cssi/SciSciGPT-SciSciNet huggingface dataset:
Role in metal homeostasis of CtpD, a Co2+ transporting P1B4‐ATPase of Mycobacterium smegmatis

Summary Genetic studies in the tuberculosis mouse model have suggested that mycobacterial metal efflux systems, such as the P1B4-ATPase CtpD, are important for pathogenesis. The specificity for substrate metals largely determines the function of these ATPases; however, various substrates have been reported for bacterial and plant P1B4-ATPases leaving their function uncertain. Here we describe the functional role of the CtpD protein of Mycobacterium smegmatis. An M. smegmatis mutant strain lacking the ctpD gene was hypersensitive to Co2+ and Ni2+ and accumulated these metals in the cytoplasm. ctpD transcription was induced by both Co2+ and superoxide stress. Biochemical characterization of heterologously expressed, affinity-purified CtpD showed that this ATPase is activated by Co2+, Ni2+ and to a lesser extend Zn2+ (20% of maximum activity). The protein was also able to bind one Co2+, Ni2+ or Zn2+ to its transmembrane transport site. These observations indicate that CtpD is important for Co2+ and Ni2+ homeostasis in M. smegmatis, and that M. tuberculosis CtpD orthologue could be involved in metal detoxification and resisting cellular oxidative stress by modulating the intracellular concentration of these metals.
Leveraging the Mouse Genome for Gene Prediction in Human: From Whole-Genome Shotgun Reads to a Global Synteny Map

The availability of draft sequences for both the mouse and human genomes makes it possible, for the first time, to annotate whole mammalian genomes using comparative methods. TWINSCAN is a gene-prediction system that combines the methods of single-genome predictors like GENSCAN with information derived from genome comparison, thereby improving accuracy. Because TWINSCAN uses genomic sequence only, it is less biased toward highly and/or ubiquitously expressed genes than GENEWISE, GENOMESCAN, and other methods based on evidence derived from transcripts. We show that TWINSCAN improves gene prediction in human using intermediate products from various stages of the sequencing and analysis of the mouse genome, from low-redundancy, whole-genome shotgun reads to the draft assembly and the synteny map. TWINSCAN improves on the prior state of the art even when alignments from only 1X coverage of the mouse genome are available. Gene prediction accuracy improves steadily from 1X through 3X, more slowly from 3X to 4X, and relatively little thereafter. The assembly and the synteny map greatly speed the computations, however. Our human annotation using the mouse assembly is conservative, predicting only 25,622 genes, and appears to be one of the best de novo annotations of the human genome to date.
Protocol Transplant Biopsies in Kidney Allografts: Why and When Are They Indicated?

Protocol biopsies have long been a controversial issue in kidney transplantation. Relative risk of complications of the procedure must be weighed against the possible benefit, and the patient must be fully informed before protocol biopsies can be obtained. Risk of performing kidney allograft biopsies has diminished over recent years, with the routine use of smaller gauge biopsy needles, bioptic devices to obtain tissue cores, and ultrasound guidance for the biopsy procedure. The allograft kidney is located closer to the body surface than the native kidney, making localization of the organ for biopsy more straightforward than for native kidney. As reviewed by Wilkinson, safety of protocol biopsies has been established. In cited series totalling >3500 protocol biopsies, the rate of serious complications varied from 0.4 to 1% and very rarely led to graft loss. The authors of one large multicenter study concluded that “it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care” (1). It is important to sample adequate renal cortex in graft biopsies to make pathologic observations on the tissue reliable and the procedure worthwhile for patient treatment. This is especially true in the setting of protocol biopsies, where the potential for benefit to the patient should outweigh any risk. Banff criteria define adequate cortical sampling as a specimen that contains at least 10 glomeruli and two arteries. Sampling of the medulla may also be desirable to optimize detection of early polyoma virus infection. It is recommended that at least two tissue cores be obtained, preferably at some distance from each other, to optimize sampling of pathologic processes such as rejection and infection, which may be focal in the allograft (2). Sampling with a 16-gauge needle provides a better tissue sample, with safety comparable to use of an 18-gauge …
VOTER IDEOLOGY, THE ECONOMY, AND THE INTERNATIONAL ENVIRONMENT IN WESTERN DEMOCRACIES, 1952-1989

Although it is commonly assumed that voters shift on an ideological spectrum over time, there has been relatively little scientific inquiry into the reasons for shifts in voter ideology. In this article, we attempt to explain why voter ideological shifts occur utilizing an interval measure of voter ideology recently developed by Kim and Fording. A pooled time-series analysis of 13 Western democracies for the period of 1952–1989 identifies several internal and external factors causing shifts in voter ideology. With respect to domestic influences, the state of the country's national economy, primarily inflation, seems to drive movement in voter ideology in a most significant way, but we find that the direction of this relationship is dependent on the ideological disposition of the incumbent government. With respect to international influences, we find significant ideological diffusion across neighboring countries of Western democracies. The effects of ideological diffusion are strongest within countries that are small relative to their neighbors. We also find that ideology is influenced by the international political environment, especially the level of East-West tension during the Cold War.
Antigen analogs as therapeutic agents

