cssi/SciSciGPT-SciSciNet huggingface dataset:
39-Year-Old Woman With an Obscure Case of Anemia

A 39-year-old woman was referred to our institution for evaluation of anemia. She was known to have multiple comorbidities and had a baseline hemoglobin concentration of approximately 10.5 g/dL. About 6 months before her referral, the patient began having recurrent episodes of severe anemia, with hemoglobin values as low as 3.5 g/dL. She had become transfusion-dependent and had received about 30 units of packed red blood cells (RBCs) in the preceding 3 months. The patient denied any history of easy bruisability, menorrhagia, or overt evidence of bleeding from any site. Additionally, she denied any change in the appearance or color of her urine and had no history of jaundice. There was no family history of anemia or any other hematologic disorder. As an outpatient, she had undergone an extensive evaluation at another institution, but results failed to provide an explanation for her anemia.
Crystallization Kinetics in Continuous Decompression Experiments: Implications for Interpreting Natural Magma Ascent Processes

Decompression experiments were performed to study the kinetics of plagioclase crystallization during ascent of hydrous rhyodacite magma. These experiments differ from previous studies in that they employ a continuous, rather than stepwise, pressure^time trajectory. Four series of experiments were performed at rates of 0·5^10MPa h , corresponding to ascent rates of 0·007^0·14 m s . Experiments quenched along each decompression path allow snapshot-style monitoring of progressive crystallization. As expected, rates of plagioclase nucleation and growth depend strongly on decompression rate. Regardless of decompression rate, approximately equal volumes of feldspar crystallize during a given decompression interval, even when the observed crystallinity is lower than the equilibrium crystallinity. Apparently, a constant degree of solidification is maintained by a crystallization mechanism striking a shifting balance between nuclei formation and growth of existing crystals. Other key results pertain to the efficacy with which experimental results allow interpretation of the decompression histories of natural rocks. Feldspar microlites do not maintain chemical equilibrium with melt. They are more anorthite-rich than equilibrium plagioclase, suggesting that interpretations of magma ascent processes in nature require comparisons with dynamic rather than static (phase equilibrium) experiments. Although decompression rate is an important element controlling final textures in volcanic rocks, no single compositional or textural parameter uniquely records this rate. Of the criteria examined, microlite number density and morphology are the best indicators of magma decompression rate. Based on a small number of comparisons between continuous and multi-step decompression style at the same time-integrated decompression rate (1MPa h ), decompression path evidently influences crystal texture, with stepwise decompression yielding textures correlative with faster decompression than indicated by the time-integrated decompression rate. Thus, consideration of magma ascent style, in addition to rate, will undoubtedly strengthen the interpretive power of experimental studies for constraining natural magma ascent processes.
The Burden of Community-Acquired Pneumonia in Seniors: Results of a Population-Based Study

Background Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease--and, in particular, the contribution of ambulatory cases to that burden--is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged >or=65 years that included both hospitalizations and outpatient visits for pneumonia. Methods The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65-69 years to 52.3 cases per 1000 person-years among those aged >or=85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that approximately 1 of every 20 persons aged >or=85 years will have a new episode of community-acquired pneumonia each year.
Effect of twist wavelength on x-ray power output in Al cable array z-pinches

Summary form only given. Recent exploratory work involving imploding Al cable array z-pinches on the COBRA pulsed power generator has shown an approximate factor of 2 increase in peak x-ray power output. A scan of cable twist wavelengths (λt) and their effect on x-ray power output, yield, effective current radius, ablation modulation and hotspot formation along the pinch axis is presented. Previous core radiographs of Ni cable arrays revealed helix-like structures of enhanced density and fan shaped regions of smooth falloff in density that appeared to follow the twist of the individual cable. We present follow-up radiographs of multi-material cable arrays which may provide insight into the mechanisms responsible for these structures seen in the core. X-ray streak spectra from imploding wire and cable arrays is also presented.
Experience with CommonLoops

CommonLoops is an object-oriented language embedded in Common Lisp. It is one of two such languages selected as starting points for the Common Lisp Object System (CLOS) which is currently being designed as a standard object-oriented extension to Common Lisp. This paper reports on experiences using the existing Portable CommonLoops (PCL) implementation of CommonLoops. The paper is divided into two parts: a report on the development of a window system application using the CommonLoops programming language, and a description of the implementation of another object-oriented language (CommonObjects) on top of the CommonLoops metaclass kernel, paralleling the two aspects of CommonLoops: the programming language and the metaclass kernel. Usage of the novel features in CommonLoops is measured quantitatively, and performance figures comparing CommonLoops, CommonObjects on CommonLoops, and the native Lisp implementation of CommonObjects are presented. The paper concludes with a discussion about the importance of quantitative assessment for programming language development.
The Hermansky-Pudlak Syndrome 3 (Cocoa) Protein Is a Component of the Biogenesis of Lysosome-related Organelles Complex-2 (BLOC-2)

