cssi/SciSciGPT-SciSciNet huggingface dataset:
Design optimization for a wearable, gamma-ray and neutron sensitive, detector array with directionality estimation

Abstract In this study, we report on a constrained optimization and tradeoff study of a hybrid, wearable detector array having directional sensing based upon gamma-ray occlusion. One resulting design uses CLYC detectors while the second feasibility design involves the coupling of gamma-ray-sensitive CsI scintillators and a rubber LiCaAlF 6 (LiCAF) neutron detector. The detector systems’ responses were investigated through simulation as a function of angle in a two-dimensional plane. The expected total counts, peak-to-total ratio, directionality performance, and detection of 40 K for accurate gain stabilization were considered in the optimization. Source directionality estimation was investigated using Bayesian algorithms. Gamma-ray energies of 122 keV, 662 keV, and 1332 keV were considered. The equivalent neutron capture response compared with 3 He was also investigated for both designs.
Digital versus conventional implant impressions for partially edentulous arches: An evaluation of accuracy

Abstract Statement of problem To the authors' knowledge, while accuracy outcomes of the TRIOS scanner have been compared with conventional impressions, no available data are available regarding the accuracy of digital scans with the Omnicam and True Definition scanners versus conventional impressions for partially edentulous arches. Purpose The purpose of this in vitro study was to compare the accuracy of digital implant scans using 2 different intraoral scanners (IOSs) with that of conventional impressions for partially edentulous arches. Material and methods Two partially edentulous mandibular casts with 2 implant analogs with a 30-degree angulation from 2 different implant systems (Replace Select RP; Nobel Biocare and Tissue level RN; Straumann) were used as controls. Sixty digital models were made from these 2 definitive casts in 6 different groups (n=10). Splinted implant-level impression procedures followed by digitization were used to produce the first 2 groups. The next 2 groups were produced by digital scanning with Omnicam. The last 2 groups were produced by digital scanning with the True Definition scanner. Accuracy was evaluated by superimposing the digital files of each test group onto the digital file of the controls with inspection software. Results The difference in 3-dimensional (3D) deviations (median ±interquartile range) among the 3 impression groups for Nobel Biocare was statistically significant among all groups ( P P =.003), except for the conventional impression (22 ±5 μm) and True Definition (17 ±5 μm) groups; the median ±interquartile range for the Omnicam group was 26 ±15 μm. The difference in 3D deviations between the 2 implant systems was significant for the Omnicam ( P =.011) and conventional ( P P =.247). Conclusions Within the limitations of this study, both the impression technique and the implant system affected accuracy. The True Definition technique had the fewest 3D deviations compared with the other 2 techniques; however, the accuracy of all impression techniques was within clinically acceptable levels, and not all differences were statistically significant.
Managing technical professionals: Speaking freely

Providing an atmosphere, to our employees to speak freely, is an important job of the manager and leader of an organization. Though this sounds obvious, and most of us might think that we are open to feedback and that our employees come to us and tell us things, it is highly likely that there are at least a few people in the organization who will not question decisions and make suggestions for a variety of reasons: They may not feel like they know the manager and therefore don’t feel comfortable speaking-up, they may fear the consequences of speaking up—fear of demotion, fear of losing their job-, they may not think their feedback would make a difference, they might think their feedback will offend the leader and that their comment would be perceived as disrespectful, they might think that their feedback is so silly that might look like a fool in front of a group of people. Whatever the reasons might be, understanding them is the first step in trying to address them, knowing full well that getting everyone in the organization to be able to speak freely is in many cases a futile effort. This, however, should not stop us from making the effort because in organizations where employees are able to freely voice their opinions retention levels and the performance of the organization are better.
Enhancing Patient Safety through the Use of a Pharmaceutical Glass Designed To Prevent Cracked Containers.

