cssi/SciSciGPT-SciSciNet huggingface dataset:
318. Development of Optimized AAV Serotype Vectors for the Potential Gene Therapy of Cystic Fibrosis

Cystic fibrosis (CF) is a single gene mutation that it is estimated to affect 30,000 children and adults in the US, and 70,000 patients worldwide. The lack of a functional gene leads to a defective ion conductance, and the associated water transport abnormalities produce increased viscosity of secretions in exocrine epithelial cells. In the respiratory airways, mucus plugging and retention produces severe lung diseases making this the main cause of mortality among CF patients. Several groups have tried to correct this defect using recombinant AAV as a vector to carry the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelial cells, but without success, mostly because of poor transduction efficiency of these cells.Although AAV vectors have been used successfully in animal models, and shown efficacy in several clinical trials, a number of steps in the life cycle of AAV, including intracellular trafficking, continue to appear to limit the effectiveness of these vectors in gene therapy. We have recently documented that the substitution of surface-exposed specific tyrosine (Y), serine (S), and threonine (T) residues on AAV capsids significantly increases the transduction efficiency of these vectors, both in vitro and in vivo, presumably by preventing phosphorylation, subsequent ubiquitination, and proteasome-mediated degradation. The current studies were undertaken to identify the optimal AAV serotype vectors with improved transduction efficiency in airway epithelial cells. First, we evaluated the transduction efficiency of several commonly used AAV serotype vectors in primary normal (CRL-40111) and CF donor-derived (CRL-4013) human airway epithelial cells. Our data indicated that AAV6 serotype vectors transduce both of these cell lines at high levels, followed by AAV2, AAV5, and AAV1. Interestingly, that transduction efficiency of AAV5 vectors, but not AAV1, 2, and 6, was higher in CRL-4013 cells compared with that in CRL-4011 cells. We have previously developed a number of single- and multiple-mutant capsid-optimized vectors for each serotype (18 for AAV1, 100 for AAV2, 15 for AAV5, and 35 for AAV6). Thus, we next evaluated the transduction efficiency of these capsid-optimized AAV serotype vectors in human airway epithelial cells. The result showed that mutations in a single serine (S) residue at position 663 for AAV1, 662 for AAV2, 651 for AAV5, and 663 for AAV6 to valine (V) increased the transduction efficiency 2-3-fold compared with the wild-type (WT) AAV vectors. Among the multiple-mutants, several beneficial combinations of Y and T residues were identified, such as AAV2-Y444-500-730F+T491V, AAV1-Y705-731F+T492V, AAV5-Y263+719F and AAV6-Y705-731F+T492V, which increased the transduction efficiency 3-5-fold compared with the WT-AAV vectors. Overall, the capsid-optimized AAV6 serotype was identified as the most efficient. Studies are currently underway to generate the optimized AAV6-CFTR vector for its use in the potential gene therapy for CF.
SGL Networked Interpreter

The chapter reveals general structure and organization of SGL interpreter which can be networked with other similar interpreters for solving tasks in parallel and distributed way. Main data structures of the interpreter, its functional processors, and their interactions are described which themselves may work together as an integral and parallel system, depending on implementation. The scenario history-based forest-like track system of the distributed interpreter allows it to serve as spatial support and control backbone providing overall awareness and processing of the returned data, while delivering new scenario code and data to the world positions reached previously, also maintaining and updating distributed information resources with their removal if not used anymore.
Abstract 236: HDAC5 is Required for Recruitment of an HDAC1/Sin3a Repressor Complex to the Ncx1 Promoter During Cardiac Hypertrophy

Background: Pressure overload can lead to aberrant gene expression and subsequent adverse hypertrophic changes in cardiac tissue. Histone deacetylases (HDACs) play an important role in alteration of gene expression during cardiac hypertrophy. We observed that class I/IIb HDAC inhibitors, TSA and Vorinostat prevent upregulation of the sodium calcium exchanger gene, Ncx1 , in response to cardiac hypertrophy. Chromatin immunoprecipitation (ChIP) demonstrates the class I HDAC, HDAC1, class IIa HDAC, HDAC5 and co-repressor, Sin3a are recruited to the Ncx1 promoter via Nkx2.5. Class IIa HDACs have very poor catalytic activity and can interact with many specific transcription factors. Thus, we hypothesized , that the class IIa, HDAC5 acts as a scaffold to recruit the class I HDAC/Sin3a complex to the Ncx1 promoter. Methods and Results: To test our hypothesis adult cardiomyocytes were treated with either vehicle (control) or class specific HDAC inhibitors: class I (Entinostat), or class IIa (dPAHA). We found that class I HDAC inhibitor, Entinostat, abrogates adrenergic stimulated upregulation of Ncx1 expression in adult cardiomyocytes to almost control levels (p Ncx1 expression (p>0.05 Student’s t; n=4). Also, Entinostat inhibits Ncx1 upregulation in a transaortic constriction (TAC) model of hypertrophy. We assessed the role class IIa HDAC5 in Ncx1 regulation, by subjecting HDAC5-Knockout mice (HDAC5-KO) to TAC. We saw no induction of Ncx1 expression post-TAC (n=5). Furthermore, Co-IP and ChIP analyses show that interactions between the Sin3a/HDAC1 complex and Nkx2.5 are lost in the absence of HDAC5 expression and fail to be recruited to the Ncx1 promoter. To conclude , our data suggests the catalytic activity of HDAC5 is not essential but rather HDAC5 is a scaffold that recruits the class I HDAC1–Sin3a complex to the Ncx1 promoter. Our novel findings provide insight into possible roles of class IIa HDACs in regulation of gene expression and efficacy of HDAC inhibitors to treat cardiac pathologies.
Document Expansion Using External Collections

