cssi/SciSciGPT-SciSciNet huggingface dataset:
Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells

Recent studies based predominantly on nucleotide hybridization techniques have identified aneuploid neurons and glia in the normal brain. To substantiate these findings and address how neural aneuploidy arises, we examined individual neural progenitor cells (NPCs) undergoing mitosis. Here we report the identification of chromosomal segregation defects in normal NPCs of the mouse cerebral cortex. Immunofluorescence in fixed tissue sections revealed the presence of supernumerary centrosomes and lagging chromosomes among mitotic NPCs. The extent of aneuploidy followed the prevalence of supernumerary centrosomes within distinct cell populations. Real-time imaging of live NPCs revealed lagging chromosomes and multipolar divisions. NPCs undergoing nondisjunction were also observed, along with interphase cells that harbored micronuclei or multiple nuclei, consistent with unbalanced nuclear division. These data independently confirm the presence of aneuploid NPCs and demonstrate the occurrence of mitotic segregation defects in normal cells that can mechanistically account for aneuploidy in the CNS.
The secretion of gonadotropins and testosterone by the neonatal male rat.

Serum LH, FSH and testosterone concentrations were measured in male rats from the early neonatal period through maturity. In four separate studies, there was a distinct LH peak at 17, 17, 19 and 20 days, respectively. In two of these studies there was a concomitant peak of serum testosterone concentration, and in a third study the testosterone peak was one day before the LH peak. FSH increased with LH in two of four studies. To test whether the observed prepubertal peaks of serum LH and testosterone were due to increased pituitary sensitivity to luteinizing hormone—releasing hormone (LH—RH), groups of male rats from 8–26 days old were given graded doses of LH—RH. Serum LH and FSH levels increased to about the same extent in all age groups 30 min after injection of LH—RH. Since the pituitary appeared equally responsive to LH—RH throughout the prepubertal period, these observations suggest that a higher central mechanism is responsible for this early activation of the pituitary—Leydig cell axis.(Endocrinolo...
Desloratadine: A Nonsedating Antihistamine

OBJECTIVE:To review information on desloratadine, a nonsedating antihistamine.DATA SOURCES:An English-language MEDLINE search was conducted (1966–July 2002). References of identified articles were subsequently reviewed for additional data. Schering Corporation provided unpublished information.STUDY SELECTION/DATA EXTRACTION:Articles and abstracts pertaining to desloratadine were considered for inclusion, with emphasis on randomized, placebo-controlled, double-blind trials.DATA SYNTHESIS:Desloratadine is approved for the treatment of symptoms associated with seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), and chronic idiopathic urticaria (CIU) in patients aged ≥12 years. In placebo-controlled trials, desloratadine demonstrated superior efficacy as a once-daily treatment of SAR, PAR, and CIU. Data suggest that desloratadine has antiinflammatory and decongestant activity.CONCLUSIONS:Desloratadine appears to be a “me-too” agent, with no major differences compared with other second-generat...
On-line optimal timing control of switched systems

This paper considers a real-time algorithm for performance optimization of switched-mode hybrid dynamical systems. The controlled parameter consists of the switching times between the modes, and the cost criterion has the form of the integral of a performance function defined on the system's state trajectory. The dynamic response functions (state equations) associated with the modes are not known in advance; rather, at each time t, they are estimated for all future times s ≥ t. A first-order algorithm is proposed and its behavior is analyzed in terms of its convergence rate. Finally, an example of a mobile robot tracking a moving target while avoiding obstacles is presented.
Nuclear signaling pathways for 1,25-dihydroxyvitamin D3 are controlled by the vitamin A metabolite, 9-cis-retinoic acid.

The vitamin A metabolite, 9-cis-retinoic acid, may be the effector molecule that controls which genes respond to the 1,25-dihydroxyvitamin D3 receptor.
Partial Nephrectomy in the Overweight Patient: an Overview

The diagnosis and treatment of kidney cancer continues to evolve with advances in imaging and surgical approaches. The use of nephron sparing surgery (NSS) has become the operation of choice for treating small renal masses. Yet, technical difficulty and a variety of approaches have left debate for best method in the overweight population. This review summarizes the current knowledge in the open, laparoscopic, and robotic approaches to identify key risk factors, general assessments, complication rates, and the influence of body habitus for each approach.
Radio-Ecological State of Absheron Oil and Gas Extracting Fields

Oil and gas have been extracted for some time in Absheron peninsula. Oil-contaminated soils and the polluted ponds, created close to such spots, have the worst effect for the weather, fauna, flora and the health of the inhabitants. The radiation background measurements conducted on the type and quantity of radionuclides in the fields and to decontaminate them. It was found that the radiation background in the oil polluted water pools and soils in some areas of oil extracting fields are much more than the natural levels.
Novelty as a determinant of spontaneous alternation in children

