cssi/SciSciGPT-SciSciNet huggingface dataset:
Petri Net Modeling of Application Server Performance for Web Services.

A study of failure rates of a web service that is deployed in a service-oriented architecture is presented. The study focuses on the HTTP requests that are rejected by the application server. The rejections may be caused by system overloading or mismanagement of configuration parameters. An analytical model and a Stochastic Activity Network (SAN) model are developed to predict the number of such failures. The performance of the models is compared against the experimental results in a LAN environment that is used as a test-bed. The models utilize the parameters extracted from the empirical testing such as the average response time and arrival rate of the web service requests. The accuracy of the SAN model suggests that the model can be beneficial to predict the rejection rate of web services and to better understand the application server performance for those cases that are difficult to replicate in a field study. KeywordsApplication Server; Simulation Model; Service Oriented Architecture; Web Service; Petri Net; Load Testing
Venous air embolism during cesarean delivery.

Recent reports have indicated that subclinical venous air embolism (VAE) may occur in 50-65% of patients during cesarean delivery, with a potential for life-threatening embolic events. We attempted to confirm this incidence using precordial Doppler monitoring and to examine the occurrence of correlative signs thought to accompany embolic events. Doppler changes, oxygen saturation (SaO2), and ECG were monitored in 63 patients during cesarean delivery; 60 received regional anesthesia, and three, general anesthesia. Six of 63 (10%) had Doppler changes consistent with VAE. Nineteen patients (30%) had small decreases in SaO2; most of these were not associated with Doppler changes or any other finding. Two patients had transient S-T segment depression. Fourteen of the 60 patients receiving regional anesthesia (23%) reported chest pain or discomfort at some point during the procedure. This incidence of Doppler changes was significantly smaller than previously reported and was not significantly correlated with other signs reported to accompany VAE. Positive signs of VAE were more frequent when the uterus was exteriorized than when it was maintained within the abdomen during surgical repair.
Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction

Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. This retrospective cohort study interrogated a single institution’s prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0–9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.
Brett Lashua, Karl Spracklen and Stephen Wagg, eds. 2014. Sounds and the City: Popular Music, Place, and Globalization. Hampshire, UK: Palgrave Macmillan. 323pp. ISBN 978-1-137-28310-8 (hbk)

Brett Lashua, Karl Spracklen and Stephen Wagg, eds. 2014. Sounds and the City: Popular Music, Place, and Globalization. Hampshire, UK: Palgrave Macmillan. 323pp. ISBN 978-1-137-28310-8 (hbk)
Hybrid System Identification via Switched System Optimal Control for Bipedal Robotic Walking

While the goal of robotic bipedal walking to date has been the development of anthropomorphic gait, the community as a whole has been unable to agree upon an appropriate model to generate such gait. In this paper, we describe a method to segment human walking data in order to generate a robotic model capable of human-like walking. Generating the model requires the determination of the sequence of contact point enforcements which requires solving a combinatorial scheduling problem. We resolve this problem by transforming the detection of contact point enforcements into a constrained switched system optimal control problem for which we develop a provably convergent algorithm. We conclude the paper by illustrating the performance of the algorithm on identifying a model for robotic bipedal walking.
Evapotranspiration is resilient in the face of land cover and climate change in a humid temperate catchment

In temperate humid catchments, evapotranspiration returns more than half of the annual precipitation to the atmosphere, thereby determining the balance available to recharge groundwaters and support stream flow and lake levels. Changes in evapotranspiration rates and therefore catchment hydrology could be driven by changes in land use or climate. Here we examine the catchment water balance over the past 50 y for a catchment in southwest Michigan covered by cropland, grassland, forest, and wetlands. Over the study period about 27% of the catchment has been abandoned from row-crop agriculture to perennial vegetation and about 20% of the catchment has reverted to deciduous forest, and the climate has warmed by 1.14 degrees C. Despite these changes in land use, precipitation and stream discharge, and by inference catchment-scale evapotranspiration, have been stable over the study period. The remarkably stable rates of evapotranspirative water loss from the catchment across a period of significant land cover change suggest that rainfed annual crops and perennial vegetation do not differ greatly in evapotranspiration rates, and this is supported by measurements of evapotranspiration from various vegetation types based on soil water monitoring in the same catchment. Compensating changes in the other meteorological drivers of evaporative water demand besides air temperature (wind speed, atmospheric humidity, and net radiation) are also possible, but cannot be evaluated due to insufficient local data across the 50-y period. Regardless of the explanation, this study shows that the water balance of this landscape has been resilient in the face of both land cover and climate change over the past 50 y.
Resilience-constrained unit commitment considering the impact of microgrids