Document expansion has been shown to improve the effectiveness of information retrieval systems by augmenting documents' term probability estimates with those of similar documents, producing higher quality document representations. We propose a method to further improve document models by utilizing external collections as part of the document expansion process. Our approach is based on relevance modeling, a popular form of pseudo-relevance feedback; however, where relevance modeling is concerned with query expansion, we are concerned with document expansion. Our experiments demonstrate that the proposed model improves ad-hoc document retrieval effectiveness on a variety of corpus types, with a particular benefit on more heterogeneous collections of documents.
Preparations for the Advanced Scintillator Compton Telescope (ASCOT) balloon flight

We describe our ongoing work to develop a new medium-energy gamma-ray Compton telescope using advanced scintillator materials combined with silicon photomultiplier readouts and fly it on a scientific balloon. There is a need in high-energy astronomy for a medium-energy gamma-ray mission covering the energy range from approximately 0.4 - 20 MeV to follow the success of the COMPTEL instrument on CGRO. We believe that directly building on the legacy of COMPTEL, using relatively robust, low-cost, off-the-shelf technologies, is the most promising path for such a mission. Fortunately, high-performance scintillators, such as Cerium Bromide (CeBr3) and p-terphenyl, and compact readout devices, such as silicon photomultipliers (SiPMs), are already commercially available and capable of meeting this need. We are now constructing an Advanced Scintillator Compton Telescope (ASCOT) with SiPM readout, with the goal of imaging the Crab Nebula at MeV energies from a high-altitude balloon flight. We expect a ~4-sigma detection at ~1 MeV in a single transit. We present calibration results of the detector modules, and updated simulations of the balloon instrument sensitivity. If successful, this project will demonstrate that the energy, timing, and position resolution of this technology are sufficient to achieve an order of magnitude improvement in sensitivity in the medium-energy gamma-ray band, were it to be applied to a ~1 cubic meter instrument on a long-duration balloon or Explorer platform.
Percutaneous Repair of Severe Eccentric Mitral Regurgitation Due to Medial Commissural Flail: Challenges for Imaging and Intervention

Percutaneous repair of severe mitral regurgitation (MR) is an important treatment option for patients deemed to be at high risk for surgical intervention.1, 2 The presence of a central regurgitant lesion is generally considered an important anatomic criterion to achieve optimal results.2 We present a case of severe eccentric MR successfully treated with a MitraClip device (Abbott Vascular, Santa Clara, CA) and discuss the uniqueness of the procedure and the role of intraprocedural guidance by two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE).
Streamlined circular proximity ligation assay provides high stringency and compatibility with low-affinity antibodies

Proximity ligation assay (PLA) is a powerful tool for quantitative detection of protein biomarkers in biological fluids and tissues. Here, we present the circular proximity ligation assay (c-PLA), a highly specific protein detection method that outperforms traditional PLA in stringency, ease of use, and compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to an analyte, providing a scaffolding that positions two free oligonucleotides such that they can be ligated into a circular DNA molecule. This assay format stabilizes antigen proximity probe complexes and enhances stringency by reducing the probability of random background ligation events. Circle formation also increases selectivity, since the uncircularized DNA can be removed enzymatically. We compare this method with traditional PLA on several biomarkers and show that the higher stringency for c-PLA improves reproducibility and enhances sensitivity in both buffer and human plasma. The limit of detection ranges from femtomolar to nanomolar concentrations for both methods. Kinetic analyses using surface plasmon resonance (SPR) and biolayer interferometry (BLI) reveal that the variation in limit of detection is due to the variation in antibody affinity and that c-PLA outperforms traditional PLA for low-affinity antibodies. The lower background signal can be used to increase proximity probe concentration while maintaining a high signal-to-noise ratio, thereby enabling the use of low-affinity reagents in a homogeneous assay format. We anticipate that the advantages of c-PLA will be useful in a variety of clinical protein detection applications where high-affinity reagents are lacking.
Substance Abuse Among American Indians and Alaska Natives: An Integrative Cultural Framework for Advancing Research

