cssi/SciSciGPT-SciSciNet huggingface dataset:
SEM imaging and automated defect analysis at advanced technology nodes (DI: Defect inspection and reduction)

As the scaling continues and industry moves to sub 1× nm nodes, Defect Review Scanning Electron Microscopy (DR-SEM) faces increasingly difficult challenges. The Defects of Interest (DOI) shrink as the features shrinks leading to imaging difficulty purely based on scale. The defect signal gets immersed in noise and the challenge of separating false from true is larger than ever. Also, more complex defect analysis is required for DOIs with 3D morphology and for previous layer DOI. A smart approach to DR-SEM must be adopted which allows for high quality imaging focused on yield improvements within a short cycle time. In this paper we demonstrate that reporting defects location in computer aided design (CAD) coordinates eliminates tool and user discrepancy in the inspection/review loop, facilitating robust DOI search at higher magnification and sensitivity. Further, smart implementation of defect analysis such as high landing energy see-through imaging, quantitative material analysis and tilt imaging on select DOI subsets allows for root-cause analysis and improved classification of defects which were previously misclassified or determined to be SNV (SEM non-visual).
Trends in healthcare expenditure among people living with HIV/AIDS in the United States: evidence from 10 Years of nationally representative data.

While previous studies have examined HIV cost expenditures within the United States, the majority of these studies focused on data collected prior to or shortly after the advent and uptake of antiretroviral therapy, focused only on a short time frame, or did not provide cost comparisons between HIV/AIDS and other chronic conditions. It is critical that researchers provide accurate and updated information regarding the costs of HIV care to assist key stakeholders with economic planning, policy development, and resource allocation. We used data from the Medical Expenditure Panel Survey-Household Component for the years 2002–2011, which represents a nationally representative U.S. civilian non-institutionalized population. Using generalized linear modeling, we estimated the adjusted direct medical expenditures by HIV/AIDS status after controlling for confounding factors. Data were from 342,732 people living with HIV/AIDS. After adjusting for socio-demographic factors, comorbidities and time trend covariates, the total direct expenditures for HIV/AIDS was $31,147 (95% CI $23,645–$38,648) or 800–900% higher when compared to those without HIV/AIDS (i.e., diabetes, stroke, and cardiovascular disease). Based on the adjusted mean, the aggregate cost of HIV/AIDS was approximately $10.7 billion higher than the costs for those without HIV/AIDS. Our estimates of cost expenditures associated with HIV care over a 10-year period show a financial burden that exceeds previous estimates of direct medical costs. There is a strong need for investment in combination prevention and intervention programs, as they have the potential to reduce HIV transmission, and facilitate longer and healthier living thereby reducing the economic burden of HIV/AIDS.
Importin-β Directly Regulates the Motor Activity and Turnover of a Kinesin-4

Summary Spatiotemporal regulation of kinesins is essential for microtubule-dependent intracellular transport. In plants, cell wall deposition depends on the FRA1 kinesin, whose abundance and motility are tightly controlled to match cellular growth rate. Here, we show that an importin-β, IMB4, regulates FRA1 activity in a developmental manner. IMB4 physically interacts with a PY motif in the FRA1 motor domain and inhibits its motility by preventing microtubule binding, while also protecting FRA1 against proteasome-mediated degradation, thus providing a mechanism to couple the motility and stability of FRA1. This regulatory mechanism is likely to be broadly applicable, based on the conservation of the PY motif in the motor domains of plant and animal kinesins and the direct interaction of multiple plant kinesins with IMB4. Together, our data establish IMB4 as a multi-functional regulator of FRA1 and reveal a mechanism for how plants control the magnitude of cargo transport needed for cell wall assembly.
Capnocytophaga keratitis in dogs: clinical, histopathologic, and microbiologic features of seven cases.

Objective To describe the clinical, microbiologic, and histopathologic features of Capnocytophaga keratitis in dogs. Animals studied Seven dogs with naturally acquired Capnocytophaga keratitis. Procedures Medical records of dogs with a clinical diagnosis of keratitis and corneal cultures positive for Capnocytophaga spp. were reviewed. Dog signalment, medical history, clinical findings, and diagnostic assay results were recorded. Results Breeds included Boston terrier (n = 3 dogs), Rat terrier (n = 2), and single cases of mixed breed and Pug. All dogs examined had expansive corneal ulceration involving the majority of the corneal surface. Marked corneal infiltrates, keratomalacia, and hypopyon were present. Progression of corneal disease was rapid with extensive dissolution of the corneal stroma. Corneal lesions progressed to catastrophic perforations within 24 h of the initial examination in three dogs, requiring enucleation. One globe was enucleated after failure to resolve with long-term medical therapy. Globes and vision were retained in three dogs following aggressive medical therapy (two dogs) or 360° conjunctival graft surgery (one dog). Capnocytophaga cynodegmi, Capnocytophaga canimorsus, or unspeciated Capnocytophaga spp. were cultured from corneal samples of all dogs. Long, thin, gram-negative rods were present during cytological evaluation of the cornea in some dogs. Histopathologic evaluation of enucleated globes revealed severe and diffuse neutrophilic and collagenolytic keratitis. Conclusions Capnocytophaga keratitis is a severe, rapidly progressive corneal infection in dogs that is associated with diffuse corneal involvement, extensive keratomalacia, and a relatively poor prognosis. Clinical features of canine Capnocytophaga keratitis are similar to human cases of this infection.
Detection and mitigation of pilot spoofing attack

