cssi/SciSciGPT-SciSciNet huggingface dataset:
Changing lipid-lowering guidelines: whom to treat and how low to go

Results of recent lipid-lowering statin trials, including the Heart Protection Study (HPS), Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER), Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL), and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT), have provided compelling evidence that both low-density lipoprotein cholesterol (LDL-C) cut-points for initiation of lipid-lowering treatment and LDL-C treatment goals in patients at high or moderately high risk of coronary heart disease have been set too high. This evidence has resulted in recent revisions to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, including recommendations for initiation of therapy in high risk patients with LDL-C � 100 mg/dL (2.6 mmol/L); optional initiation of therapy in very high risk patients with LDL-C , 100 mg/dL, with an optional target of LDL-C , 70 mg/dL (1.8 mmol/L); and optional initiation of therapy in moderately high risk patients with LDL-C of 100–129 mg/dL (2.6–3.3 mmol/L), with an optional target of , 100 mg/dL. It is also recommended that lipid-lowering therapy in patients with high or moderately high risk be initiated at an intensity sufficient to produce a 30–40% reduction in LDL-C. Results of ongoing statin trials examining the effects of treatment to low LDL-C targets on clinical events will soon be available, and these will help to further refine optimal therapeutic goals.
The energy landscape of 3-deoxy-D-manno-octulosonate 8-phosphate synthase

3-Deoxy-d-manno-octulosonate 8-phosphate (KDO8P) synthase catalyzes the condensation of arabinose 5-phosphate (A5P) and phosphoenolpyruvate (PEP) to form KDO8P, a key precursor in the biosynthesis of the endotoxin of Gram-negative bacteria. Earlier studies have established that the condensation occurs with a syn addition of water to the si side of C2PEP and of C3PEP to the re side of C1A5P. Two stepwise mechanisms have been proposed for this reaction. One involves a transient carbanion intermediate, formed by attack of water or a hydroxide ion on C2PEP. The other involves a transient oxocarbenium zwitterionic intermediate, formed by direct attack of C3PEP onto C1A5P, followed by reaction of water at C2. In both cases, the transient intermediates are expected to converge to a more stable tetrahedral intermediate, which decays into KDO8P and inorganic phosphate. In this study we calculated the potential energy surfaces (PESs) associated with all possible reaction paths in the active site of KDO8PS: the path...
Microscopic return point memory in Co/Pd multilayer films

We report soft x-ray speckle metrology measurements of microscopic return point and complementary point memory in Co/Pd magnetic films having perpendicular anisotropy. We observe that the domains assemble into a common labyrinth phase with a period that varies by nearly a factor of two between initial reversal and fields near saturation. Unlike previous studies of similar systems, the ability of the film to reproduce its domain structure after magnetic cycling through saturation varies from loop to loop, from position to position on the sample, and with the part of the speckle pattern used in the metrology measurements. We report the distribution of memory as a function of field and discuss these results in terms of the reversal process.
Testicular Sarcoidosis: Sonographic Findings:

Testicular sarcoidosis is a rare but benign entity. It is often mistaken for testicular neoplasm, leading to orchiectomy. It is, therefore, extremely important to identify and correctly diagnose testicular sarcoidosis on sonography to avoid unnecessary orchiectomy. This case study reports a young patient who had a prior history of unilateral orchiectomy for cryporchidism and presented with testicular lesions on the contralateral testis. He was later found to have skin lesions and chest symptoms that led to a diagnosis of sarcoidosis.
Time-Dependent Propensity Score for Assessing the Effect of Vaccine Exposure on Pregnancy Outcomes through Pregnancy Exposure Cohort Studies

Women are advised to be vaccinated for influenza during pregnancy and may receive vaccine at any time during their pregnancy. In observational studies evaluating vaccine safety in pregnancy, to account for such time-varying vaccine exposure, a time-dependent predictor can be used in a proportional hazards model setting for outcomes such as spontaneous abortion or preterm delivery. Also, due to the observational nature of pregnancy exposure cohort studies and relatively low event rates, propensity score (PS) methods are often used to adjust for potential confounders. Using Monte Carlo simulation experiments, we compare two different ways to model the PS for vaccine exposure: (1) logistic regression treating the exposure status as binary yes or no; (2) Cox regression treating time to exposure as time-to-event. Coverage probability of the nominal 95% confidence interval for the exposure effect is used as the main measure of performance. The performance of the logistic regression PS depends largely on how the exposure data is generated. In contrast, the Cox regression PS consistently performs well across the different data generating mechanisms that we have considered. In addition, the Cox regression PS allows adjusting for potential time-varying confounders such as season of the year or exposure to additional vaccines. The application of the Cox regression PS is illustrated using data from a recent study of the safety of pandemic H1N1 influenza vaccine during pregnancy.
Transcriptome Analysis Applied to Survival of Shewanella oneidensis MR-1 Exposed to Ionizing Radiation

