cssi/SciSciGPT-SciSciNet huggingface dataset:
Modern medical management of obesity: the role of pharmaceutical intervention.

Abstract The medical model of obesity treatment—combining diet, exercise, and behavior modification with antiobesity agents—suffered a setback when fenfluramine and dexfenfluramine were withdrawn from the market because of an association between these medications and valvular regurgitation. The Food and Drug Administration has recently approved sibutramine (Meridia), a norepinephrine and serotonin reuptake inhibitor that was originally developed as an antidepressant, but which has also been shown to reduce weight. In a 1-year placebo-controlled trial, 65% of patients receiving 15mg sibutramine daily lost more than 5% of their body weight, compared with 29% of patients receiving a placebo; 39% of patients in the sibutramine group lost more than 10% of their body weight, compared with 8% of patients in the placebo group. Health benefits observed in patients receiving sibutramine include reductions in levels of triglycerides, uric acid, total cholesterol, and low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol levels. Another antiobesity drug currently under review by the Food and Drug Administration is orlistat (Xenical), a pancreatic lipase inhibitor that reduces the absorption of dietary fat by approximately 30%, thus reducing energy intake. In a 1-year placebo-controlled trial, 55% of patients receiving orlistat lost more than 5% of their body weight, and 25% lost more than 10% of their body weight, compared with 33% and 15%, respectively, of patients in the placebo group. In addition, orlistat slowed the rate of weight regain in the second year of treatment. Health benefits demonstrated in clinical trials of orlistat include reduced LDL cholesterol levels and increased levels of HDL cholesterol, reduced blood pressure and fasting insulin levels, improved oral glucose tolerance test outcomes, and improved glycemic control in obese patients with diabetes. The future of the pharmacologic treatment of obesity is promising. Many new antiobesity agents are in the early stages of development, and our understanding of the body's weight-regulating mechanisms is advancing steadily. Human trials of recombinant leptin are underway. Other promising compounds include those that block the Neuropeptide Y5 and Y1 (NY5, NY1) and Melanocortin-4 (MC4) receptors, stimulate uncoupling proteins, and unbind corticotrophin-releasing factor from its binding protein. As better medical treatments for obesity become available, the focus in dietary prescription may shift away from reducing energy intake toward healthier eating for disease prevention. At present, a comprehensive approach, which, in some patients, may include medical therapy as an adjunct, is necessary to treat obesity effectively. J Am Diet Assoc. 1998;98(suppl 2):S23–S26 .
The Uncertain Place of Purge Within Transitional Justice, and the Limitations of International Law in the World’s Response to Mass Atrocity

I seek to ascertain the proper place of international law, relative to alternative responses, in the redress and restraint of mass atrocity. This task requires that we identify the circumstances in which these alternatives prove at least equally if not more effective. We international lawyers are too quick to assume that the best responses to these recurrent episodes, both ex post and ex ante, lie within our professional domain, and that the current, widely acknowledged limitations of this legal field body would best be cured by enlarging its scope and strength. I show that, to the contrary, several of the most promising, innovative anti-atrocity initiatives in recent years, on both the national and global planes, depend scarcely at all little on international law, strictly speaking. International law can often do very little even to institutionally bolster these promising developments, despite the fact that the humanitarian ideals such law embodies undoubtedly inspire them.
Topical rectal antiseptic at time of prostate biopsy: how a resident patient safety project has evolved into institutional practice

To report outcomes 5 years after a resident quality initiative incorporated topical rectal antiseptic into our ultrasound-guided prostate needle biopsy (TRUS PNB) protocol. A chart review was conducted on 1007 men who underwent TRUS PNB between 2010 and 2017. Comparison groups include those who received a topical rectal antiseptic (N = 437) compared to those who did not (N = 570). Povidone-iodine (N = 303) or 4% chlorhexidine solution without alcohol (N = 134) were topical agents. Outcomes of interest included post-biopsy infection (urinary tract infection and/or sepsis), hospital admission, and need for ICU monitoring. Median age and PSA of men included in this study were 64 years and 12 ng/mL. Almost 90% of patients were Caucasian, 13% had diabetes, 3% were on immunosuppression, 32% had at least one prior biopsy, 14% received antibiotics, and 7% were hospitalized in the past 6 months. 22 patients (2.2%) developed a post-biopsy infection with a significant reduction in the group receiving topical rectal antiseptic (0.8 vs. 3.3%, p = 0.01). Post-biopsy UTI rates (p = 0.04) and hospital admission (p = 0.03) were also lower in the topical antiseptic group with trends to reduction in sepsis and need for ICU monitoring. What started as a resident quality safety project 5 years ago has demonstrated a reduction in infections and hospital admissions following TRUS PNB. Our institutional practice now routinely uses povidone-iodine or chlorhexidine as an adjunct to oral quinolones for TRUS PNB perioperative prophylaxis.
Comparing performance of multiple non-invasive genetic capture–recapture methods for abundance estimation: a case study with the Sonoran pronghorn Antilocapra americana sonoriensis

