cssi/SciSciGPT-SciSciNet huggingface dataset:
Microsatellite Instability Detection by Next Generation Sequencing

BACKGROUND: Microsatellite instability (MSI) is a useful phenotype in cancer diagnosis and prognosis. Nevertheless, methods to detect MSI status from next generation DNA sequencing (NGS) data are underdeveloped. METHODS: We developed an approach to detect the MSI phenotype using NGS (mSINGS). The method was used to evaluate mononucleotide microsatellite loci that were incidentally sequenced after targeted gene enrichment and could be applied to gene or exome capture panels designed for other purposes. For each microsatellite locus, the number of differently sized repeats in experimental samples were quantified and compared to a population of normal controls. Loci were considered unstable if the experimental number of repeats was statistically greater than in the control population. MSI status was determined by the fraction of unstable microsatellite loci. RESULTS: We examined data from 324 samples generated using targeted gene capture assays of 3 different sizes, ranging from a 0.85-Mb to a 44-Mb exome design and incorporating from 15 to 2957 microsatellite markers. When we compared mSING results to MSI-PCR as a gold standard for 108 cases, we found the approach to be both diagnostically sensitive (range of 96.4% to 100% across 3 panels) and specific (range of 97.2% to 100%) for determining MSI status. The fraction of unstable microsatellite markers calculated from sequencing data correlated with the number of unstable loci detected by conventional MSI-PCR testing. CONCLUSIONS: NGS data can enable highly accurate detection of MSI, even from limited capture designs. This novel approach offers several advantages over existing PCR-based methods.
On performance improvement of tone frequency estimation

A approach for tone resolution and estimation problems in applications such as pulse Doppler processing and direction finding is presented. The approach, based on frequency-diversity signaling and coherent wideband high-resolution processing, is shown to significantly outperform those using the conventional signaling and narrowband high-resolution processing under the equal-transmitted-energy constraint with either completely correlated or independent targets. Both analytical analysis and simulations are provided, as well as some insights on issues related to the performance of narrowband high-resolution processing methods and the effectiveness of smoothing techniques. >
Expression of Wilms' tumor suppressor gene (WT1) in term human trophoblast : Regulation by cyclic adenosine 3', 5'-monophosphate

The Wilms' tumor suppressor gene (WT1), which is deleted in some Wilms' tumors, encodes a zinc finger transcription factor. We studied WT1 messenger ribonucleic acid (mRNA) in human term placenta and cytotrophoblasts differentiating into syncytiotrophoblasts in vitro by RT-PCR. The results suggest that WT1 mRNA is expressed in the trophoblasts in a cell-specific fashion. WT1 mRNA expression has been observed to decline remarkably in trophoblast cells after 72 h, when these cells are morphologically differentiated into multinucleated syncytiotrophoblasts. As it is well known that cAMP as a second messenger plays a significant role in cellular proliferation and differentiation of placental cells, we examined the effect of 8-bromo-cAMP on WT1 mRNA expression in undifferentiated cytotrophoblasts and differentiated syncytiotrophoblasts. We observed that cAMP enhanced WT1 mRNA expression in cytotrophoblasts, but remained ineffective in altering WT1 mRNA in syncytiotrophoblasts. In summary, the results of this investigation demonstrate that the WT1 gene is developmentally regulated during trophoblast differentiation. An involvement of the cAMP-mediated system in regulating the WT1 gene in the trophoblast is suggested.
The Economics of Education in Sierra Leone

With respect to investment in education, two important questions need to be examined. The first is concerned with the amount to be invested in primary and secondary schools, and the institutions of higher learning, and the second relates to the distribution of total costs among the state, private institutions, and those who receive education.This short article first evaluates the existing formal educational system in Sierra Leone with the help of the cost-benefit technique. In order to obtain guidelines for future investment policies the internal social rates of return are computed for the various levels of education. Then the supply and demand of trained personnel are estimated for the period 1975–9 on the basis of the following classification: (i) high level (those with university education), (ii) middle level (those with some secondary education and technical/vocational training), and (iii) primary- and secondary-school teachers. The projections show that shortages will occur in all three groups during the next five years, above all at the middle level where a 70 per cent increase in the expected supply will be necessary to meet the requirements.
Position-Specific Hip and Knee Kinematics in NCAA Football Athletes

Background:Femoroacetabular impingement is a debilitating hip condition commonly affecting athletes playing American football. The condition is associated with reduced hip range of motion; however,...
Advances in multifocal methods for imaging human brain activity

