cssi/SciSciGPT-SciSciNet huggingface dataset:
Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M

Epidermal growth factor receptor (EGFR) mutations, especially EGFR-exon 19 deletions and EGFR-L858R, are the most frequent actionable genomic events in lung adenocarcinomas. Tumors arise due to constitutively activated EGFR signaling and are susceptible to EGFR tyrosine kinase inhibitors (TKIs). First generation EGFR TKIs (gefitinib and erlotinib) and the second generation EGFR TKI afatinib are approved worldwide. Although targeted therapies against EGFR mutants induce dramatic initial responses, acquired resistance (through multiple biological mechanisms) to erlotinib, gefitinib and afatinib emerges within the first 1-2 years of continued monotherapy. EGFR-T790M accounts for more than half of acquired resistance to first or second generation EGFR TKIs by modifying ATP affinity and drug binding kinetics. Two new studies have shown that two covalent pyrimidine inhibitors—AZD9291 and rociletinib of EGFR-T790M (i.e., third generation EGFR TKIs) shown remarkable clinical activity in patients with acquired resistance to erlotinib, gefitinib and afatinib when the tumor carries EGFR-T790M in conjunction with an activating mutation. However, and regrettably, acquired resistance to these third generation EGFR TKIs has already been reported in preclinical models and clinical specimens; such as a tertiary mutation at EGFR-C797S that prevents covalent binding of EGFR TKIs. The experience with sequential EGFR TKI monotherapy highlights tumor heterogeneity and adaptability (i.e., relentless game of whack-a-mole played between TKIs and cancer), and will help shape future clinical development of novel combinatory approaches to manage EGFR mutated lung adenocarcinomas.
Neisseria gonorrhea and Chlamydia trachomatis screening at intrauterine device insertion and pelvic inflammatory disease.

OBJECTIVE:To evaluate the relationship between Neisseria gonorrhea and Chlamydia trachomatis screening strategies and risk of pelvic inflammatory disease (PID) after intrauterine device (IUD) insertion.METHODS:We conducted a retrospective cohort study of all IUD insertions at Kaiser Permanente North
Influence of body mass index on revision rates after primary total knee arthroplasty

Studies demonstrate that revision rates after primary total knee arthroplasty (TKA) tend to be higher in obese patients. However, the existence of a body mass index (BMI) threshold remains unexplored. We conducted a prospective cohort study of 2442 primary TKAs in 2035 patients (69.1 % women; mean age 72 years; mean follow-up 93 months, range 38–203). We evaluated the influence of BMI in five categories on all-cause revision after TKA using incidence rates (IR), hazard ratios (HR), and Kaplan–Meier survival analysis. Adjustment for baseline imbalances was performed using Cox regression analysis. Over the study period, 71 revisions occurred. Revision rates were 3.2 cases/1000 patient-years for patients of normal weight, 3.4/1000 for overweight patients and 3.0/1000 for patients classified as obese class I. At BMI ≥ 35, a significant increase in revision was noted. Comparing BMI ≥ 35 vs. < 35, there were 6.4 vs. 3.2 /1000. Crude HR was 2.0 [95 % confidence interval (CI) 1.2–3.3, p = 0.009], and the adjusted HR was 2.1 (95 % CI 1.2–3.6, p = 0.008). All-cause revision rates after primary TKA doubled in patients with a BMI of 35 but were similar in those with a BMI <35.
Matriptase Activation and Shedding through PDGF-D-mediated Extracellular Acidosis

Activation of β-platelet-derived growth factor receptor (β-PDGFR) is associated with prostate cancer (PCa) progression and recurrence after prostatectomy. Analysis of the β-PDGFR ligands in PCa rev...
Surface-Emitting QDs Laser with a Monolithically Integrated Grating Outcoupler

Grating coupled surface emitting laser diodes were designed and fabricated from a 1270nm InAs QDs epi. The integrated outcoupler’s characteristics were compared with the grating simulation data. The advanced emitter’s performance enhanced the device applications.
Effect of Cupric Sulfate on the Prophylactic Efficacy of Three Arsonic Acid Compounds Against Histomoniasis in Young Turkeys

Abstract THE addition of cupric sulfate (copper sulfate or bluestone) to poultry diets has been a common practice for many years. Only limited research data have been published relative to this practice. Hinshaw and Lloyd (1929) reported that 0.125 and 0.25 percent cupric sulfate solutions inhibited growth of various micro-organisms which contaminated the drinking water of turkeys. Underwood et al. (1956) reported that cupric sulfate in feed and water was ineffective in treating or preventing crop mycosis in chicks and poults. Bierer et al. (1965) reported that growth of several micro-organisms was inhibited by cupric sulfate. Growth of E. coli, Staphylococcus, Salmonella, and Citrobacter was inhibited on Sabouraud plates, with a 1:100 cupric sulfate solution was added to the media. This indicated that certain pathogenic micro-organisms might likewise be reduced or inhibited in the intestinal tract of animals. Thus, cupric sulfate may act much like an antibiotic in the inhibition…
Preparation and Clinical Application of Fulening, A Slow- release Membrane Drug