Power system operators commonly rely on a security-constrained unit commitment (SCUC) to schedule available generation resources for satisfying the forecasted load and addressing prevailing system constraints in response to limited components unavailability. Although widely used and proved viable, the SCUC solution cannot guarantee a useful solution when the system is subject to extreme events, i.e., severe weather events and natural disasters. In other words, even though a secure solution is obtained, the solution does not ensure the grid resilience. Considering this issue, and the growing number and intensity of extreme events, this paper proposes and formulates a resilience-constrained unit commitment (RCUC) model which ensures a resilient supply of loads even in case of multiple component outages. The role of microgrids in improving the grid response and supporting the system operator in improving grid resilience is further investigated via accurate grid-connected and islanded operation models. The RCUC model is formulated using mixed-integer linear programming (MILP), and its merits and effectiveness are demonstrated using the standard IEEE 118-bus system.
Decitabine Targets the Erythroid Progenitor/Precursor Subpopulations for the γ-Globin Gene Demethylation in Baboon.

The DNA demethylating drug (5–Az–2′–deoxycytidine) elevates fetal hemoglobin (HbF) to therapeutic levels in patients with sickle cell disease. To further investigate the mechanism of action of this drug and the role of DNA methylation in γ–globin gene silencing, we have analyzed the level of methylation of five CpG sites in the 5′ region of the γ–globin gene in highly purified subpopulations of cells representing different stages of erythroid differentiation from baboon ( P. Anubis ) using bisulfite sequencing. Baboons were treated with three different doses of decitabine (0.52, 0.26, 0.17mg/kg/day) for 10 consecutive days and pre-treatment and post-treatment adult bone marrow (ABM) were analyzed. Fetal liver (FL;n=2) and ABM cells were purified by depletion of the erythroblast subpopulation using an anti-RBC antibody (Pharmingen) in combination with immunomagnetic columns (Miltenyi) and FACS purification of CD34+CD36−, CD34+CD36+ and CD34− CD36+ subpopulations. Clonal analysis of sorted subpopulations demonstrated enrichment of CFUe in the CD34−CD36+ subpopulation, BFUe in the CD34+CD36+ subpopulation and both BFUe and CFU-GM in the CD34+CD36− subpopulation, thus confirming that these sorted subpopulations were enriched for the cells representing different stages of erythroid differentiation. A progressive decrease in the level of γ-globin gene methylation, as the degree of differentiation increased, was observed in the subpopulations purified from FL (Table 1). In pre-treatment ABM the level of γ-globin gene methylation was significantly (P
Negotiating Ambiguity in Describing Fabrics Through Technology

Designers using tangible materials like fabric may have a limited verbal language to describe the embodied experience of feeling the material. Taxonomies exist for materials like fabric, but are not served by the population of designers we studied. How can technology be designed to better explore fabric, yet not diminish any existing ambiguities in description? We chose to study both different ways to represent the fabric and different interface designs to explore fabric. We collected many descriptors, in part by crowdsourcing, and asked how designers explored fabric, leveraging off of existing practices. We designed interfaces to evaluate a designer's understanding of fabric, with the goal to provide design guidelines on how to design interfaces with ambiguous-important domains.
A Reference Model for Computer Integrated Manufacturing from the Viewpoint of Industrial Automation

Abstract This paper describes the CIM Reference Model developed by the International Purdue Workshop on Industrial Computer Systems. This work is based on a major research project carried out by the Purdue Laboratory for Applied Industrial Control in cooperation with many companies of the US and Canadian steel and paper induslries. Both organizations are based at Purdue University, West Lafayelle, Indiana. This paper will present a short overview of the complete model which has recently been published in full detail in book form [35]. The model combines the information and control hierarchy with the data flow diagram and a new implemenlation hierarchy view to present the CIM system, its architecture, its tasks and their implementation. The model is restricted to the so-called automatable functions of the plant and all functions considered to require human innovation are considered as external entities. It thus offers one way of separating the computer based funclions in a CIM system from those which must be carried out by humans, a problem which has plagued the CIM field since ils initiation. This paper will also present a survey of other CIM Reference Models existing in this field.
Abstract 110: The Estrogen-related Receptor Gamma Promotes Maturation of iPSC-derived Cardiac Myocytes

The mammalian heart has a tremendous energy requirement to support normal contractile function. Recently, our group discovered that the estrogen-related receptor γ (ERRγ) coordinately controls oxid...
Municipal tax structure and accounting disclosure

