cssi/SciSciGPT-SciSciNet huggingface dataset:
Recently certified athletic trainers' undergraduate educational preparation in psychosocial intervention and referral.

Abstract Context: “Psychosocial Intervention and Referral” is one of the 12 content areas established by the National Athletic Trainers' Association Education Council and is required to be taught i...
Hygrothermomechanical evaluation of porous media under finite deformation: Part II—model validations and field simulations

A set of field equations, the associated finite element model formulations and numerical methodology for thermomechanical response evaluations of fluid-saturated media under finite deformation have been presented in Part I of the companion manuscript.1 In this paper, the formulations and methodologies are initially validated through benchmark model comparisons prior to constitutive model sensitivity analysis and subsequent thermomechanical response determination. The responses for the testbed problems, using the developed solution algorithm, compare favourably with the reported results. The response investigations for complex geomechanical problems illustrate the general applicability of the developed finite element model simulator in predicting the long-term thermal, pore pressure, displacement and stress responses of fluid-saturated porous media subjected to thermomechanical loading, as encountered in nuclear waste management scenarios. The presented formulations and numerical procedures can also be used to investigate a wide range of engineering problems involving hygrothermomechanical response prediction.
Probabilistic Modeling of Dependencies Among Visual Short-Term Memory Representations

Extensive evidence suggests that items are not encoded independently in visual short-term memory (VSTM). However, previous research has not quantitatively considered how the encoding of an item influences the encoding of other items. Here, we model the dependencies among VSTM representations using a multivariate Gaussian distribution with a stimulus-dependent mean and covariance matrix. We report the results of an experiment designed to determine the specific form of the stimulus-dependence of the mean and the covariance matrix. We find that the magnitude of the covariance between the representations of two items is a monotonically decreasing function of the difference between the items' feature values, similar to a Gaussian process with a distance-dependent, stationary kernel function. We further show that this type of covariance function can be explained as a natural consequence of encoding multiple stimuli in a population of neurons with correlated responses.
Lipids, Proteins, and Structure of Seed Oil Bodies from Diverse Species

Oil bodies isolated from the mature seeds of rape (Brassica napus L.), mustard (Brassica juncea L.), cotton (Gossypium hirsutum L.), flax (Linus usitatis simum), maize (Zea mays L.), peanut (Arachis hypogaea L.), and sesame (Sesamum indicum L.) had average diameters that were different but within a narrow range (0.6-2.0 [mu]m), as measured from electron micrographs of serial sections. Their contents of triacylglycerols (TAG), phospholipids, and proteins (oleosins) were correlated with their sizes. The correlation fits a formula that describes a spherical particle surrounded by a shell of a monolayer of phospholipids embedded with oleosins. Oil bodies from the various species contained substantial amounts of the uncommon negatively charged phosphatidylserine and phosphatidylinositol, as well as small amounts of free fatty acids. These acidic lipids are assumed to interact with the basic amino acid residues of the oleosins on the surface of the phospholipid layer. Isoelectrofocusing revealed that the oil bodies from the various species had an isoelectric point of 5.7 to 6.6 and thus possessed a negatively charged surface at neutral pH. We conclude that seed oil bodies from diverse species are very similar in structure. In rapeseed during maturation, TAG and oleosins accumulated concomitantly. TAG-synthesizing acyltransferase activities appeared at an earlier stage and peaked during the active period of TAG accumulation. The concomitant accumulation of TAG and oleosins is similar to that reported earlier for maize and soybean, and the finding has an implication for the mode of oil body synthesis during seed maturation.
Formation of hydrogen atoms in pyrolysis of ethylbenzene behind shock waves. Rate constants for the thermal dissociation of the benzyl radical

Dilute mixtures (1–10 ppm) of ethylbenzene-d1 and ethyl-α, α-d2-benzene in argon were pyrolyzed behind incident shock waves at temperatures of 1430–1740 K and total pressure of 0.55 atm. Progress of the reaction was followed by analysis for H and D atoms by resonance absorption spectroscopy. Analysis of the data showed that no appreciable amounts of H or D atoms are formed in the initial step of ethylbenzene pyrolysis, so our results agree with the traditional ethylbenzene pyrolysis mechanism, to methyl and benzyl radicals. A first-order rate constant expression, k=5.4×1016exp(−100 kcal/RT) s−1 is found for the pyrolysis of the benzyl radical to smaller fragments, with an estimated uncertainty of a factor of 2. This expression gives rate constants a factor of 2 to 3 higher than those reported by Astholz and Troe (10).
IL-23 and IL-17A, but Not IL-12 and IL-22, Are Required for Optimal Skin Host Defense against Candida albicans