The immune system’s function is to protect us against invading pathogens such as viruses, bacteria, parasites, and even the runaway growth of cancer cells. T lymphocytes play a major role in these immune responses, and in most cases the outcome is beneficial, such as killing infected cells or helping B-cells produce antibodies. In many cases, medical science has been capable of augmenting or enhancing the beneficial immune responses. Successes are numerous. Vaccines are now available against viral diseases such as influenza, hepatitis, and polio, and against bacterial infections such as diptheria, whooping cough, and tetanus. Clearly, however, much more progress is required in developing vaccines efficacious against diseases such as cancer and AIDS.
Modified fontan operation

From November 1988 to October 1991 30 patients underwent a total extracardiac right heart bypass for complex cardiac anomalies by means of bidirectional cavopulmonary anastomosis and interposition of a conduit from the inferior vena cava to the pulmonary artery. Mean age at surgery was 6.4 years and mean weight 19.2 kg. There was 1 hospital death (3%) due to a borderline indication for a Fontan operation. 2 patients had further surgery: In 1 the repair was taken down due to the stenosis of the left pulmonary artery and the patient was left with a bidirectional cavopulmonary anastomosis only, the second patient required a revision of the cavopulmonary anastomosis due to a stenosis of the superior vena cavaright pulmonary artery junction. There were no late deaths and the survivors are in good clinical condition a mean of 15.1 months after the operation. We propose this technique as an alternative surgical option in candidates for a Fontan operation in whom atrial septation is hazardous including those with 1) hypoplasia or atresia of the left atrio-ventricular valve, 2) common atrioventricular valve, 3) anomalies of systemic and/or pulmonary venous return, or 4) auricular juxtaposition.
Tritanium acetabular wedge augments: short-term results.

Background: Reconstruction of acetabular defects in total hip arthroplasty (THA) presents a great challenge to orthopaedic surgeons. Previous studies have reported on the use and outcomes of trabecular metal acetabular augments for the reconstruction of acetabular defects. However, no study has been conducted evaluating the short-term results of tritanium acetabular wedge augments for the reconstruction of acetabular defects in THA. Methods: A retrospective study was conducted using a prospective database at a single institution including primary and revision THA patients from January 2013 to December 2014. Patients were included if they received a tritanium acetabular wedge augment system and had a minimum of 2-year follow-up (average 2.2 years ±0.3, range, 2–2.6 years). Demographic data and outcomes data [Harris Hip Score—HHS and Short Form (SF)-36] was collected. Radiographic data was also collected on THA revision cases (Paprosky classification), developmental dysplasia of the hip (DDH) cases (Crowe classification), and radiographic follow-up using DeLee and Charnley’s classification system. Results: There were 4 revision THA patients, 3 DDH patients, and 1 patient with posttraumatic arthritis. At the latest radiographic follow-up, there were no lucent lines in DeLee and Charnley Zones I, II or III. During the follow-up period, there was no open revision surgery. The SF-36 physical score significantly improved from preoperative measurement (29.6±2.2) to postoperative measurement (52.2±8.7, P=0.003), and the SF-36 mental score also significantly improved from preoperative assessment (34.5±4.5) to postoperative assessment (52.2±7.5, P=0.003). Total HHS scores also significantly improved postoperatively (P=0.02), with significant improvements in both the pain score (P=0.01) and function score (P=0.02). Conclusions: Tritanium acetabular wedge augments in this short follow-up case series exhibit high clinical outcome scores, no radiographic lucency, and no early failures.
Quantitative Assessment of Parametric Uncertainty in Northern Hemisphere PAH Concentrations

We quantitatively examine the relative importance of uncertainty in emissions and physicochemical properties (including reaction rate constants) to Northern Hemisphere (NH) and Arctic polycyclic aromatic hydrocarbon (PAH) concentrations, using a computationally efficient numerical uncertainty technique applied to the global-scale chemical transport model GEOS-Chem. Using polynomial chaos (PC) methods, we propagate uncertainties in physicochemical properties and emissions for the PAHs benzo[a]pyrene, pyrene and phenanthrene to simulated spatially resolved concentration uncertainties. We find that the leading contributors to parametric uncertainty in simulated concentrations are the black carbon-air partition coefficient and oxidation rate constant for benzo[a]pyrene, and the oxidation rate constants for phenanthrene and pyrene. NH geometric average concentrations are more sensitive to uncertainty in the atmospheric lifetime than to emissions rate. We use the PC expansions and measurement data to constrain ...
MDCT of pelvic inflammatory disease: a review of the pathophysiology, gamut of imaging findings, and treatment

