cssi/SciSciGPT-SciSciNet huggingface dataset:
Medication Errors Among Acutely Ill and Injured Children Treated in Rural Emergency Departments

Study objective We identify the incidence, nature, and consequences of medication errors among acutely ill and injured children receiving care in a sample of rural emergency departments (EDs). Methods Two pediatric pharmacists applied a medication error data collection instrument to the medical records of all critically ill children (highest triage category) treated in 4 northern California rural EDs between January 2000 and June 2003. Physician-related medication errors were defined as those involving wrong dose, wrong or inappropriate medication for condition, wrong route, or wrong dosage form. Wrong dose was determined by preset criteria, with doses above or below 10% to 25% of correct dose considered errors, depending on class of medication. Medication errors were classified into categories A through I under 3 broader categories, including errors having the potential to cause harm (A), errors that cause no harm (B to D), and errors that cause harm to the patient (E to I). Results Complete data were available from 177 (97.3%) of the 182 patients identified as having been triaged in the highest category during the study period. A total of 84 medication errors were identified among 69 patients, resulting in a medication error incidence of 39.0%. Twenty-four physician-related medication errors were identified among 21 patients, resulting in a physician-related medication error incidence of 11.9%. Among the 69 patients with medication errors, 11 had errors categorized as having the potential to cause harm (15.9%), and 58 had errors categorized as causing no harm (85.5%). Conclusion We found a high incidence of medication errors and physician-related medication errors among the acutely ill and injured children presenting to rural EDs in northern California. None of the medication errors identified caused harm to the patients included in this study.
Science in the News: A Study of Reporting Genomics

Scientists and academicians in the field of science writing agree that context and method are important components of research to be reported. This ideal is balanced by science journalists who try to relay findings with a minimum of complex and potentially confusing facts. Here, a specific report on genomics is traced from its original source in a scientific journal through to popular press publications. These data were examined in the context of previously published findings that have shown that the reader needs a clear understanding of the context of reported results to make an informed judgment about their meaning. This study reveals that these five reports, ranging from research article to popular press news article, differ in what is said rather than how it is said. This is surprising given the premise that in science reporting, the primary role of the journalist is to translate science into non-scientific language.
Vibrio cholerae HlyA hemolysin is processed by proteolysis.

Abstract The leukocidal activity of the Vibrio cholerae hemolysin (HlyA) was utilized to detect, enrich, and clone hybridoma cells expressing neutralizing monoclonal antibody in a new survivor selection protocol. A bank of 550 hybridoma clones was obtained from a mouse immunized with hemolysin by using standard techniques. The hybridoma bank was treated with a dose of HlyA hemolysin lethal to nonimmune clones. Five surviving hybridoma clones (X1 through X5) which possessed anti-HlyA activity were obtained. Western immunoblot analysis of V. cholerae culture supernatants with monoclonal antibody from clone X1 identified proteins with Mrs of 83,200, 71,600, and 60,300. Amino-terminal sequence analysis of the 71,600-Mr and 60,300-Mr forms showed homology with the published predicted sequence of HlyA. Our data indicate that proteolytic cleavage occurs between residues 120 and 121 (Glu-Leu) of the 83,200-Mr form, producing the 71,600-Mr form with the terminus NH2-L-L-F-T-P-F-D-Q-A-E-E-. Cleavage between residues 150 and 151 (Gly-Phe) releases the 60,300-Mr form with the terminus NH2-F-A-S-P-A-P-A-N-S-E-. Calculations based on the DNA sequence and the N termini indicated that the actual molecular masses of the 83,200-, 71,600-, and 60,300-Mr forms were, respectively, 79.4 kilodaltons (kDa), 68.6 kDa, and 65.3 kDa. Survivor selection and amino-terminal microsequencing offer powerful tools for the analysis of leukotoxic agents.
Auto-Inhibition and Partner Proteins, Core-Binding Factor β (CBFβ) and Ets-1, Modulate DNA Binding by CBFα2 (AML1)