In a time-division duplex (TDD) multiple antenna system, the channel state information (CSI) can be estimated using reverse training. A pilot contamination (spoofing) attack occurs when during the training phase, an adversary (spoofer) also sends identical training (pilot) signal as that of the legitimate receiver. This contaminates channel estimation and alters the legitimate beamforming design, facilitating eavesdropping. A recent approach proposed superimposing a random sequence on the training sequence at the legitimate receiver and then using the minimum description length (MDL) criterion to detect pilot contamination attack. In this paper we augment this approach with joint estimation of both legitimate receiver and eavesdropper channels, and secure beamforming, to mitigate the effects of pilot spoofing. We consider two cases: (i) the spoofer transmits only the pilot signal, (ii) the spoofer also adds a random sequence to its pilot. The proposed mitigation approach is illustrated via simulations.
Bone turnover is altered during 72 h of sleep restriction: a controlled laboratory study.

The objective of the study was to evaluate how controlled, short-term sleep restriction (SR; 72 h) alters markers of bone formation and resorption and urinary calcium (Ca) output. Ten healthy, sleep-adequate, male soldiers were housed in the research facility one day prior to and for the duration of SR. Diet was controlled to provide adequate energy balance and macronutrient distribution, meeting the recommended dietary allowance (RDA) for Ca. Subjects engaged in light activities to maintain wakefulness and were allowed 2 h of sleep per night (0430–0630 hours). Blood samples were collected each morning at 0 h (baseline) and 24, 48, and 72 h of SR. Serum was assayed for parathyroid hormone (PTH), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP), and C-terminal telopeptide of type I collagen (CTX). Urine was collected in 24 h increments during SR for measurement of Ca and creatinine (Cr). BAP was reduced at 24 h (P= 0.015) and resorption markers TRAP and CTX were increased after 48 and 72 h of SR compared to baseline (P < 0.05). The ratio of BAP:TRAP was significantly lower (P= 0.017) at 48 and 72 h of SR. In contrast, total 24 h urinary Ca and Ca/Cr excretion were unchanged. Markers of bone formation and resorption are uncoupled in response to as little as 48 h of SR even when Ca intake is at the RDA. Sleep deprivation may be a risk factor for reduced bone health due to perturbations in bone turnover.
From Play to Pedagogy: Formative Childhood Experiences and the Development of Preservice Elementary Science Educators

In this study, we explore the concerns of elementary education (ELED) teaching candidates regarding teaching science in the outdoors and how their apprehensions might have been shaped by their reco...
Care, Containment, and Countertransference: Managing the Suicidal Patient in Medical Settings

The psychiatric consultant had been paged “stat” to see an “acutely” suicidal patient whom the staff feared would jump out the window at any moment if they didn’t get help soon. Rushing breathlessly into the room, the consultant found the patient lying quietly in bed, staring off into space while a nurse paced anxiously at his side. The man, a 45-year-old former construction worker, told the consultant angrily that he wanted to throw himself from the window because of recent surgery; he feared never being able to do anything for himself again. The patient, who had suffered for years with severe peripheral vascular disease associated with diabetes, suddenly pulled back the bed coverings to display his bilateral above-the-knee amputations.
Historical development of concept of blood circulation. An anniversary memorial essay to William Harvey.

