cssi/SciSciGPT-SciSciNet huggingface dataset:
A single 1-h session of moderate-intensity aerobic exercise does not modify lipids and lipoproteins in normolipidemic obese women.

The purpose of this study was to quantify the effects of a single session of aerobic exercise on lipids and lipoproteins in women who were sedentary and obese. Women (n = 12) who were premenopausal...
The Selective Serotonin-2A Receptor Antagonist M100907 Reverses Behavioral Deficits in Dopamine Transporter Knockout Mice

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.
Bladder neck-sparing modification of radical prostatectomy adversely affects surgical margins in pathologic T3a prostate cancer

Abstract Objectives. To determine whether the bladder neck-sparing (BNS) modification of radical retropubic prostatectomy (RRP) alters the likelihood of positive surgical margins and postsurgical prostate cancer recurrence. Methods. Surgical outcomes, as measured by pathologic margin status and progression-free survival, were evaluated in 751 consecutive RRP cases, among whom 222 underwent BNS technique. To reduce selection bias, comparison of positive margin rates between BNS and standard RRP was stratified by pathologic stage. Differences in surgical margin rates were assessed using the chi-square test, and effects of bladder neck preservation on prostate-specific antigen (PSA)-free survival were assessed, using multivariable Cox proportional hazards analysis. Results. The clinical stage, Gleason score, and preoperative serum PSA profiles were similarly distributed between patients undergoing standard RRP and those undergoing the BNS modification. Surgical margins in the unstratified entire cohort were positive at rates similar to prior reports (28% BNS, 27% standard RRP). However, stratification by pathologic stage revealed that among pT3a cancers, BNS surgery was associated with significantly higher rates of positive surgical margins than was standard RRP (47% versus 20%; chi- square = 6.32, P = 0.01). Differences in positive margin rates were not seen between the two groups at other pathologic stages. The adverse effect of BNS technique on pT3a surgical margins was associated with a trend toward an adverse effect on PSA-free survival (Cox proportional hazards P = 0.016). Conclusions. The BNS modification of RRP can be associated with an increased rate of positive surgical margins specifically in cancers that have focally penetrated through the prostatic capsule (pT3a), with an associated trend toward decreased PSA-free survival in this group. BNS surgery may, therefore, compromise the ability to completely remove a subset of cancers focally penetrating the prostatic capsule.
Oceanic CO2 system: An evaluation of ten methods of investigation

ABsTRAcr By combining two or more of the parameters pH, carbonate alkalinity, total carbon dioxide, and partial pressure of carbon dioxide, six equations can be obtained to express the concentration of carbonic acid that include molecular carbon dioxide, ten equations for bicarbonate ion, and eleven equations for carbonate ion concentrations. When the presentday analytical precision and the normal oceanic variances of the above four parameters are considered, the pH-partial pressure of carbon dioxide combination is the most promising to study the oceanic COz system.
Fast and robust interface generation for ubiquitous applications

We present Supple, a novel toolkit which automatically generates interfaces for ubiquitous applications. Designers need only specify declarative models of the interface and desired hardware device and Supple uses decision-theoretic optimization to automatically generate a concrete rendering for that device. This paper provides an overview of our system and describes key extensions that barred the previous version (reported in [3]) from practical application. Specifically, we describe a functional modeling language capable of representing complex applications. We propose a new adaptation strategy, split interfaces, which speeds access to common interface features without disorienting the user. We present a customization facility that allows designers and end users to override Supple's automatic rendering decisions. We describe a distributed architecture which enables computationally-impoverished devices to benefit from Supple interfaces. Finally, we present experiments and a preliminary user-study that demonstrate the practicality of our approach.
The role of marine aquaculture in meeting the future demand for animal protein

Farm-raised seafood is expected to play a major role in meeting the future demand for animal protein; however, the growth of marine aquaculture as currently practiced is constrained by space, economics and environmental concerns. For aquaculture to continue to expand, the potential of farming offshore ocean waters must be explored. Over the past decade, there has been worldwide interest in exploring the potential for offshore production, and the USA has emerged as one of the leaders in developing and demonstrating technologies for farming in the open ocean culture. Offshore research and development projects in New Hampshire, Hawaii and Puerto Rico have led to small-scale commercial production, demonstrating that open ocean culture is indeed feasible and has great potential for future expansion. Despite the evidence that offshore farming is possible, a number of technical, economic and political challenges must be addressed before large-scale production can be realized.
Brooding and Reflection as Explanatory of Depressive Symptoms in Adolescents Experiencing Stressful Life Events

