cssi/SciSciGPT-SciSciNet huggingface dataset:
Sulfation of 4-hydroxytamoxifen is a novel pathway of tamoxifen-induced apoptosis in breast cancer cell lines

Proc Amer Assoc Cancer Res, Volume 46, 2005 5323 For the past thirty years, tamoxifen therapy for estrogen receptor positive breast cancer has been the gold standard of therapy and has been a major factor in increasing overall survival from this disease. The primary mechanism of action of tamoxifen’s effect has been thought to be mediated by binding of the active metabolite, 4-hydroxytamoxifen, to the estrogen receptor, thus blocking estrogen-stimulated cellular proliferation. However, it is known that tamoxifen exerts many effects on tumor cells, including the induction of apoptosis. 4-Hydroxytamoxifen is sulfated to form 4-sulfoxytamoxifen (4-SO4TAM) in a reaction catalyzed by human sulfotransferase 1A1 (SULT 1A1). SULT1A1 is a member of the sulfotransferase superfamily of Phase II detoxification enzymes. The net result of catalysis by SULT1A1 is generally to produce a metabolite that is more polar, and thus, more easily excretable from the organism. A single nucleotide polymorphism in exon 7 of the SULT 1A1 ( SULT 1A1*2 ) gene produces a less thermostable enzyme with approximately two-fold lower activity than that of the common allele SULT 1A1*1 . We have shown previously that the SULT1A1*2 low activity allele is associated with significantly poorer overall survival in woman treated with tamoxifen for breast cancer. Since this finding was converse to what one would expect if sulfation were an elimination step for this active metabolite, we investigated the hypothesis that 4-SO4TAM plays an important role in the anti-carcinogenic mechanism of tamoxifen through a pathway independent of detoxification. We synthesized 4-SO4TAM and compared the potential of TAM, 4-OHTAM and 4-SO4TAM to initiate DNA damage and apoptosis in various breast cancer cell lines. Comet assays revealed that at equimolar concentrations, significantly more DNA damage was evident in ZR75-1 cells exposed to 4-SO4TAM compared to the other compounds. Average olive tail moments (a measure of DNA breakage) were 3.3, 2.5 and 2.3 for 4-SO4TAM, 4-OHTAM and TAM, respectively. Cytoxicity assays showed that 4-SO4TAM had no cytotoxic properties. Subsequent flow cytometry analysis demonstrated the presence of significant numbers of apoptotic cells when ZR75-1 (ER positive) and MDA-MB231 (ER negative) cells were exposed to 4-SO4TAM. This is the first study to show that 4-SO4TAM can cause apoptosis and therefore it may play a significant role in the efficacy of tamoxifen as an anti-carcinogenic treatment.
Evolving U.S. Efforts to Support Domestic Accountability

During the review conference of the International Criminal Court in Kampala, Uganda, the large and well prepared United States delegation announced a new policy of "principled engagement" with the Court. The American Society of International Law commissioned eight expert papers on the direction that engagement should take, with particular focus on four topics: fostering state cooperation with the Court, developing complementarity between national and ICC jurisdiction, strengthening the impact of the Court on victims and witnesses, and shaping the Court’s jurisdiction over the crime of aggression. This essay was written as part of the ASIL report and proposes a series of specific recommendations designed to strengthen the principle of complementarity, which in practice may be the fulcrum supporting the long term legitimacy and effectiveness of the ICC as an apolitical arbiter of justice. The Rome Statute established a treaty-based framework for a permanent supranational prosecutorial authority built on the principle that state sovereignty can be subordinated on occasion to the goal of achieving accountability for egregious international crimes. Properly understood and implemented, the jurisdictional relationship between the ICC and sovereign states is conceived as a tiered allocation of authority to adjudicate. The creation of a vertical level of prosecutorial authority that operates as a permanent backdrop to the horizontal relations between sovereign states in large part depended on a delineated mechanism for prioritizing jurisdiction to serve the ends of authentic justice while simultaneously preserving sovereign rights. The balance of adjudicative authority between the ICC and states is therefore the bridge that carries the weight of the entire Court structure. In fact, the complementarity structure was an integral component of the overarching multilateral agreement without which the ICC would arguably not have been created. The unambiguous reaffirmation of the complementarity principle by the Assembly of States Parties at the 2010 Kampala Conference means that the U.S. policy preference for assisting states in strengthening domestic prosecutorial systems should move ahead reflecting a principled harmony of values rather than being misbranded as a manifestation of institutional hostility. In the wake of the Kampala Conference, U.S. policymakers and legislators have a clear window of opportunity to augment the efforts of the Assembly of States Parties by reinvigorating aid to domestic systems seeking to develop or enhance domestic capacity to address the enforcement gap that remains an unfortunate reality.
Dynamics of sideslip perching maneuver under dynamic stall influence