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease affecting vesicle trafficking among lysosome-related organelles. The Hps3, Hps5, and Hps6 genes are mutated in the cocoa, ruby-eye-2, and ruby-eye mouse pigment mutants, respectively, and their human orthologs are mutated in HPS3, HPS5, and HPS6 patients. These three genes encode novel proteins of unknown function. The phenotypes of Hps5/Hps5,Hps6/Hps6 and Hps3/Hps3,Hps6/Hps6 double mutant mice mimic, in coat and eye colors, in melanosome ultrastructure, and in levels of platelet dense granule serotonin, the corresponding phenotypes of single mutants. These facts suggest that the proteins encoded by these genes act within the same pathway or protein complex in vivo to regulate vesicle trafficking. Further, the Hps5 protein is destabilized within tissues of Hps3 and Hps6 mutants, as is the Hps6 protein within tissues of Hps3 and Hps5 mutants. Also, proteins encoded by these genes co-immunoprecipitate and occur in a complex of 350 kDa as determined by sucrose gradient and gel filtration analyses. Together, these results indicate that the Hps3, Hps5, and Hps6 proteins regulate vesicle trafficking to lysosome-related organelles at the physiological level as components of the BLOC-2 (biogenesis of lysosome-related organelles complex-2) protein complex and suggest that the pathogenesis and future therapies of HPS3, HPS5, and HPS6 patients are likely to be similar. Interaction of the Hps5 and Hps6 proteins within BLOC-2 is abolished by the three-amino acid deletion in the Hps6(ru) mutant allele, indicating that these three amino acids are important for normal BLOC-2 complex formation.
Predicting Near Edge X-ray Absorption Spectra with the Spin-Free Exact-Two-Component Hamiltonian and Orthogonality Constrained Density Functional Theory.

Orthogonality constrained density functional theory (OCDFT) provides near-edge X-ray absorption (NEXAS) spectra of first-row elements within one electronvolt from experimental values. However, with increasing atomic number, scalar relativistic effects become the dominant source of error in a nonrelativistic OCDFT treatment of core–valence excitations. In this work we report a novel implementation of the spin-free exact-two-component (X2C) one-electron treatment of scalar relativistic effects and its combination with a recently developed OCDFT approach to compute a manifold of core–valence excited states. The inclusion of scalar relativistic effects in OCDFT reduces the mean absolute error of second-row elements core–valence excitations from 10.3 to 2.3 eV. For all the excitations considered, the results from X2C calculations are also found to be in excellent agreement with those from low-order spin-free Douglas–Kroll–Hess relativistic Hamiltonians. The X2C-OCDFT NEXAS spectra of three organotitanium compl...
Results of Replantation Following Finger Tip Amputation

During past 7 years from 1988 to 1994, microsurgical replantations have been performed for 37 complete finger tip amputations in 34 patients. These fingers were classified according to Allen's criteria (type III-15, type IV-22). 5 of the 37 fingers resulted in failure, six fingers had partial necrosis, however the remaining 26 had no necrosis. Survival rate was 100% in clean cut amputation, 90% in blunt amputation, 60% in crush amputation and 50% in avulsion amputation.Postoperative results were evaluated in 25 fingers of 22 patients with a follow-up period more than 1 year. The paresthesia of the finger tip was present in 9 finger tips and cold intolerance was present in 8 finger tips. The average static 2 point discrimination test was 5.8mm, renging from 2-10mm. Nail deformity was seen in 3 finger tips and mallet deformity in 3 fingers. 8 finger tips had mild atrophy. Functional results by Tamai's criteria vudged 21 patients to be excellent and 1 patient good. Almost all patients wete satisfied with the results.From this study, we concluded that replantation with microvascular anastomosis is the first choice for finger tip amputation.
The Growth and Toxin Production of Bacillus diphtheriae upon Proteid-Free Media.