Objective:To prepare and develop a new type of slow release membrane drug Fulening for external use and to survey its clinical therapeutic effectiveness in the treatment of vaginitis. Methods:The drug membrane was prepared with the use of materials including tinidazole, small amount of diethylstilbestrol, and vitamine B 1, vitamine B 2, vitamine B 6, sodium carboxymethyl cellulose, polyvinyl alcohol, etc. It was used externally to treat patients with trichomonal vaginitis, colpomycosis, senile vaginitis and bacterial vaginitis, totaling 355 cases. The drug membrane was used once daily or every other day, for 5 to 7 times. Results:The slow release membrane drug Fulening was subjected to quality control. The overall effective rate in the treatment of vaginitis was 99.2% , while patients with bacterial vaginitis were 100.0% cured. No adverse reactions were noticed. Conclusion:The slow release membrane drug was shown to have a good therapeutic effect in the treatment of vaginitis. It is easy to use, has no toxic and side effects and is therefore worth spreading its application.
Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma

Purpose: Merkel cell carcinoma (MCC) is an aggressive cancer with frequent metastasis and death with few effective therapies. Because programmed death ligand-1 (PD-L1) is frequently expressed in MCC, immune checkpoint blockade has been leveraged as treatment for metastatic disease. There is therefore a critical need to understand the relationships between MCPyV status, immune profiles and patient outcomes. Experimental Design: Immunohistochemistry for CD3, CD8, PD-1, PD-L1 and MCPyV T-antigen (to determine MCPyV status) was performed on 62 primary MCCs with annotated clinical outcomes. Automated image analysis quantified immune cell density (positive cells/mm2) at discrete geographic locations (tumor periphery, center, and hotspot). T-cell receptor sequencing (TCRseq) was performed in a subset of MCCs. Results: No histopathologic variable associated with overall survival (OS) or disease-specific survival (DSS), whereas higher CD3+ (p=0.004) and CD8+ (p=0.037) T-cell density at the tumor periphery associated with improved OS. Higher CD8+ T-cell density at the tumor periphery associated with improved DSS (p=0.049). Stratifying MCCs according to MCPyV status, higher CD3+ (p=0.026) and CD8+ (p=0.015) T-cell density at the tumor periphery associated with improved OS for MCPyV+ but not MCPyV- MCC. TCRseq revealed clonal overlap among MCPyV+ samples, suggesting an antigen-specific response against a unifying antigen. Conclusions: These findings establish the tumor associated immune infiltrate at the tumor periphery as a robust prognostic indicator in MCC and provide a mechanistic rationale to further examine whether the immune infiltrate at the tumor periphery is relevant as a biomarker for response in ongoing and future checkpoint inhibitor trials in MCC.
Effect of high pressure processing on the qualities of blueberry juice

The effect of high pressure processing(HPP)(200 ~ 500MPa for 5 ~ 15min)on the quality changes of blueberry juice were studied. The results showed that microorganisms in fresh blueberry juice could be inactivated effectively by HPP. Compared with the control samples,the color,the reducing sugar and the soluble solids in blueberry juice had no significant change treated by HPP treatment,while total sugars and total phenol were decreased after HPP treatment. Anthocyanins and VC were well retained after HPP treatment.
Immunocytochemical localization of luteinizing hormone and follicle-stimulating hormone in the equine pituitary

Gonadotropin-specific primary antisera and gold-conjugated secondary antibodies were used to immunocytochemically localize gonadotropins in the anterior pituitary of intact pony mares. Electron microscopy was then used to characterize the ultrastructure and immunoreactive staining characteristics of equine gonadotropes. Cells containing LH were morphologically indistinguishable from those containing FSH. Gonadotropes were relatively large and commonly had eccentric nuclei. The rough endoplasmic reticulum was well developed and dilated. Secretory granules were present in two morphologically distinct forms. Large polymorphic granules were generally located in perinuclear cytoplasmic areas, whereas small and uniformly shaped granules were in the peripheral cytoplasm, close to the cell membrane. Double-labeling revealed cells with granules that stained for both LH and FSH as well as cells that stained for either LH or FSH. Gonadotropes constituted 15 to 32% of all pituitary cells in the anterior pituitaries from the three mares included in this study. Cells that stained for only LH constituted 2 to 16% of all pituitary cells, cells that stained for only FSH ranged from 1 to 4.5%, and cells staining for both hormones constituted 6.2 to 24% of the pituitary cells. These results indicate that there are in fact three distinct subclasses of gonadotropes in the equine anterior pituitary based on immunocytochemical staining, which is similar to the situation described for several other mammalian species.
Increasingly conflicted: an analysis of conflicts of interest reported at the annual meetings of the Orthopaedic Trauma Association.