Nursery school children traced a series of T-mazes under varying and nonvarying stimulus conditions in a situation arranged such that all external stimulus cues could be apprehended by Ss throughout the entire task. The results of the experiment were interpreted on the basis of Berlyne’s (1960) novelty hypothesis, and it was concluded that spontaneous alternation appeared to be related to the activating properties of novel stimuli.
Quantitation of minimal residual disease in acute myelogenous leukemia and myelodysplastic syndromes in complete remission by molecular cytogenetics of progenitor cells

Detection of karyotypic clonal abnormalities are prognostically useful in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS), but cytogenetic methods are not sensitive enough to detect low numbers of residual leukemic cells in patients who have achieved complete remission (CR). Fluorescence in situ hybridization (FISH) and fluorescence activated cell sorting (FACS) were used to investigate the frequency and presence of minimal residual disease (MRD) in AML and MDS patients (n = 28) with monosomy of chromosomes 7, 17 and 18 and trisomy of chromosomes 6, 8, 9 and 10 in CR. MRD was detected in all patients with monosomy 7 (n = 10) and followed by relapse in eight patients after 4.8 +/- 3.1 months. In contrast, persistent leukemic cells occurred in 11/12 patients with trisomy 8, but only three of them relapsed after 7.7 +/- 4.0 months. Cox regression analysis showed that cytogenetic class and levels of clonal cells at CR were related to time to relapse (P = 0.001). The level of MRD identified patients at high and low risk of relapse. High absolute levels of proliferating residual leukemic cells correlated with monosomy 7 and high risk of relapse.
Abstract 540: The pro-inflammatory protein S100A9 promotes pancreatic cancer cell growth

S100A9 is a pro-inflammatory protein originally found in macrophages which is felt to be important in promoting inflammatory responses and cancer cell growth. The protein is found in cancer cells of gastric, colon, breast cervical and thyroid cancer. Generally, S100A9 is a cytoplasmic, cell surface and secreted protein that promotes cancer cell growth via inflammatory mechanisms and migration of immune cells (e.g. PBMCs) to the cancer microenvironment via non-covalent interactions with glycosaminoglycans on endothelial surfaces. Previously, this protein was reported in the stroma of pancreatic cancers but not in pancreatic cancer cells themselves. This report iilustrates S100A9 up-regulation on the surface of p53 mutant pancreatic cancer cell lines BxPC3 and AsPC1 as determined by immunoblot analysis and flow cytometry. In this study, pentamidine a known inhibitor of S100B, inhibited S100A9 dependent cell growth in BxPC3 cell lines (IC50 = 20.1 +/- 10.3 μM). Pentamidine treated BxPC3 cells (20 μM for 96 hrs) exhibited 30.1% apoptotic cell death as measured by Annexin/PI statining vs less than 3% for control treated cells. Given that S100A9 was found in other cancer models to promote recruitment of pro-infammatory cells (e.g. PBMCs) and subsequent support of cancer cell growth, we studied the effect of pentamidine on PBMC migration. Pentamidine also blocked the migration of PBMC from a metastatic pancreatic cancer patient (67%) to a similar degree as an Anti-s100A9 (68%) Ab or an anti-s100A8/A9 (65%) antibody. S100A8/A9 antibody is known to bind to helix 1 of S100A8 and helix 4 of S100A9, areas of the protein considered important for target interactions. It is likely that pentamidine indiscriminately binds to both the S100A8/A9 heterodimer as well as the homodimer in addition to other S100 proteins. S100A9 levels in BxPC3 cells as detected via Western analysis also increase with 20 μM pentamidine treatment, but not 10 fold as reported in the literature for S100B. As p53 was also shown previously to bind to the S100A9 promoter and S100A9 is not as robustly expressed in mutant p53 cell lines, p53 independent pathways are clearly important for cancer cell survival. This study suggests that S100A9 is up-regulated in pancreatic cancer and that inhibition causes pancreatic cancer cell death. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 540. doi:10.1158/1538-7445.AM2011-540
A young woman concerned about mercury

A healthy 30-year-old woman is planning to conceive. She seeks advice on having her dental amalgam fillings removed because of concerns about mercury toxicity. She also asks to be tested for mercury. The patient should be asked about potential sources of elemental, inorganic and organic mercury (
Discussion of Technical Problems in Fossil Unit

A number of technical problems are studied on unit commissioning according to author's experience for many years,such as optimization for control logic,protection and system configuration,and so on,which may serve as a reference for safe and economic operation of all turbine-generators.
Self-monitoring, Psychology of