Abstract This paper presents the optimization framework and aerodynamic modeling of a sideslip perching trajectory under dynamic stall influence. Based on the optimal trajectory solutions, an impact study of dynamic stall on the spatial and state trajectories of the three-dimensional (3D) perching maneuver is also discussed. At high angles of attack, the behavioral effects of the dynamic separation point on the transient post-stall region are distinguishable with rapid changes of angles of attack and aircraft's turn rates. Introduction of three internal variables thus becomes mandatory for addressing variations in flow state influenced by the swift changes in longitudinal and lateral flight angles. These variables are then integrated into a static nonlinear aerodynamic model, developed using empirical and analytical methods, and into the simulative framework as state variables. In the absence of dynamic stall effects, there is a significant discrepancy in trajectories as opposed to counterpart trajectories inclusive of this phenomenon. The consideration of dynamic stall in longitudinal frame is found to have heightened impact on perching trajectory in response to optimized control inputs as compared to that in lateral frame. With the inclusion of dynamic stall deemed necessary, a comparative study between 2D and 3D perching models is also presented to discuss the distinct drag mechanisms involved. The 3D accommodated perch utilizes the additive combination of longitudinal and lateral drag to dispense its reliance on the gravitational force. Measured against performance parameters which include metrics of spatial cost such as perching distance, longitudinal/lateral deviations and time, the study reveals the 3D mode is an improvement over the 2D mode as the latter model's intransigent characteristic of the undershoot becomes obsolete in the 3D version.
A Positional Biofeedback Device for Sitting Balance

Impaired sitting balance is a frequent complication in the treatment of a patient shortly after the onset of stroke, and especially of a patient with bilateral involvement. These patients frequently exhibit delayed equilibrium reactions and loss of correct body-in-space awareness. Visual cues as well as proprioceptive, vestibular, and auditory input are important to help a patient regain good sitting balance. Progress with one of our bilateral stroke patients was limited because she was blind. On admission to our Center, the patient's static and dynamic sitting balance was severely impaired. The patient was unable to sit unsupported and fell spontaneously to the left and to the rear even with one-hand support from the therapist. The patient had poor body-in-space awareness, and she expressed feeling “erect” when her trunk was inclined 30 degrees to the left.…
Population Structure of Vitis rupestris, an Important Resource for Viticulture

The wild North American grapevine Vitis rupestris Scheele is an important genetic resource for viticulture, but its natural populations have been severely depleted. We collected samples from seven V. rupestris populations from the Ozark Plateau in Missouri and the Ouachita Mountains in Oklahoma and genotyped them with 14 microsatellite markers to assess allelic diversity, heterozygosity, and genetic differentiation at various levels of population structure. We found that genetic diversity in V. rupestris was similar to that measured in many V. vinifera L. ssp. sylvestris populations and in other outcrossing angiosperms. We detected significant genetic differentiation among populations (ΦPT = 0.105); there was no significant deviation from Hardy–Weinberg equilibrium in some populations, and there was moderate inbreeding in others. Pronounced differentiation between Missouri and Oklahoma populations was supported by a Bayesian clustering approach and principle coordinate analyses and was apparently a function of geographic distance. Genetic differentiation among Missouri populations was modest. We posit that population differentiation and genetic drift may be inherent characteristics of V. rupestris.
Metabolism of Coho Salmon Ig: Intraperitoneal Absorption Properties of Coho Salmon Tetrameric Ig

The intraperitoneal absorption properties of Ig purified from coho salmon serum were studied. In all experiments, aliquots of the radiolabeled immunoglobulin were compared in duplicate fish receiving the protein intraperitoneally and intraveneously. This experimental design allowed comparative absorption efficiency and kinetic measurements. The degree and kinetics of absorption were found to be temperature dependent. It was also determined that the monomeric subunit derived from the tetramer was absorbed with lower efficiency over relatively longer periods of time. Absorption results are discussed in terms of their phylogenetic significance.
Contrast-induced nephropathy in outpatients with preexisting renal impairment: a comparison between intravenous iohexol and iodixanol

Abstract Background Concern for contrast-induced nephropathy (CIN) may result in administration of more costly agents. We prospectively compared outpatient CIN incidence of iodixanol to iohexol. Methods Patients were randomized to receive 100 ml of iohexol (n = 47) or iodixanol (n = 55). We compared patients who developed CIN using the Wilson score interval and also calculated an odds ratio for the development of CIN. Results CIN rate for iohexol was 2% compared to 9% for iodixanol. Those receiving iodixanol were almost 5 times more likely to experience CIN. Conclusion These results do not suggest a benefit of iodixanol over iohexol in the study population.
Research for Promoting Re-employment of Difficulties in Finding Work Group in Beijing: Based on the Analysis of Job-seeking Desire and Behavior