Delineating etiologic mechanisms of adolescent-onset depressive disorders has implications for advances in depression recognition and prevention. Two cognitive processes, namely brooding and reflection, may be instrumental in the development of depressive symptoms. Study aims were to (1) examine the relationships among brooding, reflection, dysfunctional attitudes, negative inferential style, stressful life events, and depressive symptoms and (2) determine the unique contributions of brooding and reflection to depressive symptoms in adolescents who are experiencing stressful life events. A secondary data analysis was conducted using cross-sectional data gathered via a web-based survey (N = 111) of 12-15 year olds. Descriptive statistics, Pearson's correlations, and hierarchical linear regression modeling were used to evaluate study aims. The final regression model explained approximately 73% of the variance in depressive symptoms (Multiple R = 0.85, p < .001). After controlling for each of the study variables, both brooding (beta = .48, p < .001) and reflection (beta = .33, p < .001) demonstrated unique contributions to the prevalence of depressive symptoms. Our findings suggest that brooding and reflection are significant contributors to depressive symptoms in young adolescents experiencing stressful life events. With this knowledge, nurses are better equipped to identify adolescents at high risk for depressive symptoms and implement appropriate levels of intervention.
Prognostic Factors and Therapeutic Decisions in Axillary Node-Negative Breast Cancer

The incidence of node-negative breast cancer is increasing, and it is becoming a more commonly encountered clinical problem. Prognostic factors such as tumor size, histopathological characteristics, receptor status, proliferative markers, biochemical alterations, and gene abnormalities can be useful in assessing the risk of cancer recurrence after primary local therapy. By accurately assessing the risk of recurrence, informed decisions can be made about whether or not to treat with adjuvant systemic therapy.
Imagined Childhoods: Self and Society in Autobiographical Accounts

Imagined Childhoods: Self and Society in Autobiographical Accounts. MARIANNE GULLESTAD, ed. Oslo: Scandinavian University Press, 1996. viii + 244 pp., notes, references, contributors.
Characterization of Corrosion Interfaces by the Scanning Kelvin Probe Force Microscopy Technique

A variety of interfaces relevant to corrosion processes were examined by the scanning Kelvin probe force microscopy ~SKPFM! technique in order to study the influences of various parameters on the measured potential. SKPFM measurements performed on AA2024-T3 after solution exposure showed that surface composition is not the only parameter that controls the Volta potential difference, which is measured by SKPFM. The influence of surface oxide structure and adsorption at the oxide surface can be probed by SKPFM and lateral potential gradients can be observed in the absence of significant differences in oxide composition. The influence of tip-sample separation distance on the measured Volta potential difference was studied for different pure oxidecovered metals. SKPFM measurements were made in air on pure Ni and Pt samples withdrawn from solution at open circuit or under potential control. The Volta potential difference was found to be composed of a transient component that slowly discharged and a more permanent component associated with the charge of adsorbed species. The Volta potential difference transients measured on the samples emersed under potential control decayed much slower than the open-circuit potential transient measured in solution upon release of the potential control. These different measurements validate the use of SKPFM for the prediction of
The impact of covariate adjustment at randomization and analysis for binary outcomes: understanding differences between superiority and noninferiority trials.

The question of when to adjust for important prognostic covariates often arises in the design of clinical trials, and there remain various opinions on whether to adjust during both randomization and analysis, at randomization alone, or at analysis alone. Furthermore, little is known about the impact of covariate adjustment in the context of noninferiority (NI) designs. The current simulation-based research explores this issue in the NI setting, as compared with the typical superiority setting, by assessing the differential impact on power, type I error, and bias in the treatment estimate as well as its standard error, in the context of logistic regression under both simple and covariate adjusted permuted block randomization algorithms. In both the superiority and NI settings, failure to adjust for covariates that influence outcome in the analysis phase, regardless of prior adjustment at randomization, results in treatment estimates that are biased toward zero, with standard errors that are deflated. However, as no treatment difference is approached under the null hypothesis in superiority and under the alternative in NI, this results in decreased power and nominal or conservative (deflated) type I error in the context of superiority but inflated power and type I error under NI. Results from the simulation study suggest that, regardless of the use of the covariate in randomization, it is appropriate to adjust for important prognostic covariates in analysis, as this yields nearly unbiased estimates of treatment as well as nominal type I error.
Effects of Premature Termination Codon Polymorphisms in the Drosophila pseudoobscura Subclade

Premature termination codon (PTC) mutations can have dramatic effects—both adaptive and deleterious—on gene expression and function. Here, we examine the number and selective effects of PTC mutations within the Drosophila pseudoobscura subclade using 18 resequenced genomes aligned to the reference genome. We located and characterized 1,679 PTC mutations in 605 genes across each of these genomes relative to the D. pseudoobscura reference genome, and use RT-PCR to confirm transcription of a subset of these genes containing PTC mutations. We confirm previous findings that genes containing PTC mutations are less selectively constrained and less broadly expressed than non-PTC-containing genes, suggesting that the most of these mutations are at least mildly deleterious. Further, we find highly significant codon usage bias in regions downstream of the PTC in 38 of these PTC-containing genes, suggesting that some of these PTC mutations—if not alternatively spliced out of the transcript—have neutral effects. Ultimately, these analyzes support the view that the PTC mutations are mostly detrimental, but are nonetheless common enough in genomes that a subset could be effectively neutral.
Genome-Wide Association of Familial Late-Onset Alzheimer's Disease Replicates BIN1 and CLU and Nominates CUGBP2 in Interaction with APOE