According to self-monitoring theory, people differ in the extent to which they monitor (observe and control) their expressive behavior and self-presentation. Individuals high in self-monitoring regulate their expressive self-presentation for the sake of public appearances, and thus are highly responsive to social and interpersonal cues to situationally appropriate performances. Individuals low in self-monitoring lack the ability or motivation to regulate their expressive self-presentations for such purposes; their expressive behaviors reflect their inner states and dispositions. Research on self-monitoring typically employs a multi-item self-report measure, the Self-monitoring Scale, to identify people high and low in self-monitoring. Investigations of self-monitoring have examined the relative role of person and situation in determining behavior in diverse domains of individuals' lives, including their friendship worlds, their romantic lives, their interactions with the consumer marketplace, and their work worlds. Theory and research on self-monitoring have also served as focal points for issues in the assessment of personality, in the role of scale construction in theory building, and in examining fundamental questions about personality and social behavior, particularly those concerning how individuals incorporate inputs from their enduring dispositions and inputs from their situational contexts into agendas for action that guide their functioning as individuals and social beings.
THE ROLE OF LOGICAL SYSTEMS

This chapter discusses the role of logical systems. The logical systems provide the basic inference mechanisms for theorem provers. As such they fit within and greatly influence the form of the search representation component of the theorem provers. First-order logic provides a natural environment in which to develop the mechanisms because of its expressive power and well-understood semantics and its familiarity. The chapter highlights the manner of problem representation within first-order logic. In practice, one is limited to confirming that finite sets of formulas are valid or unsatisfiable. With care in formulation, most real-world problems and mathematical problems are representable to a large extent. The test actually is for unsatisfiability using a Skolem conjunctive form, a quantifier-free formula in conjunctive normal form with existential quantifiers replaced by Skolem functions. The keystone to all the formats or procedures considered is the Herbrand Theorem, which is painlessly obtainable from the Completeness theorem via the Compactness theorem. A formula in Skolem co-junctive form is unsatisfiable iff a related finite set of ground clauses is unsatisfiable, where each ground clause is obtained from the given formula by replacement of variables by suitable Herbrand terms. The ground clause set is testable by truth tables.
Cyclin-Dependent Kinase Inhibitors in Combination Chemotherapy

Cyclin-dependent kinase inhibitors (CDKIs) represent a new class of anticancer therapeutics. Perturbations in the cell cycle are commonly described in carcinogenesis. This novel class of anticancer therapeutics exploits these perturbations to achieve tumor-specific cytotoxicity. In the last several years, our understanding of cell-cycle regulation has improved with the emerging concepts of cell-cycle-mediated drug resistance and cell-cycle modulation to improve cytotoxic drug efficacy. It is becoming increasingly apparent that CDKIs may improve cytotoxic drug efficacy by functioning as cell-cycle modulators. In this chapter, we review the field of CDKIs as novel anticancer therapeutics, with a focus on their efficacy in drug combinations.
An effective probability distribution SAT solver on reconfigurable hardware

Boolean Satisfiability (SAT) is an important problem both theoretically and for a variety of practical applications. While the general SAT problem is NP complete, advanced solver algorithms and heuristics can provide fast and efficient solving of otherwise intractable problems. While much advancement has been made with Conflict Driven Clause Learning (CDCL) based sequential solvers, Stochastic Local Search (SLS) solvers such as WalkSAT, Sparrow and probSAT have proven effective for certain instance types. SLS solvers are well suited to parallelization and hardware implementation due to the simplified control flow and lack of data dependencies between solver instances started with different seeds. This paper presents a hardware implementation of the probSAT algorithm using High-Level Synthesis (HLS) for rapid porting of the design from the original C implementation. Specifically, the presented approach shows very strong performance on the class of small, but difficult SAT problems with speedups between 89–828x over MiniSAT and 5–99x over the software implementation of probSAT on such problems.
The Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer

Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. Furthermore, clinically meaningful improvements in PFS were seen in combination with fulvestrant for patients with prior endocrine therapy, including premenopausal women. While neutropenia is experienced by most patients, it is typically uncomplicated and palbociclib is otherwise well tolerated. Recent analysis also demonstrated improved quality of life and reassuring evidence of no compromise in benefit from subsequent therapies after progression on palbociclib. Along with palbociclib, the CDK4/6 inhibitors ribociclib and abemaciclib are being evaluated in a variety of settings (metastatic, neoadjuvant, and adjuvant), alone and in combination with endocrine therapy, chemotherapy, and targeted therapies. Future research is needed to address challenges regarding the potential competition of these agents as the preferred partner in endocrine-sensitive disease, their use as single agents or in combination in the endocrine-refractory setting, and the clinical and molecular criteria for use as an alternative to chemotherapy. Unfortunately, despite efforts to determine predictive biomarkers for response, RB1 expression and HR-positive disease have been the only clear predictors of therapeutic benefit. Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib’s impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.
Monitoring corneal crosslinking using phase-decorrelation OCT (Conference Presentation)