PURPOSE To identify trends in industry sponsorship of orthopaedic trauma research presented at the annual meetings of the Orthopaedic Trauma Association since the establishment of conflict of interest (COI) reporting policies in 1993. BACKGROUND Industry plays a large role in funding orthopaedic basic science and clinical research. The purpose of this study was to analyze the role of industrial support in orthopaedic research as documented in the final programs of the annual meetings of the Orthopaedic Trauma Association (OTA), determine the incidence and nature of COI in the papers and posters accepted for OTA presentation, and report any changes in the frequency of reporting since disclosure policies were enacted in 1993. METHODS This paper analyzes COI for all years since the adoption of the reporting policies 1993-2002. From 1993-1998, presenters of posters and papers presented at the Orthopaedic Trauma Association annual meetings were required to disclose COI greater than dollar 500, the type of monetary distribution was not recorded. From 1999-2002, presenters of posters and papers were required to acknowledge the type of COI: 1. research grant, 2. miscellaneous non-income support, 3. royalties, 4. stock, and 5. consultant fees. All COI categories were recorded for each year Linear regression was used to determine significance of trends in the pooled data. RESULTS There was an increase in the percentage of papers accepted and presented at the OTA between 1993 and 2002 with COI. The number of papers reporting COI rose from 7.6% in 1993 to 12.6% in 2002 (p = 0.0129). There was no significant increase in posters with COI over that same time period. No changes were observed in the nature of industrial involvement since the change in reporting enacted in 1999. There were no observed trends in NIH or OTA grant distribution between 1993 and 2002. DISCUSSION AND CONCLUSION Industry is playing an increasing role in the funding oforthopaedic research. The majority of industrial support is in the form of research grants. The increasing industrial support of scientific research in the public sector is to be applauded as long as it does not lead to the sequestering and suppression of information that may be disadvantageous to the industrial sponsor.
Results of 212 consecutive endopyelotomies: an 8-year followup.

AbstractBetween 1983 and 1991 we performed 212 endopyelotomies on 110 cases of primary and 102 of secondary obstruction of the ureteropelvic junction. Of the 189 patients in the series 89% have been followed for a minimum of 6 months postoperatively, 63% for more than 3 years (3 to 8-year followup). Our overall success rate has been 86% with little difference being detected between the success that we have obtained with primary and secondary obstructions (85% versus 86%). Other variables, such as patient age, sex or side of obstruction, have little bearing on the outcome of the procedure. Endopyelotomy is passing the test of time as a safe and reliable means to correct ureteropelvic junction obstruction. Endopyelotomy should be the first choice for the correction of ureteropelvic junction obstruction in most patients.
Diagnostic dermatologic methods.

Seven simple and straightforward diagnostic procedures are reviewed in this article, all of which can be performed in the pediatrician’s office.
Renal drug transporters and their significance in drug–drug interactions

The kidney is a vital organ for the elimination of therapeutic drugs and their metabolites. Renal drug transporters, which are primarily located in the renal proximal tubules, play an important role in tubular secretion and reabsorption of drug molecules in the kidney. Tubular secretion is characterized by high clearance capacities, broad substrate specificities, and distinct charge selectivity for organic cations and anions. In the past two decades, substantial progress has been made in understanding the roles of transporters in drug disposition, efficacy, toxicity and drug–drug interactions (DDIs). In the kidney, several transporters are involved in renal handling of organic cation (OC) and organic anion (OA) drugs. These transporters are increasingly recognized as the target for clinically significant DDIs. This review focuses on the functional characteristics of major human renal drug transporters and their involvement in clinically significant DDIs.
Abstract 26: Novel Role of Anticoagulant Heparan Sulfate in Antithrombin Anti-inflammatory Signaling

Antithrombin (AT) therapy reduces morbidity/mortality in systemic inflammatory response syndromes, such as septic shock. These effects stem from the ability of AT to directly initiate cell signaling, which requires AT engagement with heparan sulfate proteoglycans. It is presently unclear if this process involves anticoagulant heparan sulfate (HS AT+ ), a specific motif with high affinity for AT that is produced by endothelial cells. If HS AT+ regulates anti-inflammatory signaling, then Hs3st1 -/- mice, which lack endothelial HS AT+ , should exhibit a proinflammatory state and should not benefit from AT treatment. We tested these hypotheses using a mouse model of lipopolysaccharide (LPS)-induced septic shock. Hemodynamics were monitored with a left ventricle pressure-volume catheter. Both Hs3st1 +/+ and Hs3st1 -/- mice die of cardiogenic shock. However, Hs3st1 -/- , compared to Hs3st1 +/+ , mice exhibited a much more rapid onset of death. Left ventricular gene expression profiles of mice with systemic LPS challenge showed enhanced expression of leukocyte recruitment genes (P-selectin, Cxcl10) in Hs3st1 -/- mice. Consistent with these data, LPS-treated Hs3st1 -/- mice, compared to Hs3st1 +/+ , exhibited enhanced leukocyte rolling flux within cremaster muscle venules. Thus, mice lacking HS AT+ exhibit a proinflammatory phenotype. AT treatment of Hs3st1 +/+ mice reduced both LPS-induced lethality and leukocyte-endothelial interactions. Conversely AT treatment of Hs3st1 -/- mice enhanced both LPS-induced lethality and leukocyte-endothelial interactions. Thus, AT failed to elicit anti-inflammatory effects in mice lacking HS AT+ . Our results indicate that endothelial HS AT+ is one component that mediates AT’s anti-inflammatory activity. These findings provide an initial step towards elucidating the role of HS AT+ and AT in a novel natural anti-inflammatory pathway of the blood vessel wall. This pathway is an ideal target for developing therapeutics to combat the devastating outcomes of septic shock.
Snap, Tweet and Post: College Student Social Media Perceptions and Heutagogic Practices and Uses