Core-binding factor α2 (CBFα2; otherwise known as AML1 or PEBP2αB) is a DNA-binding subunit in the family of core-binding factors (CBFs), heterodimeric transcription factors that play pivotal roles in multiple developmental processes in mammals, including hematopoiesis and bone development. The Runt domain in CBFα2 (amino acids 51 to 178) mediates DNA binding and heterodimerization with the non-DNA-binding CBFβ subunit. Both the CBFβ subunit and the DNA-binding protein Ets-1 stimulate DNA binding by the CBFα2 protein. Here we quantify and compare the extent of cooperativity between CBFα2, CBFβ, and Ets-1. We also identify auto-inhibitory sequences within CBFα2 and sequences that modulate its interactions with CBFβ and Ets-1. We show that sequences in the CBFα2 Runt domain and sequences C terminal to amino acid 214 inhibit DNA binding. Sequences C terminal to amino acid 214 also inhibit heterodimerization with the non-DNA-binding CBFβ subunit, particularly heterodimerization off DNA. CBFβ rescinds the intramolecular inhibition of CBFα2, stimulating DNA binding approximately 40-fold. In comparison, Ets-1 stimulates CBFα2 DNA binding 7- to 10-fold. Although the Runt domain alone is sufficient for heterodimerization with CBFβ, sequences N terminal to amino acid 41 and between amino acids 190 and 214 are required for cooperative DNA binding with Ets-1. Cooperative DNA binding with Ets-1 is less pronounced with the CBFα2-CBFβ heterodimer than with CBFα2 alone. These analyses demonstrate that CBFα2 is subject to both negative regulation by intramolecular interactions, and positive regulation by two alternative partnerships.
The Degrees Below A 1-Generic Degree $< 0'$

It is shown that the nonrecursive predecessors of a 1-generic degree 0 ′ are all 1-generic. As a corollary, it is shown that the 1-generic degrees are not densely ordered.
Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4

Background: Pathways involved in androgen metabolism have been implicated in the etiology of prostate cancer. The goal of this study was to evaluate the effect of CYP3A4, a gene associated with the oxidative deactivation of testosterone, on the clinical presentation of prostate cancers. Methods: A polymerase chain reaction-based approach was used to identify sequence variants of the human CYP3A4 gene. To ascertain whether allelic variants of the CYP3A4 gene were associated with tumor stage and grade and age of the patient at diagnosis, we determined CYP3A4 genotypes in 230 Caucasian men with incident prostate cancer. Results : We identified a novel genetic variant (CYP3A4-V) that has an altered 5' regulatory element, containing an A to G mutation, upstream of the CYP3A4 gene. We then compared clinical characteristics of prostate cancers in men who did and did not carry this variant. The presence of the CYP3A4-V allele was associated with a higher tumor-lymph node-metastasis (TNM) stage and Gleason grade. The association between CYP3A4 genotype and tumor stage was most pronounced in men diagnosed at a relatively old age who reported no family history of prostate cancer. In this group, 46% of men with stage T3/T4 tumors carried CYP3A4-V, whereas only 5% of individuals with stage T1 tumors carried CYP3A4-V (adjusted odds ratio = 9.45; 95% confidence interval = 2.54-35.17; X 2 1 = 12.28; two-sided P<.001). Conclusions: We determined that a single base change in the 5' flanking region of the CYP3A4 gene was associated with higher clinical stage and grade in men with prostate tumors. Our results suggest that mutations in the CYP3A4 gene may influence prostate carcinogenesis.
Power control in three-phase grid-connected current-source boost inverter

The circuit topology and switching pattern of the proposed grid-connected current source boost inverter (CSBI) provide the capability of boosting and inverting a low dc voltage of a sustainable energy (SE) source (e.g. a photovoltaic panel or fuel cell) to the higher ac voltage of the grid, all in a single stage. This will also provide a robust grid-connected inverter to regulate the output voltage and control the injected power for stand-alone and grid-connected cases, respectively. In PV-based CSBIs, PV panels are connected in parallel, and consequently, a panel's defect or malfunction will not significantly affect the operation of the rest of the system. In this paper, a power control scheme is presented based on the previously proposed switching pattern for CSBI and verified using a 500W grid-connected inverter.
Acute and chronic systemic CB1 cannabinoid receptor blockade improves blood pressure regulation and metabolic profile in hypertensive (mRen2)27 rats

We investigated acute and chronic effects of CB1 cannabinoid receptor blockade in renin-angiotensin system-dependent hypertension using rimonabant (SR141716A), an orally active antagonist with central and peripheral actions. In transgenic (mRen2)27 rats, a model of angiotensin II-dependent hypertension with increased body mass and insulin resistance, acute systemic blockade of CB1 receptors significantly reduced blood pressure within 90 min but had no effect in Sprague-Dawley rats. No changes in metabolic hormones occurred with the acute treatment. During chronic CB1 receptor blockade, (mRen2)27 rats received daily oral administration of SR141716A (10 mg/kg/day) for 28 days. Systolic blood pressure was significantly reduced within 24 h, and at Day 21 of treatment values were 173 mmHg in vehicle versus 149 mmHg in drug-treated rats (P < 0.01). This accompanied lower cumulative weight gain (22 vs. 42 g vehicle; P < 0.001), fat mass (2.0 vs. 2.9% of body weight; P < 0.05), and serum leptin (2.8 vs. 6.0 ng/mL; P < 0.05) and insulin (1.0 vs. 1.9 ng/mL; P < 0.01), following an initial transient decrease in food consumption. Conscious hemodynamic recordings indicate twofold increases occurred in spontaneous baroreflex sensitivity (P < 0.05) and heart rate variability (P < 0.01), measures of cardiac vagal tone. The beneficial actions of CB1 receptor blockade in (mRen2)27 rats support the interpretation that an upregulated endocannabinoid system contributes to hypertension and impaired autonomic function in this angiotensin II-dependent model. We conclude that systemic CB1 receptor blockade may be an effective therapy for angiotensin II-dependent hypertension and associated metabolic syndrome.
Leadership Techniques in the Project Organization