Viscosity is often a critical characteristic of biological fluids such as blood and mucus. However, traditional rheology is often inadequate when only small quantities of sample are available. A robust method to measure viscosity of microquantities of biological samples could lead to a better understanding and diagnosis of diseases. Here, we present a method to measure viscosity by observing particle Brownian motion within a sample. M-mode optical coherence tomography (OCT) imaging, obtained with a phase-sensitive 47 kHz spectral domain system, yields a viscosity measurement from multiple 200-1000 microsecond frames. This very short period of continuous acquisition, as compared to laser speckle decorrelation, decreases sensitivity to bulk motion, thereby potentially enabling in vivo and in situ applications. The theory linking g(1) first-order image autocorrelation to viscosity is derived from first principles of Brownian motion and the Stokes-Einstein relation. To improve precision, multiple windows acquired over 500 milliseconds are analyzed and the resulting linear fit parameters are averaged. Verification experiments were performed with 200 µL samples of glycerol and water with polystyrene microbeads. Lateral bulk motion up to 2 mm/s was tolerated and accurate viscosity measurements were obtained to a depth of 400 µm or more. Additionally, the method measured a significant decrease of the apparent diffusion constant of soft tissue after formalin fixation, suggesting potential for mapping tissue stiffness over a volume.
SiC power device reliability

SiC power devices offer performance advantages over competing Si-based power devices, due to the wide bandgap and other key materials properties of 4H-SiC. For example, SiC can more easily be used to fabricate MOSFETs with very high voltage ratings (up to 10 kV), and with lower switching losses. The reliability of SiC power devices is excellent and has continued to improve due to continuing advancements in SiC substrate quality, epitaxial growth capabilities, and device processing. This has enabled the continually accelerating growth of SiC power device commercial adoption. This paper reviews the wear-out mechanisms and intrinsic reliability performance of power SiC devices as characterized by time-dependent dielectric breakdown (TDDB), accelerated life test high temperature reverse bias (ALT-HTRB), terrestrial neutron exposure, and power cycling. This paper also reviews some of the known failure mechanisms that have been characterized and addressed through technological advances. Finally, we present field return data that demonstrates less than 5 FIT (fails per billion device hours) for commercially produced SiC MOSFETs and Schottky diodes, with over 2 trillion device field hours.
Tumor p38MAPK signaling enhances breast carcinoma vascularization and growth by promoting expression and deposition of pro-tumorigenic factors

// Michelle Limoge 1 , Alfiya Safina 3 , Alexander M. Truskinovsky 2 , Ieman Aljahdali 1 , Justin Zonneville 1 , Aleksandar Gruevski 5 , Carlos L. Arteaga 4 and Andrei V. Bakin 1 1 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA 2 Department of Pathology, Roswell Park Cancer Institute, Buffalo, New York, USA 3 Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, New York, USA 4 Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA 5 State University of New York at Buffalo, Department of Biological Sciences, Buffalo, New York, USA Correspondence to: Andrei V. Bakin, email: andrei.bakin@roswellpark.org Keywords: tumor microenvironment, breast cancer, p38MAPK, angiogenesis, fibronectin Received: April 26, 2017 Accepted: May 19, 2017 Published: June 28, 2017 ABSTRACT The breast carcinoma microenvironment strikingly influences cancer progression and response to therapy. Various cell types in the carcinoma microenvironment show significant activity of p38 mitogen-activated protein kinase (MAPK), although the role of p38MAPK in breast cancer progression is still poorly understood. The present study examined the contribution of tumor p38MAPK to breast carcinoma microenvironment and metastatic capacity. Inactivation of p38MAPK signaling in metastatic breast carcinoma cells was achieved by forced expression of the kinase-inactive mutant of p38/MAPK14 (a dominant-negative p38, dn-p38). Disruption of tumor p38MAPK signaling reduced growth and metastases of breast carcinoma xenografts. Importantly, dn-p38 markedly decreased tumor blood-vessel density and lumen sizes. Mechanistic studies revealed that p38 controls expression of pro-angiogenic extracellular factors such as matrix protein Fibronectin and cytokines VEGFA, IL8, and HBEGF. Tumor-associated fibroblasts enhanced tumor growth and vasculature as well as increased expression of the pro-angiogenic factors. These effects were blunted by dn-p38. Metadata analysis showed elevated expression of p38 target genes in breast cancers and this was an unfavorable marker of disease recurrence and poor-outcome. Thus, our study demonstrates that tumor p38MAPK signaling promotes breast carcinoma growth, invasive and metastatic capacities. Importantly, p38 enhances carcinoma vascularization by facilitating expression and deposition of pro-angiogenic factors. These results argue that p38MAPK is a valuable target for anticancer therapy affecting tumor vasculature. Anti-p38 drugs may provide new therapeutic strategies against breast cancer, including metastatic disease.
Implementing and evaluating an interprofessional minority health conference for social work and healthcare professionals.

