cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacokinetic considerations in pediatric pharmacotherapy.

Purpose The changes in physiological functions as children grow and organ systems mature result in pharmacokinetic alterations throughout childhood. These alterations in children result in absorption, distribution, metabolism, and excretion of drugs that are different from those seen in the typical adult diseased population. Summary Changes in gastrointestinal motility and gastric pH in neonates and infants affect the absorption rate and bioavailability of drugs. Skin absorption rate and extent can be altered by different skin structures and perfusion in young children. Intramuscular and rectal absorption become less predictable in children due to erratic absorption site perfusion and other factors. Children's body compositions also differ greatly from that in adults. Water-soluble drugs distribute more extensively in newborns due to larger water content than in older children and adults. Drug elimination and excretion are also affected in pediatric population due to differences in liver and renal function. Immature enzyme development and renal function result in reduced clearance of drugs in young children. There are limited pharmacokinetic data available for many drugs used in children. Conclusion Considering the changes in pharmacokinetics in children can help pharmacists optimize the dosing and monitoring of drugs and do the best they can to help this vulnerable population.
Optimization Algorithms for Large-Scale Systems: From Deep Learning to Energy Markets

Brief Biography: Navid Azizan is a fifth-year PhD candidate in Computing and Mathematical Sciences (CMS) at the California Institute of Technology (Caltech), where he is co-advised by Adam Wierman and Babak Hassibi, and is a member of multiple research groups: DOLCIT, RSRG and SISL. During the summer of 2019, he was a research scientist intern at Google DeepMind. He received the B.Sc. degree in EE form Sharif University of Technology and the M.Sc. degree in ECE from the University of Southern California, in 2013 and 2015, respectively. His research interests broadly lie in mathematical optimization, machine learning, networks, and markets. He is the recipient of several awards, including the 2016 ACM GreenMetrics Best Student Paper Award, the Amazon Fellowship in Artificial Intelligence, the PIMCO Fellowship in Data Science, the Caltech CMS Fellowship, and the USC Provost's Fellowship.
Functionally engineered extracellular vesicles improve bone regeneration.

Lineage specific differentiation of host mesenchymal stem cells (MSCs) is a necessary step for bone repair/regeneration. Clinically, growth factors such as bone morphogenetic protein 2 (BMP2) are used to enhance/hasten this process to heal critical sized defects. However, the clinical application of such growth factors is fraught with dosage challenges as well as immunological and ectopic complications. The identification of extracellular vesicles (EVs) as active components of the MSC secretome suggest alternative approaches to enhancing bone regeneration. Based on our earlier studies on the properties of EVs from lineage specified MSCs, this study sought to engineer EVs to enhance osteogenic differentiation. To generate MSC EVs with enhanced osteoinductive abilities, genetically modified human bone marrow derived MSCs (HMSCs) were generated by constitutively expressing BMP2. We hypothesized that these cells would generate functionally engineered EVs (FEEs) with enhanced osteoinductive properties. Our results show that these FEEs maintained the general physical and biochemical characteristics of naive HMSC EVs in the form of size distribution, EV marker expression and endocytic properties but show increased bone regenerative potential compared to MSC EVs in a rat calvarial defect model in vivo. Mechanistic studies revealed that although BMP2 was constitutively expressed in the parental cells, the corresponding EVs (FEEs) do not contain BMP2 protein as an EV constituent. Further investigations revealed that the FEEs potentiate the BMP2 signaling cascade possibly due to an altered miRNA composition. Collectively, these studies indicate that EVs' functionality may be engineered by genetic modification of the parental MSCs to induce osteoinduction and bone regeneration. SIGNIFICANCE STATEMENT: With mounting evidence for the potential of MSC EVs in treatment of diseases and regeneration of tissues, it is imperative to evaluate if they can be modified for application specificity. The results presented here indicate the possibility for generating Functionally Engineered EVs (FEEs) from MSC sources. As a proof of concept approach, we have shown that EVs derived from genetically modified MSCs (BMP2 overexpression) can be effective as biomimetic substitutes for growth factors for enhanced tissue-specific regeneration (bone regeneration) in vivo. Mechanistic studies highlight the role of EV miRNAs in inducing pathway-specific changes. We believe that this study will be useful to researchers evaluating EVs for regenerative medicine applications.
Precision measurement of mixer noise temperature and conversion loss

Introduction Noise temperature measurements are fundamental to the development of low noise heterodyne mixers. Mixer noise and IF amplifier noise contribute to the overall system noise through the relation
192 ‘Immune-brain’: a case series of cognitive dysfunction/decline in cancer patients on immunotherapy