IL-23 and Th17 cells play important roles in host defense against systemic infections with extracellular bacteria and fungi, although their roles in immunity against localized skin infections are less well defined. Here, the contributions of IL-23 and Th17 cytokines in host defense against cutaneous Candida albicans infection were evaluated. Mice deficient in IL-23 or IL-17A demonstrated delayed healing and decreased IL-17A production after skin infection with C. albicans compared with wild-type mice or mice deficient in IL-12 or IL-22. Histologic examination revealed epidermal hyperplasia overlying infected dermis four days postinoculation in wild-type mice. In IL-23–deficient mice, fungal burden was greater in skin, neither IL-17A nor IL-22 mRNAs were expressed postinfection, and these mice demonstrated only minimal epidermal hyperplasia. Exogenous recombinant IL-17A injected at the site of skin infection promoted more rapid healing of candidiasis in both wild-type mice and mice deficient in IL-23 and IL-12. Taken together, these results demonstrate that IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal host defense against cutaneous candidiasis. In addition, recombinant IL-17A may serve as a potential therapy to enhance healing in individuals with chronic cutaneous candidiasis.
Brief Paper: Simultaneous External and Internal Stabilization for Continuous and Discrete-Time Critically Unstable Linear Systems with Saturating Actuators

The issues arising in hybrid or simultaneous external as well as internal stabilization of linear systems with saturating actuators are considered. Four different stabilization problems are studied. Roughly, these problems are (1) simultaneous semi-global external as well as semi-global internal stabilization, (2) simultaneous semi-global external as well as global internal stabilization, (3) simultaneous global external as well as semi-global internal stabilization, and (4) simultaneous global external as well as global internal stabilization. As evident from the literature, the requirement of internal stabilization alone either in the global or semi-global sense demands that the linear part of the given system be (a) stabilizable, and (b) has all its poles in the closed left half complex plane for continuous-time systems while it has all its poles inside and/or on the unit circle for discrete-time systems. This implies that the posed simultaneous stabilization problems are solvable at best only under the conditions (a) and (b). Under such conditions, we construct here explicit state as well as measurement feedback controllers for all the four problems in the case of continuous-time systems, and for the problems (1), (2) and (4) in the case of discrete-time systems. The design methodologies used to construct appropriate feedback laws are based on by now familiar low-gain and low-and-high gain design concepts or certain scheduled versions of them.
Security and privacy for body cameras used in law enforcement

The move towards deploying body cameras for law enforcement personnel makes the security and privacy of these body cameras a pressing problem. Body cameras record police interactions with the public, mainly to provide evidence of potential malicious police actions. However, since these body cameras are deployed and maintained by the police departments themselves, there is lack of trust in the integrity of the footage. Furthermore, the pervasive use of body cameras increases the surveillance of general public, causing a loss of privacy. This paper presents a system that protects the integrity of the body camera videos, as well as protect public privacy. Our approach integrates computer vision techniques onto a resource constrained body camera system, and our evaluation indicates that our approach is feasible to be applied on body cameras.
The Modulation of Sperm Function by the Oviductal Epithelium

During their sojourn in the female tract, sperm come into contact with the epithelial cells that line the tract and their secretions. In the past, much attention has been given to the nature and composition of uterine and oviductal fluid (1-3) with the aim of understanding what components of these fluids may affect the events associated with fertiliza- tion and preimplantation embryo development. A number of secretory glycoproteins have been identified in repro- ductive tract fluids of several species (3). However, with the exception of two estrus-associated oviductal glycopro- teins that may play a role in the capacitation (4, 5) and/or motility (6) of bovine sperm, the function of these glyco- proteins in relation to sperm physiology remains unclear. One remarkable aspect of sperm behavior, widely ob- served across species, is a tendency to directly contact and adhere to the epithelial cells that line the tract. Evidence is accumulating that such contacts are physiologically signif- icant. Thus, examination of the role of direct contact be- tween sperm and the epithelial cells that line the tract may provide additional insight into the mechanisms that control sperm biology in vivo. Although sperm come into contact with cervical and uterine epithelial cells during passage through the tract, oviductal epithelial-sperm cell interac- tions are of particular importance. In many species, the isth- mic region of the oviduct is an important site of sperm storage prior to fertilization (7). While resident in the lower isthmus, many sperm adhere to the apical plasma mem- brane of the ciliated and secretory epithelial cells that line this region. For all species studied so far, adhesion is spe- cific to the rostral region of the sperm head. Sperm adhe- sion to isthmic epithelial cells is temporary, and adherent sperm are capable of detaching from the epithelium and reaching the oviductal ampulla to participate in fertilization (8). Current evidence indicates that temporary adherence to the oviductal epithelium has a beneficial effect on sperm viability both in vivo (9) and in vitro (10-15). The ability of sperm to adhere to and detach from the epithelium appears to be related to their capacitation status. Capacitated hamster and bull sperm bind to oviductal epi- thelial cells with much lower frequency than uncapacitated sperm (8, 16, 17). This may be due to changes in the head plasma membrane that occur during capacitation or due to
To Ask or Not to Ask? Opinions of Pediatric Medical Inpatients about Suicide Risk Screening in the Hospital

