cssi/SciSciGPT-SciSciNet huggingface dataset:
Hörrehabilitation mit Cochleaimplantaten nach translabyrinthärer Vestibularisschwannomresektion

Die Horrehabilitation nach translabyrintharer Vestibularisschwannomresektion stellt eine Herausforderung dar. Da die Cochlea bereits einige Monate nach labyrintharer oder cochlearer Eroffnung sklerosieren kann, ist die Horrehabilitation mit Cochleaimplantaten (CI) ggf. zeitlich limitiert. Eine Option, um eine Komplettsklerosierung zu umgehen und das Intervall bis zur Cochleaimplantation zu prolongieren, ist es, bereits bei der translabyrintharen Resektion einen Platzhalter (Tiefenmesser) und das CI spater („zweizeitig“) einzusetzen. Ziel der retrospektiven Fallserie war es, den Horerfolg aller Patienten (n = 6) im Verlauf darzustellen und den Einsatz des Tiefenmessers zu beurteilen. Der Horerfolg aller Patienten mit (n = 3) und ohne (n = 3) Einlage eines Tiefenmessers wurde mittels Freiburger Einsilbertests ohne Storschall bei 65 dB gemessen. Die erste Messung wurde vor der translabyrintharen Vestibularisschwannomresektion, die letzte Messung bis zu 48 Monate nach der Cochleaimplantation durchgefuhrt. Alle 6 Patienten erreichten auf dem erkrankten Ohr vor der translabyrintharen Vestibularisschwannomresektion 22,5 ± 36,57 % und 12 Monate nach Cochleaimplantation 41,3 ± 26 %. Die Verstehenswerte der Patienten mit Tiefenmesser liegen mit 25,8 ± 16 % nach 12 Monaten unter dem Wert der ubrigen von 56,6 ± 25,0 %. Schwerwiegende intra- oder postoperative Komplikationen traten in beiden Gruppen nicht auf. Der zweizeitige Ansatz der Cochleaimplantation mit Tiefenmessereinlage scheint nach labyrintharer Eroffnung bei intaktem Nerv eine vielversprechende, sichere Variante der Horrehabilitation darzustellen. Forschung zu diesem Ansatz zu intensivieren scheint gerechtfertigt und notwendig.
Relationship Between Sever Disease and Skeletal Maturity.

Background Sever disease is a common condition in active, growing children. This condition presents as pain in the heel and is thought to be an overuse condition of the calcaneal apophysis. There are currently no defined radiographic diagnostic criteria for evaluation of Sever disease, with radiographs generally showing normal appearance of the calcaneal apophysis. A better understanding of the relationship of Sever disease and skeletal maturity may allow for improved interpretation of radiographs when trying to diagnose this condition. Methods ICD-9 code 732.5 was used to search for patients diagnosed with Sever disease from 2007 to 2015 at a single hospital. For every patient with Sever disease with available calcaneal imaging within 40 days of diagnosis, heel x-rays were staged for calcaneal maturity score using a previously described calcaneal skeletal maturity assessment system. Controls matched by age, race, and sex were evaluated for calcaneal stage to compare with the Sever patients. Results The chart review yielded 78 patients diagnosed with Sever disease by the orthopaedic attending, 39 of which have x-rays around the time of diagnosis. Calcaneal scores averaged 2.2±0.8 for all patients, 2.1±0.9 for male individuals, and 2.3±0.8 for female individuals. The average age for male individuals was 10.4±1.9 years and for female individuals, 9.2±2.2 years. The ages of diagnosis were similar for patients with and without x-rays. Twenty-two of 39 patients with Sever disease were calcaneal stage 2, and 37 of 39 were stages 1, 2, or 3. We calculated the absolute difference from stage 2 for the Sever and control groups. Mean difference from stage 2 was 0.51±0.68 for the Sever patients and 0.95±0.79 for control patients (P=0.01). Conclusion Sever disease occurs in a very narrow range of skeletal maturity, as measured by the calcaneal skeletal maturity assessment system and our observations with chronological age. When compared with age-matched and race-matched controls, stage 2 was seen more frequently in the Sever patients. If a child is not within calcaneal stages 1, 2, or 3, then a different diagnosis should be considered. Level of evidence Level III-retrospective case-control study.
Colossal Photon Bunching Driven by Phonon Recombination Dynamics

We report photon bunching g(2) (0) « 49 due to phonon sidebands in spectrally filtered cathodoluminescence from NV centers in diamond. The result is consistent with fast, phonon-mediated recombination dynamics, and supported by a stochastic model.
The Welfare State and Old-Age Pensions

This chapter and the two following chapters all deal with the legacy of Prince Bismarck, the inventor of the modern welfare state. In most modern states, this system takes up at least half of government revenue. It is usually a particularly pure redistribution with some people being taxed and other people receiving, and over a lifetime it doesn’t change people’s incomes all that much. Nevertheless, given its importance, devoting three chapters to it seems reasonable.
Printed Wiring Board Research Joint Venture

