cssi/SciSciGPT-SciSciNet huggingface dataset:
Prognostic factors and survival of patients with brain metastasis (BM) from breast cancer (BC) who underwent craniotomy.

143 Background: BC is the second most frequent cause of BM after lung cancer, with metastases occurring in 10% - 16% of all patients. BM in patients with BC is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. Methods: We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with BC between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Results: Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The mean time to BM from primary diagnosis was 49 months (ran...
Arctic ground squirrel hippocampus tolerates oxygen glucose deprivation independent of hibernation season even when not hibernating and after ATP depletion, acidosis, and glutamate efflux.

Cerebral ischemia/reperfusion (I/R) triggers a cascade of uncontrolled cellular processes that perturb cell homeostasis. The arctic ground squirrel (AGS), a seasonal hibernator resists brain damage following cerebral I/R caused by cardiac arrest and resuscitation. However, it remains unclear if tolerance to I/R injury in AGS depends on the hibernation season. Moreover, it is also not clear if events such as depletion of ATP, acidosis, and glutamate efflux that are associated with anoxic depolarization are attenuated in AGS. Here, we employ a novel microperfusion technique to test the hypothesis that tolerance to I/R injury modeled in an acute hippocampal slice preparation in AGS is independent of the hibernation season and persists even after glutamate efflux. Acute hippocampal slices were harvested from summer euthermic AGS, hibernating AGS, and interbout euthermic AGS. Slices were subjected to oxygen glucose deprivation (OGD), an in vitro model of I/R injury to determine cell death marked by lactate dehydrogenase (LDH) release. ATP was assayed using ENLITEN ATP assay. Glutamate and aspartate efflux was measured using capillary electrophoresis. For acidosis, slices were subjected to pH 6.4 or ischemic shift solution (ISS). Acute hippocampal slices from rats were used as a positive control, susceptible to I/R injury. Our results indicate that when tissue temperature is maintained at 36°C, hibernation season has no influence on OGD-induced cell death in AGS hippocampal slices. Our data also show that tolerance to OGD in AGS hippocampal slices occurs despite loss of ATP and glutamate release, and persists during conditions that mimic acidosis and ionic shifts, characteristic of cerebral I/R. Read the Editorial Comment for this article on page 10.
Progress in Highway Research

It appears that an early solution of · the more complicated problems, and from the standpoint of National well-being, the graver problems of highway transport, will be reached only in so far as the...
Optimal energy scheduling of a stand-alone multi-sourced microgrid considering environmental aspects

A standalone microgrid with renewable and regular power resources along with storage system play an important role in remote areas in order to solve power supply problems. In this research, an optimal energy management of a standalone microgrid under different operational modes is studied. The objective of the optimization model is to improve energy utilization efficiency; reduce fuel cost and gas emissions by scheduling productions of energy resources in each hour on the next day. In another word, the problem is modeled as a constrained single-objective programming to minimize cost of power and emission generations. The system is tested under two different operational policies where microgrid power generation sources work with and without battery storage system. Then the final results are compared and investigated. The results show a considerable reduction in system total cost and generated emission in comparison with previously proposed methods.
Extensor tendon injuries at the proximal interphalangeal joint.

SUMMARY From the prior discussion, it should be apparent that the multitude of operative procedures reflects the complexity inherent in the extensor mechanism and the often unpredictable outcome of operative intervention. Large studies with detailed analysis of data are few. Despite this, several themes are apparent and need to be respected. The chronic boutonniere deformity reflects long-term derangement with secondary compensation of the extensor mechanism. The surgeons rendering treatment must have a thorough appreciation of normal anatomy as well as an understanding of the evolving pathomechanics. Both physician and patient must be committed to the need for long-term treatment of this disability. The literature leaves no doubt that surgical intervention is best initiated after the attainment of full passive PIP extension. Finally, even in the chronic situation, long-term splinting and exercises may be successful and both obviate surgery and result in a superior outcome.
Work-Family Conflict, Support and Intention to Quit Among Kenyan Female Teachers in Urban Public Schools

Teaching is characterised by high reported levels of turnover and occupational stress. This study examined the nature of the relationship between work-family conflict (WFC), supervisor’s and colleagues’ support, and intention to quit among female teachers with young children in Kenyan urban public schools. The specific objectives were to: 1) compare the intention to quit of female teachers working in the city of Nairobi vis-a-vis those working in secondary urban centres; 2) examine the relationship between intention to quit and WFC; 3) examine the relationship between support and turnover intention; and 4) assess whether support moderates the relationship between WFC and intention to quit. Data were collected by means of 375 self-administered questionnaires and analysed using t-test and hierarchical regression. Questionnaires were distributed to teachers in primary and secondary schools in secondary urban centres and in the Nairobi city. Results show that intention to quit was statistically higher among secondary school teachers, and teachers working in the city. There was a positive relationship between WFC that originates from work and intention to quit, but not between WFC that originates from family and intention to quit. There was a negative relationship between supervisor’s support and intention to quit but not between colleagues’ support and intention to quit. Supervisor support did not moderate the relationship between WFC and intention to quit. Practical and theoretical implications of the study are also provided.
A Black Social Psychologist's Perspective on Racial Forgiveness