Late-onset Alzheimer’s disease (LOAD) is the most common form of dementia in the elderly. The National Institute of AgingLate Onset Alzheimer’s Disease Family Study and the National Cell Repository for Alzheimer’s Disease conducted a joint genome-wide association study (GWAS) of multiplex LOAD families (3,839 affected and unaffected individuals from 992 families plus additional unrelated neurologically evaluated normal subjects) using the 610 IlluminaQuad panel. This cohort represents the largest family-based GWAS of LOAD to date, with analyses limited here to the European-American subjects. SNPs near APOE gave highly significant results (e.g., rs2075650, p=3.2610 281 ), but no other genome-wide significant evidence for association was obtained in the full sample. Analyses that stratified on APOE genotypes identified SNPs on chromosome 10p14 in CUGBP2 with genome-wide significant evidence for association within APOE e4 homozygotes (e.g., rs201119, p=1.5610 28 ). Association in this gene was replicated in an independent sample consisting of three cohorts. There was evidence of association for recently-reported LOAD risk loci, including BIN1 (rs7561528, p=0.009 with, and p=0.03 without, APOE adjustment) and CLU (rs11136000, p=0.023 with, and p=0.008 without, APOE adjustment), with weaker support for CR1. However, our results provide strong evidence that association with PICALM (rs3851179, p=0.69 with, and p=0.039 without, APOE adjustment) and EXOC3L2 is affected by correlation with APOE, and thus may represent spurious association. Our results indicate that genetic structure coupled with ascertainment bias resulting from the strong APOE association affect genome-wide results and interpretation of some recently reported associations. We show that a locus such as APOE, with large effects and strong association with disease, can lead to samples that require appropriate adjustment for this locus to avoid both false positive and false negative evidence of association. We suggest that similar adjustments may also be needed for many other large multi-site studies.
Exploiting local and global patch rarities for saliency detection

We introduce a saliency model based on two key ideas. The first one is considering local and global image patch rarities as two complementary processes. The second one is based on our observation that for different images, one of the RGB and Lab color spaces outperforms the other in saliency detection. We propose a framework that measures patch rarities in each color space and combines them in a final map. For each color channel, first, the input image is partitioned into non-overlapping patches and then each patch is represented by a vector of coefficients that linearly reconstruct it from a learned dictionary of patches from natural scenes. Next, two measures of saliency (Local and Global) are calculated and fused to indicate saliency of each patch. Local saliency is distinctiveness of a patch from its surrounding patches. Global saliency is the inverse of a patch's probability of happening over the entire image. The final saliency map is built by normalizing and fusing local and global saliency maps of all channels from both color systems. Extensive evaluation over four benchmark eye-tracking datasets shows the significant advantage of our approach over 10 state-of-the-art saliency models.
Formal thought disorder in schizophrenia: a factor analytic study.

Abstract The Thought, Language and Communication Scale (TLC) was studied in a sample composed of 115 DSM-III-R schizophrenic patients admitted to an acute inpatient unit. A principal component analysis with varimax rotation was performed to explore the possibility of the existence of syndromes within the formal thought disturbances. Seven factors were found to have eigen values greater than 1 and five showed appropriate internal consistency. The first factor, or disorganization factor, was close to the Scale for the Assessment of Positive Symptoms (SAPS) formal thought disturbance subscale. The second, or negative factor (perseveration, proverty of speech and content), was moderately correlated with poor premorbid functioning and poor response to neuroleptic treatment. The third and fourth factors were, respectively, formed by stilted speech plus word approximations, and neologisms plus clanging. The fifth factor (distractibility and blocking), as well as the first two factors, were correlated to the Scale for the Assessment of Negative Symptoms (SANS) attention subscale.
Food Insecurity and Health Disparities: Experiences from New York City

Opportunities exist to further enhance the effectiveness of policy and programs that target the nexus of hunger and health equity. These entail intersectional action, crossing levels of government, and societal sectors. Federal nutrition assistance programs in US are an economic and moral policy lever currently used for feeding a socially acceptable subset of the full population of people living in poverty at a given time. The most fundamental approach to reducing diet-related disease disparities—and other health problems—is to reduce wealth inequality and poverty. Against this mark, it becomes clear that much of what is done to reduce food insecurity in the US, and its contribution to health inequities, falls short of addressing the root causes of modern malnutrition. As experiences of this system indicate, its reliance on free markets, restrictions on food choice, and the conditional terms of program participation, promote the hierarchical distribution of wealth and food that nutrition assistance programs should remedy. This chapter looks at these problems using New York as a case study. The chapter will address the following issues: (1) The advantages and disadvantages of nutrition assistance programs that provide electronically transferred funds for use with eligible food products, vis-a-vis general income support policies. (2) The extent to which nutrition assistance programs exclude foods with low nutritional value, and/or offer financial incentives for purchasing fruits and vegetables. (3) The role of public institutions in alleviating modern malnutrition in New York City.
Effect of Leptin Replacement on PCSK9 in ob/ob Mice and Female Lipodystrophic Patients.