Demographic monitoring is required in threatened species management, yet effective and efficient monitoring is challenging for species that are difficult to capture or susceptible to capture stress. One possible monitoring approach for such species is non-invasive genetic sampling with capture–recapture methods (genetic capture–recapture). We evaluated the performance of genetic capture–recapture in a challenging model system, monitoring the threatened Sonoran pronghorn Antilocapra americana sonoriensis. In an effort to determine the best (i.e. efficient, accurate, precise, cost-effective) method for abundance estimation, we used simulations to examine the optimal genetic capture–recapture faecal sampling design for this population. We simulated encounter histories for 100–300 individuals, with 0.33–3.33 samples/individual/session, in 1–3 sampling sessions. We explored trade-offs between sample size, number of sessions and multi-session (MARK) versus single-session (capwire) closed capture–recapture abundance estimators, and an accurate and precise estimate. We also compared the cost between the genetic capture–recapture approaches and current aerial monitoring methods. Abundance was biased positively in capwire and negatively in MARK. Bias increased and precision decreased with fewer samples/individual/session. Annual genetic capture–recapture monitoring cost was nearly twice the cost of aerial surveys, although genetic capture–recapture methods provided much higher precision. However at the current estimated abundance (c. 200), the same level of precision achieved with aerial methods can be obtained by collecting 0.75 samples/individual in a single session, for an annual cost saving of > USD 4,000. This approach of comparing estimator performance and cost can easily be applied to other systems and is a useful evaluation for managers to implement prior to designing capture–recapture studies.
Care Coordination: Overcoming Barriers to Improve Outcomes for Patients With Hematologic Malignancies in Rural Settings

BACKGROUND Most patients with cancer experience financial, emotional, and logistical barriers to care that significantly affect their adherence to and successful completion of treatment. However, patients with hematologic malignancies, particularly those who live in rural settings, must also contend with additional challenges. OBJECTIVES This article aims to synthesize the literature about barriers to timely access to care and to coordination of this care for patients with hematologic malignancies, particularly those in rural settings, as well as identify strategies to improve cancer care delivery for those patients. METHODS A search of the literature from 2008-2018 pertaining to rural health disparities for patients with hematologic malignancies, along with ways to overcome these disparities, was conducted. FINDINGS Patients with hematologic malignancies, particularly those who reside in rural settings, face complex barriers to care. These barriers cause emotional and physical distress. A team approach to care coordination that is focused on eliminating these barriers and improving outcomes is needed.
PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress

The mechanistic target of rapamycin complex-1 (mTORC1) coordinates regulation of growth, metabolism, protein synthesis and autophagy1. Its hyperactivation contributes to disease in numerous organs, including the heart1,2, although broad inhibition of mTORC1 risks interference with its homeostatic roles. Tuberin (TSC2) is a GTPase-activating protein and prominent intrinsic regulator of mTORC1 that acts through modulation of RHEB (Ras homologue enriched in brain). TSC2 constitutively inhibits mTORC1; however, this activity is modified by phosphorylation from multiple signalling kinases that in turn inhibits (AMPK and GSK-3β) or stimulates (AKT, ERK and RSK-1) mTORC1 activity3-9. Each kinase requires engagement of multiple serines, impeding analysis of their role in vivo. Here we show that phosphorylation or gain- or loss-of-function mutations at either of two adjacent serine residues in TSC2 (S1365 and S1366 in mice; S1364 and S1365 in humans) can bidirectionally control mTORC1 activity stimulated by growth factors or haemodynamic stress, and consequently modulate cell growth and autophagy. However, basal mTORC1 activity remains unchanged. In the heart, or in isolated cardiomyocytes or fibroblasts, protein kinase G1 (PKG1) phosphorylates these TSC2 sites. PKG1 is a primary effector of nitric oxide and natriuretic peptide signalling, and protects against heart disease10-13. Suppression of hypertrophy and stimulation of autophagy in cardiomyocytes by PKG1 requires TSC2 phosphorylation. Homozygous knock-in mice that express a phosphorylation-silencing mutation in TSC2 (TSC2(S1365A)) develop worse heart disease and have higher mortality after sustained pressure overload of the heart, owing to mTORC1 hyperactivity that cannot be rescued by PKG1 stimulation. However, cardiac disease is reduced and survival of heterozygote Tsc2S1365A knock-in mice subjected to the same stress is improved by PKG1 activation or expression of a phosphorylation-mimicking mutation (TSC2(S1365E)). Resting mTORC1 activity is not altered in either knock-in model. Therefore, TSC2 phosphorylation is both required and sufficient for PKG1-mediated cardiac protection against pressure overload. The serine residues identified here provide a genetic tool for bidirectional regulation of the amplitude of stress-stimulated mTORC1 activity.
Robert Furchgott (1916-2009): A scientist with a mission:

Robert Furchgott was first noted for research on drug-receptor theory, autonomic neuroeffector mechanisms, and vascular pharmacology/physiology. His studies on drug-receptor interactions provided important knowledge about the properties of drug receptors long before methodologies were developed to study them directly. However, Furchgott achieved an enduring legacy for recognizing the importance of endothelial cells for the relaxation of vascular smooth muscle. On the basis of his own experiments and those of others, he proposed that acetylcholine interacted with muscarinic receptors at the surface of endothelial cells to release a substance called endothelium relaxing factor. Endothelium relaxing factor was later identified as nitric oxide, a colorless, odorless gas. Furchgott's discovery of an entirely new mechanism by which blood vessels dilate revolutionized studies on the physiology of the vascular system. His work also suggested new treatments for hypertension and heart disease, and was a key factor in the development of the anti-impotence drug sildenafil. In 1998, Robert Furchgott shared the Nobel Prize in Physiology or Medicine with Ferid Murad and Louis Ignarro.
Side chain determinants of biopolymer function during selection and replication.

The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. Using seven sets of chemically diverse charged, polar, and nonpolar side chains, we performed cycles of artificial translation, in vitro selections for binding to either PCSK9 or IL-6 protein, and replication on libraries of random side chain-functionalized nucleic acid polymers. Polymer sequence convergence, bulk population target binding, affinity of individual polymers, and head-to-head competition among post-selection libraries collectively indicate that polymer libraries with nonpolar side chains outperformed libraries lacking these side chains. The presence of nonpolar groups, resembling functionality existing in proteins but missing from natural nucleic acids, thus may be strong determinants of binding activity. This factor may contribute to the apparent evolutionary advantage of proteins over their nucleic acid precursors for some molecular recognition tasks. A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding.
Silk Reservoirs for Local Delivery of Cisplatin for Neuroblastoma Treatment: In Vitro and In Vivo Evaluations.

Abstract Neuroblastoma is the most common extracranial childhood tumor, and current treatment requires surgical resection and multidrug chemotherapy. Local, perioperative delivery of chemotherapeutics is a promising treatment method for solid tumors that require surgical removal. In this study, we have aimed to develop a controlled-release implant system to deliver cisplatin in tumor or tumor resection area. Silk fibroin, a biodegradable, nonimmunogenic biopolymer was used to encapsulate different doses of cisplatin in a reservoir system. The physical integrity of the reservoirs was characterized by evaluating the crystalline structure of silk secondary structure using FTIR spectroscopy. The in vitro release of cisplatin was evaluated in phosphate-buffered saline at 37°C, and the reservoirs were able to release the drug up to 30 days. The cytotoxicity of cisplatin and cisplatin reservoirs were tested on KELLY cells. Cytotoxicity data showed 3.2 μg/mL cisplatin was required to kill 50% of the cell population, and the released cisplatin from the silk reservoirs showed significant cytotoxicity up to 21 days. Intratumoral implantation of silk reservoirs into an orthotopic neuroblastoma mouse model decreased tumor growth significantly when compared with control subjects. These results suggest that silk reservoirs are promising carriers for cisplatin delivery to the tumor site.
Structures of N-terminally processed KRAS provide insight into the role of N-acetylation

Although post-translational modification of the C-terminus of RAS has been studied extensively, little is known about N-terminal processing. Mass spectrometric characterization of KRAS expressed in mammalian cells showed cleavage of the initiator methionine (iMet) and N-acetylation of the nascent N-terminus. Interestingly, structural studies on GDP- and GMPPNP-bound KRAS lacking the iMet and N-acetylation resulted in Mg2+-free structures of KRAS with flexible N-termini. In the Mg2+-free KRAS-GDP structure, the flexible N-terminus causes conformational changes in the interswitch region resulting in a fully open conformation of switch I. In the Mg2+-free KRAS-GMPPNP structure, the flexible N-terminus causes conformational changes around residue A59 resulting in the loss of Mg2+ and switch I in the inactive state 1 conformation. Structural studies on N-acetylated KRAS-GDP lacking the iMet revealed the presence of Mg2+ and a conformation of switch regions also observed in the structure of GDP-bound unprocessed KRAS with the iMet. In the absence of the iMet, the N-acetyl group interacts with the central beta-sheet and stabilizes the N-terminus and the switch regions. These results suggest there is crosstalk between the N-terminus and the Mg2+ binding site, and that N-acetylation plays an important role by stabilizing the N-terminus of RAS upon excision of the iMet.
Transaction cost theory: past, present and future