Despite the changes and, perhaps, in some cases, because of them, race relations in the United States continue to be a major concern for social scientists. Eighty years of research has provided insight into the causes and pervasiveness of racial bias, strategies for eliminating racial bias, and the effects of racial bias (Fiske, 2004).
Multi-User Mobile Sequential Recommendation: An Efficient Parallel Computing Paradigm

The classic mobile sequential recommendation (MSR) problem aims to provide the optimal route to taxi drivers for minimizing the potential travel distance before they meet next passengers. However, the problem is designed from the view of a single user and may lead to overlapped recommendations and cause traffic problems. Existing approaches usually contain an offline pruning process with extremely high computational cost, given a large number of pick-up points. To this end, we formalize a new multi-user MSR (MMSR) problem that locates optimal routes for a group of drivers with different starting positions. We develop two efficient methods, PSAD and PSAD-M, for solving the MMSR problem by ganging parallel computing and simulated annealing. Our methods outperform several existing approaches, especially for high-dimensional MMSR problems, with a record-breaking performance of 180x speedup using 384 cores.
Are Individual Persons Motivated to Construct Categories or Do They Merely Intend Meanings

The problem of explanation in the psychology of personality has been what to do with the irreducible matter of the individual’s experience of the world. If such experience is solely individual, it is central to the definition of the individual, but impossible for others to study directly. Accordingly, in the name of scientific psychology, the related problems of how a person selects the objects of his experience, and what originates the selection have been separated and cast in what Max Meyer described as the “psychology of the other one” (Woodworth, 1918). In such a psychology, the onlooker can observe an impetus (stimulus) presumably impinging on the mental act of selection, and infer further from the behavioral outcome of the impetus. The experience of originating and constructing a mental object is in a separate province, locked within the walls of the individual.
Alteration of Membrane Potential

We began our investigation of cellular electrical properties, in the last chapter, with a look at the resting membrane potential, which is the ultimate power source for nervous system signaling. We will begin this chapter with a discussion of ways in which the membrane potential is altered so that signaling occurs over short distances (i.e., 10s or 100s of µm). In the second part of the chapter, we will again return to signaling based on changes in the membrane potential, but there we will emphasize long-distance signaling (i.e., up to meters).
Grafting Isobutylene from SBR

Lack of efficient, easily controllable cationic grafting techniques have, until recently, precluded the use of this technique for the preparation of well defined graft copolymers (1). The “grafting onto” approach has been used by Haas and coworkers (1). These authors alkylated poly(p-methoxystyrene) with growing styrene chains using BF3 and SnCl4. Though copolymer was obtained with polystyrene, no graft formed with vinyl butyl ether, vinyl ethyl ether, or isobutylene. Poly (2,6-dimethoxystyrene-g-styrene) was obtained by Overberger and Burns (2) using SnCl4 in a similar process. The large amounts of homopolymer formed in these experiments indicate that the “grafting onto” technique is inefficient.
Nodal Impedance-Based Stability Analysis of Dc Nanogrids

With the growing interest in electrification and interfacing of clean energy and energy storage, new challenges are emerging in stability analysis and control of such systems. Existing stability analysis methods work well for systems with pre-defined power flow and fixed architecture, and most lead to design criteria for source and load impedances. However, the methods presented in the literature are not suitable for analyzing dynamically changing systems, especially for online stability evaluation and monitoring. The nodal impedance-based stability analysis method presented in this paper extends the boundaries of the existing criteria and leads to a practical and effective solution for online stability evaluation and monitoring. Hardware results are provided to validate the proposed analysis method on a scaled-down nanogrid system.
Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions.

Abstract Background There are currently no approved targeted therapies for non-small-cell lung cancer (NSCLC) patients with EGFR exon 20 insertions (ins20), a subgroup of EGFR mutations that are generally refractory to first/second generation EGFR inhibitors. We report the final results of a phase II trial evaluating the activity of the Hsp90 inhibitor luminespib (AUY922) in NSCLC patients with EGFR ins20. Patients and methods Twenty-nine patients with stage IV NSCLC with EGFR ins20 identified on local testing and at least one prior therapy were enrolled on the trial between August 2013 and October 2016. The primary end point was objective response rate (ORR), with a pre-determined target rate of effectiveness [defined as the rate of partial response (PR) plus stable disease (SD) lasting ≥3 months] of 20%. Secondary end points were PFS, overall survival (OS), safety and response by EGFR ins20 subtype. Results Among the 29 patients (18 females, median age 60 years) the ORR was 17%, median progression-free survival was 2.9 months (95% CI 1.4–5.6) and median OS (mOS) was 13 months (95% CI 4.9–19.5). The results exceeded the pre-determined target rate of effectiveness with 11/29 (38%) patients having a PR or an SD ≥3 months. The most common luminespib-related toxicities were diarrhea (83%), visual changes (76%) and fatigue (45%). All study treatment was stopped on 28 February 2017 due to dissolution of study drug availability; 3 patients were on treatment at study termination. Conclusion The study met its primary end point, suggesting that luminespib may be an active therapy for advanced NSCLC patients with EGFR ins20. Luminespib is generally well-tolerated, though reversible low-grade ocular toxicity is common. Further study of luminespib and other hsp90 inhibitors in this population is warranted. Study registration (ClinicalTrials.gov) NCT01854034.
Apple and Microsoft Case Study