Representing an ascending, sexually spread pyogenic infection of the female genital tract, pelvic inflammatory disease (PID) is a commonly encountered cause for emergency visits and hospitalizations among young and adult female patients. Though gynecologic evaluation and sonography constitute the mainstay of diagnosis, multidetector CT imaging of the abdomen and pelvis is not uncommonly performed, often as the initial imaging modality, due to the frequently vague and indeterminate clinical presentation. As such, knowledge and attenuation to the often subtle early imaging features of PID afford the radiologist a critical chance to direct and expedite appropriate pathways of patient care, minimizing the risk for secondary complications, including infertility, ectopic pregnancy, and enteric adhesions. In this paper, we will review the pathophysiology, clinical presentation, early and late imaging features of PID as well as potential secondary complications and treatment options. Additionally, we will discuss published data metrics on CT performance regarding sensitivity and specificity for diagnosis as well as potential imaging differential diagnostic considerations.
Ultrasonic reflectivity function estimation using Cepstrum Sparse Deconvolution

The ultrasonic signals backscattered from multilayered materials using a pulse-echo method are inherently low-resolution due to the band-limited nature of the interrogating transducer. To improve resolution, the Wiener Filter (WF) based solutions have been used traditionally, although they provide limited improvement and are highly sensitive to noise. More recently, sparse deconvolution techniques (e.g., l1-regularized Least Squares Deconvolution (l1-LSD)) have proved to be effective in improving the resolution; however, they are highly dependent on pulse invariance. It is common for an ultrasonic wavelet to change its shape as it propagates through the materials due to frequency dependent attenuation, scattering and dispersion. Consequently, these changes in pulse shape limit the application of these algorithms which need a prior knowledge of pulse-wave of the system. In this paper we present an adaptive and highly efficient deconvolution technique, Cepstrum Sparse Deconvolution (CSD), which does not require any prior information of the system or the detected object but compensates for the pulse-wave variation by estimating the fundamental pulse-wave shape directly from the backscattered signal. This pulse-wave estimation is based on cepstrum processing of the signal prior to the deconvolution process. Applications and comparisons are made to evaluate the performance of CSD, WF and l1-LSD through experimental and simulated ultrasound data which contain varying-shape wavelets with respect to amplitude, center frequency, arrival time, bandwidth, and phase parameters. The Normalized Mean Absolute Score (NMAS) index, a measure of distance between the actual reflectivity function and the estimated function is used to evaluate these algorithms' performance. The results show that CSD is the fastest algorithm and offers highest resolution among these three algorithms even though the pulse-wave may have gone through a significant change.
Development and Evaluation of Chromosome Segment Substitution Lines Carrying Overlapping Chromosome Segments of the Whole Wild Rice Genome

Common wild rice (Oryza rufipogon Griff.) represents an important resource for rice improvement. Genetic populations provide the basis for a wide range of genetic and genomic studies. In particular, chromosome segment substitution lines (CSSLs) are most powerful tools for the detection and precise mapping of quantitative trait loci (QTLs). In this study, 146 CSSLs were produced; they were derived from the crossing and back-crossing of two rice cultivars: Dongnanihui 810 (Oryza sativa L.), an indica rice cultivar as the recipient, and ZhangPu wild rice, a wild rice cultivar as the donor. First, a physical map of the 146 CSSLs was constructed using 149 molecular markers. Based on this map, the total size of the 147 substituted segments in the population was 1145.65 Mb, or 3.04 times that of the rice genome. To further facilitate gene mapping, heterozygous chromosome segment substitution lines (HCSSLs) were also produced, which were heterozygous in the target regions. Second, a physical map of the 244 HCSSLs was produced using 149 molecular markers. Based on this map, the total length of substituted segments in the HCSSLs was 1683.75 Mb, or 4.47 times the total length of the rice genome. Third, using the 146 CSSLs, two QTLs for plant height, and one major QTL for apiculus coloration were identified. Using the two populations of HCSSLs, the qPa-6-2 gene was precisely mapped to an 88 kb region. These CSSLs and HCSSLs may, therefore, provide powerful tools for future whole genome large-scale gene discovery in wild rice, providing a foundation enabling the development of new rice varieties. This research will also facilitate fine mapping and cloning of quantitative trait genes, providing for the development of superior rice varieties.
Pocket Guide to Clinical Microbiology

Pocket Guide to Clinical Microbiology is now available on Wiley.comMembers, use the code ASM20 at check out to receive your 20% discount. Quick reference to clinical microbiology If you work in the clinical laboratory, this pocket guide will help you confidently identify most organisms you could encounter. This useful updated edition continues to present valuable quick-reference information to the clinical microbiology community in a small package. Along with specifics on pathogenic microorganisms, there is updated information on effectively using essential molecular diagnostic techniques for today’s challenges. You will find guidance on: MALDI-TOF MS performance for individual bacteria, mycobacteria, and fungi Nucleic acid amplification testing/PCR and help interpreting genetic sequencing results Susceptibility testing, with methods and interpretive criteria for most organism/antibiotic combinations Antimicrobial resistance mechanisms and resistance profiles for common organisms Paperback, 420 pages, index.
The impact of spatiotemporal variability in atmospheric CO 2 concentration on global terrestrial carbon fluxes

