cssi/SciSciGPT-SciSciNet huggingface dataset:
Fatal VZV Myelitis In Association With Chronic Corticosteroid and Mycophenolate Mofetil Therapy (P2.312)

Objective: To report a case of fatal VZV myelitis in association with chronic corticosteroid and mycophenolate mofetil therapy. Background: Varicella Zoster Virus (VZV) is a neurotropic virus that after primary infection becomes latent in cranial nerve, dorsal root and autonomic ganglia. With a decline in VZV-specific cell-mediated immunity the virus reactivates and may manifest as shingles, vasculitis, meningoencephalitis, meningoradiculitis, cerebellitis, or myelitis. While VZV myelitis is often insidious, progressive and sometimes fatal myelitis may be seen in immunocompromised patients. VZV myelitis has been previously identified in patients on immunosuppressive agents such as the tumor-necrosis factor alpha inhibitor adalimumab and the T lymphocyte adhesion inhibitor natalizumab, but there has been no report of such a case in a patient on mycophenolate mofetil and especially none with the extent of lesion herein. Design/Methods: Case report with accompanied neuroimaging. Results: A 77-year-old man with myasthenia gravis treated with chronic oral prednisone and mycophenolate mofetil therapy presented with subacute general malaise and bilateral lower extremity weakness. Within one week he developed new vesicular lesions on the trunk and his condition rapidly deteriorated with evolution to a locked-in state. MRI of the spinal cord revealed scattered, longitudinally extensive transverse myelitis with patchy gadolinium enhancement from the pons to the conus medullaris. CSF demonstrated a lymphocyte-predominant pleocytosis with elevated protein and normal glucose along with a positive VZV PCR. Despite aggressive medical support, discontinuation of immunosuppressive therapies and treatment with acyclovir the patient’s condition persisted as grave and he ultimately expired following adherence to previously written advance directives. Conclusions: This represents the first reported case of VZV myelitis in association with corticosteroid and mycophenolate mofetil therapy. This case demonstrates the need for consideration of VZV myelitis, especially in those who are immunocompromised, to ensure early evaluation and aggressive management with antiviral therapy. Disclosure: Dr. Spears has nothing to disclose. Dr. Soneji has nothing to disclose. Dr. Cambi has nothing to disclose.
Persistence Length, End-to-End Distance, and Structure of Coarse-Grained Polymers.

Coarse-grained (CG) polymer simulations can access longer times and larger lengths than all-atom (AA) molecular dynamics simulations; however, not all CG models correctly reproduce polymer properties on all length scales. Here we coarse-grain atomistic position data from polyethylene (PE) and polytetrafluoroethylene (PTFE) melt simulations by combining λ backbone carbon atoms in a single CG bead. Resulting CG variables have correlations along the chain backbone that depend on the coarse-graining scale λ and are generally not reproduced by independent bond-length, bond-angle and torsion-angle distributions. By constructing distributions of CG variables equivalent to those from simulated CG potentials we are able to evaluate the bond-orientation correlation for different CG models at reduced computational cost. CG models and potentials that include only nonbonded, bond-length, and bond-angle interactions computed by Boltzmann inversion correctly reproduce the CG variable distributions but do not necessarily...
The matricellular protein CCN1 in tissue injury repair

The expression of Ccn1 (Cyr61) is essential for cardiovascular development during embryogenesis, whereas in adulthood it is associated with inflammation, wound healing, injury repair, and related pathologies including fibrosis and cancer. Recent studies have found that CCN1 plays a critical role in promoting wound healing and tissue repair. Mechanistically, CCN1 functions through direct interaction with specific integrin receptors expressed in various cell types in the wound tissue microenvironment to coordinate diverse cellular functions for repair. Here we briefly summarize the current knowledge on the functions of CCN1 in tissue injury repair and discuss pertinent unanswered questions.
Blood flow distribution in sorbent beds : analysis of a new sorbent device for hemoperfusion

A new polymer-based sorbent cartridge has been recently developed for enhancing middle molecule removal during hemodialysis. The cartridge (Betasorb, Renaltech, New York, USA) has been designed to ...
Metabolomics-Edited Transcriptomics Analysis (META)

The study of the metabolome or systems biochemical functions in response to external agents such as drugs or toxicants is made possible by recent advances in nuclear magnetic resonance (NMR) and mass spectrometry (MS). To optimize a given metabolomic study, samples should be processed with maintenance of biochemical integrity and optimal or reproducible recovery of metabolites. Various approaches to accomplish these goals were given. For metabolite profiling, both NMR and MS are excellently suited for providing molecular structure and abundance information. They are also uniquely suited for deciphering stable isotopomers of various metabolites in crude extracts. By coupling such analytical technologies with the stable isotope tracer approach, it is now practical to map changes in metabolic networks with atomic resolution such that metabolic perturbations can be discerned at individual enzyme reaction levels. This information readily lends its use in guiding transcriptomic analysis for metabolic regulations at the transcriptional level – an approach we called ‘metabolomics-edited transcriptomic analysis’ or META. An example study is given to illustrate the use of uniformly 13C-labeled glucose ([U-13C]-Glc) tracer, 13C-isotopomer-based metabolomic analysis, and META for reconstructing metabolic pathways and for discerning their regulatory pathways. This involved the investigation on defining the multitargeted action of selenite in human lung adenocarcinoma A549 cells. The META approach revealed 5′ adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mediated downregulation of fatty acid and protein synthesis, in addition to negative regulation of glycolysis, pentose phosphate pathway (PPP), Krebs cycle, glutathione synthesis, and nucleotide synthesis, as well as positive regulation of Gln oxidation. The complexity of the selenite action including the induction of opposing regulatory events was resolvable with the integrated metabolomics and transcriptomics approach, which is also generally applicable to any living system including the human body.
Endophyte Effect on Drought Tolerance in Diverse Festuca Species