ABSTRACTInterprofessional education (IPE) is one strategy for addressing health inequities; however, little attention has been paid to continuing IPE for practicing social work and healthcare professionals. This article offers guidance to faculty in social work and health-related academic units on offering continuing IPE on the topic of minority health. An interprofessional group of faculty offered a day-long conference on minority health, ethics, and social justice. The conference goal was to promote interprofessional communication in a co-learning environment and promote dialogue on social determinants of health and health equity in the state. Data were obtained from surveys and analysis of work plans developed during the conference. Workshop participants were majority White (62%), social workers (79%), and practiced for 14 years on average. The most useful topics were dementia and polypharmacy. Takeaway strategies included interprofessional work, being mindful of access to resources, and engagement in ...
Design and Development of Stress-Engineered Compliant Interconnect for Microelectronic Packaging

Power and latency are fast becoming major bottlenecks in the design of high performance microprocessors and computers. Power relates to both consumption and dissipation, and therefore, effective power distribution design and thermal management solutions are required. Latency is caused by the global interconnects on the integrated circuit (IC) that span at least half a chip edge due to the resistance–capacitance (RC) and transmission line delay [1]. Limits to chip power dissipation and power density and limits on hyper-pipelining in microprocessors threaten to impede the exponential growth in microprocessor performance. In contrast, multicore processors can continue to provide a historical performance growth on most consumer and business applications provided that the power efficiency of the cores stays within reasonable power budgets. To sustain the dramatic performance growth, a rapid increase in the number of cores per die and a corresponding growth in off-chip bandwidth are required [2]. Thus, it is projected by the Semiconductor Industry Association in their International Technology Roadmap for Semiconductors (ITRS) (21.1) that by the year 2018, with the IC node size shrinking to 22 nm by 2016 and 14 nm by 2020, the chip-to-substrate area-array input–output interconnects will require a pitch of 70 μm [3]. Furthermore, to reduce the RC and transmission line delay, low-K dielectric/Cu and ultra-low-K dielectric/Cu interconnects on silicon will become increasingly common. In such ICs, the thermo-mechanical stresses induced by the chip-to-substrate interconnects could crack or delaminate the dielectric material causing reliability problems.
An Odyssey to Incomplete Data: Winfried Stute’s Contribution to Survival Analysis

In this article, we revisit Winfried Stute’s contributions to survival analysis, which constitute a significant portion of his publications. Instead of a comprehensive review of his work in survival analysis, we focus on four papers that are fundamental by themselves.
Hard Limits And Performance Tradeoffs In A Class Of Sequestration Feedback Systems

Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism implemented using the sequestration binding of two molecules. Our work develops an analytic framework for understanding the hard limits, performance tradeoffs, and architectural properties of this simple model of biological feedback control. Using tools from control theory, we show that there are simple parametric relationships that determine both the stability and the performance of these systems in terms of speed, robustness, steady-state error, and leakiness. These findings yield a holistic understanding of the behavior of sequestration feedback and contribute to a more general theory of biological control systems.
Cytokines in the Management of Advanced Renal Cell Cancer

Cytokine therapy with interferon(s) and/or interleukin-2 has been a traditional management option for patients with advanced renal cell cancer (RCC). These agents have been used in highly selected patients as single agents or in combination regimens, either with another cytokine, chemotherapy, or other biologics. Unfortunately, cytokine-based treatments have long been characterized by relatively modest activity and considerable toxicity. Uncommonly and fascinatingly, the presence of durable complete responses associated with long-term survival – particularly following high-dose Interleukin-2 (IL-2) therapy – has kept the option of cytokine therapy alive, even in the era that has ushered in newer biologic therapies that inhibit tumor angiogenesis or mammalian target of rapamycin (mTOR) signaling pathways. More recently, interferon-alfa has found a new niche in the frontline treatment of advanced RCC when combined with the angiogenesis inhibitor bevacizumab, where improved efficacy outcomes were seen when compared to interferon alone. Although the use of cytokine therapy has somewhat diminished in the early part of the twenty-first century, in part due to the emergence of more active biologic agents, continued molecular evaluation of RCC biology may offer new insights into finding the appropriate patient population that predicts benefit from cytokine-based approaches.
Changes in the Use of Lumbar Arthrodesis Procedures Within Accountable Care Organizations.