Abstract. Land carbon fluxes, e.g., gross primary production (GPP) and net biome production (NBP), are controlled in part by the responses of terrestrial ecosystems to atmospheric conditions near the Earth's surface. The Coupled Model Intercomparison Project Phase 6 (CMIP6) has recently proposed increased spatial and temporal resolutions for the surface CO2 concentrations used to calculate GPP, and yet a comprehensive evaluation of the consequences of this increased resolution for carbon cycle dynamics is missing. Here, using global offline simulations with a terrestrial biosphere model, the sensitivity of terrestrial carbon cycle fluxes to multiple facets of the spatiotemporal variability in atmospheric CO2 is quantified. Globally, the spatial variability in CO2 is found to increase the mean global GPP by a maximum of 0.05 Pg C year−1 , as more vegetated land areas benefit from higher CO2 concentrations induced by the inter-hemispheric gradient. The temporal variability in CO2 , however, compensates for this increase, acting to reduce overall global GPP; in particular, consideration of the diurnal variability in atmospheric CO2 reduces multi-year mean global annual GPP by 0.5 Pg C year−1 and net land carbon uptake by 0.1 Pg C year−1 . The relative contributions of the different facets of CO2 variability to GPP are found to vary regionally and seasonally, with the seasonal variation in atmospheric CO2 , for example, having a notable impact on GPP in boreal regions during fall. Overall, in terms of estimating global GPP, the magnitudes of the sensitivities found here are minor, indicating that the common practice of applying spatially uniform and annually increasing CO2 (without higher-frequency temporal variability) in offline studies is a reasonable approach – the small errors induced by ignoring CO2 variability are undoubtedly swamped by other uncertainties in the offline calculations. Still, for certain regional- and seasonal-scale GPP estimations, the proper treatment of spatiotemporal CO2 variability appears important.
Multilayer Encoder-Decoder Network for 3D Nuclear Segmentation in Spheroid Models of Human Mammary Epithelial Cell Lines

Nuclear segmentation is an important step in quantitative profiling of colony organization in 3D cell culture models. However, complexities arise from technical variations and biological heterogeneities. We proposed a new 3D segmentation model based on convolutional neural networks for 3D nuclear segmentation, which overcomes the complexities associated with non-uniform staining, aberrations in cellular morphologies, and cells being in different states. The uniqueness of the method originates from (i) volumetric operations to capture all the threedimensional features, and (ii) the encoder-decoder architecture, which enables segmentation of the spheroid models in one forward pass. The method is validated with four human mammary epithelial cell (HMEC) lines—each with unique genetic makeup. The performance of the proposed method is compared with the previous methods and is shown that the deep learning model has a superior pixel-based segmentation, and an F1-score of 0.95 is reported.
Managing Spasticity in a Pregnant Woman with Spinal Cord Injury: a Review

This paper aims to review the available treatment options for spasticity management that can be used for pregnant women with spinal cord injury (SCI). There are extensive reviews exploring the approach to care for the parturient with SCI. These often include a discussion on common medications used and their potential impact on pregnancy and lactation. However, there are no specific guidelines on managing spasticity in pregnancy. Existing review articles show a low level of evidence for commonly utilized physical interventions in spasticity management. There are several case reports on the use of intrathecal baclofen and focal injections with botulinum neurotoxin during pregnancy. The approach to management should recognize the interaction of pregnancy with secondary complications of SCI. Treatment decisions should be based on severity of spasticity, patient goals, and education of potential risks and benefits of different options with regard to pregnancy, lactation, maternal, and fetal outcomes.
Effects of physical and chemical surface roughness on the brightness of electron beams from photocathodes

The performance of free electron laser x-ray light sources, and systems for ultrafast electron diffraction and ultrafast electron microscopy, is limited by the brightness of the electron sources used. The intrinsic emittance, or equivalently, the mean transverse energy (MTE) of electrons emitted from the photocathode determines the maximum possible brightness in such systems. With ongoing improvements in photocathode design and synthesis, we are now at a point where the physical and chemical surface roughness of the cathode can become a limiting factor. Here we show how measurements of the spatially dependent variations in height and surface potential can be used to compute the electron beam mean transverse energy (MTE), one of the key determining factors in evaluation of brightness.
Dynamics and variability of neuronal subtype responses during regeneration and growth