Transaction cost theory emerged over 80 years ago yet still continues to exert an important influence on marketing thought. In this article, I examine the past, present and future of this important theory by exploring the work of three of its key scholars: Ronald Coase, Oliver Williamson and Yochai Benkler. This examination provides an overview of each scholar’s ideas, a look at their intellectual influences, and an assessment of their impact on marketing scholarship. In addition to this in-depth exploration of transaction cost theory, I also highlight the contextual nature of how theories form, develop and change over time. My hope is that this examination will enrich our understanding of this important theory and suggest how it can be applied to a new set of marketing topics.
Higher Order Collocation Methods for Nonlocal Problems and Their Asymptotic Compatibility

We study the convergence and asymptotic compatibility of higher order collocation methods for nonlocal operators inspired by peridynamics, a nonlocal formulation of continuum mechanics. We prove that the methods are optimally convergent with respect to the polynomial degree of the approximation. A numerical method is said to be asymptotically compatible if the sequence of approximate solutions of the nonlocal problem converges to the solution of the corresponding local problem as the horizon and the grid sizes simultaneously approach zero. We carry out a calibration process via Taylor series expansions and a scaling of the nonlocal operator via a strain energy density argument to ensure that the resulting collocation methods are asymptotically compatible. We find that, for polynomial degrees greater than or equal to two, there exists a calibration constant independent of the horizon size and the grid size such that the resulting collocation methods for the nonlocal diffusion are asymptotically compatible. We verify these findings through extensive numerical experiments.
The emergence of transcriptional identity in somatosensory neurons

More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments1–4. It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors. Neuronal targets mediate the emergence of somatosensory neuron subtypes by altering the expression of neuronal transcription factors.
Aseptic Loosening of Porous Metaphyseal Sleeves and Tantalum Cones in Revision Total Knee Arthroplasty: A Systematic Review.

Bone loss often complicates revision total knee arthroplasty (TKA). Management of metaphyseal defects varies, with no clearly superior technique. Two commonly utilized options for metaphyseal defect management include porous-coated metaphyseal sleeves and tantalum cones. A systematic review was conducted according to the international Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We combined search terms “Total knee arthroplasty” AND/OR “Sleeve,” “Cone” as either keywords or medical subject heading (MeSH) terms in multiple databases according to PRISMA recommendations. All retrieved articles were reviewed and assessed using defined inclusion and exclusion criteria. A total of 27 studies (12 sleeves and 15 cones) of revision TKAs were included. In the 12 studies on sleeve implantation in revision TKAs, 1,617 sleeves were implanted in 1,133 revision TKAs in 1,025 patients. The overall rate of reoperation was 110/1,133 (9.7%) and the total rate of aseptic loosening per sleeve was 13/1,617 (0.8%). In the 15 studies on tantalum cone implantation in revision TKAs, 701 cones were implanted into 620 revision TKAs in 612 patients. The overall rate of reoperation was 116/620 (18.7%), and the overall rate of aseptic loosening per cone was 12/701 (1.7%). Rates of aseptic loosening of the two implants were found to be similar, while the rate of reoperation was nearly double in revision TKAs utilizing tantalum cones. Variability in the selected studies and the likely multifactorial nature of failure do not allow for any definitive conclusions to be made. This review elucidates the necessity for additional literature examining revision TKA implants.
CIRCULATING ACYLCARNITINES ARE ASSOCIATED WITH HEART FAILURE PROGRESSION: TIME FOR A NEW PARADIGM TOWARDS PERSONALIZED TIMING OF ADVANCED THERAPIES

Advanced heart failure (HF) is morbid and costly with 700,000 patients estimated to reach end-stage HF and be considered for ventricular assist device (VAD) or heart transplantation (HT). The transition to VAD or HT is informed by functional class, exercise capacity, and markers of end-organ
Deep Hypothermic Circulatory Arrest Activates Neural Precursor Cells in the Neonatal Brain.

Background Use of antegrade cerebral perfusion (ACP) as an alternative neuroprotection strategy to deep hypothermic circulatory arrest (DHCA) in the setting of cardiopulmonary bypass in neonates has become a common approach, although the value of ACP over DHCA remains highly debated. This study investigated the disruption to neonatal brain homeostasis by DHCA and ACP. Methods Neonatal pigs (7 days old) undergoing bypass were assigned to 4 groups: DHCA at 18°C and ACP at 18°, 25°, and 32° for 45 minutes (n = 6 per group). ACP was initiated through the innominate artery and maintained at 40 mL/kg/min. After bypass, all animals were maintained sedated and intubated for 24 hours before being euthanized. Brain subventricular zone tissues were analyzed for histologic injury by assessing apoptosis and neural homeostasis (Nestin). Results Histologic examination showed no significant ischemic/hypoxic neuronal death at any cooling temperature among the 4 treatment groups. However, we detected a significantly higher apoptotic rate in DHCA compared with ACP at 18°C (P = .003-.017) or 25°C (P = .012-.043), whereas apoptosis at 32°C was not different from DHCA. Of note, we identified increased Nestin expression in the DHCA group compared with all ACP groups (P range = .011-.041). Conclusions Neonatal piglet ACP at 18° or 25°C provides adequate protection from increased brain cellular apoptosis. In contrast to ACP, however, DHCA induces brain Nestin expression, indicating activation of neural progenitor cells and the potential of altering neonatal neurodevelopmental progression. DHCA has potential to more profoundly disrupt neural homeostasis than does ACP.
Combined effects of biological control of an invasive shrub and fluvial processes on riparian vegetation dynamics