Abstract One of the most significant contributions to medicine—William Harvey's concept of the circulation of the blood—was quietly announced early in the 17th century with the publication of a book, De Motu Cordis . This book, a culmination of thought, observation and controlled testing with conclusions based on the results of repeated experiments, changed the course of medical thinking. The year just ended, 1978, presented at least two excellent reasons to commemorate and to honor William Harvey. First, Harvey was born on April 1, 1578, and we celebrated the 400th anniversary of his birth; second, 1978 also marked the 350th anniversary of the publication date of his epoch-making classic, De Motu Cordis .
High Levels of Morbidity and Mortality among Pediatric Hematopoietic Cell Transplant Recipients with Severe Sepsis: Insights from the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study

Objectives: Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. Design: Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. Setting: International; 128 PICUs in 26 countries. Patients: Pediatric patients with severe sepsis prospectively identified over a 1-year period. Interventions: None. Measurements and Main Results: In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27). Conclusions: In an international study of pediatric severe sepsis, history of hematopoietic cell transplant is associated with a four-fold increased odds of hospital mortality after adjustment for potential measured confounders. Hematopoietic cell transplant patients more often originated from within the hospital compared to children with severe sepsis without hematopoietic cell transplant, possibly providing an earlier opportunity for sepsis recognition and intervention in this high-risk population.
Epigenetic Regulator CoREST Controls Social Behavior in Ants

Ants acquire distinct morphological and behavioral phenotypes arising from a common genome, underscoring the importance of epigenetic regulation. In Camponotus floridanus, "Major" workers defend the colony, but can be epigenetically reprogrammed to forage for food analogously to "Minor" workers. Here, we utilize reprogramming to investigate natural behavioral specification. Reprogramming of Majors upregulates Minor-biased genes and downregulates Major-biased genes, engaging molecular pathways fundamental to foraging behavior. We discover the neuronal corepressor for element-1-silencing transcription factor (CoREST) is upregulated upon reprogramming and required for the epigenetic switch to foraging. Genome-wide profiling during reprogramming reveals CoREST represses expression of enzymes that degrade juvenile hormone (JH), a hormone elevated upon reprogramming. High CoREST, low JH-degrader expression, and high JH levels are mirrored in natural Minors, revealing parallel mechanisms of natural and reprogrammed foraging. These results unveil chromatin regulation via CoREST as central to programming of ant social behavior, with potential far-reaching implications for behavioral epigenetics.
Myasthenia Gravis Crisis and Atrial Fibrillation.

Introduction Myasthenia gravis (MG) crisis has no specific reported correlation with atrial fibrillation (AF). We present a series of patients observed from a single general neurologist's outpatient and inpatient practice over a 9-year period who experienced the combination of MG crisis and AF. Case report Retrospective chart review of patients within 1 neurologist's inpatient and outpatient practice was done. Charts were selected based on the occurrence of newly diagnosed AF during MG crisis over a 9-year period. Most patients were diagnosed in the hospital and then followed as outpatients. Charts were reviewed to determine factors that may have played a role in the co-occurrence of these 2 conditions. Eight patients were identified that had co-occurring MG crisis and AF. All patients had very active MG, and were in or had recently been in MG crisis at the time their AF was discovered. Patients tended to have late-onset MG to be male, to be acetylcholinesterase receptor antibody positive, and to have improvement or remission of their AF once the MG achieved better clinical control. Conclusion New-onset AF can occur during MG crisis. The cardiac outcome improves with treatment of the underlying disease, after initial cardiac stabilization.
Culturally Responsive Assessments of Spatial Analytical Skills and Abilities: Development, Field Testing, and Implementation:

A persistent problem in education is underrepresentation of certain cultural and linguistic groups such as American Indian, African American, and Hispanic, in special programs for exceptionally tal...
Synchronized Power Injection From PVA To Grid With Reduced THD And Dc Voltage Ripple Using PID Controller for Dc Grid Applications

In this paper, a PVA is connected to the grid in synchronization with constant voltage at the terminals of the inverter. The variable DC output voltage from the PVA concerning solar irradiation is converted to a constant DC voltage using a DC-DC booster converter. The stabilized DC voltage is converted to a three-phase AC using a three-level inverter with 12 IGBT switches. The three-level inverter operates in synchronization with the grid voltage with feedback of voltage and current at PCC. The controller used is the SRF method control system which uses Clarke's and Park's transformations for generation of reference values. The THD analysis and power balancing graphs are generated using MATLAB software regarding time.
Perspectives On Integrating Health Into The Low-Income Housing Tax Credit: A Qualitative Study.