Two competing hypotheses have been developed in the public economics literature to explain the growth of government spending. The first, termed the fiscal illusion hypothesis, holds that governments have incentives to induce a misperception in the population about the cost of government. By constructing complex systems of taxation that obscure the true cost of government services, governments can lead the taxpayer to demand a larger quantity of services. The other hypothesis, the fiscal stress hypothesis, holds that tax complexity diversifies revenues, leading to less revenue variability and, hence, lower costs. Taxpayers, then, demand more government services. The two hypotheses make very different assumptions about the incentives of governments in regard to an informed electorate. The fiscal illusion hypothesis suggests incentives to obscure information, while the fiscal stress hypothesis suggests incentives to reveal true costs. Accounting and financial reporting can play a role in revealing fiscal information to taxpayers, directly or indirectly, through information intermediaries. If the fiscal illusion hypothesis describes the behavior of governments, we would expect that such governments would attempt to protect the information advantage that is conveyed by a complex tax structure by minimizing accounting disclosures. On the other hand, the fiscal illusion hypothesis suggests that a government with a complex tax structure has no reason to minimize disclosure, and may have incentives publicize lower service costs. This study examines the association of tax complexity and financial disclosure. We find that there is more disclosure in cities with more complex tax systems, a result that supports the fiscal stress hypothesis.
Oxygen radicals and vascular damage.

The effects of topical application of agents which produce oxygen radicals on cerebral arterioles were studied in anesthetized cats. Xanthine oxidase plus xanthine, which produced superoxide anion radical, hydrogen peroxide, and hydrogen peroxide plus ferrous sulfate, which produced the free hydroxyl radical, induced sustained dilation, reduced responsiveness to the vasoconstrictor effect of hypocapnia, and destructive lesions of the endothelium and of the vascular smooth muscle. Similar effects were produced by arachidonate, 15-HPETE, and PGG2. The effect of arachidonate was inhibited by mannitol, a free hyaroxyl radical scavenger, the effect of PGG2 was inhibited by SOD, the effect of 15-HPETE was inhibited by either catalase or SOD. These results suggest that these cerebral vascular abnormalities were produced by a single destructive free radical, probably the hydroxyl free radical, generated via interaction of superoxide and hydrogen peroxide. Cerebral vascular abnormalities similar to those produced by oxygen radicals were also seen after experimental concussive brain injury or after acute hypertension. After brain injury, activation of phospholipase C and increased brain prostaglandin concentration were demonstrated. The vascular effects of brain injury and acute hypertension were inhibited by free radical scavengers. The results suggest that, in these conditions, vascular damage is induced by oxygen radicals generated from arachidonate in association with increased prostaglandin synthesis.
Airways Obstruction in Children

Airways obstruction in children may present acutely, dramatically and fatally, but more commonly has a gradual onset with chronic or progressive symptoms. General principles underpinning the major considerations will be reviewed. The lesions that cause airways obstruction in children are briefly outlined.
Total Body Handling of Bilirubin

In a symposium at which Professor Rudi Schmid has given an elegant overview of bilirubin metabolism, and at which each individual step in the production and disposition of bilirubin has been or will be the subject of a detailed presentation by an equally distinguished expert, I am at somewhat of a loss as to the proper content of a talk covering “Total Body Handling of Bilirubin”. I believe it may be most helpful if I introduce the concept of clearance, already familiar to you in the context of renal disease, and indicate the value of measurements of bilirubin clearance in the evaluation of the patient with hyperbilirubinemia.
Onychomys leucogaster (Northern grasshopper mouse)

Specimens collected by Mr. James L. Patton in Vernon, Texas, USA. Lung cultures were used for karyological studies.
Gauss's law for networks directly reveals community boundaries.

The study of network topology provides insight into the function and behavior of physical, social, and biological systems. A natural step towards discovering the organizing principles of these complex topologies is to identify a reduced network representation using cohesive subgroups or communities. This procedure often uncovers the underlying mechanisms governing the functional assembly of complex networks. A community is usually defined as a subgraph or a set of nodes that has more edges than would be expected from a simple, null distribution of edges over the graph. This view drives objective such as modularity. Another perspective, corresponding to objectives like conductance or density, is that communities are groups of nodes that have extremal properties with respect to the number of internal edges and cut edges. Here we show that identifying community boundaries rather than communities results in a more accurate decomposition of the network into informative components. We derive a network analog of Gauss’s law that relates a measure of flux through a subgraph’s boundary to the connectivity among the subgraph’s nodes. Our Gauss’s law for networks naturally characterizes a community as a subgraph with high flux through its boundary. Aggregating flux over these boundaries gives rise to a Laplacian and forms the basis of our “Laplacian modularity” quality function for community detection that is applicable to general network types. This technique allows us to determine communities that are both overlapping and hierarchically organized.
Development of a 3D, networked multi-user virtual reality environment for home therapy after stroke