Background Immunotherapy agents are now the standard of care for many types of malignancies and use of checkpoint inhibitor immunotherapy (IO) is widespread across oncology. Cognitive dysfunction/decline (CD) is a well-known side effect of conventional chemotherapy (i.e. ‘chemo-brain’), but the neuro-cognitive impact of checkpoint inhibitor immunotherapy (IO) is not well described, despite the known potential for inflammatory neurotoxicities and encephalitis. Though high grade neurologic events are reported in Methods From January 2015-Decmber 2018 at University of Vermont Medical Center, we retrospectively identified cancer patients who received at least one infusion of IO and had a concurrent diagnosis of CD on the problem list, medical history, or billing codes. We used the search terms: cognitive impairment, mild cognitive impairment, neurodegenerative cognitive impairment, memory change/memory deficit/memory difficulty/memory impairment, altered mental status, or encephalopathy to define cognitive impairment. We manually reviewed the charts of all patients meeting this criteria and excluded patients with an alternative diagnosis that was causal for CD (stroke, sepsis, seizure, brain tumor). Results We identified 55 patients and excluded 16 for CD before IO started, 23 with toxic/metabolic causes (including stroke, sepsis, medications, seizures), 4 for primary central nervous system malignancy, and 6 for CD related to new or worsening brain metastases. Six had CD possibly related to IO (table 1). Most had also received chemotherapy either concurrently or prior to starting IO, but two patients had only ever received IO cancer therapy. Four of the six had documented MMSE or neuropsychological testing. On careful chart review, no alternative diagnosis was identified as clearly causal for the change in cognition. Conclusions Patients receiving IO cancer therapy do report CD, which has not been broadly described. Though our data is corollary, it opens the question as to whether prospective pre- and post-treatment cognitive monitoring may identify more patients with neurocognitive symptoms related to immunotherapy. Future research is needed to report incidence of potential IO-related CD and to develop preventative or therapeutic strategies.
Creating trust and commitment in B2B services

Abstract In an ever-changing environment, business relationships are becoming increasingly complex. This particularly applies to the business-to-business (B2B) service sector due to its intangible nature. The combination of personal and organizational relationships further increases this complexity. However, trust can reduce uncertainty and complexity and help maintain commitment. Based on structural equation modeling and a sample of 1692 participants, this study provides insights into the drivers of trust in organizations and salespersons and their impact on commitment. The results show that both are important, but trust in a salesperson far surpasses the effect of trust in an organization. Furthermore, reputation and service quality influence trust in an organization, while social skills and low selling orientation affect trust in a salesperson. In summary, to the best of our knowledge, our study is the first to provide a comprehensive trust model in the B2B service market, and it might serve as a guide for future research.
A microfluidic device for blood plasma separation and fluorescence detection of biomarkers using acoustic microstreaming

Abstract Human blood plasma contains numerous soluble, diffusible, and secreted biomarkers that are used for clinical diagnosis and prognosis of various diseases. However, the blood of some patients is hemolyzed rapidly due to the rupture of cell membranes and releases chemicals and biological molecules that yield false-positive fluorescence detection results due to autofluorescence. The standard method for plasma separation is centrifugation, which is difficult to be integrated with various methods for downstream biomarker detection. Herein, we report development of a novel microfluidic device that is integrated with multiple functionalities on a single disposable chip. Using the principle of bubble-induced acoustic microstreaming, we have tested whole blood controls spiked with fluorescently tagged antibodies to HIV-1 p24 protein and obtained ∼ 31.8 % plasma yield with 99.9 % plasma purity within five minutes. The separated plasma was then routed to an integrated micro-mixing chamber and mixed with HIV-1 p24 antigen conjugated beads (10 μm diameter). The bound p24 antigen-antibody complexes were captured by acoustic microstreaming and detected using a fluorescence microscope. These experiments demonstrated a detection limit of ∼17 pg/μL of p24 antibody in the plasma. The microfluidic device successfully separated plasma from the whole blood control using acoustic microstreaming and integrated with acoustic micro-pumping and micro-mixing for enrichment of biomarkers by mixing p24-bound beads with fluorescently tagged antibodies. The beads with antigen-antibody complexes were efficiently captured in a separate compartment for fluorescence microscopy and detection of biomarkers. Integration of multiple functionalities on a single disposable microfluidic chip can now facilitate rapid detection of biomarkers and be used for monitoring patients’ specimen in real time.
Probabilistic Assessment of Damage from Same Shock Response Spectra due to Variations in Damping

Interpretation of field data from shock tests and subsequent assessment of product safety margins via laboratory testing are based on the shock response spectra (SRS). The SRS capture how a single degree of freedom (SDOF) structure responds to the shock at differing frequencies and, therefore, no longer contain the duration or other temporal parameters pertaining to the shock. A single duration can often be included in the technical specification or in the recreation of acceleration vs. time history from the specified SRS; however, there is little basis for that beyond technical judgment. The loss of such temporal information can result in the recreated SRS being the same while its effect on a system or component can be different. This paper attempts to quantify this deficiency as well as propose a simple method of capturing damping from shock waves that can allow the original waveform to be more accurately reconstructed from the SRS. In this study the decay rate associated with various frequencies that comprise the overall shock was varied. This variation in the decay rate leads to a variation in the acceleration vs. time history, which can be correlated to a “Damage Index” that captures the fatigue damage imparted to the object under shock. Several waveforms that have the same SRS but varying rates of decay for either high- or low-frequency components of the shock were investigated. The resulting variation in stress cycles and Damage Index is discussed in the context of the lognormal distribution of fatigue failure data. It is proposed that, along with the SRS, the decay rate is also captured to minimize the discrepancy between field data and representative laboratory tests.
Coupled Maxwell and time-dependent orbital-free density functional calculations

