cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A055: Systematic discovery of combinationimmunotherapy targets in vivo

Immunotherapy has demonstrated remarkable responses in patients with metastatic tumors. Targeting the inhibitory CTLA-4 and PD-1 receptors expressed by T cells induces durable responses in a subset of cancer patients, including advanced melanoma. However, cancers, such as melanoma, remain largely resistant to many forms of immunotherapy, most likely due to exploitation of additional, and unidentified, negative feedback loops. It is widely appreciated that combination therapies will be required to extend the benefit of checkpoint blockade. Current approaches for discovery of combination therapies emphasize a 1 + 1 approach in which an active drug is tested in combination with an experimental agent. We hypothesize that many opportunities for synergistic combinations are missed with this strategy. We propose to develop a novel in vivo technique for discovery of combination therapies in the tumor microenvironment. Single-cell RNA-seq will be used to discover genes upregulated in dysfunctional T cells during PD-1 or CTLA-4 monotherapy in a mouse model of melanoma. We will then screen a library of identified targets in CD8 T cells for synergistic combinations using checkpoint blockade along with CRSIPR/Cas9 genome editing. Enrichment within the tumor of specific targets will then be further investigated to determine the most efficacious combinations for the treatment of melanoma. Citation Format: Adam N. Cartwright, Rong En Tay, Kai W. Wucherpfennig. Systematic discovery of combinationimmunotherapy targets in vivo [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A055.
GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease in critical need of new therapeutic strategies. Here, we report that the stress-inducible 78-kDa glucose-regulated protein (GRP78/HSPA5), a key regulator of endoplasmic reticulum homeostasis and PI3K/AKT signaling, is overexpressed in the acini and PDAC of Pdx1-Cre;KrasG12D/+;p53f/+ (PKC) mice as early as 2 mo, suggesting that GRP78 could exert a protective effect on acinar cells under stress, as during PDAC development. The PKC pancreata bearing wild-type Grp78 showed detectable PDAC by 3 mo and rapid subsequent tumor growth. In contrast, the PKC pancreata bearing a Grp78f/+ allele (PKC78f/+ mice) expressing about 50% of GRP78 maintained normal sizes during the early months, with reduced proliferation and suppression of AKT, S6, ERK, and STAT3 activation. Acinar-to-ductal metaplasia (ADM) has been identified as a key tumor initiation mechanism of PDAC. Compared with PKC, the PKC78f/+ pancreata showed substantial reduction of ADM as well as pancreatic intraepithelial neoplasia-1 (PanIN-1), PanIN-2, and PanIN-3 and delayed onset of PDAC. ADM in response to transforming growth factor α was also suppressed in ex vivo cultures of acinar cell clusters isolated from mouse pancreas bearing targeted heterozygous knockout of Grp78 (c78f/+ ) and subjected to 3D culture in collagen. We further discovered that GRP78 haploinsufficiency in both the PKC78f/+ and c78f/+ pancreata leads to reduction of epidermal growth factor receptor, which is critical for ADM initiation. Collectively, our studies establish a role for GRP78 in ADM and PDAC development.
Event shape diagrams

"Event shape diagrams" are proposed as a representation for capturing the nuances of meaning of verbs that describe similar events. These diagrams represent timing, causal relationships between case roles, and typical value ranges for role fillers. Event shape diagrams are expressed in terms of primitive predicates and timing information that we believe could be computed by perceptual systems, and are intended to be a step toward the eventual connection of language systems to perceptual (vision, hearing, and touch) sensing systems. The diagrams are capable of representing modification of verbs by adverbs, can support judgements of the degree of plausibility of various interpretations of a sentence's meaning, and may be useful in figuring out the meaning of certain kinds of metaphors.
Treatment of ectopic pregnancy with single-dose methotrexate in a patient with an intrauterine device : a case report

Background Medical therapy for ectopic pregnancy is successful in 86-100% of selected patients. Patients who conceive with an intrauterine device (IUD) in place have an increased risk of ectopic pregnancy (30% of conceptions); these patients have been treated routinely by surgery. Case A 33-year-old woman at 7 weeks' gestation with a copper-containing IUD in place presented with an ectopic pregnancy based on transvaginal ultrasound, quantitative beta-human chorionic gonadotropin and physical examination findings. Because she desired to keep her IUD and avoid surgery, she was treated with intramuscular single-dose methotrexate. Conclusion This case was the first reported successful medical treatment of an ectopic pregnancy in a patient with an IUD. There appeared to be no adverse clinical interactions between the methotrexate and IUD.
Lithologic controls on hydrologic and geochemical processes in constructed Everglades tree islands