Impairment of upper extremity function is a common outcome following stroke, to the detriment of lifestyle and employment opportunities. Yet, access to treatment may be limited due to geographical and transportation constraints, especially for those living in rural areas. While stroke rates are higher in these areas, stroke survivors in these regions of the country have substantially less access to clinical therapy. Home therapy could offer an important alternative to clinical treatment, but the inherent isolation and the monotony of self-directed training can greatly reduce compliance. We developed a 3D, networked multi-user Virtual Environment for Rehabilitative Gaming Exercises (VERGE) system for home therapy. Within this environment, stroke survivors can interact with therapists and/or fellow stroke survivors in the same virtual space even though they may be physically remote. Each user’s own movement controls an avatar through kinematic measurements made with a low-cost, Kinect™ device. The system was explicitly designed to train movements important to rehabilitation and to provide real-time feedback of performance to users and clinicians. To obtain user feedback about the system, 15 stroke survivors with chronic upper extremity hemiparesis participated in a multisession pilot evaluation study, consisting of a three-week intervention in a laboratory setting. For each week, the participant performed three one-hour training sessions with one of three modalities: 1) VERGE system, 2) an existing virtual reality environment based on Alice in Wonderland (AWVR), or 3) a home exercise program (HEP). Over 85% of the subjects found the VERGE system to be an effective means of promoting repetitive practice of arm movement. Arm displacement averaged 350 m for each VERGE training session. Arm displacement was not significantly less when using VERGE than when using AWVR or HEP. Participants were split on preference for VERGE, AWVR or HEP. Importantly, almost all subjects indicated a willingness to perform the training for at least 2–3 days per week at home. Multi-user VR environments hold promise for home therapy, although the importance of reducing complexity of operation for the user in the VR system must be emphasized. A modified version of the VERGE system is currently being used in a home therapy study.
Musculoskeletal Ultrasound in Treating and Preventing Upper Extremity Injuries in Young Athletes

Musculoskeletal ultrasound in sports medicine has been gaining use over the past decade. On site ultrasound can serve to make a timely and accurate diagnosis and facilitate early treatment in youth athletes with upper extremity injuries. Musculoskeletal ultrasound offers a variety of benefits over other investigative diagnostic tools including the lack of ionizing radiation when evaluating young athletes, the ability to dynamically evaluate the athlete, rapid comparison imaging of the non-injured extremity, and the ease of portability. Ultrasound is useful in detecting subtle pathology of the more superficial structures including tendons and nerves. Dynamic evaluation of these structures allows for accurate assessment of instability or subluxation. The main disadvantages of ultrasound include the limited field of view, restriction of imaging related to bony barriers, and lack of resolution of deeper structures. This chapter aims to provide an overview of musculoskeletal ultrasound use of the upper extremity when evaluating and treating young injured athletes. Continued advancements in the field of musculoskeletal ultrasound are needed in order to integrate ultrasound use into the routine care of the young athlete with an injury to the upper extremity.
Simulation-Based Multi-Objective Optimization of institutional building renovation considering energy consumption, Life-Cycle Cost and Life-Cycle Assessment

Buildings are responsible for a significant amount of energy consumption resulting in a considerable negative environmental impact. Therefore, it is essential to decrease their energy consumption by improving the design of new buildings or renovating existing buildings. Heat losses or gains through building envelopes affect the energy use and the indoor condition. Heating, Ventilation, and Air Conditioning (HVAC) and lighting systems are responsible for 33% and 25% of the total energy consumption in office buildings, respectively. However, renovating building envelopes and energy consuming systems to lessen energy losses is usually expensive and has a long payback period. Despite the significant contribution of research on optimizing energy consumption, there is limited research focusing on the renovation of existing buildings to minimize their Life Cycle Cost (LCC) and environmental impact using Life Cycle Assessment (LCA). This paper aims to find the optimal scenario for the renovation of institutional buildings considering energy consumption and LCA while providing an efficient method to deal with the limited renovation budget. Different scenarios can be compared in a building renovation strategy to improve energy efficiency. Each scenario considers several methods including the improvement of the building envelopes, HVAC and lighting systems. However, some of these scenarios could be inconsistent and should be eliminated. Another consideration in this research is the appropriate coupling of renovation scenarios. For example, the HVAC system must be redesigned when renovating the building envelope to account for the reduced energy demand and to avoid undesirable side effects. A genetic algorithm (GA), coupled with an energy simulation tool, is used for simultaneously minimizing the energy consumption, LCC, and environmental impact of a building. A case study is developed to demonstrate the feasibility of the proposed method.
Exploring probation officer styles and goals with individual, organizational, and social characteristics:

Probation offices are organizational units that provide the structure necessary to develop shared meaning systems that influence individual level attitudes, values, and beliefs. We analyze survey r...
Interest-enhancing approaches to mathematics curriculum design: Illustrations and personalization

Two common interest-enhancement approaches in mathematics curriculum design are illustrations and personalization of problems to students’ interests. The objective of these experiments is to test a...
Prepubertal Bleeding as a Presenting Symptom of Von Willebrand Disease: A Case Report.

