cssi/SciSciGPT-SciSciNet huggingface dataset:
Combining Targeted Therapy With Immunotherapy in BRAF-Mutant Melanoma: Promise and Challenges

Recent breakthroughs in the treatment of advanced melanoma are based on scientific advances in understanding oncogenic signaling and the immunobiology of this cancer. Targeted therapy can successfully block oncogenic signaling in BRAFV600-mutant melanoma with high initial clinical responses, but relapse rates are also high. Activation of an immune response by releasing inhibitory check points can induce durable responses in a subset of patients with melanoma. These advances have driven interest in combining both modes of therapy with the goal of achieving high response rates with prolonged duration. Combining BRAF inhibitors and immunotherapy can specifically target the BRAFV600 driver mutation in the tumor cells and potentially sensitize the immune system to target tumors. However, it is becoming evident that the effects of paradoxical mitogen-activated protein kinase pathway activation by BRAF inhibitors in non–BRAF-mutant cells needs to be taken into account, which may be implicated in the problems encountered in the first clinical trial testing a combination of the BRAF inhibitor vemurafenib with ipilimumab (anti-CTLA4), with significant liver toxicities. Here, we present the concept and potential mechanisms of combinatorial activity of targeted therapy and immunotherapy, review the literature for evidence to support the combination, and discuss the potential challenges and future directions for rational conduct of clinical trials.
Heterogeneity in expression and subcellular localization of claudins 2, 3, 4, and 5 in the rat liver, pancreas, and gut

Abstract Background & Aims: Paracellular transport varies widely among epithelia of the gastrointestinal tract. We determined whether members of the claudin family of tight junction proteins are differentially expressed consistent with a potential role in creating these variable properties. Methods: Rabbit polyclonal antibodies were produced against peptides from claudins 2 through 5. The distribution of individual claudins was detected by immunoblotting, and their cell type and subcellular localization were determined by immunofluorescence on cryosections of rat liver, pancreas, stomach, and small and large intestine. Results: All antibodies detected single bands of the expected size on immunoblots and were monospecific based on peptide competition studies. Immunoblotting detected strong differences among tissues in the expression level of each claudin. Immunolocalization confirmed these differences and revealed striking variations in expression patterns. In the liver, claudin 2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, claudin 3 is uniformly expressed, claudin 4 is absent, and claudin 5 is only expressed in endothelial junctions. In the pancreas, claudin 2 is only detected in junctions of the duct epithelia, claudin 5 only in junctions of acinar cells, whereas claudin 3 and 4 are in both. Among differences in the gut are a crypt-to-villus decrease in claudin 2, a highly restricted expression of claudin 4 to colonic surface cells, and the finding that some claudins can be junctional, lateral, or show a gradient in junctional vs. lateral localization along the crypt-to-villus surface axis. Conclusions: Claudins have very different expression patterns among and within gastrointestinal tissues. We propose these patterns underlie differences in paracellular permeability properties, such as electrical resistance and ion selectivity that would complement known differences in transcellular transport. GASTROENTEROLOGY 2001;120:411-422
CDCs and Charitable Organizations in the Urban South: Mobilizing Social Capital Based on Race and Religion for Neighborhood Revitalization

This article examines how community development corporations (CDCs) and other nonprofits access social capital when constructing collaborative partnerships for urban revitalization projects. Data from interviews with the directors of CDCs and charitable organizations in Jackson, Mississippi, are used for the analysis in this research. The findings indicate that the organizations studied mobilize two mutually exclusive forms of social capital when pursuing partnerships. In some instances, social capital based on religion is mobilized. In other cases, social capital based on race is mobilized. The conclusions of the article highlight the relationship between the embeddedness of social capital in local context and the degree to which it can be mobilized to stimulate neighborhood development. Moreover, the extent to which social capital is overemphasized in current social science discourse is explored.
Lectin-like oxidized low-density lipoprotein receptor-1 modulates endothelial apoptosis in obstructive sleep apnea.

Background Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is the major receptor for oxidized low-density lipoprotein in endothelial cells, and its expression is enhanced in proatherogenic settings. The objective of this study was to investigate the association between LOX-1 in freshly harvested human venous endothelial cells and apoptotic circulating endothelial cells in patients with obstructive sleep apnea (OSA). Methods We conducted a prospective, interventional study of 38 patients with newly diagnosed OSA free of disease and 12 healthy control subjects. Plasma LOX-1 (pLOX-1) levels were measured using a commercially available enzyme-linked immunosorbent assay. Protein expression of LOX-1 was quantified by immunofluorescence in freshly harvested venous endothelial cells before and after 8 weeks of continuous positive airway pressure (CPAP) therapy. Circulating apoptotic endothelial cells (CD146 + , CD45 − , and CD31 1 ) were assessed concomitantly by flow cytometry. Results pLOX-1 levels were higher in subjects with OSA than in control subjects (326.9 ± 267.1 pg/mL and 141.1 ± 138.6 g/mL, respectively; P = .004). Patients with OSA showed a threefold increase in baseline endothelial expression of LOX-1 relative to control subjects. CPAP therapy resulted in a significant decrease in endothelial LOX-1 expression only in CPAP-adherent patients. Circulating apoptotic endothelial cells correlated directly with baseline expression of LOX-1 ( R 2 = 0.32, P = .01) after adjustment for age, BMI, and waist to hip ratio. Conclusions Increased expression of LOX-1 in vivo is associated with endothelial apoptosis. Adherence to CPAP therapy may reverse these derangements.
A Single Human Cerebral Malaria Histopathologic Study Can Be Worth a Thousand Experiments