Tall fescue (Festuca arundinacea Schreb.) drought survival is generally enhanced in high-temperature environments when infested with the fungal endophyte Neotyphodium coenophialum Glenn, Bacon, Price and Hanlin. Our group has concentrated on identifying water relations traits of the vegetative tiller base, mostly in plants from the cv. “Kentucky-31” (West, 1994). Studies on more diverse relatives of tall fescue are underway to (1) investigate whether detached-leaf conductance can serve as a screening tool for drought-stress-enhancing endophytes and (2) determine relative importance of tiller-base desiccation tolerance vs. desiccation postponement as a mode for endophyte-enhanced drought survival of the host.
Multivariate Quality Control Using Finite Intersection Tests

Multivariate quality control problems involve the evaluation of a process based on the simultaneous behavior of p variables. Most multivariate quality control procedures evaluate the in-control or out-of-control condition based upon an overall statistic..
Justifying a Surrogate's Request to Forego Oral Feeding.

Gertrude’s advance directive (AD) is coherent. It speaks to end-stage as well as terminal conditions, and why shouldn’t it, if Gertrude is equally concerned that her life not continue for years wit...
Facilitating Transformation in Workforce Training: Using Clinical Theory to Understand Psychological Self-Sufficiency

ABSTRACTAcknowledging the scarcity of a bottom up social work practice model in facilitating the development of success in workforce development programs, this study explores Psychological self-suf...
Family Change in Global Perspective: How and Why Family Systems Change

Changes in family systems that have occurred over the past half century throughout the Western world are now spreading across the globe to nations that are experiencing economic development, technological change, and shifts in cultural beliefs. Traditional family systems are adapting in different ways to a series of conditions that forced shifts in all Western nations. In this paper, I examine the causes and consequences of global family change, introducing a recently funded project using the Demographic and Health Surveys (DHS) and U.S. Census Bureau data to chart the pace and pattern of changes in marriage and family systems in low- and middle-income nations.
Impact of Primary Incident Spatiotemporal Influence Thresholds on the Detection of Secondary Crashes

Incident management agencies have been investing substantial amount of resources to devise strategies to mitigate secondary crashes (SCs). Nevertheless, detection of SCs is not a straightforward pr...
Novel mechanism of endocrine disruption by fungicides through binding to the membrane androgen receptor, ZIP9 (SLC39A9), and antagonizing rapid testosterone induction of the intrinsic apoptotic pathway

Abstract A variety of pesticides including vinclozolin, its metabolite M2 (3′,5′-dichloro-2-hydroxy-2-methylbut-3-enanilide), and prochloraz have been shown to exert antiandrogenic effects in animal models by competing with androgen binding to nuclear androgen receptors (nAR) and decreasing transcription of androgen-responsive genes. However, it is not known whether these pesticide antiandrogens also interfere with rapid (often described as nongenomic, nonclassical) androgen actions mediated by membrane androgen receptors (mARs). We recently discovered that ZIP9, a member of the zinc transporter ZIP (SLC39A) family, is a specific, high-affinity mAR that mediates rapid testosterone-dependent signaling, zinc influx, and apoptosis in breast and prostate cancer cell lines. Possible disruption by prochloraz, vinclozolin, and M2 of androgen actions through this mAR was investigated in vitro in PC-3 prostate cancer cells (nAR-) over expressing human ZIP9 (PC3-ZIP9 cells). Single-point competitive binding assays showed 1 μM and 10 μM concentrations of all three pesticides displaced specific [3H]-testosterone binding to PC3-ZIP9 cell membranes with binding affinities
Sources and Types of Big Data for Macroeconomic Forecasting

This chapter considers the types of Big Data that have proven useful for macroeconomic forecasting. It first presents the various definitions of Big Data, proposing one we believe is most useful for forecasting. The literature on both the opportunities and challenges of Big Data are presented. It then proposes a taxonomy of the types of Big Data: (1) Financial Market Data; (2) E-Commerce and Credit Cards; (3) Mobile Phones; (4) Search; (5) Social Media Data; (6) Textual Data; (7) Sensors, and The Internet of Things; (8) Transportation Data; (9) Other Administrative Data. Noteworthy studies are described throughout.
Prevalence and cropping system impacts on soybean vein necrosis disease in Delaware soybeans