While there is increasing attention to the ways in which safe and affordable housing may promote improved health, less work has focused on the role of the Low-Income Housing Tax Credit (LIHTC) prog...
A Predictive Model for Students’ Performance and Risk Level Indicators Using Machine Learning

Educational data mining has been a veritable tool for predictive analytics which aids informed decision making and policy formulation tasks in the education industry. This study identifies relevant attributes from academic data of graduate teachers at a College of Education in Nigeria and develops a model that forecasts academic performance of teachers-in-training by assigning risk levels to their academic standing dataset. The model analyses success indicators from the list of attributes and assigned risk levels is a veritable tool for monitoring and evaluation of teachers-in-training by school administrators for an improved performance before graduation. The result shows that core courses offered in the first and second semesters of the second year of studentship have a healthy level of significance in forecasting teachers-in-training overall academic performance. Any deficient in such courses, therefore increases the risk level. A noteworthy discovery is the less significance of the teaching practice program, which assigns teachers-in-training to schools for six months, in determining their final academic standing on graduation.
Trends in Antihypertensive Medication Use Among Individuals With a History of Stroke and Hypertension, 2005 to 2016

Importance Hypertension is a well-established, modifiable risk factor for stroke. National hypertension management trends among stroke survivors may provide important insight into secondary preventive treatment gaps. Objective To investigate the adequacy of blood pressure control among stroke survivors and antihypertensive treatment trends using National Health and Nutrition Examination Survey (NHANES) data. Design, Setting, and Participants Cross-sectional surveys conducted between 2005 and 2016 of nationally representative samples of the civilian US population were analyzed from March 2019 to January 2020. The NHANES is a large, nationally representative cross-sectional survey conducted in 2-year cycles in the United States. Evaluations include interviews, medication lists, physical examinations, and laboratory tests on blood samples. Among 221 982 140 adults 20 years or older in the NHANES from 2005 through 2016, a total of 4 971 136 had stroke and hypertension and were included in this analysis, with 217 011 004 excluded from the primary analysis. Exposures Hypertension was defined by self-report, antihypertensive medication use, or uncontrolled blood pressure (>140/90 mm Hg) on physical examination. Antihypertensive medication was classified as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, diuretics, β-blockers, calcium channel blockers, or other. Main Outcomes and Measures Weighted frequencies and means were reported using NHANES methods, estimating the proportion of individuals with stroke and hypertension. For all other analyses, 4 971 136 individuals with stroke and hypertension were examined, summarizing number and classes of antihypertensive medications, frequency of uncontrolled hypertension, and associations between antihypertensive classes and blood pressure control. Trends in antihypertensive medication use over time were examined. Results Among 4 971 136 individuals with a history of stroke and hypertension, the mean age was 67.1 (95% CI, 66.1-68.1) years, and 2 790 518 (56.1%) were women. In total, 37.1% (33.5%-40.8%) had uncontrolled blood pressure on examination, with 80.4% (82.0%-87.5%) taking antihypertensive medication. The most commonly used antihypertensive medications were angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (59.2%; 95% CI, 54.9%-63.4%) and β-blockers (43.8%; 95% CI, 40.3%-47.3%). Examining trends over time, diuretics have become statistically significantly less commonly used (49.4% in 2005-2006 vs 35.7% in 2015-2016,P = .005), with frequencies of other antihypertensive classes remaining constant. Conclusions and Relevance In this cross-sectional study that used national survey data, substantial undertreatment of hypertension was found in individuals with a history of stroke, and more than one-third had uncontrolled hypertension. Because hypertension is a major risk factor for stroke, these data demonstrate a missed opportunity nationally for secondary stroke prevention.
An exact method for simulating rapidly decreasing tempered stable distributions in the finite variation case

Abstract Rapidly decreasing tempered stable (RDTS) distributions are useful models for financial applications. However, there has been no exact method for simulation available in the literature. We remedy this by introducing an exact simulation method in the finite variation case. Our methodology works for the wider class of p -RDTS distributions.
Screening and Referral Care Delivery Services and Unmet Health-Related Social Needs: A Systematic Review.

Introduction Unmet health-related social needs contribute to high patient morbidity and poor population health. A potential solution to improve population health includes the adoption of care delivery models that alleviate unmet needs through screening, referral, and tracking of patients in health care settings, yet the overall impact of such models has remained unexplored. This review addresses an existing gap in the literature regarding the effectiveness of these models and assesses their overall impact on outcomes related to experience of care, population health, and costs. Methods In March 2020, we searched for peer-reviewed articles published in PubMed over the past 10 years. Studies were included if they 1) used a screening tool for identifying unmet health-related social needs in a health care setting, 2) referred patients with positive screens to appropriate resources for addressing identified unmet health-related social needs, and 3) reported any outcomes related to patient experience of care, population health, or cost. Results Of 1,821 articles identified, 35 met the inclusion criteria. All but 1 study demonstrated a tendency toward high risk of bias. Improved outcomes related to experience of care (eg, change in social needs, patient satisfaction, n = 34), population health (eg, diet quality, blood cholesterol levels, n = 7), and cost (eg, program costs, cost-effectiveness, n = 3) were reported. In some studies (n = 5), improved outcomes were found among participants who received direct referrals or additional assistance with indirect referrals compared with those who received indirect referrals only. Conclusion Effective collaborations between health care organizations and community-based organizations are essential to facilitate necessary patient connection to resources for addressing their unmet needs. Although evidence indicated a positive influence of screening and referral programs on outcomes related to experience of care and population health, no definitive conclusions can be made on overall impact because of the potentially high risk of bias in the included studies.
Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review.

Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences. Emerging evidence suggests that vitamin B-12 may have an important role in other aspects of human health, including the composition and function of the gastrointestinal (gut) microbiome. Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required for over a dozen enzymes in bacteria, compared to only two in humans. However, the impact of vitamin B-12 on the gut microbiome has not been established. This systematic review was conducted to examine the evidence that links vitamin B-12 and the gut microbiome. A structured search strategy was used to identify in vitro, animal, and human studies that assessed vitamin B-12 status, dietary intake, or supplementation, and the gut microbiome using culture-independent techniques. A total of 22 studies (3 in vitro, 8 animal, 11 human observational studies) were included. Nineteen studies reported vitamin B-12 intake, status, or supplementation was associated with gut microbiome outcomes, including beta-diversity, alpha-diversity, relative abundance of bacteria, functional capacity, or short chain fatty acid production. Evidence suggests vitamin B-12 may be associated with changes in bacterial abundance. While results from in vitro studies suggest vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), findings from animal studies and observational human studies were heterogeneous. Based on evidence from in vitro and animal studies, microbiome outcomes may differ by cobalamin form and co-intervention. To date, few prospective observational studies and no randomized trials have been conducted to examine the effects of vitamin B-12 on the human gut microbiome. The impact of vitamin B-12 on the gut microbiome needs to be elucidated to inform screening and public health interventions. Statement of significance: Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required by over a dozen enzymes in bacteria. However, to date, no systematic reviews have been conducted to evaluate the impact of vitamin B-12 on the gut microbiome, or its implications for human health.
Calcium-Dependent Pulmonary Inflammation and Pharmacological Interventions and Mediators

Pulmonary diseases present a significant burden worldwide and lead to severe morbidity and mortality. Lung inflammation caused by interactions with either viruses, bacteria or fungi is a prominent characteristic of many pulmonary diseases. Tobacco smoke and E-cig use (“vaping”) are considered major risk factors in the development of pulmonary disease as well as worsening disease prognosis. However, at present, relatively little is known about the mechanistic actions by which smoking and vaping may worsen the disease. One theory suggests that long-term vaping leads to Ca2+ signaling dysregulation. Ca2+ is an important secondary messenger in signal transduction. Cellular Ca2+ concentrations are mediated by a complex series of pumps, channels, transporters and exchangers that are responsible for triggering various intracellular processes such as cell death, proliferation and secretion. In this review, we provide a detailed understating of the complex series of components that mediate Ca2+ signaling and how their dysfunction may result in pulmonary disease. Furthermore, we summarize the recent literature investigating the negative effects of smoking and vaping on pulmonary disease, cell toxicity and Ca2+ signaling. Finally, we summarize Ca2+-mediated pharmacological interventions that could potentially lead to novel treatments for pulmonary diseases.
Maintenance of Genomic Imprinting at the IGF2 Locus in Hepatoblastoma

Genomic imprinting is the parental allele specific expression of genes and has recently been shown to occur in humans. Evidence for a role for genomic imprinting in human cancer comes from the finding of preferential retention of paternal alleles in embryonal tumors undergoing loss of heterozygosity, e.g. , Wilms' tumor and osteogenic sarcoma. Recent studies have demonstrated imprinting of the insulin-like growth factor II gene at 11p15 in normal individuals, with the paternally inherited allele expressed and the maternal allele silent. It has been shown that normal imprinting is relaxed, and gene expression is biallelic in a majority of Wilms' tumors which retain heterozygosity at this locus. In this study an intragenic Apa I polymorphism is used to examine imprinting of the insulin-like growth factor II gene in hepatoblastoma. Three of 5 tumors studied were heterozygous and hence informative. All cases showed monoallelic expression of the insulin-like growth factor II gene, indicating maintenance of normal imprinting at this locus.
Fallible humans and vulnerable systems: lessons learned from aviation

In 1959, the commercial jet transport era in the United States began with the Boeing 707. Soon after, a rather serious incident occurred over Newfoundland. A 707, flying at 35,000 feet, experienced an autopilot disconnect and began a downward spiral. The captain was in the cabin, and the copilot and flight engineer did not detect the loss of control, even after the aircraft was descending rapidly, and by then were overcome by g forces and unable to make a recovery. Somehow the captain made his way back to his seat and recovered the plane at about 6000 feet above the Atlantic (Civil Aeronautics Board, 1959). With all of its electronic sophistication, the autopilot was capable of uncoupling, and perhaps more important, the crew was seemingly incapable of detecting and remedying the situation.
Stability of estrogen receptor status in breast carcinoma