Study design A retrospective review of Medicare claims data (2009-2014). Objective The aim of this study was to evaluate changes in the use of lumbar fusion procedures following the formation of Accountable Care Organizations (ACOs). Summary of background data Within surgical care afforded by ACOs, savings are thought to be realized by improved care coordination as well as reductions in the use of preference-sensitive procedures such as lumbar fusion. Methods We queried fee-for-service claims for patients enrolled in Medicare Part A and B, identifying patients who received lumbar spine fusion, discectomy, or decompression procedures. We performed a difference-in-differences analysis comparing the use of lumbar fusion in ACOs and non-ACOs in the period before (2009-2011) and after (2012-2014) ACO formation. Propensity score adjustment was used to address differences in case-mix. Multivariable logistic regression was used to compare the likelihood of receiving a lumbar fusion in ACOs and non-ACOs in the period before and after ACO formation. Results Within organizations that would form ACOs, the raw rate of lumbar fusion increased from 50% (n = 2183) in 2009 to 2011 to 54% (n = 2283) in 2012 to 2014. Among non-ACOs, the use of fusion increased from 52% (n = 110,160) to 59% (n = 109,917). Adjusted difference in differences in the use of lumbar fusion between ACOs and non-ACOs was -2.6 percentage points (P = 0.13). When limited to patients with spinal stenosis, ACOs significantly reduced the use of fusion (-5.8 percentage points; P = 0.03). Conclusion Our results indicate that ACOs may effectively curtail the use of lumbar fusion procedures, particularly among patients with spinal stenosis. As these interventions are often associated with higher complications and need for reoperation, such practices might accrue additional health care savings for Medicare beyond those realized during the index surgical period. Level of evidence 3.
Evaluation of a method to scale muscle strength for gait simulations of children with cerebral palsy.

Abstract Cerebral palsy (CP) is a neurological disorder that results in life-long mobility impairments. Musculoskeletal models used to investigate mobility deficits for children with CP often lack subject-specific characteristics such as altered muscle strength, despite a high prevalence of muscle weakness in this population. We hypothesized that incorporating subject-specific strength scaling within musculoskeletal models of children with CP would improve accuracy of muscle excitation predictions in walking simulations. Ten children (13.5 ± 3.3 years; GMFCS level II) with spastic CP participated in a gait analysis session where lower-limb kinematics, ground reaction forces, and bilateral electromyography (EMG) of five lower-limb muscles were collected. Isometric strength was measured for each child using handheld dynamometry. Three musculoskeletal models were generated for each child including a ‘Default’ model with the generic musculoskeletal model’s muscle strength, a ‘Uniform’ model with muscle strength scaled allometrically, and a ‘Custom’ model with muscle strength scaled based on handheld dynamometry strength measures. Muscle-driven gait simulations were generated using each model for each child. Simulation accuracy was evaluated by comparing predicted muscle excitations and measured EMG signals, both in the duration of muscle activity and the root-mean-square difference (RMSD) between signals. Improved agreement with EMG were found in both the ‘Custom’ and ‘Uniform’ models compared to the ‘Default’ model indicated by improvement in RMSD summed across all muscles, as well as RMSD and duration of activity for individual muscles. Incorporating strength scaling into musculoskeletal models can improve the accuracy of walking simulations for children with CP.
The Relationship between Opportunities to Learn Algebra and Students’ Algebra Achievement: A Comparative Study

The article provides a report on the comparison of Opportunities to Learn algebra and eighth grade students’ algebra achievement in three countries: Botswana, Singapore and the United States. The study used student and teacher data from the Trends in International Mathematics and Science Study (2011 and 2015). By using a multilevel regression analysis, the study presents the models within the three countries of the relationships between Opportunities to Learn algebra and eighth-grade students’ algebra achievement of the recent TIMSS cycle. The findings indicate that the Opportunities to Learn algebra are context specific and align with the expectations of the curriculum guides from the governing bodies within the countries. Also, the study shows that students who learned particular algebra topics in the early grades had significantly higher algebra scores in the TIMSS 2015 assessment. In particular, students who had been taught properties of functions and simplifying and evaluating algebraic expressions before eighth grade in the United States had significantly higher scores. Also, Singaporean students who had been taught simple linear equations and inequalities and simultaneous equations had higher algebra scores. Implications for policy and research are discussed.
Non-Linear Effects of Tax Changes on Output: The Role of the Initial Level of Taxation

This paper estimates the effect of worldwide tax changes on output following the narrative approach developed for the United States by Romer and Romer (2010). The analysis uses a novel dataset on value-added taxes for 51 countries (21 industrial and 30 developing) for the period 1970-2014 to identify 96 tax changes. It then uses contemporaneous economic records to classify such changes as endogenous or exogenous to current (or prospective) economic conditions. In line with theoretical distortionary and disincentive-based arguments, and using only exogenous tax changes, the main finding is that the effect of tax changes on output is highly non-linear. The tax multiplier is essentially zero under relatively low/moderate initial tax rate levels and more negative as the initial tax rate and the size of the change in the tax rate increase. Based on a global sample, these novel non-linear findings suggest that the recent consensus pointing to large negative tax multipliers in industrial countries, particularly in Europe (e.g., Alesina, Favero, and Giavazzi, 2015), (i) is not a robust empirical regularity, and (ii) is mainly driven by high initial tax rates in these countries. The paper also shows that the bias introduced by misidentification of tax shocks critically depends on the procyclical or countercyclical nature of endogenous tax changes. The relevance of the arguments is evaluated both for the novel global sample and for Romer and Romer's U.S. dataset.
Predictors of Outcomes After Thoracic Surgery in Orthotopic Liver Transplant Recipients With Pleural Disease.