The ionizing radiation (IR) dose that yields 20% survival (D20) of Shewanella oneidensis MR-1 is lower by factors of 20 and 200 than those for Escherichia coli and Deinococcus radiodurans, respectively. Transcriptome analysis was used to identify the genes of MR-1 responding to 40 Gy (D20). We observed the induction of 170 genes and repression of 87 genes in MR-1 during a 1-h recovery period after irradiation. The genomic response of MR-1 to IR is very similar to its response to UV radiation (254 nm), which included induction of systems involved in DNA repair and prophage synthesis and the absence of differential regulation of tricarboxylic acid cycle activity, which occurs in IR-irradiated D. radiodurans. Furthermore, strong induction of genes encoding antioxidant enzymes in MR-1 was observed. DNA damage may not be the principal cause of high sensitivity to IR, considering that MR-1 carries genes encoding a complex set of DNA repair systems and 40 Gy IR induces less than one double-strand break in its genome. Instead, a combination of oxidative stress, protein damage, and prophage-mediated cell lysis during irradiation and recovery might underlie this organism's great sensitivity to IR.
Desensitization to Allopurinol in a Patient with Previous Failed Desensitization

OBJECTIVE:To describe an allopurinol desensitization that failed on the first attempt but was successful on the second attempt, resulting in the management of crippling tophaceous gout.CASE SUMMARY:A 64-year-old white man with a history of gouty nephropathy requiring hemodialysis developed a severe cutaneous reaction from exposure to allopurinol. The first desensitization attempt was unsuccessful, and the gouty nephropathy caused chronic cellulitus and urate microcrystal deposition on the patient's hands and feet. Continuous ambulatory peritoneal dialysis and hemodialysis were used to treat the patient's severe symptoms and increase uric acid clearance. This method, however, was ineffective. Severe tissue ischemia, requiring bilateral below-the-knee amputations, prompted the second desensitization attempt four years later. The second attempt, administered differently and with more caution, was successful and did not cause further complications.DISCUSSION:Allopurinol is the only agent available to effectiv...
Sensory stimulation and music therapy programs for treating disorders of consciousness

Until now, no treatment has shown its efficacy in patients with severe brain injury, with the exception of one pharmacological agent (i.e., Amantadine; Giacino et al., 2012). Recovery of consciousness is therefore one of the biggest challenge facing clinicians (Whyte, 2014). For years, sensory stimulation programs have been the most frequently applied treatment during patients' neurorehabilitation (Tolle and Reimer, 2003). These programs are based on the idea that an enriched environment benefits brain plasticity and improves recovery of injured brains. Theories of brain plasticity, which suggest that an adult injured brain has the capacity to reorganize itself to compensate for affected regions, have broadly been accepted for several years (Hummel and Cohen, 2005). The most famous case illustrating this phenomenon is the case of Terry Wallis (Voss et al., 2006). This patient remained in a minimally conscious state for 19 years after a traumatic brain injury and yet recovered functional verbal and motor activities. A study of this case revealed a neural change, mainly involving the precuneus which is related to consciousness, suggesting that this spectacular recovery could be explained by brain plasticity. These results stress the importance of developing therapeutics that intensify brain plasticity in severely brain-injured adults to reach full recovery of consciousness. Providing sensory stimulation may potentially stimulate affected neural networks, accelerate brain plasticity, and avoid a sensory deprivation that could slow down the patient's recovery. The efficacy of such intervention is, however, still currently debated. Recently, music therapy has been presented as another potential way to stimulate those patients and may constitute a promising alternative to sensory stimulation programs (Magee and O'Kelly, 2015).
Metal binding at the Deinococcus radiodurans Dps-1 N-terminal metal site controls dodecameric assembly and DNA binding

The prokaryotic DNA protection during starvation (Dps) proteins typically protect macromolecules against damaging agents via physical association with DNA and by oxidizing and sequestering iron. However, Deinococcus radiodurans Dps-1, which binds DNA with high affinity, fails to protect DNA against hydroxyl radicals due to iron leakage from the core, raising the question of how (•)OH-mediated damage to Dps-1-bound DNA is avoided. As shown here, Mn(II) inhibits ferroxidase activity, suggesting that ferroxidation may be prevented in vivo as D. radiodurans accumulates a high ratio of Mn:Fe. Dps-1 has an N-terminal extension with a unique metal-binding site, an extension that has been proposed to be important for DNA binding and dodecameric assembly. Electrophoretic mobility shift assays show that Mn(II) restores DNA binding to bipyridyl-treated Dps-1, whereas Fe(II) fails to do so in the presence of H(2)O(2), thus preventing DNA binding under conditions of ongoing ferroxidase activity. We also show that disruption of the N-terminal metal site leads to a significant reduction in DNA binding and to compromised oligomeric assembly, with the mutant protein assembling into a hexamer in the presence of divalent metal. We propose that securing the N-terminal loop by metal binding is required to initiate dodecameric assembly by contacting the neighboring dimer and that the absence of such optimal contacts results in formation of a hexameric assembly intermediate in which three dimers associate about one of the 3-fold axes. Once dodecameric Dps-1 is assembled, metal binding no longer affects oligomeric state; instead, differential metal binding controls DNA interaction under conditions of oxidative stress.
Pruning Lower Branches of Live Oak (Quercus virginiana Mill.) Cultivars and Seedlings during Nursery Production: Balancing Growth and Efficiency