The typical multifocal stimulus used in visual evoked potential (VEP) studies consists of about 60 checkerboard stimulus patches each independently contrast reversed according to an m-sequence. Cross correlation of the response (EEG, MEG, ERG, or fMRI) with the m-sequence results in a series of response kernels for each response channel and each stimulus patch. In the past the number and complexity of stimulus patches has been constrained by graphics hardware, namely the use of look-up-table (LUT) animation methods. To avoid such limitations we replaced the LUTs with true color graphic sprites to present arbitrary spatial patterns. To demonstrate the utility of the method we have recorded simultaneously from 192 cortically scaled stimulus patches each of which activate about 12mm 2 of cortex in area V1. Because of the sparseness of cortical folding, very small stimulus patches and robust estimation of dipole source orientation, the method opens a new window on precise spatio-temporal mapping of early visual areas. The use of sprites also enables multiplexing stimuli such that at each patch location multiple stimuli can be presented. We have presented patterns with different orientations (or spatial frequencies) at the same patch locations but independently temporally modulated, effectively doubling the number of stimulus patches, to explore cell population interactions at the same cortical locus. We have also measured nonlinear responses to adjacent pairs of patches, thereby getting an edge response that doubles the spatial sampling density to about 1.8 mm on cortex.
The Interrelationship of Canavanine and Urease in Seeds of the Lotoideae

Seeds of 29 species of canavanine-synthesizing legumes were assayed for their urease and canavanine production. All of the examined species possess detectable urease activity. In general, the leguminous seeds richest in urease also had the most canavanine. The urease content of the jack bean seed, Canavalia ensiformis (L.) DC., is formidable and disproportionally greater than the quantity of stored canavanine. The massive urease content of the seed cannot be rationalized by the magnitude of the canavanine pool. Analysis of eight species of Mucuna demonstrated that canavanine is not stored in the seeds of these plants. Mucuna species do not appear to be unique in having seeds that do not concurrently produce urease and canavanine.
The Tricuspid Valve Current Perspective and Evolving Management of Tricuspid Regurgitation

Cardiovascular specialists have entered an era of renewed interest and enthusiasm surrounding the diagnosis and treatment of valvular heart disease, driven in part by emerging percutaneous therapies for the treatment of aortic, pulmonic, and mitral valve disease. Despite this wave of investigation, little or no attention has been given to the treatment of tricuspid valve disease. Tricuspid regurgitation (TR) occurs mainly from tricuspid annular dilation, which can result from left-sided heart failure from myocardial or valvular causes, right ventricular volume and pressure overload, or dilation of cardiac chambers. If untreated at the time of surgical mitral valve repair, significant residual TR negatively impacts perioperative outcomes, functional class, and survival. TR does not reliably resolve after successful mitral valve surgery. If present at the time of mitral valve surgery, TR can usually be effectively addressed with ring annuloplasty. Because reoperations for recurrent TR carry high mortality rates, few patients are offered reoperation for redo tricuspid repair or replacement. As transcatheter therapies for mitral regurgitation arise, parallel percutaneous approaches for TR may be necessary. In this article, we review the anatomy, pathophysiology, and value of mechanical correction of TR, including potential transcatheter therapies for TR.
Adaptive storytelling through user understanding

Storytelling, when happening face to face, is a highly interactive process. A good storyteller attracts the audience by continuously observing their responses and adjusting the storytelling accordingly. The goal of this project is to simulate this process in digital storytellers. We created an automatic storytelling system that periodically estimates the user's preferences and adapts the content in the subsequent storytelling by balancing novelty and topic consistency. We have performed an empirical evaluation on the effectiveness of our approach. The results indicate that gender and age play important roles in affecting one's subjective experience. For younger subjects, stories with mixed amount of novelty and topic consistency are more preferred while for older subjects, larger amounts of variation are preferred. Additionally, in general, women enjoyed the stories more than men.
Teaching Technology Commercialization

This article introduces a special issue on "Teaching Technology Commercialization." We reflect upon the opportunities and challenges in teaching technology commercialization and we highlight the lack of connection between the literatures on entrepreneurship education and technology transfer. We also summarize the contributions to the special issue and we reflect on future research directions.
Maternal glycemic criteria for insulin therapy in gestational diabetes mellitus.

In the last decade, it has become clear that gestational diabetes is a clinical entity associated with perinatal mortality and morbidity. Thus, the attention to and management of gestational diabetes during pregnancy are mandatory. In this review, results of 58 original studies (spanning the past 20 years) addressing criteria for insulin management in gestational diabetes were assessed. The level of glycemic control and its evaluation through self-monitoring of blood glucose are the foundation for ascertaining optimal pregnancy outcome. This review addresses the criteria for insulin initiation: insulin requirements, identification of the right patient, the timing for insulin initiation, and the behavioral adjustment and compliance during insulin therapy. It is recommended that patients with fasting plasma glucose on the oral glucose tolerance test (OGTT) of 95 mg/dl on the OGTT should be referred to insulin therapy in order to minimize exposure of the fetus to a hyperglycemic environment.
Congenital flexion-adduction deformity of the thumb (congenital clasped thumb).