Objective To describe opinions about suicide risk screening in a pediatric medical inpatient sample. Study design As part of a larger instrument validation study, 200 pediatric medical inpatients (ages 10-21 years) were screened for suicide risk. Participants completed demographic self-report forms and were asked their opinions about suicide risk screening. Patient responses were recorded verbatim by trained research social workers. Qualitative data was analyzed using thematic analysis. Results The majority of adolescents who participated had not been previously asked about suicide (N = 101; 62.3%) and were supportive of suicide risk screening (81.0%). Five salient themes emerged from the qualitative analysis of patient opinions: prevention, elevated risk, emotional benefits, provider responsibility, and lack of harm in asking. Conclusions The majority of youth screened for suicide risk on medical inpatient units were supportive of suicide risk screening. Opinion data have the potential to inform screening practices and assure clinicians that suicide risk screening will be acceptable to pediatric patients and their parents. Given the lack of screening in these patients' past experiences, the medical setting is a unique opportunity to capture youth at risk for suicide.
Connection between plasma response and resonant magnetic perturbation (RMP) edge localized mode (ELM) suppression in DIII-D

Calculations of the plasma response to applied non-axisymmetric fields in several DIII-D discharges show that predicted displacements depend strongly on the edge current density. This result is found using both a linear two-fluid-MHD model (M3D-C1) and a nonlinear ideal-MHD model (VMEC). Furthermore, it is observed that the probability of a discharge being edge localized mode (ELM)-suppressed is most closely related to the edge current density, as opposed to the pressure gradient. It is found that discharges with a stronger kink response are closer to the peeling–ballooning stability limit in ELITE simulations and eventually cross into the unstable region, causing ELMs to reappear. Thus for effective ELM suppression, the RMP has to prevent the plasma from generating a large kink response, associated with ELM instability. Experimental observations are in agreement with the finding; discharges which have a strong kink response in the MHD simulations show ELMs or ELM mitigation during the RMP phase of the experiment, while discharges with a small kink response in the MHD simulations are fully ELM suppressed in the experiment by the applied resonant magnetic perturbation. The results are cross-checked against modeled 3D ideal MHD equilibria using the VMEC code. The procedure of constructing optimal 3D equilibria for diverted H-mode discharges using VMEC is presented. Kink displacements in VMEC are found to scale with the edge current density, similar to M3D-C1, but the displacements are smaller. A direct correlation in the flux surface displacements to the bootstrap current is shown.
A retrospective study of long-term treatment outcomes for reduced vocal intensity in hypokinetic dysarthria

Reduced vocal intensity is a core impairment of hypokinetic dysarthria in Parkinson’s disease (PD). Speech treatments have been developed to rehabilitate the vocal subsystems underlying this impairment. Intensive treatment programs requiring high-intensity voice and speech exercises with clinician-guided prompting and feedback have been established as effective for improving vocal function. Less is known, however, regarding long-term outcomes of clinical benefit in speakers with PD who receive these treatments. A retrospective cohort design was utilized. Data from 78 patient files across a three year period were analyzed. All patients received a structured, intensive program of voice therapy focusing on speaking intent and loudness. The dependent variable for all analyses was vocal intensity in decibels (dBSPL). Vocal intensity during sustained vowel production, reading, and novel conversational speech was compared at pre-treatment, post-treatment, six month follow-up, and twelve month follow-up periods. Statistically significant increases in vocal intensity were found at post-treatment, 6 months, and 12 month follow-up periods with intensity gains ranging from 5 to 17 dB depending on speaking condition and measurement period. Significant treatment effects were found in all three speaking conditions. Effect sizes for all outcome measures were large, suggesting a strong degree of practical significance. Significant increases in vocal intensity measured at 6 and 12 moth follow-up periods suggested that the sample of patients maintained treatment benefit for up to a year. These findings are supported by outcome studies reporting treatment outcomes within a few months post-treatment, in addition to prior studies that have reported long-term outcome results. The positive treatment outcomes experienced by the PD cohort in this study are consistent with treatment responses subsequent to other treatment approaches which focus on high-intensity, clinician guided motor learning for voice and speech production in PD. Theories regarding the underlying neurophysiological response to treatment will be discussed.
Investigating the Reactivity of 1,4-Anthracene-Incorporated Cycloparaphenylene.

Cycloparaphenylenes (CPPs) and their derivatives are unique conjugated macrocycles with novel optoelectronic and host–guest properties. A better understanding of their reactivity is essential for creating new functional materials utilizing these strained aromatic molecules as building blocks. 1,4-Anthracene-incorporated CPP 1 was synthesized and exhibited Diels–Alder reactivity but was unable to photodimerize. Comparison studies with cyclophane 2 and unstrained 3 indicated that the distorted anthracene geometry is likely the major contributor to the anomalous reactivity of 1.
RETHINKING MEDICINE : IMPROVING HEALTH OUTCOMES WITH COST-EFFECTIVE PSYCHOSOCIAL INTERVENTIONS

