cssi/SciSciGPT-SciSciNet huggingface dataset:
Permitting Protest: Parsing the Fine Geography of Dissent in America

The ability to dissent and to protest is a cornerstone of western liberal democracies. But dissent always threatens to exceed its bounds and to become a threat. The issue facing liberal states, then, has not only been how to incorporate dissent, but also how to shape dissent. In this project, the politics of public space has assumed a central role, as material public spaces have become a primary venue for the shaping of dissent. This article examines the ways in which dissent is incorporated into the liberal democratic state through a case study of protest in Washington, DC. In that city, as in others throughout North America and Western Europe, protest permit systems have evolved as a bureaucratic means to actively shape, if not directly control, public dissent. And yet, even as permit systems are becoming fully regularized, debates over their legitimacy suggest that geographically based permit systems might be inadequate to the task of incorporating dissent. As we indicate, recent protest activity shows just how important geography is to regulating, incorporating and policing dissent, even as those protests expose just how blunt and how fragile a tool that geography is. Pouvoir etre en desaccord et le manifester est l’une des pierres angulaires des democraties liberales occidentales. Pourtant, le desaccord risque toujours de depasser ses limites pour devenir une menace. La difficulte rencontree par les Etats liberaux n’etait pas tant d’integrer la divergence d’opinion que de la faconner. Dans ce projet, la politique d’espace public a joue un role central, les espaces publics physiques etant devenus un site primordial pour ce faconnage. Les methodes d’integration du desaccord dans l’Etat democratique liberal apparaissent a travers l’etude de cas de la protestation a Washington DC. La, comme dans d’autres villes d’Amerique du Nord et d’Europe de l’Ouest, les systemes d’autorisation de manifestation ont evolue en un moyen bureaucratique de faconner effectivement, si ce n’est maitriser directement, le dissentiment public. Pourtant, tandis que ces systemes se regularisent totalement, la mise en cause de leur legitimite suggere que les regimes d’autorisation de type geographique seraient inappropries pour integrer le desaccord. Recemment, l’activite de protestation a demontre l’importance de la geographie pour reguler, integrer et controler le dissentiment, meme si ces manifestations revelent aussi combien la geographie est un outil limite et fragile.
The ethics of clinical pathways and cost control.

You are the Chief of Vascular Surgery in a large community hospital that has been experiencing financial difficulties. Your division has been cited by the Utilization Review Committee for excessive lengths of stay in the ICU and hospital wards. After weeks of deliberations, with minimal input from surgeons, you are directed by the hospital Executive Committee to implement a fast-track clinical pathway for all patients undergoing major vascular procedures. Your staff surgeons believe that the data suggesting excessive lengths of stay are flawed and that the new directive may significantly increase postoperative morbidity and mortality. Your most responsible ethical action is which of the following?
Emotional State Impacts Center of Pressure Displacement Before Forward Gait Initiation

Emotional states influence whole-body movements during quiet standing, gait initiation, and steady state gait. A notable gap exists, however, in understanding how emotions affect postural changes during the period preceding the execution of planned whole-body movements. The impact of emotion-induced postural reactions on forthcoming posturomotor movements remains unknown. We sought to determine the influence of emotional reactions on center of pressure (COP) displacement before the initiation of forward gait. Participants (N = 23, 14 females) stood on a force plate and initiated forward gait at the offset of an emotional image (representing five discrete categories: attack, sad faces, erotica, happy faces, and neutral objects). COP displacement in the anteroposterior direction was quantified for a 2 second period during image presentation. Following picture onset, participants produced a posterior postural response to all image types. The greatest posterior displacement was occasioned in response to attack or threat stimuli compared with happy faces and erotica images. Results suggest the impact of emotional states on gait behavior begins during the motor planning period before the preparatory phase of gait initiation, and manifests in center of pressure displacement alterations.
Critical Role for Interferon Regulatory Factor 3 (IRF-3) and IRF-7 in Type I Interferon-Mediated Control of Murine Norovirus Replication

ABSTRACT Human noroviruses (HuNoV) are the major cause of epidemic, nonbacterial gastroenteritis in the world. The short course of HuNoV-induced symptoms has implicated innate immunity in control of norovirus (NoV) infection. Studies using murine norovirus (MNV) confirm the importance of innate immune responses during NoV infection. Type I alpha and beta interferons (IFN-α/β) limit HuNoV replicon function, restrict MNV replication in cultured cells, and control MNV replication in vivo . Therefore, the cell types and transcription factors involved in antiviral immune responses and IFN-α/β-mediated control of NoV infection are important to define. We used mice with floxed alleles of the IFNAR1 chain of the IFN-α/β receptor to identify cells expressing lysozyme M or CD11c as cells that respond to IFN-α/β to restrict MNV replication in vivo . Furthermore, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and overlapping antiviral responses to restrict MNV replication in vivo . IRF-3 and IRF-7 restrict MNV replication in both cultured macrophages and dendritic cells, are required for induction of IFN-α/β in macrophages but not dendritic cells, and are dispensable for the antiviral effects of IFN-α/β that block MNV replication. These studies suggest that expression of the IFN-α/β receptor on macrophages/neutrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses to NoV infection.
Computational methods in process optimisation: II. Variable recycle ratio or reactor length with bounded control