This paper focus on promoting the employment and re-employment of the disadvantage group in Beijing.Based on the job-seeking desire and behavior for the disadvantage group and the recognition between employment and re-employment are analyzed.Provide scientific and rigorous evidence for the perfection and improvement of the employment and re-employment,this paper also bring about applicable and feasible measure and suggestion about this program.
Computer Application and File Management

This paper files on my computer management based on the analysis of the status quo. Digital Archives from the files of the website and explore building a computer file management practice two ways computer file management and the implementation of measures on the analysis.
Study on bactericidal effect and toxicity of oral disinfection solution containing chlorhexidine acetate

Objective:To observe the disinfection effect and toxicity safety of oral chlorhexidine acetate disinfect solution.Methods:The study was carried out with quantitative bactericidal tests and animal tests.Results:The results showed that the killing log values of Escherichia coli,Staphylococcus exposed to the disinfection solution for 0.5 min were all 5.00,and that of Candida albicans exposed to the disinfection solution for 0.5 min was 4.00;the mean kill logrithm of skin natural bacteria with 1 min was2.59,the mean kill logrithm of all tests was1.00.The acute oral toxicity test in NIH little rats and SD big rats showed LD50 5000 mg/kg;acute eye irritation test showed non-irritaion;repeated 500 mg/kg~5000 mg/kg body weights dose tests using this solution indicated no mutagenesis effect on body cell;The maximum unobserved dosage was1000 mg/kg.And no main target organs were found to be sub-acute oral toxicity in rats.Conclusion:The disinfectant had good bactericidal effect,mild irritation on mucosa,and low toxicity.
An Easy and Reliable Method to Locate the Dehiscence During Middle Fossa Superior Canal Dehiscence Surgery: It is a (C)inch.

Objective The middle fossa floor lacks reliable surface landmarks. In cases of superior semicircular canal dehiscence (SSCD), multiple skull base defects may be present, further confounding the location of the labyrinth. Misidentification of the SSCD during surgery may lead to treatment failure or sensorineural hearing loss. Anecdotally, the authors have observed the distance from the lateral edge of the craniotomy to the SSCD to be consistently 1 inch. Herein, we present radiologic evidence of this practical and clinically useful relationship. Patients All patients at two tertiary care academic referral centers with high-resolution temporal bone computed tomography (CT) evidence of SSCD were retrospectively reviewed. Intervention(s) Review of high-resolution temporal bone CT. Main outcome measures The horizontal distance from the outer cortex of the squama temporalis immediately superior to the bony external auditory canal (approximating lateral edge of craniotomy) to the SSCD was measured in the coronal plane by two independent reviewers. Results A total of 151 adult ears with SSCD were analyzed. A Shapiro-Wilk goodness-of-fit test confirmed that measurements were normally distributed. Pearson inter-rater correlation was 0.95, confirming very strong agreement. The mean distance between the outer cortex of the squama temporalis and SSCD was 25.9 mm, or 1.02 inches. Sixty-eight percent of the SSCD population would fall between 0.92 and 1.12 inches and 95% would lie between 0.83 and 1.21 inches. Conclusions The horizontal distance from the outer cortex of the squama temporalis to the SSCD consistently approximates 1 inch. This easily remembered distance can aid surgeons in locating or confirming the SSCD during middle fossa surgery.
Vascularization and innervation of slits within polydimethylsiloxane sheets in the subcutaneous space of athymic nude mice

Success of cell therapy in avascular sites will depend on providing sufficient blood supply to transplanted tissues. A popular strategy of providing blood supply is to embed cells within a functionalized hydrogel implanted within the host to stimulate neovascularization. However, hydrogel systems are not always amenable for removal post-transplantation; thus, it may be advantageous to implant a device that contains cells while also providing access to the circulation so retrieval is possible. Here we investigate one instance of providing access to a vessel network, a thin sheet with through-cut slits, and determine if it can be vascularized from autologous materials. We compared the effect of slit width on vascularization of a thin sheet following subcutaneous implantation into an animal model. Polydimethylsiloxane sheets with varying slit widths (approximately 150, 300, 500, or 1500 µm) were fabricated from three-dimensional printed molds. Subcutaneous implantation of sheets in immunodeficient mice revealed that smaller slit widths have evidence of angiogenesis and new tissue growth, while larger slit widths contain native mature tissue squeezing into the space. Our results show that engineered slit sheets may provide a simple approach to cell transplantation by providing a prevascularized and innervated environment.
Legal and policy issues for animal assisted interventions with special populations