Coupled Maxwell and time-dependent orbital-free calculations are implemented and tested to describe the interaction of electromagnetic waves and matter. The currents and induced fields predicted by the orbital-free calculations are compared to time-dependent density functional calculations and very good agreement is found for various systems including jellium sheets, jellium spheres, atomistic sheets, and icosahedron clusters.
Arthroscopic Suture Fixation of Tibial Eminence Fracture

Background:Tibial eminence fractures account for up to 5% of knee injuries with an effusion in the pediatric population. Displaced fractures require reduction and operative fixation via arthroscopi...
Quantitative measurement of macromolecular tissue properties in white and gray matter in healthy aging and amnestic MCI.

Abstract Healthy and pathological aging influence brain microstructure via complex processes. Discerning these processes requires measurements that are sensitive to specific biological properties of brain tissue. We integrated a novel quantitative R1 measure with multi-shell diffusion weighted imaging to map age-associated changes in macromolecular tissue volume (MTV) along major white matter tracts in healthy older adults and patients with amnestic Mild Cognitive Impairment (aMCI). Reduced MTV in association tracts was associated with older age in healthy aging, was correlated with memory performance, and distinguished aMCI from controls. We also mapped changes in gray matter tissue properties using quantitative R1 measurements. We documented a widespread decrease in R1 with advancing age across the cortex and decreased R1 in aMCI compared with controls in regions implicated in episodic memory. Our data are the first to characterize MTV loss along major white matter tracts in aMCI and suggest that qMRI is a sensitive measure for detecting subtle degeneration of white and gray matter tissue that cannot be detected by conventional MRI and diffusion measures.
Americans' intention to visit Cuba as a medical tourism destination: A destination and country image perspective

Abstract This study focuses on Americans' perceptions of and intentional behaviors toward Cuba as a medical tourism destination. Using a survey-based quantitative method, the study examined the effects of Cuba's country image and destination image as well as the perceived cost and quality of its medical tourism services on intention to visit Cuba. The results showed that country image and perceived quality of medical tourism services had the greatest positive influence on Americans' intention to travel to Cuba for medical purposes. The study also supported the positive effect of destination image and the negative effect of perceived costs of medical tourism services on intention to visit Cuba. Lastly, the study findings revealed that the better the country and destination image of Cuba, the lower the perceived cost and the higher the perceived quality of its medical tourism services would be.
International Crime and Punishment: The Gap Through Which to Drive a Mafia

International crimes against the person are now widely recognized but lacking any cohesive enforcement. Universal principles of human dignity make it easy enough to define behaviors as illegal. What is much more difficult is finding the means and resources to deploy enforcement mechanisms. The lack of enforcement opens the path to enormously powerful and wealthy criminal organizations as well as to the unsophisticated jihadist. Mass atrocities, terrorism, slavery, and piracy may be linked in a number of ways. Terrorist tactics can be used to enslave a population, and enslaved populations can be trained in the ways of terrorism. In the modern world, human trafficking may provide both funds and camouflage for terrorist organizations. Both are linked in organized crime along with drug trafficking and piracy. Despite universal revulsion toward slavery, there are many forms of forced labor still in practice with no supra-national enforcement whatsoever. Similarly, terrorism is now subject to almost universal condemnation but virtually no transnational enforcement mechanisms. We may not see an effective international police force within my lifetime, but surely the increasing pressure for international cooperation in these arenas ultimately must lead to an effective law enforcement response. Perhaps not in my lifetime, but someday there must be an enforcement mechanism to match the world’s norms.
NADPH-dependent microsomal lipid peroxidation and the problem of pathological action at a distance: New data on induction of red cell damage

Abstract Lipid peroxidation occurs in vitro in a system consisting of rat liver microsomes and NADPH. If a small quantity of red cells is added, they will hemolyze. Lipid peroxidation (i.e. malonic dialdehyde evolution) always precedes red cell hemolysis in our system. This finding is contrary to earlier experiments of others, in which much higher concentrations of red cells were used, and in which certain other conditions varied from those used in our work. Addition of EDTA, which prevented lipid peroxidation, completely prevented red cell hemolysis. When aminopyrine was added, there was vigorous production of formaldehyde and neither lipid peroxidation nor red cell hemolysis occurred. Neither malonic dialdehyde nor hydrogen peroxide is responsible for the red cell hemolysis. If EDTA and erythrocytes are added to a microsomal system that has a prior history of NADPH-induced lipid peroxidation, the erythrocytes show prelytic damage, which can be detected by an osmotic fragility test. If erythrocytes are added to a system in which microsomal lipid peroxidation has been prevented (by the presence of EDTA), there is no evidence of osmotic fragility. These experiments suggest that some product or products arising in the peroxidizing microsomal lipids are capable of producing red cell damage.
Internationalizing Business Curriculum: Considerations and Applications