Plant community responses to biocontrol of invasive plants are understudied, despite the strong influence of the composition of replacement vegetation on ecosystem functions and services. We studied the vegetation response to a folivore beetle (Diorhabda genus, Coleoptera) that has been introduced along southwestern US river valleys to control the invasion of non-native shrubs in the genus Tamarix (Tamaricaceae). We collected detailed plant compositional and environmental data during four different surveys over 7 years (2010–2017), including two surveys prior to when substantial beetle-induced dieback occurred in summer 2012, along the lower Virgin River, Nevada. The study river was of special interest because it is one of only a few largely unregulated rivers in the region, and a large flood of 40-year return period occurred between the first and second surveys, allowing us to study the combined effects of fluvial processes, which typically drive riparian plant community assembly, and biocontrol. Vegetation trajectories differed as a function of the dominant geomorphological process. Tamarix cover declined an average of 75% and was replaced by the native shrub Pluchea sericea as the new dominant species in the floodplain, especially where sediment deposition predominated. Following deposition, and especially erosion, opportunistic native herbs, Tamarix seedlings, and noxious weeds colonized the understory layer but did not increase in cover over time. Stands of the native shrub Salix exigua, a desirable replacement species following Tamarix control, only increased slightly and remained subordinate in the floodplain. Overall, our results showed that, by successfully controlling the target non-native plant, a biocontrol agent can substantially modify the replacement plant communities in a riparian system, but that fluvial processes also strongly influence the resulting communities.
Emerging therapeutic agents for advanced non-small cell lung cancer

Advanced non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a poor prognosis and no known cure. Survival time is often short because of limited treatment options. Recent advances in targeted therapy and immunotherapy have changed the landscape for the treatment of advanced NSCLC. In the last 10 years, the US Food and Drug Administration (FDA) has approved more than 17 new medications for this devastating disease and more are coming. Molecular and immunogenic testing makes personalized medicine possible for patients with advanced NSCLC. The new medications provide promising efficacy and safety resulting in improved long-term survival for a significant number of patients. In this review, we summarize the recent advances in advanced/metastatic NSCLC therapeutics with a specific focus on first in-human or early-phase I/II clinical trials. These drugs either offer better alternatives to current standard drugs in the same class or are a completely new class of drugs with novel mechanisms of action. Advances are divided into (1) targeted agents, (2) antibody-drug conjugates, and (3) immunotherapies. Finally, we present a brief review of the emerging agents and ongoing clinical studies.
Electronic states of magnetic quantum dots

We study quantum states of electrons in magnetically doped quantum dots as a function of exchange coupling between electron and impurity spins, the strength of Coulomb interaction, confining potential and the number of electrons. The magnetic phase diagram of quantum dots, doped with a large number of magnetic Mn impurities, can be described by the energy-gap in the spectrum of electrons and the mean field electron–Mn exchange coupling. A competition between these two parameters leads to a transition between spin-unpolarized and spin-polarized states, in the absence of applied magnetic field. Tuning the energy-gap by electrostatic control of nonparabolicity of the confining potential can enable control of magnetization even at the fixed number of electrons. We illustrate our findings by directly comparing Mn-doped quantum dots with parabolic and Gaussian confining potential.
High Prevalence of Elder Abuse During the COVID-19 Pandemic: Risk and Resilience Factors.

OBJECTIVE: Before the COVID-19 pandemic, elder abuse affected one in 10 American older adults annually. It has been assumed that the pandemic has brought with it a surge in elder abuse due to individuals ordered to stay at home combined with increased interpersonal stressors. However, empirical evidence is lacking. This study aims to estimate the prevalence of, and risk and resilience factors of elder abuse during the pandemic. METHODS: The survey was conducted via two online platforms during April 23 and May 5, 2020, when all states had stay-at-home orders. The final cohort consisted of a sociodemographically diverse sample of 897 older persons in the United States. The prevalence of elder abuse was evaluated by a validated measure previously used in a population-based study of elder abuse. Pandemic-related factors were examined at the community, relational, and individual contexts. We conducted multivariate logistic regression analyses to examine determinants of elder abuse. RESULTS: One in five older persons in the study sample (nâ¯=â¯191; 21.3%) reported elder abuse, an increase of 83.6% from prevalence estimates before the pandemic. In the final models, sense of community emerged as a persistent protective factor for elder abuse (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.85-0.93). At the relational level, physical distancing was associated with reduced risk of elder abuse (OR: 0.94, 95% CI: 0.90-0.98). At the individual level, financial strain was associated with increased risk of abuse (OR: 1.08, 95% CI: 1.02-1.14). CONCLUSION: Health care professionals and policy makers must be prepared to address the increase in elder abuse associated with the evolving pandemic.
Empathic approaches in engineering capstone design projects: student beliefs and reported behaviour