Of all the problems which fall within the bounds of bacteriology today, one of the most important is that which concerns the production of toxins by certain pathogenic micro-organisms. The toxin of diphtheria has, no doubt, so far as its chemical nature and conditions of formation are concerned, received the greatest amount of study from investigators. It presents, moreover, a problem in the biochemistry of bacteria, than which, to the present time, no other has yielded more satisfactory results, considered both in their relation to pure science and to their practical application in the treatment and prevention of disease. And yet there are many points in regard to the ultimate nature of these toxic products, their relation to and interaction with the antitoxins, which, to say the least, are very far from being well understood. Furthermore, it is probable that these elements of the problem must remain a matter of speculation only, until a more adequate knowledge shall have been gained regarding the chemical nature of these toxic products, and the conditions which are either favorable or necessary to their formation. Although, in the qualitative analysis of the toxic substance produced by B. diphtheriae, the investigator can recognize certain organic or inorganic bodies, he is still in the dark with reference to the ultimate proteid body, whose exact constitution he wishes to determine. It is difficult to determine whether the albumoses are the toxic products, or whether the true toxin may not, in some way, be associated with them. Some investigators assume that the toxin itself may be an enzyme which has a proteolytic action and produces the virulent, but secondary, toxic products in the body of the animal. Whatever answer may be given to these diverse and often contradictory views, the fact remains that the diphtheria organism, growing upon a proteid-f ree medium, can synthesize a toxic substance of a proteid nature; and that the toxin is probably not (as previously claimed by Brieger
Determination of Tin in Canned Food by Microwave Digestion and HG-AFS

To establish a method for determination of tin in canned food by microwave digestion-hydride generation atomic fluorescence spectrometry(HG-AFS),the samples were dissolved in HNO3+ HCl or HNO3+HCl + H2O2 systems and digested by microwave for preparation,the thiourea-ascorbic acid were used as the pre-reducing agents,afterwards(HG-AFS) was applied to determine the tin content in canned food.The results showed that under the optimal condition,tin content linearity in the range of 0~100 μg/L,the linear correlation coefficient was 0.999 8.The detection limit of this method was 0.067 mg/kg,the recovery rate of samples ranged from 99.7%~108.3%,the coefficients of variation(CV) were 2.67%(n=6).It concludes the method is accurate,precise,sensitive,rapid,safe and green,it is suitable for determination of tin in canned food.
Inactivated poliovirus vaccine

During the final stage of global polio eradication program, universal use of inactivated poliovirus vaccine (IPV) is the most feasible option to minimize the inherent risk of oral poliovirus vaccine (OPV), such as vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to vaccine-derived polioviruses. Introduction of diphtheria, pertussis, tetanus, IPV (DPT-IPV) products, instead of OPV, to routine polio immunization should be seriously and urgently considered to minimize ongoing risk of VAPP in Japan. Accordingly, a further polio immunization strategy, including the immunization schedule using DPT-IPV, interchangeability of different DPT-IPV products, intensified polio surveillance activities, and appropriate polio vaccine stockpile, should be developed to maintain polio-free status in Japan prior to the introduction of DPT-IPV.
Electrolyte solution structure and its effect on the properties of electric double layers with surface charge regulation.

Abstract The physical origin of charged interfaces involving electrolyte solutions is in the thermodynamic equilibrium between the surface reactive groups and certain dissolved ionic species in the bulk. This equilibrium is very strongly dependent on the precise local density of these species, also known as potential determining ions in the solution. The latter, however, is determined by the overall solution structure, which is dominated by the large number of solvent molecules relative to all solutes. Hence, the solvent contribution to the molecular structure is a crucial factor that determines the properties of electric double layers. Models that explicitly account for the solvent structure are often referred to as “civilized” as opposed to the “primitive” ones that consider the solvent as a structureless continuum. In the present paper, we demonstrate that for a physically correct description of charged interfaces that involve electrolyte solutions (electric double layers), the full solution structure needs to be taken into account in conjunction with the precise surface chemistry governed by the thermodynamic equilibrium. The analysis shows how the surface charge depends on various experimentally relevant parameters, many of which are outside the realm of simple electrostatics. We present results on the effects of solvent molecular dimensions, ionic solvation, surface chemistry, solvophilicity and solvophobicity.
Abstract 2937: MEK/ERK inhibitor GDC-0623 dephosphorylates and accumulates BIM that enables a synergistic apoptosis with the Bcl-xL antagonist, ABT-263, in mutantKRAScolorectal cancer cells