Thoughts, feelings, and moods can have a significant effect on the onset of some diseases, the course of many, and the management of nearly all. Many visits to the doctor are occasioned by psychosocial distress. Even in those patients with organic medical disorders, functional health status is strongly influenced by mood, coping skills, and social support, yet the predominant approach in medicine is to treat people with physical and chemical treatments that neglect the mental, emotional, and behavioral dimensions of illness. This critical mismatch between the psychosocial health needs of people and the usual medical response leads to frustration, ineffectiveness, and wasted health care resources. There is emerging evidence that empowering patients and addressing their psychosocial needs can be health and cost effective. By helping patients manage not just their disease but also common underlying needs for psychosocial support, coping skills, and sense of control, health outcomes can be significantly improved in a cost-effective manner. Rather than targeting specific diseases or behavioral risk factors, these psychosocial interventions may operate by influencing underlying, shared determinants of health such as attitudes, beliefs, and moods that predispose toward health in general. Although the health care system cannot be expected to address all the psychosocial needs of people, clinical interventions can be brought into better alignment with the emerging evidence on shared psychosocial determinants of health by providing services that address psychosocial needs and improve adaptation to illness.
AVFSM: a framework for identifying and mitigating vulnerabilities in FSMs

A finite state machine (FSM) is responsible for controlling the overall functionality of most digital systems and, therefore, the security of the whole system can be compromised if there are vulnerabilities in the FSM. These vulnerabilities can be created by improper designs or by the synthesis tool which introduces additional don't-care states and transitions during the optimization and synthesis process. An attacker can utilize these vulnerabilities to perform fault injection attacks or insert malicious hardware modifications (Trojan) to gain unauthorized access to some specific states. To our knowledge, no systematic approaches have been proposed to analyze these vulnerabilities in FSM. In this paper, we develop a framework named Analyzing Vulnerabilities in FSM (AVFSM) which extracts the state transition graph (including the don't-care states and transitions) from a gate-level netlist using a novel Automatic Test Pattern Generation (ATPG) based approach and quantifies the vulnerabilities of the design to fault injection and hardware Trojan insertion. We demonstrate the applicability of the AVFSM framework by analyzing the vulnerabilities in the FSM of AES and RSA encryption module. We also propose a low-cost mitigation technique to make FSM more secure against these attacks.
Surgical correction of severe mitral prolapse without mitral insufficiency but with pronounced cardiac arrhythmias.

Despite what was considered adequate pharmacological treatment, the conditon of six patients with severe mitral valve prolapse but with trivial or no mitral regurgitation deteriorated. These patients had marked weakness, chest pain, dyspnea, and arrhythmias. Because these patients found their condition to be intolerable, the prolapsed mitral valve was repaired. Electrocardiography, treadmill stress testing, and left ventriculography performed following operation showed complete repair of the valve and significant improvement over the preoperative findings in all six patients. Repair of the floppy mitral valve did not eradicate all abnormalities; however, it did significantly improve the chest pain, weakness, dyspnea, and arrhythmias in all six patients. Five patients no longer require any medication. The prolapsed mitral valve contributed significantly to the symptoms and arrhythmias, but it could not have been the sole cause for these patients’ signs and symptoms. With complete correction of the prolapse in all six patients, few of the signs and symptoms of the disease persisted. Repair of severe mitral valve prolapse without mitral regurgitation is recommended only for those patients who continue to be severely symptomatic from chest pain, dyspnea, or ventricular arrhythmias after an extensive trial of adequate medical therapy.
Health Surveillance for Health Care Workers: A Vital Role for the Occupational and Environmental Health Nurse

Health surveillance for the general health care worker includes surveillance for immunity to infectious diseases such as measles, mumps, rubella, varicella, and hepatitis B. Post exposure surveillance for bloodborne pathogens includes HIV, hepatitis B, and hepatitis C. Periodic surveillance of specialty practice areas as mandated by OSHA include workers exposed to lasers, radiation, formaldehyde, ethylene oxide, hazardous drugs, anesthetic gases, and tuberculosis.
Evaluation of endometrial tissue specific complement activation in women with endometriosis.

Objective To determine if endometrial tissue specific complement (C) activation occurs in patients with endometriosis. Design Prospective. Setting University of Oklahoma Health Sciences Center, a tertiary care referral center. Patients Twenty-six women, 9 with endometriosis and 17 without endometriosis. Interventions None. Main Outcome Measures Uterine and ectopic endometria were evaluated by the immunofluorescence assay for the presence of activated products of the initial (C3d) and terminal (C5b-9) C pathway, C3 regulatory proteins (decay-accelerating factor and membrane cofactor protein), and terminal C regulatory proteins (clusterin and vitronectin). Results The initial (C3d) and terminal (C5b-9) C components were deposited on blood vessel walls in uterine and/or ectopic endometria of women with and without endometriosis. In the stromal compartment at both sites, C deposition was colocalized with terminal C inhibitors/cell-cell attachment factors, clusterin and vitronectin on elastic fibers. No specific staining for C proteins was detected on the glandular epithelium of uterine and ectopic endometrial tissues examined. Furthermore, intense staining of endometrial epithelium for C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein was noted on endometrial glands from women with and without endometriosis. Conclusions Our findings demonstrate a lack of specific deposition of C in the glandular epithelial cells of endometria of women with endometriosis. The localization of C3 regulatory proteins, decay-accelerating factor, and membrane cofactor protein on glandular epithelium may suggest the involvement of intrinsic protective mechanisms on these cells from autologous C attack in vivo.
The plasma membrane ATPase of Neurospora: a proton-pumping electroenzyme.