In April 1991, the Advanced Technology Program (ATP) announced that one of its initial eleven awards was to a joint venture led by the National Center for Manufacturing Sciences (NCMS) to research aspects of printed wiring board (PWB) interconnect systems. The ATP project description follows: Printed wiring boards (PWBs) are often overlooked in discussions of microchips and other advance electronic components, but they form the backbone of virtually every electronic product, providing connections between individual electronic devices. Although to date PWB technology has kept pace with the increased speed and complexity of microelectronics, it is approaching fundamental limits in materials and processes that must be overcome if the U.S> industry is to maintain a competitive position. (The U.S. share of the $25billion world market dropped from 42 to 29 percent in 3 years.) Four memebers of the NCMS consortium, AT&T, Texas Instruments, the Digital Equipment Corporation, and Hamilton Standard Interconnect, Inc., will work with the Sandia National Laboratories (U.S. Department of Energy) to develop a more consistent epoxy glass material with improved mechanical characteristics of PWBs, improved processes and process-control techniques to produce more reliable solder connections, improved methods and technologies for fine-line imaging on the boards, and a better technical understanding of the chemistry underlying key copper-planting processes.
Audience segmentation to disseminate behavioral health evidence to legislators: an empirical clustering analysis

Elected officials (e.g., legislators) are an important but understudied population in dissemination research. Audience segmentation is essential in developing dissemination strategies that are tailored for legislators with different characteristics, but sophisticated audience segmentation analyses have not been conducted with this population. An empirical clustering audience segmentation study was conducted to (1) identify behavioral health (i.e., mental health and substance abuse) audience segments among US state legislators, (2) identify legislator characteristics that are predictive of segment membership, and (3) determine whether segment membership is predictive of support for state behavioral health parity laws. Latent class analysis (LCA) was used. Data were from a multi-modal (post-mail, e-mail, telephone) survey of state legislators fielded in 2017 (N = 475). Nine variables were included in the LCA (e.g., perceptions of behavioral health treatment effectiveness, mental illness stigma). Binary logistic regression tested associations between legislator characteristics (e.g., political party, gender, ideology) and segment membership. Multi-level logistic regression assessed the predictive validity of segment membership on support for parity laws. A name was developed for each segment that captured its most salient features. Three audience segments were identified. Budget-oriented skeptics with stigma (47% of legislators) had the least faith in behavioral health treatment effectiveness, had the most mental illness stigma, and were most influenced by budget impact. This segment was predominantly male, Republican, and ideologically conservative. Action-oriented supporters (24%) were most likely to have introduced a behavioral health bill, most likely to identify behavioral health issues as policy priorities, and most influenced by research evidence. This was the most politically and ideologically diverse segment. Passive supporters (29%) had the greatest faith in treatment effectiveness and the least stigma, but were also least likely to have introduced a behavioral health bill. Segment membership was a stronger predictor of support for parity laws than almost all other legislator characteristics. State legislators are a heterogeneous audience when it comes to behavioral health. There is a need to develop and test behavioral health evidence dissemination strategies that are tailored for legislators in different audience segments. Empirical clustering approaches to audience segmentation are a potentially valuable tool for dissemination science.
On Constraints in Parameter Estimation and Model Misspecification

Under perfect model specification several deterministic (non-Bayesian) parameter bounds have been established, including the Cramer-Rae, Bhattacharyya, and the Barankin bound; where each is known to apply only to estimators sharing the same mean as a function of the true parameter. This requirement of common mean represents a constraint on the class of estimators. While consideration of model misspecification is an additional complexity, the need for constraints remains a necessary consequence of applying the covariance inequality. These inherent constraints will be examined more closely under misspecification and discussed in detail along with a review of Vuong's original contribution of the misspecified Cramer-Rao bound (MCRB). Recent work derives the same MCRB as Vuong via a different approach, but applicable only to a class of estimators that is more restrictive. An argument is presented herein, however, that broadens this class to include all unbiased estimators of the pseudo-true parameters and strengthens the tie to Vuong's work. Interestingly, an inherent constraint of the covariance inequality, when satisfied by the choice in score function, yields a generalization of the necessary conditions identified by Blyth and Roberts to obtain an inequality of the Cramer-Rae type.
Script Training Using Telepractice with Two Adults With Chronic Non-fluent Aphasia

Two male participants with chronic (> 2 years), non-fluent aphasia and their family members participated in script training using videoconferencing. Functional scripts were developed by people with aphasia (PWA) and their family members. Accuracy of scripts was measured by total target words produced per turn. Participant 1 with Broca's aphasia produced scripts with 0% accuracy pre-treatment and 87.5% accuracy post-treatment. Participant 2 with Transcortical Motor aphasia produced scripts with 20.2% accuracy pre-treatment and 63.5% accuracy post-treatment. Pre- and post-questionnaires for communication effectiveness and the use of telepractice for speech therapy indicated improvements in answering yes/no questions, participating in conversations with strangers, and increasing confidence and satisfaction with technology delivered treatment. The use of videoconferencing to deliver script training appears beneficial for individuals with chronic aphasia.
UNIT 4.10 Identification of Newly Transcribed RNA