The nearly ubiquitous access to technology and the diversity of social media sites has provided students with easy access to a wide range of information and opportunities for interaction with other individuals. The nature of social media creates a context in which students can determine when they view information, the duration of the viewing, where they view their social media and why they choose to view the media. The conditions of social media interactions present an opportunity for self-determined learning, or heutagogy. While heutagogy takes place multiple time during a student’s average day, the self-determined nature of the learning may lead to issues associated with self-regulation and anti-social behaviors. To study student self-determined perceptions and engagement with social media we developed a mixed methods survey gathering quantitative and qualitative data from 71 undergraduate students. Our results reveal students do self-determine their engagement with social media and will also self-determine the norms they use for engagement. We also found that the students perceived that they gave up other activities to engage in social media, and were likely to spend more time studying, exercising, and bettering themselves of they did not spend time interacting with social media.
DSM-5 cannabis use disorder in the National Epidemiologic Survey on Alcohol and Related Conditions-III: Gender-specific profiles.

Abstract Objective The objective of this study was to present current information on the prevalence, correlates, comorbidity and quality of life among men and women with cannabis use disorder (CUD). Methods In 2012–2013, 36,309 respondents ≥ 18 years old participated in face-to-face interviews in the National Epidemiologic Survey on Alcohol and Related Conditions-III. Results Prevalence of 12-month CUD was greater among men (3.5%) than women (1.7%). Women experienced shorter duration from onset of cannabis use to onset of CUD than men (mean = 5.8 years, men; mean = 4.7 years, women). In both men and women, prevalences of CUD were greater among young adults, Blacks, and those with lower income and greater among Native American women relative to White women. CUD was highly comorbid with other substance use disorders, PTSD, ASPD and borderline and schizotypal PDs for men and women. Quality of life for individuals with CUD was low regardless of gender. Conclusions DSM-5 CUD among men and women is highly prevalent, comorbid and characterized by low quality of life. Results highlighted the need for integrated treatment of CUD and comorbid disorders and the urgency of identifying and implementing effective prevention and intervention approaches, especially for those sociodemographic subgroups for which both men and women are at greater risk for the disorder.
Challenges of developing a valid dietary glucosinolate database

Abstract Glucosinolates are a group of important cancer chemo-preventive sulfur-containing compounds in cruciferous vegetables. To estimate their dietary intake, there is a great need to develop a valid glucosinolate database. The aim of this study was to investigate the key challenges in developing such database. First, three commonly used enzyme deactivation methods (blanching, steaming and microwaving) were compared with samples of raw untreated broccoli and kale. Steaming and microwaving were found to effectively deactivate myrosinase, both led to significantly higher glucosinolate values that blanching (∼15–50% higher). Glucosinolates in untreated broccoli was similar to that of blanching broccoli, while glucosinolates were not detected in untreated kale. Heat treatment was also shown to alter the profiles of individual glucosinolate. Quantification of total glucosinolates of four common vegetables was compared by the two most commonly used analytical methods (ISO 9167-1 method and cyclocondensation method). Except for kale, the results from ISO 9167-1 were much higher (∼6–8 fold) than that from cyclocondensation method in other three vegetables. In conclusion, the sample preparation procedure, analytical method for quantification and the compounds to be measured must be considered and validated in order to develop a valid dietary glucosinolate database.
Vigilance in Mitral Regurgitation: Variation and the Way Forward.