Background: We are interested in how nervous systems regenerate during whole-body axis regeneration. During whole-body axis regeneration, lost tissues are replaced to restore normal adult morphology. Typically, regenerates are smaller than their pre-amputated parent and have normal proportionality, suggesting that tissue scaling occurs in regenerates. The cell dynamics and responses of neuronal subtypes during nervous system regeneration in animals undergoing whole-body axis regeneration are not well understood in any system. The cnidarian sea anemone Nematostella vectensis is capable of whole-body axis regeneration, and its transparent, simple body plan, and the availability of fluorescent reporter lines, allows for the ability and resolution to track neural subtypes throughout the entire regenerative process. We utilized the NvLWamide-like::mCherry neuronal subtype transgenic reporter line to determine the in vivo response of neuronal subtypes during Nematostella vectensis nerve net regeneration and scaling. Results: Regenerates were smaller than their pre-amputated size, and the regenerated nerve nets were reduced in neuronal number. Different neuronal subtypes had several distinct responses that included consistent, no, and conditional regeneration. Conditional regeneration relied in part on the size of the remnant fragment. Regenerates showed normal behaviors, indicating that the reduced nerve net retains functionality. These observations led us to investigate nerve net scaling. Neuronal numbers decreased as animals shrunk, and increased as they grew, and the changes were reversible. As with regenerates, behaviors present prior to the nervous system adjusting in size were also present after, regardless of whether the number of neurons increased or decreased. Conclusion: These data suggest that the Nematostella nerve net is dynamic, capable of scaling with changes in body size, and that neuronal subtypes display differential regenerative capabilities, which is likely linked to the scale-state of the regenerating nervous system.
Abstract 2598: Developing small molecule inhibitors that target androgen receptor signaling in castration-resistant prostate cancer

The transcription factor, androgen receptor (AR) is a key driver and plays an important role in prostate cancer. Androgen ablation therapy and brachytherapy remains the standard treatment of advanced prostate cancer, but unfortunately, it is not curative, and eventually the disease returns as lethal castration-resistant prostate cancer (CRPC). Previously we have reported that Urolithin A (Uro A), a natural compound, inhibits AR signaling and suppresses the growth of CRPC. Now, we have developed a series of pro-drug conjugates of Uro A and our initial structure-activity relationship (SAR) studies led to the identification of three small molecules as lead compounds. Hence, we investigated the effects of all three compounds and dissected their molecular mechanism in cell culture and mouse models of CRPC. All the three compounds more effectively inhibited the growth CRPC cell lines than the parent compound Uro A. Based on their IC 50 concentration; we identified a novel compound (ASR-600) that demonstrated better efficacy by inhibiting AR signaling in CRPC cell lines than the parental compound Uro A. The model system and molecular dynamics (MD) stimulation studies suggest that ASR600 bind to the ligand-binding domains of AR and blocks the conformation changes, that allows AR to phosphorylate and degrade in the cytosol. Further, our thermal shift assay confirmed ASR 600 binds to AR in presence and absence of Dihydrotestostreone. Our ongoing in vivo studies, may suggest whether oral administration of ASR-600 effectively inhibits the tumor growth raised from CRPC cell lines (C4-2B, 22RV1 and enzalutamide resistance C4-2B) in xenografted mice. These observations provide a rationale for devising novel therapeutic agent based on ASR 600 for the treatment of CRPC Citation Format: Balaji Chandrasekaran, Ashish Tyagi, Venkatesh Kolluru, Aakash M. Vadhanam, Becca von Baby, Suresh Gorle, Suman Sirimulla, Srinivasa R. Ramisetti, Arun K. Sharma, Murali K Ankem, Chendil damodaran. Developing small molecule inhibitors that target androgen receptor signaling in castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2598.
Dimension Reduction in High Dimensional Multivariate Time Series Analysis

The vector autoregressive (VAR) and vector autoregressive moving average (VARMA) models have been widely used to model multivariate time series, because of their capability to represent the dynamic relationships among variables in a system and their usefulness in forecasting unknown future values. However, when the dimension is very high, the number of parameters often exceed the number of available observations, and it is impossible to estimate the parameters. A suitable solution is clearly needed. After introducing some existing methods, we will suggest the use of contemporal aggregation as a dimension reduction method, which is very natural and simple to use. We will compare our proposed method with other existing methods in terms of forecast accuracy through both simulations and empirical examples. The presentation is based on the invited talk at the 2017 ICSA Applied Statistics Symposium in Chicago.
Buckling Load Maximization of Curvilinearly Stiffened Tow-Steered Laminates

Under certain loading conditions, curvilinearly stiffened panels are seen to have better structural performance while being lighter in mass when compared to panels with straight stiffeners. A curvi...
Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

Background For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. Methods All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). Results Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. Conclusion The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.
Doing the locomotion: Insights and potential pitfalls associated with using locomotor activity as a readout of the circadian rhythm in larval zebrafish.