An essential role of packaging material for the storage and delivery of drug products is to provide adequate protection against contamination and loss of sterility. This is especially important for parenteral containers, as lack of sterility or contamination can result in serious adverse events including death. Nonetheless, cracked parenteral containers are an important source of container integrity failures for injectable drugs and pose a serious risk for patients. Despite significant investments in inspection technology, each year many injectable drugs are investigated and recalled for sterility risks associated with cracked borosilicate containers. Multiple studies and the many difficulties in detection of cracked containers suggest that the magnitude of the public health risk is even larger than the recall rate would suggest. Here we show that the root cause of cracked parenteral containers (low internal energy following annealing) is inherent to the glasses currently used for primary packaging of the majority of injectable drugs. We also describe a strengthened aluminosilicate glass that has been designed to prevent cracks in parenteral containers through the use of an engineered stress profile in the glass. Laboratory tests that simulate common filling line damage events show that the strengthened aluminosilicate glass is highly effective at preventing cracks. Significant safety benefits have been demonstrated in other industries from the use of special stress profiles in glass components to mitigate failure modes that may result in harm to humans. Those examples combined with the results described here suggest that a significant improvement in patient safety can be achieved through the use of strengthened aluminosilicate glass for parenteral containers.
Dialysis Dependence Predicts Complications, Intensive Care Unit Care, Length of Stay, and Skilled Nursing Needs in Elective Primary Total Knee and Hip Arthroplasty

Abstract Background Limited data describe risks and perioperative resource needs of total joint arthroplasty (TJA) in dialysis-dependent patients. Methods Retrospective multiple cohort analysis of dialysis-dependent American College of Surgeons National Surgical Quality Improvement Program patients undergoing primary elective total hip and knee arthroplasty compared to non–dialysis-dependent controls from 2005 to 2015. Relative risks (RRs) of 30-day adverse events were determined by multivariate regression adjusting for baseline differences. Results Six hundred forty-five (0.2%) dialysis-dependent patients of 342,730 TJA patients were dialysis-dependent and more likely to be dependent, under weight, anemic, hypoalbuminemic, and have cardiopulmonary disease. In total hip arthroplasty patients, dialysis was associated with greater risk of any adverse event (RR = 1.1, P Conclusion Dialysis-dependence is an independent risk factor for 30-day adverse events, ICU care, longer admission, and rehabilitation needs in TJA patients. Thirty days is not sufficient to detect infectious complications among these patients. These findings inform shared decision-making, perioperative resource planning, and risk adjustment under alternative reimbursement models.
Relating Stool Microbial Metabolite Levels, Inflammatory Markers and Dietary Behaviors to Screening Colonoscopy Findings in a Racially/Ethnically Diverse Patient Population.

Colorectal cancer (CRC) is the third leading cause of cancer death for both men and women in the United States, yet it is treatable and preventable. African Americans have higher incidence of CRC than other racial/ethnic groups, however, it is unclear whether this disparity is primarily due to environmental or biological factors. Short chain fatty acids (SCFAs) are metabolites produced by bacteria in the colon and are known to be inversely related to CRC progression. The aim of this study is to investigate how stool SCFA levels, markers of inflammation in stool and dietary intake relate to colonoscopy findings in a diverse patient population. Stool samples from forty-eight participants were analyzed for SCFA levels and inflammatory markers (lysozyme, secretory IgA, lactoferrin). Additionally, participants completed the National Cancer Institute’s Diet History Questionnaire II (DHQ II) to report dietary intake over the past year. Subsequently, the majority of participants underwent screening colonoscopy. Our results showed that African Americans had higher total levels of SCFAs in stool than other racial/ethnic groups, significantly lower intake of non-starchy vegetables and similar inflammatory marker expression and colonoscopy outcomes, compared to others. This work is an initial exploration into the biological and clinical factors that may ultimately inform personalized screening approaches and clinical decision-making to improve colorectal cancer disparities for African Americans.
Use of EOS Low-Dose Biplanar X-Ray for Shunt Series in Children with Hydrocephalus: A Preliminary Study.

Introduction Shunt series (SS) are a common diagnostic tool used to verify shunt integrity. SS include X-ray films of the skull, chest, and abdomen and often are performed either when a shunted patient presents with suspected shunt malfunction or as a screening test to identify shunt disconnections or dislodgment. EOS low-dose biplanar X-rays are associated with significantly reduced radiation doses compared with ordinary X-rays and are used for various indications. This is the first publication on the use of EOS as a SS technique. Methods Over a period of 6 months, EOS were performed at our center for various orthopedic indications, mostly for scoliosis evaluation. Nine children ( Results Three patients had bilateral shunts, and 8 had previous X-rays for comparison. In all patients, the shunt integrity was easily demonstrated on the EOS images. Two patients had an identified shunt disconnection confirmed on the EOS images. No shunt-related information was missed on the EOS compared with the other X-ray images. Conclusions These preliminary results suggest that EOS may be used as an alternative technology to demonstrate shunt integrity instead of regular X-ray SS. Favorable shunt visibility without the need for multiple radiation exposures and image processing (such as stitching) results in a significantly shorter examination time and significant less radiation.
A −80dBm BLE-compliant, FSK wake-up receiver with system and within-bit dutycycling for scalable power and latency