Soybean vein necrosis disease (SVN) is the most widespread virus of soybeans in the United States. This thrip-vetcored virus can cause foliar chlorosis and necrosis, and it can reduce soybean oil c...
Hybrid Approach: Defect Closure

Transcatheter closure of septal defects in small children is technically challenging. In particular, there is difficulty in passing the long delivery sheath without compromising valvar and ventricular function. While surgical closure is often appropriate in these patients, when the defect is inaccessible without a ventriculotomy, then a hybrid approach produces the greatest benefit to the patient. Through the open chest, a purse-string suture is placed in the right ventricle opposite the site of the VSD. Using transoesophageal or epicardial echocardiography, a guidewire is placed across the defect after needle puncture of the right ventricular free wall. A short sheath is then advanced across the defect and using echocardiographic monitoring a septal occluder deployed to close the defect. Once a satisfactory position is obtained, the device is detached from the delivery cable and the purse-string suture tightened after sheath withdrawal. While usually performed electively off bypass, the procedure can also be performed while on cardiopulmonary bypass as an adjunct to concomitant surgery or when a defect is unexpectedly unable to be closed surgically.
Evaluation of the potential effect of dacomitinib, an EGFR tyrosine kinase inhibitor, on ECG parameters in patients with advanced non-small cell lung cancer

Purpose The study evaluated the potential effect of dacomitinib, a small molecule epidermal growth factor receptor (EGFR) inhibitor, on the electrocardiogram (ECG) parameters in adult patients with advanced non-small cell lung cancer enrolled in a multicenter, open-label, phase 2 study. Methods Patients received dacomitinib for six doses of 45 mg every 12 h in a 7-day lead-in cycle (cycle 0), then 60 mg every 12 h for six doses in a 14-day cycle (cycle 1). Clock time-matched triplicate ECGs were performed at 0, 2, 4, 6, 8 and 10 h on day 1 (baseline) and day 4 of cycle 0, and prior to dose on days 1 and 4 of cycle 1. The QT interval was corrected for heart rate using Fridericia’s correction (QTcF) and a study specific correction factor (QTcS). Results Thirty-two patients in the study comprised the QTc-evaluable population. Dacomitinib had no effect on the heart rate. The upper limits of the 95% confidence interval (CI) for the mean change from baseline in QTcF and QTcS were < 10 ms at all time points. A lack of relationship between plasma concentrations of dacomitinib or total active moiety on QTcF and QTcS was evidenced. All upper 90% CIs of the PR intervals were < 200 ms, although a small mean increase from baseline (2.7–6.6 ms) was observed. Conclusions There was a lack of a clinically relevant effect of dacomitinib on ECG parameters at dacomitinib concentrations comparable to those obtained at its highest therapeutic dosing regimen of 45 mg once daily. ClinicalTrials.gov identifier: NCT01858389.
The small protein RmpD drives hypermucoviscosity in Klebsiella pneumoniae

Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: Classical strains that are a notable problem in healthcare settings due to multidrug resistance, and hypervirulent (hv) strains that are drug sensitive, but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene is rmpA that encodes a transcriptional regulator required for maximal capsule (cps) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new cps regulator, RmpC, and {Delta}rmpC mutants have reduced cps expression but remain HMV, suggesting that capsule and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV, but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv K. pneumoniae strains. Expression of rmpD in trans complements both {Delta}rmpD and {Delta}rmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, within an operon regulated by RmpA. This data, combined with our previous work, suggests a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression. SIGNIFICANCECapsule is a critical virulence factor in Klebsiella pneumoniae, in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscous (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene (rmpD) required for HMV but does not contribute to capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.
Design and Scheduling of Semibatch Chemical-Looping Reactors

Chemical-looping combustion is explored as a chemical reactor design problem. The continuous operation of fixed bed reactors using gaseous fuels for the purpose of power generation through integrat...
Mesoscopic Liquid Clusters Represent a Distinct Condensate of Mutant p53

Abstract The oncogenic properties of mutant p53 have been ascribed to destabilization of the p53 conformation, followed by aggregation into insoluble fibrils. Here we combine immunofluorescent 3D confocal microscopy of breast cancer cells expressing the p53 mutant Arg248Gln (R248Q) with light scattering from solutions of the purified protein and molecular simulations to probe the mechanisms that govern phase behaviors of the mutant across multiple length scales, from cellular to molecular. We establish that p53 R248Q forms mesoscopic protein-rich clusters, an anomalous liquid phase with several unique properties. We demonstrate that the clusters host and facilitate the nucleation of amyloid fibrils. The distinct characteristics of the clusters of R248Q and wild-type p53 and theoretical models indicate that p53 condensation into clusters is driven by the structural destabilization of the core domain and not by interactions of its extensive disordered region. Two-step nucleation of mutant p53 amyloids suggests means to control fibrillization and the associated pathologies through modifying the cluster behaviors. In a broader context, our findings exemplify interactions between distinct protein phases that activate complex physicochemical mechanisms operating in biological systems.
Migrant and resident female songbirds differ in gonadal response to upstream stimulation during seasonal sympatry.