The timing of surgical intervention in primary mitral regurgitation (MR) remains a subject of controversy, as the decision must balance the risks of surgery against the adverse outcomes associated with advanced left ventricular remodeling. To provide clinicians with a management framework, national standards documents identify the presence of symptoms, left ventricular dysfunction, enlarged left ventricular dimensions, and elevated pulmonary pressures as triggers for surgery in chronic severe primary MR.1–3 Achieving optimal outcomes in primary MR rests on the timely identification of these surgical triggers, which, in turn, is incumbent on careful, longitudinal, clinical, and echocardiographic follow-up.2 As such, specific echocardiographic follow-up intervals are recommended for mild, moderate, and severe MR by American College of Cardiology/American Heart Association/European Society of Cardiology guidelines and Appropriate Use Criteria (AUC).1,3,4 Yet, real-world adherence to these recommendations in this group of patients is not clearly known. See Article by Tanguturi et al In this issue of the Journal, Tanguturi et al5, in this cleverly designed study, assessed the echocardiographic follow-up intervals used by healthcare providers for monitoring primary MR. This work represents an important effort aiming to understand healthcare delivery and practice patterns in the care of patients with primary MR and evaluating compliance with guideline recommendations. In the setting of a high-volume center and a reputable echo laboratory, and using a carefully selected population that eliminated most other causes for repeat studies, the investigators found that for severe MR, the mean interval for echocardiographic follow-up was 12.4 months. The mean echocardiographic follow-up intervals for less severe disease were longer: 17 months for moderate MR, 18.3 months for mild MR, and 17.4 months for trace MR. There was considerable variation in intervals based on specialty with primary care physicians in general having the longest …
Systematic Review of Normal Tissue Complication Models Relevant to Standard Fractionation Radiation Therapy of the Head and Neck Region Published After the QUANTEC Reports.

There has recently been an increasing interest in model-based evaluation and comparison of different treatment options in radiation oncology studies. This is partly driven by the considerable technical advancements in radiation therapy of the last decade, leaving radiation oncologists with a multitude of options to consider. In lieu of randomized trials comparing all of these different treatment options for varying indications, which is unfeasible, treatment evaluations based on normal tissue complication probability (NTCP) models offer a practical alternative. The Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) effort, culminating in a number of reports published in 2010, provided a basis for many of the since-implemented dose–response models and dose–volume constraints and was a key component for model-based treatment evaluations. Given that 7 years have passed since the QUANTEC publications and that patient-reported outcomes have emerged as an important consideration in recent years, an updated summary of the published radiation dose–response literature, which includes a focus on patient-reported quality of life outcomes, is warranted. Here we provide a systematic review of quantitative dose–response models published after January 1, 2010 for endpoints relevant to radiation therapy for head and neck cancer, because these patients are typically at risk for a variety of treatment-induced normal tissue complications.
Technical note: Validation of the BHBCheck blood β-hydroxybutyrate meter as a diagnostic tool for hyperketonemia in dairy cows

Accurate cow-side blood β-hydroxybutyrate (BHB) detection meters are valuable tools for rapid diagnosis of hyperketonemia. The main objective of this study was to compare the blood BHB measured in whole blood by the BHBCheck meter (PortaCheck, Moorestown, NJ) to a previously validated meter, Precision Xtra meter (Abbott Laboratories, Abbott Park, IL) and a colorimetric laboratory assay. Samples (n = 426) were collected from postpartum primiparous and multiparous Holstein cows (n = 79 cows) enrolled in 1 of 2 experiments (Exp) with different sampling schedules (Exp 1: n = 39 cows, 58 samples; Exp 2: n = 40 cows, 368 samples). In both Exp, whole-blood samples were collected from the coccygeal vessels after morning milking, before morning feeding. Blood samples were used immediately for BHB quantification via the BHBCheck meter and the Precision Xtra meter. Blood was also collected into evacuated tubes containing no additive (Exp 1) or potassium oxalate/sodium fluoride (Exp 2), which were centrifuged for serum or plasma separation and stored at -20°C for subsequent analysis. Laboratory quantification of BHB concentration was done by the BHB LiquiColor Assay (EKF Diagnostics-Stanbio, Boerne, TX; certified for serum and plasma). Data were analyzed by UNIVARIATE, CORR, FREQ, REG, and LOGISTIC procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). Within this sample set, average parity was 3.3 lactations and DIM was 14 d. The proportion of samples classified as hyperketonemia (BHB ≥1.2 mmol/L) was 25, 28, and 31% as determined by the colorimetric assay, BHBCheck meter, and Precision Xtra meter, respectively. The correlation for BHBCheck meter BHB concentration compared with the colorimetric assay concentrations was r = 0.96, with a sensitivity of 91% and specificity of 93%. Correlation, sensitivity, and specificity of the Precision Xtra meter concentrations were 0.97, 98%, and 92%, respectively. Bland-Altman plots demonstrated minimal bias for both meters. Area under the receiver operator characteristic curve suggests adequate diagnostic accuracy of both meters. Overall, accuracy, sensitivity, and specificity of the BHBCheck meter was similar to the Precision Xtra meter and laboratory assay, indicating the BHBCheck meter is appropriate for use as a cow-side diagnostic test for hyperketonemia in dairy cows.
LncRNA Seduction of GOT2 Goes Viral.