Tree production requires time for pruning to meet customer expectations, yet pruning can slow growth and increase the time (and cost) to prepare trees for market. Our research quantifies trade-of fs between growth and pruning. In two separate locations, over two time periods, we found no difference in caliper growth between trees with only the lar gest one or two low branches removed at each pruning, compared with trees having all lower branches shortened. Acorn-propagated and Cathedral Oak ® Quercus virginiana (Mill.) with all branches removed from the lower 1.37 m (4.5 ft) of trunk (temporary branches destined to be removed to produce a trunk clear of branches and a distinct canopy) by 18 months after planting had smaller caliper than other pruning treatments; however , pruning these branches had no impact on the Highrise ® cultivar. Removing the largest one or two low branches at each pruning was the most ef ficient pruning method tested. Removing all temporary branches in February of the last year of production (2004) did not reduce caliper , height, or canopy spread compared to removing half in February and half in October . Since there was no difference in time required for pruning, we suggest removing branches early in the last growing season for more completely closed wounds and enhanced customer appeal. Index words: tree nursery, production protocol, shoot pruning, temporary branches, Quercus virginiana, Highrise
Crafting a Party System: The Return of German Party Politics and the Beginning of Licensing Regimes

Beginning in August 1945 in the United States zone of Germany, September 1945 in the British, and December 1945 in the French, German political parties could form again — subject to Allied licensing. Throughout the occupation, the Allies’ licensing regimes would perpetuate their influence over the nascent party system by forcing all would-be parties to apply for Allied permission. If successful, parties would gain a license and the ability to operate publicly as a party, although, as will be seen shortly, a party in a country without a government and without guaranteed constitutional civil liberties might have little in common with parties in the occupiers’ own countries. The differing means of licensing among the three Allies revealed at times sharp distinctions between their goals for Germany’s political re-birth and their conceptions of how political parties should operate. This chapter will illustrate the differences in licensing procedure.
Think Tanks, Public Policy, and the Politics of Expertise: Details on the Characteristics, Perceptions, and Visibility of Think Tanks

This appendix provides additional information on the methodology used in calculating the number of think tanks active in American policy making by the mid-1990s, as well as details about the characteristics, perceptions, and visibility of think tanks. Counting Think Tanks My estimate of the number of think tanks operating in American politics in the 1990s, as reported in Chapter 1, is based on an examination of a variety of sources and background materials. I draw on references from directories, books, and scholarly articles about think tanks as well as newspaper and magazine clippings to arrive at a count of 306 organizations. The single most comprehensive source of think tank listings, and the one upon which I depend most, is Hellebust's Think Tank Directory . In sorting through Hellebust's entries, I excluded from my database organizations that are not independent or not oriented toward affecting public policy debates. After I narrowed Hellebust's list of organizations, 302 institutions qualified as think tanks according to my definition. I included an additional four think tanks in the database based on references made in a variety of other sources. The four organizations added were Campaign for America's Future, a liberal/progressive think tank founded in 1996; Institute for Energy Research, a conservative, Texas-based think tank founded in 1989; Institute for Gay and Lesbian Strategic Studies, a scholarly, liberal-oriented research organization started in 1994; and, the German Marshall Fund, a research and grantmaking institution founded in 1972. The first three may have been overlooked by Hellebust because they are new and relatively small.
Surf and Turf (1901–1903)

According to Savage-Landor’s August 1901 observation, two-thirds of Gilan’s trade was in Russian hands. The shops in Rasht were the final repository for unsold inventory of canned goods, wines, and liquors that had been shipped from Baku and other Russian towns. The traditional French loaf sugar had been displaced by the cheaper Russian sugar. Tobacco products were of Russian and Turkish origin. The other one-third or so of Gilan’s import trade was in the form of English goods, principally from Manchester and largely in the form of shirting, whose good quality had given it a dominant market position despite the cheaper Russian, German, Austrian, Italian, and Dutch products.1
Manganese and Nutritional Immunity

Abstract All of life requires manganese, including bacterial pathogens. Hosts, including humans, take advantage of this fact by limiting the availability of manganese in the body so that bacteria become manganese starved during infection. Starving pathogens of essential nutrients is known as nutritional immunity. Manganese is restricted at the site of infection by manganese-binding proteins, including the neutrophil protein calprotectin and the macrophage protein natural resistance-associated macrophage protein-1 (NRAMP1). Calprotectin binds manganese in the extracellular environment, which is important for defense against bacteria such as Staphylococcus aureus . NRAMP1 transports manganese out of the macrophage phagosome, a compartment where some bacteria such as Salmonella replicate. These strategies are both important for manganese-starving bacteria, but many pathogens combat manganese limitation by expressing manganese import proteins on their surfaces. These importers allow pathogens to cause disease. In this chapter, we discuss the host and bacterial side of manganese nutritional immunity and raise some important unanswered questions for this field.
Directed self-assembly: A dress code for block copolymers