Severe malaria is a density-dependent disease that comprises infected-erythrocyte sequestration, with or without monocytic infiltration, as seen in renal, placental, and lung tissues from severe malaria patients. HIV induces a chronic proinflammatory state with higher numbers of inflammasome-activated monocytes and platelets circulating. The epidemiological and pathological study of S. E. Hochman et al. that was published in a recent issue of mBio (Hochman SE, Madaline TF, Wassmer SC, Mbale E, Choi N, et al., mBio 6:e01390-15, 2015, doi:10.1128/mBio.01390-15) analyzes a large cohort of Malawian children and shows that cerebral malaria in younger HIV-negative children presents as an acute disease predominated by sequestered infected erythrocytes. In contrast, they show that case presentation in older HIV-positive children is as a more lethal acute on chronic disease marked by double the monocytic infiltrates and 5 times as many platelets. This study suggests that cerebral involvement in severe malaria is a pathology similar to that of other organ involvement of severe malaria, with a bias in HIV-positive individuals toward more monocytic infiltrates. The study also addresses the important association of severe malaria and HIV prevalence.
Natural IgM Switches the Function of Lipopolysaccharide-Activated Murine Bone Marrow–Derived Dendritic Cells to a Regulatory Dendritic Cell That Suppresses Innate Inflammation

We have previously shown that polyclonal natural IgM protects mice from renal ischemia/reperfusion injury (IRI) by inhibiting the reperfusion inflammatory response. We hypothesized that a potential mechanism involved IgM modulation of dendritic cells (DC), as we observed high IgM binding to splenic DC. To test this hypothesis, we pretreated bone marrow-derived DC (BMDC) with polyclonal murine or human IgM prior to LPS activation and demonstrated that 0.5 × 10(6) IgM/LPS-pretreated BMDC, when injected into wild-type C57BL/6 mice 24 h before renal ischemia, protect mice from developing renal IRI. We show that this switching of LPS-activated BMDC to a regulatory phenotype requires modulation of BMDC function that is mediated by IgM binding to nonapoptotic BMDC receptors. Regulatory BMDC require IL-10 and programmed death 1 as well as downregulation of CD40 and p65 NF-κB phosphorylation to protect in renal IRI. Blocking the programmed death ligand 1 binding site just before i.v. injection of IgM/LPS-pretreated BMDC or using IL-10 knockout BMDC fails to induce protection. Similarly, IgM/LPS-pretreated BMDC are rendered nonprotective by increasing CD40 expression and phosphorylation of p65 NF-κB. How IgM/LPS regulatory BMDC suppress in vivo ischemia-induced innate inflammation remains to be determined. However, we show that suppression is dependent on other in vivo regulatory mechanisms in the host, that is, CD25(+) T cells, B cells, IL-10, and circulating IgM. There was no increase in Foxp3(+) regulatory T cells in the spleen either before or after renal IRI. Collectively, these findings show that natural IgM anti-leukocyte Abs can switch BMDC to a regulatory phenotype despite the presence of LPS that ordinarily induces BMDC maturation.
Do You Hear Their Voices

What follows is the keynote address by Dai Sil Kim-Gibson to the "World Conference on Japanese Military Sexual Slavery: Honoring the Bravery and the Struggles of Survivors," given at the UCLA School of Law on October 5, 2007. Kim-Gibson recounts her interviews with former Korean "comfort women," humanizing these women and sharing their stories that they want the world to hear.
Donor Product‐Subsidies to Increase Consumption: Implications of Consumer Awareness and Profit‐Maximizing Intermediaries

Donor Product-Subsidies to Increase Consumption: Implications of Consumer Awareness and Profit-Maximizing Intermediaries Terry A. Taylor and Wenqiang Xiao Haas School of Business, University of California, Berkeley Stern School of Business, New York University September 2014 Abstract Increasingly, donors that subsidize socially-desirable products in the developing world are shift- ing from distributing through non-commercial to commercial channels, ceding control of the product price to for-profit intermediaries. This paper advises a donor as to how the donor’s loss of price con- trol and the level of consumer awareness–defined as the fraction of the consumer population that is informed of the product’s benefits–influence the donor’s optimal subsidy and utility: First, in shifting to the commercial channel, the donor should increase (decrease) the subsidy when consumer awareness is low (high). Second, with the commercial channel, the donor should be prepared to increase the subsidy as awareness increases, which is contrary to her actions with a non-commercial channel. Third, contrary to the lesson obtained with non-commercial distribution, with commer- cial distribution the donor can be hurt by increased awareness. This occurs when awareness is moderate, and the implication is that then the donor should be wary of encouraging entities (e.g., governments, non-governmental organizations) to institute campaigns that increase the awareness of the product’s benefits. The intermediary’s decision of whether to target either only informed consumers or the broad market drives our results. Introduction Donors fund subsidies to lower the price, and hence increase the purchase and use, of socially- beneficial products in the developing world. For example, malaria is estimated to cause more than 200 million illnesses and 600,000 deaths annually (World Health Organization 2013). Because the recommended drugs to treat malaria, artemisinin combination therapies (ACTs), are expensive to produce, they are unaﬀordable to many in sub-Saharan Africa, the region which bears the heaviest burden of malaria (Morris et al. 2014). Historically, donor eﬀorts to lower the cost of malaria drugs have focused on non-commercial channels, such as public health systems. In recent years, donors have shifted their eﬀorts in subsidizing recommended malaria drugs to commercial channels,
CAR T Cells Advance to the Next Level