The three commonly used tools available for any financial statement analysis are: (i) the horizontal analysis, (ii) the vertical analysis, and (iii) the ratios’ analysis. Besides, financial analyst must assess and break down the reported earnings. A comparative financial ratios’ analysis assists the expert to assess the performance and earning within the industry.
Visual Diagnosis: Melena in a 13-month-old Girl.

1. Malinda Wu, MD* 2. Meghan Kessler, MD† 3. Brett W. Engbrecht, MD, MPH‡ 4. Mark Tulchinsky, MD§ 5. Michael M. Moore, MD§ 6. Chandran P. Alexander, MBBS, MD* 1. *Department of Pediatrics, Penn State Hershey Children’s Hospital, Hershey, PA 2. †Department of Pathology, Penn State Hershey Medical Center, Hershey, PA 3. ‡Department of Pediatric Surgery, Penn State Hershey Children’s Hospital, Hershey, PA 4. §Department of Radiology, Penn State Hershey Children’s Hospital, Hershey, PA A previously healthy 13-month-old girl presents to the emergency department after a bowel movement with copious dark maroon blood with clots (Fig 1). She is fussy during the bowel movement, which is typical for her, and becomes pale thereafter. She does not have a history of constipation. On physical examination she is afebrile, mildly tachycardic, normotensive, and oxygenating well on room air. She is nontoxic appearing, pale, has a soft and flat abdomen that is nontender, without masses, and there is no anal fissure. She has a congenital nevus on her lower back. Figure 1. Patient’s initial maroon-colored stool with clots. Laboratory tests in the emergency department are notable for an elevated blood urea nitrogen level (24 mg/dL [8.57 mmol/L]) with a normal serum creatinine concentration (0.36 mg/dL [31.8 µmol/L]) and glomerular filtration rate (101 mL/min/1.73 m2), microcytic anemia (hemoglobin level, 8 g/dL [80 g/L]; hematocrit, 24.7%; mean corpuscular volume, 69 fL), and unremarkable coagulation studies. Supine and lateral decubitus plain films demonstrate an unusual air-filled, mildly dilated bowel loop with some wall thickening in the middle abdomen. Ultrasonography of the abdomen demonstrates focally dilated loops of bowel in the right lower quadrant containing stool but no evidence of intussusception. A Meckel scan performed 6 hours after intravenous administration of ranitidine (2 mg/kg) shows abnormal small-bowel uptake in the …
Protective transcriptional mechanisms in cardiomyocytes and cardiac fibroblasts

Heart failure is the leading cause of morbidity and mortality worldwide. Several lines of evidence suggest that physical activity and exercise can pre-condition the heart to improve the response to acute cardiac injury such as myocardial infarction or ischemia/reperfusion injury, preventing the progression to heart failure. It is becoming more apparent that cardioprotection is a concerted effort between multiple cell types and converging signaling pathways. However, the molecular mechanisms of cardioprotection are not completely understood. What is clear is that the mechanisms underlying this protection involve acute activation of transcriptional activators and their corresponding gene expression programs. Here, we review the known stress-dependent transcriptional programs that are activated in cardiomyocytes and cardiac fibroblasts to preserve function in the adult heart after injury. Focus is given to prominent transcriptional pathways such as mechanical stress or reactive oxygen species (ROS)-dependent activation of myocardin-related transcription factors (MRTFs) and transforming growth factor beta (TGFβ), and gene expression that positively regulates protective PI3K/Akt signaling. Together, these pathways modulate both beneficial and pathological responses to cardiac injury in a cell-specific manner.
Researching Science Teaching and Learning

I frame my study on the problem of reforming the teaching and learning of science in higher education in the United States. I address the shift from modernism in science to postmodernism in science education research, and the need to address this shift in the teaching of science in college and university classrooms (National Research Council (NRC) 1997, 1999, 2001, 2003; Taylor et al. 2002; Sunal et al. 2004; Druger et al. 2004). Teaching science within a sociocultural frame influences not only future scientists but also encourages future science teachers to think differently about science, teaching, and learning (NRC 2001).
Testing the Structure of a Gaussian Graphical Model With Reduced Transmissions in a Distributed Setting

