.Materials and Methods: Retrospective data regarding prenatal work-up (serology, genetic testing and imaging), and neonatal outcomes of 198 IUGR pregnancies (estimated fetal weight <10th percentile) were analyzed.Results: IUGR was isolated in 72 cases. Work-up performed in 158 (80%) cases was positive in 4 (2.5%). No abnormalities were detected in prenatal genetic testing. Echocardiogram performed in 27 cases was abnormal in 3 (11.1%). Serological testing performed in 150 pregnancies (75.8%) detected 1 case (0.7%) of cytomegalovirus (CMV) infection. Thirteen neonates (6.5%) were diagnosed with significant health problems. A positive work-up and significant postnatal health problems were not correlated with IUGR severity, symmetry or additional concurrent findings.Conclusion: The yield of IUGR work-up is not clear and is probably highest for fetal echocardiography. The rate of significant adverse outcomes after birth is increased in IUGR pregnancies. [ABSTRACT FROM AUTHOR]
Myeloablative doses of busulfan (Bu) with fludarabine (Flu) have reduced toxicity, however, limited by an increased relapse rate. We aimed to improve outcome of Flu-Bu regimen by augmentation with thiotepa (TT) (10 mg/kg). Eighty-nine patients with AML, 44 patients conditioned with Flu-Bu (group 1), and 45 patients augmented with TT (Flu-Bu-TT, group 2), were retrospectively analyzed. Primary objectives were toxicity and outcomes. Major toxicities were comparable: mucositis (p = 1.0), sepsis (p =.7), severe venocclusive disease of liver (VOD) (p = 1.0), and non-relapse mortality (NRM) (22 vs. 22%, p =.7). Five-year disease-free survival was significantly better in group 2 compared to group 1 (62 vs. 38%, p =.02). Five-year overall survival (OS) showed trend toward benefit in group 2 (62 vs. 42%, p =.06). Lower relapse rate in group 2 (14 vs. 46%, p =.005) contributed to better outcomes. Augmented regimen has better disease-free survival (DFS) (mainly due to reduced relapse rate) and similar toxicities as compared to Flu-Bu. Assessing the addition of TT to myeloablative conditioning (Flu, Bu) in patients undergoing allogeneic stem cell transplant for acute myeloid leukemia with regard to relapse rate, disease-free survival and toxicity. Addition of thiotepa improves disease-free survival and shows trend toward benefit in overall survival, by reducing relapses without additional toxicity. [ABSTRACT FROM AUTHOR]
Introduction: The aim of this study was to assess the correlation between fetal lateral ventricle width and biometric measurements. Material and methods: A prospective study on 335 fetuses, 101 fetuses with isolated mild ventriculomegaly and a control group of 234 fetuses with a normal US examination. All fetuses underwent a detailed brain ultrasound scan and a full biometric evaluation. To further compare biometric parameters, we matched, according to gestational week and gender, 91 fetuses from the study group to 91 fetuses from the control group. Results: The mean gestational week during the exam was significantly different between the groups (29.6 weeks in the study group versus 28.3 in the control group, p = .001). The mean maternal age, obstetrical history, mode of conception, or fetal gender did not differ between the groups. After matching according to gestational age and fetal gender, the mean gestational week between the matched groups did not differ and was 29 + 5 weeks in both groups. The study group had significantly larger head circumference (p =.009), biparietal diameter (p < .001), femur length (p = .023), and estimated fetal weight (p =.024) compared with the control group. Conclusions: Isolated mild ventriculomegaly could be related to other larger fetal biometric measurements and does not necessarily mean a pathological condition. [ABSTRACT FROM AUTHOR]
SEPTUM (Brain), MAGNETIC resonance imaging of fetal brain abnormalities, FETAL development, PRENATAL diagnosis, ULTRASONIC imaging, ANATOMY, MAGNETIC resonance imaging, RETROSPECTIVE studies
Abstract
Purpose: The purpose of this study is to describe the morphological characteristics of fetal MRIs and outcome of prenatally-detected abnormal width of the CSP (cavum septum pellucidum).Material and Methods: A retrospective study of cases with abnormal width of the CSP demonstrated prenatally on MRI. Data collected included: prenatal history, MRI features, sonographic follow up, and neurodevelopmental outcome.Results: Most of the cases referred (34/39) had an abnormal CSP on MRI. Thirty cases had an abnormal width: 23 had narrow CSP and seven had wide CSP. Only three out of 12 cases that were referred with US diagnosis of absent CSP were confirmed by MRI, the rest had narrow CSP. Follow up was performed in 24 out of 30 cases with an abnormal CSP width; all had normal neurodevelopment.Conclusion: To the best of our knowledge, this is the first study to examine the outcome in narrow and wide CSPs detected prenatally. An abnormal width of the CSP prenatally, without an associated fetal abnormality such as aneuploidy, appears to have normal outcome. MRI should be offered when an absence of the CSP is suspected on US to rule out narrow CSP, which seems to be a benign finding. [ABSTRACT FROM AUTHOR]