Research consistently highlights the high prevalence of substance-related psychopathology in the American Indian/Alaska Native (AIAN) population. Recent epidemiological literature suggests that these trends are not diminishing, despite decades of etiological work and prevention programs. The aim of this article was to examine the literature on risk and protective factors for substance-related psychopathology in the AIAN population from the perspective of Betancourt’s integrative model of culture, psychological processes, and behavior (Betancourt et al. 1993, 2010, 2011). This model specifies the structure of relations among sociostructural (e.g., income and education), cultural (e.g., values and norms), and psychological (e.g., cognition and emotion) factors influencing behavior. Articles were reviewed that identified one or more determinants of substance-related psychopathology in the AIAN population. An analysis of the reviewed articles revealed that the factors investigated in relation to substance-related psychopathology have typically been studied independently of each other. Also, most studies have examined factors that are rather distal from behavior (e.g., sociostructural). Results suggest that research on the interrelations among cultural and psychological, in addition to sociostructural, determinants may enhance our understanding of substance-related psychopathology in this population. To this end, suggestions for future research are derived from results of the studies reviewed. Such theoretically driven research may contribute to more effective interventions and the reduction of substance-related disparities among the AIAN population.
A Machine Learning Approach Predicts Tissue-Specific Drug Adverse Events

One of the main causes for failure in the drug development pipeline or withdrawal post approval is the unexpected occurrence of severe drug adverse events. Even though such events should be detected by in vitro, in vivo, and human trials, they continue to unexpectedly arise at different stages of drug development causing costly clinical trial failures and market withdrawal. Inspired by the "moneyball" approach used in baseball to integrate diverse features to predict player success, we hypothesized that a similar approach could leverage existing adverse event and tissue-specific toxicity data to learn how to predict adverse events. We introduce MAESTER, a data-driven machine learning approach that integrates information on a compound9s structure, targets, and phenotypic effects with tissue-wide genomic profiling and our toxic target database to predict the probability of a compound presenting with different types of tissue-specific adverse events. When tested on 6 different types of adverse events MAESTER maintains a high accuracy, sensitivity, and specificity across both the training data and new test sets. Additionally, MAESTER scores could flag a number of drugs that were approved, but later withdrawn due to unknown adverse events - highlighting its potential to identify events missed by traditional methods. MAESTER can also be used to identify toxic targets for each tissue type. Overall MAESTER provides a broadly applicable framework to identify toxic targets and predict specific adverse events and can accelerate the drug development pipeline and drive the design of new safer compounds.
In-Liquid Streamer Characterization and Fractal Analysis

Streamer discharges provide efficient means for chemical change in a variety of applications, some of which are ozone generation, water purification, and hydrogen and syngas production. Better understanding of the streamer growth process, and simple physical characteristics, such as size and geometry, could lead to an increase in product yield for these plasma-based applications. This report focuses in particular on the size and geometry of streamers formed in liquid, with an underlying goal to generate hydrogen gas and syngas via plasma-induced hydrocarbon reformation. The examination of size and geometry was performed with a measurement of the streamer length and area, and a fractal analysis, respectively. The fractal analysis used a box counting method to quantify the geometry of the streamer with a metric of complexity called the fractal dimension. This technique was explored for its possible use in characterizing streamers in regards to volume and surface area as such direct measurements can be difficult to obtain. The streamers discussed in this paper were induced under different operating conditions and liquid parameters, namely electrical conductivity of the liquid, voltage polarity, and carbon chain length of the liquid.
ACTH and the metabolism of adrenal cell cultures.

Publisher Summary This chapter discusses the mechanism by which ACTH exerts its metabolic effects on the adrenal cell and which has been the focus of investigation in a number of laboratories. It presents data to demonstrate the usefulness of stable cultures of functional adrenal cells for the investigation of the mechanisms of steroid synthesis and ACTH action. ACTH can effect simultaneous alterations in carbohydrate, lipid, and steroid metabolism. The ability to dissociate some of these effects in short-term experiments does not necessarily rule out the importance of this interplay in the maintenance of the functional integrity of the cell, particularly during longer periods of stimulation. Although the acute response to ACTH may not be associated with the induction of synthesis of new proteins, long-term experiments demonstrate that ACTH can induce increases in the levels of specific enzyme proteins. The isolation of cell lines with the differences in biochemical properties may provide a useful approach for assessing the role of cyclic AMP and other nucleotides in the regulation of steroid synthesis.
Neurosteroids in Cortical Development and the Etiology of Schizophrenia