Of the five cases of congenital flexion-adduction deformity presented in this report, all were bilateral except Case 3. The patient in Case 3 had a congenital absence of the left thumb. In each instance of the deformity, the thumb was firmly clasped beneath the flexed fingers and did not exhibit active extension. Three patients also had an associated tightness of the web space between the thumb and index finger. All the patients had abnormal mobility of the metacarpophalangeal joints of their thumbs. In three of the patients, seen one to three months after birth (Cases 1, 2, and 5), plaster immobilization gave excellent results. In the fourth patient, seen at the age of two years (Case 4), a fair to good result was achieved after three months' immobilization. In another patient, seen at age nine (Case 3), a fair result was obtained by fusion of the metacarpophalangeal joint of the thumb. Congenital flexion-adduction deformity of the thumb should be corrected by plaster immobilization in functional position at the earliest possible time, before permanent joint and tendon changes occur. If active extension does not return, tendon transfer is indicated to restore active extension to the thumb.
Extracting the Density of States of Copper Phthalocyanine at the SiO2 Interface with Electronic Sum Frequency Generation

Organic semiconductors (OSCs) constitute an attractive platform for optoelectronics design due to the ease of their processability and chemically tunable properties. Incorporating OSCs into electrical circuits requires forming junctions between them and other materials, yet the change in dielectric properties about these junctions can strongly perturb the electronic structure of the OSC. Here we adapt an interface-selective optical technique, electronic sum frequency generation (ESFG), to the study of a model OSC thin-film system, copper phthalocyanine (CuPc) deposited on SiO2. We find that by modeling the thickness dependence of our measured spectra, we can identify changes in CuPc’s electronic density of states at both its buried interface with SiO2 and air-exposed surface. Our work demonstrates that ESFG can be used to noninvasively probe the interfacial electronic structure of optically thick OSC films, indicating that it can be used for the study of OSC-based optoelectronics in situ.
Accessibility-Based Transportation Planning: Literature and Applications for Shrinking Cities

For 15 years, scholars have claimed that accessibility-based transportation planning was at the brink of becoming a new paradigm, and yet this hope remains unrealized. Its implementation may lag due to vague definitions when compared to mobility, or because those who would benefit from accessibility-based planning lack political power to rally its support. Possibly, the lag in implementation reflects the missing linkages between theory and application for many contexts. This literature review synthesizes knowledge regarding the applications for accessibility-based transportation planning for shrinking cities along the themes of environmental, social, and economic sustainability. While residents in shrinking cities might especially benefit from such applications, context-specific challenges will require attention.
Survival of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes on inoculated almonds and pistachios stored at -19, 4, and 24° C.

The survival of Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes was determined on almonds and pistachios held at typical storage temperatures. Almond kernels and inshell pistachios were inoculated with four- to six-strain cocktails of nalidixic acid–resistant Salmonella, E. coli O157:H7, or L. monocytogenes at 6 log CFU/g and then dried for 72 h. After drying, inoculated nuts were stored at −19, 4, or 24°C for up to 12 months. During the initial drying period after inoculation, levels of all pathogens declined by 1 to 2 log CFU/g on both almonds and pistachios. During storage, moisture content (4.8%) and water activity (0.4) of the almonds and pistachios were consistent at −19°C; increased slowly to 6% and 0.6, respectively, at 4°C; and fluctuated from 4 to 5% and 0.3 to 0.5 at 24°C, respectively. Every 1 or 2 months, levels of each pathogen were enumerated by plating; samples were enriched when levels fell below the limit of detection. No reduction in population level was observed at −19...
PIN diode-based transmit-receive switch for 7 T MRI

A study using a PIN diode switched version of a linear balanced duplexer (LBD) for use in a 7 T (298 MHz) magnetic resonance imaging application is described. A prototype LBD TR switch was fabricated on FR-4 and modeled using a complex impedance model of the PIN diode and shows good insertion loss and isolation performance at 298 MHz. The scattering matrix analysis presented in the paper is verified with experimental data that show good agreement with the model.
Up-to-date review of nuclear medicine applications in pediatric thoracic imaging

Nuclear medicine has an important role in the evaluation of various congenital and acquired pediatric chest diseases. Although the radiopharmaceuticals and nuclear medicine examinations used in children are broadly the same as in adults, there are some key differences in clinical indications and underlying disorders. This article provides the reader with an up-to-date review of practice of nuclear medicine as it relates to the pediatric chest, including its current role and future applications.
Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review