Project managers, because of their inherent “authority-gap”, have developed a handful of techniques for supplementing their authority. The importance of these techniques will often vary with the do...
Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

Aims Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.
Interaction of Tumor with Its Micro-environment: A Mathematical Model

This paper is concerned with early development of transformed epithelial cells (TECs) in the presence of fibroblasts in the tumor micro-environment. These two types of cells interact by means of cytokines such as transforming growth factor (TGF-β) and epidermal growth factor (EGF) secreted, respectively, by the TECs and the fibroblasts. As this interaction proceeds, TGF-β induces fibroblasts to differentiate into myofibroblasts which secrete EGF at a larger rate than fibroblasts. We monitor the entire process in silico, in a setup which mimics experiments in a Tumor Chamber Invasion Assay, where a semi-permeable membrane coated by extracellular matrix (ECM) is placed between two chambers, one containing TECs and another containing fibroblasts. We develop a mathematical model, based on a system of PDEs, that includes the interaction between TECs, fibroblasts, myofibroblasts, TGF-β, and EGF, and we show how model parameters affect tumor progression. The model is used to generate several hypotheses on how to slow tumor growth and invasion. In an Appendix, it is proved that the mathematical model has a unique global in-time solution.
Performance of Trichogramma ostriniae (Hymenoptera: Trichogrammatidae) Reared on Factitious Hosts, Including the Target Host, Ostrinia nubilalis (Lepidoptera: Crambidae)

Abstract The performance of the parasitoid Trichogramma ostriniae (Pang et Chen) on eggs of four factitious hosts, Ostrinia nubilalis (Hubner), Sitotroga cerealella (Olivier), Trichoplusia ni (Hubner), and irradiated Ephestia kuhniella (Zeller), is presented. We measured parasitoid longevity, individual and population levels of parasitism, survival of progeny to emergence, and progeny sex ratio for 9 to 11 generations in laboratory colonies. Wasps reared from each source were tested on the source host and on the target host, European corn borer (O. nubilalis). Under the conditions tested, E. kuhniella was a poor host, T. ni and O. nubilalis were good hosts, and S. cerealella was intermediate. We found no evidence that being reared for many generations on an alternate host decreased the performance on the target host, O. nubilalis. Sex ratio was female biased and did not change over time. There may have been an increase in performance of wasps reared on S. cerealella and E. kuhniella over time. We discuss the information gained from different measures of parasitoid performance and the possible causes for variation in performance over time under laboratory conditions.
Alignment of Citation Behaviors of Philosophy Graduate Students and Faculty

Objective – This study analyzes sources cited by graduate students in philosophy at the University of Colorado Boulder (UCB) in 55 PhD dissertations and master’s theses submitted between 2005 and 2010, to discover their language, age, format, discipline, whether or not they were held by the library, and how they were acquired. Results were compared to data previously collected about sources cited by philosophy faculty at UCB, in books published between 2004 and 2009, to identify how closely citation behaviors aligned between the two groups. Methods – Citations were counted in the PhD dissertations and master’s theses. Citations to monographs were searched against the local catalog to determine ownership and call number. Comparison numbers for faculty research were collected from a previous study. Results were grouped according to academic rank and analyzed by format, language, age, call number, ownership, and method of purchase. Results – Graduate students cited mostly books, though fewer than commonly found in other studies. Citations were almost entirely of English language sources. Master’s students cited slightly newer materials than doctoral students, who in turn cited newer materials than faculty. The library owned most cited books, and most of those were purchased on an approval plan. Doctoral students most frequently cited resources outside the discipline of philosophy, in contrast to master’s students and faculty. Conclusions – The citation behavior of graduate students in philosophy largely, but not entirely, mirrors that of the faculty. Further study of citation behavior in humanities disciplines would be useful. Understanding the behavior of philosophers can help philosophy librarians make informed choices about how to spend library funds.
Limited Evidence for Classic Selective Sweeps in African Populations