Schizophrenia is thought to be a neurodevelopmental disorder, and both genetic and non-genetic risk factors associated with the disease are related to neural development and function. However, no one mechanism has yet been proposed that explains the entire pathology of the disorder. One pathway that is clearly involved, however, is signaling via GABA. Post-mortem investigations reveal deficits in GABA transmission and altered localization of some GABAergic interneurons in the brains of schizophrenic patients. Furthermore, GABAergic signaling during early cortical development influences neuronal migration and later enhances synapse formation. Modulators of GABA signaling, including the neuroactive steroids, are therefore critical for normal neurodevelopment. Neurosteroids, including allopregnanolone, are potent, endogenous, stress-responsive modulators of GABA A receptor function. Cortical neurosteroid levels are dynamically regulated across embryonic and early postnatal development, and may differentially affect GABA A receptor function across distinct ontological periods. Furthermore, neuroactive steroid levels are increased in response to gestational stress or infection, both of which are risk factors associated with the development of a schizophrenia-vulnerable phenotype. The unique situation of neurosteroids at the junction of stress and GABA transmission makes them an important mechanism linking stress and neurodevelopmental vulnerability, as in the etiology of schizophrenia.
COMPARATIVE ANALYSIS OF PRECLASSIC AND PROTOCLASSIC BURIAL PRACTICES AT IZAPA AND IN SOUTHEASTERN MESOAMERICA

Extensive investigation at the archaeological site of Izapa in southern Chiapas, Mexico, by the New World Archaeological Foundation yielded few burials at the site's core ceremonial precinct. Those found were located on the acropolis that supports Mound 30a and defines the north side of Izapa Group B. The majority of caches found in this zone date to the Protoclassic Hato and Itstapa phases (100 b.c.–a.d. 250). The shift in mortuary practices ca. 100 b.c. was accompanied by several changes to the site's occupation and architectural patterns. Study of these mortuary traditions provides important insights regarding the reconfiguration of Izapa's political organization at the turn of the millennium. Comparisons of mortuary practices at Izapa with those of neighboring civic-ceremonial centers El Ujuxte, Takalik Abaj, and Kaminaljuyu during the Preclassic and Protoclassic transitions contextualizes the practices found at Izapa at a regional level.
Lifetime Achievement and Quality of Life in Adult Survivors of Pediatric Heart Transplant

Purpose As survival in pediatric heart transplant (HTx) improves, an increasing proportion of children receiving HTx are entering adulthood. Many quality of life (QOL) studies have looked at adult HTx patients, but only a few have looked at the population who received a HTx as a child. It is important to examine how this chronic illness affects children's development and eventual transition to adulthood, so that we may improve counseling of future patients. Methods Patients who received a HTx with the pediatric program at Columbia University Medical Center from 1984 through August 1, 2007, who are now > 18 years old and have survived over 10 years since HTx were asked to complete 2 surveys: (1) CHONY Pediatric Heart Transplant Life Achievement Survey, which examines marital and employment status, education level, personal income, health insurance status, and living environment, and (2) Quality of Life Index (QLI) by Ferrans and Powers, which scores life satisfaction from 0 (least satisfied) to 1 (most satisfied) as an overall score, and in 4 distinct domains (health/function, socioeconomic, psych/spiritual, and family). Results The Life Achievement Survey was completed by 54 patients (median age 8 years at transplant and 25 years at time of survey, 44% female, 26% transplanted for congenital heart disease). Fifteen patients have either been married (1 divorced) or part of an unmarried couple, and 7 have children (6 biological including 1 female). Thirty-seven patients are either employed or a student, and 16 earn over $25,000 annually. Almost a third of patients (n=16) live independently, while 5 are homeowners. Fifty patients completed the QLI and reported a mean overall QLI 0.76±0.14. The scores in the health/function, socioeconomic, psych/spiritual, and family domains were 0.77, 0.74, 0.74, and 0.8, respectively. Conclusion Our cohort of adult survivors of pediatric HTx have achieved many standard adult milestones such as receiving an education, maintaining relationships, being employed, and living independently. Additionally, they report a suitable QOL, especially in the health/function and family domains.
Cost-Benefit Analysis of Implementing Telemedicine in the ICU

Tele-ICU implementation costs can be significant, and it is important for organizations to understand the various components of the costs involved. A careful cost-benefit analysis is highly recommended given the unique needs and goals of each organization. In the absence of direct commercial revenues from insurers for patient encounters via tele-ICU services, organizations might consider evaluating financial benefits in a more global context factoring in indirect revenue sources, cost avoidance, and cost reductions due to enhanced efficiency of service delivery. In order to demonstrate tangible financial benefits, deep integration into bedside ICU services is essential. This chapter provides an overview of implementation costs, revenue sources, and a framework for cost-benefit analysis for tele-ICU implementation.
Colloidal Silver Ingestion Associated with Leukocytoclastic Vasculitis in an Adolescent Female