Abstract Tree islands have been hypothesized to induce calcite precipitation by concentrating ions in the groundwater through evapotranspiration processes. This research investigates how lithology regulates the hydrologic and geochemical conditions within two types of constructed Everglades tree islands: peat-based and limestone-core surrounded by peat. Three years of hydrochemical and hydrologic data (2013–2015) obtained from the constructed tree islands suggest that under current climatic and managed hydrologic conditions, calcite dissolution is prevalent within the top meter of soil in both types of tree islands. Mass-balance calculations along groundwater flow paths in one peat-based tree island that contained clay at depth, indicated that calcite precipitation is likely 1 m below the soil surface. The lithological characteristics of that peat-based island supported a persistently depressed groundwater table, while tree islands with elevated ratios of peat-to-sand content did not. Limestone-core tree islands also supported a depressed water table, particularly during the dry season. This study determined that the lithology of a set of man-made Everglades tree islands played a primary role in regulating the seasonal fluctuation of the water table and hydrogeochemical processes. Understanding the mechanisms of tree-island formation and maintenance is important for preserving the overall ecosystem function of the freshwater-Everglades.
The combination index (CI < 1) as the definition of synergism and of synergy claims

Abstract The unified theory of the median-effect equation (MEE) of the mass-action law (MAL) indicates that dose and effect are interchangeable, and all dose-effect curves can be transformed into straight-lines by the median-effect plot. Therefore, it allows pharmacodynamics (PD) analysis using small size experimentation for in vitro and in vivo studies. Further, extension of MEE has proven that the Combination Index Equation (CIE) which defines Synergism (CI 1), can be automatically simulated by CompuSyn software within one second after data entries. With adequate experimental accuracy of measurements, the minimum number of only 10 data points are required for quantitative synergy determination in two-drug combinations, even in animals or in clinical trials. Three articles introducing the CI method (in 1984), the review (2006), and the perspectives (2011) have been well recognized and cited 5516, 2382, and 1701 times in 1117, 768 and 530 biomedical journals, respectively (as of 2.10.2018) [Google Scholar Citations- Ting-Chao Chou]. However, the academic societies and governmental regulatory agencies are still lack of guideline on synergy definition, despite over 20 arbitrary, non-quantitative synergy definitions are still applied and reported. As drug combination is the most widely used therapies for the most dreadful diseases such as cancer and AIDS, a call for open forum on scientific credibility and accountability in these matters is warranted.
Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan–Meier method. OS was analyzed with Cox regression. Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.
Design and Characterization of Nozzle-Injection Assemblies Integrated with High-Frequency Microactuators

Two active nozzle-injection assemblies integrated with high-frequency, resonance-enhanced microactuators have been developed and characterized in this paper. In design 1, four injection nozzles eac...
Equilateral Sets in {\mathcal{l}}_{p}^{d}

If X is a Minkowski space, i.e., a finite-dimensional real normed space, then \(S \subset X\) is an equilateral set if all pairs of points of S determine the same distance with respect to the norm. Kusner conjectured that \(e({\mathcal{l}}_{p}^{d}) = d + 1\) for \(1 0 such that \(e({\mathcal{l}}_{p}^{d}) \leq {C}_{p}{d}^{1+2/(p-1)}\).
Paternalism, Resistance, and Hegemony

The Jackson Iron Company’s paternalistic efforts at Fayette included the provision of housing and medical services, both of which were paid for by employees through rent and deductions in pay. In an early example of green engineering, the company provided a baseball field and racetrack for public entertainment and may have set aside greenspaces for public promenades, in keeping with Victorian ideals regarding health and morality. High-ranking company employees frequently held public political offices until the company’s economic power waned in the late 1880s. The company shared similar moralistic ideals with Protestant and Victorian ideologies, particularly regarding alcohol, and some employees apparently subscribed to this hegemony to a certain extent. However, many households throughout Fayette’s class hierarchy probably consumed alcohol, indicating a complex power dynamic.
Implications of behavioral sensitization and kindling for stress-induced behavioral change.

Psychomotor stimulant-induced behavioral sensitization and electrophysiological kindling are not animal models of stress with obvious face validity; however, we discuss them here as they may guide us to new principles concerning changes in long-term responsivity in behavior that may be relevant to some stress situations. Moreover, there is an extensive literature indicating that there are important interactions between psychomotor stimulant-induced behavioral sensitization and stress-induced behavioral alterations. Stimulants such as amphetamine and cocaine are thought to exert many of their actions by potentiating noradrenergic and dopaminergic neurotransmission. Stresses, in many instances, are also capable of acting on these catecholamine and related neurochemical substrates. Thus, it is not surprising that under some conditions, stresses may facilitate subsequent reactivity to psychomotor stimulants and, vice-versa, that psychomotor stimulant pretreatment may enhance stress responsivity. Seymour Antelman and colleagues have reviewed elsewhere (1,2) evidence for cross-sensitization between stress and stimulants. It is not the point of this paper to argue that this is a universal principle; we and others have observed in some instances that stresses may decrease subsequent stimulant-induced behavior. What we are suggesting is that, in many instances, stimulant-induced effects on short- and long-term alterations in behavior may be mediated by the same neurochemical systems that are relevant to the consideration of stress-induced changes in behavior.
Real-Time Traffic Video Analysis Using Intel Viewmont Coprocessor