Testing a covariance matrix following a Gaussian graphical model (GGM) is considered in this paper based on observations made at a set of distributed sensors grouped into clusters. Ordered transmissions are proposed to achieve the same Bayes risk as the optimum centralized energy unconstrained approach but with fewer transmissions and a completely distributed approach. In this approach, we represent the Bayes optimum test statistic as a sum of local test statistics which can be calculated by only utilizing the observations available at one cluster. We select one sensor to be the cluster head (CH) to collect and summarize the observed data in each cluster and intercluster communications are assumed to be inexpensive. The CHs with more informative observations transmit their data to the fusion center (FC) first. By halting before all transmissions have taken place, transmissions can be saved without performance loss. It is shown that this ordering approach can guarantee a lower bound on the average number of transmissions saved for any given GGM and the lower bound can approach approximately half the number of clusters when the minimum eigenvalue of the covariance matrix under the alternative hypothesis in each cluster becomes sufficiently large.
Xanthomonas translucens commandeers the host rate-limiting step in ABA biosynthesis for disease susceptibility.

Plants are vulnerable to disease through pathogen manipulation of phytohormone levels, which otherwise regulate development, abiotic, and biotic responses. Here, we show that the wheat pathogen Xanthomonas translucens pv. undulosa elevates expression of the host gene encoding 9-cis-epoxycarotenoid dioxygenase (TaNCED-5BS), which catalyzes the rate-limiting step in the biosynthesis of the phytohormone abscisic acid and a component of a major abiotic stress-response pathway, to promote disease susceptibility. Gene induction is mediated by a type III transcription activator-like effector. The induction of TaNCED-5BS results in elevated abscisic acid levels, reduced host transpiration and water loss, enhanced spread of bacteria in infected leaves, and decreased expression of the central defense gene TaNPR1. The results represent an appropriation of host physiology by a bacterial virulence effector.
Outcomes after long-term mechanical ventilation of cancer patients

The probability of weaning and of long-term survival of chronically mechanically ventilated cancer patients is unknown, with incomplete information available to guide therapeutic decisions. We sought to determine the probability of weaning and overall survival of cancer patients requiring long-term mechanical ventilation in a specialized weaning unit. A single-institution retrospective review of patients requiring mechanical ventilation outside of a critical care setting from 2008 to 2012 and from January 1 to December 31, 2018, was performed. Demographic and clinical data were recorded, including cancer specifics, comorbidities, treatments, and outcomes. Overall survival was determined using the Kaplan-Meier approach. Time to weaning was analyzed using the cumulative incidence function, with death considered a competing risk. Prognostic factors were evaluated for use in prospective evaluations of weaning protocols. Between 2008 and 2012, 122 patients required mechanical ventilation outside of a critical care setting with weaning as a goal of care. The cumulative incidence of weaning after discharge from the intensive care unit was 42% at 21 days, 49% at 30 days, 58% at 60 days, 61% at 90 days, and 61% at 120 days. The median survival was 0.16 years (95% CI, 0.12 to 0.33) for those not weaned and 1.05 years (95% CI, 0.60 to 1.34) for those weaned. Overall survival at 1 year and 2 years was 52 and 32% among those weaned and 16 and 9% among those not weaned. During 2018, 36 patients at our institution required mechanical ventilation outside of a critical care setting, with weaning as a goal of care. Overall, with a median follow-up of 140 days (range, 0–425 days; average, 141 days), 25% of patients requiring long-term mechanical ventilation (9 of 36) are alive. Cancer patients can be weaned from long-term mechanical ventilation, even after prolonged periods of support. Implementation of a resource-intensive weaning program did not improve rates of successful weaning. No clear time on mechanical ventilation could be identified beyond which weaning was unprecedented. Short-term overall survival for these patients is poor.
Complementary In Vivo Approaches Reveal Quiescent Melanocytes in Anagen Outside the Hair Follicle Bulge

ABSTRACT Melanocyte stem cells (McSCs) are key components of the hair follicle (HF) stem cell system that are derived from neural crest during embryogenesis and are responsible for regeneration of differentiated melanocytes during successive HF cycles. Our previous research has shown presence of two subsets of phenotypically and functionally distinct McSCs exist in murine telogen HFs, CD34+ McSCs in the bulge/lower permanent portion (LPP) and CD34− McSCs in the secondary hair germ (SHG). Whether these subsets are maintained independently or exist in a developmental hierarchy is not yet known. Using Dct-H2BGFP mice, we analyzed the quiescent and proliferative properties of McSCs and melanocytes in anagen and telogen. We found unexpectedly that Kit+Nestin− quiescent melanocytes are maintained outside of the bulge/LPP region throughout anagen in addition to the Kit+Nestin+ quiescent melanocytes of the bulge/LPP. Both subpopulations express lower levels of melanocyte differentiation markers Mitf, Pax3, Dct, Tyrp1 and Tyr compared to differentiated melanocytes of the HF bulb/matrix. These results suggest that quiescent melanocytes localized in the outer root sheath, both in and below the bulge/LPP) retain the stem cell phenotype observed in quiescent McSCs during telogen. This finding has implications for maintenance of distinct subsets of McSCs throughout successive HF cycles.
CO as a substrate and inhibitor of H+ reduction for the Mo-, V-, and Fe-nitrogenase isozymes.