CAR T cells have been making headlines since 2011, when five patients with various B cell malignancies responded to this new form of cell therapy. CAR T cells are autologous T cells that are collected from patients and genetically modified with a viral vector to express a chimeric antigen receptor or “CAR.” Now, two new reports demonstrate that most patients with relapsed or refractory acute lymphoblastic leukemia benefit from treatment with CAR T cells. In these studies, the CAR redirects the T cells to the CD19 protein, which is expressed on B cells and on tumors derived from the B cell lineage. The Lee et al. study reports the results of an intention-to-treat phase I dose-escalation trial. Over 2 years, 21 patients were enrolled and were infused with CD19 CAR T cells. All but two of these patients were able to receive the intended dose of T cells, which demonstrates the feasibility of making CAR T cells from patients with leukemia. Transient toxicities such as fever and low neutrophil counts were common; severe cytokine release syndrome occurred in 14% of the patients but could be treated and reversed. The complete response rate was 67%, and overall survival was over 50% at 10 months. Ten of the 12 patients who had no detectable disease after CAR T cell treatment went on to receive hematopoietic stem cell transplants. Maude et al. report on 25 pediatric patients and 5 adult patients with the same disease. The complete response rate was 90%, and of these 27 patients, 19 had sustained remissions for a median follow-up time of 7 months. At 6 months, the overall survival rate was 78%. All patients had cytokine release syndrome, which was mild or moderate in 73% but severe enough to require intensive care in the other 27%. In all cases reported, this syndrome was reversible with administration of tocilizumab, a monoclonal antibody that blocks the IL-6 receptor. Three of the 30 patients went on to receive hematopoietic stem cell transplants. The cell products used in the two studies were biologically different because of differences in the cell culture methods and viral vectors used and because of the different signaling domains built into the CARs. Yet, both cell treatments have similar mechanisms of action and both were effective. CAR T cells are changing the landscape in leukemia and in immunotherapy, and these two seminal reports are a real triumph of academic translational medicine. D. W. Lee et al ., T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet 10.1016/S0140-6736(14)61403-3 (2014). [[Full Text]][1] S. L. Maude et al ., Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371 , 1507–1517 (2014). [[Full Text]][2] [1]: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61403-3/fulltext [2]: http://www.nejm.org/doi/full/10.1056/NEJMoa1407222
Women, Youth, and the Egyptian Arab Spring

Throughout history, societies have faced popular protests and revolts that have stemmed from a host of reasons and have attracted the participation of all groups in society regardless of gender, re...
WORT: Wind-Oriented Trap for Simultaneous Evaluation of Several Pheromone Blends

A wind-oriented trap (WORT) for evaluating two or more different blends of sex pheromone simultaneously was designed and field-tested against fall army worm, Spodoptera frugiperda (J. E. Smith), and velvet bean caterpillar (VBC), Anticarsia gemmatalis Hubner. Moth captures showed that these speciescan detect differences in pheromone blends positioned as close as 1m apart. Up to four different blends of VBC pheromone were evaluated on the same WORT, and responding males demonstrated a preference for a specific blend compared with other blends of the same pheromonal components. WORTs baited with rubber septa containing either 0.2 or 0.5 mg pheromone per septum caught about the same number of VBC males. However, a 20-fold increase in pheromone per septum (10 mg dose) resulted in reduced catches compared with an adjacent bucket trap on the same WORT (buckets 1m apart) baited with 0.5 mg pheromone per septum. The WORT is an excellent tool for evaluating pheromone blends and pheromone release rates for optimum trap captures.
BeamDyn: a high-fidelity wind turbine blade solver in the FAST modular framework

This paper presents a numerical implementation of the geometrically exact beam theory based on the Legendre-spectral-finite-element (LSFE) method. The displacement-based geometrically exact beam theory is presented, and the special treatment of three-dimensional rotation parameters is reviewed. An LSFE is a high-order finite element with nodes located at the Gauss–Legendre–Lobatto points. These elements can be an order of magnitude more computationally efficient than low-order finite elements for a given accuracy level. The new module, BeamDyn, is implemented in the FAST modularization framework for dynamic simulation of highly flexible composite-material wind turbine blades within the FAST aeroelastic engineering model. The framework allows for fully interactive simulations of turbine blades in operating conditions. Numerical examples are provided to validate BeamDyn and examine the LSFE performance as well as the coupling algorithm in the FAST modularization framework. BeamDyn can also be used as a stand-alone high-fidelity beam tool. Copyright © 2017 John Wiley & Sons, Ltd.
Orthorhombic Bipyramidal Sulfur Coated with Polypyrrole Nanolayers As a Cathode Material for Lithium–Sulfur Batteries