SUMMARY The trend towards internationalizing the business curriculum is undoubtedly one of the most significant developments in academia. Recognizing the importance of imbuing students with a global perspective, business schools, one after the other, are either developing new courses with an international focus or incorporating international materials in existing courses. As the internationalization process continues, pedagogical concerns such as course content, teaching approach, student evaluation, and course improvement are at the center Stage.
Association Between Transcatheter Aortic Valve Implantation Volume and Outcomes in the United States

With the rapid advance of transcatheter aortic valve implantation (TAVI), it is important to evaluate the relationship between TAVI volumes and outcomes. The aim of this study was to analyze in-hospital outcomes after TAVI stratified according to hospital volumes. Using the National Inpatient Sample files from 2012, hospitals performing transfemoral (TF)-TAVI and transapical (TA)-TAVI were divided into high-volume and low-volume centers. A total of 7,660 patients underwent TAVI in 256 hospitals in 2012. In the TF-TAVI cohort, multivariate logistic regression analyses demonstrated that low TF-TAVI volume status was an independent predictor of death and bleeding. In the TA-TAVI cohort, low volume status was a predictor of death, myocardial infarction, and need for permanent pacemaker. In addition, hospitals that performed low TA-TAVI volume were associated with significantly higher rate of death after surgical aortic valve replacement in comparison with the hospitals that perform high TA-TAVI volume (3.6% vs 2.3%, p <0.001). In conclusion, centers with lower volume of TAVI had more frequent adverse events compared with higher volume centers.
MARGINALIDADE E EXCLUSÃO SOCIAL: UMA LEITURA DO CONTO “LIXO E PURPURINA”

Nesse artigo, aborda-se a marginalidade e a exclusao social problematizada no conto “Lixo e purpurina”, de Ovelhas negras, de Caio Fernando Abreu, procurando apontar as estrategias esteticas arroladas no texto para problematizar o nao-lugar do protagonista da narrativa, um personagem que nao se realiza plenamente como sujeito no seu pais nem no estrangeiro. MARGINALITY AND SOCIAL EXCLUSION: A READING OF SHORT STORY "LIXO E PURPURINA" In this paper, we address the marginality and social exclusion problematic in the short story "Lixo e purpurina," of Ovelhas negras, of Caio Fernando Abreu, trying to point out the aesthetic strategies enrolled in the text to discuss the non-place of the protagonist of the narrative, a character not fully realized as a subject in your country or abroad.
Overexpression of Activation-Induced Cytidine Deaminase in B Cells Is Associated with Production of Highly Pathogenic Autoantibodies

Defective receptor editing or defective B cell checkpoints have been associated with increased frequency of multireactive autoantibodies in autoimmune disease. However, Ig somatic hypermutation and/or class switch recombination may be mechanisms enabling the development of pathogenic multireactive autoantibodies. In this study, we report that, in the BXD2 mouse model of autoimmune disease, elevated expression of activation-induced cytidine deaminase (AID) in recirculating follicular CD86 + subsets of B cells and increased germinal center B cell activity are associated with the production of pathogenic multireactive autoantibodies. CD4 T cells from BXD2 mice that expressed increased levels of CD28 and an increased proliferative response to anti-CD3 and anti-CD28 stimulation are required for this process. Inhibition of the CD28-CD86 interaction in BXD2 mice with AdCTLA4-Ig resulted in normalization of AID in the B cells and suppression of IgG autoantibodies. This treatment also prevented the development of germinal center autoantibody-producing B cells, suggesting that an optimal microenvironment enabling AID function is important for the formation of pathogenic autoantibodies. Taken together, our data indicate that AID expression in B cells is a promising therapeutic target for the treatment of autoimmune diseases and that suppression of this gene may be a molecular target of CTLA4-Ig therapy.
Where is the "Quality Movement" in Law Practice?

The "Quality Movement" that originated in industrial production and has since influenced the professions prescribes standardized work, root cause analysis of errors, peer review, and performance measurement. While these reforms have transformed medicine and some other professions, their influence has lagged in the legal profession. This Essay reviews the limited progress of the reforms in law and assesses the cultural, institutional, and doctrinal obstacles they face.
Leber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X-linked locus.

LHON has been suggested to involve both mitochondrial and X-chromosome-linked loci. By extending two-locus mitochondrial and nuclear gene analytic methods, we recently proposed that a proportion of affected females are likely heterozygous at the X-linked locus and affected due to unfortunate X-chromosome inactivation. Assuming that the optic tissue is the primary site of action of the mutant gene(s), we further propose here that there should be no fewer than six embryonic precursor cells for the involved optic tissue at the stage in early development when X-chromosome inactivation occurs. We also estimate that the disease threshold (i.e. proportion of cells with abnormal X-chromosome active in the responsible tissue at the time of X-chromosome inactivation) for a heterozygous female is in the range of 0.60 to 0.83.
Psychological support for women with metastatic carcinoma