Leptin treatment has beneficial effects on plasma lipids in patients with lipodystrophy, but the underlying mechanism is unknown. Proprotein convertase subtilisin/kexin type 9 (PCSK9) decreases low-density lipoprotein (LDL) clearance, promotes hypercholesterolemia, and has recently emerged as a novel therapeutic target. To determine the effect of leptin on PCSK9, we treated male and female ob/ob mice with leptin for 4 days via sc osmotic pumps (∼24 μg/d). Leptin reduced body weight and food intake in all mice, but the effects of leptin on plasma PCSK9 and lipids differed markedly between the sexes. In male mice, leptin suppressed PCSK9 but had no effect on plasma triglycerides or cholesterol. In female mice, leptin suppressed plasma triglycerides and cholesterol but had no effect on plasma PCSK9. In parallel, we treated female lipodystrophic patients (8 females, ages 5–23 y) with sc metreleptin injections (∼4.4 mg/d) for 4–6 months. In this case, leptin reduced plasma PCSK9 by 26% (298 ± 109 vs 221 ± 102 ...
Identification of the cardiac sarcolemmal Na+−Ca2+ exchanger using monoclonal antibodies

We have previously partially purified the sarcolemmal Na+−Ca2+ exchange protein and produced rabbit polyclonal antibodies to the exchanger (Philipson, K. D., Longoni, S., Ward, R. 1988.Biochim. Biophys.Acta945:298–306). We now describe the generation of three stable murine hybridoma lines which secrete monoclonal antibodies (MAb's) to the exchanger. These MAb's immunoprecipitate 50–75% of solubilized Na+−Ca2+ exchange activity. The MAb's appear to be reactive with native conformation-dependent expitopes on the Na+−Ca2+ exchanger since they do not react on immunoblots. An indirect method was used to identify Na+−Ca2+ exchange proteins. A column containing Na+−Ca2+ exchanger immobilized by MAb's was used to affinity purify the rabbit polyclonal antibody. The affinity-purified polyclonal antibody reacted with proteinsof, apparent molecular weights of 70, 120, and 160 kDa on immunoblots of sarcolemma. The data provide strong support for our prevous association of Na+−Ca2+ exchange with these proteins.
Number of holes contained within the Fermi surface volume in underdoped high-temperature superconductors

We provide a potential solution to the longstanding problem relating Fermi surface reconstruction to the number of holes contained within the Fermi surface volume in underdoped high ${T}_{\mathrm{c}}$ superconductors. On considering uniaxial and biaxial charge-density wave order, we show that there exists a relationship between the ordering wave vector, the hole doping, and the cross-sectional area of the reconstructed Fermi surface whose precise form depends on the volume of the starting Fermi surface. We consider a ``large'' starting Fermi surface comprising $1+p$ hole carriers, as predicted by band structure calculations, and a ``small'' starting Fermi surface comprising $p$ hole carriers, as proposed in models in which the Coulomb repulsion remains the dominant energy. Using the reconstructed Fermi surface cross-sectional area obtained in quantum oscillation experiments in ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{6+x}$ and ${\mathrm{HgBa}}_{2}{\mathrm{CuO}}_{4+x}$ and the established methods for estimating the chemical hole doping, we find the ordering vectors obtained from x-ray scattering measurements to show a close correspondence with those expected for the small starting Fermi surface. We therefore show the quantum oscillation frequency and charge-density wave vectors provide accurate estimates for the number of holes contributing to the Fermi surface volume in the pseudogap regime.
The Theory of Information and Coding: Student Edition

This is a revised edition of McEliece's classic, published with students in mind. It is a self-contained introduction to all basic results in the theory of information and coding. This theory was developed to deal with the fundamental problem of communication, that of reproducing at one point, either exactly or approximately, a message selected at another point. There is a short and elementary overview introducing the reader to the concept of coding. Then, following the main results, the channel and source coding theorems, there is a study of specific coding schemes which can be used for channel and source coding. This volume can be used either for self-study, or for a graduate/undergraduate level course at university. It includes dozens of worked examples and several hundred problems for solution. The exposition will be easily comprehensible to readers with some prior knowledge of probability and linear algebra.
'Nurses don't deal with these issues': nurses' role in advance care planning for lesbian, gay, bisexual and transgender patients.