BACKGROUND: The purposes of this study were to address a persistent controversy as to whether the ER status of a primary tumor remains stable during progression to metastasis and to evaluate the influence of disease course and prior systemic therapy on ER status. METHODS: Breast carcinomas from 227 women with known ER status in both primary tumor and paired metastasis were retrospectively reviewed. ER status was compared between primary and metastatic tumors with respect to metastatic site, interval between two ER assays, and intervening chemotherapy and endocrine therapy. Semiquantitative comparison of ER values was performed for 92 tumor pairs. RESULTS: ER status agreed in 210 (92.5%) patients, including 147 positive and 63 negative. Of the 17 patients (7.5%) with discordant ER status, both negative to positive conversion (n = 7) and positive to negative conversion (n = 10) were observed. ER discordance was not significantly associated with metastatic site (locoregional vs distant), time interval between assays (<5 years vs. ≥5 years), or intervening chemotherapy and endocrine therapy. Semiquantitative levels of ER expression were similar between primary and metastatic tumors. In discordant cases, variations in testing methods and marginal scores were common. CONCLUSIONS: ER status in breast carcinoma is generally stable during progression to metastasis. Preanalytical and analytical variability may contribute to discordance in some cases. Given the importance of ER status for clinical management, ER testing in metastatic breast carcinoma should be repeated, especially for patients whose clinical courses are not compatible with stated ER status. Cancer 2011. © 2010 American Cancer Society.
Towards improved privacy policy coverage in healthcare using policy refinement

It is now mandatory for healthcare organizations to specify and publish their privacy policies. This has made privacy management initiatives in the healthcare sector increasingly important. However, several recent reports in the public media and the research community about healthcare privacy [1,2] indicate that the use of privacy policies is not necessarily a strong indication of adequate privacy protection for the patient. These observations highlight the fact that the current state of privacy management in healthcare organizations needs improvement. In this paper, we present PRIMA, a PRIvacy Management Architecture, as a first step in addressing this concern. The fundamental idea behind PRIMA is to exploit policy refinement techniques to gradually and seamlessly embed privacy controls into the clinical workflow based on the actual practices of the organization in order to improve the coverage of the privacy policy. PRIMA effectively enables the transition from the current state of perceived to be privacy-preserving systems to actually privacy-preserving systems.
Evo-Devo Branches Out

Developmental Genetics and Plant Evolution. Quentin C. B. Cronk, Richard M. Bateman, and Julie A. Hawkins, Eds. Taylor and Francis, London, 2002. 559 pp. $168, £105. ISBN 0-415-25790-5. Paper, $72, £45. ISBN 0-415-25791-3. Combining contributions from the fields of molecular genetics, systematics, morphology, and evolution, the authors offer an "evo-devo" perspective on the diversification of terrestrial plants.
FTIR Microspectroscopic Analysis of Normal Human Cortical and Trabecular Bone

Fourier transform infrared microspectroscopy (FTIRM) has been used to study the changes in mineral and matrix content and composition in replicate biopsies of nonosteoporotic human cortical and trabecular bone. Changes in osteonal bone in these same samples were reported previously. Spectral maps along and across the lamellae were obtained from iliac crest biopsies of two necropsy cases. Mineral:matrix ratios, calculated from the integrated areas of the phosphate ν1, ν3 band at 900–1200 cm−1 and the amide I band at ≈1585–1725 cm−1, respectively, were relatively constant in both directions of analysis, i.e., along and across the lamellae. Analysis of the components of the ν1, ν3 phosphate band with a combination of second-derivative spectroscopy and curve fitting revealed the presence of 11 major underlying moieties. Of these, the ratio of the relative areas of the two underlying bands at ≈1020 and ≈1030 cm−1 has been shown to be a sensitive index of variation in crystal perfection in both human osteonal bone and in synthetic, poorly crystalline apatites. This ratio was calculated in both cortical and trabecular bone from human iliac crest biopsies along and across the lamellae. The ratio decreased, going from the periosteum to the medullary cavity in the cortical bone, and from the periphery towards the center of trabeculae. These observations were consistent within serial sections obtained from the same biopsy, multiple biopsies obtained from the same necropsy specimen, and biopsies obtained from the two different necropsy specimens. The results presented here along with previously reported changes in osteonal bone show a relation between bone age and ``crystallinity/maturity'' (a parameter dependent on crystallite size, hydroxyapatite-like stoichiometry, abundance of substituting ions such as CO32−; the more crystalline/mature, the more hydroxyapatite-like stoichiometry, the bigger the crystallite size, the less the ion substitution by ions such as CO32−) as deduced by the 1020/1030 cm−1 ratio. Invariably, younger normal bone is less mature/crystalline than older. These results provide a ``baseline'' for description of mineral properties, to which diseased bones may be compared.
Differential N-Demethylation of l-α-Acetylmethadol (LAAM) and norLAAM by Cytochrome P450s 2B6, 2C18, and 3A4