Abstract Timing of seasonal reproduction is driven by environmental cues acting on the hypothalamic-pituitary–gonadal (HPG) axis. Groups of individuals, or populations, of the same species can exhibit different phenology despite facing similar environmental cues or living in the same habitat (i.e., seasonal sympatry). The mechanisms giving rise to population-level differences in reproductive timing are not fully understood, particularly for females. We studied the dark-eyed junco, a songbird with migratory and sedentary (i.e., resident) populations that live in overlapping distributions during winter. In early spring, residents initiate breeding and associated behaviors, including territory establishment and formation of pair bonds, while migrants prepare to depart for their breeding grounds. We tested whether migrant and resident hormonal response to upstream hormonal stimulation differed during this time period. We collected blood from free-living females in early spring, and challenged them with repeated gonadotropin-releasing hormone (GnRH) injections to measure testosterone (T) response. We predicted that if migrants are less sensitive to upstream stimulation than residents, then they would exhibit lower response to the repeated GnRH challenges in migrants. We found that migrant and resident females both responded to an initial challenge by elevating T, but residents responded more robustly, indicating that the ovary plays a role in population-level differences in reproductive timing. We also found that migrants and residents attenuated their response to repeated challenges, and did not differ from one another in final T levels. We speculate that the explanation for the generally reduced T response after repeated GnRH injections need not be the same for migrants and residents, but possible explanations include suppression of upstream stimulation owing to negative feedback after the initial injection or aromatization of T to estradiol between sampling time points. We suggest that future studies experimentally explore how the ovarian response to upstream stimulation changes during the transition to reproduction.
Comparison of institutional guidelines with established early onset sepsis risk calculator in reducing antibiotic use in an inner-city NICU in US.

Abstract Objectives Early onset sepsis (EOS) incidence has decreased since national guidelines and intrapartum prophylaxis were introduced. However, there has been a rising concern in antibiotic overtreatment for suspicion of EOS. A web-based EOS calculator has recently been used to evaluate the risk in newborns ≥34 weeks. Our purpose was to compare local strategies with the EOS calculator in our setting with an EOS incidence of 2/1000 live births. Methods A retrospective review of all newborns born ≥34 weeks from 1 January 2016 to 31 December 2017 was completed after receiving IRB approval. We applied the calculator to those eligible using an EOS incidence of 0.6/1000 and 2/1000 live births and divided the patients into four cohorts. The rate of antibiotic use was compared between local evidence-based guidelines and the EOS calculator. Results Of the 1367 newborns included in the study, 679 received antibiotics. Over the 2 years, antibiotic utilization decreased by 38%. The calculator would have recommended antibiotics for 468 patients (31% decrease) for an EOS incidence of 0.6/1000, but with a 2/1000 incidence rate the calculator recommended antibiotics for 673 patients (1% decrease). Conclusions The EOS calculator has been helpful in optimizing antibiotic use, but its use may result in suboptimal treatment without the knowledge of local EOS incidence. Our local antibiotic stewardship guidelines seemed to be comparable to the EOS calculator, especially by the last 6 months of the study period.
Nonlinear Normal Mode Estimation with Near-Resonant Steady State Inputs

Nonlinear normal modes (NNMs) have been widely used for understanding and characterizing the motion of nonlinear structures, yet current methods to measure them experimentally are time-consuming and not always reliable. Since the structural nonlinearities usually occur when the sample oscillates at high amplitudes, specimens can be damaged or at least develop fatigue cracks when the testing is lengthy. Moreover, the interaction between the shaker and the structure can lead to distortions of the excitation force and can impact the quality of the measured test data. In our previous work, we proposed an NNM estimation algorithm that can help to overcome the issues mentioned above. The approach uses near-resonant data together with an algorithm based on the Single Nonlinear Resonant Mode (SNRM) method to then estimate the NNM backbone. The SNRM algorithm, in its original form, requires vibration modes to be well-separated and assumes no internal resonances between them. This work proposes a possible modification to the algorithm that will allow the modal coupling to be detected as well. The final version of the algorithm will be first tested with data generated numerically using a reduced model of a curved beam experiencing modal interactions. Then the method will be used to estimate the NNMs of a curved steel beam that exhibits significant modal interactions. The results will be validated against those obtained using well-established testing approaches.
Interventions to improve dietary intake behaviors among children and adolescents

Abstract This paper focuses on the most proximate determinants of dietary intake: food behaviors of caregivers, children and adolescents. Utilizing a case study approach, we explored cultural-ecological factors that have been shown to affect behavioral interventions aimed improving diet quality. The results provide insights about facilitators and barriers to uptake of interventions aimed at improving dietary behaviors in children and adolescents and highlight their implications for planning and monitoring future interventions. We applaud and advocate for the continuing momentum in implementation science in nutrition, which are reflected in the selection of case studies. This momentum will result in further acquisition of empirical knowledge and stronger theoretical underpinnings for the design and execution of the behavior change interventions.
The Gap Gets Bigger: Changes in Mortality and Life Expectancy, by Education, 1981-2000

In this paper we examine educational disparities in mortality and life expectancy among non-Hispanic blacks and whites in the 1980s and 1990s. Despite increased attention and substantial dollars directed to groups with low socioeconomic status, within race and gender groups, the educational gap in life expectancy is rising, mainly because of rising differentials among the elderly. With the exception of black males, all recent gains in life expectancy at age twenty-five have occurred among better-educated groups, raising educational differentials in life expectancy by 30 percent. Differential trends in smoking-related diseases explain at least 20 percent of this trend.
Immune activation kickstarts the gut microbiota.