ABSTRACTIn order to protect themselves and their animals, persons involved in animal-assisted interventions, as well as those providing therapeutic interventions involving animals and those seeking to study such situations should understand when a law provides a right to be accompanied by an assistance or service animal. Using applicable federal laws in the United States, this article defines service, assistance, and therapy animals and analyzes the circumstances under which persons utilizing these animals have the legal right of access to public places and housing. The article also discusses the intersection of federal, state, and local law in the United States and provides ways state and local laws may provide for greater access for persons accompanied by service, assistance, and therapy animals.
Diagnosis of a North American Polar–Subtropical Jet Superposition Employing Piecewise Potential Vorticity Inversion

AbstractThe polar jet (PJ) and subtropical jet (STJ) often reside in different climatological latitude bands. On occasion, the meridional separation between the two jets can vanish, resulting in a relatively rare vertical superposition of the PJ and STJ. A large-scale environment conducive to jet superposition can be conceptualized as one that facilitates the simultaneous advection of tropopause-level potential vorticity (PV) perturbations along the polar and subtropical waveguides toward midlatitudes. Once these PV perturbations are transported into close proximity to one another, interactions between tropopause-level, lower-tropospheric, and diabatically generated PV perturbations work to restructure the tropopause into the two-step, pole-to-equator tropopause structure characteristic of a jet superposition.This study employs piecewise PV inversion to diagnose the interactions between large-scale PV perturbations throughout the development of a jet superposition during the 18–20 December 2009 mid-Atlant...
Persistent Electrochemical Performance in Epitaxial VO2(B)

Discovering high-performance energy storage materials is indispensable for renewable energy, electric vehicle performance, and mobile computing. Owing to the open atomic framework and good room temperature conductivity, bronze-phase vanadium dioxide [VO2(B)] has been regarded as a highly promising electrode material for Li ion batteries. However, previous attempts were unsuccessful to show the desired cycling performance and capacity without chemical modification. Here, we show with epitaxial VO2(B) films that one can accomplish the theoretical limit for capacity with persistent charging–discharging cyclability owing to the high structural stability and unique open pathways for Li ion conduction. Atomic-scale characterization by scanning transmission electron microscopy and density functional theory calculations also reveal that the unique open pathways in VO2(B) provide the most stable sites for Li adsorption and diffusion. Thus, this work ultimately demonstrates that VO2(B) is a highly promising energy ...
Engineering of RuMb: Toward a Green Catalyst for Carbene Insertion Reactions.

The small, stable heme protein myoglobin (Mb) was modified through cofactor substitution and mutagenesis to develop a new catalyst for carbene transfer reactions. The native heme was removed from wild-type Mb and several Mb His64 mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were characterized by UV–vis and circular dichroism spectroscopy and were used as catalysts for the N–H insertion of aniline derivatives and the cyclopropanation of styrene derivatives. The best catalysts for each reaction were able to achieve turnover numbers (TON) up to 520 for the N–H insertion of aniline, and 350 TON for the cyclopropanation of vinyl anisole. Our results show that RuMb is an effective catalyst for N–H insertion, with the potential to further increase the activity and stereoselectivity of the catalyst in future studies. Compared to native Mb (“FeMb”), RuMb is a more active catalyst for carbene transfer reactio...
The bachelorette: Female Siamese fighting fish avoid males exposed to an estrogen mimic

Due to improper disposal and a lack of removal during the wastewater treatment process, endocrine disrupting chemicals enter aquatic ecosystems where they exert detrimental effects on fish behavior and physiology. Perhaps the most well-studied and prevalent EDC is 17α-ethinylestradiol (EE2), an active ingredient in oral contraceptives, which is known to cause dramatic reductions in male-typical behaviors. While it is likely that alterations in male courtship behavior decrease reproductive fitness, this is rarely explicitly examined. To this end, whether EE2 exposure reduces male attractiveness to female Siamese fighting fish, Betta splendens, was investigated by showing females video images of exposed and unexposed males. Females were randomly assigned to one of two exposure conditions (exposed to EE2, control) and each subject then viewed four different video combinations of male conspecifics (courting exposed+exposed; courting unexposed+unexposed; courting unexposed+exposed; swimming unexposed+exposed). Females, regardless of whether or not they were exposed to EE2, directed markedly less behavior towards exposed males, especially when they viewed an exposed male and an unexposed male simultaneously. These findings demonstrate that EE2 can have significant individual- and population-level consequences on fitness by disrupting sexual selection and, ultimately, the success of exposed males.
Drawn to landscape: the pioneering work of J.B. Jackson

This edited volume is a tribute to the life and scholarship of John Brinckerhoff (J.B.) Jackson (1909–1996) by fellow artists and scholars who knew him well. Part biography, part personal reminisce...
Longitudinal Assessment of Bone Mineral Density and Body Composition in Competitive Cyclists