Importance Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections. Objective To provide an update on diagnosis, treatment, and prevention of tick-borne infections. Evidence Review Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015. Findings The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration–approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment. Conclusions and Relevance Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription of a 14-day course of oral doxycycline for early neurologic Lyme disease in ambulatory patients. The duration of antimicrobial therapy for babesiosis in severely immunocompromised patients should be extended to 6 weeks or longer.
Institutional Trust, Sector Confidence, and Charitable Giving

Trust influences charitable-giving behavior. However, prevailing theoretical discussion and empirical study of the effects of trust suffer from confusion over different dimensions of trust. In addition to the distinction between particularistic trust in individual organizations and generalized trust in unknown others, we differentiate generalized trust in strangers, institutions, and charitable organizations writ large. An empirical analysis concentrates on the latter two, finding that charitable confidence directly influences charitable giving while institutional trust does not. We assert that the influence of charitable confidence on giving may help explain how individuals previously unaware of particular organizations or brands may be susceptible to cold calls and solicitations.
Adult linear IgA bullous dermatosis: a polymorphic disorder.

Abstract We report on two patients with unusual forms of adult linear IgA bullous dermatosis. One was a middle-aged woman who had targetoid lesions and bullae on her trunk and extremities. This patient first presented with lesions that clinically resembled erythema multiforme, but these evolved into a widespread eruption with bulging, elongated bullae. Examination of a biopsy specimen showed changes compatible with dermatitis herpetiformis and bullous pemphigoid. Findings on immunofluorescence studies showed deposition of linear IgA at the basement membrane zone. The second patient was an elderly woman with intensely pruritic vesicles whom we classified as having vesicular pemphigoid, until the linear IgA band on direct immunofluorescent test results became the predominant immunofluorescent finding. These cases are reported because of their unusual clinical presentations. The mechanism for the targetoid lesions in the first patient is discussed.
Fracture toughness of hydrogels: measurement and interpretation

The fracture mechanics of hydrogels, especially those with significantly enhanced toughness, has attracted extensive research interests. In this article we discuss the experimental measurement and theoretical interpretation of the fracture toughness for soft hydrogels. We first review the definition of fracture toughness for elastic materials, and the commonly used experimental configurations to measure it. In reality most gels are inelastic. For gels that are rate insensitive, we discuss how to interpret the fracture toughness associated with two distinct scenarios: crack initiation and steady-state crack propagation. A formulation to estimate energy dissipation during steady-state crack propagation is developed, and connections to previous models in the literature are made. For gels with rate-dependent behaviors, we review the physical mechanisms responsible for the rate-dependence, and outline the difficulties to rigorously define the fracture toughness for both crack initiation and propagation. We conclude by discussing a few fundamental questions on the fracture of tough gels that are yet to be answered.
Portfolio Theory: Origins, Markowitz and CAPM Based Selection

We trace the Treynor development of the CAPM extending the work of markowitz in portfolio selection. The Treynor work illuminates issues regarding the estimation of security beta, the role played by i diosyncratic risk, and the optimal composition of efficient portfolios. It offer a systematic way in which managers might insert their evolving items of market rates and associated risk.
Isolation, Bioactivity, and Synthesis of Nagelamides

The nagelamides are a subfamily of the sponge-derived oroidin alkaloids which have been isolated from members of the Agelas group of sponges. These sponge-derived metabolites have been found in Pacific and Caribbean variants of the sponge. This review describes all known family members along with their biological activity. An overview of their potential biosynthetic relationships and a description of the synthetic efforts toward these natural products are provided.
Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies

The discovery of antidepressant medications more than 50 years ago was one of the major breakthroughs in medical science. Today, the field of antidepressant drug development is experiencing a paradigm shift. Changing perceptions regarding the neurobiology of depression and the serendipitous discovery of ketamine’s rapid antidepressant effects have ushered in a new era of innovative research and novel drug development. This chapter provides a selective review of the suspected mechanisms of ketamine’s rapid antidepressant action in human subjects gleaned from multiple controlled and open-label trials. We also briefly review the underlying neurobiology of depression, potential biomarkers of ketamine response, the efficacy and safety profile of ketamine, current limitations to its widespread use, and considerations for novel drug development that hold promise for improved psychotherapeutic treatments for depressive and trauma-related disorders.
Disruptive Effects of Feedback

Although feedback can help in detecting and correcting errors, and in learning new behaviors, feedback can also disrupt ongoing action. Many perceptual-motor systems exhibit feedback-induced disruptions, and speech production under conditions of “delayed auditory feedback” provides the most dramatic and carefully studied example. When auditory feedback from speech is recorded and then played back with amplification to the ears after a delay of about 0.2 s, speech becomes severely disrupted. Under these conditions, proficient speakers repeat, prolong, and substitute speech sounds, sometimes producing phonemes that are not part of any language familiar to them (B. S. Lee, 1950). The present chapter examines this and other feedback-induced disruptions and the constraints they impose on theoretical relationships between perception and action.
Identification of Full-Field Dynamic Loads on Structures Using Computer Vision and Unsupervised Machine Learning