Vision-based traffic flow analysis is getting more attention due to its non-intrusive nature. However, real-time video processing techniques are CPU-intensive so accuracy of extracted traffic flow data from such techniques may be sacrificed in practice. Moreover, the traffic measurements extracted from cameras have hardly been validated with real dataset due to the limited availability of real world traffic data. This study provides a case study to demonstrate the performance enhancement of vision-based traffic flow data extraction algorithm using a hardware device, Intel Viewmont video analytics coprocessor, and also to evaluate the accuracy of the extracted data by comparing them to real data from traffic loop detector sensors in Los Angeles County. Our experimental results show that comparable traffic flow data to existing sensor data can be obtained in a cost effective way with Viewmont hardware.
Commentary: Managing Pension and Retirement Assets: An International Perspective

Zvi Bodie’s article encompasses a lot of material. I like his summary of our past, present, and future pension system. I have a few comments on details and then I will address the future for pension funds and how we should think about them.
Low-Level Temperature Structure under Alaskan Ice Fog Conditions *

Wiresonde temperature soundings were taken during two winters at Eielson Air Force Base, near Fairbanks, Alaska, as part of an ice fog investigation. Correlations were found between the depths of the visible fog layers and the steep portions of the temperature inversions. The steep portions of the temperature inversions were usually confined to the lowest 100 feet of the atmosphere. The frequency of occurrence of strong surface inversions was less than had previously been expected for an arctic continental area with temperatures in the vicinity of −40C. This is attributed to the modifying effect of the ice fog, which was usually present in the observation area at temperatures below −30C.
Calling on the Patient's Perspective in Emergency Medicine: Analysis of 1 Year of a Patient Callback Program.

Background:Patient-centered approaches in the evaluation of patient experience are increasingly important priorities for quality improvement in health-care delivery. Our objective was to investigat...
Drug Use and Postoperative Mortality Following Valve Surgery for Infective Endocarditis: A Systematic Review and Meta-analysis

Background Infective endocarditis (IE) often requires surgical intervention. An increasingly common cause of IE is injection drug use (IDU-IE). There is conflicting evidence on whether postoperative mortality differs between people with IDU-IE and people with IE from etiologies other than injection drug use (non-IDU-IE). In this manuscript, we compare short-term postoperative mortality in IDU-IE vs non-IDU-IE through systematic review and meta-analysis. Methods The review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication databases were queried for key terms included in articles up to September 2017. Randomized controlled trials, prospective cohorts, or retrospective cohorts that reported on 30-day mortality or in-hospital/operative mortality following valve surgery and that compared outcomes between IDU-IE and non-IDU-IE were included. Results Thirteen studies with 1593 patients (n = 341 [21.4%] IDU-IE) were included in the meta-analysis. IDU-IE patients more frequently had tricuspid valve infection, Staphylococcus infection, and heart failure before surgery. Meta-analysis revealed no statistically significant difference in 30-day postsurgical mortality or in-hospital mortality between the 2 groups. Conclusions Despite differing preoperative clinical characteristics, early postoperative mortality does not differ between IDU-IE and non-IDU-IE patients who undergo valve surgery. Future research on long-term outcomes following valve replacement is needed to identify opportunities for improved healthcare delivery with IDU-IE.
Resilience-Oriented Design of Distribution Systems

Climatic hazards, such as hurricanes and ice storms, pose a top threat to power distribution systems. This paper proposes a resilience-enhancing strategy to make distribution systems more resilient to climatic hazards. The proposed strategy consists of three resilience-oriented design (ROD) measures, namely line hardening, installing backup distributed generators (DGs), and adding automatic switches. The main challenges of this problem are modeling the spatio-temporal correlation among ROD decisions and uncertainties, capturing the entire failure-recovery-cost process, and solving the resultant large-scale mixed-integer stochastic problem efficiently. To deal with these challenges, we propose a hybrid stochastic process with deterministic casual structure to model the spatio-temporal correlations of uncertainties. A new two-stage stochastic mixed-integer linear program is formulated to capture the impacts of ROD decisions and uncertainties on system's responses to climatic hazards. The objective is to minimize the ROD investment cost in the first stage and the expected costs of loss of load, DG operation, and damage repairs in the second stage. A dual decomposition algorithm with branch-and-bound is developed to solve the proposed model with binary variables in both stages. Case studies on the IEEE 123-bus test feeder show the proposed approach can improve the system resilience at minimum costs.
Real-Time Monitoring of Spray Drift from Three Different Orchard Sprayers.