While hundreds of loci have been identified as reflecting strong-positive selection in human populations, connections between candidate loci and specific selective pressures often remain obscure. This study investigates broader patterns of selection in African populations, which are underrepresented despite their potential to offer key insights into human adaptation. We scan for hard selective sweeps using several haplotype and allele-frequency statistics with a data set of nearly 500,000 genome-wide single-nucleotide polymorphisms in 12 highly diverged African populations that span a range of environments and subsistence strategies. We find that positive selection does not appear to be a strong determinant of allele-frequency differentiation among these African populations. Haplotype statistics do identify putatively selected regions that are shared across African populations. However, as assessed by extensive simulations, patterns of haplotype sharing between African populations follow neutral expectations and suggest that tails of the empirical distributions contain false-positive signals. After highlighting several genomic regions where positive selection can be inferred with higher confidence, we use a novel method to identify biological functions enriched among populations’ empirical tail genomic windows, such as immune response in agricultural groups. In general, however, it seems that current methods for selection scans are poorly suited to populations that, like the African populations in this study, are affected by ascertainment bias and have low levels of linkage disequilibrium, possibly old selective sweeps, and potentially reduced phasing accuracy. Additionally, population history can confound the interpretation of selection statistics, suggesting that greater care is needed in attributing broad genetic patterns to human adaptation.
A Root-Finding Method for Assessing SRAM Stability

In this paper, we propose a closed form method to evaluate the read stability of an SRAM cell via quartic root finding. By utilizing a simplified MOSFET device model, we model SRAM cell stability by a system of quartic equations. The algebraic nature of the equations along with simplified region boundaries provide the insight that only a few combinations of device operating regions correspond to the stability of the cell, instead of 729 combinations in the brutal force approach. Such an insight not only makes it possible to have a quick "litmus test" to determine cell stability under variability, but also significantly speeds up the analysis, compared to a traditional SPICE approach. Experimental results using industrial bulk CMOS models show that the results are in excellent agreement with SPICE results and 65times faster.
Subcellular Distribution of Opioid Peptides in Rat Hypothalamus and Pituitary

Homogenates of rat anterior lobe (AL) and neurointermediate lobe (NIL) pituitary and rat hypothalamus were subjected to subcellular fractionation and density gradient centrifugation. The subcellular distribution of immunoreactive dynorophin A (ir-Dyn A) in NIL was found to be similar to that of ir-arginine vasopressin (ir-AVP). ir-Dyn A migrated as a discrete band on sucrose density gradients, which corresponded in sedimentation rate to that of ir-AVP, suggesting that these two peptides are stored within organelles of similar size and density. Two other products of prodynorphin, ir-alpha-neoendorphin (ir-alpha-nEND) and ir-Dyn A-(1-8) also comigrated with ir-AVP. ir-[Leu5]-enkephalin (ir-LE), which may be a product of prodynorphin or proenkephalin, was also found to migrate in this region of the gradient. When a homogenate of rat hypothalamus was prepared using a method that has been developed for synaptosome isolation, ir-Dyn A was found to comigrate with Na+/K+-activated adenosine triphosphatase (Na/K-ATPase), a synaptosomal marker enzyme. Using a more concentrated homogenate ir-Dyn A was found to migrate to a less dense region where peptide-containing synaptic vesicles have previously been localized. When a synaptosomal preparation was lysed in hypotonic solution a shift was seen in the migration rate of ir-Dyn A to this region of the gradient (containing putative synaptic vesicles). Thus the bulk of hypothalamic dynorphin appears to be present within synaptosome-like structures which, upon lysis, release a less dense, smaller subcellular organelle corresponding in sedimentation characteristics to other types of peptide-containing synaptic vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)
The rehabilitation of a dismissed scientist

There is a standard narrative about the radical psychoanalyst Wilhelm Reich that includes the claims that following an admittedly brilliant youthful career in Vienna he became mentally ill and that his supposed laboratory work related to life energy was based on self-delusion at best, or conscious deceit at worst. To the US Food and Drug Administration of the early 1950s Reich was little more than a cancer quack, abusing desperate patients with his fraudulent claims about a new form of energy, ‘‘orgone energy,’’ and a simple enclosure for accumulating it (the orgone energy accumulator, usually referred to derisively as ‘‘the orgone box’’), used by Reich in experimental treatment of cancer patients. The FDA pursued him with a vengeance and was able to have all of his books that include the word ‘‘orgone’’ legally designated as ‘‘labels’’ for the allegedly worthless accumulator. Once his books were no longer books but mere labels, destroying them was not an outrageous act of censorship, but akin to disposing of worthless pills or some brochures lying about in a doctor’s office, or the so the Government reasoned. As pointed out in the book under review, Reich is probably the only person in history to have his books burned in both the USA and Nazi Germany. Strick devotes his book to Reich’s so-called pseudoscientific work on life energy, specifically the laboratory work on microscopic entities Reich named ‘‘bions’’ conducted in his well-funded research facility in Oslo between the years 1934 and 1939. It was during this period that Reich the psychoanalyst, sexologist, political activist, Marxist social theorist, therapist, became Reich the biologist—thus Strick’s chosen title. Focusing on but one aspect of Reich’s multi-varied work allows the author to examine Reich’s laboratory work in great depth. The result of this
Assessing Farm Competitiveness in Bulgaria