A sacrificial overcoat layer directs self-assembly of block copolymers into lamellae with features smaller than 10 nm.
Establishing Conventions for Citing Educational Materials (Abstract Only)

Course syllabi, exercises, assignments, and project specifications are creative acts of design. But there are no conventions for citing such works, as one would cite a research paper or patent. There are several potentially important reasons for establishing conventions for citing educational content, and thus tracking their diffusion and influence. (1) Design of courseware is at least as important to teaching as is delivering lectures and grading assessments. If citation conventions were established, then the degree of adoption by others could be part of a teaching-faculty member's professional evaluation. (2) Research grants often include education and outreach plans, and being able to track the influence of materials under such plans would be valuable for funding agencies and principal investigators. (3) Establishing citation conventions may raise consciousness about citing any and all creative works that an instructor uses, particularly when we want our students to embrace citation best practices. After all, what most undergraduates will see of the scholarship modeled by faculty will be through teaching. (4) Conferences like SIGCSE are increasingly competitive, and publishing a paper that reports on educational material, thereby enabling "conventional citation" may be difficult. But we still want to cite and track uptake of the educational material. This lightning talk argues that citation conventions be adapted for educational materials, and describes a sample convention. The goal of the lightening talk is to gauge interest and solicit collaborators.
The ABCD Study of Neurodevelopment: Identifying Neurocircuit Targets for Prevention and Treatment of Adolescent Substance Abuse

Substance use disorders (SUD) can be considered developmental disorders in light of their frequent origins in substance initiation during adolescence. Cross-sectional functional magnetic resonance imaging (fMRI) studies of adolescent substance users or adolescents with SUD have indicated aberrations in brain structures or circuits implicated in motivation, self-control, and mood-regulation. However, attributing these differences to the neurotoxicological effects of chronic substance use has been problematic in that these circuits are also aberrant in at-risk children, such as those with prenatal substance exposure, externalizing disorders (such as conduct disorder), or prodromal internalizing disorders such as depression. To better isolate the effects of substance exposure on the adolescent brain, the newly-launched Adolescent Brain Cognitive Development (ABCD) study, funded by the National Institutes of Health, will follow the neurodevelopmental trajectories of over 11,000 American 9/10-year-olds for 10 years, into emerging adulthood. This study will provide a rich open-access dataset on longitudinal interactions of neurodevelopment, environmental exposures, and childhood psychopathology that confer addiction risk. The ABCD twin study will further clarify genetic versus experiential influences (e.g., substance use) on neurodevelopmental and psychosocial outcomes. Neurocircuitry thought to regulate mood and behavior has been directly normalized by administration of psychoactive medications and by cognitive therapies in adults. Because of this, we contend that ABCD project data will be a crucial resource for prevention and treatment of SUD in adolescence because its cutting-edge neuroimaging and childhood assessments hold potential for discovery of additional targetable brain differences earlier in development that are prognostic of (or aberrant in) SUD. The ABCD sample size will also have the power to illuminate how sex differences, environmental interactions and other individual differences interact with neurodevelopment to inform treatment in different groups of adolescents.
Experimental Study of Optimal Measurements for Quantum State Tomography

U.S. National Science Foundation [PHY-1521439, PHY-1521431, PHY 1521016]; U.S. Department of Defense
Histone Deacetylase 1 Depletion Activates Human Cardiac Mesenchymal Stromal Cell Proangiogenic Paracrine Signaling Through a Mechanism Requiring Enhanced Basic Fibroblast Growth Factor Synthesis and Secretion

BackgroundCardiac mesenchymal cell (CMC) administration improves cardiac function in animal models of heart failure. Although the precise mechanisms remain unclear, transdifferentiation and paracri...
P-014 Beyond diagnostic angiography: the transradial approach as first line for both anterior and posterior circulation interventions