Abstract In Washington State, half of all pesticide-related illnesses in agriculture result from drift, the off-target movement of pesticides. Of these, a significant proportion involve workers on another farm and orchard airblast applications. We compared the spray drift exposure reduction potential of two modern tower sprayers – directed air tower (DAT) and multi-headed fan tower (MFT), in relation to a traditional axial fan airblast (AFA) sprayer. We employed real-time particle monitors (Dylos DC1100) during a randomized control trial of orchard spray applications. Sections of a field were randomly sprayed by three alternating spray technologies – AFA, DAT and MFT – while monitors sampled particulate matter above and below the canopy at various downwind locations in a neighboring field. Geometric mean particle mass concentrations (PMC) outside the intended spray area were elevated during all applications at all of our sampling distances (16–74 m, 51–244 ft). After adjusting for wind speed and sampling height, the 75th percentile (95% confidence interval) PMC level was significantly greater during spray events than background levels by 105 (93, 120) μg/m3, 49 (45, 54) μg/m3 and 26 (22, 31) μg/m3 during AFA, DAT and MFT applications, respectively. Adjusted PMC levels were significantly different between all three sprayers. In this study, tower sprayers significantly reduced spray drift exposures in a neighboring orchard field when compared to the AFA sprayer, with the MFT sprayer producing the least drift; however these tower sprayers did do not fully eliminate drift.
Metabolic rate predicts the lifespan of workers in the bumble bee Bombus impatiens

The rate of living theory posits that higher metabolic rates negatively affect lifespan. This relationship would influence trade-offs among life history traits associated with energy production and allocation. These trade-offs may also apply within a species, resulting in differences among individuals in life history traits. In this study, we use the bumble bee Bombus impatiens to test for a relationship between metabolic rate and lifespan. We measured the resting metabolic rates of workers throughout their lives and noted their lifespans in the laboratory. Our results show that (1) resting metabolic rate inversely correlated with potential lifespan and (2) resting metabolic rate was not affected by age. These results suggest that within a species, individual differences in life-history trade-offs may exist as predicted by the rate of living theory.
Influence of social determinants of health and substance use characteristics on persons who use drugs pursuit of care for hepatitis C virus infection.

Abstract Background Social determinants of health (SDOH), i.e., social, behavioral and environmental factors, are increasingly recognized for their important influence on health outcomes. Data are limited on the influence of SDOH, substance use characteristics, and their interactions on pursuit of hepatitis C virus (HCV) care among individuals with opioid use disorder (OUD). Linkage to HCV care remains low in this population despite high HCV prevalence and incidence. Aims To investigate the influence of SDOH, substance use factors, and their interactions on HCV treatment uptake among OUD patients in a methadone treatment program. Methods Information on patient demographics, SDOH, substance use characteristics, and co-morbid medical conditions were obtained from the paper and electronic medical records of OUD patients on methadone. We applied multiple correspondence analysis, k-means algorithm, and logistic regression with least absolute shrinkage and selection operator penalty to identify variables and clusters associated with pursuit of HCV care. Results Data from 161 patients (57% male, 60% Caucasian, mean age 45 years) were evaluated. Being employed, the absence of support systems, and a history of foster care were the strongest positive predictors of treatment pursuit. The use of crack/cocaine as the initial illicit substance, criminal activity without incarceration, and the absence of a family history of chemical dependency were the strongest negative predictors. We identified clusters among persons with OUD based upon their likelihood to pursue HCV management. Conclusion Utilizing data from the medical record, we were able to identify factors positively and negatively associated with linkage-to-care for HCV. We were also able to divide patients into clusters of factors associated with linkage-to-care for HCV. These results could be used to identify individuals with OUD based upon their readiness for HCV care.
Detection, pharmacokinetics, and selected pharmacodynamic effects of methamphetamine following a single transmucosal and intravenous administration to exercised Thoroughbred horses