BACKGROUND Leukocytoclastic vasculitis is a disease of the small vessels and is uncommon in children. In this case report, we present an adolescent case of leukocytoclastic vasculitis associated with the ingestion of colloidal silver, a naturopathic drug. This report highlights the rarity of the patient's presentation and inducing agent. CASE REPORT A 19-year-old female presented in the Emergency Department with severe rash on the face, and neck, and then continued to spread in a craniocaudal fashion during the day of presentation to involve trunk, back, upper and lower extremities. There was no recent travel, no pets and a negative family history for rheumatologic or autoimmune diseases. Her home medications included colloidal silver for "internal cleansing" for 4 weeks prior to Emergency Department presentation. Once the clinicians were aware of the continued ingestion of colloidal silver, the patient was advised to discontinue the drug. The patient was started on methylprednisolone with preliminary diagnosis of vasculitis, as well as concurrent therapy with colchicine. The rash was noted to be receding from the face within 24 hours. Over a hospital course of 5 days, the patient's rash and pruritus continued to slowly improve. CONCLUSIONS The ingestion of a naturopathic drug, colloidal silver, caused vast leukocytoclastic vasculitis in our patient warranting hospitalization due to the extent of the disease. The symptoms resolved after discontinuation of colloidal silver ingestion. Due to unknown safe ingestion concentrations and potential side effects, use of colloidal silver should be discouraged.
Preoperative Performance of PROMIS in Patients With Patellofemoral Malalignment and Chondral Disease.

Background:Use of the Patient-Reported Outcomes Measurement Information System (PROMIS) instrument has not yet been validated in patients undergoing operative treatment for patellofemoral malalignm...
Inefficient Asset Price Booms

Endogenous movements in the wealth distribution can generate asset price booms in which financial intermediaries increasingly engage in moral hazard and originate low-quality assets that are excessively exposed to aggregate risk. Central to the mechanism is a pecuniary externality whereby buyers of financial assets do not internalize that high asset prices harm origination incentives. Inefficient asset price booms occur only if risk-averse savers are sufficiently wealthy initially, and incentives decline only after a sufficiently long macroeconomic expansion. During the run-up, increasing asset prices instead allow for an efficient expansion of aggregate credit. I discuss implications for monetary policy and financial regulation.
Wellness, burnout, and the dermatologist: Fundamentals for practice longevity.

Abstract Physician wellness is a critical component of any effective health care system, as physicians serve essential roles as diagnosticians, surgeons, and leaders in medical care. Physician burnout, defined as a combination of the presence of emotional exhaustion, depersonalization, and a diminished sense of personal accomplishment, is an increasingly recognized problem in the US health care system, as rates of burnout among physicians are on the rise, now exceeding 50%. To date, few studies have examined the impact of burnout on dermatologists specifically, but existing studies evaluating physicians collectively have shed light on the problem that exists in our specialty. This review focuses on the causes of physician dissatisfaction and burnout and provides an overview on interventions to mitigate them while emphasizing wellness; where applicable, special emphasis is placed on dermatologists.
Focused Transthoracic Cardiac Ultrasound: A Survey of Training Practices

Objective The role of focused assessment by transthoracic echocardiography or focused cardiac ultrasound (FoCUS) in the perioperative setting is uncertain and evolving. To the authors’ knowledge, there are no studies that evaluate the current teaching practices regarding FoCUS in US anesthesiology residencies. The authors surveyed residents and residency program directors to examine the frequency, type, and variability of instruction regarding training of FoCUS. Design A survey study. Setting Anesthesiology residency programs in the United States. Participants All 133 Accreditation Council for Graduate Medical Education anesthesiology program directors and their residents were invited to participate in an anonymous electronic survey. Measurements and Main Results In all, 292 respondents replied to the survey, and 245 were included in the analysis. Overall response rate was 30% for program directors. The majority of the respondents were trainees (83.7%). FoCUS training was reported to be present by 36% of respondents. Respondents from institutions in which>10% of attending physicians used FoCUS were nearly 3 times as likely as those in which fewer attending physicians used FoCUS to report presence of FoCUS training program. The most common training mode is lectures with simulation (34%), followed by bedside training (31%). The most frequently reported responsible training parties were anesthesiologists (75%), followed by cardiologists (14%). Although FoCUS training is relatively rare, most respondents (187 of 205 residents and 26 of 40 program directors) said that FoCUS should be the standard in training for anesthesia residents. Conclusions Despite the increasing availability and use of ultrasound in clinical practice, FoCUS-related use and training remain uncommon in anesthesiology. Trainees in anesthesiology are not receiving adequate instruction in FoCUS despite their desire to acquire this skill.
Diagnosing the column-integrated moist static energy budget associated with the northward-propagating boreal summer intraseasonal oscillation

Column-integrated moist static energy (MSE) budgets associated with the northward-propagating boreal summer intraseasonal oscillation (BSISO) are diagnosed for the Bay of Bangel (BoB) and western North Pacific (WNP) regions. While an active BSISO convection is in phase with a positive column-integrated MSE perturbation, the MSE tendency exhibits a marked north–south asymmetry about the convection, with positive (negative) anomaly to its north (south). An MSE budget diagnosis reveals that the advection of anomalous MSE by the background southwesterly plays a dominant role in causing such an asymmetry and thus promotes the northward propagation, as the anomalous rainband associated with the BSISO has a northwest-southeast tilted structure. The anomalous BSISO wind plays a negative role, because the low-level easterly anomaly to the north of the BSISO convection tends to suppress the surface evaporation through reduced near-surface wind speed, inhibiting the north–south asymmetry. In addition, as maximum background MSE appears over the Asian land region, the advection by the low-level easterly anomaly contributes negatively over the WNP while it has little impact over the BoB. When the BSISO convection is near the equator, a much stronger subsidence anomaly appears to the north than the south due to the equatorial asymmetry of the summer mean state. This leads to a greater MSE tendency north of the equator due to greater anomalous vertical MSE advection, supporting the initiation of the northward propagation.
Catheter-based treatments for ventricular septal defects