The work of Part I on the optimal design of a tubular reactor, in which a second-order reversible exothermic reaction is being conducted, with recycle of unconverted reactant, is here extended to the cases where either the residence time (reactor length) or the recycle ratio is not specified in advance. Bounds are imposed on the control variable, which is here the local heat transfer conductance from the cooling jacket to the reactor. A gradient technique in control space, accompanied by a search for the optimal switch points, was again effective. With this combined technique singular control arcs were located by the appearance of rapid oscillations of the switching variable. Le travail de la Partie 1 relatif a la conception la plus efficace d'un reacteur tubulaire dans lequel se fait une reaction isothermique, reversible et de second ordre, avec recyclage du reactif non transforme, est applique aux cas ou soit le temps de sejour moyen (en rapport avec la longueur du reacteur), soit le taux de recyclage n'est pas specifie d'avance. On impose des limites a la variable de contro'le qui, dans le cas present, est la conductivite de la transmission locale de la chaleur, de la chemise de refroi-dissement au reacteur. Une methode a base de gradient dans l'espace ou se fait le controle, accompagnee d'une etude des meilleurs points pour celui-ci, s'est averee de nouveau efficace. Gra'ce a cette technique combinee, on a pu localiser des arcs singuliers de contro'le au moyen de l'apparence d'oscillations rapides de la variable de contro'le.
An industrial application of Cleanroom software engineering-benefits through tailoring

Cleanroom is a set of software engineering principles that support the development of reliable software. The Systems group at Raytheon TI Systems, a SEI level 3 organization, successfully adopted Cleanroom into a pilot CMM level 5 project. The successful introduction of this technology was a result of the principles of Cleanroom being based on fundamental computer science foundations. As with any other methodology, a certain amount of tailoring was required for the technology to be most effective. Our tailoring approach was based on our project needs, our schedule constraints, and how comfortable we felt with the various components of the technology. The paper describes the tailoring approaches used for the insertion of Cleanroom and the pros and cons of the Cleanroom approach as described by practitioners using the technology day to day. The result of our approach is a model for software development that we feel is very effective at producing quality software.
Planning Future Strategies for Domestic and International NeuroAIDS Research, July 24–25, 2008

The National Institute of Mental Health in cooperation with the National Institute on Drug Abuse and the National Institute of Neurological Disorders and Stroke organized a meeting on July 24–25, 2008 to develop novel research directions for neuroAIDS research. The deliberations of this meeting are outlined in this brief report. Several critical research areas in neuroAIDS were identified as areas of emphasis. Opportunities for collaborations between large NIH-funded projects were also discussed.
Lightweight hyper-redundant binary elements for planetary exploration robots

Presents the design of a new lightweight, hyper-redundant, deployable binary robotic articulated intelligent device (BRAID), for space robotic systems. The BRAID element is intended to meet the challenges of future space robotic systems that need to perform more complex tasks than are currently feasible. It is lightweight, has a high degree of freedom and a large workspace. The device is based on embedded muscle type binary actuators and flexure linkages. Such a system may be used for a wide range of tasks, and requires minimal control computation and power resources.
Slow variations in continuum mechanics

Publisher Summary This chapter describes the slow variations in continuum mechanics. The hydraulic approximation is a simple and useful idea, which as the quasicylindrical approximation has its counterpart in other branches of mechanics. The key to treating a slow variation is to rescale the coordinates in different directions so that the variation formally becomes normal. This transfers the perturbation parameter from the boundary conditions to the differential equations, which can accordingly be simplified by approximation. It is remarkable that this simplification also renders the approximate solution uniformly valid. The method of slow variations has been applied mostly to thin two-dimensional shapes in the plane, or slender axisymmetric ones in three dimensions.. It is found that axisymmetric problems of slow variation can be treated in exactly the same way as symmetric plane problems, and the results have a similar structure.
EXPERIENTIAL AVOIDANCE AND FORGIVENESS AS MEDIATORS IN THE RELATION BETWEEN TRAUMATIC INTERPERSONAL EVENTS AND POSTTRAUMATIC STRESS DISORDER SYMPTOMS

The present study investigates experiential avoidance and forgiveness, two general response styles to emotional distress that may impact reactions to trauma exposure, as potential mediators of the link between interpersonal trauma exposure and Posttraumatic Stress Disorder (PTSD) symptoms in a cross–sectional survey of 229 undergraduate students reporting interpersonal trauma exposure. Utilizing structural equation modeling techniques, both constructs were found to significantly partially mediate the relation between interpersonal trauma exposure and PTSD symptoms; experiential avoidance reduced the relation between interpersonal trauma exposure and PTSD symptoms by 22% while forgiveness reduced this relation by 14%. Thus, individuals who were lower in forgiveness and higher in experiential avoidance reported higher PTSD symptoms than those higher in forgiveness and lower in experiential avoidance. Implications for treatment and prevention of PTSD symptoms are discussed.
Approximate solution of initial-boundary wave equation problems by boundary-value techniques