Real-world structures, such as civil and aerospace structures, are subjected to various dynamic loads which are spatially local and distributed. Assessment of operational performance, prediction of the dynamic responses, and prognosis of the remaining service life of the structure therefore requires accurate, high-resolution measurements, and modeling of the dynamic loads. This is extremely difficult, if not impossible, with the current state of the art. First, dynamic loads on structures usually come from a wide spectrum of sources, some of which are extremely challenging to accurately measure, such as the traffic loads on a bridge. Also, it is impractical to instrument a dense array of force measurement devices on the structure due to the high cost, the effect of mass-loading, and modification of the structure’s surface. On the other hand, digital video cameras are non-contact measurement device that are relatively low-cost, agile, and able to provide high spatial resolution, simultaneous, pixel measurements. This study develops a novel method for identification of the high-resolution, full-field loads on the structure from the video of the operational structures by leveraging advanced computer vision and unsupervised learning techniques. Impact and wind loads were applied on a cable structure to experimentally validate the method. The non-contact, remote, simultaneous sensing capability of the proposed technique should enable truly high-resolution, full-field force estimation that was previously not feasible.
Testing a Web-Based, Trained-Peer Model to Build Capacity for Evidence-Based Practices in Community Mental Health Systems

Objective:Use of expert-led workshops plus consultation has been established as an effective strategy for training community mental health (CMH) clinicians in evidence-based practices (EBPs). Becau...
Tabu Search Strategies for Variable Speed Limit Control at a Lane Drop Bottleneck

AbstractA tabu search–based algorithm is developed in this study and applied for optimizing a variable speed limit (VSL) control system. A macroscopic traffic flow model is used to predict the traf...
Periprosthetic shoulder infections are less elusive to diagnostic arthroscopy: commentary on an article by Matthew F. Dilisio, MD, et al.: "arthroscopic tissue culture for the evaluation of periprosthetic shoulder infection".

Establishing the diagnosis of deep infection as a complication of shoulder arthroplasty continues to be a challenge1. Preoperative evaluation to identify deep infection after arthroplasty involving a lower extremity (hip or knee replacement) relies mainly on radiographic findings as well as various analyses of peripheral blood (CBC [complete blood-cell count], ESR [erythrocyte sedimentation rate], and CRP [C-reactive protein]) and of synovial fluid (cell count, differential cell count, Gram stain, culture, and various other investigational markers). The sensitivity, specificity, and predictive values of these investigations have turned out to be suboptimal when used after shoulder arthroplasty2,3. This is believed to be due partly to the higher prevalence of infection with low-virulence bacteria, primarily Propionibacterium acnes . To further complicate matters, the clinical importance of intraoperative cultures that are unexpectedly positive for P. acnes is not fully understood4,5. Selected patients presenting with a failed shoulder arthroplasty may be suspected of having a deep infection despite negative preoperative investigations. When the index of suspicion is high, the safest approach may be staged revision surgery, with the goal of the first stage being to remove the failed prosthesis and obtain tissue samples for culture. However, this approach has a substantial …
The health of the patient, the health of the public: goals in tension.

A resident in obstetrics and gynecology introduces a Virtual Mentor issue devoted to the ethical dilemmas physicians face in balancing the dual interests embodied by pregnant patients and in other circumstances of parental-fetal conflict. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
The hypertext/hypermedia solution—but what exactly is the problem?

We have come a long way in the last thirty or so years, from the general acceptance of the behaviorist definition of learning as a “specific change in behavior or capacity to behave”, to cognitivist formulations that lay stress on the aquisition and internal organization of knowledge in the learner’s mind. Recently, the development of schema theory has put particular stress on the internal organization of knowledge. Learning is seen “as a process of change in the way that the individual views something, rather than the mere aggregation of facts,” as Peter Whalley states in his chapter.
Industry-Insurer Relationships—A Dynamic Interaction

A gradual but accelerating change is taking place in the relationships between carriers of health insurance and their industrial clients. Fiscal arrangements that were nearly universal twenty years ago—conventional insurance coverage with the carrier holding full reserves and administering the plan—have given way to a wide range of alternatives. “Conventional insurance” is no longer the norm.
Finding the right BCR-ABL1 tyrosine kinase inhibitor: a case report of successful treatment of a patient with chronic myeloid leukemia and a V299L mutation using nilotinib.