Abstract Ventricular septal defects (VSDs) are a common form of congenital heart disease and those defects that do not close spontaneously often require intervention. While surgical closure of VSDs in the current era are associated with low morbidity and mortality, transcatheter-based approaches often avoid the need for a sternotomy, avoid the need for cardiopulmonary bypass, allow for shorter recovery times, and are potentially less costly. Percutaneous approaches, however, remain limited in smaller infants and children secondary to complicated wire and catheter courses that can result in hemodynamic instability, potential injury to heart valves or peripheral vasculature, and procedural failure. Intraoperative approaches, with and without the use of cardiopulmonary bypass, have also been described since 1993 [48] with procedural refinements and advances in device technologies allowing for improved outcomes over time. This chapter will discuss the history of device closure of perimembranous and muscular VSDs, as well as transcatheter and intraoperative closure in the current era.
Correction to: Deliberative framing: opening up discussions for local-level public engagement on climate change

Part of the reference section on the article was included as Supplementary Material with the article online. The full reference section for the article is included here.
Machine Learning Algorithms Predict Clinically Significant Improvements in Satisfaction After Hip Arthroscopy.

Purpose To develop machine learning algorithms to predict failure to achieve clinically significant satisfaction after hip arthroscopy. Methods We queried a clinical repository for consecutive primary hip arthroscopy patients treated between January 2012 and January 2017. Five supervised machine learning algorithms were developed in a training set of patients and internally validated in an independent testing set of patients by discrimination, Brier score, calibration, and decision-curve analysis. The minimal clinically important difference (MCID) for the visual analog scale (VAS) score for satisfaction was derived by an anchor-based method and used as the primary outcome. Results A total of 935 patients were included, of whom 148 (15.8%) did not achieve the MCID for the VAS satisfaction score at a minimum of 2 years postoperatively. The best-performing algorithm was the neural network model (C statistic, 0.94; calibration intercept, –0.43; calibration slope, 0.94; and Brier score, 0.050). The 5 most important features to predict failure to achieve the MCID for the VAS satisfaction score were history of anxiety or depression, lateral center-edge angle, preoperative symptom duration exceeding 2 years, presence of 1 or more drug allergies, and Workers’ Compensation. Conclusions Supervised machine learning algorithms conferred excellent discrimination and performance for predicting clinically significant satisfaction after hip arthroscopy, although this analysis was performed in a single population of patients. External validation is required to confirm the performance of these algorithms. Level of Evidence Level III, therapeutic case-control study.
Non-native regal demoiselle, Neopomacentrus cyanomos, presence, abundance, and habitat factors in the North-Central Gulf of Mexico

Remotely operated vehicle (ROV) surveys were conducted at reef sites in the northern Gulf of Mexico (nGOM) during 2018–2019. Artificial (AR = 63) and natural (NR = 139) reefs were located in a 2 × 105 km2 area south of Mobile, AL to Destin, FL at depths of 13–75 m. We observed a total of 5371 damselfishes (Family: Pomacentridae) belonging to eight taxa. The non-native regal demoiselle (regal), Neopomacentrus cyanomos, was present at 30.2% of ARs but only 1.4% of NRs with densities ranging from 0.19 to 18.11 fish per 100 m2. Regals were most dense at shallow ARs, comprising 53% of the damselfish community, and least dense at deeper reefs comprising < 1% of observed damselfishes. Results from generalized linear mixed models (GLMMs) indicated the interaction among reef type, complexity, relief, and depth had a significant effect on regal density but that reef type (36%) and the interaction between reef type and depth (25%) explained the greatest proportions of variance in the data (partial η2) while the interaction among all four main effects explained only a small amount (2%). Our data indicate regals prefer shallow artificial structures with low complexity but can occupy deeper reefs, including NRs, despite less-favorable conditions. Our data document the persistence of regals in the nGOM and identify habitat factors that are significantly related to their presence and density in the region. However, the dynamics controlling their distribution are still uncertain and potential negative impacts on native reef fish communities remain unclear.
The Bootstrap Framework: Generalization Through the Lens of Online Optimization