A new boundary-value technique is proposed for the treatment of initial-boundary-value problems for linear and mildly non-linear wave equations. Several illustrative examples are offered to demonstrate the ease with which the method can be applied.
Laser Doppler flowmetry for measurement of laminar capillary blood flow in the horse

Current methods for in vivo evaluation of digital hemodynamics in the horse include angiography, scintigraphy, Doppler ultrasound, electromagnetic flow and isolated extracorporeal pump perfused digit preparations. These techniques are either non-quantifiable, do not allow for continuous measurement, require destruction of the horse orare invasive, inducing non- physiologic variables. In vitro techniques have also been reported for the evaluation of the effects of vasoactive agents on the digital vessels. The in vitro techniques are non-physiologic and have evaluated the vasculature proximal to the coronary band. Lastly, many of these techniques require general anesthesia or euthanasia of the animal. Laser Doppler flowmetry is a non-invasive, continuous measure of capillary blood flow. Laser Doppler flowmetry has been used to measure capillary blood flow in many tissues. The principle of this method is to measure the Doppler shift, that is, the frequency change that light undergoes when reflected by moving objects, such as red blood cells. Laser Doppler flowmetry records a continuous measurement of the red cell motion in the outer layer of the tissue under study, with little or no influence on physiologic blood flow. This output value constitutes the flux of red cells and is reported as capillary perfusion units. No direct information concerning oxygen, nutrient or waste metabolite exchange in the surrounding tissue is obtained. The relationship between the flowmeter output signal and the flux of red blood cells is linear. The principles of laser Doppler flowmetry will be discussed and the technique for laminar capillary blood flow measurements will be presented.© (1998) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
A fractal investigation of solute travel time in a heterogeneous aquifer: transition probability/Markov chain representation

Solute transport behavior in heterogeneous type structures is generally assessed in terms of its basic statistical properties, such as mean, variance, and correlation. With increasing evidence that the solute transport process in subsurface aquifers exhibits some degree of order at multiple scales (i.e. fractal or scaling), it is crucial to investigate if random representations of aquifers could also explain fractal solute transport behavior. Here, we investigate transport processes that occur in first order Markov chain-type aquifer structures, defined by transition probabilities between constituent hydrofacies. Markov chain structures possess certain advantages with respect to data requirements when compared to traditional Gaussian approaches. The statistical moment scaling function method is employed to investigate solute travel times. The results indicate the potential presence of multi-fractal behavior in the solute transport process, revealing the ability of the transition probability/Markov chain (TP/MC) approach to represent aquifer structures that give rise to fractal solute transport. A sensitivity analysis of the solute transport behavior to the four principal hydrostratigraphic parameters in the TP/MC approach indicates that the degree of fractality increases with an increase in: (1) the number of facies; (2) the volume proportions of the coarse sediments; (3) the dip to vertical mean length ratio; and (4) the order of bedding sequences.
Phagocytosis of insect haemocytes as a new alternative model

Phagocytosis is an important function of both insect haemocytes and mammalian blood cells. Linden bugs and cotton leaf worms have been suggested as new alternative models for ecological and drug toxicology but no data on their haemocyte physiology have been published. Our assays with particle ingestion of the NBT test were carried out on prohaemocytes, granulocytes, plasmatocytes and spherulocytes of adult linden bug and cotton leaf worm larvae. We found that phagocytic activity is on average 10% in the linden bug, and 50% in cotton leaf worm haemocytes: the phagocytic index is 3.5 in both species and nitroblue tetrazolium reduction is 0.5 in the linden bug and 3.2 in the cotton leaf worm. Phagocytic charactersitics of the prohaemocytes and granulocytes in the cotton leaf worm are closed to mammalian neutrophil physiology. Our data suggest that cotton leaf worm haemocytes may be a new potential alternative model for screening of phagocytosis.
Unveiling wild-type transthyretin cardiac amyloidosis as a significant and potentially modifiable cause of heart failure with preserved ejection fraction