This paper presents an FSK wake-up receiver with a −80 dBm sensitivity using a packet structure and a duty cycling scheme compliant with the Bluetooth Low Energy (BLE) protocol trading off power with latency. Event-driven applications achieve power lower than 240nW from a 0.75V supply while latency-critical systems wake up in almost 200μ« at a 230μW consumption. A within-bit LC oscillator duty-cycling scheme is proposed to provide an extra 24% power reduction. Additionally, a custom FSK transmitter can trigger wake-up at 17nW only for an average latency of 5 seconds.
Induction and regulation of interleukin-8 gene expression

A variety of disease states are characterized by a significant infiltrate of polymorphonuclear leukocytes. These acute disorders can range from immune complex-mediated inflammation, such as glomerulonephritis and rheumatoid arthritis, to more enigmatic diseases (e.g. adult respiratory distress syndrome and psoriasis). An interesting aspect of many acute inflammatory reactions is the infiltrate that occurs during the initial reaction is nearly a pure population of neutrophils. If the inflammatory reaction persists, the histological picture evolves into a heterogeneous population of immune cells. Therefore, the recruitment of cells from the vascular compartment to the inflammatory lesion is a dynamic process and changes as the immune response evolves. This characteristic of an inflammatory lesion is a good example of the host’s ability to synthesize specific agents, which can elicit specific white blood cells, at specific time intervals of an inflammatory response.
ISDB: a database toolkit for storing and analyzing viral integration site data.

Summary We introduce ISDB, a set of software tools for the creation and administration of relational databases of viral integration site (IS) data. Using ISDB, investigators can curate a private database from any heterogeneous set of data sources, including previously-published datasets and internal, work-in-progress data. To make data visible and accessible to collaborators with varying degrees of computational expertise, ISDB automatically generates web sites describing database contents and data exports in several common formats. Compared to a public depository database, the ability to build local, private databases makes ISDB suitable for use in testing hypotheses and developing analyses in the long pre-publication phase of most research. Availability and implementation Installation and usage documentation for ISDB are provided on our website https://mullinslab.microbiol.washington.edu/isdb/. Source code is available under the open source MIT license from https://github.com/MullinsLab/ISDB. Supplementary information Supplementary data are available at Bioinformatics online.
Archaeological Research on the Early Post-Contact Period at Miloli‘i, Kaua’i, Hawaiian Islands

Our recent archaeological research project in Miloli‘i, Kaua‘i, focuses on the investigation of intra-island diversity in the Hawaiian Islands. We ask how settlements in hinterlands such as Miloli‘...
Flow Compensation with Oxygen Equilibrium Curve Shifts

Publisher Summary This chapter discusses flow compensations with oxygen equilibrium curve (OEC) shifts. Oxygen transfer from the blood to tissue depends upon the oxygen pressure gradient. Direct measurements indicate that tissue PO2 values vary considerably throughout a tissue with some values approaching the arterial PO2 and others lying close to zero. This heterogeneity reflect the varying distances of measuring sites from capillaries and local variation in capillary perfusion and tissue oxygen consumption. There is little information regarding the relationship between the normal oxygen pressure profile in tissue and the actual pressures necessary to sustain normal oxygenation. Oxygen delivery can be critically compromised by a left shift of the OEC. Alternately, it is possible that gas exchange is confined to the left half of the OEC, where oxygen pressures may appreciably exceed those required for adequate oxygen delivery to cells. Subsequently, OEC shifts form an ideal method for changing the PO2 profile in tissue as other methods—hypoxemia, anemia, ischemia, and carboxyhemoglobinemia alter total oxygen transport to tissue.
Imager-Based Characterization of Viscoelastic Material Properties