Newly transcribed RNA can be identified using the nuclear runoff transcription assay. Isolated nuclei, free of membranes and cytoplasmic debris, are required for the assay. Cell lysis that does not allow the isolation of nuclei free of cell membranes and cytoplasmic material often results in poor incorporation of 32P-labeled UTP into nascent transcripts. Although there is no way to predict what cell types present this problem, many adherent cell lines and lymphocytes isolated from murine spleen or thymus do. Interestingly, very few nonadherent cell lines have posed this problem. As described in this unit, isolating nuclei by detergent lysis of cells works well for many tissue culture cell lines but may not be appropriate for all cell lines and many tissues. Protocols for detergent lysis and Dounce homogenization or cell lysis in an isoosmotic solution and centrifugation through a sucrose cushion are described along with a Support Protocol for the preparation of the cDNA nitrocellulose filter strips that are used to detect the presence of specific transcripts in the nuclear runoff transcription assay.
Flavonoid complexes in Pisum sativum—III.

Abstract A method has been developed for the separation and estimation of kaempferol-3- p -coumaroyl-triglucoside (KGC) and quercetin-3- p -coumaroyltriglucoside (QGC) from Pisum sativum . A study of these two flavonoids in dark grown and in light treated pea plants has shown that the KGC concentration is unaffected by low intensity red light or by high intensity white light. On the other hand the synthesis of QGC is triggered by red light and thus appears to be under the control of the phytochrome system which might therefore control 3′-hydroxylation. In young green plants the highest concentration of the flavonoids is in the fully expanded leaves.
Safety in the nonoperating room anesthesia suite is not an accident: lessons from the National Transportation Safety Board

Purpose of review To review the findings of National Transportation Safety Board-related aviation near misses and catastrophes and apply these principles to the nonoperating room anesthesia (NORA) suite. Recent findings NORA is a specialty that has seen tremendous growth. In 2019, NORA contributes to a larger proportion of anesthesia practice than ever before. With this growth, the NORA anesthesiologist and team are challenged to provide safe, high-quality care for more patients, often with complex comorbidities, and are forced to utilize deeper levels of sedation and anesthesia than ever before. These added pressures create new avenues for human error and adverse outcomes. Summary Safety in modern anesthesia practice often draws comparison to the aviation industry. From distinct preoperational checklists, defined courses of action, safety monitoring and the process of guiding individuals through a journey, there are many similarities between the practice of anesthesia and flying an airplane. Consistent human performance is paramount to creating safe outcomes. Although human errors are inevitable in any complex process, the goal for both the pilot and physician is to ensure the safety of their passengers and patients, respectively. As the aviation industry has had proven success at managing human error with a dramatic improvement in safety, a deeper look at several key examples will allow for comparisons of how to implement these strategies to improve NORA safety.
Nuclear translocation of the pro-apoptotic Bcl-2 family member Bok induce apotosis

3499 Induction of apoptosis by the pro-apoptotic Bcl-2 family member Bok is not antagonized by either Bcl-2 or Bcl-XL suggesting that Bok might have a unique role in the apoptotic cascade. We show that human Bok is the only member of the Bcl-2 family having a leucine rich sequence indicative of a nuclear export sequence [NES] within the BH3 domain. Bok is detectable both in the nucleus and cytoplasm of cells and its nuclear concentration increases following treatment with leptomycin B. Mutating the NES of Bok results in an increase in its nuclear localization and apoptotic activity. Further, we show that Crm1 interacted with wildtype Bok. These results suggest that nuclear export of Bok is a regulated process mediated by Crm1 and for the first time link the association between the apoptotic activity and nuclear localization of a pro-apoptotic Bcl-2 family member.
Data-Driven Machine-Learning Quantifies Differences in the Voiding Initiation Network in Neurogenic Voiding Dysfunction in Women With Multiple Sclerosis.

Purpose To quantify the relative importance of brain regions responsible for reduced functional connectivity (FC) in their Voiding Initiation Network in female multiple sclerosis (MS) patients with neurogenic lower urinary tract dysfunction (NLUTD) and voiding dysfunction (VD). A data-driven machine-learning approach is utilized for quantification. Methods Twenty-seven ambulatory female patients with MS and NLUTD (group 1: voiders, n=15 and group 2: VD, n=12) participated in a functional magnetic resonance imaging (fMRI) voiding study. Brain activity was recorded by fMRI with simultaneous urodynamic testing. The Voiding Initiation Network was identified from averaged fMRI activation maps. Four machine-learning algorithms were employed to optimize the area under curve (AUC) of the receiver-operating characteristic curve. The optimal model was used to identify the relative importance of relevant brain regions. Results The Voiding Initiation Network exhibited stronger FC for voiders in frontal regions and stronger disassociation in cerebellar regions. Highest AUC values were obtained with 'random forests' (0.86) and 'partial least squares' algorithms (0.89). While brain regions with highest relative importance (>75%) included superior, middle, inferior frontal and cingulate regions, relative importance was larger than 60% for 186 of the 227 brain regions of the Voiding Initiation Network, indicating a global effect. Conclusion Voiders and VD patients showed distinctly different FC in their Voiding Initiation Network. Machine-learning is able to identify brain centers contributing to these observed differences. Knowledge of these centers and their connectivity may allow phenotyping patients to centrally focused treatments such as cortical modulation.
Meta-analysis of the General Coral Stress Response: Acropora corals show opposing responses depending on stress intensity