Baker, BS and Reiser II, RF. A longitudinal assessment of bone mineral density and body composition in competitive cyclists. J Strength Cond Res 31(11): 2969-2976, 2017-Competitive cycling has been associated with low bone mineral density (BMD); however, BMD is a multifaceted issue. The purpose of this study was to investigate how age (18-49 years), sex, USA Cycling Category (elite-4), and racing type (road and multiple bikes), influenced body composition across a season in competitive cyclists. February marked the preseason, where 42 participants (22 males, 20 females) completed a health history and cycling questionnaire, 4-day dietary log and a dual-energy X-ray absorptiometry scan, and repeated the measures 180 ± 11 days later. Preseason BMD and Z-Scores were within healthy ranges and similar between sexes, age groups, competition levels and racing-type groups (p ≥ 0.053). Age was significantly correlated with whole group BMD (r = 0.309; p = 0.047). Postseason analysis revealed very encouraging findings as no significant changes in BMD or Z-Score were observed in any group (p ≥ 0.067). A significant main effect for time was found in all groups as lean mass (LM) decreased and fat mass increased across the season (p ≤ 0.001). Additional analysis showed a significant time × group interaction as cat. 1 riders decreased body mass and body mass index, whereas cat. 4 riders responded in the opposite direction (p ≤ 0.037). Postseason correlations highlighted significant positive relationships between BMD and age, LM, and Kcal ingested (r ≥ 0.309; p ≤ 0.047). The only significant negative correlate of BMD was percent body fat (r = -0.359; p = 0.020). Armed with this information, cyclists and coaches should aim to prioritize balance between body mass and caloric intake while meeting the demands of training to minimize risk of cycling related low bone mass.
Reliability of Physician-Level Measures of Patient Experience in Primary Care.

Patient experience measures are widely used to compare performance at the individual physician level. To assess the impact of unmeasured patient characteristics on visit-level patient experience measures and the sample sizes required to reliably measure patient experience at the primary care physician (PCP) level. Repeated cross-sectional design. Academic family medicine practice in California. One thousand one hundred forty-one adult patients attending 1319 visits with 56 PCPs (including 45 resident and 11 faculty physicians). Post-visit patient experience surveys including patient measures used for standard adjustment as recommend by the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Consortium and additional patient characteristics used for expanded adjustment (including attitudes toward healthcare, global life satisfaction, patient personality, current symptom bother, and marital status). The amount of variance in patient experience explained doubled with expanded adjustment for patient characteristics compared with standard adjustment (R2 = 20.0% vs. 9.6%, respectively). With expanded adjustment, the amount of variance attributable to the PCP dropped from 6.1% to 3.4% and the required sample size to achieve a reliability of 0.90 in the physician-level patient experience measure increased from 138 to 255 patients per physician. After ranking of the 56 PCPs by average patient experience, 8 were reclassified into or out of the top or bottom quartiles of average experience with expanded as compared to standard adjustment [14.3% (95% CI: 7.0–25.2%)]. Widely used methods for measuring PCP-level patient experience may not account sufficiently for influential patient characteristics. If methods were adapted to account for these characteristics, patient sample sizes for reliable between-physician comparisons may be too large for most practices to obtain.
Termination of re-entrant atrial tachycardia via optogenetic stimulation with optimized spatial targeting: insights from computational models.

KEY POINTS Optogenetics has emerged as a potential alternative to electrotherapy for treating heart rhythm disorders, but its applicability for terminating atrial arrhythmias remains largely unexplored. We used computational models reconstructed from clinical MRI scans of fibrotic patient atria to explore the feasibility of optogenetic termination of atrial tachycardia (AT), comparing two different illumination strategies: distributed vs. targeted. We show that targeted optogenetic stimulation based on automated, non-invasive flow-network analysis of patient-specific re-entry morphology may be a reliable approach for identifying the optimal illumination target in each individual (i.e. the critical AT isthmus). The above-described approach yields very high success rates (up to 100%) and requires dramatically less input power than distributed illumination We conclude that simulations in patient-specific models show that targeted light pulses lasting longer than the AT cycle length can efficiently and reliably terminate AT if the human atria can be successfully light-sensitized via gene delivery of ChR2. ABSTRACT Optogenetics has emerged as a potential alternative to electrotherapy for treating arrhythmia, but feasibility studies have been limited to ventricular defibrillation via epicardial light application. Here, we assess the efficacy of optogenetic atrial tachycardia (AT) termination in human hearts using a strategy that targets for illumination specific regions identified in an automated manner. In three patient-specific models reconstructed from late gadolinium-enhanced MRI scans, we simulated channelrhodopsin-2 (ChR2) expression via gene delivery. In all three models, we attempted to terminate re-entrant AT (induced via rapid pacing) via optogenetic stimulation. We compared two strategies: (1) distributed illumination of the endocardium by multi-optrode grids (number of optrodes, Nopt = 64, 128, 256) and (2) targeted illumination of the critical isthmus, which was identified via analysis of simulated activation patterns using an algorithm based on flow networks. The illuminated area and input power were smaller for the targeted approach (19-57.8 mm2 ; 0.6-1.8 W) compared to the sparsest distributed arrays (Nopt = 64; 124.9 ± 6.3 mm2 ; 3.9 ± 0.2 W). AT termination rates for distributed illumination were low, ranging from <5% for short pulses (1/10 ms long) to ∼20% for longer stimuli (100/1000 ms). When we attempted to terminate the same AT episodes with targeted illumination, outcomes were similar for short pulses (1/10 ms long: 0% success) but improved for longer stimuli (100 ms: 54% success; 1000 ms: 90% success). We conclude that simulations in patient-specific models show that light pulses lasting longer than the AT cycle length can efficiently and reliably terminate AT in atria light-sensitized via gene delivery. We show that targeted optogenetic stimulation based on analysis of AT morphology may be a reliable approach for defibrillation and requires less power than distributed illumination.
Cardiac Magnetic Resonance in Sudden Cardiac Arrest Survivors.