In this work we explore the use of emerging full-field, high-resolution, modal identification techniques from video to characterize the viscoelastic properties of a material. Currently, there are no cost-effective methods to directly measure viscoelastic material properties at intermediate strain rates. These properties can be measured at low strain rates using quasi-static loading techniques, while Split-Hopkinson’s bar tests are used at high strain rates. Determining material properties at the intermediate strain rate regime is challenging as it requires large, expensive testing apparatuses and involves complex experimental protocols. An imager-based technique would provide a simpler, more affordable method for measuring viscoelastic material properties at these strain rates. To obtain measurements for intermediate strain rates of viscoelastic materials, we develop a testing protocol that involves creating a simple structure from the material-under-test and measuring its vibrational response using an imager. A finite-element model of the viscoelastic testing structure is also constructed. We extract full-field, high resolution mode shapes and modal coordinates from the video measurements of the structure as it vibrates in the desired strain regime. The frequencies of oscillation and the damping ratios are then identified. This information is intended to be used to perform model updating on the viscoelastic material properties of the finite-element model, resulting in an improved estimate of the material properties. Imager-based techniques are particularly attractive for explosive testing applications because the optics can be adapted to address the small sample sizes necessary for explosive testing. In addition to advancing viscoelastic material modeling, this work points toward the development of an imager-based modal analysis technique for identifying the structural dynamics of micro-scale structures. At this small scale, conventional contact-based sensors would result in mass-loading effects, yielding inaccurate measurements. As a solution, our full-field, high-resolution imager-based technique provides a method to characterize viscoelastic material properties while also demonstrating potential for future work in identifying structural dynamics of micro-scale structures.
Real-world safety of pemetrexed, carboplatin, and pembrolizumab in U.S. NSCLC patients.

50Background: A Phase 3 KEYNOTE-189 clinical trial showed improved clinical benefit with acceptable toxicity of pemetrexed combined with pembrolizumab and platinum (Gandhi, 2018). However, the safe...
When it comes to Satisfaction … It depends: An empirical examination of social commerce users

Abstract Although reports on the success of social commerce indicate an astronomical growth in the next decade, understanding the complexities of the antecedents of its continuous use by consumers is limited. This study attempts to bridge this gap by using a mature IS continuance model in the social commerce context. The study also significantly extends this continuance model by theorizing and testing non-linear effects. The IS continuance model argues that all the links among confirmation, perceived usefulness, satisfaction, and continuance in the model are positive and linear. However, there is a strong theoretical basis to suggest that some relationships in the model are complex and non-linear, especially the antecedents and consequences of satisfaction. Perceived usefulness is modeled as a second order construct of social, hedonic, and utility benefits to more richly account for contexts relevant to making continuous use decisions for social commerce. Data from 531 current social commerce users provide support to our assertions. The results revealed quadratic relationships between perceived usefulness and satisfaction and between satisfaction and continuance use intentions. Perceived usefulness has a positive relationship with satisfaction for females and experienced social commerce users but an inverse-U relationship for males and inexperienced users. Satisfaction in turn has a positive relationship with continuance use intentions for females but an inverse-U relationship for males.
On the Transition to Attendinghood.

Medical education and training consists of a series of stepped transitions, each marked by increasing autonomy and responsibility. Perhaps the most formidable transition begins upon the completion of one’s training and stretches well into the first year of “attendinghood.” This period is often defined by colossal changes that can extend far beyond the workplace and that are largely inconceivable beforehand. These changes can have important implications for job satisfaction, well-being, and resilience, especially in oncology, where rates of work-related burnout are particularly high. Unfortunately there is no “standard of care” or evidence-based guideline on how best to approach this period. However, it must be highlighted and deliberately discussed among current fellows and recent graduates not only to stimulate further study but also to provide support and community for those approaching or going through this transition.
Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study.

Abstract Background The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time. Methods From a cohort of 128 subjects (Cohort A) with CT scans done 3–36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort). Results CTs were abnormal in 16% and 85% at 24–36 and 3–6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (−12.8); CTS II: Low density mass confined to pancreas (−9.5), CTS III: Peri-pancreatic infiltration (−5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04). Conclusion Starting 12–18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.
Experimental observations of exploding bridgewire detonator function

Exploding bridgewire detonators are an industry standard technology used for over 75 years and valued for their precise timing and safety characteristics. Despite widespread use, their functional mechanism remains controversial with both shock and non-shock mechanisms attributed. In this work, we reexamine the bridgewire detonator function with a suite of modern diagnostics and compare these observations with the existing literature. Traditional detonator observations consisted of voltage applied to the bridgewire and time dependent current, integral response measurements such as case motion, and more recently Schlieren imaging of the detonator surface. In this work, we add visible light emission, x-ray transmission, proton radiography, and temperature measurements during detonator function in addition to voltage, current, and function times. The addition of in situ observations of light emission, temperature, and density gives us new insight into the mechanisms of explosive bridgewire detonator function. We see a distinct separation in time, location, symmetry, and velocity of bridgewire output and detonation onset. During the time between bridgewire burst and the initiation of detonation, we observe a temperature ramp in the input pellet. In this paper, we present the suite of measurements and comparisons with the literature on integral response measurements.
Ureteral Arterial Fistula - A Role for Open Operation in the 21st Century.