Probably the best marker enzyme for plasma membranes of eukaryotic cells is a magnesium-dependent, vanadate-inhibited ATPase whose primary function is the transmembrane transport of cations. In animal cells, different species of the enzyme transport different cations: sodium ions released in unequal exchange for potassium ions, calcium ions extruded alone (perhaps), or protons secreted in equal exchange for potassium ions. But in plants and fungi only proton secretion has been clearly demonstrated. A useful model cell for studying the proton-secreting ATPase has been the ascomycete fungusNeurospora, in which the enzyme drives an outward current of protons that can exceed 50 µA/cm2 and can support membrane potentials greater than 300 mV. Both thermodynamic and kinetic studies have shown that the proton-pumping ATPase ofNeurospora normally transports only a single proton for each ATP molecule split; and kinetic modelling studies have suggested (contrary to conventional assumptions) that the fast steps in the overall reaction are transmembrane transit of the proton and its dissociation following transport, while the slow steps are the binding of protons and/or ATP. The primary structure of theNeurospora enzyme, recently deduced by gene sequencing, is very close to that of the yeast (Saccharomyces) enzyme, and the hydropathic patterns for both closely resemble those for the animal-cell plasma-membrane ATPases. All of these enzymes appear to have 6–10 membrane-spanning α-helices, plus a large cytoplasmic headgroup which bears the catalytic nucleotide-binding site. Structural data, taken together with the electrical-kinetic behavior, suggest that the catalytic headgroup functions as an energized gate for protons. From a geometric point of view, action of such a gate would transfer the membrane field across the “transported” ion, rather than vice versa.
Pharmacological Treatment of Underactive Bladder

Current standard pharmacotherapy for underactive bladder (UAB) and detrusor underactivity (DUA) includes muscarinic receptor agonists, such as bethanechol and carbachol to stimulate detrusor muscarinic receptors, choline esterase inhibitors, like distigmine to reduce the degradation of acetylcholine, and α-adrenoceptor antagonists to block α-adrenoceptors in the outflow region. α-Adrenoceptor antagonists may have a beneficial effect on UAB/DUA in some cases of functional outflow obstruction, caused by benign prostatic hyperplasia or neurogenic bladder, however, available information shows that little clinically useful effect of muscarinic receptor agonists or choline esterase inhibitors can be obtained in preventing or treating the condition. Other types of drug, such as transient receptor potential channel agonists and prostanoids have so far had no or limited success. Even if theoretically the condition can be improved by agents that increase detrusor contractile activity and decrease bladder capacity, and/or decrease outlet resistance, the multifactorial pathophysiology of UAB/DUA, involving both central and peripheral factors, has to be considered, and to be successful, therapy has to be directed to both the major mechanism involved and to the associated morbidities.
Financial Implications of the Emergency Medicine Interview Process

Background Emergency medicine (EM) residency interviews are an important, yet costly process for programs and applicants. The total economic burden of the EM interviewing process is previously unstudied. Graduate medical education funding and student finances are both fragile shifting sources, which appear to fund most of these economic expenditures. Objectives The total economic impact of the EM interview season is unknown. This study sought to calculate total dollars spent by EM residency programs and senior medical students (M4) during interview season. Potential solutions for reducing this burden will be outlined. Methods Institutional review board–approved, piloted e-mail surveys were sent to accredited (Accreditation Council for Graduate Medical Education [ACGME] and American Osteopathic Association [AOA]) EM program directors (PDs) and M4 student members of EMRA. PDs were queried after the 2014–2015 interview season. PDs questions included demographics, estimated faculty, and resident and administrative time used, along with dollars spent during the 2014–2015 interview season. M4 questions included demographics and dollars spent during the 2015–2016 season. Results were reported using descriptive statistics. Financial data for EM programs were calculated with academic EM faculty, resident, and administrative assistant salaries along with reported hours used during the interview season. Results A total of 82 of 223 EM PDs completed the survey, reporting an mean annual cost of $210,649.04 per program to review, screen, and interview applicants based on time spent by faculty, resident, and administrative assistants. A total of 84.6% of EM program costs were due to faculty hours. A total of 180 of 1,425 EM-bound M4 students completed the survey, reporting a mean annual estimate of US$5,065.44 per student to apply and interview. Seventy-two percent of estimated costs were due to airfare and lodging. Loans and credit cards were the top two methods of payments of these interview costs by students. Extrapolating the cost of EM personnel with hours spent, the economic burden of an interview season for EM programs is approximately US$46,974,735.92. M4 students spent US$19,724,823.40 for application fees and interview-related expenses. Conclusions Emergency medicine residency programs and applicants appear to spend over US$66 million per cycle on the interview process. EM residency programs may save resources by reducing faculty hours associated with the interview process and leveraging administrative and resident resources. Creation of regional or national fixed interview locations may also be appropriate. Applicants may reduce travel costs by participating in video interviews, reducing program applications, and attending regionalized interview days. A full conversation among all specialties and organized medicine needs to take place to reform the systems in place to reduce the economic burden on students and residency programs.
Improved Prognosis of Chronic Lymphocytic Leukemia (CLL) Patients with Increased IgVH Mutations May Reflect Greater Alteration of the B-Cell Receptor (BCR) Binding Site