This editorial refers to ‘Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction’, by F. Gonzalez-Lopez et al ., on page doi:10.1093/eurheartj/ehv338. Heart failure with a normal or preserved ejection fraction (HFnEF/HFpEF) is a heterogeneous clinical syndrome without proven treatments. Numerous biological mechanisms have been implicated in the genesis of HFnEF/HFpEF and include intrinsic cardiomyocyte stiffness related to abnormal calcium homeostasis, and cytoskeletal and extracellular matrix (ECM) abnormalities. Given the lack of efficacy of pharmacological therapies, there is a growing emphasis on how co-morbidities influence the development of this clinical syndrome,1 with an emerging hypothesis that co-morbidities drive its phenotypic expression.2 Characterization of HFnEF/HFpEF stratified by aetiological subgroups may therefore identify relevant cohorts for investigation and treatable pathophysiological mechanisms.3 Figure 1 Screening and treatment paradigm for unveiling transthyretin amyloid (ATTR) as a potentially modifiable cause of heart failure with preserved ejection fraction (HFpEF). The diagnosis of TTR cardiac amyloidosis among patients hospitalized with heart failure ( A ) can be ascertained using technetium 99 m bone tracers ( B ) so that emerging therapies may …
Quality of Administrative Provisions for Physical Education in New York State

Abstract In this study, there were examined the relationships between the quality of the non-instructional provisions for physical education in 100 secondary schools of New York State and factors involving size of school, wealth of community, and training and experience of the physical education director. The quality of the provisions was more closely related to wealth of the community than to any other factor. Secondary schools enrolling less than 200 pupils tended to lack essential provisions. Amount of training of the director was more closely related to the quality of provisions than amount of experience.
Unsupervised Learning Techniques for Detection of Regions of Interest in Solar Images

Identifying regions of interest (ROIs) in images is a very active research problem as it highly depends on the types and characteristics of images. In this paper we present a comparative evaluation of unsupervised learning methods, in particular clustering, to identify ROIs in solar images from the Solar Dynamics Observatory (SDO) mission. With the purpose of finding regions within the solar images that contain potential solar phenomena, this work focuses on describing an automated, non-supervised methodology that will allow us to reduce the image search space when trying to find similar solar phenomenon between multiple sets of images. By experimenting with multiple methods, we identify a successful approach to automatically detecting ROIs for a more refined and robust search in the SDO Content-Based Image-Retrieval (CBIR) system. We then present an extensive experimental evaluation to identify the best performing parameters for our methodology in terms of overlap with expert curated ROIs. Finally we present an exhaustive evaluation of the proposed approach in several image retrieval scenarios to demonstrate that the performance of the identified ROIs is very similar to that of ROIs identified by dedicated science modules of the SDO mission.
Us and Them: The Unequal Allocation of Resources in Domestic and International Criminal Investigations

The crimes typically investigated by the International Criminal Court (ICC) are at least as grave and complex as the most serious mass atrocity crimes investigated by states. Yet a comparison of the investigative resources available to the ICC and the investigative resources committed to domestic investigations of mass atrocities shows that national governments are willing to devote vastly more resources to domestic investigations. There is also a stark difference in the way states talk about national and international investigations. The rhetoric of national responses to mass atrocities usually involves a commitment to “make every effort,” “pursue every lead,” and “use all means at our disposal” to bring those responsible to justice. In contrast, while most states are generally supportive of the idea of the ICC, their rhetoric often changes dramatically when it comes to discussions about funding the Court. Some of the states that have been most supportive of the Court in their public statements have vigorously opposed attempts to increase the ICC’s budget to adequately fund its investigations.This Article draws three principal conclusions from its analysis. First and most importantly, the ICC is enormously under-resourced compared to domestic mass atrocity investigations. Second, this lack of resources is at least partly to blame for some of the difficulties the ICC has encountered. The ICC would probably be more successful if it had more resources. Third and finally, some of the ICC’s strongest supporters, like Britain and France, are being hypocritical and discriminatory by opposing any increase in the ICC’s investigative capacity while simultaneously devoting nearly unlimited resources to their own domestic mass atrocity investigations.
Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium

Purpose Lipofuscin (LF) accumulation within RPE cells is considered pathogenic in AMD. To test whether LF contributes to RPE cell loss in aging and to provide a cellular basis for fundus autofluorescence (AF) we created maps of human RPE cell number and histologic AF. Methods Retinal pigment epithelium-Bruch's membrane flat mounts were prepared from 20 donor eyes (10 ≤ 51 and 10 > 80 years; postmortem: ≤4.2 hours; no retinal pathologies), preserving foveal position. Phalloidin-binding RPE cytoskeleton and LF-AF (488-nm excitation) were imaged at up to 90 predefined positions. Maps were assembled from 83,330 cells in 1470 locations. From Voronoi regions representing each cell, the number of neighbors, cell area, and total AF intensity normalized to an AF standard was determined. Results Highly variable between individuals, RPE-AF increases significantly with age. A perifoveal ring of high AF mirrors rod photoreceptor topography and fundus-AF. Retinal pigment epithelium cell density peaks at the fovea, independent of age, yet no net RPE cell loss is detectable. The RPE monolayer undergoes considerable lifelong re-modeling. The relationship of cell size and AF, a surrogate for LF concentration, is orderly and linear in both groups. Autofluorescence topography differs distinctly from the topography of age-related rod loss. Conclusions Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD.
Cuffed Endotracheal Tubes in Infants and Children A Technique to Ensure an Acceptable Intracuff Pressure