Sudden cardiac arrest (SCA) is a major challenge in medicine despite significant advances in cardiology over the last few decades. Identification of causes of SCA has major implications for patient management, primary and secondary prevention of sudden cardiac death, and all-cause mortality. SCA predominantly affects individuals with underlying heart disease, especially ischemic heart disease occurring 6 to 9 times more often in postinfarction patients than in patients without myocardial infarction.1 In the landmark Maastricht Circulatory Arrest Registry,1 among 224 SCA victims, only 4% were because of an acute myocardial infarction but 92 of them (41%) had a prior myocardial infarction at a median of 9 years before SCA. Furthermore, the incidence of SCA is substantially increasing after the age of 65 years in males and later in females, coinciding with an increasing incidence of ischemic heart disease in this population.2 However, the incidence and risk of SCA in ischemic patients has decreased over the past 2 decades because of primary coronary intervention, widespread use of statins, and other contemporary medications.3 At the same time, the relative proportion of nonischemic causes of SCA is increasing and plays a particularly important role at the age <65 years.4,5 Ruling out coronary disease as a cause of SCA is an initial step of diagnosis, but subsequent differential diagnosis of nonischemic causes remains challenging. See Article by Rodrigues et al Cardiac magnetic resonance (CMR) …
Identifying biomarkers from SELDI-TOF MS data of ovarian cancer

590 In recent years, there has been an increased interest in using protein mass spectroscopy to identify molecular markers to discriminate diseased from healthy individuals. Existing methods are tailored towards classifying observation into nominal categories. Sometimes, however, the outcome of interest may be measured ordered scale. Ignoring this natural ordering may result in loss of information. In this paper, we propose a Bayesian model for the analysis of mass spectrometry data with ordered outcome. The method provides a unified approach for identifying relevant markers and predicting class membership. This is accomplished by building a stochastic search variable selection method with an ordinal outcome model. We apply the methodology to mass spectrometry data on ovarian cancer cases and healthy individuals. We also utilize wavelet-based techniques to denoise the mass spectra prior to analysis. We identified protein markers associated with being healthy, a low grade case, or a high grade case. For comparison, we repeated the analysis using conventional classification procedures and found improved predictive accuracy with our method. One of the most predictive peaks, m/z value 3,271 we believe is inter-alpha tyrpsin inhibitor heavy chain 4 (ITIH4), that has been found to predict ovarian cancer in the previous studies.
Smoking and weight loss among smokers with overweight and obesity in Look AHEAD.

Smoking cessation is associated with increases in body weight, but little is known about the relationship between participation in a weight loss intervention and smoking. Objective To determine whether (a) weight losses at 1 year differ as a function of baseline smoking status (never smoker, current smoker, ex-smoker) and (b) participation in a weight loss intervention affects smoking behavior. Method This analysis addressed these questions using the publicly available database from Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE; control condition) among individuals with overweight/obesity and Type 2 diabetes, and included 4,387 participants who had self-reported smoking and objective weight measures available at baseline and at 1 year. Results Although participants in ILI lost a significantly greater percentage of weight than those in DSE at 1 year (ILI, M = -8.8%, SD = 6.8; DSE, M = -0.7%, SD = 4.7), there were no differences in weight loss outcomes between never smokers (n = 2,297), ex-smokers (n = 2,115), and current smokers (n = 188) within either condition. Participation in ILI was not associated with compensatory smoking or likelihood of quitting smoking or relapsing. Conclusions Smokers in a weight loss intervention had reductions in weight that were comparable to individuals who did not smoke without any evidence of compensatory smoking to manage eating and appetite. Smokers with obesity should be encouraged to pursue weight loss without concerns regarding the impact on smoking behavior. (PsycINFO Database Record
Developing finer-grained methods for analyzing word recognition performance by individuals with cochlear implants