Mechanisms of viral infection are active areas of investigation. In a recent issue of Science, Wang et al. (2017) reveal an additional function of a host-encoded long non-coding RNA (lncRNA) in regulating viral expression by binding a host metabolic enzyme to enhance its catalytic activity.
Circular Reasoning in Climate Change Research

A literature review shows that the circular reasoning fallacy is common in climate change research. It is facilitated by confirmation bias and by activism such that the prior conviction of researchers is subsumed into the methodology. Example research papers on the impact of fossil fuel emissions on tropical cyclones, on sea level rise, and on the carbon cycle demonstrate that the conclusions drawn by researchers about their anthropogenic cause derive from circular reasoning. The validity of the anthropogenic nature of global warming and climate change and that of the effectiveness of proposed measures for climate action may therefore be questioned solely on this basis.
WOLFF PARKINSON-WHITE SYNDROME CAUSING NON-ST ELEVATION MYOCARDIAL INFARCTION

Wolff-Parkinson-White [WPW] syndrome has classically been described in younger patients and is rarely seen in the elderly as they are treated early or the accessory pathway may lose its conductive properties with age. An 83 year old female with recently diagnosed WPW on EKG presented with chest
Deletion of Orai1 leads to bone loss aggravated with aging and impairs function of osteoblast lineage cells

Osteoblast lineage cells, a group of cells including mesenchymal progenitors, osteoblasts, and osteocytes, are tightly controlled for differentiation, proliferation and stage-specific functions in processes of skeletal development, growth and maintenance. Recently, the plasma membrane calcium channel Orai1 was highlighted for its role in skeletal development and osteoblast differentiation. Yet the roles of Orai1 in osteoblast lineage cells at various stages of maturation have not been investigated. Herein we report the severe bone loss that occurred in Orai1-/- mice, aggravated by aging, as shown by the microcomputed tomography (mCT) and bone histomorphometry analysis of 8-week and 12-week old Orai1-/- mice and sex-matched WT littermates. We also report that Orai1 deficiency affected the differentiation, proliferation, and type I collagen secretion of primary calvarial osteoblasts, mesenchymal progenitors, and osteocytes in Orai1-/- mice; specifically, our study revealed a significant decrease in the expression of osteocytic genes Fgf23, DMP1 and Phex in the cortical long bone of Orai1-/- mice; a defective cellular and nuclear morphology of Orai1-/- osteocytes; and defective osteogenic differentiation of Orai1-/- primary calvarial osteoblasts (pOBs), including a decrease in extracellular-secretion of type I collagen. An increase in the mesenchymal progenitor population of Orai1-/- bone marrow cells was indicated by a colony forming unit-fibroblasts (CFU-F) assay, and the increased proliferation of Orai1-/- pOBs was indicated by an MTT assay. Notably, Orai1 deficiency reduced the nuclear localization and transcription activity of the Nuclear Factor of Activated T-cell c1 (NFATc1), a calcium-regulated transcription factor, in pOBs. Altogether, our study demonstrated the crucial role of Orai1 in bone development and maintenance, via its diverse effects on osteoblast lineage cells from mesenchymal progenitors to osteocytes.
Administrative Issues Involving Behavioral Approaches in Autism

Administrators and clinicians are becoming more aware that reliable, sophisticated, and effective behavior management technologies often are insufficient to implement and maintain changes in the challenging behavior of individuals with autism. As interventions have moved from highly controlled settings to the community, research and practice have been both expanded and complicated (Rappaport, 1977). Several writers have argued that attention to the organizational system with recognition of the social, cultural, political, and economic forces impacting those in the system is essential (Fisher, 1983; Greenblatt, 1983; Powers & Franks, 1988). Although it seems obvious that scientific inquiries in the applied arena must always be cognizant of these forces, it is more typically the case that such factors are systematically ignored. Sarason (1981) notes that the theories of individual change to which most human service professionals are exposed in their own training are insufficient for developing a coherent theory of systemic change.
GENERAL PROPERTIES OF MOLECULES

In passing from atoms to molecules, a new, higher level of organization in the structure of matter is obtained. Although atomic properties play an essential role in the description of molecular properties, the latter are not merely sums over atomic properties. Thus, a molecule is not only quantitatively but also qualitatively different from its constituent atoms. The complexities of molecular structure require a variety of approximations whose general objective is to isolate different features of the problem and to treat them separately. This chapter discusses some of these methods. The significance of the Hellmann–Feynman theorem is that within the Born–Oppenheimer approximation, the forces acting on nuclei are derivable from the classical potential and the electronic wave function. The chapter also discusses some general aspects of the electronic problem.
Pioneering in the Water Works Field

In selecting a subject for this paper, the writer had in mind the various exhaustive reports that had already been made on the subject of the Rochester Water Works, ranging over a long period of years. The data for these papers were assembled and arranged for presentation either as reports to the Rochester City Council or as papers read before local engineering societies and water works conventions. Among the list was a paper read in 1932 before the Rochester Academy of Science by Edwin A. Fisher, then City Engineer of Rochester, covering the history of the Rochester Water Works in its first century, commencing in 1834. Another paper covering the same subject, and prepared by Irving Matthews, formerly Superintendent of the Rochester Water Works, was read before the New York section of the American Water Works Association at Rochester in 1927. Another elaborate report was published in 1913 by John F. Skinner, Principal Assistant Engineer, covering conduits Nos. 1 and 2 of the Hemlock Lake System. With these data available, I take no credit for anything original in the following paper, but as a water works engineer I have been greatly impressed by the number of interesting facts brought out in the early history of these works. With this in mind, it appeared worth while to stress again those particular instances wherein Rochester appears in the role of "trail blazer" or pioneer in the water works field. In order not to repeat the many details already covered by the former papers, I have confined myself to the more salient features and with particular emphasis on those of most historic importance. Many long strides forward have been taken since the events here narrated.
Ozone, air pollution, and respiratory health