Introduction Transradial access (TRA) has become standard of care for cardiac interventions given its improved safety over transfemoral access (TFA). Like many advances in interventional cardiology, adoption in neurointervention has lagged behind. At our center we have been using TRA routinely for diagnostic angiography and posterior circulation interventions. We recently expanded this “Radial First” philosophy to include all interventional procedures, with an emphasis on anterior circulation interventions. In this study we report our favorable experience using TRA in 74 consecutive patients undergoing interventional procedures, the majority of which were anterior circulation procedures. Methods Our prospectively maintained database was retrospectively reviewed for patients from our institution who underwent neurointerventions from August 2015 to March 2017. Patients undergoing an interventional procedure where TRA was either used or attempted were included in this study. Diagnostic angiography was excluded. Operative reports were reviewed for patient demographics, clinical and procedural details. Results A total of 74 patients met the inclusion criteria with an average age of 64.4 years (±17.8 years). Transradial access was used for anterior circulation pathology in 77% (n=57) of the cases. The targeted vessel was successfully reached in 90.5% (n=67) of all cases. The majority of the cases were performed for aneurysm treatment (27%, n=20) or acute ischemic stroke (33.8%, n=25). Other interventions performed included treatment of AVMS and dAVF, tumor embolization, angioplasty, balloon test occlusion, prolonged infusions and vessel sacrifice (see table). Seven of the cases represented a conversion from a failed attempt at TFA. Conversion to a transfemoral approach was required in 7 cases (9.5%). The right radial artery was used for 93% (n=69) of the cases. The average fluoroscopy time of all cases was 62.4 min (±37.9 min). The majority of cases used an 070 guide catheter, including flow diversion cases. A Simmons 2 shaped catheter was most frequently used to select the desired vessel off the aortic arch and then the 070 guide catheter was telescoped over the diagnostic catheter. There were no complications related to radial access. Conclusions This represents the largest series of TRA for anterior circulation neurointerventional procedures. The targeted intervention was successfully performed via the radial approach in 91% of the cases, for a wide variety of pathologies, with no access-related complications. Given this technical success and improved access safety profile, we now employ the transradial approach as first line for interventional procedures. Disclosures J. Caplan: None. B. Snelling: None. S. Sur: None. P. Khandelwal: None. R. Starke: None. D. Yavagal: 2; C; Medtronic. E. Peterson: 2; C; Codman, Stryker, Medtronic.
On the origin of silt laminae in laminated shales

Abstract Experiments with mixtures of quartz silt and clays, under conditions where pure silt and clay suspensions form bedload ripples (non-cohesive silt, flocculated clay) show that coarse silt does segregate from clays during transport. As bedload transport proceeds, ripples of coarse silt and flocculated mud migrate over the bed surface simultaneously. Migrating ripples leave behind a thin veneer of silt grains or clay floccules, and over time a laminated deposit, consisting of thin parallel silt and clay laminae, builds up. If silt of a wide size range (60 μm to a few microns) is used, the coarse silt ends up in ripples and silt laminae, whereas the fine silt (20 μm or less) is integrated into clay floccules and stays mixed and suspended in the flocculated clay matrix. In natural laminated mudstones, coarse silt is typically found in thin laminae, whereas fine silt occurs mainly in the interlaminated clays. These experiments produce an analogous particle distribution and therefore suggest a likely way in which laminated mudstones of the rock record were formed.
Abstract 206: High False Positive Rates of Atrial Fibrillation Detection Among Stroke Patients who Receive Medtronic Implantable Loop Recorders

Introduction: Atrial fibrillation is a known risk factor for the development of stroke. Implantable loop recorders (ILRs) have specific algorithms to detect occult atrial fibrillation and can be used in patients with cryptogenic stroke. There is limited data on the frequency of false positive atrial fibrillation detected by the Medtronic ILR. Hypothesis: Medtronic ILRs have a high rate of false positives but despite this are still effective at detecting atrial fibrillation in patients with cryptogenic stroke. Methods: All stroke patients who underwent ILR placement from Jan 1, 2013 to June 30, 2015 were prospectively collected through an administrative database. Baseline and clinical characteristics were retrospectively obtained. A random sampling of ILR tracings identified as atrial fibrillation by the Medtronic algorithm was adjudicated by a board certified electrophysiologist for accuracy. Results: Among 52 patients with a history of ischemic stroke or TIA (mean age 68±14 years, 58% male, 83% white), there were 166 rhythm strips identified as atrial fibrillation by the Medtronic algorithm which were adjudicated. Of the 166 strips reviewed, 140 (84%) were incorrectly identified as atrial fibrillation; of those false positives, adjudication identified 57% as premature atrial complexes(PACs), 22% as T wave over-sensing, 10% due to noise, 5.0% due to premature ventricular complexes (PVCs), 2.9% due to under-sensing, and 2.9% due to sinus arrhythmia. Of the 38 (73%) patients who had ILR implantation for cryptogenic stroke, 4 (11%) were identified as having true atrial fibrillation by ILR after adjudication over 413 patient-months of monitoring; mean time to atrial fibrillation detection was 93 days after implantation. Conclusions: Stroke patients who undergo Medtronic ILR placement have high false positive rates of atrial fibrillation detected with the Medtronic algorithm. When adequately reviewed by a trained cardiologist for accuracy, the Medtronic ILRs remain effective at detecting atrial fibrillation in cryptogenic stroke patients.
The role of radiation therapy in the treatment of Stage II endometrial cancer: A large database study.