Purpose: To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range.Materials and Methods: A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed.Results: Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001). This correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r2 = 0.423, p < .001). After aggregation of the mean AOP per FHS, the relative predicted centiles values and standard deviation were calculated. The mean Z score between measured and predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006).Conclusions: Our results demonstrate a significant correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor. [ABSTRACT FROM AUTHOR]
Objective: The objective of this study is to determine the clinical significance of maternal and fetal ultrasound Doppler flow indices in postdates pregnancies.Methods: This prospective study comprised 120 low-risk pregnant women beyond 40 weeks of gestation. All participants underwent Doppler assessment including of fetal middle cerebral artery (MCA), umbilical, and uterine arteries. Perinatal outcomes were recorded and evaluated for possible associations with Doppler flow values. Adverse perinatal outcomes were defined as umbilical cord arterial pH <7.1, Apgar score <7 at 5 min, neonatal admission to a neonatal intensive care unit, and emergency cesarean section due to abnormal intrapartum cardiotocogram Results: Adverse perinatal outcome rate was 17.5% (n = 21). Doppler indices of umbilical artery, MCA, uterine artery and the cerebroplacental ratio (CPR) did not differ significantly between pregnant women with and without adverse perinatal outcomes. Neonatal birth weight was found to correlate negatively with umbilical artery Doppler indices, including the peak systolic to end diastolic ratio (p = .04), the resistance index (p = .02), and the pulsatility index (p = .01). Doppler values of the uterine artery, MCA and CPR did not correlate with neonatal birth weight.Conclusions: The contribution of maternal and fetal ultrasound Doppler to the prediction of adverse perinatal outcomes in low-risk postdates pregnancies is low. Hence, performing routine Doppler examination as part of postdates pregnancy assessments is unlikely to yield significant clinical benefit. [ABSTRACT FROM AUTHOR]
Objectives: To assess if measurement of the head progression distance (PD) during the first stage of labor in nulliparous women can predict the delivery method.Methods: A prospective study was conducted on consecutive nulliparous women beyond 37 week's gestation during the first stage of labor. Transperineal ultrasound was performed to assess the PD. Analysis was performed on the relationships between PD during rest and during voluntary pushing and the fetal and maternal characteristics, delivery mode, and immediate postnatal outcomes.Results: Eighty seven suitable nulliparous women were suitable for analysis. PD was found to be significantly longer in women who delivered vaginally (VD) compared to those who underwent a cesarean section (CS) for obstructed labor: PD at rest was 2.51 ± 1.71 cm in women who delivered vaginally compared to 1.48 ± 1.9 cm in women who delivered by CS (p = .01). The PD during pushing was 3.43 ± 1.8 cm for a VD compared to 1.5 ± 2.1 cm for CS (p = .015). Logistic regression and receiver-operating characteristics curve analysis demonstrated a moderate predictive value of PD with respect to the mode of delivery (area under the curve was 0.67 during both resting and pushing period).Conclusion: PD measurements during the first stage of labor among nulliparous women differ significantly both in rest and during pushing between patients who delivered vaginally compared to CS and can therefore assist in predicting the mode of delivery. [ABSTRACT FROM AUTHOR]
Terry, W. Robert, Karni, Reuven, and Yang-Jenq Huang
Subjects
CUTTING machines, PRODUCTION engineering, MACHINE tool design, MACHINE design
Abstract