Methamphetamine is a central and peripheral nervous system stimulant. There is only a single study that describes exposure to and disposition of this compound in horses. The potential for abuse and inadvertent exposure in equine athletes along with the limited data available necessitates further study. The objectives of the current study were to describe drug and metabolite concentrations, develop an analytical method that could be used to regulate its use, and describe selected pharmacodynamic effects. In phase 1, six horses were randomized into three transmucosal dose groups (n = 2/group; 0.5, 1.0 or 10 mg). In phase 2, horses received a single 10 mg intravenous dose. In phase 3, the effects of urinary pH on elimination were studied. Blood and urine samples were collected for up to 72 hours post drug administration. Concentrations of methamphetamine were measured using liquid chromatography-tandem mass spectrometry. Methamphetamine was below the limit of detection (LOD) in blood by 2, 4, and 18 hours following transmucosal administration of 0.5, 1, and 10 mg, respectively. Following intravenous administration, methamphetamine fell below the LOD between 12 and 18 hours. Following urinary acidification, methamphetamine fell below the limit of quantitation (LOQ) by 12 hours. In urine, methamphetamine was no longer detected at 48, 48, and 72 hours in the 0.5, 1, and 10 mg transmucosal groups and 18 hours in the intravenous group. Increased urinary pH resulted in urinary concentrations of methamphetamine falling below detectable levels by 48 hours post transmucosal administration. While the number of animals was small, behavioral, stimulatory, and cardiac effects were minimal.
Response to systemic therapy and survival outcomes in de-novo (D1) metastatic castration-sensitive prostate cancer (mCSPC) versus mCSPC with prior local therapy (D0).

46Background: A real-world study (n= 436, PMID: 29707790) suggest that D1 mCSPC has worse outcomes than D0 mCSPC. The objective of our study is to validate these findings in a real-world setting, a...
Opioid Consumption After Arthroscopic Meniscal Procedures and Anterior Cruciate Ligament Reconstruction.

Background:Procedure-specific opioid-prescribing guidelines have the potential to decrease the number of unused pills in the home without compromising patient satisfaction. However, there is a pauc...
Preparing for the Quit Day: Comparing Beliefs of Nondaily Versus Daily Young Adult Smokers as They Prepare for a Quit Attempt

INTRODUCTION Most smoking cessation approaches are modeled on heavy daily smoking. With increasing prevalence of nondaily smoking, it may be necessary to modify these approaches for nondaily smokers. AIMS To provide information about beliefs and attitudes relevant to smoking cessation for nondaily smokers. METHODS Secondary analysis of two prospective studies on young adult smokers (18-24 years of age) provided brief advice to quit smoking. Measures include baseline levels of constructs relevant to smoking cessation counseling and perceived benefits of and barriers to smoking cessation. RESULTS Participants (n = 40 nondaily, 122 daily smokers) were predominantly White (70% and 84%, respectively), gender-balanced (50% and 43% female), full-time college students (89% and 95%). At baseline, nondaily smokers reported lower levels of nicotine dependence (p < .001; nondaily: Fagerstrom Test for Nicotine Dependence (FTND) = 0.8 ± 1.5, daily: FTND = 3.1 ± 1.9), lower urge to smoke (p < .001), greater self-efficacy when facing external smoking stimuli (p = .03), expecting to experience fewer positive effects (reduced negative affect, p = <.001, stimulation, p = .02), and valuing the importance of smoking effects less (ps < .01) than daily smokers. During counseling, nondaily smokers generated both fewer benefits of cessation (Wald X2(df = 1) = 4.91, p = .027) and fewer barriers (Wald X2(df = 1) = 5.99, p =.014) than daily smokers. Withdrawal was not listed by nondaily smokers as a barrier (p < .01). CONCLUSIONS Constructs relevant to smoking cessation for daily smokers were less salient to young nondaily smokers, compared with moderately addicted young daily smokers, as indicated by responses to standardized scales and by the generation of fewer benefits and barriers in counseling. Interventions may need to find novel ways to engage nondaily smokers, particularly young adult, in smoking cessation efforts. IMPLICATIONS This study is unique in eliciting benefits and barriers from nondaily smokers as they are about to make a quit attempt. This is a critically important point in time, as this is the point in time in which an action plan is formed and can be informed and enhanced by smoking cessation support. Our study further allowed direct comparison to daily smokers undergoing the same procedures, which allowed the identification of unique factors that may impact nondaily smokers in their quit attempt, which may guide intervention efforts. Use of a mixed method design further strengthen the rigor of this study.
Identifiability of Tissue Material Parameters from Uniaxial Tests using Multi-start Optimization