Abstract Incubation of l-α-acetylmethadol (LAAM) or norLAAM with cDNA-expressed P450s 3A4, 2B6, and 2C18 produced significant N-demethylation products. P450s 2C19, 2C8, 3A5, 2C9, 3A7, 1A1, and 2D6 (norLAAM only), also produced detectable product. Coexpression of cytochrome b5 enhanced LAAM N-demethylation, most dramatically for 3A4, but had marginal effects on norLAAM N-demethylation. Modeling total liver metabolism using immunoquantification and relative activity factors of P450s suggests contributions of P450 3A4 > 2B6 > 2C18, with the importance of 2B6 to 2C isozymes enhanced by relative activity factors. The ratio of dinorLAAM to norLAAM plus dinorLAAM formed from LAAM did not exceed 20%, and was isozyme and cytochrome b5 coexpression dependent. This ratio decreased with concentration with 3A4, but was relatively constant for 2B6 and 2C18. The human liver microsomes substrate-concentration response was similar to cDNA-expressed 3A4, but the ratio was higher. Changes in the environment of cDNA-expressed 3A4 also effected the magnitude of the ratio, but not the concentration-dependent decrease. These studies show that the N-demethylation of LAAM and norLAAM is not restricted to P450 3A4, particularly P450s 2B6 and 2C18, and suggest that the mechanism of sequential metabolism for 3A4 differs from that of 2B6 and 2C18.
A review of the Pikes Peak batholith, Front Range, central Colorado A “type example” of A-type granitic magmatism

The ∼1.08-Ga Pikes Peak composite batholith of central Colorado is a type example of an A-type granitic system. From the 1970s through the 1990s, details of the field relations, mineralogy, major and trace element compositions, and isotopic geochemistry of Pikes Peak rocks were documented, and they reveal the existence of two chemical groups, a potassic and a sodic series. The potassic series (∼64–78 wt % SiO 2 ) includes the Pikes Peak Granite, which is mostly coarse-grained biotite ± hornblende syenogranite and minor monzogranite that dominates the batholith. The potassic series also includes fine- to medium-grained biotite granite found in numerous, small, late-stage plutons throughout the batholith. The sodic series is found in seven plutons comprised of a wide range of rock types (∼44–78 wt % SiO 2 ), including gabbro, diabase, syenite/quartz syenite, and fayalite and sodic amphibole granite. Differences in petrologic and geochemical characteristics between the sodic and potassic series indicate different petrogenetic histories. Major and trace element and strontium and oxygen isotopic data were used by some workers to hypothesize that mantle-derived alkali basalt underwent crystal fractionation and reaction with lower crustal rocks to generate syenitic magmas of the sodic series, which subsequently underwent further fractionation to produce sodic granites. Recent studies involving estimates of oxygen fugacities, along with additional trace element and neodymium isotopic data, also support a basalt fractionation model for the sodic series, but suggest only minor crustal involvement. Gabbros and diabase dikes associated with the sodic series appear to have been derived from mantle sources that previously had been affected by a subduction event, based on neodymium isotopic and trace element data. Some workers propose that the potassic series also formed by fractionation of syenitic and/or basaltic magmas coupled with reaction with intermediate rather than lower crust. Other workers propose a model in which genesis of the potassic series was dominated by partial melting involving tonalitic sources, with fractionation and perhaps magma mixing playing subordinate roles in generating compositional diversity among the potassic granitoids. The Pikes Peak batholith thus formed by emplacement of at least two petrogenetically different granite types, which were emplaced close together in space and time and which exhibit geochemical characteristics typical of A-type granites.
Effects of syntactic complexity and sentence-structure priming on speech initiation time in adults who stutter.