Background. Oncogenic KRAS mutations occur in nearly one-half of colorectal cancers (CRC) where they contribute to de novo apoptosis resistance and treatment failure. Inhibition of MEK/ERK is a promising strategy to sensitize KRAS mutant tumors to apoptosis that may involve upregulation of pro-apoptotic BH3-only proteins, including BIM. However, BH3-only proteins can be neutralized by anti-apoptotic Bcl-xL that we found was upregulated in isogenic KRAS mutant compared to wild-type HCT116 and DLD1 CRC cells. Aims. We determined the ability and mechanism by which a novel MEK/ERK inhibitor, GDC-0623, can induce BIM to promote apoptotic signaling. A strategy of concurrent induction of BH3-only proteins and antagonism of Bcl-xL was studied to overcome mutant KRAS-mediated apoptosis resistance. Results. Using isogenic KRAS HCT116 cells and KRAS mutant SW620 cells, we found that GDC-0623 can potently induce the BH3-only protein BIM, and to a lesser extent BIK, in both KRAS wild-type and mutant cells. Only KRAS mutant cells remained resistant to GDC-0623-induced apoptosis. Knockdown of Bcl-xL or use of a BH3 mimetic drug, ABT-263, sensitized KRAS mutant cells to GDC-0623-mediated apoptosis. GDC-0623 and ABT-263 were shown to interact synergistically to promote apoptosis in KRAS mutant cells. Dependence on BIM or BIK for synergy between GDC-0623 and ABT-263 was shown by shRNA knockdown that each attenuated drug-induced apoptosis. Mechanistically, ABT-263 treatment was shown to release BIM from its binding to Bcl-xL using immunoprecipitation. The ability of GDC-0623 to induce apoptosis occurred via BIM that was phosphorylated by MEK/ERK activation leading to BIM degradation. GDC-0623 was shown to dephosphorylate BIM at serine 69 in cells with wild-type BIM or a phospho-mimic mutation (S69E). However, GDC-06239s ability to dephosphorylate BIM was lost in cells containing a phosphorylation-defective BIM mutation (S69G) that showed delayed BIM degradation. Conclusion. GDC-0623 was shown to dephosphorylate BIM to enhance its accumulation and to promote apoptosis. Concurrent induction of BIM/BIK and antagonism of Bcl-xL can overcome mutant KRAS-mediated apoptosis resistance, suggesting a promising therapeutic strategy against KRAS mutant CRCs. Note: This abstract was not presented at the meeting. Citation Format: Aziz Zaanan, Koichi Okamoto, Hisato Kawakami, Shengbing Huang, Frank Sinicrope. MEK/ERK inhibitor GDC-0623 dephosphorylates and accumulates BIM that enables a synergistic apoptosis with the Bcl-xL antagonist, ABT-263, in mutant KRAS colorectal cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2937. doi:10.1158/1538-7445.AM2015-2937
THE EFFECTS OF BENZYL ALCOHOL AND PROPYLENE GLYCOL ON L1-MEDIATED ACTIVATION OF ERK1/2

Introduction Inert ingredients in neonatal medications have led to adverse effects including death. Benzyl alcohol, a preservative, has been associated with death, developmental delay and cerebral palsy in neonates. Propylene glycol, a solubiliser in medications, is associated with lactic acidosis, central nervous system depression and seizures. Objective To show that benzyl alcohol and propylene glycol act similarly to ethanol, inhibiting L1-mediated activation of the ERK1/2 signalling pathway. We have previously shown that ethanol inhibits L1 signal transduction and thus L1-mediated neurite outgrowth. We hypothesise that by exposing neurons to benzyl alcohol and propylene glycol, activation of ERK1/2 decreases. Methods Cerebellar granule neurons from postnatal day 6 rat pups were plated overnight on poly-l-lysine. Cells were serum starved 3 h before triggering. Benzyl alcohol, propylene glycol and ethanol were added 1 h before triggering. The cells were triggered by clustering L1. At 10 minutes, the cells were placed on ice, scraped and lysed. Lysates were immunoblotted for phospho ERK1/2, then stripped and reblotted for total ERK. Results Benzyl alcohol and propylene glycol inhibited L1-mediated activation of ERK1/2 by 52% and 39%. Results, however, were not statistically significant, with respective p values of 0.055 and 0.124. Conclusion Benzyl alcohol and propylene glycol seem to inhibit activation of ERK1/2 similarly to ethanol and subsequently are likely to affect L1-mediated neurite outgrowth. Our small sample size, however, was not statistically significant. With further refinement this assay may allow simple screening to test the safety of inert ingredients in neonatal medications.
MicroRNAs in Pancreas and Islet Development

Abstract MicroRNAs (miRNAs) control pancreatic and islet development, as well as β cell physiology. For this reason they have an important role in the regulation of gene expression in health and in disease, including diabetes. Each phase of human pancreatic development exhibits a specific miRNA profile. The expression of multiple miRNAs is inversely correlated with the expression of involved critical genes, suggesting miRNA-mediated regulation. Modulation of miRNAs to restore β cells is a potential strategy in diabetes treatment. However, current therapeutic approaches based on manipulation of miRNA expression are more feasible in vitro than in vivo because of difficulties with specific delivery. This chapter discusses the miRNAs involved in islet and pancreas development in the context of diabetes. It also looks at their potential role in the generation of surrogate β cells for transplantation.
Drug use in renal failure