Abstract Determining tissue biomechanical material properties from mechanical test data is frequently required in a variety of applications, e.g. tissue engineering. However, the validity of the resulting constitutive model parameters is the subject of debate in the field. Common methods to perform fitting, such as nonlinear least-squares, are known to be subject to several limitations, most notably the uniqueness of the fitting results. Parameter optimization in tissue mechanics often comes down to the “identifiability” or “uniqueness” of constitutive model parameters; however, despite advances in formulating complex constitutive relations and many classic and creative curve-fitting approaches, there is no accessible framework to study the identifiability of tissue material parameters. Our objective was to assess the identifiability of material parameters for established constitutive models of fiber-reinforced soft tissues, biomaterials, and tissue-engineered constructs. To do so, we generated synthetic experimental data by simulating uniaxial tension and compression tests, commonly used in biomechanics. We considered tendon and sclera as example tissues, using constitutive models that describe these fiber-reinforced tissues. We demonstrated that not all of the model parameters of these constitutive models were identifiable from uniaxial mechanical tests, despite achieving virtually identical fits to the stress-stretch response. We further show that when the lateral strain was considered as an additional fitting criterion, more parameters are identifiable, but some remain unidentified. This work provides a practical approach for addressing parameter identifiability in tissue mechanics. Statement of Significance Data fitting is a powerful technique commonly used to extract tissue material parameters from experimental data, and which thus has applications in tissue biomechanics and engineering. However, the problem of “uniqueness” or “identifiability” of the fit parameters is a significant issue, limiting the fit results’ validity. Here we provide a novel method to evaluate data fitting and assess the uniqueness of results in the tissue mechanics constitutive models. Our results indicate that the uniaxial stress-stretch experimental data are not adequate to identify all the tissue material parameters. This study is of potential interest to a wide range of readers because of its application for the characterization of other engineering materials, while addressing the problem of uniqueness of the fitted results.
Attention deficit hyperactivity disorder medications and BMI trajectories: The role of medication type, sex and age

OBJECTIVES Attention deficit hyperactivity disorder (ADHD) and the medications used to treat it are associated with obesity. Stimulants lead to weight loss, while antipsychotics and antidepressants lead to weight gain. Little is known, however, how alpha-2-agonists impact weight, or the independent effect on BMI of these four classes of medications, which are often prescribed concurrently. We aimed to estimate the proximal change in BMI associated with start of medication and to assess whether medication-specific departures in BMI varied by age and sex. STUDY DESIGN We analysed longitudinal electronic health records from children (4-19 years) with an ADHD diagnosis seen at one healthcare system (2011-2018). Their BMI z-scores were fit as a cubic function of age via a mixed model, separately by sex and adjusting for race/ethnicity. From this model, we estimated annual changes in BMI-z after medication, allowing changes to vary by age and sex. RESULTS Among the 22 714 children with ADHD (mean initial age = 10.0), 4335 (19.1%) were never prescribed ADHD medication. The others (80.9%) experienced departures in BMI-z after start of all four medication classes, which varied across age and sex (interaction P-values < .01). All medications had larger impacts at younger ages. As expected, decreased BMI-z was observed with stimulants, while antidepressants and antipsychotics led to BMI-z increases; alpha-agonists also were associated with BMI-z increases. CONCLUSIONS This longitudinal study revealed that ADHD medications are independently associated with proximal changes in BMI-z after initiation, significantly varying by sex and age. Future research should study further the interactions of these medications on long-term impacts on obesity.
A Qualitative Study of Developing Competency in Thyroid Surgery: A Resident's Perspective With 5 Year Follow Up.

Objectives:The Accreditation Council for Graduate Medical Education has guidelines on assessing surgical qualifications based on experience. Attending surgeons have various assumptions on how their...
The relationship between parental food parenting practices & child eating behavior: A comparison of mothers and fathers.

Abstract The objective of this study was to compare the relationships between food parenting practices and child eating behavior among mothers and fathers of young children. This cross-sectional study recruited mothers (n = 127) and fathers (n = 118) of children (4.2 ± 1.3 years old) to complete surveys (face-to-face and online). Each parent completed the Comprehensive Food Parenting Questionnaire, Children's Eating Behavior Questionnaire, and demographic questions. Linear regressions were used to compare the relationships between parental food parenting practices and children's eating behaviors with parent sex as a moderator. Child age and sex served as control variables in each regression. Parent sex was a significant moderator in several relationships between parent food parenting practices and child eating behavior. In the relationship between parental restriction for health (s = -.14, p = .014) and monitoring (s = -.13, p = .028) and child slowness in eating, the slope of the interaction was significantly higher for mothers, meaning that when mothers and fathers use the same level of restriction for health and monitoring, child slowness in eating is higher for children of mothers. When mothers and fathers used the same level of restriction for weight, child food responsiveness (s = .13, p = .003) and emotional overeating (s = .12, p = .046) was significantly higher for children of fathers. There may be differences in how mothers and fathers implement food parenting practices and/or differences in how these practices impact children. Specifically, for fathers, it seems that the use of restriction for weight is more detrimental for children's eating behaviors compared to when mothers use the same level of restriction for weight.
Investigating correlations between illness and defensive behaviour approach: A case of twin cities of Pakistan.