Abstract Background Von Willebrand disease (VWD) affects approximately 1% of the population and is often diagnosed after the presentation of mucocutaneous bleeding. Case A 7-year-old girl with eczema and constipation presented to clinic reporting vaginal bleeding. External genital examination findings were normal, and results of a workup for precocious puberty were negative. Vaginoscopy revealed an atypical appearance with increased vascularity and friability. Oral mucosal bleeding at the time of extubation prompted additional workup and hematology referral, which led to diagnosis of type I VWD. Summary and Conclusion It is important to keep bleeding disorders on the differential, for unexplained prepubertal vaginal bleeding, to aid in prompt diagnosis.
The Common Carrier Privacy Model

The Federal Communications Commission (“FCC”), in its landmark and controversial “network neutrality” 2015 Open Internet Order, prohibited internet service providers, such as Comcast and Verizon, from discriminating against non-affiliated content-providers. In doing so, the FCC relied upon the Communications Act of 1934’s section 201’s “common carrier” jurisdiction. While section 201 gives the FCC vast power to curb anti-competitive network practices, section 201 also permits the FCC to regulate common carriers’ privacy policies. Specifically, section 201 allows imposition of the duty not to disclose the content of messages entrusted to carriers and gives individuals rights to recover upon breach. This Article is the first modern examination of section 201 privacy obligations — which have been largely forgotten since the late nineteenth century. Recent court decisions have ruled that the FCC’s common carrier jurisdiction preempts the Federal Trade Commission’s (“FTC’s”) jurisdiction over internet firms, giving common carrier privacy sudden policy prominence. Because common carrier privacy gives individuals the option to protect the confidentiality of messages and the right to recover damages upon breach, common carriage privacy contrasts with dominant top-down approaches to privacy, such as the Health Insurance Portability and Accountability Act (“HIPAA”) and the Fair Credit Reporting Act (“FCRA”), in which regulators determine what information receives protection and on what terms. Studies consistently show that consumers typically neither know nor appreciate their rights under these privacy regimes. In this way, forgotten common carrier privacy offers a new set of both practical and theoretical tools.
The Gender Gap in Sex Offender Punishment

This paper tests theoretical arguments that suggest court actors hold gendered views of sex offenders that result in a gender gap in sex offender punishment, where women who commit sexual offenses are treated more leniently than their male counterparts. We test this argument with precision matching analyses using 15 years of data on all felony sex offenders sentenced in a single state. Results indicate that gender disparities in sex offender sentencing exist and are pervasive across sex offense types. Specifically, male sex offenders are more likely to be sentenced to prison, and given longer terms, than female sex offenders. Findings are similar across sex offense severity and whether the offense involved a minor victim. These findings suggest that female sex offenders are treated more leniently than their matched male counterparts, even in instances of more serious sex offenses and those involving minor victims. Findings support theoretical arguments that contend that court decision-making is influenced by legally-irrelevant characteristics and raise questions about the source of gendered views of sex offenders and their effects on punishment approaches. Findings also raise questions about the virtue of get-tough sentencing policies that provide leeway for such dramatic variation across different groups of people.
Synthesis of hydroxyethylene dipeptide isosteres that mimic A cyclic amino acid at the P1' subsite

Abstract Addition of a cyclic allylsilane to N-protected α-amino aldehydes in the presence of a Lewis acid affords the corresponding (S)-homoallylic alcohols. Elaboration to the cyclic hydroxyethylene isosteres is described.
GP111 Incident reporting and the non-consultant hospital doctor in a general hospital

Aim and background Incident reporting though poorly named is one of the pillars are of patient safety. Non-Consultant Hospital Doctors (NCHDs), while actively involved in patient care contribute minimally to incident reporting overall. This study evaluated NCHD knowledge of the incident reporting process and undertook an education module Methods All NCHDS at Mayo University Hospital were invited to participate. Three scenarios were devised, reflective of actual cases, in conjunction with the authors and the quality improvement department. These cases were weighed and considered by the NCHD committee to ascertain clinical relevance for the trainees. A formal small group 30-minute instructional lecture with case discussion and actual case inputting was developed lead by the quality improvement team. Pre and post-test questionnaires on the reporting process were devised that had a direct relevance and trainee perceptions on the training process and barriers to reporting were elicited through thematic evaluation of the post training discussions which were recorded. Results Forty (48%) trainees volunteered 23 SHO and 17 Registrars. The mean knowledge scores were 52 pre-test and 67 post-test. Trainees uniformly enjoyed being ‘walked through’ the reporting process and actually having a test opportunity to complete made it more real. Thematic evaluation suggest that trainees are not clear as to what constitutes an incident, have misconceptions of the incident reporting process and operate in an environment that is not conducive to reporting. Patient safety and incident reporting are not viewed as being interconnected. Conclusions This educational module enhanced trainee knowledge, corrected misperceptions on its role and suggests that they are more likely to report on clinical incidents. The reporting tool, however, is not geared to the end user which is a hinderance in reporting and the language used facilitates a negative connotation.
OBJECTIVELY MEASURED SLEEP CHARACTERISTICS OF OLDER ADULTS WITH AND WITHOUT ALZHEIMER’S DISEASE