The spectrum of interaction between drugs and the kidney is broad. Most drugs are excreted at least partially by the kidney, and renal function affects drug bioavailability, volume of drug distribution, and drug metabolism and rate of drug elimination. Drug therapy not only is potentially hazardous in patients with renal failure but also can cause a number of renal diseases. The clinician should be familiar with the pharmacologic and potential toxic effects of any drug used in a patient with uremia and should monitor creatinine clearance or at least serum creatinine level as a gauge of renal function. The drug regimen can be modified according to these measurements, either by administering a constant dose and varying the interval or by varying the dose and keeping the interval constant.
Mechanisms for Generation and Development of the Ningaloo Niño

AbstractGeneration and development mechanisms of the Ningaloo Nino are investigated using ocean and atmospheric general circulation model experiments. Consistent with previous studies, northerly wi...
Development of information sharing in language neocortex in childhood-onset drug-resistant epilepsy

Objective We studied age-related dynamics of information sharing among cortical language regions with electrocorticographic high-gamma modulation during picture-naming and story-listening tasks. Methods Seventeen epilepsy patients aged 4-19 years, undergoing extraoperative monitoring with left-hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial-averaged 70-150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis. Results During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age-related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions. Significance Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery.
Experiences of gender-based violence in women asylum seekers from El Salvador, Honduras, and Guatemala: a retrospective, qualitative study

Abstract Background In 2016, around 65 000 women fled gender-based violence in the Northern Triangle (NTCA) countries of El Salvador, Honduras, and Guatemala, and attempted to seek asylum in the USA. Some women participate in medical evaluations by clinicians to document the effect of these human rights violations as part of the asylum process. The aim of this study is to elucidate the forms of persecution experienced by women in this region, and the physical and psychological sequelae of this violence. Methods We undertook a retrospective, qualitative study of asylum-seeking adult women fleeing gender-based violence from the NTCA who were seen by evaluators in the Mount Sinai Human Rights Program from February, 2014, to August, 2018. We included any case in which the client self-identified as female, came from an NTCA country, and received a psychological evaluation. This study was approved by the Mount Sinai Institutional Review Board. We used a modified consensual qualitative research (CQR-M) approach to identify themes found across the archived and de-identified affidavits written as part of the medical evaluation. Findings We included data from 70 women; mean age was 29·4 years (SD 6·5; range 18–55 years]. 24 women identified as Salvadoran, 15 as Guatemalan, and 31 as Honduran. All women reported violence perpetrated by their communities, families, intimate partners, and/or powerful gangs, and faced justice systems in their countries that they felt would not protect them. They had been subject to: verbal (50 women [71%]), physical (57 [81%]), and sexual (59 [84%]) assaults; death threats (58 [83%]); control (40 [57%]); extortion (24 [34%]); and harm, or threats of harm, to their children (50 [43%] and 22 [31%], respectively). Evaluators identified psychological symptoms associated with anxiety (56 women [80%]), depression (64 [91%]), and post-traumatic stress disorder (56 [80%]), as well as suicidality (33 [47%]). Women also reported physical injury including bruising, head injury and loss of consciousness, and gynaecological harm including miscarriage and forced sterilisation. Many women had been displaced within their own countries before fleeing and stated that they travelled with their children, experienced hazardous conditions and violence during their journey, and were detained on arrival in the USA. Finally, the women reported resilience associated with their religious beliefs, family, temperament, and ability to make meaning from their experiences. Interpretation This study highlights the systemic nature of gender-based violence in the NTCA. The results also describe the perils that women from the NTCA encountered during their migration and demonstrate the continued structural violence that awaits them if they are denied asylum and returned to their countries of origin. Funding None.
Repeated faint quasinormal bursts in extreme-mass-ratio inspiral waveforms: Evidence from frequency-domain scalar self-force calculations on generic Kerr orbits