Abstract Municipal solid waste (MSW) management has emerged as a major problem for modern societies in recent decades. An optimal waste management system is essential to prevent the pollution burden and associated health related issues. This study carries out an empirical evaluation of the illness caused by inadequate solid waste management in the metropolitan of Rawalpindi-Islamabad. The model is based on utility-maximizing consumer behavior and predicted probability of disease in the household is estimated by employing “seemingly uncorrelated bivariate probit model”. Primary data obtained through multistage random sampling that comprises of 849 respondents. The findings show that irregular waste disposal sites in the vicinity of residences cause illness. The key findings indicate that distance from dumpsites and use of contaminated water adversely affect the health outcomes. Furthermore, the results show that respondents were unable to engage in defensive activities due to a lack of awareness. Oft-times, the waste is dumped in illegal sites that is burnt thus causing excessive air and ground water pollution. The results shed light on the respondents' understanding of the negative consequences of excessive waste disposal and study suggests measures that motivate households to engage in defensive activities through effective campaigns and capacity building programmes that ensure sustainable solid waste management.
Extrapulmonary sarcoidosis with a focus on cardiac, nervous system, and ocular involvement

Sarcoidosis is a poorly understood granulomatous disease that involves the lungs and/or intrathoracic lymph nodes in more than 90% of cases. Although pulmonary sarcoidosis is the leading cause of mortality in this disease, this review focuses on three sites of extrapulmonary involvement (heart, nervous system, and eyes), since involvement of any of these sites can be catastrophic, leading to death, debilitation, or blindness. Patients with cardiac, ocular and neurosarcoidosis necessitate a multidisciplinary approach with careful and long-term follow-up. Prompt diagnosis with imaging and/or biopsy and treatment is required to avoid irreversible damage. Corticosteroids are the mainstay of therapy and are often associated with rapid and durable remissions. Immunosuppressive or biologic agents are reserved for patients failing or experiencing side effects from steroids. Managing sarcoidosis requires vigilance, judgement, and awareness of the vagaries of this fascinating disease.
Nonlinear association of nurse staffing and readmissions uncovered in machine learning analysis

Objective Several studies of nurse staffing and patient outcomes found a curvilinear or U-shaped relationship, with benefits from additional nurse staffing diminishing or reversing at high staffing levels. This study examined potential diminishing returns to nurse staffing and the existence of a "tipping point" or the level of staffing after which higher nurse staffing no longer improves and may worsen readmissions. Data sources/study setting The Readiness Evaluation And Discharge Interventions (READI) study database of over 130,000 adult (18+) inpatient discharges from 62 medical, surgical, and medical-surgical (noncritical care) units from 31 United States (US) hospitals during October 2014-March 2017. Study design Observational cross-sectional study using a fully nonparametric random forest machine learning method. Primary exposure was nurse hours per patient day (HPPD) broken down by registered nurses (nonovertime and overtime) and nonlicensed nursing personnel. The outcome was 30-day all-cause same-hospital readmission. Partial dependence plots were used to visualize the pattern of predicted patient readmission risk along a range of unit staffing levels, holding all other patient characteristics and hospital and unit structural variables constant. Data collection/extraction methods Secondary analysis of the READI data. Missing values were imputed using the missing forest algorithm in R. Principal findings Partial dependence plots were U-shaped, showing the readmission risk first declining and then rising with additional nurse staffing. The tipping points were at 6.95 and 0.21 HPPD for registered nurse staffing (nonovertime and overtime, respectively) and 2.91 HPPD of nonlicensed nursing personnel. Conclusions The U-shaped association was consistent with diminishing returns to nurse staffing suggesting that incremental gains in readmission reduction from additional nurse staffing taper off and could reverse at high staffing levels. If confirmed in future causal analyses across multiple outcomes, accompanying investments in infrastructure and human resources may be needed to maximize nursing performance outcomes at higher levels of nurse staffing.
Lighting Detection System using Standard Interface with Power and Communication Separation Technology

In the field of LED lighting, power supply and communication modules are usually included in lamps. Since there are many types of wired/wireless communication, before the communication interface and communication package are not uniformly defined, different system manufacturers or lamp manufacturers have customary communication modules and packet formats, this will make it difficult for each company’s systems and lamps to be used interchangeably. If the originally installed system or lamp manufacturer cannot continue the warranty, or even the manufacturer closes down, it will cause product orphans. Therefore, this paper proposes the concept of separation of power and communication, which puts the communication module outside the lamp. This paper defined the communication interface (named standard interface) and packet format, and proposed the translator circuit. If the system and the lamp manufacturer follow this protocol, the products of each factory will be interchangeable, the entire control system or lamps will no longer be limited to some manufacturers, and there is no need to worry about product orphans in the future. TaiSEIA is an application layer protocol for smart home appliances. It allows smart home appliances and other devices in the home to be interconnected via wired or wireless networks. This protocol has become a national standard (CNS16014), and it is also the current smart home IoT communication protocol that is currently being promoted in Taiwan. This paper focuses on the regulation needs of LED lamps, including settings, control and query functions, and defines the standard interface and packet format. Using the proposed translator circuit, a lamp with a standard interface will become a household appliance conforming to the TaiSEIA protocol.
Renewable Portfolio Standards and the Dormant Commerce Clause: The Case for In-Region Location Requirements