Summary The gut microbiota regulates intestinal immunity, but whether immune activation reciprocally alters gut commensals is unknown. In this issue of Cell Host & Microbe, Becattini et al. used a reductionist approach, incorporating gnotobiotic mouse models and multi-omics analyses, to address how gut commensals respond and adapt to acute immune activation.
Salmonella Aortitis in an Elderly Male, a Rare but Deadly Cause of Abdominal Pain: A Case Report.

Author(s): Yanushefski, Kevin M.; Kaur, Sukhdip; Eberhardt, Mary | Abstract: Introduction: Infectious aortitis is a rare condition with mortality rates approaching 100% without surgical intervention. Symptoms and findings may be vague. Computed tomography (CT) with intravenous (IV) contrast, once the gold standard of diagnosis, may only show subtle findings. More recently, CT angiography (CTA) and magnetic resonance angiography have become the diagnostic modalities of choice.Case Report: A 58-year-old diabetic male presented to our emergency department with nausea, vomiting, diarrhea, fevers, and abdominal pain of two weeks duration. The patient had been seen just days before at another facility with the same complaints. He received an abdominal CT with IV contrast that was reported as negative and discharged with the diagnosis of gastroenteritis. He failed to improve and presented to our facility. On presentation, the patient was diaphoretic and uncomfortable. A repeat abdominal CT with IV contrast revealed a mantle of low density around the aorta. The patient was started on IV antibiotics, and a follow-up CTA of the abdomen and pelvis showed an irregular saccular aneurysm. Vascular surgery was consulted, and the patient underwent vascular reconstruction.Conclusion: Because of the high level of mortality seen in infectious aortitis and improvement in patient outcomes with surgical intervention, a high index of suspicion needs to be maintained in patients presenting with fever and chest, abdominal, and back pain, especially in the setting of risk factors and bacteremia. The clinician should be aware that the usual modality for the evaluation of abdominal pain, CT with IV contrast, may not be adequate to make the diagnosis.
Nanopore tweezers measurements of RecQ conformational changes reveal the energy landscape of helicase motion

Helicases are essential for nearly all nucleic acid processes across the tree of life. Using Nanopore Tweezers we observed the small, fast steps taken by single RecQ helicases as they step along and unwind DNA at ultrahigh spatiotemporal resolution. By directly measuring conformational substates of RecQ we determine the coupling between helicase domain motions and chemical reactions that together produce forward motion along the DNA. Application of assisting and opposing forces shows that RecQ has a highly asymmetric energy landscape that reduces its sensitivity to opposing mechanical forces that could be encountered in vivo by molecular roadblocks such as DNA bound proteins. This energy landscape enables RecQ to maintain speed against an opposing load.
Adoption of New Risk Stratification Technologies Within US Hospital Referral Regions and Association With Prostate Cancer Management.

Importance The clinical decisions that arise from prostate magnetic resonance imaging (MRI) and genomic testing in patients with prostate cancer are not well understood. Objective To evaluate the association between regional uptake of prostate MRI and genomic testing and observation vs treatment for prostate cancer. Design, Setting, and Participants This retrospective cohort study of commercial insurance claims for prostate MRI and genomic testing included 65 530 patients 40 to 89 years of age newly diagnosed with prostate cancer from July 1, 2012, through June 30, 2019. Exposures Patient- and regional-level use of prostate MRI and genomic testing. Main Outcomes and Measures Observation vs definitive treatment for prostate cancer. Patient-level analyses examined the association between receipt of testing or residing in a hospital referral region (HRR) that adopted testing and observation. In regional-level analyses, the dependent variable was the change in the proportion of patients observed for prostate cancer at the HRR level between 2 periods: July 1, 2012, to June 30, 2014, and July 1, 2017, to June 20, 2019. The independent study variables included HRR-level changes in the proportion of men undergoing prostate MRI and genomic testing between these periods, and the models were adjusted for contextual factors associated with prostate cancer care and socioeconomic status. Results This study identified 65 530 patients, including 27 679 in the early period (mean [SD] age, 58.0 [5.9] years) and 37 851 in the late period (mean [SD] age, 59.0 [5.7] years). Use of prostate MRI increased significantly from 7.2% (95% CI, 6.9%-7.5%) to 16.7% (95% CI, 16.3%-17.1%) from the early to late period. Use of genomic testing increased significantly from 1.3% (95% CI, 1.1%-1.4%) to 12.7% (95% CI, 12.3%-13.0%) from the early to late period. Compared with the lowest, the highest HRR quartiles of prostate MRI and genomic testing uptake were associated with an adjusted 4.1% (SE, 1.1%; P < .001) and 2.5% (SE, 1.1%; P = .03) absolute increase in the proportion of patients receiving observation, respectively. Conclusions and Relevance In this cohort study, uptake of prostate MRI and genomic testing was associated with increased use of initial observation vs treatment for prostate cancer. Marked geographic variation supports the need for further patient-level research to optimize the dissemination and outcome of testing.
A kinematic constraint method for stability analysis of articulated vehicles