We report development of a code to calculate the scalar self-force on a scalar-charged particle moving on generic bound orbits in the Kerr spacetime. The scalar self-force model allows rapid development of computational techniques relevant to generic gravitational extreme-mass-ratio inspirals (EMRIs). Our frequency-domain calculations are made with arbitrary numerical precision code written in Mathematica. We extend spectral source integration techniques to the Kerr spacetime, increasing computational efficiency. We model orbits with nearly arbitrary inclinations $0\ensuremath{\le}\ensuremath{\iota}l\ensuremath{\pi}/2$ and eccentricities up to $e\ensuremath{\lesssim}0.8$. This effort extends earlier work by Warburton and Barack where motion was restricted to the equatorial plane or to inclined spherical orbits. Consistent with a recent discovery by Thornburg and Wardell in time-domain calculations, we observe self-force oscillations during the radially outbound portion of highly eccentric orbits around a rapidly rotating black hole. As noted previously, these oscillations reflect coupling into the self-force by quasinormal modes excited during pericenter passage. Our results confirm the effect with a frequency-domain code. More importantly, we find that quasinormal bursts (QNBs) appear directly in the waveform following each periastron passage. These faint bursts are shown to be a superposition of the least-damped overtone (i.e., fundamental) of at least four ($l=m\ensuremath{\le}4$) quasinormal modes. Our results suggest that QNBs should appear in gravitational waveforms, and thus provide a gauge-invariant signal. Potentially observable in high signal-to-noise ratio EMRIs, QNBs would provide high-frequency components to the parameter estimation problem that would complement low-frequency elements of the waveform.
Optimized Sound and Complete Data Race Detection in Structured Parallel Programs.

Task parallel programs that are free of data race are guaranteed to be deterministic, serializable, and free of deadlock. Techniques for verification of data race freedom vary in both accuracy and asymptotic complexity. One work is particularly well suited to task parallel programs with isolation and lightweight threads. It uses the Java Pathfinder model checker to reason about different schedules and proves the presence or absence of data race in a program on a fixed input. However, it uses a direct and inefficient transitive closure on the happens-before relation to reason about data race. This paper presents Zipper, an alternative to this naive algorithm, which identifies the presence or absence of data race in asymptotically superior time. Zipper is optimized for lightweight threads and, in the presence of many threads, has superior time complexity to leading vector clock algorithms. This paper includes an empirical study of Zipper and a comparison against the naive computation graph algorithm, demonstrating the superior performance it achieves.
One step at a time: Physical activity is linked to positive interpretations of ambiguity.

Background Extensive research has established a clear positive relationship between physical activity (PA), even in small amounts, and psychological well-being, including benefits for emotional and mental health (e.g., decreased depression). However, little research has examined the relationship between PA and decision-making within emotionally ambiguous contexts. The purpose of the present cross-sectional study was to examine the relationship between reported amount and intensity of PA and interpretations of emotional ambiguity. Methods Adults (n = 611) recruited through Amazon’s Mechanical Turk were assessed on their interpretations of ambiguous and clear (unambiguous) emotional stimuli and reported habitual PA and exercise. Results More positive ratings of ambiguity were associated with greater amount of vigorous activity (p = .002), but not with moderate activity (p = .826) or walking (p = .673). Subsequent analyses demonstrated that this relationship between vigorous PA and positive interpretations of ambiguity was most pronounced when comparing individuals who reported any amount of vigorous PA to those who reported no vigorous activity at all. Conclusions Our findings suggest that higher amounts of vigorous, but not moderate, PA are associated with more positive interpretations of ambiguity, and that even small amounts of PA seem to be sufficient to promote this more positive valence bias when compared to individuals conducting no vigorous PA at all. Future work should examine the longitudinal effects of PA among individuals participating in structured activity programs.
Introduction to Zebrafish Husbandry

Abstract In the following chapters of the Husbandry Section of this text, we will describe the cultivation, control, and management of the zebrafish (Danio rerio) for biomedical research. The use of zebrafish in biomedical research has increased exponentially in recent years, both for modeling of human disease and for basic research. It is critically important that the models used for these purposes be supported optimally so that any deficiency in their well-being does not become a variable that would confound the research results. To this end, the following chapters describe optimal care and support of the zebrafish. Since the zebrafish is a newcomer to science, relative to other species, its care and support will continue to be refined; however, this work represents state-of-the-art guidance from the leading experts in the field. These chapters describe the best practices in the care and use of this species for biomedical research. There is also a section on regulatory compliance as applies for zebrafish.
Visualization of oxidative stress-induced carbonylation in live mammalian cells