This paper presents the economics of broaching operations, as analysed within the framework of concurrent design of the broach tool and its operating conditions. The tool is specified by its cutting teeth—tooth structure, tooth pitch and the number of such teeth—which in turn determine the length of the tool. Its operation is specified by the depth of cut per tooth and by the speed of broaching. Design constraints include broaching machine capabilities and surface finish requirements. A nonlinear mathematical optimization model, which incorporates all design variables and constraints, is developed and used to analyse broach design and operation for an illustrative case. [ABSTRACT FROM AUTHOR]
JUST-in-time systems, PRODUCTION (Economic theory), INVENTORY control, PRODUCT management, INVENTORIES, PRODUCTION control
Abstract
This paper develops a decision rule to enable an a priori classification of a production system that should utilize a JIT- or WIP-type inventory control policy. A two-station deterministic serial production system is analysed. A parameter α- the ratio between WIP and maximum shortage -- is defined, and a cost function K =f(α) is modelled. It is shown that α* -- an optimum value of α -- is a characteristic parameter of the system, can be evaluated a priori based on known parameters, and can serve to identify a production system as JIT type or WIP type. The concept of an OC curve of a system is introduced and it is concluded that JIT is not always favourable over WIP. An extension of the deterministic case shows that α* can be expressed, among others, in terms of MTBF and MTTR. The paper concludes with a numerical example. [ABSTRACT FROM AUTHOR]
MATERIAL requirements planning, PRODUCTION planning, MANUFACTURING processes, MANUFACTURING resource planning, INDUSTRIAL capacity, PRODUCTION engineering
Abstract
The central problem of manufacturing planning is to reconcile due dates, derived from customer delivery timetables, with schedule dates, developed from production capabilities. Conventional capacity planning techniques utilize the technological sequencing of material flow in order to build up production schedules. As they ignore interactions between work stations, and override due date requirements, these techniques are often unsatisfactory. Wight and Belt have suggested a new approach to the problem, and this paper presents a systematic methodology based on their ideas, to characterize and analyse the flow of workthrough a work station, and relate this flow to the nominal capacity of the station. Operation of the station is measured by work in process, delay and underload (operation below nominal capacity); flow between stations is measured by queue length and lead times (process plus wait time). Performance is evaluated by the degree of underload and overload planned for the station--the degree to which available capacity is utilized, and the degree to which lead times, imposed by the Material requirements Plan, can be achieved. Achievable average and maximum lead times are shown to be a function of both nominal work station capacity and the input work load profile--not a constant value for the work station. A more correct study of planable lead times, a production loads vary, allows the necessary connection to be made between due dates and schedule dates. [ABSTRACT FROM AUTHOR]
The flow of work through a work station is analysed in terms of planned input from previous stations, planned output to subsequent stations, planned work-in-process waiting for processing, and the planned queue of unprocessed work delayed for processing during some subsequent period. The planner is assumed to have some leeway in determining the maximum throughput during each period--the planned capacity--and is thus interested in determining the optimal capacity, to be maintained at some constant value throughout the planning horizon. This paper presents a methodology for finding the optimal planned capacity of a work station, which minimizes total costs cover the planning horizon. These costs are of three types: costs of establishing and maintaining the capacity level; costs of work processing; and costs of holding up work in the queue owing to insufficient capacity at any period. Various constraints are considered when characterizing the operating environment of the work station: minimum and maximum permissible queue lengths, delays, work-in-process amounts, lead times, underloading and backlogging. It is shown that these restrictions may be transformed into minimum and maximum bounds on allowable capacity levels, so that the problem becomes one of constrained optimization in a single decision variable--the planned capacity. For complex cost functions or when underloading is permissible, complete enumeration of all feasible solutions provides the simplest approach. For linear or quadratic cost functions and no underloading, the shape and smoothness of the total cost curve indicates that set of feasible capacities within which the optimal capacity lies. [ABSTRACT FROM AUTHOR]