Abstract Purpose The optimum adjuvant treatment for Stage II endometrial cancer patients is unknown. External beam radiation therapy (EBRT) is often considered the standard of care; however, retrospective series suggest that brachytherapy (BT) alone may be sufficient for selected patients. As randomized data are lacking, we used a large database to explore this question. Methods and Materials The National Cancer Data Base was queried for patients with pathologic International Federation of Gynecology and Obstetrics Stage II disease. Demographic, clinic-pathologic, and treatment details were compared between patients. Multivariable analysis was used to determine factors associated with receiving radiation therapy (RT). To account for imbalances between groups, a matched-pair analysis was completed. Results Eight thousand one hundred forty patients were included. RT was associated with overall survival (OS), with EBRT (hazard ratio [HR] 0.64), BT (HR 0.47), and combination (HR 0.54) showing increased OS on univariate analysis. Facility, urban location, diagnosis year, hysterectomy type, and chemotherapy did not reach significance. On multivariate analysis, RT was associated with OS, with EBRT (HR 0.69), BT (HR 0.60), and combination (HR 0.54) showing benefit. Using propensity-score matching, RT continued to show improved OS regardless of type: BT (82% vs. 73% 5-year OS) and EBRT (77% vs. 71%). BT as compared to EBRT had equivalent survival (81% vs. 79%, not statistically significant). Conclusion This study of over 8,000 patients demonstrates that adjuvant RT confers a survival benefit in Stage II endometrial cancer and supports the continued use of RT in these patients. BT alone may be reasonable in carefully selected patients.
Do Older Listeners With Hearing Loss Benefit From Dynamic Pitch for Speech Recognition in Noise

Purpose Dynamic pitch, the variation in the fundamental frequency of speech, aids older listeners' speech perception in noise. It is unclear, however, whether some older listeners with hearing loss...
Toward a Multi-method Approach: Lossy Data Compression for Climate Simulation Data

Earth System Model (ESM) simulations are increasingly constrained by the amount of data that they generate rather than by computational resources. The use of lossy data compression on model output can reduce storage costs and data transmission overheads, but care must be taken to ensure that science results are not impacted. Choosing appropriate compression algorithms and parameters is not trivial given the diversity of data produced by ESMs and requires an understanding of both the attributes of the data and the properties of the chosen compression methods. Here we discuss the properties of two distinct approaches for lossy compression in the context of a well-known ESM, demonstrating the different strengths of each, to motivate the development of an automated multi-method approach for compression of climate model output.
Immunogenetics. Soaring costs in defence.

The most intensively studied element of the immune system is the major histocompatibility complex, to which various gene families contribute. Two papers which provide complete nucleotide sequences of these complexes in the human and chicken allow more thorough comparison of them than ever before.
Integrating mathematical optimization in devs for nuclear medicine patient and resource scheduling

Nuclear medicine is a subspecialty of radiology that uses advanced technology and radiopharmaceuticals for the diagnosis and treatment of medical conditions. Procedures in nuclear medicine require the use of radiopharmaceuticals, are multi-step, and have to be performed under strict time windows constraints. These characteristics make the scheduling of patients and resources in nuclear medicine challenging. In this work, we integrate DEVS and CPLEX, a mathematical programming optimization software, to develop a simulation-optimization scheduling methodology for nuclear medicine clinics. We report on computational results of the new model based on a real clinic, historical data, and both patient and management performance measures. The results show that new methodology provides on average an increase of 3% on patient throughput and a decrease of 20% on patient waiting time over a scheduling policy that was used in the clinic in the past.
Mechanisms of Mucosal Protection

The analysis of mechanisms of mucosal protection cannot be separated from often referring to the pathogenesis of mucosal injury. Deductions from studies on the mechanisms of gastrointestinal (GI) mucosal damage are frequently applicable to the understanding of mucosal protection. One of the key aspects of these extrapolations is that, according to conclusions derived during the last decade of research on mucosal injury and protection, both processes seem to be multifac-torial or pluricausal. Empirical studies and theoretical analyses performed during the nineteenth century and the early twentieth century generally centered on one damaging element, e. g., acid, pepsin, infection, ischemia. Consequently, protection was also postulated to be operational only against that single damaging agent. Therefore, the development and clinical use of specific protective drugs, such as antacids, antisecretory agents, and antibiotics. The recent popularity of infectious theory of origin of ulcer disease is actually the recurrence of cyclical trends (in intervals of about 15–20 years) following the first extensive implication by Virchow of apparent infectious agents in the etiology of gastric and duodenal ulcers. The consideration of those factors subsequently included bacteria, parasites, and viruses.
Induction of proliferation of purified human myeloid progenitor cells: a rapid assay for granulocyte colony-stimulating factors.

The proliferation and differentiation of granulocyte and monocyte progenitor cells (CFU-C) in vitro is dependent on the presence of a group of closely related glycoproteins termed colony-stimulating factors (CSF). In order to investigate the interaction of these factors with CFU-C, we purified CFU-C from the peripheral blood of chronic myeloid leukemia patients with an immune rosette technique using specific monoclonal antibodies (mean 74-fold enrichment, 45% cloning efficiency). Colony formation by purified CFU-C demonstrated an absolute dependence on an exogenous source of CSF. Liquid culture of small aliquots of enriched CFU-C with CSF-containing medium resulted in a rapid, time- and concentration-dependent induction of DNA synthesis as measured by 3H-thymidine incorporation. This specific CSF induction of DNA synthesis by enriched CFU-C was used to develop a microassay system for CSF activity. CSF activity could be reproducibly quantitated in 24–48 hr. The proliferating cells in this assay system were shown to be myeloid progenitor cells by examining the morphology of their progeny and by determining the surface antigen phenotype of the responding cells (Ia+, T3-, B1-, Mo1-). This microassay provides a quantitative assessment of CSF activity that may be useful in the purification of human CSF and in the generation of monoclonal antibodies to CFU-C surface structures.
Synthesis of the Four Stereoisomers of N-Fmoc-O-t-Bu-4,4,4- trifluorothreonine