BACKGROUND: IgVH mutation status is a well accepted prognostic marker in CLL. Typically >98% sequence homology to the most similar germline gene is considered unmutated, and ≤98% is considered mutated. The 98% cutoff was originally chosen to account for undefined IgVH polymorphisms that could be responsible for DNA sequence disparity. Prior data showed that mutated patients have a more benign course of disease vs. unmutated patients. Although it has been presumed that this is due to a structural change in the BCR, specific consideration of the nature of the mutations (silent or replacement) and the relation to clinical course has not been made. We recently showed that IgVH somatic mutation correlates to disease course in a continuous fashion; prognosis improves as the number of mutations increases. Therefore, the present study was designed to determine if replacement mutations were more important than silent mutations or if the “mutation process” (reflected as the total number of mutations, irrespective of their structural impact) was responsible for improved survival METHODS: We sought to determine if further characterization of mutations (replacement vs. silent) and location thereof (framework (FR) v. complementarity determining region (CDR)) changed with increasing number of mutations. We hypothesized the ratio of replacement-to-silent (R:S) mutations would be greater in those with better prognosis because such changes could significantly alter the structure of the antigen-binding site and that this would be more pronounced in the CDRs. Survival analysis (Kaplan-Meier, logrank test (overall and adjusted pairwise), Cox regression) was used to analyze both outcomes of time to treatment (TTT) and survival (OS). Quartiles of numbers of mutations were used to determine how outcome varied accordingly. The range of mutation in each quartile divided as follows: 1–9; 10–15; 11–20; and 21–39. We examined the ratio of R:S mutations to determine whether the ratios varied according to quartile (Mann-Whitney test). RESULTS: 353 patients were analyzed. 89 of 334 (27%) had received treatment and 53 of 353 (15%) had died. The lower quartile of mutations (1–9) had a significantly shorter TTT and OS than the three higher quartiles (P CONCLUSION: The association of better prognosis with more IgVH mutations may reflect the higher ratio of R:S mutations in the CDR. These data have implications as to the role of the CLL B-cell receptor (BCR) and its specificity in clinical outcome. Assuming that in vivo BCR stimulation causes CLL cell proliferation, increased replacement mutations in the CDRs would lead to more binding site structural or conformational change and thereby narrow antigen-binding range. This would limit the diversity of antigens capable of delivering a stimulatory signal. That no increase in R:S was found in the FRs is consistent with these regions’ function as a scaffolding to the BCR, the structural alteration of which could render the BCR ineffective.
Incorporation of Axial Chirality into Phosphino-Imidazoline Ligands for Enantioselective Catalysis

A complementary strategy for ligand tuning that enables controlling ligand conformation is described here. The concept is demonstrated with new ligands that are employed in the catalytic enantioselective preparation of the highly important C2-aminoalkyl five-membered heterocycle motif. The alkynylation/cyclization sequence developed here is convergent, highly modular, and allows for a complementary scope to the heteroarylation of imines. This new ligand platform should offer new possibilities for expanding the use of PHIM-type ligands in a large variety of new transformations.
Annular Dehn fillings

We show that if a simple 3-manifold M has two Dehn fillings at distance $ \Delta \geq 4 $ , each of which contains an essential annulus, then M is one of three specific 2-component link exteriors in S 3 . One of these has such a pair of annular fillings with $ \Delta = 5 $ , and the other two have pairs with $ \Delta = 4 $ .
Ablation of Visual Areas in the Central Nervous System