Engineering design decisions have non-trivial implications, and empathic approaches are one way that engineers can understand and translate the perspectives of diverse stakeholders. Prior literatur...
Acute Effect of Herbs and Spices Intake on Endothelial Function and Metabolic Markers in Overweight or Obese Adults

Objectives Herbs and Spices (H/S) contain an array of bioactive compounds with purported health benefits. This study investigated the effect of acute H/S intake on vascular and metabolic health indicators, including flow-mediated vasodilation (FMD), glucose control and inflammatory markers over 24 h in overweight or obese individuals.
Could experience disconfirm the propositions of arithmetic

Critique de la these d'A. Casullo selon laquelle l'experience peut invalider les propositions arithmetiques telles que 2+2=4. Rejetant l'idee d'une independance entre la theorie arithmetique et nos procedures ordinaires de calcul, l'A. montre que l'argument de Casullo ne parvient a saper l'argument de l'irrefutabilite etabli par Mill, fonde sur les conditions de stabilite et d'exactitude du calcul.
Satiation, satiety and the daily intake pattern

Abstract: The present chapter describes the influence of satiety on intake as it occurs in the complex, multi-determinant environments where intake normally occurs. Rhythms, social facilitation, stomach contents, palatability, dietary density, restraint, and the built environment have all been shown to have significant, genetically affected, influences on intake, independent of each other and of the influence of satiety. Hence, in the real-world environments of humans, satiety appears to play a role affecting intake, but its impact is relatively small and embedded among a myriad of other factors.
Molecular methods for isolation of signal transduction pathway mutants

Publisher Summary This chapter reviews the methodology for Arabidopsis transformation, mutagenesis, and positive and negative genetic selections based on selectable marker gene cassettes. Several criteria need to be met for performing these types of molecular genetic studies in higher plants. The plant system chosen must be easily transformable and a good genetic organism. The signal transduction or developmental pathway under analysis should have well-defined downstream events that are manifested by tightly regulated transcriptional activation or repression. To isolate mutants that overexpressed CAB in the dark, 98,000 M2 seeds are screened. From these, 375 putative mutants are selected as hygromycin resistant. After rescreening for the expression of both reporter genes in the next few generations, eight mutants consistently shows longer hypocotyls on hygromycin-containing media and have higher GUS (β-glucuronidase) activity than the wild type in the dark. The experiments described in the chapter have identified at least seven new regulatory genes that control CAB gene expression under a variety of conditions.
State of the art: noninvasive imaging and management of neurovascular trauma

Neurotrauma represents a significant public health problem, accounting for a significant proportion of the morbidity and mortality associated with all traumatic injuries. Both blunt and penetrating injuries to cervicocerebral vessels are significant and are likely more common than previously recognized. Imaging of such injuries is an important component in the evaluation of individuals presenting with such potential injuries, made all the more important since many of the vascular injuries are clinically silent. Management of injuries, particularly those caused by blunt trauma, is constantly evolving. This article addresses the current state of imaging and treatment of such injuries.
Identification of epidermal growth factor receptor and its inhibitory microRNA141 as novel targets of Krüppel-like factor 8 in breast cancer.

// Tianshu Li 1, 2 , Heng Lu 1 , Debarati Mukherjee 1 , Satadru K. Lahiri 1 , Chao Shen 1, 3 , Lin Yu 1 , Jihe Zhao 1 1 Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL, USA 2 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA 3 College of Life Sciences, Wuhan University, Wuhan, China Correspondence to: Jihe Zhao, e-mail: Jihe.Zhao@ucf.edu Keywords: KLF8, EGFR, microRNA141, invasion and metastasis, breast cancer Received: March 17, 2015 Accepted: May 14, 2015 Published: May 27, 2015 ABSTRACT Kruppel-like factor 8 (KLF8) is a dual transcriptional factor critical for breast cancer progression. Epidermal growth factor receptor (EGFR) is frequently overexpressed in aggressive such as triple-negative breast cancer and associated with poor clinical outcomes. Here we report a novel KLF8-EGFR signaling axis in breast cancer. We identified a highly correlated co-overexpression between KLF8 and EGFR in invasive breast cancer cells and patient tumor samples. Overexpression of KLF8 in the non-tumorigenic MCF-10A cells induced the expression of EGFR, whereas knockdown of KLF8 from the MDA-MB-231 cells decreased it. Promoter activation and binding assays indicated that KLF8 promotes the EGFR expression by directly binding its gene promoter. We also revealed that KLF8 directly represses the promoter of miR141 and miR141 targets the 3′-untranslational region of EGFR transcript to inhibit EGFR translation. Treatment with the EGFR inhibitor AG1478 or overexpression of miR141 blocked the activity of ERK downstream of EGFR and inhibited KLF8-depndent cell invasiveness, proliferation and viability in cell culture and invasive growth and lung metastasis in nude mice. Conversely, overexpression of an inhibitory sponge of miR141 led to the opposite phenotypes. Taken together, these findings demonstrate a novel KLF8 to miR141/EGFR signaling pathway potentially crucial for breast cancer malignancy.
Chapter XV Evaluation of Growth by Physical and Chemical Means