Abstract As climate change progresses, reef-building corals must contend more often with suboptimal conditions, motivating a need to understand coral stress response. Here we test the hypothesis that there is a stereotyped transcriptional response that corals enact under any stressful conditions, functionally characterized by downregulation of growth and activation of cell death, response to reactive oxygen species, immunity, and protein homeostasis. We analyze RNA-seq and Tag-Seq data from 14 previously published studies and supplement them with four new experiments involving different stressors, totaling over 600 gene expression profiles from the genus Acropora. Contrary to expectations, we found not one, but two distinct types of response. The type A response was observed under all kinds of high-intensity stress, showed strong correlations between independent projects, and was functionally consistent with the hypothesized stereotyped response. Higher similarity of type A responses irrespective of stress type supports its role as the General Coral Stress Response providing a blanket solution to severely stressful conditions. The distinct type B response was observed under lower intensity stress and was weaker and more variable among studies than type A. Unexpectedly, the type B response was broadly opposite the type A response: biological processes up-regulated under type A response tended to be down-regulated under type B response, and vice versa. Gene network analysis indicated that type B response does not involve specific co-regulated gene groups and is simply the opposite of type A response. We speculate that these paradoxically opposing responses may result from an inherent negative association between stress response and cell proliferation.
A comparative analysis of dynamic evaporator models for organic Rankine cycle waste heat recovery systems

Abstract As the Organic Rankine Cycle Waste Heat Recovery (ORC-WHR) gained research attention in recent years, the evaporator models are required in plant modeling and model-based controls. However, model comparison and selection works are lacking in ORC-WHR application. Different from the modeling work in literature, this paper aims to first time present a comparative study of three evaporator models for Organic Rankine Cycle Waste Heat Recovery (ORC-WHR) systems using the same set of identification parameters and experimental data. Finite volume model and moving boundary model are the most popular modeling methodologies in the field of ORC-WHR. Meanwhile, 0-D lumped models attract some research attention thanks to their low computational cost and least modeling effort. This paper first presents the three models, which are then validated with experiments data collected in a heavy-duty diesel engine ORC-WHR system. In the model comparison process, accuracy, computational cost and modeling effort are evaluated. All three models exhibit decent working fluid vapor temperature prediction accuracy with 6.6 K of mean error and 1.27% mean error percentage both in steady state and transient conditions. 0-D lumped model is found to be accurate enough for many application purposes, which is not found in literature. Based on the comparison results, model selection recommendation is given based on disparate application purposes and different phases of ORC-WHR system development.
Denying Systemic Equality: The Last Words of the Kennedy Court

This Article examines the Supreme Court’s voting, speech, and religion decisions in the 2017-18 term, Justice Kennedy’s last on the Court, arguing that their unifying feature is the denial of systemic equality. In a series of end-of-term constitutional rights decisions, the Court resolutely insisted on viewing equality in atomistic terms. In so doing, the Court ignored and even exacerbated systemic inequalities in each of these realms. Justice Kennedy was part of the majority in all of these decisions. Partisan gerrymandering is the classic systemic harm, yet the Court insisted on an individualized showing of injury in holding that Wisconsin plaintiffs had failed to demonstrate standing in their statewide challenge to a state districting plan (Gill v. Whitford). The Court also denied relief for an alleged gerrymander in Maryland (Benisek v. Lamone). In another redistricting case (Abbott v. Perez), the Court upheld Texas’s congressional and state legislative districts, eliding the evidence of systemic injury to Latinx voters. In two critical free speech decisions, the Court struck down a California law imposing certain notification requirements on pregnancy-related clinics (National Institute of Family and Life Advocates v. Becerra), and a state agency fee law for public sector labor unions (Janus v. AFSCME). Both decisions focus myopically on individual speakers, while ignoring the systemic viewpoint discrimination that arises from the Court’s First Amendment precedent. The Court’s disregard for systemic equality is also evident in two high-profile decisions involving claims of religious discrimination. The majority squinted hard to find evidence that the civil rights commissioners discriminated against a Christian baker who refused to make a cake for a same-sex wedding (Masterpiece Cakeshop v. Colorado Civil Rights Commission), while upholding an entry ban on people from six Muslim-majority countries despite overwhelming evidence of discriminatory animus against Muslims (Trump v. Hawaii). This Article describes and criticizes the last-term Kennedy Court’s inattention to—and in some cases hostility toward—systemic equality. It argues that the Court’s relentlessly atomistic approach to discrimination has obscured and intensified systemic inequalities in the public sphere.
Attribution Methods Reveal Flaws in Fingerprint-Based Virtual Screening