Objectives: No study thus far has evaluated the LUS thickness in active labor. In this study, we endeavored to assess the LUS during active labor.Methods: Using transabdominal sonography in the mid-sagittal position with a full urinary bladder, the thickness of the LUS was measured during active labor phase in women with or without a history of a previous cesarean section.Results: A total of 28 women with a previous cesarean delivery were compared to 29 women without a history of uterine surgery. The median LUS was significantly thinner in women with a uterine scar both during (4 versus 5 mm, p = .001) and between contractions (5 versus 7 mm, p = .011). Paired comparison of LUS thickness between and during contractions within each group showed that thinning of LUS during contraction was significant for both the previous CS group (p < .001) and the control group (p < .001). We found no correlation between LUS thickness and chances of successful TOLAC.Conclusions: In this study, we characterized for the first time the LUS during active labor. We found that LUS was significantly thinner in women after a previous CS and that the LUS was significantly thinner during contraction. [ABSTRACT FROM AUTHOR]
Purpose: The aim of our study was to assess the agreement between pre- and post-natal measurements in prenatal isolated ventriculomegaly.Methods: Ninety-two women were referred for lateral ventricular abnormality and followed prospectively. Cases with at least one dilated lateral ventricle ≥10 mm and a normal work up (serological tests, detailed anatomical scan, fetal brain MR imaging, genetic counseling, and amniocentesis) were considered idiopathic ventriculomegaly and comprised the study group for post-natal follow up. Prenatal measurements were performed by ultrasound and MR imaging. Post-natal measurements were performed by cranial sonography at age of 1-3 months. Measurements were performed in the customary plane for each modality. Paired Student's t test was used to assess the mean difference between pre- and postnatal measurements.Results: Forty three cases comprised the study group for post-natal measurements. A statistically significant decrease in ventricular width (p < .001) was observed between pre- and post-natal measurements. On clinical follow up for 24 months, all cases were normal except three who demonstrated very mild neurological deficits.Conclusions: Our study indicates statistically significant regression of prenatal isolated ventriculomegaly in the post-natal period. [ABSTRACT FROM AUTHOR]
Burke, Michael J., Devidas, Meenakshi, Maloney, Kelly, Angiolillo, Anne, Schore, Reuven, Dunsmore, Kimberly, Larsen, Eric, Mattano, Len A., Salzer, Wanda, Winter, Stuart S., Carroll, William, Winick, Naomi J., Loh, Mignon L., Raetz, Elizabeth, Hunger, Stephen P., and Bleyer, Archie
Subjects
ASPARAGINASE, ALLERGY in children, INTRAVENOUS therapy, INTRAMUSCULAR injections, ONCOLOGY pharmacy, LYMPHOBLASTIC leukemia in children, TUMORS in children, LEUKEMIA treatment, THERAPEUTICS, TUMOR treatment
Abstract
PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children’s Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection. [ABSTRACT FROM AUTHOR]
Purpose: To assess the mid-trimester triple test biomarkers among women diagnosed with vasa previa (VP).Methods: The study included 43 singleton pregnancies diagnosed with vasa previa between the years 1988 and 2011. The mid-gestation screening test for Down syndrome was calculated from the combination of triple serum markers and maternal age, and expressed as a multiple of the gestation specific normal mean (MoM). Reference MoM values were calculated from the local population. The levels of mid-gestation maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) of patients with VP were compared with control reference group.Results: The mean hCG and αFP levels of women diagnosed with VP was significantly higher compared to control reference group (1.42 versus 0.99 MoM; p < .002 and 1.24 versus1.01 MoM; p < .001, respectively). In contrast, there was no significant difference in uE3 levels between these two groups (0.99 versus 0.98 MoM; p = .71).Conclusions: Our findings suggest that increased mid-gestation hCG and AFP were found among pregnancies complicated with VP. Clinicians should consider targeted scanning of pregnant women with risk factors for VP, including unexplained high maternal levels of hCG and αFP of the triple test, while conducting mid-gestation anomaly scan. [ABSTRACT FROM AUTHOR]
Wangtiraumnuay, Nutsuchar, Alnabi, Waleed Abed, Tsukikawa, Mai, Thau, Avrey, Capasso, Jenina, Sharony, Reuven, Inglehearn, Chris F., and Levin, Alex V.