Abstract The author reports his experiences over a four-year period with group therapy for women with metastatic carcinoma and meetings with their families. Among the major concerns that emerged-and that the group discussions helped to meet-were issues having to do with dying; improvement of direct communication and establishment of a collaborative relationship between patients and physicians; and mobilization of the family as a support system for the patient. The importance of the patient's developing a sense of mastery of the final stages of life is stressed.
Coded Wire Tag Placement Affects Homing Ability of Pink Salmon

Abstract Coded wire tags (CWTs) are routinely injected into the snouts of Pacific salmon Oncorhynchus spp. as fry to estimate contributions of tagged populations to spawning escapements and near-shore fisheries and to assess straying. Because not all fish are tagged, tag recoveries are extrapolated to include contributions of nontagged fish released at the same time and location. A key assumption in the extrapolations is that CWTs do not affect homing ability and therefore migratory pathways. We studied tag position within the heads of homing and straying adult pink salmon O. gorbuscha returning to Prince William Sound, Alaska, to test the hypothesis that poor tag position induces straying. Heads from straying and homing tagged adults were recovered in 1992 and 1994 and X-rayed. Tag locations were categorized into critical and noncritical areas, based on tag position relative to olfactory organs and nerves. In 1992, the 37 analyzed pink salmon that strayed were more likely to have tags in critical positio...
Meeting the Needs of Artistically Talented Students Who Reside in Real and Virtual, Rural Communities in the United States

In response to a lack of attention to developing the abilities of talented art students who reside in rural communities, three art educators present a discussion of community-based art education as a strategy for addressing the needs of these students. They consider a variety of artistically talented student populations who reside in geographically rural communities. Some reside in real, rural communities and some may participate in virtual, global communities. A federally funded project in the United States is reported that focused on the identification, art curricula, and assessment procedures for artistically talented students in local, community-based art education programs. In addition, they describe a university-supported study in the United States that focuses on students who share their artwork online in virtual communities. Resources within real and virtual communities are suggested that can support the interests and development of artistically talented art students.
Diaspora identity, acculturation policy and FDI: The Indian diaspora in Canada and the United States

We use the Indian diaspora in Canada and the United States to explore the effect that host-country acculturation policies can have on the attitudes that immigrants hold toward the home and host countries, and how these attitudes can affect the flow of foreign direct investment (FDI) from host to home countries. Our results reveal that Indo-Canadians feel more at home in Canada than Indian-Americans do in the United States, and that they are less likely to invest in India. This indicates that attitudes toward both the home and host country are important factors affecting diaspora FDI, and that a host country’s acculturation mode significantly affects a diaspora’s attitude toward both the home and host countries.
Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufficiency.

Background 25-OH Vitamin D (VitD) plays a role in serum calcium (Ca) and parathyroid hormone (PTH) homeostasis. VitD insufficiency in patients with primary hyperparathyroidism (HPT) may be associated with greater disease severity and a higher incidence of multi-gland disease and postoperative normocalcemic PTH elevation. Materials and Methods One hundred ten patients with HPT undergoing parathyroidectomy had preoperative VitD levels as follows: levels were insufficient (≤20 ng/mL) in 55 patients (group 1) and sufficient (>20 ng/mL) in 55 patients (group 2). All patients had preoperative localizing sestamibi scans and/or ultrasounds and postoperative serum Ca and PTH levels. A focused approach was performed when possible, and intraoperative PTH monitoring (IPM) was used in all patients. Results Patients with VitD insufficiency had significantly higher preoperative Ca (11.3 ± 1.2 versus 10.8 ± 0.9 mg/dL, P = 0.012) and PTH levels (204 ± 138 versus 156 ± 179 pg/mL; P = 0.006) as well as higher bone specific alkaline phosphatase ( P = 0.006). Localization studies were similar. IPM levels were significantly higher in group 1 at all time intervals. Both groups were similar in operative time, conversions to bilateral explorations, number of glands removed, and number of frozen sections. The glands in group 1 were larger (1757 versus 524 g; P = 0.005). Postoperative Ca levels, PTH levels, rates of eucalcemia, and rates of eucalcemic PTH elevation were all similar. Conclusion Patients with HPT and VitD insufficiency may have significantly more severe disease based on preoperative serum Ca and PTH levels, bone markers, and gland size. IPM levels in these patients are higher but can be used to predict postoperative eucalcemia, an outcome which appears be independent of VitD status.
Atrial Natriuretic Peptide Gene Delivery Reduces Stroke-Induced Mortality Rate in Dahl Salt-Sensitive Rats