Background Ureteral arterial fistula is a rare and challenging clinical entity. The diagnosis and management of ureteral arterial fistula present a unique disease process that requires a dual specialty approach, involving both vascular and urologic surgeons. There are different options for repair, including both open and endovascular techniques. Methods and Results A 78-year-old male presented to the emergency department (ED) in septic shock secondary to a urinary tract infection and was admitted to the intensive care unit (ICU) for further management and resuscitation. The patient had previously undergone radical cystoprostatectomy with ileal conduit creation in 2011 for recurrent bladder cancer. Following creation of his ileal conduit, he required long-term indwelling ureteral stents bilaterally due to recurrent stricturing at the ureteroneocystostomy with stent exchanges performed 2–3 times per year due to frequent urinary tract infections. During his hospitalization for sepsis, the urology service performed an exchange of his left indwelling ureteral stent. However, pulsatile bleeding was observed from the junction of the ileal conduit and left ureter. The stent was replaced at the bedside, and the bleeding ceased. Vascular surgery consultation and a computed tomography angiogram (CTA) gave support to the diagnosis of a ureteral arterial fistula. A plan was developed to exchange the stent in the operating room with vascular surgery assistance. It was determined that a definitive open repair with excision of the fistula would be the most appropriate course. Conclusions In the setting of hemodynamically significant bleeding, we recommend an endovascular approach to obtain hemostasis. However, an open approach provides both reconstruction and infectious resistance in an already soiled field. Open repair may provide a more definitive reconstruction.
Short-Term Low Back Pain Relief with Placebo.

Over three weeks, patients with long-term low back pain who knowingly took placebo twice a day reported less pain and disability than those continuing with treatment as usual.
Fundamental solutions for the Dirac equation in curved spacetime and generalized Euler-Poisson-Darboux equation

Abstract We present the fundamental solutions for the spin-1/2 fields propagating in spacetimes with power type expansion/contraction and the fundamental solution of the Cauchy problem for the Dirac equation. The derivation of these fundamental solutions is based on formulas for the solutions to the generalized Euler-Poisson-Darboux equation, which are obtained by the integral transform approach.
Nalmefene, a mu opioid receptor antagonist/kappa opioid receptor partial agonist, potentiates cocaine motivation but not intake with extended access self-administration in adult male mice

Abstract The mu opioid receptor antagonist/kappa opioid receptor (KOR) partial agonist nalmefene (NMF), a close structural analog of naltrexone (NTX), has been shown to reduce cocaine reward in preclinical models. Given the greater KOR potency and improved bioavailability compared to NTX, NMF may be a promising pharmacotherapeutic for cocaine use disorder (CUD). Here we examine the effects of NMF pretreatment on chronic daily extended access (4h) cocaine intravenous self-administration (IVSA) in adult male C57Bl/6J mice. Methods: separate groups of mice had daily 4h cocaine IVSA sessions (0.25 or 0.5 mg/kg/inf, FR1) for 14 days. Starting on day 8, mice were pretreated with NMF (0, 1, or 10 mg/kg) 30m before each session. A separate group of mice acquired cocaine IVSA [seven days FR1 then four FR3 of 4h daily sessions (0.5 mg/kg/inf)] prior to a single progressive ratio 3 session to examine the effect of 1 mg/kg NMF on cocaine motivation. Results: No significant effect of NMF pretreatment on cocaine intake was observed. Acute pretreatment of 1 mg/kg NMF significantly potentiated cocaine motivation as measured by progressive ratio breakpoint. Conclusions: NMF did not significantly attenuate cocaine intake and increased motivation for cocaine suggesting that NMF may not be suitable for non-abstinent CUD patients. Further research is needed with KOR selective partial or full agonists to determine their effect on cocaine reinforcement.
How the clinical research community responded to the COVID-19 pandemic: an analysis of the COVID-19 clinical studies in ClinicalTrials.gov