Abstract Background Zebrafish have been used as a model to study circadian rhythms (CRs) for over 20 years by analyzing various endpoints including locomotor activity. Such studies often utilize high-throughput analysis monitoring activity of larvae placed in well plates numbering >48 wells per plate. Although the CR can be influenced by numerous factors, it is not clear if such effects are permanent. Here, we investigated the variability of CRs of larvae analyzed in different types of well plates and determined the permanency of experimentally-induced aberrations in CRs. New method Utilized the tracking software Ethovision XT to investigate how different well plate sizes influence the CR. Re-tested subjects for recovery from long-term CR disruptions and evaluated CR patterns at the individual level. Results CR tracking using locomotion as a readout is best in 24 well plates. CR consistency is not maintained in larvae tracked in 48 or 96 well plates. A perturbed CR due to constant light recovered after just 3 days of a normal light/dark cycle. Comparison with existing methods Unlike other CR locomotor-based assays, our approach allowed for a medium-throughput analysis of individual CRs, minimized variability and allowed for the re-evaluation of larval CRs 4–5 days later. Conclusions This medium-throughput locomotor CR analysis allows for a standardized, less variable approach whereby larvae can be re-tested to identify potential long-term changes after experimental manipulations. Long-term behavioral experiments in 48 or 96 well plates may impart stress on the larvae due to space constraints which could impact nervous system function and/or behavior.
Aperture: Fast Visualizations Over Spatiotemporal Datasets

One of the most powerful ways to explore data is to visualize it. Visualizations underpin data wrangling, feature space explorations, and understanding the dynamics of phenomena. Here, we explore interactive visualizations of voluminous, spatiotemporal datasets. Our system, Aperture, makes novel use of data sketches to reconcile I/O overheads, in particular the speed differential across the memory hierarchy, and data volumes. Queries underpin several aspects of our methodology. This includes support for a diversity of queries that are aligned with the construction of visual artifacts, facilitating their effective evaluation over the server (distributed) backend, and generating speculative queries based on a user's exploration trajectory. Aperture includes support for different visual artifacts, animations, and multilinked views via scalable brushing-and-linking. Finally, we also explore issues in effective containerization to support visualization workloads. Our empirical benchmarks profile several aspects of visualization performance and demonstrate the suitability of our methodology.
Linear and Nonlinear Measures of Postural Control in a Toddler With Cerebral Palsy: Brief Report.

Purpose The purpose of this study was to describe changes in linear and nonlinear measures of postural control along with motor outcomes in a young child with cerebral palsy. Summary of key points Posturography in sitting and standing, the Gross Motor Function Measure-66 (GMFM-66), and the Early Clinical Assessment of Balance (ECAB) were performed prior to, during, and after physical therapy. The child demonstrated independent sitting throughout the study and developed independent standing during the study. He made improvements in the GMFM-66 and ECAB throughout the study. Higher average values were found in all linear and nonlinear measures in standing when compared to sitting, which may indicate less predictable movement due to less experience with standing. Recommendations for clinical practice Greater variability and lower predictability in postural control likely reflect early stages of skill acquisition. Research is needed to understand the optimal levels of movement variability and predictability.
News story aggregation and perceived credibility

The practice of aggregating news content—repurposing content created by other news organizations—raises questions about credibility. This experimental study suggests that news organizations can boo...
When I compliacted understood loss and grief.

What is known about the subject A parent's mental illness was viewed as a loss, like a death, causing profound grief. I learned how important parent-child communication is as an important factor in managing my own grief. What the paper adds to existing knowledge A child's grief, in this case, from loss of a parent due to mental illness, as in death, was profound at the time and did affect many aspects of my life. The failure to intervene in a timely fashion impaired effective resolution of that grief. Implications for mental health nursing Assessment of family dynamics and communication is critical to building coping skills for any young child dealing with loss of parental support due to mental illness. Early intervention with young children in need of emotional support and security is needed to assist them with effective adaptation to grief and loss. Abstract It is expected that loss of a parent from death will undoubtedly cause children to grieve. With supportive interventions, children can recover and grow into healthy, well-adjusted adults. Severe mental illness in a parent, however, also creates loss by altering the parent-child relationship, often leaving children confused, frightened and feeling alone. In the past, family members, especially the remaining parent, might not have recognized the symptoms of a grieving child and the system at that time was not well prepared to assist them in meeting that need. This is the story of one such child.
PHYSICAL CONSTRAINTS ON FAST RADIO BURSTS

Fast radio bursts (FRBs) are isolated, ms radio pulses with dispersion measure (DM) of order 10^3 pc cm^(–3). Galactic candidates for the DM of high latitude bursts detected at GHz frequencies are easily dismissed. DM from bursts emitted in stellar coronas are limited by free-free absorption and those from H II regions are bounded by the nondetection of associated free-free emission at radio wavelengths. Thus, if astronomical, FRBs are probably extragalactic. FRB 110220 has a scattering tail of ~5.6 ± 0.1 ms. If the electron density fluctuations arise from a turbulent cascade, the scattering is unlikely to be due to propagation through the diffuse intergalactic plasma. A more plausible explanation is that this burst sits in the central region of its host galaxy. Pulse durations of order ms constrain the sizes of FRB sources implying high brightness temperatures that indicates coherent emission. Electric fields near FRBs at cosmological distances would be so strong that they could accelerate free electrons from rest to relativistic energies in a single wave period.
Monomeric/dimeric forms of Fgf15/FGF19 show differential activity in hepatocyte proliferation and metabolic function.