Introduction Fluorination of peptide can lead to many benefits, such as increased stability, lipophilicity, and unique NMR signals. Hence, the synthesis of enantiomerically pure fluorinated amino acids in their protected forms ready for solid-phase peptide synthesis is of great value to engineering fluorinated peptides. In this regard, NFmoc-O-t-Bu-4,4,4-trifluorothreonine (tfT) poses a unique challenge as it has two chiral centers and hence four stereoisomers: (2S, 3S)-N-Fmoc-O-t-Bu-tfT 1, (2S, 3R)-N-Fmoc-O-t-Bu-tfT 2, (2R, 3S)-N-Fmoc-O-t-Bu-tfT 3, (2R, 3R)-N-Fmoc-O-tBu-tfT 4 (Fig. 1). Although there are some reports on synthesis of tfT [1,2], those methods have great difficulties in introducing protective groups. Herein, we report some convenient methods for the stereoselective synthesis of all four isomers of tfT on 10g 20g scale in high yield and good optical purity in 9-10 steps.
Analytical Platforms and Techniques to Study Stem Cell Metabolism

Over the past decade, advances in systems biology or 'omics techniques have enabled unprecedented insights into the biological processes that occur in cells, tissues, and on the organism level. One of these technologies is the metabolomics, which examines the whole content of the metabolites in a given sample. In a biological system, a stem cell for instance, there are thousands of single components, such as genes, RNA, proteins, and metabolites. These multiple molecular species interact with each other and these interactions may change over the life-time of a cell or in response to specific stimuli, adding to the complexity of the system. Using metabolomics, we can obtain an instantaneous snapshot of the biological status of a cell, tissue, or organism and gain insights on the pattern(s) of numerous analytes, both known and unknown, that result because of a given biological condition. Here, we outline the main methods to study the metabolism of stem cells, including a relatively recent technology of mass spectrometry imaging. Given the abundant and increasing interest in stem cell metabolism in both physiological and pathological conditions, we hope that this chapter will provide incentives for more research in these areas to ultimately reach wide network of applications in biomedical, pharmaceutical, and nutritional research and clinical medicine.
Deterministic transfection and genetic manipulation of organotypic brain slice cultures for ex vivo imaging

The organotypic brain slice culture has been used to great effect for many studies, from electrophysiology to cell fate determination. However, a major limitation of this technique is the difficult...
Transcriptional regulation of metabolic flux: A Caenorhabditis elegans perspective

Abstract Metabolic reactions form the basis of life to generate biomass, produce energy, and eliminate waste. Together, metabolic reactions function in the context of a highly interconnected metabolic network. Flux through this network needs to be adaptable depending on nutrient availability or metabolite buildup. Metabolic flux can be changed by different regulatory mechanisms, including the allosteric regulation of metabolic enzyme activity by small molecules and by changes in metabolic gene expression. For the transcriptional control of metabolic genes to happen accurately, the metabolic status of the system needs to be relayed to the regulators of gene expression, such as transcription factors. Allosteric regulation of metabolic enzymes can only be studied for individual proteins, whereas the transcriptional control of metabolism can increasingly be examined at a systems, or network level. Here, we discuss recent studies regarding the interplay between metabolic and gene regulatory networks using the nematode Caenorhabditis elegans. We discuss why C. elegans provides an elegant model system for studying the transcriptional regulation of metabolism and describe recent insights into its gene regulatory and metabolic networks. We then describe a recently discovered mechanism by which the buildup of a cellular metabolite can transcriptionally rewire metabolism. Finally, we discuss the future challenge of integrating large transcriptomic, proteomic, and metabolomic data sets to fully understand the transcriptional regulation of metabolic flux.
Discovery of mammalian regulators of ribosome biogenesis

It is well known that in cancer an increased size and number of nucleoli correlates with increased malignant potential. Nucleoli make ribosomes, the essential protein synthesizers of the cell. Prev...
Principles of Economic Design

There are three central principles of good economic design: (1) Freedom of choice leads to good outcomes. (2) Charging (crediting) people for the cost (benefits) of their choices yields efficient outcomes. (3) Goodwill is highly productive. These central principles lead to free markets, Pigouvian taxes and subsidies, lump-sum taxes on land, mechanisms that apply marginal-cost pricing to participation in decisions, and money creation by interest-free lending to citizens, in proportion to their expected demand for cash balances. However, every improvement in efficiency can be introduced in myriad ways, with different distributional consequences, leading to conflict that inhibits improvements. Therefore greater consensus about distributional equity is necessary to improve economic design.
Survival analysis of the Black Death: Social inequality of women and the perils of life and death in Medieval London.