Background. Over the past 5 to 10 years, there has been a change in the clinical practice of pediatric anesthesiology with a transition to the use of cuffed instead of uncuffed endotracheal tubes (ETTs) in infants and children. When such tubes are used in clinical practice, it is imperative to ensure that the intracuff pressure is ≤30 cm H2O. To date, there are limited data regarding techniques to ensure this practice. Methods. Following endotracheal intubation with a cuffed ETT, a stethoscope was placed in the sternal notch and continuous positive airway pressure of 20 to 25 cm H2O held. The fresh gas flow was increased as needed to achieve a gradual rise of the airway pressure. Using a syringe, air was added to the cuff until no air escape or leak was heard. The intracuff pressure was checked using a handheld manometer (Posey Cufflator Endotracheal Tube Inflator and Manometer, JT Posey Company, Arcadia, CA). Results. The cohort for the study included 200 patients ranging in age from 6 months to 18 years...
Fracture analysis of matrix microcracking in composite laminates

A microcracking model which is based on the principle of stationary complementary energy has been developed to study the microcracking behavior of ((S)/90n)S laminates, where (S) is any supporting sublaminate. In this model, an assumption that the longitudinal normal stresses in both the supporting sublaminate and 90-deg ply group are functions of both x and z coordinates is made. Such a model can be used to calculate the energy release rate for formation of a completely new microcrack and thus can be used to estimate the microcrack (intralaminar) fracture toughness of the composite material. The upper bound of the compliance and the lower bound of the effective (reduced) modulus can also be obtained from this model. (Author)
Metabolic half-life of somatostatin and peptidase activities are altered in Alzheimer's disease.

Several reports have described decreased immunoreactive somatostatin levels in specific regions of post-mortem brain tissue from patients diagnosed with senile dementia of the Alzheimer type (SDAT). In an attempt to determine if the metabolism of somatostatin is also altered as a result of SDAT, we examined the regional metabolic half-life of somatostatin-28 (SS-28) and somatostatin-14 (SS-14). The activity of the following peptidases was also determined: neutral endopeptidase E.C. 3.4.24.11; metalloendopeptidase E.C. 3.4.24.15; carboxypeptidase E (E.C. 3.4.17.10); and trypsin-like serine protease. The metabolic half-life of SS-28 was significantly reduced in post-mortem Brodmann Area 22 of SDAT tissue. This decrease in SS-28 metabolic half-life was correlated with a significant increase in trypsin-like serine protease activity in the same SDAT brain region. The formation rate of SS-14 from SS-28 incubated with Brodmann Area 22 homogenates was also increased in SDAT tissues as compared to controls. A regional variation in neutral endopeptidase E.C. 3.4.24.11 was also noted in both controls and SDAT samples. Although postmortem intervals of samples varied significantly, no effect was seen on any biochemical parameter measured. Results from this study provide evidence that a correlation can be made between changes in metabolic half-life somatostatin and alterations in neuropeptidase activities due to SDAT. As these data show alterations in both proteolytic metabolism and peptidase activities, many other biologically active peptide substrates could also be affected in SDAT.
THE MOLECULAR BASIS OF INHERITED DISORDERS OF THE GASTROINTESTINAL AND HEPATOBILIARY TRACTS: An Update on Recent Progress

In this article, genetic disorders of the gastrointestinal and hepatobiliary tracts ranging from common to very rare are reviewed. The first portion of each section highlights the clinical manifestations of the disorder; the second and more detailed portion of each section discusses what is currently known about the biology and genetics of the disorder. The potential use of gene therapy to treat many of these disorders is also reviewed.
Influenza-Associated Encephalitis/Encephalopathy

The role of influenza A and influenza B in acute childhood encephalitis and encephalopathy (ACE) was evaluated prospectively in all children admitted to the Hospital for Sick Children, Toronto, Canada, during an 11-year period from Jan 1994- Dec 2004.
Associations between health literacy and preventive health behaviors among older adults: findings from the health and retirement study

While the association between inadequate health literacy and adverse health outcomes has been well documented, less is known about the impact of health literacy on health perceptions, such as perceptions of control over health, and preventive health behaviors. We identified a subsample of participants (N = 707) from the Health and Retirement Study (HRS), a nationally representative sample of older adults, who participated in health literacy testing. Self-reported health literacy was measured with a literacy screening question, and objective health literacy with a summed score of items from the Test of Functional Health Literacy. We compared answers on these items to those related to participation in health behaviors such as cancer screening, exercise, and tobacco use, as well as self-referencing health beliefs. In logistic regression models adjusted for gender, education, race, and age, participants with adequate self-reported health literacy (compared to poorer levels of health literacy) had greater odds of participation in mammography within the last 2 years (Odds ratio [OR] = 2.215, p = 0.01) and participation in moderate exercise two or more times per week (OR = 1.512, p = 0.03). Participants with adequate objective health literacy had reduced odds of participation in monthly breast self-exams (OR = 0.369, p = 0.004) and reduced odds of current tobacco use (OR = 0.456, p = 0.03). In adjusted linear regression analyses, self-reported health literacy made a small but significant contribution to explaining perceived control of health (β 0.151, p = <0.001) and perceived social standing (β 0.112, p = 0.002). In a subsample of older adult participants of the HRS, measures of health literacy were positively related to several health promoting behaviors and health-related beliefs and non-use of breast self-exams, a screening behavior of questionable benefit. These relationships varied however, between self-reported and objectively-measured health literacy. Further investigation into the specific mechanisms that lead higher literacy people to pursue health promoting actions appears clearly warranted.
HER2 expression identifies dynamic functional states within circulating breast cancer cells

Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER+/HER2- primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2. Cultured circulating tumour cells maintain discrete HER2+ and HER2- subpopulations: HER2+ circulating tumour cells are more proliferative but not addicted to HER2, consistent with activation of multiple signalling pathways; HER2- circulating tumour cells show activation of Notch and DNA damage pathways, exhibiting resistance to cytotoxic chemotherapy, but sensitivity to Notch inhibition. HER2+ and HER2- circulating tumour cells interconvert spontaneously, with cells of one phenotype producing daughters of the opposite within four cell doublings. Although HER2+ and HER2- circulating tumour cells have comparable tumour initiating potential, differential proliferation favours the HER2+ state, while oxidative stress or cytotoxic chemotherapy enhances transition to the HER2- phenotype. Simultaneous treatment with paclitaxel and Notch inhibitors achieves sustained suppression of tumorigenesis in orthotopic circulating tumour cell-derived tumour models. Together, these results point to distinct yet interconverting phenotypes within patient-derived circulating tumour cells, contributing to progression of breast cancer and acquisition of drug resistance.
Informed Consent, Body Property, and Self-Sovereignty:

Recent cases involving biosamples taken from indigenous tribes and newborn babies reveal the emptiness of informed consent. This venerable doctrine often functions as a charade, a collective fiction which thinly masks the uncomfortable fact that the subjects of human research are not actually afforded full information regarding the types of research that may be contemplated, nor do they provide meaningful consent. But if informed consent fails to provide adequate protection to the donors of biological materials, why not turn to principles of property law? Property is power, yet current law permits everyone except for those who donate biological materials to possess property rights. The reluctance to invoke property probably stems from fears of resurrecting slavery and the commodification of human beings. But ironically, avoidance of property transforms the subjects of human research into objects that can be owned only by others, resulting in new forms of oppression and exploitation. Human research subjects are autonomous individuals who should not only possess the power to contribute their biological materials, but also the right to help control the course of research, and to share in the resulting benefits or profits. Conferring body property might enable research subjects to regain power and a measure of self-sovereignty.
The Effect of Medical Student Volunteering in a Student-Run Clinic on Specialty Choice for Residency.

Introduction: Student-run free clinics (SRFCs) are a recent popular addition to medical school education, and a subset of studies has looked at the influence of SRFC volunteering on the medical student’s career development. The majority of the research done in this area has focused on understanding if these SRFCs produce physicians who are more likely to practice medicine in underserved communities, caring for the uninsured. The remainder of the research has investigated if volunteering in an SRFC influences the specialty choice of medical school students. The results of these specialty choice studies give no definitive answer as to whether medical students chose primary or specialty care residencies as a result of their SRFC experience. Keeping Neighbors in Good Health through Service (KNIGHTS) is the SRFC of the University of Central Florida College of Medicine (UCF COM). Both primary and specialty care is offered at the clinic. It is the goal of this study to determine if volunteering in the KNIGHTS SRFC influences UCF COM medical students to choose primary care, thereby helping to meet the rising need for primary care physicians in the United States. Methods: A survey was distributed to first, second, and third-year medical students at the UCF COM to collect data on demographics, prior volunteering experience, and specialty choice for residency. Responses were then combined with records of volunteer hours from the KNIGHTS Clinic and analyzed for correlations. We analyzed the frequency and Pearson’s chi-squared values. A p value of less than 0.05 was considered statistically significant. Results: Our survey had a total response rate of 39.8%. We found that neither the act of becoming a KNIGHTS Clinic volunteer nor the hours volunteered at the KNIGHTS Clinic influenced the UCF COM student’s choice to enter a primary care specialty (p = NS). Additionally, prior volunteering/clinical experience or the gender of the medical school student did not influence a student’s choice to volunteer at the KNIGHTS Clinic. Discussion: Volunteering at KNIGHTS Clinic did not increase student choice to enter primary care, with students choosing other specialties at equal rates, probably due to the variety of specialties present at the KNIGHTS Clinic. This suggests that the volunteer attending physicians present at an SRFC may influence the choice of residency for students. It also suggests that SFRCs are not a viable tool to increase the number of primary care doctors in the United States.
More misinformation on breast cancer screening

There are now three papers denigrating the value of mammography screening that should have never passed peer review, but have been published in the prestigious New England Journal of Medicine (NEJM) (1-3). The papers falsely claimed that mammography has had little effect on breast cancer in the U.S. while also falsely claiming that mammography screening was leading to massive “overdiagnosis” of breast cancers that would have regressed or disappeared had they not been detected by screening. They are all based on scientifically unsupportable estimates as to what the incidence of breast cancer would have been had screening not begun in the United States in the mid 1980’s.
Results of a Randomized Phase 2 Study of Clofarabine Plus Cytarabine (CA) Vs Clofarabine Plus Idarubicin (CI) Vs Clofarabine, Idarubicin, Plus Cytarabine (CIA) as Salvage Therapy in Acute Myeloid Leukemia (AML).