Abstract Three known nitrogenase isozymes, Mo-, V-, and Fe-, catalyze biological reduction of dinitrogen (N2) to ammonia (NH3). All three utilize the same reductive elimination mechanism: an intermediate with two metal-bound hydrides reductively-eliminates hydrogen gas (H2) in a reaction coupled to binding and activation of N2. Nonetheless, the three isozymes show dramatically different relative rates of H2 formation and N2 reduction, revealing important differences in reactivity with substrates. Carbon monoxide (CO) has been characterized as both an inhibitor and substrate for Mo- and V‑nitrogenases, but not for the Fe‑nitrogenase. Here, we present a comparative study of the reactivity of the three isozymes with CO, examining CO both as a substrate and as an inhibitor of proton (H+) reduction under steady-state conditions. For Mo‑nitrogenase, there is neither detectable reduction of CO nor inhibition of H+ reduction. Fe- and V‑nitrogenase show CO reduction and inhibition of H+ reduction that depends on the CO partial pressure. For V‑nitrogenase, ethylene (C2H4) is the major reduction product with a maximum specific activity of ~7.5 nmol C2H4/nmol VFe protein/min at 1 atm CO. The major product of CO reduction for Fe‑nitrogenase is methane (CH4) with a maximum specific activity of ~4.8 nmol CH4/nmol FeFe protein/min at 0.05 atm CO. The rate of CH4 production by Fe‑nitrogenase progressively increases to a maximum at 0.05 atm CO and then declines by ~90% with increasing CO partial pressure up to 1 atm. CO does not inhibit proton reduction in Mo‑nitrogenase but shows 16% inhibition for V‑nitrogenase and 35% for Fe‑nitrogenase.
The Right to Self-Determination of Cultural, Religious and Linguistic Communities in South Africa

This edition, one of the most voluminous to date, opens with an oratio by IT Cohen Professor of International Law and Human Rights, Emory University School of Law, Johan van der Vyver. The paper was delivered in the HL Swanepoel series of lectures on 26 May in Potchefstroom. In a well documented paper covering historical perspectives on the right to self-determination, the definition thereof and limitations thereupon, Van der Vyver concludes that the 'drafters of the South African Constitution rejected segregation of rival ethnic, religious and linguistic communities, as well as the promotion of cultural, religious or linguistic homogeneity within our nation, as a means of counteracting group-related tensions in the country's social construct. . . . The new constitutional dispensation accordingly seeks to promote pride in one's group identities.' He also points out that 'pluralism, tolerance and broadmindedness have been singled out by the European Court of Human Rights as indispensable components of a democratic society.' A link to video material of the lecture is also included.
Conceiving the Indian Buddhist Patriarchs, by Stuart H. Young.

Conceiving the Indian Buddhist Patriarchs, by Stuart H. Young. Honolulu, HI: University of Hawaii Press, 2015. ix + 338 pp., $60.00 (hb). ISBN 9780824841201.
A Return to Culture: Literature as Ecology

Literature is an important part of French national identity and cultural patrimony, as seen in the hype around the literary rentree each year and the prestige economy that continues to mark French ...
Term-limit evasions and the non-compliance cycle

Executive term limits are evidently under stress in many jurisdictions. One mode in which they are evaded is through the formal revision or abrogation of a constitution. Such a process accelerates a pernicious cycle in which constitutional non-compliance begets constitutional instability, which in turn begets subsequent non-compliance. Such a non-compliance cycle is a core problem in law, and one that deserves more careful examination in various domains. This essay unearths original historical evidence of term-limit provisions and executive tenure in an effort to illuminate and evaluate the phenomenon. A background concern is that of international (and domestic) approaches to term-limit evasion. One intellectual response is that of militant democracy. The logic of that approach would imply the entrenchment and protection of term limits, which would presumably disrupt the cycle of non-compliance.
A case of a primary myelofibrosis with progression and related literature review of progression phase genetics

Philadelphia (BCR-ABL)-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN can transform into an accelerated or a blast phase, which is associated with poor response to standard therapy and low overall median survival. We present an interesting case of a patient with a history of PMF and progression and summarize the current studies on genetic features of myeloproliferative neoplasms in blast phase (MPN-BP) with an emphasis on PMF. Although MPN-BP show ≥20% blasts in peripheral blood or bone marrow, it is not considered as acute myeloid leukemia (AML) according to the WHO classification. While MPNs-BP typically lack genetic mutations seen in de novo AML, they commonly harbor IDH1/2, SRSF2, ASXL1, and TP53 mutations, similar to the genetic profiles of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).
Database Management and Information Systems