Oxidative stress (OS) is associated with a wide variety of diseases and disorders. Detection of oxidative stress in living systems typically relies on fluorescent probes for reactive oxygen species (ROS), which is challenging because of their short life span and high reactivity. Oxidative damage caused by OS produces a more stable signal, but these biomarkers are usually detected using techniques that are not compatible with live cells. OS-induced biomolecule carbonylation is a stable modification that also possesses a chemically reactive functional group, and its detection typically employs a chemical reaction with a hydrazine-containing probe within the process. These hydrazone-forming reactions require strong acid catalysis or nucleophilic catalysis with an aromatic amine when performed on isolated biomaterial or on fixed cells. In live cells, however, hydrazone-forming reactions are surprisingly facile. Fluorophores possessing hydrazine or hydrazide functional groups can undergo reaction with carbonylated biomolecules in live cells, and these products can be observed using fluorescence microscopy. In this chapter, standard methods for detection of biomolecule carbonylation in cell lysate and in intact cells are enumerated. Protocols for fluorescently labeling biomolecule carbonylation in live cells are provided for commercially available fluorophores. Also described is a one-step protocol that employs one of the hydrazine-modified fluorophores developed in our lab, which are designed to be live-cell compatible and to undergo a spectral change upon hydrazone formation. Finally, a procedure for observing both biomolecule carbonylation and ROS production simultaneously is provided.
Affine analysis for quantitative PCR measurements

Motivated by the current COVID-19 health crisis, we consider data analysis for quantitative polymerase chain-reaction (qPCR) measurements. We derive a theoretical result specifying the conditions under which all qPCR amplification curves (including their plateau phases) are identical up to an affine transformation, i.e. a multiplicative factor and horizontal shift. We use this result to develop a data analysis procedure for determining when an amplification curve exhibits characteristics of a true signal. The main idea behind this approach is to invoke a criterion based on constrained optimization that assesses when a measurement signal can be mapped to a master reference curve. We demonstrate that this approach: (i) can decrease the fluorescence detection threshold by up to a decade; and (ii) simultaneously improve confidence in interpretations of late-cycle amplification curves. Moreover, we demonstrate that the master curve is transferable reference data that can harmonize analyses between different labs and across several years. Application to reverse-transcriptase qPCR measurements of a SARS-CoV-2 RNA construct points to the usefulness of this approach for improving confidence and reducing limits of detection in diagnostic testing of emerging diseases. Graphical Abstract Left: a collection of qPCR amplification curves. Right: Example of data collapse after affine transformation.
Uterine conservation in placenta accrete spectrum (PAS) disorders: A retrospective case series: Is expectant management beneficial in reducing maternal morbidity?

Abstract Objective To examine whether expectant management confers any benefit on operative morbidity for the management of placenta accrete spectrum (PAS) disorders. Study design This was a single center retrospective cohort study at a tertiary referral center In Singapore. Women with PAS disorder between January 2006 and December 2017 were identified from the hospital register. Antenatal features, surgical factors and post-operative morbidity were compared between women having caesarean hysterectomy, those having caesarean section with placental removal and women having expectant management, defined as caesarean section with retention of placenta using the student’s t and Chi square tests. The natural course, complications and preservation of fertility were examined for women having expectant management. Results Ninety women with PAS were included. The incidence of PAS was 0.064 %. Mean gestational age (GA) at diagnosis was 26.4 weeks. Elective and emergency deliveries were performed at 36.7 and 32.4 weeks respectively (p = Caesarean hysterectomy, Caesarean section with placenta removal and expectant management (EM) were performed in 51(56.7 %),16(17.8 %) and 23(25.6 %) women respectively. The mean blood loss (MBL) and surgical time for EM were significantly lower than those for caesarean hysterectomy 0.52 L vs 3.17 L (p Uterine preservation with EM was successful in 61 % (14/23) women. Although nine women (39 %) in this group needed hysterectomy most complications were minor and presented within three months. The mean follow up overall was 13 months. Conclusion Traditionally caesarean hysterectomy has been the main surgical approach for PAS. Our study consolidates existing evidence for expectant management being an option for a select group of patients to avoid complications associated with hysterectomy and allow uterine preservation.
Cost-effectiveness of endovascular thrombectomy in patients with acute stroke and M2 occlusion.

Background The cost-effectiveness of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to M2 branch occlusion remains uncertain. Objective To evaluate the cost-effectiveness of EVT compared with medical management in patients with acute stroke presenting with M2 occlusion using a decision-analytic model. Methods A decision-analytic study was performed with Markov modeling to estimate the lifetime quality-adjusted life years and associated costs of EVT-treated patients compared with no-EVT/medical management. The study was performed over a lifetime horizon with a societal perspective in the Unites States setting. Base case, one-way, two-way, and probabilistic sensitivity analyses were performed. Results EVT was the long-term cost-effective strategy in 93.37% of the iterations in the probabilistic sensitivity analysis, and resulted in difference in health benefit of 1.66 QALYs in the 65-year-old age groups, equivalent to 606 days in perfect health. Varying the outcomes after both strategies shows that EVT was more cost-effective when the probability of good outcome after EVT was only 4–6% higher relative to medical management in clinically likely scenarios. EVT remained cost-effective even when its cost exceeded US$200 000 (threshold was US$209 111). EVT was even more cost-effective for 55-year-olds than for 65-year-old patients. Conclusion Our study suggests that EVT is cost-effective for treatment of acute M2 branch occlusions. Faster and improved reperfusion techniques would increase the relative cost-effectiveness of EVT even further in these patients.
Dietary Pattern Trajectories in Middle Age and Physical Function in Older Age