Fingerprint-based models for protein-ligand binding have demonstrated outstanding success on benchmark datasets; however, these models may not learn the correct binding rules. To assess this concern, we use in silico datasets with known binding rules to develop a general framework for evaluating model attribution. This framework identifies fragments that a model considers necessary to achieve a particular score, sidestepping the need for a model to be differentiable. Our results confirm that high-performing models may not learn the correct binding rule, and suggest concrete steps that can remedy this situation. We show that adding fragment-matched inactive molecules (decoys) to the data reduces attribution false negatives, while attribution false positives largely arise from the background correlation structure of molecular data. Normalizing for these background correlations helps to reveal the true binding logic. Our work highlights the danger of trusting attributions from high-performing models and suggests that a closer examination of fingerprint correlation structure and better decoy selection may help reduce misattributions.
Choice of local therapy for young women with early-stage breast cancer who have young-aged children.

Background Decision making regarding the initial treatment of women with breast cancer is complicated. In the current study, the authors examined the relationship between treatment choices and their children's ages among young women with early-stage breast cancer. Methods Using the MarketScan Commercial Claims and Encounters database, the authors identified women aged 20 to 50 years who underwent lumpectomy or mastectomy for early-stage breast cancer between 2008 and 2014. Predictors of compliance with radiotherapy after undergoing lumpectomy and of undergoing mastectomy were determined using multinomial logistic regression. The authors conducted sensitivity analyses to explore the impact of the number of young-aged children and a reduction in the sample size in 2014 due to the attrition of health plans contributing to MarketScan. Results A total of 21,052 women were included in the current analysis. Among women with at least 1 child aged Conclusions Among privately insured women with breast cancer, having young children was found to be strongly associated with the omission of postlumpectomy radiotherapy or undergoing mastectomy. Having >1 young-aged child further amplified these associations. The findings of the current study suggested that caring for young children may present unique challenges to young women with breast cancer.
Role of electron pathway in dimensionally increasing water splitting reaction sites in liquid electrolytes

Abstract Hydrogen from water splitting is one of the most promising alternatives for fossil fuels in solving the global energy crisis, while its electrochemical reaction mechanism, especially in liquid electrolytes, remains unclear. Herein, how the electrode conductivity affects the reaction sites of oxygen evolution reactions (OERs) in acidic and alkaline solutions was investigated by employing visualization system and electrochemical testing. Inserting Au nanolayers greatly increased electrode conductivities, improved OER kinetics and reduced cell ohmic resistance, leading to excellent water splitting performances in both acidic and alkaline electrolytes. Furthermore, the in-situ visualization results showed more reaction sites and higher catalyst utilizations were achieved by augmenting the electrode conductivity, and reaction sites increased from 1-dimension to 2-dimension. It was discovered that electrical conductivities of acidic and alkaline solutions are insufficient to overcome the sharp drop of potential in the electrical double layer for activating OER uniformly on low-conductivity catalysts, indicating the importance of electrical conductivity of the electrode in acidic and alkaline water electrolyzers. This study provided a guidance on how to develop efficient and compact electrodes for acidic and alkaline water electrolyzer stacks and other electrochemical devices, such as fuel cell, N2 reduction, CO2 conversion, etc.
Online Learning Demands in Max-min Fairness.

We describe mechanisms for the allocation of a scarce resource among multiple users in a way that is efficient, fair, and strategy-proof, but when users do not know their resource requirements. The mechanism is repeated for multiple rounds and a user's requirements can change on each round. At the end of each round, users provide feedback about the allocation they received, enabling the mechanism to learn user preferences over time. Such situations are common in the shared usage of a compute cluster among many users in an organisation, where all teams may not precisely know the amount of resources needed to execute their jobs. By understating their requirements, users will receive less than they need and consequently not achieve their goals. By overstating them, they may siphon away precious resources that could be useful to others in the organisation. We formalise this task of online learning in fair division via notions of efficiency, fairness, and strategy-proofness applicable to this setting, and study this problem under three types of feedback: when the users' observations are deterministic, when they are stochastic and follow a parametric model, and when they are stochastic and nonparametric. We derive mechanisms inspired by the classical max-min fairness procedure that achieve these requisites, and quantify the extent to which they are achieved via asymptotic rates. We corroborate these insights with an experimental evaluation on synthetic problems and a web-serving task.
Optimizing In Vitro Osteogenesis in Canine Autologous and Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells with Dexamethasone and BMP-2.