In this paper we shall review some major recent developments in database management methodology which have significant implication for information systems. Chief among these is the general acceptance of the necessity for a user-interface which is at once simple, implementation independent, and powerful. These objectives are admirably fulfilled by the relational data model and the calculus-like query language which were proposed by Codd.
Chapter 17 Prostacyclin, Thromboxanes and the Arachidonic Acid Cascade

Publisher Summary This chapter reviews the recent progress in the synthesis and biology of prostacyclins and thromboxanes. The biologically opposing effects of these substances apparently are of crucial importance to normal health and an imbalance in their production may lead to disorders, such as abnormal blood pressure, atherosclerosis, stroke, and heart-attack. Therefore, the synthesis of these compounds and the search for more stable prostacyclins and thromboxanes become highly desirable not only to provide useful biological tools but also compounds of therapeutic potential. The search focuses mainly on stable and selective biological agonists or antagonists of the natural molecules, as well as selective inhibitors of various enzymes involved in their biosynthesis. PGI 2 , its sodium salt, and methyl ester have been efficiently synthesized from PGF 2α systems. The most extensively studied analog of this series, 6, 9-thiaprostacyclin, showed 0.2-0.5 times the potency of PGI 2 blood platelet aggregation, but was a constrictor of the isolated cat coronary artery rather than a dilator. The carbocyclic prostacyclin and three of its isomers (C-5 and C-15) were synthesized recently. Isomer 21 exhibited higher potency than PGE 1 , but lower than PGI 2 as an inhibitor or platelet aggregation, and as a dilator of smooth muscle. The 12-fluoro- and 14-fluoroprostacyclins have been synthesized, and found to be potent agonists of PGI 2 . Thromboxane B 2 (TXB 2 ), however, with its more accessible structure has been synthesized by several groups and is readily available. Inhibition of thromboxane synthetase has received a great deal of attention and a number of inhibitors of this enzyme have been reported. It seems possible that these hydroperoxides may perform a negative feedback role to inhibit excess thromboxane or PGI 2 formation.
French Colonial Archaeology at Old Mobile: An Introduction

Twelve years of excavation and analysis of the Old Mobile archaeological site (1MB94) are revealing the physical and social dimensions of the capital of French colonial Louisiana between 1702 and 1711. The specialized studies included in this thematic issue document the interplay of French colonists, enslaved and free Native Americans, and Hispanic trade contacts as a new colonial society developed on the northern Gulf Coast at the turn of the 18th century.
Benign-appearing urothelial tissue fragments in noninstrumented voided urine specimens are associated with low rates of urothelial neoplasia.

BACKGROUND The presence of urothelial tissue fragments (UTF) in voided urine (VU) is often considered an abnormal finding that may be associated with the presence of urothelial papillary neoplasms. In the current study, the authors reviewed VU specimens containing benign-appearing UTF (BUTF) to determine the associated rate of urothelial neoplasia at the study institution. METHODS A retrospective search of the electronic pathology database system over a 5-year period (2009-2013) revealed 1131 VU specimens containing UTF. Of these, 459 cases (40.6%) did not have a recent history of instrumentation. Fifteen cases were excluded because the slides were not available for review. In the remaining 444 cases, 274 cases (61.7%) had BUTF. A total of 170 cases (38.3%) had UTF with atypical cytologic features and were therefore excluded. RESULTS Of the 274 cases, 29 (10.6%) had follow-up surgical pathology specimens available. The overall rate of urothelial neoplasia on follow-up was 3.6% for low-grade urothelial neoplasia (10 cases) and 0.7% for high-grade urothelial carcinoma (2 cases). Forty-five cases (16.4%) were determined to have urinary tract stones on follow-up. CONCLUSIONS The presence of BUTF in VU specimens requires careful examination of the medical history because their presence may be explained by recent instrumentation. If recent instrumentation is not identified, the etiology of BUTF is not usually determined; in the current study, BUTF were found to be associated with urinary tract stones in 16.4% of cases. They also present a low risk of low-grade urothelial neoplasia (3.6%) and high-grade urothelial carcinoma (0.7%) when compared with the overall benign category at the study institution (2.3% [P =.15] and 0.7%, respectively). Cancer (Cancer Cytopathol) 2015. © 2015 American Cancer Society. Cancer (Cancer Cytopathol) 2015;123:180–185. © 2014 American Cancer Society.
Developmental Precursors of Number of Sexual Partners from Ages 16 to 22.