This paper suggests a holistic framework for assessing farm competitiveness, and analyses competitiveness of different type of Bulgarian farms. First, it present a new approach for assessing farm competitiveness defining farm competitiveness and its three criteria (efficiency, adaptability and sustainability), and identifying indicators for assessing the individual aspects and the overall competitiveness of farms. Next, it analyzes evolution and efficiency of farming organizations during post communist transition and EU integration in Bulgaria, and assesses levels and factors of farms competitiveness in the conditions of CAP implementation.
Factors Affecting the Acceptance of Smartphone Diet Applications

This article investigated factors affecting customers’ intention to use smartphone diet applications (apps) when ordering food and bev- erages at foodservice businesses. An online questionnaire was designed and empirical data was collected from 395 respondents.Study participants were asked to interact with a smartphone diet app simulation prior to responding the survey questions. Structural equation modeling was used to analyze the data. Study results indicate that individuals are more likely to adopt smartphone dietapps if they are perceived to be useful and enjoyable. Social norms appear to play a significant role in adopting smartphone apps. Individuals with higher personal innovativeness tend to use such apps more often. Study results can assist restaurant operators in developing specific marketing strategies to target particular segments by designing such diet apps and developing menus for niche segments. This is one of the first studies looking at whether smartphone apps can assist individuals in or...
Time-dependent loss of adenosine 5'-monophosphate deaminase activity may explain elevated adenosine 5'-triphosphate levels in senescent erythrocytes

Senescent erythrocytes from rabbits were previously shown to have elevated levels of adenine nucleotides. The present study documents that aged red blood cells have a normal synthetic capacity for adenine nucleotides, as indicated by normal levels of adenosine kinase. However, senescent erythrocytes do have decreased levels of adenosine 5′-monophosphate deaminase, the critical enzyme involved in degrading adenine nucleotides. These circumstances of a normal synthetic capacity in the presence of decreased catabolic ability were observed previously in a human genetic deficiency of adenosine 5′-monophosphate deaminase; the red blood cells in these patients accumulate adenosine 5′- triphosphate as do senescent erythrocytes in rabbits.
Orbital modes in superfluid 3 He

The equation describing the rotation of the orbital coordinate in superfluid3He is obtained. It is shown that the orbital modes obey a diffusion-like equation with a finite energy gap. The transient behavior of the\(\hat l\) vector in the A phase after thed vector is suddenly rotated is considered.
THE ORIGIN OF CLARKIA UNGULATA

An unusual Clarkia was discovered in 1947 in the canyon of the Merced River, California, by the senior author. It appeared to be a simple variant, with unlobed petals, of C. biloba (Dur.) Nels. & Macbr., a species which occurs abundantly in the same canyon. Examination of microsporocytes showed, however, that this variant had genomes of 9 chromosomes, rather than the 8 characteristic of C. biloba. Furthermore, the hybrid between them was nearly sterile. Consequently, the new entity was described as a species, C. lingulata (Lewis and Lewis, 1953). The purpose of this paper is to compare these two species phenotypically and cytogenetically in order to ascertain the factors which led to speciation.
Catamenial Epilepsy: Discovery of an Extrasynaptic Molecular Mechanism for Targeted Therapy

Catamenial epilepsy is a type of refractory epilepsy characterized by seizure clusters around perimenstrual or periovulatory period. The pathophysiology of catamenial epilepsy still remains unclear, yet there are few animal models to study this gender-specific disorder. The pathophysiology of perimenstrual catamenial epilepsy involves the withdrawal of the progesterone-derived GABAergic neurosteroids due to the decline in progesterone level at the time of menstruation. These manifestations can be faithfully reproduced in rodents by specific neuroendocrine manipulations. Since mice and rats, like humans, have ovarian cycles with circulating hormones, they appear to be suitable animal models for studies of perimenstrual seizures. Recently, we created specific experimental models to mimic perimenstrual seizures. Studies in rat and mouse models of catamenial epilepsy show enhanced susceptibility to seizures or increased seizure exacerbations following neurosteroid withdrawal. During such a seizure exacerbation period, there is a striking decrease in the anticonvulsant effect of commonly prescribed antiepileptics, such as benzodiazepines, but an increase in the anticonvulsant potency of exogenous neurosteroids. We discovered an extrasynaptic molecular mechanism of catamenial epilepsy. In essence, extrasynaptic δGABA-A receptors are upregulated during perimenstrual-like neuroendocrine milieu. Consequently, there is enhanced antiseizure efficacy of neurosteroids in catamenial models because δGABA-A receptors confer neurosteroid sensitivity and greater seizure protection. Molecular mechanisms such as these offer a strong rationale for the clinical development of a neurosteroid replacement therapy for catamenial epilepsy.
P18: MULTIPLE DIAGNOSIS OR CONTINUUM OF DISEASE: MULTICENTRIC CASTLEMAN'S DISEASE