Objective In the past few months, a large number of clinical studies on the novel coronavirus disease (COVID-19) have been initiated worldwide to find effective therapeutics, vaccines, and preventive strategies for COVID-19. In this study, we aim to understand the landscape of COVID-19 clinical research and identify the issues that may cause recruitment difficulty or reduce study generalizability. Methods We analyzed 3765 COVID-19 studies registered in the largest public registry-ClinicalTrials.gov, leveraging natural language processing (NLP) and using descriptive, association, and clustering analyses. We first characterized COVID-19 studies by study features such as phase and tested intervention. We then took a deep dive and analyzed their eligibility criteria to understand whether these studies: (1) considered the reported underlying health conditions that may lead to severe illnesses, and (2) excluded older adults, either explicitly or implicitly, which may reduce the generalizability of these studies to the older adults population. Results Our analysis included 2295 interventional studies and 1470 observational studies. Most trials did not explicitly exclude older adults with common chronic conditions. However, known risk factors such as diabetes and hypertension were considered by less than 5% of trials based on their trial description. Pregnant women were excluded by 34.9% of the studies. Conclusions Most COVID-19 clinical studies included both genders and older adults. However, risk factors such as diabetes, hypertension, and pregnancy were under-represented, likely skewing the population that was sampled. A careful examination of existing COVID-19 studies can inform future COVID-19 trial design towards balanced internal validity and generalizability.
Fostering climate change consensus: The role of intimacy in group discussions.

This study examined if creating intimacy in a group discussion is more effective toward reaching consensus about climate change than a focus on information. Participants were randomly assigned to e...
The Long Arm of Early Exclusionary School Discipline? A Multi-Model Analysis:

In this analysis, we consider how a potentially important triggering event in the life course—exclusionary school discipline—may affect students’ high school outcomes. We extend the literature to f...
Decentralized Control of Two Agents with Nested Accessible Information

In this paper, we investigate a decentralized stochastic control problem with two agents, where a part of the memory of the second agent is also available to the first agent. We derive a structural form for optimal control strategies which allows us to restrict their domain to a set which does not grow in size with time. We also present a dynamic programming (DP) decomposition which can utilize our results to derive optimal strategies for arbitrarily long time horizons. Since obtaining optimal control strategies by solving this DP decomposition is computationally intensive, we present potential resolutions in the form of simplified strategies by imposing additional conditions on our model, and an approximation technique which can be used to implement our results with a bounded loss of optimality.
Voltage-activated complexation of α-synuclein with three diverse β-barrel channels: VDAC, MspA, and α-hemolysin.

Voltage-activated complexation is the process by which a transmembrane potential drives complex formation between a membrane-embedded channel and a soluble or membrane-peripheral target protein. Metabolite and calcium flux across the mitochondrial outer membrane is thought to be regulated by voltage-activated complexation of the voltage-dependent anion channel (VDAC) and either dimeric tubulin or α-synuclein (αSyn). The roles played by VDAC's characteristic attributes-its anion selectivity and voltage gating behavior-have remained unclear. Here, we compare in vitro measurements of voltage-activated complexation of αSyn with three well-characterized β-barrel channels-VDAC, MspA, and α-hemolysin-that differ widely in their organism of origin, structure, geometry, charge density distribution, and voltage gating behavior. The voltage dependences of the complexation dynamics for the different channels are observed to differ quantitatively but have similar qualitative features. In each case, energy landscape modeling describes the complexation dynamics in a manner consistent with the known properties of the individual channels, while voltage gating does not appear to play a role. The reaction free energy landscapes thus calculated reveal a non-trivial dependence of the αSyn/channel complex stability on the surface density of αSyn. This article is protected by copyright. All rights reserved.
Exploring naturally occurring ivy nanoparticles as an alternative biomaterial

Abstract Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9 ± 3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications. Statement of Significance Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy ( H. helix ), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo . Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.
Slices and Lumps

This brief essay, delivered in slightly different form as the 2008 Coase Lecture at the University of Chicago Law School, addresses problems involving the aggregation and division of entitlements. Fragments held by multiple parties - such as parcels of land, effort, or segments of a bridge - often must be assembled together to be worth much. Conversely, a presently unified entitlement may be more valuable if it can be split into separate pieces held by different parties. The essay examines these lumping and slicing problems (which turn out to be two sides of the same coin), shows how they turn up in both interpersonal and intrapersonal contexts, and discusses some tools for responding to them.
A new spin on black-hole masses

The extreme environment surrounding a black hole provides an ideal test bed for the predictions of general relativity. New observations of a spinning black hole push current theories to their limits.
An activation process for increased sensitivity of a SAW gas microsensor