A sulfur–polypyrrole composite consisting of orthorhombic bipyramidal sulfur particles (63.3 wt %) coated with a polypyrrole nanolayer has been synthesized by a low-cost, scalable, environmentally benign process and investigated as a cathode material for Li-ion batteries. Cathodes containing the sulfur–polypyrrole composite have been evaluated in half cells by cyclic voltammetry, galvanostatic cycling, and electrochemical impedance spectroscopy. The sulfur–polypyrrole composite cathode shows better electrochemical stability, cyclability, and rate capability than pristine sulfur as the polypyrrole coating acts as a conductive matrix for electron transfer while prohibiting lithium polysulfide dissolution. At C/5 rate, the sulfur–polypyrrole composite cathode exhibits ∼200 mAh/g higher capacity than the pristine sulfur after 50 cycles. At C/2 and 1C rates, the composite shows significantly better capacity retention than the pristine sulfur over 100 cycles.
Urinary tract infections in children.

Screening and diagnostic procedures for preschool and school-age children are described, when surgery might be appropriate is discussed, and a guide is provided for drug therapy in initial and recurrent episodes of infection.
Enhancing case adaptation with introspective reasoning and web mining

Case-based problem-solving systems reason by retrieving relevant prior cases and adapting their solutions to fit new circumstances. The ability of case-based reasoning (CBR) to reason from ungeneralized episodes can benefit knowledge acquisition, but acquiring the needed case adaptation knowledge has proven challenging. This paper presents a method for alleviating this problem with justin-time gathering of case adaptation knowledge, based on introspective reasoning and mining of Web knowledge sources. The approach combines knowledge planning with introspective reasoning to guide recovery from case adaptation failures and reinforcement learning to guide selection of knowledge sources. The failure recovery and knowledge source selection methods have been tested in three highly different domains with encouraging results. The paper closes with a discussion of limitations and future steps.
Vesicoureteral Reflux in Children With Myelodysplasia: Natural History and Results of Treatment

A total of 58 children with myelodysplasia underwent radiographic and cystometric evaluation and were followed periodically for an average of 58 months. Of this group 30 (52 per cent) demonstrated vesicoureteral reflux, including 16 with low grade and 14 with high grade reflux. In 6 children low grade vesicoureteral reflux resolved with prophylactic antibacterials only, while decompressive treatment was required in 6, antireflux surgery was required in 2 and 2 were lost to followup. Despite adequate decompressive treatment 12 of the 14 children with high grade vesicoureteral reflux required an antireflux operation and 2 were lost to followup. Among those who underwent an operation there has been no recurrent reflux but 3 children have shown evidence of upper urinary tract deterioration. We describe our current approach to the treatment of vesicoureteral reflux in children with neurogenic bladder dysfunction and suggest a management protocol based on urodynamic findings.
Biofuel conversion pathways service learning projects and case studies

Abstract This chapter presents the biofuel conversion pathways related to service learning projects undertaken by students in a northeastern region of United States over many years as part of the Bioenergy Program1. The students' experiences are described. Particularly three different case studies are presented authored by the respective students who successfully completed their projects. The first case study, “Biodiesel project: an educational experience converting waste cooking oil to biodiesel,” started the project with these objectives: define the chemical process required to convert waste cooking oil into useable biodiesel; develop a standardized local procedure to convert waste cooking oil into biodiesel; design a machine that will implement the procedure; develop a method to evaluate the quality of the biodiesel produced; and develop a plan to utilize the waste product of biodiesel (glycerol) in a sustainable manner. The second case study, “Use of magnetite for enhanced harvesting of wastewater biogas feedstock,” was done in partnership with a municipal wastewater treatment plant producing biogas. The third case study, “Feasibility of the fungal breakdown of lignocellulosic biomass” based on interviews with three established companies as case studies for analysis, developed a concept pilot system and explored its commercialization. Similar projects can be undertaken in any location in partnership with the local solid biofuel–based businesses, farms, and communities.
Use of Wireless Smart Sensors for Detecting Human Falls through Structural Vibrations

Falls are the leading cause of accidental deaths for people over the age of 65 because of the fall, fall related injury itself or related complications including hypothermia, dehydration, pressure sores and pneumonia. Several fall detection systems are commercially available including Life Alert, Life Link, and Alert One where the person wears a pendant that can be pressed in the case of an emergency or with newer models activates automatically when there is no motion. Pendant-based emergency systems become ineffective if the person is not wearing the pendant (refuses or forgets) or cannot press the pendant’s button, for example when falling in a prone position on top of the device. In addition, the elderly are hesitant to use emergency systems for several reasons such as the concern of bothering others and personal pride. This paper proposes the use of structural vibrations to determine if a person has fallen. An Imote2 and an ITS400CA sensor board are used for the collection of structural vibrations induced by human activity, including falls. These sensors are discrete, and have shown potential for the data collection and diagnostic processing needed to detect human falls. The use of wireless smart sensors in the structure provides a non-intrusive method for human fall detection that does not require the use of any device by the person. A preliminary study of the classification of human induced vibration in a typical structure using traditional wired sensors is also discussed as well as a sensing framework used to study structural vibrations induced by human falls.
Modeling Production from Shale