Human Fibroblast Growth Factor 19 (FGF19) and mouse ortholog Fgf15 play similar roles in liver regeneration and metabolism via the activation of Fgfr4/b-klotho (Klb). Monomeric FGF19 and dimeric Fgf15 are both necessary for liver regeneration and proper bile acid (BA) metabolism. FGF19 elicits stronger effects than Fgf15 on glucose and fatty acid metabolism and only FGF19 induces hepatocellular carcinoma (HCC). However, inhibiting FGF19/FGFR4 signaling in HCC patients is associated with toxicity due to elevated BA levels. Here, we examine the structure/function relationship in Fgf15/FGF19 to better understand the molecular basis for their distinct functions. We demonstrate that FGF19 is a more effective activator of Fgfr4 and of downstream signaling (Erk, Plcg1) than Fgf15. Furthermore, we use site-directed mutagenesis to show that the presence or absence of an unpaired cysteine in Fgf15/19 modulates ligand structure and determines the ability of these molecules to induce hepatocyte proliferation, with monomers being more potent activators. Consistent with these findings, an engineered dimeric variant of FGF19 is less effective than wild-type FGF19 at inducing liver growth in cooperation with the Wnt-enhancer RSPO3. In contrast to effects on proliferation, monomeric and dimeric ligands equally inhibited the expression of Cyp7a1, the enzyme catalyzing the rate limiting step in BA production. Thus, structure and function of Fgf15/FGF19 are intricately linked, explaining why FGF19, but not Fgf15, induces liver tumorigenesis. Our data provide insight into FGF19/FGFR4 signaling and may inform strategies to target this pathway while limiting on-target toxicity due to dysregulation of BA production or induction of hepatocyte proliferation.
Current Advances in Characterization of Nano-porous Materials: Pore Size Distribution and Surface Area

Methods for characterizing the most important textural properties of porous materials, particularly pore size distribution (PSD) and specific surface area (SSA), using theoretical models to analyze standard experimental physisorption isotherms are reviewed. For PSD analysis, we explain the basics of the classical methods, including those based on the Kelvin equation and adsorption potential theory, as well as the modern molecular methods based on the density functional theory (DFT) and molecular simulation. For SSA analysis, the discussion is focused on kinetic theory, and primarily on the application of the Brunauer-Emmett-Teller (BET) method for characterization of microporous materials. Current advances and extensions of model-based methods are discussed, including those related to machine learning techniques. We reflect on the limitations of the current state-of-the-art methods and point out some possible directions for future studies.
State Anxiety Prior to and After Participating in Lockdown Drills Among Students in a Rural High School

Widespread concern exists that participating in lockdown and active shooter drills, practices that although discussed synonymously are different, may be similarly traumatizing for students. This st...
An FDA Analysis of Inspected Entities After Receiving Official Action Indicated Letters for Good Clinical Practice Violations

Limited research has been conducted to examine whether clinical investigators (CIs), sponsors (SPs), contract research organizations (CROs), and sponsor-investigators (SIs) continue conducting clinical trials following issuance of FDA Official Action Indicated (OAI) letters. FDA issues OAI letters for significant regulatory violations. The objective of this study was to evaluate the status of inspected entities who received OAI letters in the conduct of Center for Drug Evaluation and Research (CDER)-regulated clinical trials (CRCTs). This cross-sectional study included an analysis of inspectional data from CDER’s Good Clinical Practice (GCP) inspections for OAI letters issued from October 1, 2010, to September 30, 2015, with an in-depth analysis of post-OAI status of inspected entities, including OAI follow-up inspections. Of the 2248 GCP letters issued during this period, 104 (4.6%) OAI letters were sent: 95 (4.2%) to CIs (91% of OAIs), 7 (0.3%) to SPs (7% of OAIs), and 2 (0.08%) to SIs (2% of OAIs). Majority of OAI letters were issued as a result of a for-cause inspection. Five CIs were excluded from analysis. No OAI letters were sent to CROs. Only 30% of CIs (27 out of 90) continued to conduct CRCTs. OAI follow-up inspections were completed for these CIs resulting in 16 No Action Indicated (NAI), 11 Voluntary Action Indicated (VAI), and no OAI letters. Majority (64%) of the VAI letters noted repeated but not significant violations. Majority (70%) of CIs who received an OAI letter were no longer conducting CRCTs at the time of follow-up. Of the 27 CIs continuing CRCTs, 16 (59%) OAI follow-up inspections resulted in NAI classifications and 11 (41%) in VAI.
Effectiveness of virtual classroom training in improving the knowledge and key maternal neonatal health skills of general nurse midwifery students in Bihar, India: A pre- and post-intervention study