A growing body of work suggests that canine mesenchymal stromal cells (cMSCs) require additional agonists such as bone morphogenic protein-2 (BMP-2) for consistent in vitro osteogenic differentiati...
Delivery and neuraxial technique outcomes in patients with hemophilia and in hemophilia carriers: a systematic review

Female carriers are more common than males with hemophilia and unrecognized factor VIII or IX deficiency is associated with intrauterine growth retardation, epidural hematomas, blood transfusion, and peripartum hemorrhage. A review was conducted to assess the evidence for professional society recommendations for > 50% factor levels during labor. Two searches of Pubmed, CINAHL, Cochrane, and Google Scholar were completed in October 2019. The first for case reports and series described neuraxial techniques in patients with hemophilia—regardless of sex, age, or pregnant status. The second for case reports and series described bleeding outcomes of parturients with hemophilia. Primary outcomes were diagnosis of neuraxial hematoma (first search) and postpartum bleeding complications (second search). Thirteen articles (n = 134) described neuraxial techniques in patients with hemophilia. Neuraxial hematoma with paraplegia occurred in 3/134 patients—all had a factor level of 1%. Nineteen articles (2712 deliveries in 2657 women) described bleeding outcomes. Postpartum hemorrhage occurred in 7.1% (193/2712) of deliveries, of which 60% necessitated blood transfusion. Postpartum bleeding complications were twice as likely (51.0% [25/49] vs. 25.6% [52/203], P < 0.001) with factor activity < 50%. Therefore, factor levels should be assessed and increased above 50% prior to neuraxial technique and delivery. Trial registration: PROSPERO 2018 CRD42018110215.
Squalene-Based Influenza Vaccine Adjuvants and Their Impact on the Hemagglutinin-Specific B Cell Response

Influenza infections continue to cause significant annual morbidity and mortality despite ongoing influenza vaccine research. Adjuvants are administered in conjunction with influenza vaccines to enhance the immune response and strengthen protection against disease. Squalene-based emulsion adjuvants including MF59, AS03, and AF03, are registered for administration with influenza vaccines and are widely used in many countries. Squalene-based emulsion adjuvants induce a strong innate immune response, enhancing antigen presentation both quantitively and qualitatively to generate strong B cell responses and antibody production. They also diversify the reactivity profiles and strengthen the affinities of antibodies against the influenza hemagglutinin, increasing protection across virus clades. In this review, we consider the mechanisms of the enhancement of innate and adaptive immune responses by squalene-based emulsionSE adjuvants and the resulting increase in magnitude and breadth of hemagglutinin-specific B cell responses. We relate observed effects of SE adjuvants and current mechanistic understandings to events in responding lymph nodes. These insights will guide the rational design and optimization of influenza vaccines to provide broad and effective protection.
99529 The Role of ATF6-Mediated Signaling in PARP Inhibitor Resistant Ovarian Cancer

ABSTRACT IMPACT: This work has the potential to identify targetable pathways conveying resistance to PARP inhibitors that may improve ovarian cancer patient outcomes. OBJECTIVES/GOALS: High grade serous ovarian cancer is the deadliest gynecologic malignancy. PARP inhibitors are an FDA approved targeted therapy that is being used more and more frequently in the clinic. It is vital to understand mechanisms driving resistance to this therapy in order to develop treatments to improve patient responses. METHODS/STUDY POPULATION: RNA-sequencing and transcription factor analysis was used to identify pathways of interest. An AP-1 transcriptional reporter assays was used to confirm results of the transcription factor analysis. An unbiased lentiviral shRNA screen was used to identify AP-1 subunits promoting PARP inhibitor resistance. Lentiviral transduction allowed for the knockdown ATF6. Comet assays and two-plasmid systems were used to determine levels of DNA damage and levels of DNA damage repair respectively. RESULTS/ANTICIPATED RESULTS: PARP inhibitor resistant cell lines have increased WNT signaling which promotes to increased DNA damage repair. PARP inhibitor resistant cell lines also have increased AP-1 transcriptional activity, ATF6 expression, and active p38. ATF6 knockdown and p38 inhibition is sufficient to resensitize cells to PARP inhibition. Upon treatment with PARP inhibitors, ATF6 knockdown as well as p38 inhibition lead to increased DNA damage in PARP inhibitor resistant cell lines. RNA-sequencing reveals a signifcant overlap in downregulated genes in cells treated with a β-catenin inhibitor and cells with an ATF6 knockdown. DISCUSSION/SIGNIFICANCE OF FINDINGS: Due to the increasing prevalence of PARP inhibitors in the clinic, it is vital to uncover mechanisms contributing to resistance. This work has the potential to identify targetable pathways conveying resistance to PARP inhibitors that may improve ovarian cancer patient outcomes.
Development of patient reported outcomes-based machine learning algorithm for the six-month mortality prediction in patients with advanced cancer.