Electricity generation facilities are the single largest source of greenhouse gas emissions in the United States. Although renewable generation facilities offer a cleaner alternative to traditional, carbon-intensive methods of electricity generation, output from renewable facilities is less reliable and more costly relative to facilities that burn fossil fuels. Therefore, in an unfettered marketplace, investment in renewable energy facilities would be slow if not stagnant. In response to concerns regarding anthropogenic climate change and fuel diversity, an increasing number of state governments have implemented statutory and regulatory regimes to incentivize the construction of renewable generation facilities within state or regional borders. These programs run the risk of violating the dormant Commerce Clause because they provide for differential treatment of electricity based, at least in part, upon the commodity’s geographic origin. This Note argues that state programs that condition benefits upon the in-region location of a renewable generation facility or physical delivery of electricity from a facility in a neighboring region can survive scrutiny under the dormant Commerce Clause.
Two Dimensional Wave Propagation in a Model of Dictyostelium Discoideum

We summarize a continuum model for cyclic AMP wave propagation in Dictyostelium discoideum, and show that this model predicts the correct amplitude and period for spiral waves. Particular attention is given to the numerical method used in our simulations.
A Review of “Green Cities of Europe: Global Lessons on Green Urbanism”

The article reviews the book "Green Cities of Europe: Global Lessons on Green Urbanism," edited by Timothy Beatley.
MORSE THEORY, GRAPHS, AND STRING TOPOLOGY

In these lecture notes we discuss a body of work in which Morse theory is used to construct various homology and cohomology operations. In the classical setting of algebraic topology this is done by constructing a moduli space of graph flows, us- ing homotopy theoretic methods to construct a virtual fundamental class, and evaluating cohomology classes on this fundamental class. By using similar constructions based on "fat" or ribbon graphs, we describe how to construct string topology operations on the loop space of a manifold, using Morse theoretic techniques. Finally, we discuss how to relate these string topology operations to the counting of J-holomorphic curves in the cotangent bundle. We end with speculations about the relationship between the absolute and relative Gromov - Witten theory of the cotangent bundle, and the open-closed string topology of the underlying manifold.
Pancreatic acinar cell regeneration following copper deficiency-induced pancreatic necrosis

Rats maintained on a diet deficient in copper for up to 8–10 weeks exhibit marked necrosis and depletion of acinar cells in the pancreas. When these animals are subsequently fed a copper-supplemented diet, foci of hepatocyte differentiation emerge by about 12 weeks [9]. The present study deals with pancreatic changes during copper depletion and determines the extent of regenerative capacity of the pancreas during the early phases of copper supplementation. During the period of copper depletion, the pancreas gradually decreased in size, and by eight weeks of deficiency weighed approx. 30% as much as the control pancreas. Light-microscopic examination showed focal necrosis of acinar cells at 4 weeks, loss of lobular architecture by six weeks and loss of 85–90% of acinar tissue by eight weeks. Regeneration of the pancreas was initiated by feeding copper-supplemented diet at the end of eight weeks of copper deficiency. The wet weight of the pancreas increased gradually, and by 17 days it weighed 50% more than on the first day of regeneration. Mitotic activity was observed mainly in the acinar cells, beginning at 24 h and reaching a maximum of 19±1/1000 acinar cells at 72 h, and decreasing steadily thereafter. [3H]Thymidine autoradiography showed a labeling index of 51±1.7/1000 acinar cell nuclei at 24 h, reaching a peak value of 261±5.5/1000 acinar cells at 96 h. By 17 days, pancreatic regeneration was only partially complete; however, the proliferative activity was still persistent, albeit at a slower pace. Morphometric analysis of the pancreas on the 17th day of regeneration showed that acinar tissue occupied only 37% of the volume, as compared to 84% in the normal pancreas. These studies clearly demonstrate that acinar tissue of the pancreas following copper deficiency is capable of regeneration, but that the recovery of the pancreas is only partial Additional studies are necessary to establish the role of this early acinar cell regeneration in pancreatic hepatocyte differentiation.
PowerWeb: a tool for evaluating economic and reliability impacts of electric power market designs

This paper describes a Web-based electric power market simulation tool called PowerWeb. It can be used as an experimental economics research tool to evaluate the economic and reliability impacts of given market designs as well as to train and educate students, industry professionals and policy makers. It is unique in its ability to combine the human behavior characteristics of a market structure with the operational and reliability aspects of the underlying power system.