This work examines a method of analyzing the handling response and stability of an articulated vehicle. The method consists of replacing the tyre force–slip angle relationships, that are typically used in handling analysis, with a kinematic constraint formulation. A vehicle model was analyzed using both the standard slip angle approach and the constraint method. The model examined is a simplified four degree–of–freedom model of a tractor–trailer system. The results of each analysis method are compared. These results indicate that use of the constraint method can afford greater ease in problem set up and solution and can eliminate the requirement for a tyre model. The results also indicate that the constraint method can provide an accurate estimate of tyre loading and vehicle stability boundaries.
Sites of Binding of Copper(II) Ion by Peptide (1–24) of Bovine Serum Albumin

Abstract 1. The amino-terminal peptide (1–24) of bovine serum albumin was subjected to carboxymethylation by 0.2 m bromoacetate at pH 6.8 in the presence of 0, 1, and 2 eq of copper(II) ion. The treatment with bromoacetate in the absence of copper(II) caused almost quantitative carboxymethylation of the imidazole groups of the 3 histidyl residues at positions 3, 9, and 18 in the sequences. In addition, the terminal α-amino group was apparently modified. Spectral measurements on the copper-containing complexes showed little or no effect on the copper chelation by the alkylation treatment. 2. Binding of 1 eq of copper(II) protects quantitatively the terminal α-amino group and histidyl residue 3, and appears to reduce somewhat the reactivity of histidyl residue 18. 3. Binding of 2 eq of copper(II) also protects the components of the preferred terminal site, but, in addition, both histidyl residues 9 and 18 are largely, and about equally, protected from alkylation. The binding of the 2nd eq therefore appears to involve both histidyl residues, in keeping with spectral and titration results. An intramolecular chelate structure or intermolecular chelates involving dimers or higher polymers are suggested. 4. The tetrapeptide l-aspartyl-l-threonyl-l-histidyl-l-lysine, which corresponds to the first 4 residues of peptide (1–24), was shown by titration, absorbance, and circular dichroism measurements to form an equimolar complex with copper(II) that has substantially the properties of the complex of peptide (1–24) containing 1 eq of copper(II) ion. Similar measurements on the equimolar complex of bovine serum albumin fill out a continuity that is especially evident from measurements of circular dichroism.
Medical Child Abuse/Munchausen by Proxy

Medical child abuse (MCA) is the form of child maltreatment characterized by a child receiving unnecessary and harmful or potentially harmful medical care as the result of actions of a parent or caregiver. Previously known as Munchausen syndrome by proxy, pediatric condition falsification, or factitious disorder by proxy, MCA is similar to other forms of child maltreatment in many ways but differs in having the parent inflict harm by inserting false information in the medical treatment process. A parent can cause his or her child to have a symptom and then lie about it, falsify or exaggerate a symptom, or otherwise induce medical care providers to give care that is not necessary. Perpetrators may have many different motivations. Treatment consists of stopping the unnecessary care, reversing the harmful effects, and inducing the offending parent to interact with the medical care community in a healthy way. Keywords: fabricated or induced illness by a caretaker; factitious disorder by proxy; medical child abuse; Munchausen syndrome by proxy; pediatric condition falsification; children; disability; health; trauma; victim
Jus in bello, Rape and the British Army in the American Revolutionary War

This essay offers a case study in jus in bello in the American Revolutionary War by focusing on responses to sexual violence committed against American women by soldiers in the occupying British army and their Loyalist auxiliaries. Two main bodies of sources are juxtaposed in order to explore the contexts and manner in which jus in bello was adjudicated: British courts-martial and American Congressional investigations documenting British and Loyalist breaches of the codes of war. By putting the fragmentary evidence of instances of rape in the context of contemporary legal and sociocultural practices of sexual violence in peacetime, as well as of the British army's disciplinary regime, we can elucidate the horizon of experiences and expectations against which survivors, assailants and prosecutors acted. The British army disciplined some soldiers for sexual offenses that violated military law and the codes of war, and it executed a few of them at a time when even their home society featured very low prosecu...
Cross references in step-by-step procedures: uses, usability problems, and possible solutions

It is noted that the step-by-step format is geared towards the presentation of linear information, and the incorporation of nonlinear information, such as cross references, into this format can lead to substantial usability problems. However, the step-by-step format is also flexible and can be tailored to minimize these problems by (1) minimizing cross references, (2) formatting cross references effectively, and (3) incorporating place-keeping aids into manuals that contain cross references. >
The Many Mendelsohn 'Me Too' Missteps: An Alliterative Response to Professor Rubinstein