Experiments utilizing ablation of cerebral tissue fall into two classes, those which leave a particular behavior undisturbed and thus demonstrate that the tissue removed is nonessential to the behavior; and those which disrupt the behavior under study. Results in the former case may be trivial, as they frequently were prior to adequate knowledge of the functional anatomy of the cerebral cortex. For instance, Franz (1911) performed a careful study of vision following occipital lobectomy in monkeys, but came to erroneous conclusions by missing what is now known to be the representation of the fovea in the far lateral striate cortex (and probably also the deeply concealed anterior tip of the striate area). Presently available techniques should preclude repetition of this type of error. The functional state of surviving tissue can be assayed electrophysiologically and the extent and location of a neocortical lesion can be checked against retrograde thalamic degeneration1. Using such criteria it is now apparent that visual pattern discrimination (Fig. 4) in the cat (Doty, 1961b, 1971; Spear and Braun, 1969; Wetzel et al., 1965; Winans, 1967) and possibly in the tree shrew (Snyder and Diamond, 1968) or rat (Lewellyn et al., 1969), can survive loss of the striate cortex. In view of the elaborate physiological processing of visual information known to occur in the striate cortex (e.g., Hubel and Wiesel, 1962) this result is clearly unexpected and raises difficult questions concerning the functions and organization of the neocortical visual system.
High-dose methotrexate with and without rituximab for the treatment of newly diagnosed primary CNS lymphoma: Johns Hopkins Hospital experience.

2034 Background: The current institutional standard for treatment of patients with newly-diagnosed primary CNS lymphomas (PCNSL) at Johns Hopkins Hospital (JHH) consists of treatment with high-dose...
Effect of Environmental Impedance Surrounding a Radiofrequency Ablation Catheter Electrode on Lesion Characteristics

Environmental Impedance and Ablation LesionsIntroduction The electrical conductivity of the environment surrounding a catheter electrode may affect radiofrequency (RF) current. A higher impedance environment enveloping a catheter tip can be insulating and thus direct RF preferentially into targeted cardiac tissue. We sought to evaluate whether different environmental impedances will affect RF lesions. Methods An ex vivo model using bovine myocardium, load cell, and 4 mm ablation catheter was tested using a circulating bath of normal (0.9%; NS) and half normal (0.45%; HNS) saline. Ablations were performed at 50 W. In addition, using a porcine thigh prep model, warmed heparinized blood was circulated at 350 mL/min. Prior to ablation, circulating bath impedance was altered with NS and HNS. RF was applied at 30 W with a force-sensing, open irrigated catheter. Results Ex vivo RF with a 4 mm catheter using an HNS bath led to larger lesions, 286.7 ± 64 mm³ versus 198.9 ± 61 mm³ (P < 0.001), compared to an NS bath. In the porcine thigh prep, for RF in the high impedance (HNS) bath, initial and final impedances were higher, and the measured impedance reductions during ablation were larger, compared to RF in the low impedance (NS) bath. In vivo ablation within a higher impedance bath created larger lesion sizes, compared to a lower impedance bath, 222.4 ± 63.4 mm3 versus 135.4 ± 61.7 mm3 (P < 0.001). Conclusions A higher impedance surrounding an RF catheter can facilitate more effective RF and thereby increase lesion size. This may have implications for RF safety and efficacy, especially in the epicardium where pericardial fluid can be altered with infusion of ionic solutions.
Neutrophils: positive or negative?

In this issue of Blood, Valgardsdottir et al demonstrate that human neutrophils do not kill chronic lymphocytic leukemia (CLL) B cells opsonized with the CD20 monoclonal antibody (mAb) rituximab (RTX) or obinutuzumab (OBZ); instead, the neutrophils remove both CD20 and bound mAbs from B cells by trogocytosis.1
Surgery versus optimal medical management of early-stage small cell lung cancer.

8511Background: Differences in the use and impact of surgery versus optimal medical management (concurrent chemoradiation) for patients with cT1-2N0M0 SCLC have never been evaluated in population-b...
Municipal Vehicles as Sensor Platforms to Monitor Roadway Traffic

Urban traffic monitoring is important for applications ranging from real-time traffic-responsive signal control to long-term estimations for planning and infrastructure health. Current urban roadway traffic monitoring suffers from two problems: generally the monitoring locations are at discrete locations that are spatially sparse, and in many cases the collection lasts only a few days during a multiyear interval. As a result, most of the network is unmonitored. To supplement conventional traffic monitoring, this study explored the possibility of using municipal or public vehicles as moving sensor platforms to monitor the surrounding roadway traffic, thereby extending data collection to a large portion of the currently unmonitored network. The study used many hours of empirical sensor data collected from a prototype instrumented vehicle to identify and count passing vehicles, measure their speed, and classify the target vehicles according to measured shape and size. The instrumented vehicle is equipped wit...
Complement regulator CD59 prevents peripheral organ injury in rats made seropositive for neuromyelitis optica immunoglobulin G.