Chronic myeloid leukemia can be effectively treated with BCR-ABL1 tyrosine kinase inhibitors. However, BCR-ABL1 mutations can develop and cause secondary resistance to these inhibitors. For each of the available BCR-ABL1 inhibitors, certain mutations are known to be associated with resistance, although most mutations that confer resistance to one tyrosine kinase inhibitor remain sensitive to one or more of the other available inhibitors. For patients displaying poor response or loss of response to frontline treatment, the possibility that they have developed a new BCR-ABL1 mutation must be considered, and selection of a second-line treatment must consider the patient’s mutational profile. Here we describe a case in which a patient developed a V299L mutation; although this mutation is known to be associated with resistance to dasatinib while remaining sensitive to nilotinib, limited information is currently available regarding the use of second-line nilotinib following development of a V299L mutation while receiving dasatinib. A 73-year-old man presenting with fatigue and drenching night sweats lasting for 2 weeks was diagnosed with chronic myeloid leukemia based on an analysis of a bone marrow biopsy and detection of the BCR-ABL1 fusion gene in peripheral blood. The patient initiated frontline treatment with dasatinib. A good treatment response was seen initially, with a complete hematologic response by month 2 of treatment. By month 20 however, BCR-ABL1 transcript levels rose markedly, and a mutational analysis revealed a BCR-ABL1 V299L mutation. Based on the identification of this specific mutation, the patient switched treatment to nilotinib; by month 18 of nilotinib treatment, the patient achieved a deeper reduction in BCR-ABL1 transcript levels than was seen with dasatinib. To date, in month 34 of treatment with nilotinib, the patient has shown good tolerance of the drug and has no clinical evidence of disease progression. Our case report illustrates the benefit of having multiple drugs available to treat chronic myeloid leukemia, each with the ability to inhibit a distinct set of BCR-ABL1 mutations. This patient’s case suggests that switching to nilotinib can be an effective treatment option for patients who develop a BCR-ABL1 V299L mutation while receiving dasatinib.
On Multi-Cause Approaches to Causal Inference with Unobserved Counfounding: Two Cautionary Failure Cases and A Promising Alternative

Unobserved confounding is a central barrier to drawing causal inferences from observational data. Several authors have recently proposed that this barrier can be overcome in the case where one attempts to infer the effects of several variables simultaneously. In this paper, we present two simple, analytical counterexamples that challenge the general claims that are central to these approaches. We discuss some reasons for these failures and suggest directions for obtaining sufficient conditions for causal identifiaciton. Despite these negative results, we show that a simple modification to the multi-cause setting, incorporating a proxy or negative control variable, solves many of the problems highlighted by the examples, and suggest a way forward for causal inference with high-dimensional action spaces.
Closed transventricular pulmonary valvotomy in infants.

In an effort to reassess the efficacy of closed transventricular valvotomy in infants with severe pulmonary stenosis, we reviewed 24 consecutive patients who underwent closed transventricular valvotomy. The age range was 1 day to 11 months (median 53 days), with 10 patients under 1 month and 21 under 6 months of age. The weight range was 2.6 to 9.4 kg (median 4.1 kg). The long-term results were assessed by comparing the postoperative to the preoperative clinical and hemodynamic data. The 20 survivors were followed up for 3 to 133 months (median 54 months). All were asymptomatic upon the last follow-up visit, and their electrocardiograms and chest x-ray films were normal or improved. In 12 patients who had cardiac catheterization 7 to 85 months (median 50 months) after operation, the range for the right ventricular-to-left ventricular, or systemic arterial, peak systolic pressure ratio (RV:LV) was 0.97 to 1.7 preoperatively (mean 1.31) and 0.22 to 0.94 postoperatively (mean 0.42) (p
Cotinine as a Possible Allosteric Modulator of Nicotine Effects in Various Models

Abstract Nicotine is widely considered as one of the most addictive substances known, and its effects on a specific target define a whole class of receptors involved in a multiplicity of neuromuscular and neurological, physiological, and pathological phenomena: the nicotinic acetylcholine receptors. Cotinine is a nicotine metabolite present in small amounts in tobacco, and it is nicotine's main metabolite in humans. Cotinine is under intensive study using a variety of approaches, from the molecular to the behavioral level, in the hopes to develop pharmacotherapies for a series of nAChR-related neurological conditions. We recently reported that cotinine acts as a nicotine behavioral antagonist in an invertebrate model, planarians. This chapter focuses on reviewing known nicotine-cotinine interactions and on presenting a hypothesis that might account for some of these interactions: cotinine seems to act as an allosteric modulator of nicotine.
Scale-up of Q‑carbon and nanodiamonds by pulsed laser annealing