Objectives Described as an indiscriminate killer by many chroniclers, the Black Death descended on London during the 14th century. To best understand the pattern of transmission among demographic groups, models should include multiple demographic and health covariates concurrently, something rarely done when examining Black Death, but implemented in this study to identify which demographic groups had a higher susceptibility. Female predisposition to the Black Death was also explored, focusing on whether social inequality added to vulnerability. Materials and methods Three attritional cemeteries from the Wellcome Osteological Research Database were compared with the Black Death cemetery, East Smithfield. A Cox proportional hazards regression estimated hazards ratios of dying of the Black Death, using transition analysis ages-at-death as the time variable, and sex and frailty as covariates. Additionally, a binomial logistic regression generated odds ratios for age-at-death, sex, and frailty. Results The Cox model produced a significant hazards ratio for individuals deemed frail. Similarly, the logit model calculated significantly increased odds ratios for frail individuals, and decreased odds for individuals aged 65+. Discussion The older individuals were not undergoing growth during times of great stress in London pre-dating the Black Death epidemic, which may explain the decreased odds of contracting the Black Death. Further, although women dealt with social inequality, which partially led to the demographic puzzle of the Medieval "missing" women, women's susceptibility to infection by the Black Death was not increased. The phenomenon of the missing women may be due to a combination of factors, including infant and child mortality and preservation.
Efficacy and safety of airway stenting to treat anastomotic complications after lung transplant: a cohort study

Background Airway complications affect roughly 15-20% of lung transplant patients. Airway stents are an attractive therapeutic option; however, no experimental or controlled observational data exists to draw firm conclusions regarding airway stent efficacy and safety in this population. Methods We performed a retrospective cohort study of patients who underwent airway stent placement for post-transplant anastomotic airway complications. The primary outcomes were improvements in FEV1 and reduction in bronchoscopies post-stent. Results We identified 36 patients who underwent airway stenting between October 2012 and October 2017. A total of 47 airways underwent stent placement. Improvement in FEV1 after stent placement was only observed in patients who ultimately were able to undergo stent removal. Patients who expired prior to stent removal had no immediate FEV1 improvement after stent placement. Among subjects who underwent stent removal, there was a statistically significant reduction in number of bronchoscopies per month after stent removal compared to pre-stent placement. Male gender was the only predictor of FEV1 improvement after stent placement while male gender and dehiscence prior to stent placement predicted increased number of bronchoscopies after stent placement. Mucous plugging and granulation tissue formation were the most common stent related complications. Conclusions Only select patients benefit from stent placement for airways stenosis after lung transplant. Complications related to stent placement are common. Patients with airway complications treated with airway stents undergo a high volume of repeat procedures.
Life on File: Archival Epistemology and Theory

History’s epistemological dilemma equally applies to sociology: how can we make claims about persons, events, and processes on the basis of archival records? This article develops a framework called Life on File that combines sociological strengths in qualitative methodologies and an interest in how states shape populations, with library and information sciences’ attention to documentary production and anthropological and historical insights into the intersections of archives, knowledge, and power. The framework has three components: the act of recovery of life, processes, and events; the turning of life into a record; and the movement of a file from collection to preservation and use. The result is a methodologically rigorous and globally mobile theory. Empirically, the piece draws on comparative historical fieldwork on state-led racial classification and naturalization practices preserved in Japanese and German archives. While the framework is grounded in research on state archives, its utility extends across types of archives and records. In addition, it provides sociologists with a roadmap on how to use archives in single case as well as comparative and transnational research.
A revised phylogeny of the New Caledonian endemic genus Troglosiro (Opiliones : Cyphophthalmi : Troglosironidae) with the description of four new species

The Cyphophthalmi genus Troglosiro (the only genus of the family Troglosironidae) is endemic to New Caledonia, representing one of the oldest lineages of this emerged part of Zealandia. Its species are short-range endemics, many known from single localities. Here we examined the phylogenetic relationships of Troglosironidae using standard Sanger-sequenced markers (nuclear 18S rRNA, 28S rRNA, and mitochondrial 16S rRNA and cytochrome c oxidase subunit I) and a combination of phylogenetic methods, including parsimony under Direct Optimization and maximum likelihood with static homology. We also applied a diversity of species delimitation methods, including distance-based, topology-based and unsupervised machine learning to evaluate previous species designations. Finally, we used a combination of genetic and morphological information to describe four new species – T. dogny sp. nov., T. pin sp. nov., T. pseudojuberthiei sp. nov. and T. sharmai sp. nov. – and discuss them in the broader context of the phylogeny and biogeographic history of the family. A key to the species of Troglosiro is also provided. urn:lsid:zoobank.org:pub:93541314-8309-468C-BB77-B34C3A81137E
International Bond Markets

The international bond market allows investors to diversify their portfolio, preserve their wealth, and realize attractive returns on their investment. International bond markets are not unified into a single market (like FX and Eurocurrency market), therefore, they can be done OTC. International bond market participants are those involved in the issuance and trading of debt securities. It primarily includes government-issued and corporate debt securities.