Pathogenesis in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorders (herein called NMO) involves complement-dependent cytotoxicity initiated by AQP4-IgG binding to astrocyte AQP4. We recently reported that rats lacking complement inhibitor protein CD59 were highly susceptible to development of NMO pathology in brain and spinal cord following direct AQP4-IgG administration (Yao and Verkman, Acta Neuropath Commun 2017, 5:15). Here, we report evidence that CD59 is responsible for protection of peripheral, AQP4-expressing tissues in seropositive NMO. Rats made seropositive by intraperitoneal injection of AQP4-IgG developed marked weakness by 24 h and died soon thereafter. Serum creatine phosphokinase at 24 h was >900-fold greater in seropositive CD59−/− rats than in seropositive CD59+/+ (or control) rats. AQP4-expressing cells in skeletal muscle and kidney, but not in stomach, of seropositive CD59−/− rats showed injury with deposition of AQP4-IgG and activated complement C5b-9, and inflammation. Organ injury in seropositive CD59−/− rats was prevented by a complement inhibitor. Significant pathological changes in seropositive CD59−/− rats were not seen in optic nerve, spinal cord or brain, including circumventricular tissue. These results implicate a major protective role of CD59 outside of the central nervous system in seropositive NMO, and hence offer an explanation as to why peripheral, AQP4-expressing cells are largely unaffected in NMO.
Sex hormones and the development of sexual size dimorphism: 5α-dihydrotestosterone inhibits growth in a female-larger lizard (Sceloporus undulatus).

ABSTRACT Sexual differences in adult body size [sexual size dimorphism (SSD)] and color (sexual dichromatism) are widespread, and both male- and female-biased dimorphisms are observed even among closely related species. A growing body of evidence indicates testosterone can regulate growth, thus the development of SSD, and sexual dichromatism. However, the mechanism(s) underlying these effects are conjectural, including possible conversions of testosterone to estradiol (E2) or 5α-dihydrotestosterone (DHT). In the present study, we hypothesized that the effects of testosterone are physiological responses mediated by androgen receptors, and we tested two specific predictions: (1) that DHT would mimic the effects of testosterone by inhibiting growth and enhancing coloration, and (2) that removal of endogenous testosterone via surgical castration would stimulate growth. We also hypothesized that females share downstream regulatory networks with males and predicted that females and males would respond similarly to DHT. We conducted experiments on eastern fence lizards (Sceloporus undulatus), a female-larger species with striking sexual dichromatism. We implanted Silastic® tubules containing 150 µg DHT into intact females and intact and castrated males. We measured linear growth rates and quantified color for ventral and dorsal surfaces. We found that DHT decreased growth rate and enhanced male-typical coloration in both males and females. We also found that, given adequate time, castration alone is sufficient to stimulate growth rate in males. The results presented here suggest that: (1) the effects of testosterone on growth and coloration are mediated by androgen receptors without requiring aromatization of testosterone into E2, and (2) females possess the androgen-receptor-mediated regulatory networks required for initiating male-typical inhibition of growth and enhanced coloration in response to androgens.
Child Abuse and Dissociative Identity Disorder/Multiple Personality Disorder: The Documentation of Childhood Maltreatment and the Corroboration of Symptoms

There is a consensus in the literature that early, severe maltreatment antedates dissociative identity disorder/multiple personality disorder (DID/MPD). Most data on maltreatment, however, are gathered retrospectively from the patient only. This article presents the cases of six violent, incarcerated men with DID/MPD. It documents from records and family interviews their childhood and adult dissociative symptoms and signs and their abusive childhood experiences.
Combining Qualitative and Quantitative Temporal Reasoning for Criminal Forensics

The paper presents an application of temporal knowledge representation and reasoning techniques to forensic analysis, especially in answering certain investigative questions relating to time-sensitive information about a criminal or terrorist activity. A brief introduction to a temporal formalism called Point-Interval Logic is presented. A set of qualitative and quantitative temporal facts is taken from the London bombing incident that took place on July 7, 2005, to illustrate the use of temporal reasoning for criminal forensics. The information used in the illustration is gathered through the online news sites. A hypothetical investigation on the information is carried out to identify certain time intervals of potential interest to counterterrorist investigators. A software tool called Temper that implements Point-Interval Logic is used to run the analysis and reasoning presented in the paper.
Lazy Self-composition for Security Verification

The secure information flow problem, which checks whether low-security outputs of a program are influenced by high-security inputs, has many applications in verifying security properties in programs. In this paper we present lazy self-composition, an approach for verifying secure information flow. It is based on self-composition, where two copies of a program are created on which a safety property is checked. However, rather than an eager duplication of the given program, it uses duplication lazily to reduce the cost of verification. This lazy self-composition is guided by an interplay between symbolic taint analysis on an abstract (single copy) model and safety verification on a refined (two copy) model. We propose two verification methods based on lazy self-composition. The first is a CEGAR-style procedure, where the abstract model associated with taint analysis is refined, on demand, by using a model generated by lazy self-composition. The second is a method based on bounded model checking, where taint queries are generated dynamically during program unrolling to guide lazy self-composition and to conclude an adequate bound for correctness. We have implemented these methods on top of the SeaHorn verification platform and our evaluations show the effectiveness of lazy self-composition.
Racial disparities in the diagnosis, surgical management and survival of right sided and left sided colon cancers.

e15660Background: Higher Colorectal cancer (CRC) incidence and mortality in African American (AA) is largely attributed to molecular characteristics, advanced stage of diagnosis, and inadequate acc...