Mitchell and his team of geologists and engineers began working on the shale challenge in 1981, trying different combinations of processes and technologies before ultimately succeeding in 1997.
CRISPR/Cas9-Mediated Genome Editing Corrects Dystrophin Mutation in Skeletal Muscle Stem Cells in a Mouse Model of Muscle Dystrophy.

Muscle stem cells (MuSCs) hold great therapeutic potential for muscle genetic disorders, such as Duchenne muscular dystrophy (DMD). The CRISP/Cas9-based genome editing is a promising technology for correcting genetic alterations in mutant genes. In this study, we used fibrin-gel culture system to selectively expand MuSCs from crude skeletal muscle cells of mdx mice, a mouse model of DMD. By CRISP/Cas9-based genome editing, we corrected the dystrophin mutation in expanded MuSCs and restored the skeletal muscle dystrophin expression upon transplantation in mdx mice. Our studies established a reliable and feasible platform for gene correction in MuSCs by genome editing, thus greatly advancing tissue stem cell-based therapies for DMD and other muscle disorders.
Double Government, National Security Powers, and the Trump Administration

The Obama administration attempted to forge a new approach for counter-terrorism, which was neither the law enforcement paradigm nor the “war on terror” approach of the George W. Bush administration. This alternative approach had five key elements and was intended as a model that would not treat terrorism as a crime or war, but would instead incorporate elements of both the state’s criminal law system and the limited use of special military forces in specific instances. The paper explores the Trump administration in light of this and Michael Glennon’s book National Security and Double Government offering a research agenda. Possible avenues to examine include: if Glennon’s theory of a double government with Madisonian institutions and a Trumanite network is valid, the amount of national security policy continuity between the Obama administration and the Trump administration will be high, despite the rhetoric from the Trump campaign that indicates sharp differences. If there is a discernable break (and not merely a rhetorical break), researchers should be able to measure that in areas like drone strikes and targeting practices, detention policies, and surveillance guidelines. Other issues: how will the use of the phrase “radical Islamic terrorism” influence foreign and security policies in the Trump administration?
Vision Training and Sports

The five senses provide us with continual information regarding their on-going status. If all information from each of the senses were processed fully, “sensory overload” would result due to channel capacity limitations. Thus, much of the input information both within and between each sense must be neurologically “filtered” to rid the brain of unwanted and unnecessary aspects via attentional and related/other mechanisms (Welford, 1960; Pashler, 1997) Figure 16.1. Then, this information is “weighted” with respect to the immediate relevance in relation to the task on hand Abernethy et al, 1997 Dosher and Lu, 1999), such as batting a baseball Watts and Bahill, 1990.
Magnetic Control of Lateral Migration of Ellipsoidal Microparticles in Microscale Flows

This study demonstrates a simple, effective, and tunable technique to control the lateral migration of ellipsoidal microparticles by combining microscale shear flows with a uniform magnetic field. Adjusting the direction of the magnetic field results in versatile control of symmetric and asymmetric rotation of the particles, and their shape-dependent lateral migration of the particles. This approach has great potential for selective microfluidic manipulation of micrometer-sized biological objects such as cells, bacteria, and viruses, by means of their nonspherical shapes.
Low dose aflatoxin B1 toxicokinetics and intervention in human volunteers: a pilot study