A procedure for increasing the response of a SAW (surface acoustic wave) H/sub 2/S sensor using WO/sub 3/ as the sensing film is described. When the devices are heated to high temperatures, the film undergoes a structural phase change which significantly increases the film's sensitivity to H/sub 2/S. This activation effect can be seen by monitoring the sheet conductivity of the film during the activation procedure. Sample results illustrate the increased conductivity changes in the film when exposed to H/sub 2/S as well as the effect that this conductivity change has on the attenuation of a SAW sensor. The increased change in sheet conductivity corresponds to an increased change in SAW velocity and attenuation, allowing significantly lower concentrations of H/sub 2/S to be detected than with the unactivated film. >
Hepatic dysfunction as a complication of combined valproate and ketogenic diet.

Abstract Background The ketogenic diet has long been shown to be an effective therapy for children with medication-refractory seizures. Most complications of the ketogenic diet include short-lived gastrointestinal disturbances, acidosis, and dyslipidemia. Hepatic dysfunction and pancreatitis are among the less common but more serious complications of the ketogenic diet. Many patients on the ketogenic diet receive adjunct treatment with an anticonvulsant drug, and valproate is frequently used. Methods and Results We describe a child who developed hepatic dysfunction in association with the combined use of valproate and the ketogenic diet. After stopping the valproate and then restarting the ketogenic diet, her liver enzymes normalized, and she was able to achieve markedly improved seizure control and quality of life. Conclusions Although caution should be advised when using both treatments simultaneously, the development of hepatic dysfunction should not preclude continuation of the ketogenic diet, as the hepatotoxic effects may be completely reversed once the valproate is stopped.
The intellectual characteristics of the information field: Heritage and substance

As the information field (IField) becomes more recognized by different constituencies for education and research, the need to better understand its intellectual characteristics becomes more compelling. Although there are various conceptualizations of the IField, to date, in-depth studies based on empirical evidence are scarce. This article reports a study that fills this gap. We focus on the first five ISchools in the ICaucus as a proxy to represent the IField. The intellectual characteristics are depicted by two independent sets of data on tenure track faculty as knowledge contributors: their intellectual heritages and the intellectual substance in their journal publications. We use a critical analysis method to examine doctoral training areas and 3 years of journal publications. Our results indicate that (a) the IField can be better conceptualized with empirical support by a four-component model that includes People, Information, Technology, and Management, as predicted by the I-Model (Zhang & Benjamin, 2007); (b) the ISchools' faculty members are diverse, interdisciplinary, and multidisciplinary as shown by their intellectual heritages, by their research foci, by journals in which they publish, by the contexts within which they conduct research, and by the levels of analysis in research investigations; (c) the five ISchools share similarities while evincing differences in both faculty heritages and intellectual substances; (d) ISchool tenure track faculty members do not collaborate much with each other within or across schools although there is great potential; and (e) intellectual heritages are not good predictors of scholars' intellectual substance. We conclude by discussing the implications of the findings on IField identity, IField development, new ISchool formation and existing ISchool evolution, faculty career development, and collaboration within the IField.
Neuromuscular Blockade in the Management of Cerebral Palsy

Neuromuscular blocking agents-45% alcohol, 4% to 6% aqueous phenol, local anesthetics, and botulinum A toxin-have been used for many years in the evaluation and management of spasticity and movement disorders in children with cerebral palsy. Recent reports suggest that longer-acting neuromuscular blocking agents may impact positively on the natural history of dynamic deformity and improve health-related quality of life. This review includes the mechanism of action, techniques, indications, complications, and clinical outcomes associated with these agents.
Adeno-associated virus type 2: a latent life cycle

Publisher Summary This chapter discusses the structure and the genetic map of adeno-associated viruses (AAV). AAV constitute the Dependouirus genus of the family Parvoviridae , which are small DNA viruses, with a host range, extending from insects to humans. Those with vertebrate hosts belong to the subfamily Parvovirinae , whose members include both viruses with life cycles that are predominantly, if not completely, characterized by productive infection and viruses that establish latent infections as a prominent component of their life cycles. The AAV are members of the latter group; as such, they do not normally undergo a productive infection in cell culture unless there is coinfection with a helper virus, either an adeno- or a herpesvirus. The crystal structures of several parvoviruses closely related to AAV have been determined. An interesting feature of the interior capsid is the existence of 60 pockets, each capable of accommodating, and thus immobilizing 11 bases of the genome. There are three structural proteins, with overlapping amino-acid sequences, that differ in size, by the extension of the NH,-terminus. The genome of AAV, the most common human AAV, has been sequenced. There is an inverted terminal repeat of 145 bases, of which the terminal 125 bases are symmetrical. This chapter also describes the establishment of latency, integration, rescue, and replication of AAV.
Psychometric properties of the AHRQ Community Pharmacy Survey on Patient Safety Culture: a factor analysis