Purpose of Study Multicentric Castleman9s disease (MCD) is a rare lymphoproliferative disorder characterized by peripheral lymphadenopathy (LAD), hepatosplenomegaly(HSM), and B symptoms. It is associated with HIV and HHV8 infection. We report a case of young woman presented with B symptoms, workup suggestive of lupus but lymph node biopsy (BX) was consistent with MCD. Association of SLE with MCD is rare. We report this case to increase awareness of this potential diagnostic and therapeutic dilemma. Methods Used Patient is a 27 yr old black woman presented with malaise, fevers, cough, weight loss, arthralgia, alopecia, numbness of extremities and Raynaud9s phenomenon. Patient had skin tightness around the mouth, telangiectasia, digital ulcers, HSM, pitting edema, diffuse LAD and moderate pericardial effusion. Laboratory results consistent with hemolytic anemia with Hb 5.6 g/dl, direct coombs positive, elevated reticulocyte count, LDH and low haptoglobin. Initial RF, ANA, and all infectious work up including HIV were normal. She was transfused cautiously, with inconclusive LN and bone marrow Bx. Patient left hospital against medical advice. She presented two days later with altered mental status (AMS) and hypotension. CT head and Lumbar puncture were negative. Hypotension responded to fluids, but no response in AMS. Repeat ANA, AntiSSB, AntiSm, AntiRNP, and Antihistone antibodies were positive. Patient met diagnostic criteria for SLE and was subsequently treated for lupus cerebritis with pulse steroids, with moderate improvement in mental status. Repeat LNBX revealed reactive lymphadenitis with features of MCD, HHV8 negative. Patient was treated with IL-6 inhibitor Siltuximab, with significant improvement in mental status. Summary of Results MCD is a rare angiolymphoproliferative disorder of unclear etiology. Most cases occur in middle aged men and are associated with immunosuppression where as SLE is common in women of child bearing age. Reported cases of MCD in association with SLE are common in immunocompetent young women. Our patient is a young woman, HIV/HHV8 negative with good response to Siltuximab, favoring MCD. Conclusions It is unclear whether this finding of MCD and SLE represents an overlap or a pure association. However, this phenomenon needs further investigation.
The Guinea pig model of legionnaires' disease.

Publisher Summary Legionnaires' disease is a type of acute bacterial pneumonia caused by bacteria of the genus Legionella, most commonly L. pneumophila. L. pneumophila is an intracellular pathogen, which is transmitted to man via water containing the bacterium. The most common route of infection is by aerosol inhalation, although there is also some evidence that microaspiration of contaminated water may on occasion cause the disease. Intraperitoneal inoculation of clinical material into guinea pigs was used for the isolation of Legionella species for several decades before the recognition of legionnaires' disease, when these bacteria were thought to be rickettsia-like bacteria. The guinea-pig model mimics legionnaires' disease as seen in immunocompromised humans, with high untreated fatality rates, and as such lends itself to studies of experimental chemotherapy. Guinea-pig infection is the most often used method to assess the relative virulences of different Legionella bacterial strains, and has also been used to study host immune defenses. Preoperative observation and conditioning of the animals for 4–7 days is required to ensure that all animals are healthy and have recovered from the stress of shipment. Supplementation of guinea-pig food with vitamin C is important to prevent naturally occurring pneumonia. Adequate anesthesia is crucial for the surgical success of this model. A mixture of ketamine and xylazine is given intramuscularly, followed by local anesthesia using lidocaine. Withholding of food or water before anesthetic administration is not required. Adequate ketamine/xylazine anesthesia causes unconsciousness but does not impair the rate or depth of respiration.
The double-edged effect of Sir Francis Galton: a search for the motives in the biometrician-Mendelian debate.