Cochlear implant (CI) listeners experience overall improvement in speech recognition abilities, but a considerable amount of variability still remains among these individuals. Data from simulated CI listening conditions also show wide variability in monosyllabic word recognition ability. In an adverse simulated condition (2 spectral channels using sinusoidal carriers), the word score can be nearly 0 for some adults with normal hearing. These floor effects pose a challenge for researchers, as they lead to data compression. When analyzing the performance by phonemes, the increase in scores may remove the floor effect. The purpose of this study is to establish the chance performance rate for NU-6 consonant-vowel-consonant (CVC) word lists analyzed by phonemes. To determine this, we randomly paired words from the NU-6 list with CVC words from an on-line corpus of English, the English Lexicon Project, and scored the matches by phonemes using dictionary pronunciations. Thousands of runs of these random pairings were used to generate expected baseline accuracy ranges. These results were compared with individual, behavioral data from people listening to NU-6 words processed using 2-channel sinusoidal vocoders to determine if participants were performing better than chance when scoring by phonemes.
Transcriptional Regulation of the Metazoan Stress Protein Response

This review provides an updated account of the regulation of the metazoan stress protein response. Where indicated, observations made with yeasts are also included. However, a discussion of the plant stress protein response is intentionally omitted (for a review, see 1). The stress protein response, as discussed hereafter, is understood to relate to the response by virtually all cells to heat and other stressors that results in the induced expression of so-called heat shock or stress genes. The protein products of these genes localize largely to the cytoplasm, nucleus, or organelles. An analogous response controls the expression of related genes, whose products reside in the endoplasmic reticulum. The response, termed ER stress response or unfolded protein response, is mediated by a separate regulation system that is not discussed in this review. Note, however, that recent work suggests the existence of commonalities between the regulatory systems controlling the stress protein and ER stress responses (2).
Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation.

Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.
Fundamentals of rare earth flotation surface chemistry: Electrokinetic phenomena

In flotation, the electrical nature of the mineral surface is described by an electrokinetic potential known as the zeta potential. The aim of this research is to illustrate the potential determining ions (PDIs) of the rare-earth mineral bastnaesite ((Ce,La)FCO3) and its associated gangue minerals, calcite (CaCO3) and barite (BaSO4). Initially, pure mineral samples were hand sorted and ground to -32 μm using a mortar and pestle. Sample characterization was performed using inductively coupled plasma mass spectrometry (ICP-MS) in conjunction with X-ray diffraction (XRD) to ensure sample purity. Prior to electrokinetic measurement, 0.1 g/L samples were conditioned for 24 hours on a shaking table. Measurements were performed using a Microtrac Stabino instrument (streaming potential). Each measurement was performed three times for experimental reliability purposes. Generally, an ion is said to be potentially determining if its adsorption causes a shift in the isoelectric point (IEP) of that mineral. To illustrate whether or not an ion was potentially determining, zeta potential measurements of the minerals in the absence of any metallic salts were measured. After this, samples were added to solutions containing 10-3 and 10-4 M of metallic salts postulated to contain PDIs for the respective minerals (Table 1). Electrokinetic measurements for barite show that, as the sulfate concentration (SO42-) is increased, the IEP shifts toward the alkaline direction and, as the Ba2+ concentration is increased, the IEP shifts in the acidic direction. This is illustrated in Fig. 1. Results for calcite show that the IEP shifts in the alkaline direction as the carbonate concentration is increased and, as the Ca2+ concentration is increased, the IEP shifts in the acidic direction. Finally, PDI electrokinetic measurements for bastnaesite show that the IEP shifts in the alkaline direction as the carbonate (Na2CO3) concentration is increased. Conversely, as the amount of cerium is increased, the IEP shifts in the acidic direction. All results obtained were compared with the respective speciation diagrams of each of the mineral/water systems. This provided insight into which species were present in the system to act as potential determining ions. By understanding how PDIs affect the mineral’s zeta potential, it may be possible to manipulate the system, using new reagent schemes, to ultimately increase the grade/recovery of rare earth flotation concentrates.
A History of the Center for Advanced Research in Phenomenology, Inc.

This chapter introduces the history of the CARP, the “Center for Advanced Research in Phenomenology”.
“A” Is for Activating

The concept of patient activation is one of an array of concepts designed to help health professionals encourage patients, particularly patients with chronic illnesses, to be active in caring for themselves. These concepts were developed in response to the evidence that simply instructing patients on how to care for themselves was inadequate to produce the required health behaviors, especially for patients with complex biological, psychological, and social challenges. The Patient Activation Measure has proved to do an excellent job at distinguishing which patients are most likely to be successful at self-care. In general, patients identified as having low activation are the same patients designated as multiply-disadvantaged patients in previous chapters. We have described previously the way in which a solution-focused approach can be adapted to fostering patient empowerment. If we consider the evidence of the impact of changing expectations between helper and client, we find support for an approach that uses explicit attributions about patients to change the expectation of their success at self-management on the part of both health professionals and the patients themselves. Attributions that are believable to patients about themselves, when delivered by health professionals, can have an activating impact on patients toward better self-management.
Optimization-simulation model for real-time pump and valve operation of water distribution systems under critical conditions