Atrial natriuretic peptide (ANP) is a powerful hormone with hypotensive, natriuretic, diuretic, and many other beneficial effects. Direct infusion of ANP in therapeutics has limited success because of its short half-life in the circulation. Our previous studies have shown that ANP gene delivery attenuates hypertension, cardiac hypertrophy, and renal injury in Dahl salt-sensitive (Dahl-SS) rats. To investigate the potential therapeutic value of ANP gene delivery on salt-induced stroke and cerebrovascular disorders, an adenovirus harboring the human ANP gene (Ad.RSV-cANP) was injected into Dahl-SS rats on a high salt diet. A single intravenous injection of the ANP gene caused a significant reduction of blood pressure that lasted for more than 3 weeks. A maximal blood pressure reduction of 28 mm Hg was observed 2 weeks after gene delivery as compared with that of control rats injected with adenovirus harboring the LacZ gene under the control of the Rous sarcoma virus promoter (Ad.RSV-LacZ). Immunoreactive human ANP can be detected in the heart, lung, kidney, and brain of rats after gene delivery. The stroke mortality rate of Dahl-SS rats was significantly decreased (from 54% to 17% at 3 weeks and from 70% to 50% at 4 weeks after ANP gene delivery as compared with rats injected with control virus). ANP gene delivery also significantly attenuates salt-induced aortic hypertrophy as evidenced by reduced thickness of the aortic wall. This is the first study to demonstrate the potential of ANP gene delivery in reducing the mortality rate caused by cerebrovascular disorders and stroke. Successful application of this technology may have potential value in treating individuals with a high risk of stroke.
Error-Prone DNA Polymerase IV Is Regulated by the Heat Shock Chaperone GroE in Escherichia coli

An insertion in the promoter of the operon that encodes the molecular chaperone GroE was isolated as an antimutator for stationary-phase or adaptive mutation. The groE operon consists of two genes, groES and groEL; point mutations in either gene conferred the same phenotype, reducing Lac+ adaptive mutation 10- to 20-fold. groE mutant strains had 1/10 the amount of error-prone DNA polymerase IV (Pol IV). In recG+ strains, the reduction in Pol IV was sufficient to account for their low rate of adaptive mutation, but in recG mutant strains, a deficiency of GroE had some additional effect on adaptive mutation. Pol IV is induced as part of the SOS response, but the effect of GroE on Pol IV was independent of LexA. We were unable to show that GroE interacts directly with Pol IV, suggesting that GroE may act indirectly. Together with previous results, these findings indicate that Pol IV is a component of several cellular stress responses.
Comparative toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in four (sub)strains of adult male rats

Four (sub)strains of adult male rats were given single oral doses of various concentrations of TCDD to establish and compare the oral 30-day LD50 values. The strains of rats were Fischer (F/334N) supplied by Harlan Industries, Frederick Cancer Research Center, and Charles River Breeding Laboratories; and CD supplied by Charles River Breeding Laboratories. The Charles River/Fischer rats were most sensitive to TCDD (LD50 = 164, 95% confidence limits 104-217 micrograms/kg), the Frederick/Fischer and Charles River/CD rats were moderately sensitive to TCDD (LD50 = 303, 250-360; and 297, 240-360 micrograms/kg, respectively), and the Harlan/Fischer rats were most resistant to TCDD (LD50 = 340, 281-409 micrograms/kg). The mean times of death were from 24.5 +/- 1.0 to 28.3 +/- 0.5 days and the percentage body weight loss at death was 37.4 +/- 1.2 to 42.7 +/- 1.3%. One week after exposure of the Charles River/Fischer animal to 45 micrograms TCDD/kg (1/4 the established 30-day LD50 dose), the same serum profile was induced as previously observed in the Harlan/Fischer rat, which includes hypoglycemia, hypertriglyceridemia, and hypercholesterolemia. These results emphasize the importance of indicating the precise dose, strain of rat, and time after dosing before termination in reporting the effects of TCDD on a particular biological response.
Complications of pediatric colonoscopy: a five-year multicenter experience.

Colonoscopy has become a routine modality for the evaluation and treatment of colonic disorders in children. Although generally considered a safe procedure, colonoscopy has the potential for complications. Most informed consent forms describe adverse effects of sedative medicines, perforation, infection, and bleeding as possible risks of colonoscopy. However, the frequency of these complications remains unclear. There are limited pediatric data showing complication rates, and most prior studies involved small numbers of procedures. Furthermore, there might be additional complications that need to be added to consent protocols, because most current complication data are extrapolated from the much larger experience in adult populations. A review of pediatric literature demonstrated a wide array of potential complications and no large multicenter studies during the past 25 years. The largest study was conducted in 1978–1979 and included a survey of 1400 proctosigmoidoscopies performed during an 18-month period at 25 medical centers in the U.S.1 This study was only published in abstract form and reported complications in 0.2% of all colonoscopy procedures. These complications included one hemorrhage requiring transfusion and one perforation. In the second largest study, Stringer et al2 prospectively described a series of 250 flexible colonoscopies done in the United Kingdom during a 3.5-year period with no adverse events. Several other studies reported complications (Table 1) in pediatric colonoscopy, but the majority of these studies examined a small number of procedures. Table 1 Complication Rates of Colonoscopy in Pediatric Literature Arranged by Sample Size in Descending Order Determination of potential colonoscopy-related complications and their expected frequency in children can lead to enhanced risk-benefit analysis by physicians and patients and improved informed consent. There is a lack of systematic, multicenter studies in the pediatric population. Therefore, we conducted the current study to examine the frequency, type, and clinical determinants of immediate complications encountered during pediatric colonoscopies performed in 12 U.S. centers by using Pediatric Endoscopy Database System–Clinical Outcomes Research Initiative (PEDS-CORI) database.
Enhancement of track-etched membrane performance via stretching