The Darwinian theory of evolution contained many inconsistencies in the pre-Mendelian period. Faced with a lack of any clear conception of the hereditary system on which selection operated, the early theorists assumed the truth of the common-sensical notion that the constitution of an offspring somehow resulted from the blending of the constitutions of its parents. But this simplistic view contained numerous weaknessess: it did not account for the so-called sports of nature familiar to breeders; it was not sufficient to explain phenomena of depletion and increase in a species' store of variations; it provided no way of distinguishing between the hereditary and the environmental. As long as such weaknesses were left unresolved, evolution theorists were doomed to be plagued by countless anomalies. The problems of hereditary transmission remained unresolved and poorly formulated until the Mendelian revolution. In a review of the contemporary state of evolutionary theory, C. H. Waddington has offered this naive picture of Mendelism's inception:
Review of Voltammetric Methods for the Study of Electrode Reactions

Three classes of voltammetric methods are reviewed: steady-state voltammetry, potential step voltammetry and linear sweep voltammetry. In the first class are included rotating disk electrode voltammetry and polarography. Normal pulse voltammetry, reverse pulse voltammetry and differential pulse voltammetry are included in the second category. The emphasis of the review is directed to the implementation of the techniques with electrodes of conventional size but the effect of spherical diffusion is introduced to portend the discussion of the methods as used with microelectrodes.
Altered Differential Control of Sympathetic Outflow Following Sedentary Conditions: Role of Subregional Neuroplasticity in the RVLM.

Despite the classically held belief of an “all-or-none” activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA) can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10-12 weeks on running wheels) or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM) into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals.
Development Of Core Ion Temperature Gradients And Edge Sheared Flows In A Helicon Plasma Device Investigated By Laser Induced Fluorescence Measurements

We report experimental observation of ion heating and subsequent development of a prominent ion temperature gradient in the core of a linear magnetized plasma device, and the controlled shear de-correlation experiment. Simultaneously, we also observe the development of strong sheared flows at the edge of the device. Both the ion temperature and the azimuthal velocity profiles are quite flat at low magnetic fields. As the magnetic field is increased, the core ion temperature increases, producing centrally peaked ion temperature profiles and therefore strong radial gradients in the ion temperature. Similarly, we observe the development of large azimuthal flows at the edge, with increasing magnetic field, leading to strong radially sheared plasma flows. The ion velocities and temperatures are derived from laser induced fluorescence measurements of Doppler resolved velocity distribution functions of argon ions. These features are consistent with the previous observations of simultaneously existing radially separated multiple plasma instabilities that exhibit complex plasma dynamics in a very simple plasma system. The ion temperature gradients in the core and the radially sheared azimuthal velocities at the edge point to mechanisms that can drive the multiple plasma instabilities, that were reported earlier.
Cognitive Conflict as Possible Origin of the Uncanny Valley

In social robotics, the term Uncanny Valley describes the phenomenon that linear increases in human-likeness of an agent do not entail an equally linear increase in favorable reactions towards that agent. Instead, a pronounced dip or ‘valley’ at around 70% human-likeness emerges. One currently popular view to explain this drop in favorable reactions is delivered by the Categorical Perception Hypothesis. It is suggested that categorization of agents with mixed human and non-human features is associated with additional cognitive costs and that these costs are the cause of the Uncanny Valley. However, the nature of the cognitive costs is still matter of debate. The current study explores whether the cognitive costs associated with stimulus categorization around the Uncanny Valley could be due to cognitive conflict as evoked by simultaneous activation of two categories. Using the mouse tracking technique, we show that cognitive conflict indeed peaks around the Uncanny Valley region of human-likeness. Our find...
Mortality of Myocardial Infarction by Sex, Age, and Obstructive Coronary Artery Disease Status in the ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines)

Background— Sex differences in early mortality after myocardial infarction (MI) vary by age. MI with nonobstructive coronary arteries (MINOCA [ Methods and Results— Adults who underwent coronary angiography for acute ST-segment–elevation and non–ST-segment–elevation MI in the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines) from 2007 to 2014 were identified. Patients with cardiac arrest, thrombolytic therapy, prior revascularization, or missing demographic or angiographic data were excluded. The primary outcome was all-cause, in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. Demographics, clinical history, presentation, and in-hospital treatments were compared by sex and CAD status (MI-CAD or MINOCA). Mortality and major adverse cardiovascular outcomes were analyzed by age, sex, and CAD status. Among 322 523 patients with MI, MINOCA occurred in 18 918 (5.9%). MINOCA was more common in women than men (10.5% versus 3.4%; P P P P P =0.84). The higher risk of post-MI death among women with MI-CAD was most pronounced at younger ages. Conclusions— MINOCA was associated with lower mortality than MI-CAD. Higher risk of post-MI death among women in comparison to men was restricted to patients with MI-CAD.
Bone’s Intrinsic Traits: Inferring Species, Sex, and Age