We propose a new framework for reasoning about generalization in deep learning. The core idea is to couple the Real World, where optimizers take stochastic gradient steps on the empirical loss, to an Ideal World, where optimizers take steps on the population loss. This leads to an alternate decomposition of test error into: (1) the Ideal World test error plus (2) the gap between the two worlds. If the gap (2) is universally small, this reduces the problem of generalization in offline learning to the problem of optimization in online learning. We then give empirical evidence that this gap between worlds can be small in realistic deep learning settings, in particular supervised image classification. For example, CNNs generalize better than MLPs on image distributions in the Real World, but this is "because" they optimize faster on the population loss in the Ideal World. This suggests our framework is a useful tool for understanding generalization in deep learning, and lays the foundation for future research in this direction.
The reasons women choose and stay in a geology major: a qualitative multi-case analysis

Despite earning half of all science and engineering undergraduate degrees between 2007 and 2016 in the USA, women were awarded only 39% of earth science degrees in the same time period. In order to better understand why women are both choosing and staying in geology programs, we conducted a multi-case study of nine current female undergraduate geology majors at a large public university in the USA within a department that is at gender parity among its undergraduate majors. The main data source was audio-recorded critical incident interviews of each participant. Data from the interviews were analyzed through an iterative coding process using codes adapted from previous studies that focused on factors both internal and external to the department. The students said that personal interests, influence by others outside of the department, and introductory classes attracted them to the geology program, but once declared, departmental factors such as relationship with faculty caused them to stay. We also found an emphasis on female role models, especially those teaching introductory courses. We believe this study offers important insights into the ways in which factors leading to recruitment and retention play out in the lived experiences of female geology majors.
India and the soft power rubric: the relevance of migrants, students, visitors and movies

Much has been written about India’s soft power – how much it has, its sources and origins, and its deficits and applications. This article aims to place India’s soft power in context of other natio...
Dental therapy and dental patient-reported outcomes (dPROs)

Abstract Dental therapy was introduced into the dental team as an advanced practice provider with the intention to increase access to care while providing high quality care in a cost-effective manner. It is essential that the dental therapist is able to provide patient-centered care to minimize patients’ suffering. In order to assess patients’ suffering, it is critical to understand the impact of care and dental patient-reported outcomes (dPROs). The use of dPROs in evidence-based clinical practice can assess the impact that the advanced practice provider has in dentistry. The presence of dPROs in evidence-based clinical practice will show the equivalence and differences in impact of the dental therapist and dentist. Currently, there is limited research regarding the use of dPROs in dental therapy . A roadmap in this paper demonstrates possible ways to collect dPROs in dental therapy and advance evidence-based dental practice . Recommendations in ways to achieve the roadmap, possible research designs, and expansion in knowledge of dental therapy and dPROs are provided. It is important to explore the advanced practice provider and the possibilities in evidence-based dentistry with the usage of dPROs.
Inhibition of T Lymphocyte Activation and Apoptotic Cell Death by Cyclosporin a and Tacrolimus (FK506)

Theoretically, drugs that inhibit programmed cell death could be used to inhibit the increased apoptotic decay of lymphocyte populations in human immunodeficiency virus (HIV) infection. The concept that immunopathologic processes cause immune suppression provides a further rationale for the use of agents such as cyclosporin A (CsA) or tacrolimus (formerly known as FK506) early in HIV infection to reduce cytotoxic CD8+ T cell-mediated destruction of HIV-infected target cells.
The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy.

Objective To characterize cellular infiltrates in muscle biopsies from patients with anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMGCR)-associated myopathy.
Radon–Nikodym Theorem: Definitions and Applications

The Radon–Nikodym Theorem, in the context of probability measures, states that if all events having probability 0 under one probability measure also have probability 0 under a second measure, then the second measure is obtained by integrating some density function with respect to the first measure. Applications in probability and statistics arise in the contexts of likelihood functions, conditional expectation, Girsanov's formula, spectral measures and local time. The theorem and these applications are discussed. Keywords: density; Radon–Nikodym derivative; conditional expectation; likelihood; Girsanov's formula
Developing Development Theory: Law & Development Orthodoxies and Northeast Asian Experience

First, while intellectual histories of law and development theory are now common, no work that I am aware of employs the actual experience of Northeast Asia to interrogate these theories, yet it is in Northeast Asia where modern history's most outstanding development success stories can be found. Because this seemingly obvious step is not taken, theories of law and development remain disconnected from historical experience, and seem to attract adherents based upon unstated and untested assumptions. Second, this paper offers a way forward for law and development work which builds upon the Northeast Asian experience, but does so in a way that has not been suggested before. Law and development work affects literally billions of people in developing countries, and costs taxpayers and foundations in developed countries billions of dollars, yet many law and development practitioners express serious reservations about the utility of their work. Whatever reservations one might have about this work, it has an enormous impact on the world, and it is going to continue for the foreseeable future. It is therefore crucial that we think about new ways to assist legal reform in developing countries. Although on one level this paper is about law and development and Northeast Asia, the issues it addresses are also at the core of our understandings of law and social organization in any society. The theorists it discusses, from Max Weber, to Friedrich Hayek, to Douglass North, are likewise at the heart of our theorizing about law, society and politics generally. This paper thus contributes to debates at the core of our legal intellectual tradition, and by bringing in the experience of Northeast Asia can enrich this tradition.
So, You've Created an App?