This is a pre-copyedited, author-produced version of an article accepted for publication in Innovation in Aging following peer review. The version of record Laffer, A., Hicks, H. J., Losinski, G., & Watts, A. (2019). OBJECTIVELY MEASURED SLEEP CHARACTERISTICS OF OLDER ADULTS WITH AND WITHOUT ALZHEIMER’S DISEASE. Innovation in Aging, 3(Suppl 1), S1–S2. https://doi.org/10.1093/geroni/igz038.002 is available online at: https://doi.org/10.1093/geroni/igz038.002. This work is licensed under a Creative Commons Attribution 4.0 International License.
Ethnic Differences in Hematologic Toxicity from Imatinib in Patients with Gastrointestinal Stromal Cell Tumor (GIST): Coincidence or a Real Phenomenon.

Objectives There is a wide variability in the pharmacokinetics, pharmacodynamics and tolerance of anticancer drugs based on ethnicity. GIST is a rare cancer, (~1% of GI cancers). Imatinib is used in the neo-adjuvant, adjuvant and metastatic setting. The purpose of this study was to report the difference in hematologic toxicities to imatinib among different ethnicities when treated for GIST either in the adjuvant or metastatic setting. Methods We performed a retrospective study to collect data on patients with GIST (in any stage), who were on imatinib and presenting with grade 2 or more anemia, neutropenia and/or thrombocytopenia from July 1, 2005 to January 31, 2018. The degree of cytopenia was graded as per National Cancer Institute Common Toxicity criteria; version 4.0. We collected included age, gender, ethnicity, pathology, adverse effects-hematologic and non-hematologic, management of toxicities including dose modifications and administration of pegfilgrastim. Results Among 57 patients (median age 61 years, M: F=41:16 (F); ethnicities: White 65%, African-American (AA 19%, Asian 12% and Hispanic 4%), neutropenia (Grade 3 & 4) was seen in 6 patients (10%): 5 AA and 1 Asian. 45% of all AA patients developed neutropenia. Median absolute neutrophil count (ANC) nadir was 700/μL, median duration on drug prior to onset of neutropenia was 4.5 weeks and median duration of neutropenia was 4 weeks. One patient developed febrile neutropenia. Dose interruptions were needed in 3, dose-reductions in all patients, and 3 patients required pegfilgrastim. One patient had to discontinue imatinib, while one patient was escalated back to 400mg daily dose. Conclusion This is the first study to examine ethnic variations in myelosuppression following imatinib in patients with GIST.
Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells and protects against liver fibrosis

Abstract Background and Aims Liver fibrosis develops in the context of excessive oxidative stress, cell death and accumulation of myofibroblasts (MFs) derived from hepatic stellate cells (HSCs). Ferroptosis is a type of regulated cell death that can be caused by inhibiting the cystine/glutamate antiporter xCT. However, while xCT is induced in various liver diseases, its role in HSC activation and liver fibrosis is unknown. We hypothesized that xCT is required for HSCs to antagonize ferroptosis and remain myofibroblastic. Methods xCT activity was disrupted by siRNA or pharmacological inhibitors in MF-HSC cell lines to determine its effect on redox homeostasis, growth, myofibroblastic activity and viability. xCT expression was then determined by RNA sequencing and RT-PCR during primary HSC activation, and its role in HSC trans-differentiation was assessed. For comparison, xCT expression and function were also determined in primary hepatocytes. Finally, the roles of xCT in HSC accumulation and liver fibrosis were assessed in mice treated acutely with CCl4. Results Inhibiting xCT in MF-HSCs decreased intracellular glutathione (GSH), suppressed growth and fibrogenesis, and induced cell death. These effects were rescued by antioxidants, an iron chelator, and a canonical ferroptosis inhibitor, but not by inhibitors of apoptosis or necrosis. xCT was dramatically up-regulated during primary HSC activation, and inhibiting xCT suppressed myofibroblastic trans-differentiation and induced ferroptosis. In contrast, healthy hepatocytes were relatively insensitive to ferroptosis induced by xCT inhibition. In vivo, inhibiting xCT systemically reduced MF-HSC accumulation and liver fibrosis after a single dose of CCl4 without exacerbating liver injury or reducing hepatocyte regeneration. Conclusion Compared to healthy hepatocytes, MF-HSCs are exquisitely sensitive to ferroptosis induced by inhibiting xCT. In acutely injured livers, systemic inhibitors of xCT can inhibit fibrosis without worsening liver injury. Further research is needed to determine if this therapeutic window remains sufficiently robust to safely target MF-HSCs and inhibit fibrogenesis in chronically injured liver.
Introduction to the practice of adult genetics