Subjects
RETINAL degeneration, EYE inflammation, GENETIC mutation, MEDICAL records, RETROLENTAL fibroplasia
Abstract
Background/Aims: Pigmentary retinal dystrophy and macular dystrophy have been previously reported in Heimler syndrome due to mutations in PEX1. Here we reported the ocular manifestations in Heimler syndrome due to mutations in PEX6.Materials and methods: Medical records were reviewed to identify patient demographics, ophthalmic and systemic findings, and results of diagnostic testing including whole genome sequencing. Results: Patient 1 is 12-year-old boy with a novel mutation c.275T>G (p.Val92Gly) and known mutation c.1802G>A (p.Arg601Gln) in PEX6. Patient 2 is a 7-year-old girl with the same known c.1802G>A (p.Arg601Gln) mutation and another novel missense mutation c.296G>T (p.Arg99Leu). Both patients exhibited a pigmentary retinopathy. Visual acuity in patient 1 was 20/80 and 20/25 following treatment of intraretinal cystoid spaces with carbonic anhydrase inhibitors, while patient 2 had visual acuity of 20/20 in both eyes without intraretinal cysts. Fundus autofluorescence showed a multitude of hyperfluorescent deposits in the paramacular area of both eyes. OCTs revealed significant depletion of photoreceptors in both patients and macular intraretinal cystoid spaces in one patient. Full field electroretinograms showed normal or abnormal photopic but normal scotopic responses. Multifocal electroretinograms were abnormal. Conclusions: Heimler syndrome due to biallelic PEX6 mutations demonstrates a macular dystrophy with characteristic fundus autofluorescence and may be complicated by intraretinal cystoid spaces. [ABSTRACT FROM AUTHOR]
PRENATAL diagnosis, THUMB, FETAL ultrasonic imaging, PREGNANCY complications, THIRD trimester of pregnancy, DISEASES, ABORTION, GENETIC counseling, GESTATIONAL age, HAND abnormalities, RETROSPECTIVE studies, MULTIPLE human abnormalities, DIAGNOSIS
Abstract
Purpose: One of the greatest challenges with the finding of adducted thumbs in the prenatal setting is the determination of whether this finding is associated with an underlying genetic syndrome. The aim of the present study is to describe the characteristics and outcome of prenatal sonographic diagnosis of adducted thumbs.Methods: A retrospective study was conducted over a period of 17 years in a tertiary referral center. All fetuses diagnosed prenatally with adducted thumbs comprised the study group. Prenatal sonographic assessment and neonatal outcome are presented.Results: Six fetuses were evaluated for adducted thumbs over the 17-year period. In three cases, the parents elected termination of pregnancy for severe associated anomalies. In one case partial resolution was observed during the third trimester. Of the remaining two fetuses, one had a single umbilical artery and in the second the adducted thumbs were an isolated finding. Post-natal evaluation in both cases revealed bilateral adducted thumbs. Apart from orthopedic follow up no further interventions were needed.Conclusions: Prenatal diagnosis of adducted thumbs should be followed by a meticulous fetal ultrasound examination combined with genetic counseling. According to our cohort, if associated anomalies are excluded, isolated cases seem to have a favorable diagnosis. [ABSTRACT FROM AUTHOR]
The purpose of this study was to analyse the association between free beta hCG (fβhCG) increased levels and pregnancy complications (PC), foetal growth restriction (FGR) and preeclampsia (PE). This connection was evaluated in two stages (i) investigating the association between those PC with first trimester fβhCG and second trimester intact hCG (ihCG), and (ii) studying the association between these two analytes in the same pregnancy. This was a retrospective study in two settings: medical centre that provided data on fβhCG and ihCG levels in pregnancies with FGR and PE, and central laboratory that provided fβhCG and ihCG levels that were compared in the same pregnancy. No association was found between those PC and the hCG analytes, except for elevated ihCG levels and FGR. Elevated fβhCG (>3.00 MoM) was found in 570/16,849 (3.4%) women. However, only 14% of whom had elevated second trimester ihCG. A positive correlation was found between the magnitude of first trimester fβhCG levels and the percentage of women who had elevated second trimester ihCG. This association was determined by the magnitude of the elevation of fβhCG levels. Impact statement What is already known on this subject: The two analytes, first trimester fβhCG and second trimester ihCG, are independently produced and parameters of the biochemical screening during pregnancy. What the results of this study add: Referring to 3.00 MoM as cut-off levels, most pregnancies with elevated levels of first trimester fβhCG will have normal ihCG second trimester levels. What the implications are of these findings for clinical practice and/or further research: The risk of developing pregnancy complications, FGR and PE should be associated with second trimester ihCG levels. About 3.5% of women had high fβhCG levels during the first trimester. However, only 14% also had increased ihCG levels, defined as >3.00 MoM; additional studies are needed to explore the association between increased first trimester fβhCG levels and the risk of developing pregnancy complications, independent of ihCG levels in the second trimester. [ABSTRACT FROM AUTHOR]