Publisher Summary This chapter considers the evaluation of growth by physical and chemical means. All chemical and many physical techniques estimate the total amount of biological material. These methods can be converted into population estimates only by means of suitable calibrations, which, as will be seen, are accurate only for particular conditions. The chapter also presents general problem of accuracy versus precision. These two terms are variously defined in several more or less related ways. Accuracy is often referred to qualitatively as the difference between the meaning of a set of measurements and the true or actual value of the parameter under investigation. Stated slightly differently, accuracy is an index of the systematic error in a set of measurements. On the other hand, precision refers to the magnitude of the differences between the repeated measurements themselves without reference to the true value. Accuracy in the measurement of bacterial growth is subject to the same kinds of theoretical and practical problems as other types of analytical operations. In addition, turbidimetry-nephelometry is explained.
Authority, Status, and the Dynamics of Insider–Outsider Partnerships at the District Level

As school districts move toward systemic approaches to instructional reform, they are increasingly collaborating with outside organizations in this complex work. While emerging research touts the benefits of insider–outsider collaboration, we know little about the underlying processes by which partnerships are negotiated and maintained at the district level. Drawing on data from a longitudinal case study of a collaborative effort between an urban school district and a university-based research center, we investigate the role of authority and status in an insider–outsider partnership at the district level. We use conceptual tools from frame analysis and sociological theories of authority to describe the process by which authority and status relations develop. We then show that both authority and status shape how negotiation between insiders and outsiders unfolds. We argue that those with authority have a greater range of tools for negotiation and thus have greater influence. Status relations are important ...
PVODE, an ODE Solver for Parallel Computers

PVODE is a general-purpose solver for ordinary differential equation (ODE) systems that implements methods for both stiff and nonstiff systems. The code is designed for single-program multiple-data environments. It is written in ANSI standard C, with a highly modular structure. The version being distributed uses the message-passing interface (MPI) system for communication. In the stiff case, PVODE uses a backward differentiation formula method combined with preconditioned GMRES iteration. Parallelism is achieved by distributing the ODE solution vector into user-specified segments and parallelizing a set of vector kernels accordingly. For PDE-based ODE systems, we provide a module that generates a band block-diagonal preconditioner for use with the GMRES iteration. We also provide a set of interfaces to accommodate Fortran applications. The paper includes a stiff example problem and test results on a Cray-T3D with three different message-passing systems. PVODE is publicly available.
"Quantifying Bias in Social and Mainstream Media" by Yu-Ru Lin, James P. Bagrow, and David Lazer with Ching-man Au Yeung as coordinator

Social media, such as blogs, are often seen as democratic entities that allow more voices to be heard than the conventional mainstream media as well as a balancing force against the arguably slanted elite media. A systematic comparison between social and mainstream media is necessary but challenging due to the scale and dynamic nature of modern communication. We propose empirical measures to quantify the extent and dynamics of social (blog) and mainstream (news) media bias. We focus on a particular form of bias|coverage quantity|as applied to stories about the 111th US Congress. We compare observed coverage of Members of Congress against a null model of unbiased coverage, testing for biases with respect to political party, popular front runners, regions of the country, and more. Our measures suggest distinct characteristics in news and blog media. A simple generative model, in agreement with data, reveals differences in the process of coverage selection between the two media.
Optical monitoring of high power direct diode laser cladding

Abstract Laser cladding is one of the most advanced surface modification techniques which can be used to build and repair high-value components. High power direct diode laser (HPDDL) offers unique quality and cost advantages over other lasers (CO2, Nd:YAG). Especially its rectangular laser beam with top-hat intensity distribution makes HPDDL an ideal tool for large area cladding. In order to utilize this technique successfully, the development of on-line monitoring and process control is necessary. In this study, an optical monitoring system consisting of a high-speed CCD camera, a pyrometer, and an infrared camera was used to analyze the mass- and heat-transfer in the cladding process. The particle transport in flight was viewed by a high-speed CCD camera; the interaction between powder flow and laser beam was observed by an infrared camera; and the thermal behavior of the molten pool was recorded by the pyrometer and the infrared camera. The effects of the processing parameters on the laser attenuation, particle heating and clad properties were investigated based on the obtained signals. The optical monitoring method improved the understanding about mutual interrelated phenomena in the cladding process.
Nonparabolicity and exciton effects in two-photon absorption in zincblende semiconductors