Although one might have the misimpression that the missteps referred to in the title of this paper indicate a criticism of the U.S. Supreme Court's ADEA decision of Mendelsohn v. Sprint/United Management Co., it does not. I believe the unanimous Court opinion is correct: 'Me too' evidence should be admissible in certain instances based on evidentiary principles and based on the overriding importance of context in such cases, as further discussed in Professor Mitchell Rubinstein's Colloquy Essay, 'Mendelsohn v. Sprint/United Management; The Supreme Court Appears to Punt Whether 'Me Too' Evidence of Discrimination is Admissible or Does It?' Rather, the missteps I have in mind are three and include: (1) my own misstep for writing in a previous Workplace Prof Blog post, before the decision, that a per se rule against this type of evidence would be adopted by the usual conservative Supreme Court Justice suspects; (2) the misstep made by the Supreme Court for granting certiorari in the first place in this rather mundane (legally speaking) employment discrimination case; and (3) the misstep of Professor Rubinstein in suggesting that the decision in Mendelsohn will provide 'important medicine' for employment discrimination plaintiffs and in concluding that this 'me too' evidentiary issue may again raise its narcissistic head before the Court.
Nucleon elastic form factors - Current status of the experimental effort

The nucleon form factors are still the subject of active investigation even after an experimental effort spanning 50 years. This is because they are of critical importance to our understanding of the electromagnetic properties of nuclei and provide a unique testing ground for QCD motivated models of nucleon structure. Progress in polarized beams, polarized targets and recoil polarimetry have allowed an important and precise set of data to be collected over the last decade. I will review the experimental status of elastic electron scattering from the nucleon along with an outlook for future progress.
Bioavailability of vitamin B-6 from wheat bread in humans.

ABSTRACT Bioavailability of vitamin B-6 from three types of bread wasstudied in nine men. Each week one of the three types of bread, whole wheat(WHW), white (W) and W enriched with vitamin B-6 (WB6) was fed (570-600g/day) to each subject using a Latin square design. The WHW, WB6 and W breadsupplied 1.20, 1.18 and 0.35 mg of B-6 daily, respectively. The remaining constant diet supplied 0.38 mg of B-6. When W was fed, the subjects also receivedan oral dose of pyridoxine to maintain a daily intake of 1.5 mg of vitamin B-6.Dietary, urinary, fecal and blood samples were analyzed for vitamin B-6. Urinewas analyzed for 4-pyridoxic acid and the three forms of vitamin B-6. The predominant forms of vitamin B-6 in the diet and urine were pyridoxine and pyridoxal,respectively. Fecal vitamin B-6 excretion was significantly higher (P s 0.01) andurinary 4-pyridoxic acid excretion significantly lower (P s 0.05) when WHW breadwas fed than when either WB6 or W bread was fed. The plasma pyridoxal phosphate level was slightly lower when WHW bread was consumed as comparedto when WB6 was fed. There were no significant differences in urinary B-6,plasma B-6 or the activity of the erythrocyte transaminases in relation to thetype of bread fed. These data suggest that vitamin B-6 is 5-10% less availablefrom WHW than from WB6 or W bread and an oral dose of B-6. The enrichmentof refined wheat flour with pyridoxine is feasible based on the nutritional indicesdetermined in this study. J. Nutr. 110: 1819-1828, 1980.INDEXING KEY WORDS vitamin B-6 â€¢bioavailability â€¢wheat bread
Forgiveness Or Fairness

AbstractSeveral philosophers who argue that forgiveness is an important virtue also wish to maintain the moral value of retributive emotions that forgiveness is meant to overcome. As such, these accounts explicate forgiveness as an Aristotelian mean between too much resentment and too little resentment. I argue that such an account ends up making forgiveness superfluous: it turns out that the forgiving person is not praised for a greater willingness to let go of her resentment, but rather for her fairness or good judgment. I conclude by arguing that the virtue of fair-mindedness is more compatible with maintaining the value of the retributive emotions than the virtue of forgiveness.
Endovascular Coil Embolization in the Treatment of a Rare Case of Post-Traumatic Abdominal Aortic Pseudoaneurysms: Brief Report and Review of Literature

Traumatic aortic injury, a consequence of penetrating injuries or blunt trauma, is a life threatening condition which requires prompt diagnosis and management. Most abdominal aortic injuries have been repaired via an open surgical approach with endovascular stent graft as an alternative. Traumatic pseudoaneurysms (PSA) of the abdominal aorta are uncommon, and they are managed similar to other abdominal aortic injuries. However, the presence of a perianeurysmal hematoma and the potential risk of an associated concomitant bowel communication could make surgery and endovascular stent graft placement risky. In such patients, coil embolization could be a valued option. In this article, we present a case in which traumatic PSAs are repaired using coil embolization with technical and clinical success. Endovascular coil embolization could be an alternative approach for PSAs that cannot be treated by stent grafting or open surgical repair, in the appropriate anatomy and by using the right coil material and technique.
Software-based fault-tolerant control design for improved power plant operation