Abstract Many genetic disorders do not manifest until adulthood and multiple genetic factors may interact with multiple environmental factors over an individual’s lifespan to produce a clinical phenotype. Likewise, with earlier diagnosis and improvements in management, many individuals with congenital or childhood-onset conditions are now surviving into adulthood and seeking to transition their genetic care to an adult setting. Hence, the practice of adult genetics has emerged and continues to evolve.
Molecular changes in transcription and metabolic pathways underlying muscle atrophy in the CuZnSOD null mouse model of sarcopenia

Mice lacking the superoxide anion scavenger CuZn superoxide dismutase (Sod1−/− mice) develop a number of age-related phenotypes, including an early progression of muscle atrophy and weakness (sarcopenia) associated with loss of innervation. The purpose of this study was to delineate the early development of sarcopenia in the Sod1−/− mice and to measure changes in the muscle transcriptome, proteome, and eicosanoid profile at the stage when sarcopenia is markedly induced in this model (7–9 months of age). We found a strong correlation between muscle atrophy and mitochondrial state 1 hydroperoxide production, which was 40% higher in isolated mitochondria from Sod1−/− mouse gastrocnemius muscle by 2 months of age. The primary pathways showing altered gene expression in Sod1−/− mice identified by RNA-seq transcriptomic analysis are protein ubiquitination, synaptic long-term potentiation, calcium signaling, phospholipase C signaling, AMPK, and TWEAK signaling. Targeted proteomics shows elevated expression of mitochondrial proteins, fatty acid metabolism enzymes, tricarboxylic acid (TCA) cycle enzymes, and antioxidants, while enzymes involved in carbohydrate metabolism are downregulated in Sod1−/− mice. LC-MS analysis of lipids in gastrocnemius muscle detected 78 eicosanoids, of which 31 are significantly elevated in muscle from Sod1−/− mice. These data suggest that mitochondrial hydroperoxide generation is elevated prior to muscle atrophy and may be a potential driving factor of changes in the transcriptome, proteome, and eicosanoid profile of the Sod1−/− mice. Together, these analyses revealed important molecular events that occur during muscle atrophy, which will pave the way for future studies using new approaches to treat sarcopenia.
Ex Vivo Expansion of Adult Hematopoietic Stem and Progenitor Cells with Valproic Acid

Umbilical cord blood (UCB) units provide an alternative source of human hematopoietic stem cells (HSCs) for patients who require allogeneic stem cell transplantation but lack a matched donor. However, the limited number of HSCs within each UCB unit remains a major challenge for their use in regenerative medicine and HSC transplantation in adults. Efficient expansion of human HSCs in ex vivo cultures initiated with CD34+ cells isolated from UCBs can overcome this limitation. The method described here utilizes a deacetylase inhibitor, valproic acid (VPA), to rapidly expand to a high degree the numbers of functional HSCs and committed progenitors (HPCs). The expanded HSCs are capable of establishing both short-term and long-term multilineage hematopoietic reconstitution. This highly reproducible and simple protocol can be also applied to expansion of both HSCs and HPCs from different sources including the bone marrow and peripheral blood.
Learning to Read: Successful Program-Based Remediation Using the Surgical Council on Resident Education (SCORE) Curriculum.

Background The Surgical Council on Resident Education (SCORE) curriculum is aligned with the American Board of Surgery (ABS) objectives. Our program adopted the SCORE curriculum in 2015 after poor ABS In-Training Examination (ABSITE) performance and lowest quartile ABS Certifying Exam (CE) and Qualifying Exam (QE) first-time pass rates. We examined the association of SCORE use with ABSITE performance and ABS board exam first-time pass rate. Study design At a single institution, a retrospective review of surgery residents’ SCORE metrics and ABSITE percentile was conducted for academic years 2015 to 2019. Metrics analyzed on the SCORE web portal were mean total minutes and total visits per resident for all residents using SCORE that year. First-time pass rates of the ABS QE and CE were examined from 2013 to 2019. Chi-square and linear regression analysis were performed, and a 95% level of confidence was assumed (alpha = 0.05). Results Yearly data from categorical general surgery residents showed a significant increase in total minutes, total visits, and ABSITE percentile. Combined first time pass rates for the ABS QE and CE significant increased from 70.8% in 2013 to 2015 to 93.9% in 2016 to 2019 (p = 0.018). Conclusions Increased longitudinal use of the SCORE curriculum was associated with programmatic improvements in ABSITE performance and ABS board exam first-time pass rate.
Huawei Goes to India: Can the Dragon and the Elephant Marry?