FIRST trimester of pregnancy, FETAL brain abnormalities, PRENATAL care, ULTRASONIC imaging, TRANSLUCENCY (Optics), ANEUPLOIDY, ABORTION
Abstract
Purpose: The purpose of this study was to describe fetal brain anomalies identified during nuchal translucency (NT) examination and their clinical management. Materials and methods: In this retrospective study, we evaluated charts of pregnant women performed the first trimester scan (FTS) between 1.1.2011 and 31.12.14 in a tertiary referral center. Study population consisted of 952 patients scheduled for routine NT scan for aneuploidy screening between 11.0 and 13.6 gestational weeks, and 32 referred patients due to suspicious CNS finding during previous NT scan. Targeted brain assessment was performed according to clinical judgment during routine scans and in all referred cases. Patients with suspicious CNS findings were referred to pregnancy termination or further evaluation including genetic consultation and second trimester anatomical scan. Results: Thirty-one fetuses were diagnosed with variable brain anomalies. Acrania/anencephaly was the most common defect (nine cases) while the rarest findings were inter-hemispheric cyst, microcephaly, and Walker--Warburg Syndrome (one case each). Genetic testing revealed variable results. Twenty-six (83.9%) couples decided to terminate their pregnancies. Conclusions: The current report highlights the evolving ability to detect CNS malformation during NT scan. FTS novel findings expand our embryological understanding of early fetal development. While severe anomalies can be managed by early termination, other defects necessitate comprehensive evaluation and repetitive imaging. [ABSTRACT FROM AUTHOR]
Mechanical designers strive to create a simple design that will reduce product's cost and increase its reliability. This paper presents an experimental method for measuring the simplicity of a mechanical design. It also presents a quantitative metric for evaluating the simplicity of product design based on quantifiable design parameters. The simplicity metric was developed by using experts’ evaluations of functionally equivalent products. The dominant parameter for predicting an expert's simplicity rating is the number of features required to fully define the examined computer-aided design (CAD) model. This parameter is highly correlated with two additional measured design parameters: number of parts and number of interfaces between parts. [ABSTRACT FROM PUBLISHER]
PIWI-interacting RNAs (piRNAs) and associated proteins comprise a conserved pathway for silencing transposons in metazoan germlines. piRNA pathway components are also expressed in multipotent somatic stem cells in various organisms. piRNA functions have been extensively explored in bilaterian model systems, however, comprehensive studies in non-bilaterian phyla remain limited. Here we investigate the piRNA pathway during the development ofNematostella vectensis, a well-established model system belonging to Cnidaria, the sister group to Bilateria. To date, no population of somatic stem cells has been identified in this organism, despite its long life-span and regenerative capacities that require a constant cell-renewal. We show thatNematostellapiRNA pathway components are broadly expressed in early developmental stages, while piRNAs themselves show differential expression, suggesting specific developmental roles of distinct piRNA families. In adults, piRNA associated proteins are enriched in the germline but also expressed in somatic cells, indicating putative stem cell properties. Furthermore, we provide experimental evidence thatNematostellapiRNAs cleave transposable elements as well as protein-coding genes. Our results demonstrate that somatic expression of piRNA associated proteins as well as the roles of piRNAs in transposon repression and gene regulation are likely ancestral features that evolved before the split between Cnidaria and Bilateria. [ABSTRACT FROM PUBLISHER]
Huynh, Van, Laetsch, Theodore W., Schore, Reuven J., Gaynon, Paul, and O'Brien, Maureen M.
Subjects
LEUKEMIA in children, PROGNOSTIC tests, PEDIATRIC therapy, CLINICAL trials, BONE marrow, LEUKEMIA treatment
Abstract
Technologies for the detection of minimal residual disease (MRD) in leukemia and our understanding of the prognostic implications of MRD at different phases of treatment have significantly improved over the past decade. As a result, definitions of treatment failure based on bone marrow morphology by light microscopy are becoming increasingly inadequate for clinical care and trial design. In addition, novel therapies that may have increased efficacy and decreased toxicity in the setting of MRD compared to overt disease are changing clinical practice and challenging investigators to redefine treatment failure, the role of disease surveillance in remission, and clinical trial eligibility in the era of MRD. [ABSTRACT FROM AUTHOR]