The use of fault-tolerance has increasingly become an important requirement for power plant control because of safety and availability considerations. Typical applications in process control employ redundant hardware for data acquisition and processing. The primary objective is to maintain the operation of the plant, even in the presence of anomalies in instrument channels. The performance of a system with existing hardware can be improved by the additional design of diverse, digital control systems in the form of software redundancy. This design has been integrated with signal and command validation with option for manual and automatic control through a graphical user interface. The fault-tolerant design has been demonstrated with application to the steam generator system control in a pressurized water reactor plant. >
Cell Cycle-Dependent Regulation of Ca2+ in Young and Senescent WI-38 Cells

During the in vitro senescence of the normal human diploid cell line WI-38, there is a loss of ability to initiate DNA synthesis in response to mitogens. This loss of replicative capacity is reflected in an increasing average length of G1 and a decreasing fraction of cells in the rapidly proliferating pool. Calcium ion (Ca2+) has been shown to be important for progression through the cell cycle and we have measured two processes which contribute to the regulation of intracellular Ca2+ in the early, mid, and late G1 phase of the cell cycle. Basal intracellular Ca2+ concentrations in quiescent cells as well as initial transient mobilization of Ca2+ stores following mitogenic stimulation by growth factors were equivalent in young and senescent cells. Calmodulin levels in young, quiescent cells decreased 50% in the first 4-6 h after stimulation with fresh serum and then increased two- to fourfold immediately prior to entry into DNA synthesis. Senescent cells did not exhibit this cell cycle-dependent pattern and calmodulin levels remained generally constant throughout G1, sometimes increasing slightly, prior to S phase. These data suggest that perhaps the intracellular Ca2+ concentration is regulated differently in young and senescent cells. Indeed, the cell cycle regulation of calmodulin may be uncoupled from the cell cycle regulation of calmodulin mRNA. This difference could provide one mechanism for the failure of senescent cells to synthesize DNA following mitogenic stimulation.
Interaction of catechol and non-catechol substrates with externally or internally facing dopamine transporters.

Our previous work suggested that collapsing the Na+ gradient and membrane potential converts the dopamine (DA) transporter (DAT) to an inward-facing conformation with a different substrate binding profile. Here, DAT expressing human embryonic kidney 293 cells were permeabilized with digitonin, disrupting ion/voltage gradients and allowing passage of DAT substrates. The potency of p-tyramine and other non-catechols (d-amphetamine, β-phenethylamine, MPP+) in inhibiting cocaine analog binding to DAT in digitonin-treated cells was markedly weakened to a level similar to that observed in cell-free membranes. In contrast, the potency of DA and another catechol, norepinephrine, was not significantly changed by the same treatment, whereas epinephrine showed only a modest reduction. These findings suggest that catechol substrates interact symmetrically with both sides of DAT and non-catechol substrates, favoring binding to outward-facing transporter. In the cocaine analog binding assay, the mutant W84L displayed enhanced intrinsic binding affinity for substrates in interacting with both outward- and inward-facing states; D313N showed wild-type-like symmetric binding; but D267L and E428Q showed an apparent improvement in the permeation pathway from the external face towards the substrate site. Thus, the structure of both substrate and transporter play a role in the sidedness and mode of interaction between them.
Chemopreventive agents: protease inhibitors

Certain protease inhibitors, called the anticarcinogenic protease inhibitors in this review, are capable of preventing carcinogenesis in a wide variety of in vivo and in vitro model systems. The anticarcinogenic protease inhibitors are extremely potent agents with the ability to prevent cancer, with some unique characteristics as anticarcinogenic agents. The anticarcinogenic protease inhibitors have the ability to irreversibly suppress the carcinogenic process. They do not have to be continuously present to suppress carcinogenesis. They can be effective when applied in both in vivo and in vitro carcinogenesis assay systems at long time periods after carcinogen exposure, and are effective as anticarcinogenic agents at extremely low molar concentrations. While several different types of protease inhibitors can prevent the carcinogenic process, the most potent of the anticarcinogenic protease inhibitors on a molar basis are those with the ability to inhibit chymotrypsin or chymotrypsin-like proteases. The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is a potent chymotrypsin inhibitor that has been extensively studied for its ability to prevent carcinogenesis in many different model systems. Much of this review is focused on the characteristics of BBI as the anticarcinogenic protease inhibitor, as this is the protease inhibitor that has risen to the human trial stage as a human cancer chemopreventive agent. Part of this review hypothesizes that the Bowman-Birk family of protease inhibitors plays a role in plants similar to that of alpha1-antichymotrypsin in people. Both BBI and alpha1-antichymotrypsin are potent inhibitors of chymotrypsin and chymotrypsin-like enzymes, are highly anti-inflammatory, and are thought to play important roles in the defense of their respective organisms. It is believed that BBI will be shown to play a major role in the prevention and/or treatment of several different diseases, in addition to cancer.