Background Increasingly, lifestyle factors in midlife are reported to impact health and functional status in old age. This work examines associations between dietary trajectories in middle age and subsequent impairments in physical function. Method Data are from 851 participants (61% men, mean age at first dietary assessment = 47 years, range 30-59 years) from the Baltimore Longitudinal Study of Aging. We used latent class analysis to derive dietary trajectories based on adherence to the Alternative Healthy Eating Index-2010 (AHEI), and further classified them based on tertiles, as poor (score 48.9). Physical function was assessed with the Short Physical Performance Battery (SPPB). Random effects tobit regression models were used to examine associations between dietary trajectories and later physical function. Results Two latent classes of AHEI scores were generated and labeled "greatly improved" or "moderately improved." In the greatly improved class, participants showed a trend in overall AHEI score from poor/intermediate to good diet categories across dietary assessments with age, over time. In the moderately improved class, the overall AHEI score shifted from poor to intermediate diet categories over time, and the prevalence of the good diet category remained low. Mean AHEI score between ages 30 and 59 years was higher in the greatly, than moderately, improved class. The moderately improved class had 1.6 points lower SPPB score (indicating poorer physical function) at older age than the greatly improved class (p = .022). Conclusions Findings suggest that improving diet quality in middle age may contribute to better physical function in older age.
A Less-Paved Road: Switching Careers and Taking an Unorthodox Path

Ophthalmologists are often quite focused on developing a career as an academician, productive clinician, or administrator. As health care systems increasingly change, more opportunities are arising to use medical and ophthalmic training in different ways. Dr. Fung shares her journey – typical and atypical – from college to ophthalmic training to a successful practice to biotech, describing how unexpected opportunities, following curiosity, and anchoring to core values have guided her down a less-paved but most rewarding path. A few select tools are shared at the end of the chapter to provoke reflection and new perspectives on our own journeys.
Hypertension in Pregnancy

This article reviews the hypertensive complications of pregnancy, focusing on the pathophysiology and management of pre-eclampsia. These are areas where data are sparse and authoritative disagreements loud. We advocate an intermediate approach where treatment regimens aim at a successful conclusion of the pregnancy, without residual pathology in the mother.
Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations.

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.
Treatment optimization of maintenance immunosuppressive agents in pediatric renal transplant recipients

Introduction: Graft survival in pediatric kidney transplant patients has increased significantly within the last three decades, correlating with the discovery and utilization of new immunosuppressants as well as improvements in patient care. Despite these developments in graft survival for patients, there is still improvement needed, particularly in long-term care in pediatric patients receiving grafts from deceased donor patients. Maintenance immunosuppressive therapies have narrow therapeutic indices and are associated with high inter-individual and intra-individual variability.Areas covered: In this review, we examine the impact of pharmacokinetic variability on renal transplantation and its association with age, genetic polymorphisms, drug-drug interactions, drug-disease interactions, renal insufficiency, route of administration, and branded versus generic drug formulation. Pharmacodynamics are outlined in terms of the mechanism of action for each immunosuppressant, potential adverse effects, and the utility of pharmacodynamic biomarkers.Expert opinion: Acquiring abetter quantitative understanding of immunosuppressant pharmacokinetics and pharmacodynamic components should help clinicians implement treatment regimens to maintain the balance between therapeutic efficacy and drug-related toxicity.
Convergence to Fair Wage Growth? Evidence from European Countries on the Link between Productivity and Real Compensation Growth, 1970–2017

This Working Paper addresses the issue of ‘fair’ wage growth over the last few decades. It assesses whether growth in real compensation is systematically associated with labour productivity growth and, if so, whether the two have ‘decoupled’ in recent years. The paper examines country-specific evidence from 25 Member States and finds evidence for a widening of the wage-productivity gap in the 1970s and 1980s which has only been partially closed in recent years.
Science of Compassion

This paper presents a scientific pathway for compassion. The framework presented is for individual, organizational, national, and global transformation and peace. With the framework, an individual may progress to any extent possible for a human being all the way to enlightenment. However, there may be an upper limit to how much progress is possible for specific nations or on a global scale but diligent pursuit of the ideas and concepts should lead to more compassionate nations and a more peaceful world.