Chapter 6 reviews the bases for species identification, size estimation, and sex and age determination from bones. Age determinations based on mammal teeth will be discussed in Chap. 7. How a vertebrate moves in the landscape and how it obtains and processes its food are reflected in its osteology. An individual’s skeletal traits are in turn shaped by its species’ genetic inheritance, ecological setting, breeding system, and life history. Such distinctive physical characteristics allow taxonomic identification and sex determination. Vertebrates have limited lifespans, and their patterns of growth may produce characteristic markers on skeletal elements, and traits can often be used to estimate an animal’s age at death, using contemporary studies of a species’ growth and development as an analogical reference point. As Chap. 6 reviews these topics, readers are directed toward useful reference materials and means of learning distinctive traits.
Reversal of the Eutrophication Process: A Case Study

Bayou Texar, Pensacola, Florida, is a bayou estuary which was advancing toward eutrophy, due to nutrient loadings from various sources. The occurrence of characteristic symptoms of eutrophication, coupled with the closing of the bayou for water contact recreation, led to the initiation of an intensive seven-year study. Initial results indicated that Carpenter’s Creek is a prime source of most nitrogen species and that an exchange exists between dissolved phosphates and those adsorbed onto sediments. Carbon fixation rates varied, with the stations closest to Carpenters Creek exhibiting the most productivity. It also appeared that nitrates may be more important in controlling rates of carbon fixation than phosphates. An ensuing study directed at phosphate exchange suggested that reducing conditions in the muds cause substantial release of iron-bound PO4 from the sediment-water interface followed by adsorption onto particles in the aerobic flocculent layer above the interface. This mechanism could allow sufficiently rapid exchange of PO4 between sediment and water resulting in a low, stable concentration in the water as observed. Other investigations involving bacterioplankton, dissolved glucose, and heterotrophic production indicated that algal primary productivity is the major source of dissolved glucose. A final study demonstrated a paucity of benthic macroinvertebrates, probably due to a graded suspension of particles at the sediment-water interface and the absence of a sharply defined bottom. The zooplankton community exhibited low diversity while numbers of individual species were high. The phytoplankton community was composed primarily of dinoflagellates, with diatoms, cryptophytes, chlorophytes and microflagellates occurring in lesser quantities. It was also suggested that the importance from algal blooms to fish kills may be greater than previously indicated. Specific recommendations made after the fourth year of the study were implemented in most part and led to a substantial improvement of water quality and the subsequent opening of the bayou to the public for recreational use.
Atrial Switch, Arterial Switch, and Rastelli

Patients born with congenital heart disease may require a series of operative procedures to ensure adequate pulmonary and systemic circulation. This section will review procedures that divert blood flow at the atrial level (atrial switch), arterial level (arterial switch), and ventricular level (Rastelli procedure). The indications and implication of each procedure will also be discussed.
The Formation of the Arab League and the United Nations, 1944–5:

While the Great Powers were meeting in Washington at the Dumbarton Oaks Conference, representatives of the Arab states were meeting in Egypt to draft the Alexandria Protocol, the document that woul...
Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations.

Nonsynonymous gene mutations can be beneficial, neutral, or detrimental to the stability, structure, and biological function of the encoded protein, but the effects of these mutations are often not readily predictable. For example, the β-propeller olfactomedin domain of myocilin (mOLF) exhibits a complex interrelationship among structure(s), stability, and aggregation. Numerous mutations within mOLF are linked to glaucoma; the resulting variants are less stable, aggregation-prone, and sequestered intracellularly, causing cytotoxicity. Here, we report the first stable mOLF variants carrying substitutions in the calcium-binding site that exhibit solution characteristics indistinguishable from those of glaucoma variants. Crystal structures of these stable variants at 1.8–2.0-A resolution revealed features that we could not predict by molecular dynamics simulations, including loss of loop structure, helix unwinding, and a blade shift. Double mutants that combined a stabilizing substitution and a selected glaucoma-causing single-point mutant rescued in vitro folding and stability defects. In the context of full-length myocilin, secretion of stable single variants was indistinguishable from that of the WT protein, and the double mutants were secreted to varying extents. In summary, our finding that mOLF can tolerate particular substitutions that render the protein stable despite a conformational switch emphasizes the complexities in differentiating between benign and glaucoma-causing variants and provides new insight into the possible biological function of myocilin.
Nature-Derived Sodium-Ion Battery: Mechanistic Insights into Na-Ion Coordination within Sustainable Molecular Cathode Materials

Ongoing research in sustainable battery technologies aims to implement the sodium-ion battery (SIB) as a lower-cost alternative to the lithium-ion battery (LIB), thus reducing the susceptibility of...