Huawei is not yet a major player in India’s competitive smartphone market. The company has a low-end brand, called the “Honor” brand in India, and they expect that the Indian smartphone market will use Huawei brand for high-end devices. Both brands had a combined market share of 3.4 percent in 2018. Huawei, by the end of 2018, has chartered out a three-year plan for the Indian market through its dual-brand strategy, backed by investments of over $100 million starting from 2019 with an expansion of local manufacturing activities. Will this global telecom giant become a major player in India? The current chapter explores the issue in light of the Sino-India relationship and the alleged security issues related to Huawei.
Long-Distance Dermatology: Lessons From an Interview on Remote Practice During a Pandemic and Beyond

The COVID-19 pandemic resulted in profound changes to most facets of medical practice. The field of dermatology has adapted by rapidly incorporating teledermatology as a means of evaluating, treating, and staying connected with our patients. Broader dermatology access, convenience to patients, and value to payers are benefits to this rapidly evolving practice model and suggest that teledermatology will be a part of day-to-day practice even as the worst of the pandemic is behind us. This interview provides one recent dermatology resident graduate's experiences incorporating teledermatology into his practice model and provides advice for future residents on preparing to do the same.
Body Vandalism: Lady Gaga, Disability, and Popular Culture

This essay investigates the employment of disability by the pop star Lady Gaga. Working through different illustrations of disability in her videos it is argued that Lady Gaga ushers in a new aesthetic and political platform on which disability can be redefined. In particular, the author argues that Lady Gaga unconsciously performs within the space of what Siebers has named a disability aesthetic in which the different bodies reformulate the expectations and desires of the art object. The context of popular culture is explained as a necessary component of this reframing.
Common sense based joint training of human activity recognizers

Given sensors to detect object use, commonsense priors of object usage in activities can reduce the need for labeled data in learning activity models. It is often useful, however, to understand how an object is being used, i.e., the action performed on it. We show how to add personal sensor data (e.g., accelerometers) to obtain this detail, with little labeling and feature selection overhead. By synchronizing the personal sensor data with object-use data, it is possible to use easily specified commonsense models to minimize labeling overhead. Further, combining a generative common sense model of activity with a discriminative model of actions can automate feature selection. On observed activity data, automatically trained action classifiers give 40/85% precision/recall on 10 actions. Adding actions to pure object-use improves precision/recall from 76/85% to 81/90% over 12 activities.
Chromatography of alkylating agents: I. Aziridines, nitrogen and sulfur mustards and related derivatives

Abstract We have attempted to stress the major areas of diverse chromatographic procedures for the analyses of a broad spectrum of alkylating agents and related derivatives. Chromatographic analyses have played a singularly important role in the elaboration of compound homogeneity, metabolism, degradation and mode of action of these agents. This aspect is to importance in the light of the anticipated increase in the utility of a variety of alkylating agents, e.g. , chemosterilant aziridines.
A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain.

Abstract Study Objective: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. Methods: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. Results: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. Conclusion: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain. [Dribben WH, Kirk MA, Trippi JA, Cordell WH. A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain. Ann Emerg Med. July 2001;38:42-48.]
Tailored domain patterns in piezoelectric crystals

Twinning is generally considered to be a nuisance which degrades the performance of piezoelectric oscillators, but this need not be so. Domain configurations can be designed to enhance certain modes of motion, or to eliminate others. Experiments on crystals of gadolinium molybdate and lead germanate have been performed to demonstrate the feasibility of the tailored-domain concept. Multi-domain crystals and ceramics can also be used as high-frequency resonators and as focused acoustic tranducers. Es wird allgemein angenommen, das Zwillingsbildung einen unerwunschten Effekt darstellt, der das Betriebsverhalten piezoelektrischer Oszillatoren beeintrachtigt, jedoch braucht dies nicht so zu sein. Domanenkonfigurationen lassen sich so entwerfen, das sie bestimmte Bewegungsmoden verstarken oder andere eliminieren. Experimente an Gadoliniummolybdat- und Bleigermanat-Kristallen werden durchgefuhrt, um die Brauchbarkeit eines Konzepts mit „geschneiderten” Domanen zu zeigen. Multi-Domanen-Kristalle und -Keramiken lassen sich auch als Hochfrequenz-Resonatoren und als fokussierte akustische Wandler benutzen.