Clofarabine is a second-generation deoxyadenosine analog with activity in adult AML. To improve single agent activity, various combinations of clofarabine are being studied. In two dose-finding phase I studies, we have previously established the MTD and DLT of the CI and CIA combinations in AML salvage (Blood2006; 108: 51a). Here we report the outcome of a subsequent adaptively (Bayesian) randomized phase 2 study comparing the two anthracycline-containing combinations CI and CIA with CA. Eligible were patients (pts) for first salvage therapy with first relapse or primary refractory AML. Drug doses and schedules were as follows: CI - clofarabine 22.5 mg/m 2 iv d 1–5 and idarubicin 10 mg/m 2 iv d 1–3; CIA – clofarabine 22.5 mg/m 2 iv d 1–5, idarubicin 6 mg/m 2 iv d 1–3, cytarabine 0.75 g/m 2 d 1–5; CA - clofarabine 40 mg/m 2 iv d 1–5 and cytarabine 1g/m 2 iv d 1–5. Up to 2 induction and 4 consolidation cycles were allowed. Eighty-five patients were enrolled of whom 80 are evaluable. Pretreatment characteristics were similar with respect to median age (CI 57 yrs [range 25–73], CIA 56 [21–81], CA 55 [39–73]), proportion of pts with secondary AML (CI 33%, CIA 28%, CA 29%), proportion of pts with primary refractory disease (CI 31%, CIA 50%, CA 41%), prior median CR duration (CI 6 mos [1–108], CIA 6 [1–18], CA 10 [2–27]), prior exposure to at least intermediate doses of cytarabine (CI 78%, CIA 63%, CA 65%), and proportion of pts with FLT3/ITD abnormalities (CI 25%, CIA 17%, CA 18%). Thirty-three pts received CI, 31 CIA, and 16 CA. Overall, 31 (39%) pts responded (28% CR, 9% CRp). No difference in response was observed according to treatment arm (CI - CR 27%, CRp 12%; CIA - CR 29%, CRp 13%; CA - CR 25%, CRp 6%). Median CR duration was 6.4 mos (0.2–18) with CI, and not reached (1–12+) with CIA and CA (0.3–24) (p=0.07). Overall survival was 5.5 mos (0.3–25.5+) for CI, 5.1 mos (0.4– 13.4+) for CIA, and 5.1 mos (0.4–27+) for CA (p=0.94). Adverse events were comparable to the preceding phase 1 studies and as have been described with clofarabine in the past. Induction deaths occurred in 6% (CI), 16% (CIA), and 25% (CA), respectively (p>.05), and were due to myelosuppression-associated infectious complications. In summary, the response rate of the clofarabine combinations in AML salvage is 39% (CR+CRp). Response duration and overall survival are not significantly different between the treatment arms.
Proclaiming the reign of God in a suffering world: The movement from development to liberation:

Today’s missionary, whether long-term or short-term, church-based or part of a faith-based NGO, is faced with grinding poverty and the extreme isolation and marginalization of vulnerable population...
The relative utilities of genome-wide, gene panel, and individual gene sequencing in clinical practice

Advances in technology that have transpired over the past 2 decades have enabled the analysis of cancer samples for genomic alterations to understand their biologic function and to translate that knowledge into clinical practice. With the power to analyze entire genomes in a clinically relevant time frame and with manageable costs comes the question of whether we ought to and when. This review focuses on the relative merits of 3 approaches to molecular diagnostics in hematologic malignancies: indication-specific single gene assays, gene panel assays that test for genes selected for their roles in cancer, and genome-wide assays that broadly analyze the tumor exomes or genomes. After addressing these in general terms, we review specific use cases in myeloid and lymphoid malignancies to highlight the utility of single gene testing and/or larger panels.
The Analysis of U.S. FBR R&D Program Dynamics to Maintain the Technological Capability

Abstract The mechanism to maintain the technological capability of Fast Breeder Reactor (FBR) technologies in the United States, after the cancelation of Clinch River Breeder Reactor(CRBR) project, is analyzed. The analytical framework and the necessary conditions to maintain the technological capability are identified. It is found that a large scale demonstration project is not essential to maintain a technological capability, and despite the steep budget cut in FBR R&D programs, its technological capability has been successfully maintained. The lessons for Japanese FBR program are also discussed.
Space Environments and Survivability