Of the outdoor air pollutants regulated by the Clean Air Act of 1970 (and recently revised in 1990), ozone has been the one pollutant most difficult to control within the federal standards. The known human health effects are all on the respiratory system. At concentrations of ozone which occur during summer air-pollution episodes in many urban metropolitan areas of the United States, a portion of the healthy population is likely to experience symptoms and reversible effects on lung function, particularly if exercising heavily outdoors. More prolonged increase in airway responsiveness and the presence of inflammatory cells and mediators in the airway lining fluid may also result from these naturally occurring exposures. Serial exposures to peak levels of ozone on several consecutive days are more characteristic of pollution episodes in the Northeast United States and may be associated with recurrent symptoms. No "high-risk" or more sensitive group has been found, in contrast to the case of sulfur dioxide, to which asthmatics are more susceptible than normals. The occurrence of multiple exposure episodes within a single year over many years in some areas of California has led to studies looking for chronic effects of ozone exposure on the lung. To date, no conclusive studies have been reported, although further work is under way. Much of what we know about the effects of this gas on the lung are based on controlled exposures to pure gas within an environmental exposure laboratory. Interactions between substances which commonly co-occur in air-pollution episodes are also under investigation.
Verified reference implementations of WS-Security protocols

We describe a new reference implementation of the web services security specifications. The implementation is structured as a library in the functional programming language F#. Applications written using this library can interoperate with other compliant web services, such as those written using Microsoft WSE and WCF frameworks. Moreover, the security of such applications can be automatically verified by translating them to the applied pi calculus and using an automated theorem prover. We illustrate the use of our reference implementation through examples drawn from the sample applications included with WSE and WCF. We formally verify their security properties. We also experimentally evaluate their interoperability and performance.
Crystallins, genes and cataract

Far from being a physical entity, assembled of inanimate structural proteins, the ocular lens epitomizes the biological ingenuity that sustains an essential and near-perfect physical system of immaculate optics. Crystallins (α,β, and γ) provide transparency by dint of their high concentration, but it is debatable whether proteins that provide transparency are any different, biologically or structurally, from those that are present in non-transparent structures or tissues. It is becoming increasingly clear that crystallins may have a plethora of metabolic and regulatory functions, both within the lens as well as outside of it. α-Crystallins are members of a small heat shock family of proteins and β/γ-crystallins belong to the family of epidermis-specific differentiation proteins. Crystallin gene expression has been studied from the perspective of the lens specificity of their promoters. Mutations in α-, β-, and γ- crystallins are linked with the phenotype of the loss of transparency. Understanding catalytic, non-structural properties of crystallins may be critical for understanding the malfunction in molecular cascades that lead to cataractogenesis and its eventual therapeutic amelioration.
Reducing the impact of transient effects in rate-constant estimation using the weighted ensemble strategy

We present a new method for improving the efficiency of calculating rate constants using the weighted ensemble path sampling strategy. This method reduces the sensitivity of rate-constant estimation to the earliest (and least typical) pathways reaching the target state by incorporating the distribution of event durations (excluding dwell time in the initial stable state) that correspond to pathways captured by the simulation. We demonstrate that the improved method enables accurate estimation of the rate constant for a protein conformational switching process using a fraction of the simulation time required by the original weighted ensemble method. Importantly, our method accounts for systematic error when using data from the entire simulation. Our method is relevant to any simulation strategy that involves unbiased trajectories of similar length to the typical event duration, including weighted ensemble and standard simulations.
CONSIDERATIONS OF ELDER ABUSE IN RURAL AMERICA

Over 10 million persons aged 65 and older live in small towns and other rural areas, some of whom experience elder abuse. The structure and culture of rural environments may inadvertently conceal abuse and thereby inhibit prevention and treatment efforts. Few studies exist about vulnerable elders living in rural places and experiencing types of elder abuse. Similar to younger adults, older adults may be trapped in abusive situations because of their lack of education and resources. Different from their younger counterparts, the passage of time can exacerbate these deficits. Also, advanced age and, for some, poor physical and emotional health creates impediments to leaving abusive situations. A lack of qualified care providers may also increase older adults’ susceptibility to elder abuse. This presentation discusses mechanisms for leveraging insufficient personal and community resources so that intervention and prevention efforts better target older adults living in rural areas who experience elder abuse.
The environmental effects of trade within and across sectors