The objective of this paper is to demonstrate that membrane performance (flux, rejection, and permeate particle size distribution as a function of time) can be influenced by modifying the membrane pore size characteristics. Poly(ethylene teraphthalate) (PET) track-etched (T-E) membranes with nominal pores sizes ranging from 0.2 to 10 μm were uniaxially stretched to increase the major axis, aspect ratio, pore area, and porosity while decreasing the minor axis. Permeation results for pure water feed as well as separate feed suspensions of spherical particles and irregular-shaped particles showed that flux can be increased and flux decline decreased by stretching membranes. Additionally, rejection of both irregular-shaped and spherical particles was increased by stretching membranes.
Computer exploration of fast-speech rules

A set of fast-speech rules has been tested on the computer using the phonological grammar tester (PGT) program of Friedman and Morin. We examine the types of difficulties encountered in the rules and discuss ways in which the program can be made more useful for studying fast-speech rules.
Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry.

The LysR-type transcriptional regulator MvfR (PqsR) (multiple virulence factor regulator) plays a critical role in Pseudomonas aeruginosa pathogenicity via the transcriptional regulation of multiple quorum-sensing (QS)-regulated virulence factors. LasR activates full mvfR transcription, and MvfR subsequently activates pqsA–E expression. This study identifies and characterizes the key cis-regulatory elements through which mvfR and pqsA–E transcription is regulated in the highly virulent P. aeruginosa strain PA14. Deletion and site-directed mutagenesis indicate that: (1) LasR activates mvfR transcription by binding to a las/rhl box, CTAACAAAAGACATAG, centred at −513 bp upstream of the MvfR translational start site; and (2) RhlR represses pqsA transcription by binding to a las/rhl box, CTGTGAGATTTGGGAG, centred at −311 bp upstream of the pqsA transcriptional initiation site. Furthermore, it is shown that MvfR activates pqsA–E transcription by binding to a LysR box, TTCGGACTCCGAA, centred at −45 bp relative to the pqsA transcriptional initiation site, demonstrating that this LysR box has a critical role in the physical interaction between the MvfR protein and the pqsA promoter. These results provide new insights into the regulatory relationships between LasR and mvfR, and between MvfR/RhlR and the pqs operon, and elucidate further the complex regulation of the P. aeruginosa QS circuitry.
The origin of light hydrocarbons

The light hydrocarbons (LHs) are probably intermediates in the catalytic decomposition of oil to gas. Two lines of evidence support this possibility. First, the reaction was duplicated experimentally under moderate conditions. Second, natural LHs exhibit the characteristics of catalytic products, in particular a proportionality between isomers: (xy{sub i})/(x{sub i}y) = {alpha} (where x and x{sub i} are isomers; y and y{sub i} are isomers that are structurally similar to x and x{sub i}; and {alpha} is a constant). All oils exhibit this relationship with coefficients of correlation reaching 0.99. Isomer ratios change systematically with concentrations, some approaching thermodynamic equilibrium, others not. The correlations reported are the strongest yet disclosed for the LHs. Isomers are related in triads (e.g., n-hexane {leftrightarrow} 2-methylpentane {leftrightarrow} 3-methylpentane), consistent with cyclopropane precursors. The LHs obtained experimentally are indistinguishable from natural LHs in (xy{sub i})/(x{sub i}y). These relationships are not explained by physical fractionations, equilibrium control, or noncatalytic modes of origin. A catalytic origin, on the other hand, has precedence, economy and experimental support.
GENERATION OF U- AND D-QUARK MASSES BY WEAK INTERACTIONS

The masses of the u and d quarks are calculated as finite contributions from one-loop diagrams in an SU/sub L/(4) x SU/sub R/(4) x U(1) gauge model of the weak and electromagnetic interactions. The parameters in our model can be chosen in such a way that the low-energy phenomenology resembles closely that of the Weinberg-Salam model.
The Utstein template and the effect of in-hospital decisions: the impact of do-not-attempt resuscitation status on survival to discharge statistics.