273Background: To date, studies of machine learning (ML) algorithms within oncology for mortality prediction have focused on structured electronic health record (EHR) data. Given the complex sympto...
The Viral Hypothesis in Parkinson’s Disease and in Alzheimer’s Disease

The most crucial unanswered question in Parkinson’s disease is its fundamental cause. Since Carlsson’s original suggestion that dopamine may be a transmitter in the central nervous system involved in the control of motor function and that it may be involved in the parkinsonian syndrome (Carlsson, 1959) and the now-classic paper by Ehringer and Hornykiewicz (1960) that definitively showed the significant reduction of dopamine concentration in the neostriatum of cases of idiopathic Parkinson’s disease and postencephalitic parkinsonism, the vast amount of work on the subject has focused on the biochemical and pharmacological correlates of this dopaminergic system failure involving particularly the nigrostriatal pathways. The concept of a specific neurotransmitter deficiency associated with a specific neurological syndrome potentially amenable to replacement therapy has appropriately generated a considerable degree of clinical and research interest for almost 25 years, but, with few recent exceptions, there has been hardly any focused or conceited research effort on looking at direct causal factors or primary initiating events in this disease process. As in Alzheimer’s disease (discussed in Section 2), another of the degenerative diseases of the brain of unknown origin with a specific biochemical substrate, any etiologic hypothesis for Parkinson’s disease—whether an age-related immune system dysfunction, a genetic factor, a missing —trophic— substance, an exogenous or endogenous toxin, or a virus (conventional or unconventional)—would have to explain the selective involvement of specific transmitter-defined neuronal pathways, the relative nonspecificity of the brain lesions that define the disease, and the clinical involvement of a sizable segment of the aging population.
An Overview of Serine Proteases

This unit summarizes the families of serine proteases and their mechanism of catalysis. Methods for assays and determining substrate specificity are briefly described. The mode of action of commonly available inhibitors is also included.
Representation Operators and Computation

This paper analyses the impact of representation and search operators on Computational Complexity. A model of computation is introduced based on a directed graph, and representation and search are defined to be the vertices and edges of this graph respectively. Changing either the representation or the search algorithm leads to different possible complexity classes. The final section explores the role of representation in reducing time complexity in Artificial Intelligence.
Excitation of T Phases from Shallow and Intermediate-Depth Earthquakes in the Sourhten Vanuatu (New Hebrides) Arc,

Abstract : In this paper, we present observations on the excitation of T phases from shallow and intermediate-depth earthquakes located along the southern Vanuatu (New Hebrides) Island arc and recorded at short-period, vertical-component seismic stations on the Loyalty Islands of Lifou and Mare. Most of these earthquakes are part of the northeasterly dipping Benioff zone that defines the descending Australian plate in the upper 300 km of the mantle beneath the Vanuatu arc. The Loyalty Islands are uniquely situated on the oceanic Australian plate at distances of about 100 to 200 km in front of the southern Vanuatu trench axis. The main objectives of this study are: (1) to investigate in detail the nature and pattern of the excitation of T phases from sources of considerably varying depths, and (2) to study the effects of submarine physiography on the observed pattern. This study was particularly desirable because of the relatively unique geometry of the sources and the recording stations and because the events used in this study are well-located using local land and ocean-bottom seismic networks (Coudert et al., 1981).
Escherichia coli mutants defective in membrane phospholipid synthesis: binding and metabolism of 1-oleoylglycerol 3-phosphate by a plsB deep rough mutant.

Abstract Mutants of Escherichia coli containing a defective sn-glycerol 3-phosphate acyltransferase are conditionally defective in the synthesis of acylglycerol phosphate (acylglycerol-P). Incubation of a deep rough derivative of one of these plsB strains with 1-[3H]oleoylglycerol-32P resulted in the binding of up to 70 nmol of oleoylglycerol-P per 100 nmol of cellular phospholipid. The binding was dependent on time, oleoylglycerol-P concentration, and the quantity of cells employed. The rate and extent of oleoylglycerol-P binding was affected by the deep rough mutation. The altered phospholipid composition due to oleoylglycerol-P binding was without consequence on cell growth and viability, but caused the appearance of intracellular multilamellar structures. Use of the double-labeled oleoylglycerol P demonstrated that the entire molecule was bound to the cell. Intact [3H]-oleoylglycerol-32P was converted to phosphatidylethanolamine and phosphotidyl-glycerol at a rate about 40% of that of de novo phospholipid synthesis. These data demonstrate the transmembrane movement of oleoylglycerol-P to the inner surface of the cytoplasmic membrane and suggest that it may become possible to supplement plsB strains of E. coli with acylglycerol-P's.
Reaction of the Sulfhydryl Group of Papain with Chloroacetic Acid

The kinetics of the alkylation of the essential sulfhydryl group of papain with chloroacetic acid was studied. The variation of the second order rate constant with pH at 4.5° and 30.5°, Γ/2 = 0.07, is bell-shaped, with rate constants at a maximum near neutrality, approaching zero at low pH, and approaching a positive minimum at high pH. These profiles are described by a formulation which relates the apparent rate constants both with the states of dissociation of the sulfhydryl and other groups in papain and with the absolute rate constants for sulfhydryl reaction under specific conditions of pH. This formulation, as well as the absolute rate constants and the dissociation constants, have been used to suggest the presence of groups near the active center sulfhydryl group which affect the pH dependence of both the alkylation and the catalytic reactions of papain.
Pore scale consideration in unstable gravity driven finger flow

[2] To explain the dynamic behavior of the matric potential at the wetting front of gravity driven fingers, we take into account the pressure across the interface that is not continuous and depends on the radius of the meniscus, which is a function of pore size and the dynamic contact angle θd. θd depends on a number of factors including velocity of the water and can be found by the Hoffman-Jiang equation that was modified for gravity effects. By assuming that water at the wetting front imbibes one pore at a time, realistic velocities are obtained that can explain the capillary pressures observed in unstable flow experiments in wettable and water repellent sands.
Border tax adjustments: Do they distort trade?