This study examines family and child characteristics, parent and peer relationships, and early adolescent behavior as statistical predictors of trajectories of number of sexual partners from mid-adolescence through early adulthood using data from 527 participants in the Child Development Project. Early adolescent developmental antecedents accounted for modest variance in number of sexual partners. Latent growth models revealed that African American race, more advanced pubertal development, lower parental monitoring knowledge, association with more deviant peers, and lower GPA in early adolescence each predicted having more sexual partners at age 16. In addition, non-African American race, lower child IQ, higher parental monitoring knowledge, and lower early adolescent internalizing problems each was associated with a higher rate of growth in number of sexual partners over time at the ages following 16. Latent growth mixture modeling identified subgroups with distinct trajectories of involvement with sexual partners that were associated with family and child characteristics, parent and peer relationships, and behavior in early adolescence.
Gamma-Spectra from Radiative Pion Capture in Carbon

We have completed an experiment at the Berkeley 184 inch-cy-clotron set up to study radiative capture of pions on nuclei, i.e. the process π−N(A,Z) -4- γN*(A,Z-1).
A Systematic Review of the Efficacy and Safety of Atypical Antipsychotics in Patients with Psychological and Behavioral Symptoms of Dementia

Although the Food and Drug Administration (FDA) has not approved atypical antipsychotics for use in patients with dementia, they are commonly prescribed in this population. Recent concerns about increased risk of cerebrovascular events and mortality have led to warnings. A systematic review was conducted to assess the benefits and harms of atypical antipsychotics when used in patients with behavioral and psychological symptoms of dementia. Electronic searches (through March 2005) of the Cochrane Library, Medline, Embase, and PsycINFO were supplemented with hand searches of reference lists, dossiers submitted by pharmaceutical companies, and a review of the FDA Website and industry-sponsored results database. Using predetermined criteria, each study was assessed for inclusion, and data about study design, population, interventions, and outcomes were abstracted. An overall quality rating (good, fair, or poor) was assigned based on internal validity. The evidence for olanzapine and risperidone supports their effectiveness compared with placebo. Short-term adverse events were similar to placebo. Risperidone had no advantage over haloperidol on efficacy measures in the better-quality studies. Risperidone had an advantage over haloperidol on some measures of extrapyramidal symptoms. Evidence for the other atypical antipsychotics is too limited to assess efficacy and safety. Trials were short term and conducted in highly selected populations. The potential for increased risk of cerebrovascular adverse events and mortality is a serious concern. To make judgments about when the benefits of atypical antipsychotics outweigh the potential harms, clinicians need more information. Additional data from existing trials and more-complete reporting of trial results could provide this information.
Digital anisotropy: A variable elasticity rapid prototyping platform

Functional anisotropic material gradients on multiple length scales and locations are omnipresent in natural systems. However, the vast majority of industrially fabricated objects, even those designed to augment, coexist and interact with natural systems, are homogenous or discrete in material composition. This paper presents an exploration into rapid fabrication with material gradients in the form of a variable property printing platform. A digital anisotropy approach and a variable-elasticity fabrication platform demonstrating the approach are presented. Prototype development methods and processes are presented and discussed in the context of its design applications. Current and future technological implications for functionally graded rapid prototyping across micro, meso and macro scales are reviewed and future directions discussed.
Dynamic monitoring of blood–brain barrier integrity using water exchange index (WEI) during mannitol and CO2 challenges in mouse brain

The integrity of the blood-brain barrier (BBB) is critical to normal brain function. Traditional techniques for the assessment of BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. However, such methods based on the leakage of relatively large molecules are not suitable for the detection of subtle BBB impairment or for the performance of repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for the quantification of the BBB integrity. To estimate WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here, we confirm that WEI is sensitive to even very subtle changes in the integrity of the BBB caused by: (i) systemic hypercapnia and (ii) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of WEI as a biomarker of WER using computer simulation. In particular, the dependence of the WEI-WER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization and transcytolemmal water exchange was explored. Simulated WEI was found to vary linearly with WER for typically encountered exchange rate constants (1-4 Hz), regardless of the blood volume. However, for very high WER (>5 Hz), WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important WERs (WER < 4 Hz). Variation in cellular T1 had no effect on WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for the monitoring of BBB integrity.
The use of generalized Michaelis-Menten kinetics to measure sensitivity in gastric acid secretion.

Abstract The Michaelis-Menton equation as used to describe production of HCl in response to histamine, pentagastrin, and others is generalized to adjust for endogeneous stimulation and its resultant basal secretory rate. It is further modified so that, near zero stimulation, small changes in stimulation produce either large or small changes in production of HCl as would be the case with hypersensitive and hyposensitive individuals. An example including statistical steps is included using data from five duodenal ulcer patients and two normal subjects. Equivalences between the constants adjusted by the computer and the parameters and derived measures are included.
FINANCIAL INCENTIVES FOR WEIGHT LOSS: A ONE-YEAR RANDOMIZED CONTROLLED CLINICAL TRIAL

Many employers and insurers have instituted workplace wellness programs and most of these now include financial incentives aimed at improving engagement and outcomes. Prior trials have failed to demonstrate sustained weight loss after removal of such incentives. This trial investigates
Idiopathic thrombocytopenic purpura in childhood: a 10-year audit.