Abstract The two-photon absorption coefficient is calculated from perturbation theory for direct-gap zincblende semiconductors using exact nonparabolic energies and matrix elements. The enhancement due to exciton effects is included. The results are compared to experiment and to other theories including the tunneling or Keldysh theory.
Polymer-induced membrane fusion: potential mechanism and relation to cell fusion events

Abstract Poly(ethylene glycol) (PEG) is used widely to mediate cell-cell fusion in the production of somatic cell hybrids and in the fusion injection of macromolecules into cultured cells from erythrocytes or liposomes. However, little is known about the mechanism by which PEG induces fusion of cell membranes, making its use much more an art than a science. This article considers possible molecular events involved in biomembrane fusion and summarizes what we have learned about these in recent years from studies of fusion of well-defined model membranes. In addition, it recounts observations made over the past several years about the process of PEG-mediated fusion of model membranes. These observations have defined the process to an extent sufficient to allow us to propose a model for the molecular events involved in the process. It is suggested that dehydration leads to asymmetry in the lipid packing pressure in the two leaflets of the membrane bilayer leading to formation of a single bilayer septum at a point of close apposition of two membranes. The single bilayer septum then decays during formation of the initial fusion pore. Agents that enhance or alleviate the dehydration-induced asymmetric packing stress will favor or inhibit fusion. Although the proposed picture is consistent with much accumulated data, it is not yet proven; experiments must now be devised to test its details. Finally, the proposed model is discussed in terms of potential implications for the mechanisms available to a cell in controlling more complex in vivo cell fusion processes such as endocytosis, exocytosis, protein sorting/transport, and viral budding/infection.
Effects of southern flying squirrels Glaucomys volans on red-cockaded woodpecker Picoides borealis reproductive success

Anecdotal data gathered from many populations suggest that southern flying squirrel (SFS, Glaucomys volans ) use of the endangered red-cockaded woodpecker's (RCW, Picoides borealis ) nest and roost cavities may negatively affect RCW populations. We conducted a controlled experiment to determine the effects of SFSs on RCW reproductive success. During the 1994 and 1995 breeding seasons, SFSs were removed from 30 RCW clusters and 32 clusters served as controls. SFSs were the most frequently encountered occupants of RCW cavities and used 20–33% of RCW cavities in control and treatment clusters over both years. Treatment groups produced significantly more successful nests (≥ 1 fledgling) than control groups in 1994. In 1995 however, there was no difference in the number of successful nests. In both years, RCW groups nesting in treatment clusters produced significantly more fledglings than groups in control clusters in each of four experimental areas, averaging approximately 0.7 additional fledglings per nesting group. Loss of entire clutches or broods, possibly as a result of predation or abandonment, was a major factor limiting reproduction in control groups in 1994. In contrast, differences in partial brood loss appeared to be the cause of differential fledging success in 1995. Usurpation of RCW roost cavities by SFSs may have placed greater energetic demands on RCWs for cavity defence or thermoregulation, thus reducing energy available for reproduction. Our results show that SFS use of RCW cavities during the breeding season has a significant impact on RCWs and that management of RCW populations should include activities that either minimize SFS populations in RCW clusters or limit access of SFSs to RCW cavities.
Understanding Mortality as a Quality Indicator After Esophagectomy

Background Postoperative death is an important outcome after esophagectomy, and the Centers for Medicare & Medicaid Services currently uses 30-day mortality as a quality indicator for this operation. However, 30-day mortality may underestimate a patient's true postoperative death risk. The purpose of this study was to evaluate different mortality definitions using a large registry of patients undergoing esophagectomy for cancer. Methods Data were extracted from the Surveillance, Epidemiology and End Results-Medicare registry for patients with esophageal cancer who underwent esophagectomy between 2006 and 2009. Postoperative death was compared using four different definitions: 30-day, in-hospital, perioperative (in-hospital or 30-day), and 90-day mortality. Hierarchical logistic regression models evaluated the association between patient and tumor characteristics with survival at 30 and 90 days and the ability of death to differentiate between good hospitals and those that perform poorly. Results We identified 634 patients from 188 hospitals. The 90-day mortality rate (13.3%) was more than double the 30-day mortality rate (6.0%) in this patient population. Advanced age and diagnosis of chronic obstructive pulmonary disease were associated with an increased risk of 90-day mortality. Good or poor performers could not be determined using the 30-day or 90-day mortality rate. Conclusions There are clinically meaningful differences between postoperative mortality definitions after esophagectomy. Thirty-day mortality significantly underestimates a patient's true risk of death because this number more than doubles at 90 days in this elderly, Medicare population. Although neither 90-day nor 30-day mortality are adequate quality measures after esophagectomy, 90-day mortality is a better outcome measure because it provides a better understanding of true death risk for the surgeon and patient.