Aims and objectives We used a question from the Healthcare Equality Index to explore nurses’ knowledge and understanding of medical advance directives, medical power of attorney and other legal documents for lesbian, gay, bisexual and transgender patients. Background Until the landmark ruling in Obergefell vs. Hodges, lesbian, gay, bisexual and transgender individuals and same-sex couples have had limited relationship rights as only a few states recognised marriages and provided legal protections for same-sex couples. Health care providers’ knowledge of and attitudes towards advance care planning plays a significant role in determining whether or not individuals successfully complete advance directives, yet advance care planning for lesbian, gay, bisexual and transgender individuals is poorly understood among both health care providers and same-sex couples. Design These data were part of a larger research study that explored the current state of lesbian, gay, bisexual and transgender-sensitive nursing practice. Method Undergraduate nursing students recruited and interviewed nurse key informants (n = 268) about medical advance directives, medical power of attorney and other legal documents for lesbian, gay, bisexual and transgender patients. Results Nearly 50% of key informants indicated a lack of knowledge of advance directives, over 26% reported the difficulties nurses face regarding advance directives are the same for both lesbian, gay, bisexual and transgender and heterosexual patients, and nearly 25% indicated difficulties including having to decide who has the legal right to make decisions for the patient. Conclusion The study demonstrated the need for education and training for practising nurses in advance care planning for lesbian, gay, bisexual and transgender patients and same-sex couples. Relevance to clinical practice Nurses are in a position to act as educators, advocates and decision makers for their patients. Nurse's lack of understanding of advance care planning may negatively impact the type and quality of care lesbian, gay, bisexual and transgender patients receive.
Documentation of HEART score discordance between emergency physician and cardiologist evaluations of ED patients with chest pain.

Abstract Introduction A triage cardiology program, in which cardiologists provide consultation to the Emergency Department (ED), may safely reduce admissions. For patients with chest pain, the HEART Pathway may obviate the need for cardiology involvement, unless there is a difference between ED and cardiology assessments. Therefore, in a cohort concurrently evaluated by both specialties, we analyzed discordance between ED and cardiology HEART scores. Methods We performed a single-center, cross-sectional, retrospective study of adults presenting to the ED with chest pain who had a documented bedside evaluation by a triage cardiologist. Separate ED and cardiology HEART scores were computed based on documentation by the respective physicians. Discrepancies in HEART score between ED physicians and cardiologists were quantified using Cohen κ coefficient. Results Thirty-three patients underwent concurrent ED physician and cardiologist evaluation. Twenty-three patients (70%) had discordant HEART scores ( κ = 0.13; 95% confidence interval, −0.02 to 0.32). Discrepancies in the description of patients' chest pain were the most common source of discordance and were present in more than 50% of cases. HEART scores calculated by ED physicians tended to overestimate the scores calculated by cardiologists. When categorized into low-risk or high-risk by the HEART Pathway, more than 25% of patients were classified as high risk by the ED physician, but low risk by the cardiologist. Conclusion There is substantial discordance in HEART scores between ED physicians and cardiologists. A triage cardiology system may help refine risk stratification of patients presenting to the ED with chest pain, even when the HEART Pathway tool is used.
Co-constructionism: What is (and is not) in a name?

Discussion of co-constructionism as a theoretical orientation participates in parallel in two social discourses. First, it serves as a re-classificatory device for the discourse about developmental psychology as a scientific discipline. Secondly, it acts as a conceptual canalizer for the construction of developmental methodology. It is in the latter discourse that co-constructionism can lead to novel solutions to old problems in developmental psychology. Elaborations in the realm of developmentally adequate methodology lead to the centrality of irreversible time and emerging phenomena in any theory construction.
Targeted Multifunctional Lipid ECO Plasmid DNA Nanoparticles as Efficient Non-viral Gene Therapy for Leber's Congenital Amaurosis.

Development of a gene delivery system with high efficiency and a good safety profile is essential for successful gene therapy. Here we developed a targeted non-viral delivery system using a multifunctional lipid ECO for treating Leber’s congenital amaurosis type 2 (LCA2) and tested this in a mouse model. ECO formed stable nanoparticles with plasmid DNA (pDNA) at a low amine to phosphate (N/P) ratio and mediated high gene transfection efficiency in ARPE-19 cells because of their intrinsic properties of pH-sensitive amphiphilic endosomal escape and reductive cytosolic release (PERC). All-trans-retinylamine, which binds to interphotoreceptor retinoid-binding protein (IRBP), was incorporated into the nanoparticles via a polyethylene glycol (PEG) spacer for targeted delivery of pDNA into the retinal pigmented epithelium. The targeted ECO/pDNA nanoparticles provided high GFP expression in the RPE of 1-month-old Rpe65−/− mice after subretinal injection. Such mice also exhibited a significant increase in electroretinographic activity, and this therapeutic effect continued for at least 120 days. A safety study in wild-type BALB/c mice indicated no irreversible retinal damage following subretinal injection of these targeted nanoparticles. All-trans-retinylamine-modified ECO/pDNA nanoparticles provide a promising non-viral platform for safe and effective treatment of RPE-specific monogenic eye diseases such as LCA2.
Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress

We have previously shown that acute erythropoietic (Ep) stress by hemolysis or hypobaric hypoxia causes elevations of HbF in the baboon. The magnitude of these elevations is genetically determined, ranging from 3% to 60% (low, intermediate, and high responders). These genetic differences in HbF levels among animals are mainly due to differences in the number of HbF-containing cells (“F-cells”). The present study was undertaken to study the influence of prolongation and of the severity of Ep stress on HbF levels and the number of F-cells. The packed cell volume (PCV) of the blood of 4 animals, approximately 3 yr old, was maintained at 20% by daily phlebotomies, and the animals were exposed to varying degrees of hypobaric hypoxia for up to 40 days. In these experiments, the number of F-cells increased rapidly and reached individually constant levels ranging from 60% to 80%, when the PCV reached 20%, and no further increase was observed regardless of the subsequent degree of hypoxia. On the other hand, HbF levels, and with it the values for HbF per F-cell, increased proportionally to the severity of the Ep stress and could be maintained at a constant level dependent on the degree of the hypoxia, e.g., at 19,000 feet HbF levels of one animal remained 20%-25% throughout the duration of the exposure of 14 days. These data are indicative of separate control of F-cell numbers and of the levels of HbF per F-cell. It appears that with the increase of Ep stress, those Ep stem cells that have retained the HbF program are mobilized into maturation. A model, attempting to explain this phenomenon is presented.
Clustering MeSH Representations of Biomedical Literature

Biomedical literature contains vital information for the analysis and interpretation of experiments in the biological sciences. Human reasoning is the primary method for extracting, synthesizing, and interpreting the results contained in the literature, yet the rate at which publications are produced is exponential. With the advent of digital, full-text publication and increasing computational power, automated techniques for knowledge discovery and synthesis are being developed to assist humans in making sense of growing literature databases. We investigate the use of ontological information provided by the Medical Subject Headings (MeSH) project to discover groupings within a collection of medical literature stored in PubMed. Vector representations of documents based on MeSH terms are presented. Results of agglomerative hierachical clustering on two collections of biomedical literature, the Rat Genome Database and Tourette’s Syndrome related research, suggest novel and understandable groupings are obtainable.
The Young Male Experience with Treatment for Nonseminomatous Testicular Cancer

This is a qualitative study where young men who underwent treatment for nonseminomatous testicular cancer told of their experiences. Using an ethnographic method, three themes emerged from the data: 1) feelings of shock, disbelief, and despair, 2) physical and emotional trauma, and 3) a renewed appreciation of life. These themes often occurred within stages of treatment. Stage 1) symptoms, first surgery (orchiectomy, which includes biopsy), diagnosis, and recovery period; Stage 2) second surgery (lymphadenectomy); diagnostic tests for metastases, and recovery period; Stage 3) chemotherapy regimens; and Stage 4) 3-year disease free period following treatment. This research adds to the dearth of information available on how young males experience treatment for a potentially lethal disease.
Biocompatibility in clinical practice: predictable and unpredictable outcomes

At the present time, there is a significant public and political debate about the safety of implantable medical devices. The debate has centered on the biocompatibility of materials that are used in such devices. It has become clear that, whether the concerns expressed about adverse events in patients are actually caused by the devices or just coincidentally arise in these patients, we are usually unable to address and explain the phenomena that are described. This is very damaging to the medical device industry and the relevant clinical disciplines; it is, however, not surprising, since current ideas about the mechanisms of biocompatibility and the development of the host response are well out-of-date and do not take into account knowledge about inflammation, immunity and fibrosis. This perspectives paper discusses this new knowledge and presents the outline of new biocompatibility paradigms, involving mechanotransduction and sterile inflammation. Based on these ideas, totally new procedures for the determination of biological safety are proposed which, if implemented, could improve patient safety and confidence in the performance of implanted devices.
What's Wrong with Central Bank Websites

Most central banks use their websites intelligently. However, Steve Hanke and Michael Morgenstern from Johns Hopkins University find that some central banks are failing to pass elementary tests of transparency.
Young Children’s Embodied Experiences: A Classroom-Based Yoga Intervention