Abstract A familiar proposition asserting the trade-neutrality of uniform, indirect taxes under both the origin and destination principles is re-examined in the context of a world with trade in intermediate goods. A uniform, general sales tax is shown to be trade-neutral under the destination principle, but trade-distorting under the origin principle. A ‘stage of processing’ value added tax is nondistorting under either border tax adjustment principle. The discussion is then related to a proposed change in GATT rules that would require origin principle administration of the European value added tax.
Normalization of Left Ventricular Ejection Fraction after Cardiac Resynchronization Therapy Also Normalizes Survival

Background Earlier studies in patients with reduced left ventricular ejection fraction (LVEF) ≤35% and prolonged QRS showed better survival outcomes with cardiac resynchronization therapy (CRT). Some patients respond dramatically to CRT by improving their LVEF to the normal range and are considered “super-responders.” Our aim was to determine whether super-responders survival increases to levels comparable to the general population. We compared the survival of super-responders to the general population matched for age and sex. Methods Of 909 patients with CRT device implantation between September 1998 and July 2008, 814 patients had pre- and post-CRT echocardiogram. A total of 95 patients with LVEF ≥ 50% following CRT were classified as super-responders. For 92 super-responders, who had U.S. Social Security numbers, an age- and sex-matched example was selected from the Social Security Life Tables. An expected survival plot of the matched population was then compared to the actual survival of super-responders. Results Super-responders had comparable survival to the age-sex matched general population (P = 0.53), and Kaplan-Meier survival analysis in 92 patients showed that super-responders with CRT pacemakers had similar survival to those with CRT implantable cardioverter defibrillators (P = 0.77). Super-responders were more likely to be females (54% vs 25%, P < 0.001) and less likely to have significant coronary artery disease (62% vs 42%, P < 0.001). Conclusions Normalization of LVEF by CRT improves survival to levels comparable to the general population. This observation favors the concept that some CRT candidates have a cardiomyopathy likely generated by the conduction abnormality that is reversible through biventricular pacing.
Assessing North American Spanish

Over the last 50 years Spanish has become the predominant second language of choice in the academic context in the US. Although Spanish is taught at all levels of the US curriculum (from elementary to college level), it is mostly at the college level that a variety of standardized tests appeared; and these tests are used at the national level to assess second language competence in general. Arguably some limited progress has been made in the assessment of Spanish. Nevertheless, the two biggest challenges continue to be (1) a clear description of the theoretical construct that represents competence in Spanish as a second language; and, concomitantly, (2) the identification of efficient procedures for measuring the target construct. This chapter describes these challenges and argues that the responsibility for improving the assessment models should be shared by testing agencies and academic institutions. Keywords: Assessment methods; Northern America; Second language acquisition
Journey through relativity

Einstein's Universe. Written by Nigel Calder. Narrated by Peter Ustinov. Produced by Martin Freeth. (BBC-TV: London; WGBH: Boston, 1979.) First UK transmission: 14 March, 1979, BBC-2, 1900 h. Repeated 18 March.
Inability of debilitated Escherichia coli χ1776 to colonise germ-free rodents

The potential hazards of recombinant DNA research have focused attention on the development of a strain of bacteria that will not survive outside the laboratory. A genetically engineered strain of Escherichia coli K-12 has been developed that not only has several growth requirements (including diaminopimelic acid), but also exhibits high sensitivity to ultraviolet radiation, bile salts, detergents, antibiotics and temperature. This debilitated strain has been designated E. coli χ1776 and has been widely recommended for use in recombinant DNA research1. So far only conventional animals have been used to test the ability of a genetically engineered bacterium to replicate in vivo. We postulated that lack of competition from the normal bacterial flora, due to disease state or to antibiotic therapy, might increase susceptibility to colonisation by E. coli χ1776. The germ-free animal represents an extreme state in which resistance to bacterial colonisation is decreased by lack of indigenous microbial competition and by an underdeveloped immune system 2. We therefore attempted to colonise germ-free rats and mice (maintained at the University of Wisconsin, Gnotobiotic Laboratory) with E. coli χ1776. Each of several attempts to colonise the gastrointestinal tract was unsuccessful; viable organisms could not be cultured from either fecal material or tissue samples for up to 2 months after inoculation.