Abstract Q‑carbon is a densely-packed metastable phase of carbon, which is harder than diamond. It is formed by nanosecond laser melting and ultrafast quenching of amorphous carbon films. The formation of Q‑carbon is a strictly undercooling driven phenomenon and requires uniform sp3/sp2 composition of as-deposited diamond-like carbon (DLC) films. This study illustrates the growth of wafer-scale DLC and its conversion into Q‑carbon and diamond by nanosecond pulsed laser annealing (PLA). A two-dimensional transient heat conduction model was created to analyze the melt front and regrowth conditions of PLA processing, utilizing a temporal and spatial Gaussian heat source at a laser fluence of 800 mJ/cm2. The transient temperature and melt-depth profiles obtained revealed successful melting of carbon with regrowth of Q‑carbon phase. By optimizing laser plume energetics, uniformity in sp3 content (~40%) of DLC films was achieved, which led to the formation of Q‑carbon over a large area. Here, the challenges associated with the scale-up of Q‑carbon are discussed along with analysis of the interfacial bonding between the undercooled layers using atomic-force and electron microscopy techniques. The wafer scale-up of DLC films with controlled sp3/sp2 content will be useful for making scalable Q‑carbon based longer-lasting protective coatings and Q‑carbon based electronic devices. These findings should help to further the development of Q‑carbon and diamond-related materials technology for commercialization of high-performance systems.
Injury frequency and severity in crayfish communities as indicators of physical habitat quality and water quality within agricultural headwater streams

Crayfishes (Decapoda) are common inhabitants of agricultural headwater streams in the Midwestern USA that have been impacted by physical habitat degradation and contamination by agricultural pollutants. The frequency and severity of injuries within crayfish communities are indicators of crayfish aggression, which is influenced by physical, chemical, and biotic factors. Previous studies have not evaluated the relationships of the frequency and severity of crayfish injuries with physical habitat quality, water quality, and biotic factors within agricultural headwater streams. Understanding these relationships will assist with determining if crayfish injury variables can serve as an indicator of physical habitat quality or water quality in these small degraded streams. We sampled crayfishes, documented the frequency and type of injuries, and measured instream habitat and water chemistry in 2014 and 2015 within 12 agricultural headwater streams in Indiana, Michigan, and Ohio. We documented five native crayfish species from 1641 adult captures. The most abundant species were Faxonius rusticus, Faxonius immunis, and Faxonius propinquus. Linear mixed effect model analyses indicated that four crayfish injury response variables were positively correlated (p < 0.05) with crayfish density, physical habitat quality, and water velocity diversity and that crayfish injury response variables were more strongly correlated with crayfish density than physical habitat quality or water quality. Our results indicate that response variables describing the severity and frequency of crayfish injuries can be effective indicators of physical habitat quality in agricultural headwater streams.
Matching Mechanism of Death With Mechanism of Action: Considerations for Drug Development for Hospitalized Heart Failure

Despite available therapies and quality improvement initiatives, within 90 days of discharge, hospitalized patients with heart failure (HF) experience post-discharge mortality and rehospitalization rates as high as 15% and 30%, respectively [(1,2)][1]. With 1 possible exception [(3)][2], a decade
Homa: An Efficient Topology and Route Management Approach in SD-WAN Overlays

This paper presents an efficient topology and route management approach in Software-Defined Wide Area Networks (SD-WAN). Traditional WANs suffer from low utilization and lack of global view of the network. Therefore, during failures, topology/service/traffic changes, or new policy requirements, the system does not always converge to the global optimal state. Using Software Defined Networking architectures in WANs provides the opportunity to design WANs with higher fault tolerance, scalability, and manageability. We exploit the correlation matrix derived from monitoring system between the virtual links to infer the underlying route topology and propose a route update approach that minimizes the total route update cost on all flows. We formulate the problem as an integer linear programming optimization problem and provide a centralized control approach that minimizes the total cost while satisfying the quality of service (QoS) on all flows. Experimental results on real network topologies demonstrate the effectiveness of the proposed approach in terms of disruption cost and average disrupted flows.
Crimes Against Women in India: Evaluating the Role of a Gender Representative Police Force

Violence against women in India has gathered considerable attention in recent years with increasing public policy debates on urgent legal reforms. A factor which has perhaps not received enough attention is women’s participation in law enforcement. In the year 2014, women comprised only 6.1% of the police force in India. This paper combines this narrative with the theory of representative bureaucracy which implies better outcomes for a section of society through increased representation in public decision-making bodies. Using state-level annual data from 2001 to 2012, I estimate the difference in effects of female and male police force on arrest outcomes for crimes against women. Results suggest that increasing women at the inspector ranks plays a significantly higher role in arrests for such crimes, compared to increasing male inspectors. I find considerable heterogeneity across different types of crimes against women and states by female literacy levels and degree of urbanization.
Why go home? Pearl Jam's ‘Home Shows’ & hotel demand

Abstract We use daily hotel data on price, occupancy, and revenue to analyze the effect of Pearl Jam’s ‘Home Shows’ in Seattle, WA on hotel demand. We find that the Home Shows generated approximately 230,000 hotel nights before, during, and after the two concerts. With an increase in the average daily room rate ranging from $12 six days prior to $144 on concert days, hotel revenue in Seattle increased by over $58 million from the Home Shows. We estimate that increased demand from Pearl Jam fans increased hotel tax revenue between $6.69 million and $9.15 million. We argue that our results represent a `best case' scenario on the public revenue side of large cultural events that attract tourists.
Natural unblinding of BCG vaccination trials.