Just as spacecraft design teams are increasingly approaching the design and construction of a spacecraft as an integrated system, the overall environment and survivability of the spacecraft should be approached in a similar fashion. Typically perceived as either too expensive or design limiting, design for environmental survivability, whether it be from thermal, radiation, atomic oxygen, or spacecraft charging effects, is usually done strictly on an ad hoc basis. Unfortunately, ‘faster, better, cheaper’ (FBC) missions seldom consider anything much beyond thermal effects and, independently, radiation effects on selected parts.
Customer Characteristics and Shopping Patterns Associated with Healthy and Unhealthy Purchases at Small and Non-traditional Food Stores

Small and non-traditional food stores (e.g., corner stores) are often the most accessible source of food for residents of lower income urban neighborhoods in the U.S. Although healthy options are often limited at these stores, little is known about customers who purchase healthy, versus less healthy, foods/beverages in these venues. We conducted 661 customer intercept interviews at 105 stores (corner stores, gas marts, pharmacies, dollar stores) in Minneapolis/St. Paul, Minnesota, assessing all food and beverage items purchased. We defined three categories of "healthy" and four categories of "unhealthy" purchases. Interviews assessed customer characteristics [e.g., demographics, body-mass index (BMI)]. We examined associations between healthy versus unhealthy purchases categories and customer characteristics. Overall, 11% of customers purchased ≥1 serving of healthy foods/beverages in one or more of the three categories: 8% purchased fruits/vegetables, 2% whole grains, and 1% non-/low-fat dairy. Seventy-one percent of customers purchased ≥1 serving of unhealthy foods/beverages in one or more of four categories: 46% purchased sugar-sweetened beverages, 17% savory snacks, 15% candy, and 13% sweet baked goods. Male (vs. female) customers, those with a lower education levels, and those who reported shopping at the store for convenience (vs. other reasons) were less likely to purchase fruits/vegetables. Unhealthy purchases were more common among customers with a BMI ≥30 kg/m2 (vs. lower BMI). Results suggest intervention opportunities to increase healthy purchases at small and non-traditional food stores, particularly interventions aimed at male residents, those with lower education levels and residents living close to the store.
Agent-based network model predicts strong benefits to youth-centered HIV treatment-as-prevention efforts

We used an agent-based network model to examine the effect of targeting different risk groups with unsuppressed HIV viral load for linkage or re-linkage to HIV-related treatment services in a heterosexual population with annual testing. Our model identifies prevention strategies that can reduce incidence to negligible levels (i.e., less than 0.1 infections per 100 person-years) 20 years after a targeted Treatment-as-Prevention (TasP) campaign. The model assumes that most (default 95%) of the population is reachable (i.e., could, in principle, be linked to effective care) and a modest (default 5% per year) probability of a treated person dropping out of care. Under random allocation or CD4-based targeting, the default version of our model predicts that the TasP campaign would need to suppress viral replication in ~80% of infected people to halt the epidemic. Under age-based strategies, by contrast, this percentage drops to 50% to 60% (for strategies targeting those
Enhancing research careers: an example of a US national diversity-focused, grant-writing training and coaching experiment.

Preparing a successful research proposal is one of the most complex skills required of professional scientists, yet this skill is rarely if ever, taught. A major goal of the National Research Mentoring Network (NRMN) in the United States (U.S.) is to support the professional advancement of postdoctoral fellows and junior faculty from diverse populations by offering intensive coaching in the development of grant proposals early in their careers. This article highlights the National Institutes of Health’s (NIH) NRMN initiative to prepare diverse constituencies of early-stage biomedicine scientists for research careers by implementation of an evidence-based nationwide program of comprehensive grant writing and professional development. NRMN delivers four unique but complementary coaching models: the Proposal Preparation Program from the University of Minnesota (UMN); Grantwriters Coaching Groups from Northwestern University (NU); Grantwriting Uncovered: Maximizing Strategies, Help, Opportunities, Experiences from the University of Colorado Anschutz Medical Campus (UC) and Washington State University (WSU); and Steps Towards Academic Research from the University of North Texas Health Science Center (UNTHSC). Because these programs cater to scientists at different career stages, rather than employ a single approach, each is uniquely tailored to test its efficacy at the national level. The first two models prioritize scientists with reasonably well-developed research projects who are ready to write proposals for specific NIH research competitions. The other two models target postdoctoral fellows and early-career faculty who need more extensive guidance in proposal development plans. To achieve scalability, all programs also recruit faculty as Coaches-in-Training to learn approaches and acquire particular group facilitation skills required by each model. These efforts exemplify NRMN’s potential to enhance the career development of diverse trainees on a national scale, building research skills, competitiveness for obtaining faculty positions and capacities that will result in high quality research proposals from a diverse pool of applicants, thereby advancing innovations in science and diversifying the U.S. biomedical workforce.