The app craze has opened new opportunities for small entrepreneurs and software development businesses hoping to create the next Angry Birds®. Apple® alone advertises in excess of 500,000 downloadable iPhone apps in their online store. When advising clients (including third party developers), legal practitioners and attorneys should be vigilant in ensuring, in particular, that IP infringement actions are avoided, that a business’s goodwill is protected, and that IP assets are not tarnished.
Upland Controls on the Hydrological Functioning of Riparian Zones in Glacial Till Valleys of the Midwest1

: Identifying relationships between landscape hydrogeological setting, riparian hydrological functioning and riparian zone sensitivity to climate and water quality changes is critical in order to best use riparian zones as best management practices in the future. In this study, we investigate water table dynamics, water flow path and the relative importance of precipitation, deep ground water (DG) and seep water as sources of water to a riparian zone in a deeply incised glacial till valley of the Midwest. Data indicate that water table fluctuations are strongly influenced by soil texture and to a lesser extent by upland sediment stratigraphy producing seeps near the slope bottom. The occurrence of till in the upland and at 1.7-2 m in the riparian zone contributes to maintaining flow parallel to the ground surface at this site. Lateral ground-water fluxes at this site with a steep topography in the upland (16%) and loam soil near the slope bottom are small (<10 l/d/m stream length) and intermittent. A shift in flow path from a lateral direction to a down valley direction is observed in the summer despite the steep concave topography and the occurrence of seeps at the slope bottom. Principal component and discriminant analysis indicate that riparian water is most similar to seep water throughout the year and that DG originating from imbedded sand and gravel layers in the lower till unit is not a major source of water to riparian zones in this setting. Water quality data and the dependence of the riparian zone for recharge on seep water suggest that sites in this setting may be highly sensitive to changes in precipitation and water quality in the upland in the future. A conceptual framework describing the hydrological functioning of riparian zones on this setting is presented to generalize the finding of this study.
Lymphocyte reactivity in vitro: I. Cellular reconstitution of purified lymphocyte response

Abstract The in vitro mitotic response of human peripheral blood leukocytes to antigens to which the donor of the cells is sensitized or to allogeneic cells is not obtained if highly purified lymphocytes are used in culture. The addition to such nonresponding lymphocytes of a mitomycin C-treated adherent-cell preparation (enriched in macrophages) reconstitutes this response of the purified lymphocytes to either soluble antigen or purified allogeneic-stimulating cells. The data obtained are consistent with an essential role for the added cells, which can be either isogeneic or allogeneic to the responding lymphocytes. The degree of reconstitution is variable but depends to some extent on the number of added cells.
My Life's Journey as Researcher

In this narrative of my life as a researcher, I have presented my understanding of research practice, basing it of course on a sample of size one--myself, nonetheless observed carefully for over four decades now. Therefore, the readers may take it as a trigger to clarify their own self-understanding as researchers. In my life’s journey as a researcher, I have followed my passions and charted new territory, sometimes inadvertently. Research has been for me a life-long journey of discovery--of who I am, of the world around me, and the meaning of life. This has driven me beyond the boundaries of received tradition, often into uncharted territory. Over the years I have put together my own tool kit, sharpening my intellectual skills as needed for the problem at hand. The focus of my research has been myth and image in their cultural context. My research on the miniature paintings of India, and their organic links with certain texts and cultural modes of being, have transformed me in fundamental ways. I have come to regard my own experience of being a woman as central to my experience of the world. In the more recent years, I have been inquiring into the religion of the Mother Goddess. This has brought me to Orissa for fieldwork in a living tradition--that of the village goddess. I have reached so far in my journey of research by continuously expanding my intellectual boundaries as well as pushing the edges of my discipline into new frontiers.
Cross-platform normalization of microarray and RNA-seq data for machine learning applications

Large, publicly available gene expression datasets are often analyzed with the aid of machine learning algorithms. Although RNA-seq is increasingly the technology of choice, a wealth of expression data already exist in the form of microarray data. If machine learning models built from legacy data can be applied to RNA-seq data, larger, more diverse training datasets can be created and validation can be performed on newly generated data. We developed Training Distribution Matching (TDM), which transforms RNA-seq data for use with models constructed from legacy platforms. We evaluated TDM, as well as quantile normalization, nonparanormal transformation, and a simple log 2 transformation, on both simulated and biological datasets of gene expression. Our evaluation included both supervised and unsupervised machine learning approaches. We found that TDM exhibited consistently strong performance across settings and that quantile normalization also performed well in many circumstances. We also provide a TDM package for the R programming language.
Solid-phase synthesis of constrained terminal and internal lactam peptidomimetics

Lactams are key components of many peptidomimetic structures. Five- and six-membered lactam peptidomimetics with hydrogen or amino acid side chains at the alpha-position can be constructed from peptide precursors during a solid-phase synthesis. There is no significant racemization of remote stereocenters during synthesis.