Abstract Background: Variables for reporting outcome of pre-hospital cardiac arrest have been delineated in the Utstein style template. The primary outcome statistic is survival to hospital discharge (SHD). The template allows comparisons of pre-hospital care systems and has been used to determine the benefit of pre-hospital interventions. Post-resuscitation care has not been standardized and in-hospital events that affect SHD are not considered in the template. Study purpose: To determine the frequency and timing with which do-not-attempt resuscitation (DNAR) status is conferred following resuscitation from pre-hospital cardiac arrest and to assess the impact of this action on SHD. Methods: A 4-year retrospective, observational cohort study of all adult patients successfully resuscitated from nontraumatic pre-hospital cardiac arrest and admitted to a single municipal teaching hospital. Study variables included age, witnessed arrest, bystander cardiopulmonary resuscitation (CPR), initial rhythm documented by paramedics, hospital admission rate, frequency and time at which DNAR status was conferred, and SHD. Results: Four hundred and eighteen adult patients experienced pre-hospital arrest and received standard advanced cardiac life support interventions during the study period. Seventy-nine patients (19%; 95% confidence interval (CI), 15–23%) survived to be admitted to the hospital. Fifty-four of these patients (68%; 96% CI, 57–78%) were subsequently placed in DNAR status. Only one of these patients had a living will or advanced directive prior to cardiopulmonary arrest. In 37 DNAR patients (68%; 95% CI, 54–81%), DNAR status was conferred within 24 h of hospital admission. For patients made DNAR within 24 h of admission, 38% had a witnessed arrest, 22% had ventricular fibrillation as the first documented arrest rhythm, and 29% received bystander CPR. When patients made DNAR are included in the calculation of SHD rate, the SHD rate for the study period was 5.3% (95% CI, 3.3–7.8%). If DNAR patients are excluded, the SHD was 6.1% (95% CI, 3.8–9.0%), representing a 15% increase in SHD rate. Conclusion: In-hospital care and medical decision making are not considered in the Utstein template and can have a significant effect on reported survival statistics. When assessing the benefit of pre-hospital interventions, it may be preferable to consider survival to hospital admission as the primary outcome statistic until such time as post-resuscitation care after hospital admission is rigidly standardized.
The clinician and reactions to cosmetics

Physicians often see patients who have reactions to cosmetics, including toiletries, but when one considers that the current annual expenditure for beauty products in the United States is estimated at 3.5 billion dollars (Newsweek, 1968), it is surprising that significant adverse reactions to these products do not occur more frequently. In fact, beauty products generally are safe for consumer use. It is difficult to determine the true incidence of reactions to cosmetics (Burks, 1962; Reiss, 1958; Hjorth, 1959). The severity of untoward responses to cosmetics varies greatly, and undoubtedly people who develop adverse reactions to cosmetics often discontinue using a product and change brands without reporting the reaction to the manufacturer or to a physician. Only reactions that are severe and prolonged bring the user to the physician, and only a small undetermined percentage of these physicians are allergists or dermatologists. What kinds of reactions to cosmetics make people seek medical treatment? A classification of these is presented in Table 1. They range from aberrations of sensation (pruritus, burning), through dermatitis with the entire spectrum of inflammation, to systemic reactions.
Columnar Distribution of Cortico-Cortical Fibers in the Frontal Association, Limbic, and Motor Cortex of the Developing Rhesus Monkey

The terminal distribution of cortico-cortical connections was examined by autoradiography 7–8 days following injections of tritium labeled amino acids into the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex in monkeys ranging in age from 4 days to 5.5 months. Labeled axons originating in these various regions of the frontal lobe have topographically diverse ipsilateral and contralateral destinations but virtually all of these projections share a common mode of distribution: they terminate in distinct vertically oriented columns, 200–500 μm wide, that extend across all layers of cortex and alternate in regular sequence with columns of comparable width in which grains do not exceed background. Spatial periodicity in the pattern of transported label in such regions as the prefrontal association cortex, the retro-splenial limbic cortex and the motor cortex indicates that columniation in the intra-cortical distribution of afferent fibers is not unique to sensory specific cortex but is instead a general feature of neocortical organization.
A Distorted Tetrahedral Metal Oxide Cluster inside an Icosahedral Carbon Cage. Synthesis, Isolation, and Structural Characterization of Sc4(μ3-O)2@Ih-C80

The remarkably large cluster Sc4(μ3-O)2 has been obtained trapped inside an Ih-C80 cage by conducting the vaporization of graphite rods doped with copper(II) nitrate and scandium(III) oxide in an electric arc under a low pressure helium atmosphere with an added flow of air. The product has been isolated by chromatography and identified by high-resolution mass spectrometry. The structure of Sc4(μ3-O)2@Ih-C80 has been determined by X-ray crystallography on a crystal of Sc4(μ3-O)2@Ih-C80·NiII(OEP)·2(C6H6). The Sc4(μ3-O)2 unit consists of a distorted tetrahedron of scandium atoms with oxygen atoms bridging two of its faces. The Sc−Sc distances range from 2.946(7) to 3.379(7) A.
Feeding and hunger reflexes in human neonates.

Abstract Two additional neonatal reflexes-one related to feeding and one to hunger-are described. When feeding. there is reflex arm abduction with the dorsi of the hands held anteriorly and fingers and forearms flexed. When hungry. a reflex with two phases occurs: the search phase consists of midline arm adduction, hand extension, and the infant's hands searching; the tactile phase follows when the infant finds a body part of the caretaker and touches or rubs it. This phase seems to be an additional social releaser.
Teaching with Stories: Engaging Students in Critical Self-Reflection about Policing and In/Justice

In a course entitled “Policing and In/Justice” we elicited stories about police-citizen encounters through a narrative-based writing assignment. The assignment required students to identify competing perspectives of the story's events. Building on these perspectives, students engaged in assessment and evaluation of police decision-making. We suggest similar assignments may be relevant to courses with students anticipating or engaged in policing careers. The growing emphasis on community policing raises expectations that officers be creative problem-solvers, not just law enforcers. In addition to establishing the significance of the assignment, we explain how we accomplished it, and report on what students gained from it.