Abstract This paper presents a model that combines within and across sector channels through which trade affects our environment by embedding heterogeneous firms and fixed costs into a two-sector framework with an endogenous response to environmental policy. In contrast to existing literature that tends to examine these channels separately, the combined framework developed here shows how cross-sector comparative advantage and within-sector responses to trade and environmental policy or factor endowments interact to affect our environment through three channels: changes in output, cross-sector market share, and emissions intensity. In contrast to a single-sector model with neutral productivity, consideration of two sectors allows for trade liberalization to affect the allocation of inputs in each sector and thereby affect total pollution output. The additional consideration of heterogeneous firm responses to falling trade costs will generate endogenous increases in productivity that increase output, reduce aggregate emissions intensity, and moderate the cross-sector resource adjustment, relative to a representative-firm model. Simulation results show how the combined framework can replicate existing empirical outcomes, and provide concise ceteris paribus insights regarding the potential role of trade and environmental policy changes and factor expansion in driving observed outcomes and their contribution to each of the three channels.
A novel adaptor system enables endovascular access through extracorporeal life support circuits.

Abstract Objective Extracorporeal life support has traditionally been used as a supportive platform for patients with cardiopulmonary failure. Many of these patients require endovascular access for the performance of diagnostic or therapeutic procedures, and obtaining vascular access in these patients can be problematic. We sought to develop a novel system that allows the extracorporeal life support circuit to serve as an access point to the cardiovascular system. Methods By using computer-aided design, modeling, and 3-dimensional printing, a novel adaptor that can be easily inserted and removed from an extracorporeal life support circuit was developed. A mock loop was used to measure flow and pressure at various pump speeds with insertion of guidewires and catheters through the adaptor. The ability of the system to enable performance of endovascular procedures in vivo was then tested in a porcine extracorporeal life support model. Results By using a small arterial cannula (15F) at 3500 RPM and 3.2 LPM, 15% and 24% decrements in circuit flow were observed when a 0.035” guidewire and 5F angiography catheter, respectively, were passed through the adaptor (P Conclusions This novel system successfully enables endovascular access through an extracorporeal life support circuit. This technology may transform extracorporeal life support from a purely supportive strategy to a platform for endovascular intervention.
MORTALITY RISK AFTER HEART FAILURE DIAGNOSIS IN HIV PATIENTS

Although HIV infected (HIV+) people have an excess risk of incident heart failure (HF) compared to those who are uninfected (HIV-), it is unclear if HIV+ individuals have an excess risk of mortality after a new diagnosis of HF. We analyzed data on 10,791 (3,035 HIV+; 7,756 HIV-) participants with
International Board Certified Lactation Consultants' Practices Regarding Supplemental Feeding Methods for Breastfed Infants.

Background:According to the Baby Friendly Hospital Initiative, when supplementary feeding occurs, mothers should be counseled on the use and risks of feeding bottles and teats. To help support this...
Analyzing Physician Assistant Library Resources: Equal Access in a Time of Rapid Growth?

This study examines libraries that support physician assistant (PA) programs by analyzing subscription data for eight key resources. Previous studies have noted the cost of providing resources to PA programs and have included some mention of resources, but these studies have not broadly explored the issue. After analyzing when these PA programs were first accredited, this study looks closely at the following three areas: the percentage of libraries that subscribe to each of the eight resources; the average number of resources purchased by libraries that support medical colleges and those that do not; and the average number of resources per library, controlled for accreditation date. Given the substantial difference in resource availability among PA libraries, librarians at colleges or universities that are implementing PA programs should use caution and advocate for funding, particularly if their libraries do not already support a medical school.
Disrupting the humanities and social science binary: framing communication studies as a transformative discipline

ABSTRACTDebates whether communication studies should be housed with the humanities or social sciences have raged on for decades. In response to attacks on the humanities, we argue that the discipline has much to gain from seeing how the humanities contributes to the social sciences and the potential benefits of integrating humanistic and social scientific approaches. Specifically, we present two case studies that illuminate ways humanities-informed thinking has contributed to and benefited social science theory, method, and data. First, we review Jeffrey A. Bennett's Banning Queer Blood to illustrate the importance of reflexivity and practice when analyzing interview data. Then, we highlight how the philosophy of Mikhail Bakhtin influenced Leslie A. Baxter's most recent articulation of relational dialectics theory and development of contrapuntal analysis. Finally, we discuss obstacles and opportunities for engaging in transformative research.
Tunneling in Surface Diffusion

A description is provided of experimental data for tunneling diffusion of atoms on single crystal planes as obtained using field emission-fluctuation spectroscopy. A focus is made upon the significantly weaker than anticipated isotope effect for H/W(110) tunneling diffusion and on the coverage dependence which suggests an influence of the nuclear statistics on the diffusion. A unified analysis of both the tunneling and thermally activated regions provides insight into the nature of the interactions between the adsorbed hydrogen atom and the tungsten lattice, and these interactions, in turn, provide an explanation of the observed anomolous isotope effect for diffusion of H/W(110).