ABSTRACTA new methodology is developed for the real-time operation of water distribution systems (WDS) under critical conditions of limited electrical energy and/or water availability due to emerge...
Construction hazard prevention through design: Review of perspectives, evidence, and future objective research agenda

Abstract Construction Hazard Prevention through Design (CHPtD) is the consideration for worker safety in the design phase of a construction project. CHPtD theory has seen an abundance of research in recent years, most of which research has been conducted to validate the CHPtD concept using logical argument and qualitative evidence. However, there is a dearth of objective evidence validating the concept and the actual risk reduced via design decisions over a project lifecycle remains unknown. Although CHPtD is supported by many government agencies around the world and has even become legislation in some, objective validation could serve as a catalyst of implementation. This paper provides a detailed review of CHPtD literature and a careful distinction between scientific evidence and theory. Additionally, a distinction between experimental, quasi-experimental, and nonexperimental research is noted. Specifically, literature is reviewed as it relates to the efficacy of CHPtD, available tools to assist designers with hazard recognition, and use of technology to enable CHPtD. The review contributes to the current literature by uncovering vital knowledge gaps and creating a set of testable research questions that define a viable scientific research agenda for the domain. Themes of future objective research include understanding hazard recognition during design using available documentation and technological platforms, experimentally testing the efficacy of CHPtD tools, and the lifecycle safety risk assessments of proposed CHPtD solutions. In addition to providing an agenda, this paper may serve as a single resource for researchers and practitioners that summarizes and codifies a large and dispersed body of knowledge.
Left atrial appendage closure: A therapy uniquely suited for specific populations of patients with atrial fibrillation

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and confers a fivefold increased risk for stroke. Cardioembolic stroke secondary to AF is a devastating event, but is largely preventable with appropriate oral anticoagulation (OAC). The PROTECT and PREVAIL trials demonstrated that the WATCHMAN left atrial appendage closure (LAAC) device in combination with short-term warfarin therapy is noninferior to long-term warfarin with respect to a composite endpoint of stroke, cardiovascular death, and systemic embolism. Importantly, the WATCHMAN confers a significant reduction in life-threatening bleeding compared to OAC. Although direct-acting oral anticoagulant (DOAC) are superior to warfarin in eligible patients, several important AF populations exist in whom left atrial appendage (LAA) closure may be preferable to DOAC. Populations warranting strong consideration of LAAC include patients with contraindications to DOAC, end-stage renal disease, prior intracranial hemorrhage, recurrent gastrointestinal bleeding, and patients undergoing transcatheter aortic valve replacement or left atrial electrical isolation. Device-related thrombosis is an important complication of LAAC, and DOAC may be preferential to warfarin for prevention and treatment of this complication remains unexplored. Prospective clinical trials comparing DOAC to LAAC in these unique populations are either ongoing or needed.
Expedited Removal of a Radial Hemostatic Compression Device Following Cardiac Catheterization Is Safe and Associated With Reduced Time to Discharge.

Background: Radial access for cardiac catheterization has become increasingly adopted, owing much of its popularity to decreased bleeding complications compared with the femoral approach. Hemostatic compression devices (HCDs) for radial catheterization play a key role in this advantage, but the optimal duration of compression is unknown. A shorter duration of compression is encouraged by guidelines, but removing an HCD too quickly could result in serious bleeding. We aimed to evaluate the safety and effectiveness of expedited removal of a radial HCD after cardiac catheterization. Methods: We conducted a prospective study of patients undergoing radial cardiac catheterization and/or percutaneous coronary intervention at a tertiary care academic medical center. Patients underwent HCD application using a TR Band ® (Terumo Interventional Systems) which was removed after a prespecified amount of time in each of three sequential temporal cohorts: 2-h, 1-h, or 0.5-h. Each patient was monitored for development of bleeding or hematoma and for serious complications. Results: A total of 354 patients participated in our study, with similar numbers in each group. There was a greater rate of minor bleeding in the 0.5-h (12%) and 1-h (19%) groups compared with the 2-h group (8%), but there were no serious complications (need for surgical consultation, transfusion, or unplanned admission) in any group. The average time to discharge was shorter in the 0.5-h and 1-h groups compared with the 2-h group. Conclusions: Deflating the radial HCD at 0.5 h is safe with no increase in the observed rate of major complications and is associated with reduced time to discharge after coronary angiography or percutaneous coronary intervention using the radial arterial approach. Cardiol Res. 2019;10(6):331-335 doi: https://doi.org/10.14740/cr953