Over the years, mindfulness and yoga-based interventions have been widely implemented in schools and demonstrated promising results. Despite the benefits, there is limited literature on the effects that yoga may have for young children. Furthermore, extant research on yoga and young children has primarily used quantitative methodologies. The objective of this study was to investigate pre-kindergarteners’ and kindergartners’ experiences with yoga through a qualitative-exploratory approach. This qualitative-exploratory study used interview methods and the application of grounded theory to learn about children’s perceptions (n = 154) of participating in a randomized waitlist-controlled trial an eight-week yoga intervention that targeted self-regulation and emotion regulation. The post-intervention child interview findings are reported here. Two themes, grounded in the dataset and most relevant to the topic of children’s experiences in practicing the yoga, emerged in the analysis: (1) children’s positive emotions about the yoga; and (2) children’s knowledge of yoga and self-regulation skills. Children were often eager to share their feelings and knowledge about the yoga and demonstrated their embodied expertise regarding their own emotions and bodies and thus ability to serve as active participants in the research process. This qualitative-exploratory study contributes to the research on the physical, cognitive, and emotional benefits of yoga for young children. Future researchers may work towards understanding how yoga promotes children’s development at a young age and conduct follow-up investigations into the embodied experiences and benefits of yoga practices with children.
The Effect of Promiscuous Aggregation on in Vitro Drug Metabolism Assays

Many bioactive molecules show a type of solution phase behavior, termed promiscuous aggregation, whereby at micromolar concentrations, colloidal drug-rich aggregates are formed in aqueous solution. These aggregates are known to be a major cause of false positives and false negatives in select enzymatic high-throughput screening assays. The goal of this study was to investigate the impact of drug-rich aggregates on in vitro drug screening metabolism assays. Cilnidipine was selected as an aggregate former and its impact on drug metabolism was evaluated against rCYP2D6, rCYP1A2, rCYP2C9 and human liver microsomes. The cilnidipine aggregates were shown to non-specifically inhibit multiple cytochrome P450 enzymes with an IC50 comparable with the IC50 of potent model inhibitors. This newly demonstrated mode of “promiscuous inhibition” is of great importance as it can lead to false positives during drug metabolism evaluations and thus it needs to be considered in the future to better predict in vivo drug-drug interactions.
Foveal gravity: A robust illusion of color-location misbinding

Some types of object features, such as color, shape, or location, can be processed separately within the visual system, requiring that they be correctly "bound" to a single object via attentional selection of a subset of visual information. Forcing selection to spread too widely can cause an illusion where these features misbind to objects, creating illusory objects that were never present. Here, we present a novel display that produces a robust color-location misbinding illusion that we call foveal gravity (viewable at https://osf.io/2bndg/). When observers selected only a set of colored objects, colors were largely perceived in their correct locations. When observers additionally selected objects in the far periphery, colors in the near periphery migrated closer to the fovea on over 35% of trials. We speculate that foveal gravity occurs because locations closer to the fovea are more likely to defeat more peripheral locations in competitive interactions to "win" the task-relevant color.
A Path to Protection: Collateral Crime Vacatur for Wisconsin's Victims of Sex Trafficking

Sex trafficking is a form of human trafficking in which a trafficker compels a victim to engage in commercial sex acts. Traffickers often control victims using physical violence, sexual abuse, psychological abuse, isolation, and by introducing victims to illegal drugs. Throughout the course of their victimization, many victims of sex trafficking experience such distress that they turn to drugs to cope or steal to meet their basic needs. Unfortunately, the trauma of trafficking is prolonged and exacerbated when victims are prosecuted for and convicted of crimes they committed as a direct result of trafficking. In addition to prostitution convictions, many victims of trafficking accrue criminal records for “collateral” offenses such as drug possession, theft, disorderly conduct, or weapons offenses. When victims of trafficking have criminal records, they encounter barriers to housing and employment, subjecting victims to lives of poverty, which increases their risk of being re-trafficked. Wisconsin provides victims of sex trafficking with two forms of decriminalization: (1) an affirmative defense to avoid conviction of any crime committed as a direct result of being a victim of trafficking and (2) a pathway for victims of sex trafficking to expunge or vacate prostitution convictions that were a result of being trafficked. Both pathways are insufficient remedies for victims because victim identification is poor and, more importantly, only prostitution convictions are eligible for vacatur or expungement, which leaves victims with criminal records for the collateral crimes they committed as a direct result of being a victim of sex trafficking. Wisconsin should expand its vacatur statute for victims of trafficking to allow victims to vacate or expunge any nonviolent conviction committed as a direct result of being a victim of trafficking. Moreover, an expansion of the vacatur statute for victims of trafficking would better protect victims and help them to reintegrate into life outside of trafficking.
System organizations for speech understanding: implications of network and multiprocessor computer architectures for AI