Summary Background In 2008–09, the National Health Systems Resource Center of India reported overall quality of nurse-midwifery education in Bihar as grossly sub-optimal. To address this, we implemented a competency-based training using virtual classrooms in two general nurse midwives (GNM) schools of Bihar. The students from remotely located nursing institutions were now able to see live demonstrations of maternal and newborn health (MNH) practices performed by a trained faculty on simulation models at instructor location. Objective To evaluate the effectiveness of virtual classroom training in improving the MNH-related skills of the nursing-midwifery students in Bihar, India. Design This study used a pre- and post-intervention design without a control group. Settings Students from two public GNM schools of Bihar. Participants Final-year students from both the GNM schools who have completed their coursework in MNH. Method A total of 83 students from selected GNM schools were assessed for their competencies in six key MNH practices using objective structured clinical examination method prior to intervention. A 72 hour standardized training package was then implemented in these schools through virtual classroom approach. Post-intervention, 92 students from the next batch who attended virtual training were assessed for the same competencies. Results The mean student score assessed before the intervention was 21.3 (95% CI, 19.9–22.6), which increased to 62.0 (95% CI, 60.3–63.7) post-intervention. This difference was statistically significant. When adjusted for clustering using linear regression analysis, the students in post-intervention scored 52.3 (95% CI, 49.4%–55.3%) percentage points higher than pre-intervention, and this was statistically significant. Conclusion Virtual classroom training was found to be effective in improving knowledge and key MNH skills of GNM students in Bihar, India.
Mesenchymal stem cells: no longer second class marrow citizens.

Osteogenesis Imperfeca study raises new hopes and questions for mesenchymal and stem cell therapies (pages 309–313).
The War on Terrorism: A Collision of Values, Strategies, and Societies

Globalization, Ideology, and the Clash of Societies The Clash of Societies Religion, Moral Certainty, and Fundamentalism Our Fragile Environment: How Societies Collapse The Management and Mitigation of Risk The Role of the University and Research in the War on Terrorism Terrorism, Islamic Insurgency, and Religious War The Global War on Terrorism-Instruments of Statecraft Terrorism: Characteristics and Ideology Organizational Skills of the Terrorist Leader The World Wide Web and WorldWide Terrorism Targets of Terrorists The Challenge of Protecting Our Nation Protecting Critical Infrastructure and Key Assets Research and Development in Support of Critical Infrastructure Focus on Targets, Not Terrorists Weapons of Mass Destruction Broken Borders and Illicit Trafficking in Nuclear Materials Nuclear Terrorism Biological Terrorism Chemical Terrorism Agroterrorism Our Intelligence Community Office of the Director of National Intelligence National Intelligence Program Agencies Military Intelligence Program Agencies Congressional Oversight Committees The Intelligence Process The Reform and Reorganization of Our Intelligence Community Historical Emergence of Intelligence Organizations The Cold War Years: 1947-1989 Two Gulf Wars and Middle East Terrorist Activity September 11, 2001 Attack and Categories of Failure Transforming the Intelligence Community National Security and Counterterrorism Policy Formulation: Transformational Issues and Challenges Instruments of Statecraft Transformational Issues and Challenges Future Trends in Global Terrorism: Mapping the Strategy to Defeat an Ideology Globalization, Ideology, and Security Trends in Global Terrorism Global Trends-2015 and Mapping the Global Future-2020 21st Century Nation-State Issues and Challenges Bibliography Appendices Index
The individual's transactions demand for money: A utility maximization approach

Abstract This model of the transactions demand shows how an individual may simultaneously choose patterns of consumption, money holdings, and bond holdings over time that maximize utility when faced with a wide variety of possible cyclical patterns in his flow of income. Interesting conclusions about the transactions demand and the real balance effect are derived. For example, there is no theoretical reason to believe that a single individual's demand for money is proportional to his income, and a small excess stock of money is likely to cause a large increase in his level of consumption.
Fine Structural Changes of Acetobacter suboxydans During Growth in a Defined Medium

Cytological differences were observed between stationary- and exponentialphase cells of Acetobacter suboxydans grown in a defined medium. Unstained cells observed with the light microscope just after entering the stationary phase differed from exponentially growing cells in that the former exhibited localized increases in density, particularly in the polar regions. Electron microscopy of thin sections revealed that early stationary-phase cells possessed predominantly polar complexes of intracytoplasmic membranes accompanied by polar increases in ribosomal material. When cultures were allowed to continue far into the stationary phase, cells contained extensive aggregations of membrane-like material as the predominant fine-structural feature. In contrast, thin sections of exponentially growing cells exhibited only occasional indications of intracytoplasmic membranes. Intracytoplasmic membranes heretofore have been observed only rarely in the heterotrophic Pseudomonadales.