Orthotopic liver transplant (OLT) recipients are at high risk for postoperative pulmonary complications. We aim to determine factors associated with morbidity and mortality in OLT recipients that required thoracic surgery for pleural space complications. A retrospective review was performed of 42 patients who underwent thoracic surgery after OLT between 2005 and 2015. Preoperative data and postoperative outcomes were reviewed. Time to mortality was summarized using Kaplan-Meier curves. Outcomes associated with 30-day morbidity and mortality as well as long-term mortality were analyzed with univariate analysis. Between 2005 and 2015, 1735 OLTs were performed at our institution. We identified 42 patients who required thoracic surgery. Of these 42 OLT recipients, 33 patients required thoracic surgery for pleural space complications. The median interval between OLT and thoracic surgery for pleural space complications was 5.7 months (interquartile range 2.2–14.1). The most common surgical indications were chronic pleural effusion (n = 12, 36.4%) and empyema (n = 10, 30.3%). The most common thoracic operations were decortication and empyema evacuation. The 30-day morbidity was 69.7%. Bilirubin and empyema were significantly associated with 30-day morbidity (odds ratio [OR] = 2.3, P = 0.023; OR = 16.3, P = 0.015). The 30-day, 1-year, and 5-year mortality rates were 15.2%, 57.6%, and 70.2%, respectively. Vasopressor requirement was significantly associated with 30-day mortality (OR = 10.2, P = 0.031). The development of pleural space complications requiring surgery in OLT recipients suggests a poor prognosis. Hyperbilirubinemia and pleural space infections were associated with high postoperative morbidity in OLT recipients requiring thoracic surgery for pleural space complications.
Identification of Disease Risk DNA Variations is Shaping the Future of Precision Health

In recent years, the knowledge generated by decoding the human genome has allowed groundbreaking genetic research to better understand genomic architecture and heritability in healthy and disease states. The vast amount of data generated over time and yet to be generated provides the basis for translational research towards the development of preventive and therapeutic strategies for many conditions. In this special issue, we highlight the discoveries of disease-associated and protective DNA variations in common human diseases and developmental disorders.
Vanilla (Vanilla spp.) Breeding

Vanilla planifolia is the botanical source of vanilla extract, but has not generally benefited from strategic plant breeding. V. planifolia was cultivated in pre-Columbian Mesoamerica for its desirable aroma, and spread globally by vegetative cuttings starting in the 1500s. In 1837 a method to artificially pollinate Vanilla flowers enabled commercial production outside the native range. Today, Madagascar leads Vanilla production with significant contributions from other nations. The mass propagation of a few foundational clones has resulted in a global industry reliant on a very narrow germplasm base with threats from multiple biotic and abiotic stresses. Further, the lack of molecular, genomic and definitive phenotypic characterization inhibits improvement within this genus. The establishment of modern Vanilla breeding programs could leverage increasingly accessible technologies including advances in genomics and biotechnology to rapidly improve this species for high priority traits like disease resistance, total bean yield, pod uniformity, vigor, non-splitting pods, flower longevity, extract quality and flowers that are able to self-pollinate without manual intervention. While plant breeding is generally a long-term prospect, the potential benefits are justified by the increasing demand for premium ingredients like natural vanilla extract. In the future, genetic improvement of this species could result in more resilient and higher-quality cultivars that reduce price volatility, support growers, improve sustainability and excite modern consumers.
Numerical modeling of transient heat transfer in a phase change composite thermal energy storage (PCC-TES) system for air conditioning applications

Abstract This paper presents a detailed numerical analysis to describe the transient heat transfer in a phase change composite-thermal energy storage (PCC-TES) system exchanging heat with a heat transfer fluid. The “PCC-TES” is precisely composed of 78% low temperature paraffin, namely n-Tetradecane (C14H30) and 22% expanded graphite) and a heat transfer fluid (namely, ethylene glycol). Such detailed numerical approach to precisely describe the heat exchange between this specifically proposed phase change composite thermal energy storage (PCC-TES) and the heat transfer fluid has not been yet addressed in literature. The mathematical modeling of the PCC-TES involves formulating two PDEs that represent conduction within the PCC (phase 1) and advection within the heat transfer fluid (phase 2). The two coupled PDEs were solved with a finite difference method. Numerics were implemented using Fortran. Results were validated using experimental data and demonstrated acceptable agreement and an accurate representation of this specific transient heat transfer problem. The variations between experimental time traces of temperature and numerically calculated data are estimated at approximately (4–9%) and attributed to the heat loss in the actual experiment. Accordingly, the slabs in the actual experiment needed a longer time to reach the temperature of the Ethylene Glycol entering the PCC-TES structure from the inlet at the top. The paper also demonstrated that a lumped-parameter ODE model can perform an incredibly good job of predicting the enthalpy uptake of the PCC precisely matching the PDE results for the enthalpy uptake of the PCC due to the high thermal conductivity of the graphite. The proposed PCC-TES system will be integrated with air conditioning systems to efficiently meet cooling demand and reduce emissions. Previous work by our research group has demonstrated that the [AC + PCC-TES] hybrid design can reduce compressor size by 50%, double the compressor efficiency (COP) during mid/off-peak hours, reduce electricity consumption by 30%, and cut CO2 emissions by 30% – all without compromising overall system performance or building comfort level.
Advance Cardiac Life Support