This paper considers various factors affecting system organization for speech understanding research. The structure of the Hearsay system based on a set of cooperating, independent processes using the hypothesize-and-test paradigm is presented. Design considerations for the effective use of multiprocessor and network architectures in speech understanding systems are presented: control of processes, interprocess communication and data sharing, resource allocation, and debugging are discussed.
Feelings about language brokering: The contribution of formal interpreter education

Abstract Young language brokers have a complex emotional relationship with the translation and interpreting tasks that they engage in for their families and communities. Whereas they often report feeling happy, useful and proud of themselves for being able to contribute to their families’ well-being, they also struggle with frustration, pressure from their loved ones, and cognitive and emotional burdens. This study aims to map the evolution of feelings regarding language brokering among young adults and to reveal the effects that formal interpreting education might have in this process. For these purposes, it examines the narratives of 75 self-identified former and/or current language brokers who are registered in an undergraduate interpreting program in the United States. Quantitative and qualitative analyses of these narratives (collected at three different points during their course of study) indicate that the participants feel more positively than negatively about their brokering tasks and that positive emotions increase overall throughout their interpreter education (with a noticeable peak halfway through the program). These analyses also reveal how triggers for positive and negative emotion shift through time: whereas their enhanced skills contribute to positive feelings, poor working conditions and brokering settings beyond their immediate families become new stressors.
Laser scanning GLIM (LS-GLIM) for label-free imaging of turbid samples

We propose a multimodal imaging system, LS-GLIM, consisting of the light scanning microscope (LSM 900, Zeiss) and the gradient light interference microscope (GLIM) module [1], with photomultiplier tube (PMT) detection. GLIM upgrades a differential interference microscope with a liquid crystal variable retarder (LCVR), which introduces further controlled phase shifts between the x and y polarized light. The quantitative phase information can be retrieved from the four frames corresponding to each phase shift in the GLIM. We anticipate a broad range of applications that LS-GLIM will enable through phase imaging with computational specificity (PICS), especially in thick, highly-scattering samples.
Trends in the proportion of second or later primaries among all newly diagnosed malignant cancers

Background Improvements in cancer survival mean that an increasing number of survivors may live long enough beyond their initial cancer to be diagnosed with additional independent primary cancers. The proportion of newly diagnosed cancers that are second- or higher-order primaries and how this proportion has changed over the past several decades were examined. Methods Data from the Surveillance, Epidemiology, and End Results (SEER) program were used to identify incident malignant primaries diagnosed between 1975 and 2017. Using the SEER sequence number, the authors tabulated the proportion of all cancers in each calendar year that were second- or higher-order primaries. The average annual percent change (AAPC) was then calculated to assess how this proportion has changed over time. Results Analyses included nearly 4.9 million incident cancers diagnosed during 1975-2017. The proportion of all cancers that were second- or higher-order increased steadily from 9.77% during 1975-1984 to 21.03% during 2015-2017, reflecting an AAPC of 2.41% (95% CI, 2.16%-2.65%). In 2015-2017, second- or higher-order cancers were most prevalent among cancers of the bladder (28.79%), followed by lung and bronchus (28.07%), melanoma (27.88%), and leukemia (26.10%). The highest AAPCs over the study period were observed for melanoma (4.05%), leukemia (3.51%), and lung and bronchus (3.36%). Conclusions The proportion of newly diagnosed cancers that are second- or higher-order has grown rapidly over the past several decades and currently exceeds 20%. Continued monitoring of second and later primaries will be critical for anticipating the future impact on cancer treatment and survivorship care.
Single-molecule imaging of IQGAP1 regulating actin filament dynamics in real time

IQGAP is a conserved family of actin-binding proteins with essential roles in cell motility, cytokinesis, and cell adhesion, yet it has remained poorly understood how IQGAP proteins directly regulate actin filament dynamics. To close this gap, we used single-molecule and single-filament TIRF microscopy to directly visualize IQGAP regulating actin dynamics in real time. To our knowledge, this is the first study to do so. Our results show that full-length human IQGAP1 forms dimers that stably bind to filament sides and transiently cap barbed ends. These interactions organize actin filaments into thin bundles, suppress barbed end growth, and inhibit filament disassembly. Surprisingly, each activity depends on distinct combinations of IQGAP1 domains and/or dimerization, suggesting that different mechanisms underlie each functional effect on actin. These observations have important implications for how IQGAP functions as a direct actin regulator in vivo, and how it is deployed and regulated in different biological settings.
Understanding improvements in coalesced epilayers grown over nanopatterned substrates

Nanopatterned substrates provide opportunities for reducing costs of high-efficiency III-V devices through methods such as substrate reuse and growth on cheaper substrates. In this work, we aim to better understand some of the fundamental challenges of growing high quality III-V material on nanopatterned substrates. Through specific pattern orientations and control of overgrowth morphology, we report that smooth and defect-free coalesced III-V epilayers are attainable over nanopatterned GaAs substrates.