Abstract Objectives: To evaluate clinical course, treatment modalities, complications and referral pattern in paediatric patients treated over a 10-year period. Design: A retrospective, descriptive, hospital based study. Setting and subjects: 123 patients were diagnosed with ITP at Tygerberg Hospital from January 1996 to December 2006. Thirteen were excluded. The information of 106 patients was examined in detail. Outcome measures: Comparison of presenting platelet counts, special investigations, response and complications. Results: The mean age at presentation was 4·9 years (range 2 months – 13 years 3 months). A history of a preceding infection was obtained in 51% of patients. The mean presenting platelet count at diagnosis was 11·5 × 109/L (range 1 × 109 to 104 × 109/L). In 25 patients observation alone was the treatment choice. Specific treatment for ITP was given to 81 patients; steroids were used in 46 patients and intravenous immunoglobulin (IVIG) in seven patients. A combination of steroids and IV...
The role of Kupffer cell α2-adrenoceptors in norepinephrine-induced TNF-α production

Although previous studies have demonstrated that plasma levels of the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) increase during early sepsis, the precise mechanism responsible for its upregulation remains to be elucidated. Since recent studies have shown that the gut is an important source of norepinephrine (NE) release during early sepsis and enterectomy prior to the onset of sepsis attenuates TNF-alpha production, we hypothesized that gut-derived NE plays a major role in upregulating TNF-alpha via the activation of alpha(2)-adrenoceptors on Kupffer cells. To confirm that NE increases TNF-alpha synthesis and release, Kupffer cells were isolated from normal rats and incubated with NE (20 or 50 nM) or another alpha(2)-adrenergic agonist clonidine (50 nM) without addition of Escherichia coli endotoxin. Supernatant levels of TNF-alpha were then measured. In additional animals, intraportal infusion of NE (20 microM) with or without the specific alpha(2)-adrenergic antagonist yohimbine (1 mM) at a rate of 13 microl/min was carried out for 2 h. Plasma and Kupffer cell levels of TNF-alpha were assayed thereafter. Moreover, the effects of NE and yohimbine on TNF-alpha production was further examined using an isolated perfused liver preparation. The results indicate that both NE and clonidine increased TNF-alpha release by approximately 4-7-fold in the isolated cultured Kupffer cells. Similarly, intraportal infusion of NE in vivo or in isolated livers increased TNF-alpha synthesis and release which was inhibited by co-infusion of yohimbine. Furthermore, the increased cellular levels of TNF-alpha in Kupffer cells after in vivo administration of NE was also blocked by yohimbine. These results, taken together, suggest that gut-derived NE upregulates TNF-alpha production in Kupffer cells through an alpha(2)-adrenergic pathway, which appears to be responsible at least in part for the increased levels of circulating TNF-alpha observed during early sepsis as well as other pathophysiologic conditions such as trauma, hemorrhagic shock, or gut ischemia/reperfusion.
Mice Lacking the Long Splice Variant of the γ2 Subunit of the GABAA Receptor Are More Sensitive to Benzodiazepines

Abstract The γ2 subunit is required for benzodiazepine modulation of the GABA A receptor. Alternate splicing of precursor GABA A γ2 mRNA results in two splice variants, a short (γ2S) and a long (γ2L) variant. We investigated the roles of these splice variants in benzodiazepine pharmacology using mice lacking genes for the γ2L splice variant. Sleep time responses to midazolam and zolpidem were 20 and 18% greater, respectively, in null allele mice compared with wild-type mice, while responses to nonbenzodiazepine agents such as etomidate and pentobarbital were unchanged. Although the GABA A receptor number was not altered in null allele mice, there was a corresponding increase in affinity of brain membranes for benzodiazepine agonists (midazolam, diazepam, and zolpidem), while affinity for benzodiazepine inverse agonists (βCCM and Ro15-4513) was decreased. These changes were not observed in inbred mice of the parental strains (C57BL/6J and 129/SvJ) used to create the genetically altered mice, indicating that differences between γ2L null allele and wild-type mice were unlikely to be simply due to cosegregation of linked alleles. Absence of the γ2L splice variant increases the affinity of receptors for benzodiazepine agonists, and is associated with a modest increase in behavioral sensitivity to benzodiazepine agonists. Lack of the γ2L subunits may shift the GABA A receptor from an inverse agonist-preferring toward an agonist-preferring configuration.
Exact solution of a phase separation model with conserved order parameter dynamics.

A pairwise particle-exchange model on a linear lattice is solved exactly by a new rate-equation method. Lattice sites are occupied by particles A and B which can exchange irreversibly provided the local energy is reduced. Thus, the model corresponds to a zero-temperature Kawasaki-type phase separation process. As a result of local order parameter conservation, the dynamics reaches a frozen state at large times, the structure of which depends on the initial conditions.
Proopiomelanocortin Signaling System Is Operating in Mast Cells

The proopiomelanocortin (POMC) system is the central coordinator of the systemic endocrine responses to sustained stress. It has been recently discovered that mast cells also display regulated production of POMC peptides. Since at the tissue level mast cells integrate stress responses into the neuroimmune regulatory network, it is likely that the POMC system is involved in mast cells' functions in tissue homeostasis.