There is significant public and clinical interest in the potential for Bacillus Calmette-Guerin (BCG) vaccination to protect against type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) induced COVID-19. This question could be best answered by blinded and placebo controlled clinical trials. However, a skin reaction occurs within days at the site of BCG injection, making it rather challenging to blind this vaccination. Here, we examined registered clinical trials in ClinicalTrials.gov on BCG against COVID-19 by October 9th 2020, and found that 94.7% of such trials were listed as placebo controlled (all with normal saline as placebo), and single to quadruple blinded. The mode of overcoming the natural unblinding by the BCG induced skin reaction was not clarified on the website in either of the trials. We conclude that detailed description of the strategy towards overcoming the BCG vaccination induced skin reaction associated unblinding hurdle will be important for the interpretation of the theoretically blinded COVID-19 directed clinical trials.
Neonatal outcomes of births in freestanding birth centers and hospitals in the United States, 2016-2019.

Background Births in freestanding birth centers have more than doubled between 2007 and 2019. Although birthing centers, which are defined by the American College of Obstetricians and Gynecologists as “. . . freestanding facilities that are not hospitals,” are being promoted as offering women fewer interventions than hospitals, there are limited recent data available on neonatal outcomes in these settings. Objective To compare several important measures of neonatal safety between 2 United States birth settings and birth attendants: deliveries in freestanding birth centers and hospital deliveries by midwives and physicians. Study Design This is a retrospective cohort study using the United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, and Division of Vital Statistics natality online database for the years 2016 to 2019. All term, singleton, low-risk births were eligible for inclusion. The study outcomes were several neonatal outcomes including neonatal death, neonatal seizures, 5-minute Apgar scores of Results The study population consisted of 9,894,978 births; 8,689,467 births (87.82%) were in-hospital births by MDs and DOs, 1,131,398 (11.43%) were in-hospital births by midwives, and 74,113 (0.75%) were births in freestanding birth centers. Freestanding birth center deliveries were less likely to be to non-Hispanic Black or Hispanic, less likely to women with public insurance, less likely to be women with their first pregnancy, and more likely to be women with advanced education and to have pregnancies at ≥40 weeks’ gestation. Births in freestanding birth center had a 4-fold increase in neonatal deaths (3.64 vs 0.95 per 10,000 births: adjusted odds ratio, 4.00; 95% confidence interval, 2.62–6.1), a more than 7-fold increase in neonatal deaths for nulliparous patients (6.8 vs 0.92 per 10,000 births: adjusted odds ratio, 7.7; 95% confidence interval, 4.42–13.76), a more than 2-fold increase in neonatal seizures (3.91 vs 1.94 per 10,000 births: adjusted odds ratio, 2.19; 95% confidence interval, 1.48–3.22), and a more than 7-fold increase of a 5-minute Apgar score of Conclusion Births in United States freestanding birth centers are associated with an increased risk of adverse neonatal outcomes such as neonatal deaths, seizures, and low 5-minute Apgar scores. Therefore, when counseling women about the location of birth, it should be conveyed that births in freestanding birth centers are not among the safest birth settings for neonates compared with hospital births attended by either midwives or physicians.
Variations in deceased donor kidney procurement biopsy practice patterns: A survey of U.S. organ procurement organizations.

Background Procurement biopsies have become a common practice in the evaluation and allocation of deceased donor kidneys in the United States despite questions about their value and reproducibility. We sought to determine the extent of OPO-level differences in criteria used to decide which deceased donor kidneys undergo a procurement biopsy and to assess the degree of variability in procurement biopsy technique and interpretation across OPOs. Methods Each of the country's 58 OPOs were invited to participate in the survey. OPOs were divided into two groups based on organ availability ratio and deceased donor kidney discard rate. Results and conclusions Fifty-out-of-fifty-eight invited OPOs (86% response rate) responded to the survey between November 2020 and December 2020. Thirty (60%) OPOs reported that they have formal criteria for performing kidney procurement biopsy, but for 29 of these OPOs, transplant centers can request biopsy on kidneys that do not meet criteria. OPOs used a total of seven different variables and 12 different numerical thresholds to define impaired kidney function that would prompt a procurement biopsy. Additionally, wide variability was seen in biopsy technique and procedures for biopsy interpretation and reporting of findings to transplant programs. These findings identify a clear opportunity for standardization of procurement biopsies to best practices.