1665 We have previously shown that chlorophyll (Chl) and its derivative chlorophyllin (CHL) reduce carcinogen bioavailability, biomarker damage, and tumorigenicity in trout and rats. These findings have been partially extended to humans, where CHL was found to reduce urinary excretion of aflatoxin B1 (AFB1)-DNA repair products in rural Chinese unavoidably exposed to dietary AFB1. However, no AFB1 pharmacokinetic data were gathered by that study, and Chl was not included. To address this a small un-blinded crossover study is under way to establish AFB1 toxicokinetic parameters in human volunteers, and the effects of CHL or Chl co-treatment on those parameters. For protocol 1, fasted subjects received an IRB-approved dose of 14C-AFB1 (31.2 ng, 5 nCi) by gelatin capsule with 100 ml water, followed by normal eating and drinking after hr 2. Blood and total urine samples were collected at specified intervals over 72 hr, and 14C-AFB1 equivalents were determined by accelerator mass spectrometry. The protocol was repeated 3 times for each volunteer. Plasma sample analysis revealed a rapid absorption phase, reaching a Cmax of 0.567 ± 0.095 fg/ml at 1 hr (Tmax) (volunteer 1) and 0.534 ± 0.083 fg/ml at 0.92 ± 0.52 hr (volunteer 2). A two compartment model with first-order input and elimination was fitted to each plasma data set, yielding absorption rate constants for volunteers 1 and 2 of 7.22 ± 4.34 hr-1 and 12.46 ± 7.92 hr-1, mean plasma distribution half-lifes (t1/2 α) of 2.02 ± 0.35 hrs and 4.41 ± 2.79 hrs, terminal half-lifes (t1/2 β) of 68.52 ± 49.27 and 92.04 ± 31.18, and AUC(0-24) of 7.26 ± 2.27 pg hr/L and 7.40 ± 0.46 pg hr/L, resp. Urine eliminated over 0-24 hr contained 28.0 ± 2.2% and 35.0 ± 7.9% of the administered dose for volunteers 1 and 2, resp. Protocols 2 and 3 were similar except capsules also contained 150 mg of Chl purified from spinach, or CHL, resp. Though still in progress, single-trial results suggest CHL delayed AFB1 absorption and reduced Cmax and AUC., whereas Chla reduced absorption, Cmax and AUC. These initial results are providing AFB1 toxicokinetic parameters previously unavailable for humans, and suggest that Chl and CHL may limit the bioavailability of aflatoxin in humans as in animals. (Partially supported by NIH grants ES00210, ES03850, CA90890. The AMS work was performed under the auspices of the U.S. D. O.E. by University of California, Lawrence Livermore National Laboratory under Contract No. W-7405-Eng-48.)
Case 3: Skull Depression in a 9-month-old Girl.

1. Alvaro Galvis, MD, PhD* 2. Anthony Shoo, MD* 3. Aaron R. Shedlock, MD* 1. *Department of Pediatrics, University of Nevada Las Vegas School of Medicine, Las Vegas, NV A 9-month-old unvaccinated African American girl presents to the emergency department for the evaluation of an abnormal head “bump.” The mother reports that 5 days before presentation the patient rolled over off a bed and fell 3 feet to the ground. After the fall the girl exhibited no behavioral changes, apparent pain, or emesis. Since the incident, the mother reports that the patient has been doing well, although she became concerned 2 days ago when she noticed a depression on her daughter’s head while bathing her. The infant was born full term but small for gestational age. The mother reports no complications with the birth but that a radiograph was obtained in the nursery showing bilateral “bowed legs.” However, the patient was lost to follow-up after nursery discharge with no establishment of a primary care physician. On examination in the emergency department, her vital signs are as follows: temperature, 98°F (36.7°C); heart rate, 156 beats/min; respiratory rate, 34 breaths/min; and oxygen saturation, 98% on room air. The patient’s weight and height are both below the third percentile. The patient is interactive and playful. There is a small depression 1.6 in (4 cm) in diameter on the left parietal region of her head, with no crepitus or tenderness to palpation. The remaining physical examination findings are normal except for yellowish translucent teeth. Laboratory studies are obtained and show a complete blood cell count and complete metabolic profile within normal limits. A head computed tomographic scan without contrast illustrates a 13-mm depressed comminuted left parietal skull fracture with possible small underlying subarachnoid hemorrhage (Fig 1). Additional imaging and laboratory evaluation lead …
The Future of Computer Applications in Biomedicine

After reading this chapter, you should know the answers to these questions: What are possible future directions for biomedical informatics? What are the forces that are driving these changes?
Left ventricular remodeling with age in normal men versus women: Novel insights using three-dimensional magnetic resonance imaging

Echocardiographic left ventricular (LV) wall thickness increases with age, suggesting LV hypertrophy. However, autopsy studies have shown no change, or even a decrease, in LV mass with age. With many pathologies, LV remodeling results in changes in ventricular shape. Age-associated LV shape change might explain this discrepancy, although this has not been studied. Magnetic resonance imaging (MRI) was used in 336 healthy, normotensive adults (mean age 56 +/- 18 years; 200 women, 136 men) to measure LV mass, end-diastolic LV wall thickness, length, diameter, and shape. Echocardiographic LV mass was measured in a subset of 86 subjects by a standard algorithm. In women, LV wall thickness increased by 14% (r = 0.19, p <0.02), whereas LV length decreased by 9% (r = -0.26, p = 0.0006); LV diameter was unchanged. Thus, LV mass did not vary with age (r -0.04, p = 0.06) and the sphericity index decreased (r = -0.165, p <0.05). In men, LV wall thickness and diameter were unrelated to age, but there was an 11% decrease in LV length (r = -0.29, p = 0.003); therefore, there was an 11% decrease in LV mass (r = -0.20, p = 0.019) and a decrease in the sphericity index (r = -0.218, p <0.04). No change occurred in echocardiographic LV mass with age in either gender, although echocardiographic LV wall thickness increased in both. The left ventricle becomes more spherical with age in normal adults due to reduced LV length. In women, increased LV wall thickness offsets the decreasing LV length, whereas in men, LV wall thickness fails to compensate, resulting in decreased LV mass with age.
Weak LP-Spaces and Weighted Norm Inequalities for the Fourier Transform on Locally Compact Vilenkin Groups