This chapter contains 13 tables on advanced cardiac life support. It features algorithmic tables on ACLS pulseless arrest, ventricular fibrillation/pulseless ventricular tachycardia, pulseless electrical activity, asystole, bradycardias, tachycardias, synchronized cardioversion, common drugs utilized during ACLS, and the management of anaphylaxis/anaphylactoid reactions.
Modelling the value of risk-stratified skin cancer screening of asymptomatic patients by dermatologists

Background Total-body skin examination (TBSE) by dermatologists detects incidental skin cancers, but there is insufficient evidence for screening guidelines. As a result, the decision to perform screening TBSE in patients presenting for a focused visit is left to the dermatologist's discretion. Objectives To model the financial and time tradeoffs of risk-stratified skin cancer screening by dermatologists in patients presenting with unrelated focused complaints. Methods We performed an economic evaluation incorporating data from a previously published prospective multicentre international study in addition to US demographic data on age and skin phototype (SPT). Results The mean number needed to examine (NNE) for all US adults was 105 at an additional cost of $3796 per skin cancer detected when performing TBSE on a patient who presents for a focused exam. The NNE consistently decreased with increasing age and lighter SPT for every age and SPT screening threshold. The cost per person screened increased with higher age and lighter SPT owing to the higher likelihood of incurring diagnostic biopsies. The additional face-to-face time required per skin cancer detected by performing TBSE in patients who present for a focused visit was 4·5 h for all adults. We used a diverse cohort of international patients that did not include Americans and because of a low event rate, we combined detection of melanoma and nonmelanoma skin cancer. Conclusions Incidental skin cancers are detected by screening TBSE and its value can be enhanced through consideration of patients' age and SPT, which are established and readily identifiable skin cancer risk factors. What is already known about this topic? Risk stratification of asymptomatic individuals using age and skin phototype (SPT) can enhance the value of total-body skin examination when performed in the clinic by a dermatologist. What does this study add? For every age and SPT screening threshold, the number needed to examine to identify one skin cancer consistently decreased with increasing age and lighter SPT. When deciding to perform a screening skin examination in patients presenting with a focused complaint, dermatologists may wish to consider a patient's risk using age and SPT to enhance the yield of this intervention. Linked Comment: Ferris. Br J Dermatol 2020; 183:417-418.
Use of Single-Photon Emission Computed Tomography Imaging for Hypermetabolic Facet Identification in Diagnosis of Cervical and Axial Back Pain.

Background Few studies have used hybrid single-photon emission computed tomography (SPECT)/computed tomography (CT) scan to identify degenerative facet disease. We aimed to determine the incidence of hypermetabolic facets on SPECT/CT imaging in patients with axial neck or back pain to elucidate the value of SPECT/CT scan in identifying pain generators. Methods A retrospective review of adult patients with axial neck or back pain was conducted. A total of 190 patients underwent high-resolution SPECT/CT imaging using a standardized protocol from January 2010 to April 2018. Facet joints with increased radionuclide uptake on SPECT imaging were characterized as hypermetabolic. Number, level, and laterality of hypermetabolic facets were recorded based on review of imaging and radiologist impressions. Results The average age of the patients was 58 ± 13 years, and 51% of patients were men. A total of 85 patients (48%) demonstrated zygapophyseal joint hypermetabolism (ZJH) on SPECT imaging. A total of 202 hypermetabolic facets were identified, indicating the average number of facets with ZJH was 2.38 ± 1.91. Of patients with a positive scan, lumbar facets were most commonly affected (69% of ZJH) followed by cervical (24%) and thoracic regions (6%). C1-2 and C2-3 (22% each of cervical ZJH) and L4-5 (32% of lumbar ZJH) were most commonly affected in the cervical and lumbar regions, respectively. Conclusions Nearly half of all patients with axial neck or back pain demonstrated ZJH on SPECT/CT imaging, supporting ZJH sites as potential pain generators and targets for treatment. Our results support the role for SPECT/CT imaging in the workup of patients with axial neck or back pain, which may reduce invasive diagnostic procedures and aid in treatment planning.