Background The U.S. Agency for Healthcare Research and Quality (AHRQ) developed a hospital patient safety culture survey in 2004 and has adapted this survey to other healthcare settings, such as nursing homes and medical offices, and most recently, community pharmacies. However, it is unknown whether safety culture dimensions developed for hospitals can be transferred to community pharmacies. The aim of this study was to assess the psychometric properties of the Community Pharmacy Survey on Patient Safety Culture. Method The survey was administered to 543 community pharmacists in Wisconsin, USA. Confirmatory factor analysis was used to assess the fit of our data with the proposed AHRQ model. Exploratory factor analysis was used to determine the underlying factor structure. Internal consistency reliabilities were calculated. Results A total of 433 usable surveys were returned (response rate 80%). Results from the confirmatory factor analysis showed inadequate model fit for the original 36 item, 11-factor structure. Exploratory factor analysis showed that a modified 27-item, four-factor structure better reflected the underlying safety culture dimensions in community pharmacies. The communication openness factor, with three items, dropped in its entirety while six items dropped from multiple factors. The remaining 27 items redistributed to form the four-factor structure: safety-related communication, staff training and work environment, organisational response to safety events, and staffing, work pressure and pace. Cronbach's α of 0.95 suggested good internal consistency. Conclusions Our findings suggest that validation studies need to be conducted before applying safety dimensions from other healthcare settings into community pharmacies.
Long-Term Outcomes of Successful Chronic Total Occlusion Percutaneous Coronary Interventions Using the Antegrade and Retrograde Approach

Objective To compare long-term clinical outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using the retrograde and antegrade approach. Background There is limited long-term clinical outcomes data on the retrograde approach to CTO PCI. Methods We performed a retrospective analysis of the long-term clinical outcomes of 193 consecutive patients who underwent successful CTO PCI at our institution between March 2008 and December 2011. Results Mean age was 63.6 ± 8.3 years. The target vessel was right coronary artery in 52.6%, left anterior descending artery in 24.5% and circumflex in 21.4% of cases. The retrograde approach was used in 41 patients (21.2%). The mean stent length was longer in the retrograde group (83 ± 32 vs. 64 ± 32 mm, P = 0.001). Two major procedural complications occurred, both in the retrograde group (P = 0.012). During a median follow-up of 2.0 years compared to the antegrade CTO PCI group, patients who underwent retrograde CTO PCI were more likely to undergo target lesion revascularization (TLR) (45.6% vs. 25.7%, P = 0.006). No significant difference was observed in the incidence of all-cause mortality, myocardial infarction, non-target vessel revascularization, or coronary artery bypass graft surgery between the 2 groups. On multivariate analysis, stent length was the only independent predictor of TLR during follow-up. Conclusions Retrograde CTO PCI was associated with higher incidence of TLR, but similar incidence of death and myocardial infarction compared to antegrade CTO PCI. These findings likely reflect the higher complexity of CTO lesions treated with the retrograde approach. (J Interven Cardiol 2014;27:465–471)
Study on the Reaction Mechanism and Kinetics of the Thermal Decomposition of Nitroethane

Despite many theoretical and experimental advances in understanding the macroscopic properties of energetic materials, much work remains to be done to understand their microscale mechanism. In this work, the reaction mechanism and kinetics of thermal decomposition of nitroethane were studied by density functional theory (DFT) calculations, automatic pressure tracking adiabatic calorimeter (APTAC) measurements, and gas chromatography (GC) analysis. The APTAC results were used to determine Arrhenius parameters of A = 1013.5±0.2 and Ea = 46.2 ± 0.5 kcal/mol. The decomposition process includes three initial steps: concerted molecular elimination of HONO, nitro−nitrite isomerization, and rupture of C−NO2. Followed these initial reactions, a detailed mechanism that consists of 23 elementary steps was proposed. Numerical simulations of the proposed mechanism reproduce reasonably well the distributions of major products over the temperature range. It was found that the relative concentrations of NO and C2H4 depen...