Abstract In this paper we consider the weighted norm inequality problem for the Fourier transform for functions defined on a certain class of topological groups. We study the case in which the weight functions belong to suitable weak L p -spaces.
Large scale simulations of hippocampal-neocortical interactions in a parallel version of genesis

A hippocampal-CA3 memory model was constructed with PGENESIS, a recently developed version of GENESIS that allows for distributed processing of a neural network simulation. A number of neural models of the human memory system have identified the CA3 region of the hippocampus as storing the declarative memory trace. However, computational models designed to assess the viability of the putative mechanisms of storage and retrieval have generally been too abstract to allow comparison with empirical data. Recent experimental evidence has shown that selective knock-out of NMDA receptors in the CA1 of mice leads to reduced stability of firing specificity in place cells. Here a similar reduction of stability of input specificity is demonstrated in a biologically plausible neural network model of the CA3 region, under conditions of Hebbian synaptic plasticity versus an absence of plasticity.
Turbulence-driven reverse lift on two-dimensional and three-dimensional structures

Using laboratory experiments and simplified theoretical arguments, we show that the level of turbulence may reverse the direction of the mean lift on two- and three-dimensional structures with relatively short, deflected splitters. Planar particle image velocimetry and a high-resolution load cell were used to characterize the near wake region and the instantaneous lift of the structures for various geometric configurations, deflection angles and turbulence levels at Reynolds number $\mathrm{Re}=2\ifmmode\times\else\texttimes\fi{}{10}^{4}$ based on the body width. The possibility of reverse lift may occur within a critical deflection angle, which depends on the splitter length and turbulence level. This particular phenomenon is explained quantitatively with a simple formulation that accounts for the effects of the body geometry and turbulence. The distinctive role of turbulence in structures with splitters provides insight to control hydrodynamic force in various environments.
H 2 self-shielding with non-LTE rovibrational populations: implications for cooling in protogalaxies

The abundance of molecular hydrogen (H2), the primary coolant in primordial gas, is critical for the thermodynamic evolution and star-formation histories in early protogalaxies. Determining the photodissociation rate of H2 by an incident Lyman-Werner (LW) flux is thus crucial, but prohibitively expensive to calculate on the fly in simulations. The rate is sensitive to the H2 rovibrational distribution, which in turn depends on the gas density, temperature, and incident LW radiation field. We use the publicly available cloudy package to model primordial gas clouds and compare exact photodissociation rate calculations to commonly-used fitting formulae. We find the fit from Wolcott-Green et al. (2011) is most accurate for moderate densities n~10^3 cm^{-3} and temperatures, T~10^3K, and we provide a new fit, which captures the increase in the rate at higher densities and temperatures, owing to the increased excited rovibrational populations in this regime. Our new fit has typical errors of a few percent percent up to n = 10^3 and n < 10^2 cm^{-3}. This may lower the "critical flux" at which primordial gas remains H2-poor in some protogalaxies, enabling massive black hole seed formation.
Forests of North Carolina, 2015

This periodic resource update provides an overview of forest resources in North Carolina based on an inventory conducted by the U.S. Forest Service, Forest Inventory and Analysis (FIA) program at the Southern Research Station in cooperation with the North Carolina Forest Service. Data estimates are based on field data collected using the FIA annualized sample design and are updated yearly. The estimates presented in this update are for the measurement year 2015 with comparisons made to data reported in 2013 (the latest 5-year analytical report for the State).
Trends in Memory Problems and Race/Ethnicity in the National Health and Examination Survey, 1999-2014.

Background: Little data exist to describe serial population-level trends in cognitive impairment– especially among minority communities. Because memory problems are among the first warning signs of cogni­tive impairment, they provide a potential method for monitoring changes in cogni­tive health at the population level. This exploratory study aimed to: 1) estimate prevalence of memory problems among US residents by race/ethnicity, age category; and 2) examine whether racial/ethnic dif­ferences in subjective cognitive concerns (memory problems) varied across recent time periods. Design and Setting: Serial cross-sectional analysis of self-reported data from the National Health and Examination Survey (NHANES), 1999-2014. Participants: 20,585 participants aged ≥45 years during 1999-2014, who reported race/ethnicity as non-Hispanic White (NHW), non-Hispanic Black (NHB), and Latino/Hispanic. Measurements: The outcome of interest was subjective cognitive concerns, identi­fied as self-reported memory problems. The frequencies of memory problems were examined for each 4-year period, across racial/ethnic groups. Results: In adjusted analyses, compared with older (aged ³65 years) NHWs, dispari­ties in subjective cognitive concerns were observed for older Latinos for most periods (range of AOR: 1.43 – 2.01, P<.05). Ad­ditionally, Latinos without a high school education had significantly higher odds of reporting memory problems than NHW in multiple periods (range of AOR: 1.95 – 2.17, P<.005), while Latino high school graduates did not. There were no significant changes in racial/ethnic differences in sub­jective cognitive concerns over time. Conclusions: The prevalence of sub­jective cognitive concerns across time periods points to a need to engage patients – particularly older and less-educated Latinos – about warning signs for cogni­tive impairment. The impact of education on subjective cognitive concerns in older Latinos may be related to acculturation and warrant further investigation. Ethn Dis. 2019;29(3):525-534; doi:10.18865/ ed.29.3.525
Word Level Plagiarism Detection of Marathi Text Using N-Gram Approach

Plagiarism is increasing day by day. Plagiarism detection is one of the most complex, but a must requirement. This paper deals with word level plagiarism detection for Marathi text by using N-gram language model and a Marathi corpus. This is most simple in form still provides good depth for understanding and emphasing copy-paste and paraphrased plagiarism detection. It forms basis for sentence as well as paragraph level processing
Twitter sentimental analysis

This paper presents the effectiveness of linguistic features to identify the sentiment of Twitter messages using the apache storm framework. We calculate the effectiveness of present lexical resources and features that capture information about the informal and creative language used in microblogging. In the past few years, there has been a huge growth in the use of microblogging platforms such as Twitter. Influenced by intensification, companies, and media organizations are increasingly seeking ways to excavate Twitter information about what people think and feel about their products and services. Here we download Twitter messages for a particular hashtag and carry out sentiment analysis i.e. to find a positive, negative or neutral sense of that tweet using apache storm framework. Each hashtag may have 1000 of comments and new comments are added every minute, in order to handle so many live tweets we are using apache storm framework.
In primary care, CRP testing reduced antibiotic use in COPD exacerbations without worsening health.

Source Citation Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med. 2019;381:111-20. 31291514
Cortical Superficial Siderosis: A Descriptive Analysis in a Memory Clinic Population.

BACKGROUND Cortical superficial siderosis (cSS) is a hemorrhagic marker of blood-brain barrier disruption detected in brain MRI. Together with cerebral microbleeds (CMB), they are recognized as a small vessel disease marker associated with cerebral amyloid angiopathy. OBJECTIVE This study aims to determine the prevalence and the characteristics of cSS in a memory clinic population. METHODS Cross-sectional retrospective analysis of 613 patients from Geneva University Hospitals memory clinic. All patients underwent standardized brain MRI and neuropsychological assessment with diagnosis confirmed by an expert. The presence of cSS was visually assessed and classified as focal (restricted to 3 sulci) or disseminated within the correspondent topography. CMB were classified according to the Microbleed Anatomical Rating Scale. RESULTS cSS was detected in 26/613 patients (4.2%), classified as disseminated in 5/26 cases (19%). Alzheimer's disease (AD) and AD associated with a significant vascular component were the diagnoses more frequently related to cSS (18/26; 69%). Patients with cSS had an increased prevalence of both hypertension (81% versus 57%; p = 0.015) and WMH burden (p = 0.012). The overall prevalence of cerebral microbleeds (69% versus 32%; p < 0.01), as well as their mean number (0.69±0.47 versus 0.32±0.46; p < 0.01) were both increased in patients with cSS. In the logistic regression model, the presence of 5 or more CMB (OR 11.35; 95% CI 4.68-27.55; p < 0.01) and hypertension (OR 3.31; 95% CI 1.19-9.15; p = 0.021) were significantly associated with cSS. CONCLUSIONS cSS is observed in patients diagnosed with AD and AD with a vascular component, being independently associated with multiple CMB and hypertension.
1 – Many Perus

Publisher Summary Peru is the third largest South American country. It is a country of great natural riches and vast topological and climatic contrasts. The dominant theme in Peruvian geography, history, and national life is division. This theme is basic to the understanding of how and why Peruvian education has reached its present state of development. There are many Perus and a great variety of Peruvians. This chapter discusses geographical and cultural influences that have helped to both bring about and sustain this fragmentation.. . Peru's geography, by itself, has been a formidable factor in the retardation of political, cultural, and economical unification of the country. These geographical barriers, among the most formidable in the American hemisphere, serve to reinforce the dominance and isolation of the small elite groups who have centralized nearly all power and influence in Lima, and who have demonstrated little interest in problems of regional development. Moreover, geographical barriers, along with the resulting isolation of population and perpetuation of regional rivalries as between the coast and the highlands have exerted powerful influences in preventing Peru from becoming one nation.
Minimally invasive treatment of lateral epicondylitis

Lateral epicondylitis (LE), also known as tennis elbow, is the most common cause of elbow pain in adults, with approximately 1-3% of the general population being afflicted. Although the condition is usually self-limiting, pain can be a major hindrance, limiting daily activity and the work capacity of patients. As a result, many treatment options have become available with the aim to shorten the duration of the disease and increase the quality of life. Steroid injections, NSAIDs, topical creams, platelet-rich plasma, physical therapy, and kinesiotaping are considered conservative treatments, while surgical options are last-resort treatments reserved for refractory LE. In this review, we will provide a brief summary of LE and focus on addressing conservative and minimally invasive interventional options for the treatment of LE.
The seriality problem for weakly Sylow-permutable subgroups in locally finite groups

Abstract The question of whether weakly Sylow-permutable subgroups of locally finite groups are serial is studied. An affirmative answer is obtained for many types of group, particularly groups satisfying finiteness conditions or with some degree of commutativity.