Purpose To test the hypotheses that adults who stutter will be slower in producing syntactically complex sentences than fluent adults and will benefit more from sentence-structure priming than will fluent adults. Method Adults who stutter (n = 15) and fluent adults (n = 15) participated in 2 experiments. In Experiment 1, adults in both groups were administered a task that required memorization and production of sentences that varied in syntactic complexity. The same individuals who participated in Experiment 1 also participated in Experiment 2. The second experiment required all participants to create and produce sentences under primed and unprimed sentence-structure conditions. Results Relative to adults who do not stutter, the speech initiation time of fluent utterances of adults who stutter became increasingly slower as syntactic complexity increased, and they exhibited greater facilitative effects of sentence-structure priming. In addition, adults who stutter showed a significant correlation between s...
On hysteretic response and stationary phase fronts in rubber

We consider the dynamic response of natural, latex and synthetic, nitrile rubbers under non-monotonic dynamic loading conditions; in particular, we recreate an experiment first considered by Kolsky (Nature 224:1301, 1969) in which two segments of a long rubber specimen are initially maintained at different strain levels by external force and then allowed to evolve dynamically towards equilibrium. We show that as a result of the hysteretic behavior, a phase boundary that is stationary with respect to the material points can be established in both these materials. We also show that this phase boundary persists indefinitely in strain-crystallizing natural, latex rubber, but disappears quickly in the non-crystallizing nitrile rubber.
Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia

Fibromyalgia is a common, disabling syndrome that includes chronic widespread pain plus diverse additional symptoms. No specific objective abnormalities have been identified, which precludes definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by the dysfunction and degeneration of peripheral small-fiber neurons. SFPN has established causes, some diagnosable and definitively treatable, eg, diabetes. To evaluate the hypothesis that some patients labeled as having fibromyalgia have unrecognized SFPN that is causing their illness symptoms, we analyzed SFPN-associated symptoms, neurological examinations, and pathological and physiological markers in 27 patients with fibromyalgia and in 30 matched normal controls. Patients with fibromyalgia had to satisfy the 2010 American College of Rheumatology criteria plus present evidence of a physician's actual diagnosis of fibromyalgia. The study's instruments comprised the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, plus autonomic-function testing (AFT). We found that 41% of skin biopsies from subjects with fibromyalgia vs 3% of biopsies from control subjects were diagnostic for SFPN, and MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects (all P ≤ 0.001). Abnormal AFTs were equally prevalent, suggesting that fibromyalgia-associated SFPN is primarily somatic. Blood tests from subjects with fibromyalgia and SFPN-diagnostic skin biopsies provided insights into causes. All glucose tolerance tests were normal, but 8 subjects had dysimmune markers, 2 had hepatitis C serologies, and 1 family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as fibromyalgia have unrecognized SFPN, a distinct disease that can be tested for objectively and sometimes treated definitively.
Does Accuracy Make a Difference? Examining the Miscues of Proficient and Less Than Proficient Adult Readers

One theory of reading posits that “mistakes” made by readers are something that need to be corrected. An alternate theory of reading views “mistakes” as miscues and part of the natural reading process. This research study examined the miscues of proficient and less than proficient adult readers. Less than proficient adult readers produced more miscues, but when a miscue was made the proficient adult readers were no better at correcting their miscues than the less than proficient readers. When examining the types of miscues produced (i.e., insertion, omission, substitution, or misarticulation) each group of readers produced very similar percentage rates for each category.
Using Glow Stick Chemistry for Biological Imaging

This study describes an imaging strategy based on glow stick chemistry to non-invasively image oxidative stress and reactive oxygen species (ROS) production in living animals. Upon stimulation, phagocytes produce toxic levels of ROS to kill engulfed microorganisms. The mitochondrial respiratory chain continually generates low levels of superoxide (O2·−) that serve as a source for generation of downstream ROS, which function as regulatory signaling intermediaries. A ROS-reacting substrate, 2-methyl-6-[4-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin-3-one hydrochloride, was used as the chemical energy donor for generating energy transfer luminescence in phagosomes and mitochondria. Using targeted photoluminescent dyes with specific subcellular localization that serve as chemical energy recipients, our imaging data demonstrate proof-of-concept for using glow stick chemistry to visualize ROS production associated with phagocytosis and mitochondrial respiration in living mice. Glow stick imaging is a complementary hybrid of chemiluminescence and photoluminescence imaging, capable of generating red or far-red emission for deep tissue imaging.
Utility of CT head in the acute setting: value of contrast and non-contrast studies.

Introduction To examine the added diagnostic value of emergent contrast enhanced CT head (CECTH) in patients who present to the emergency department (ED) with acute non-traumatic symptoms referable to the brain, and to assess the financial implications of CECTH in the emergent setting.
Damage control sternotomy for penetrating mediastinal vascular injury

Whilst temporary vacuum-assisted wound management has become a mainstay in the treatment of patients with severe abdominal trauma in extremis, the use of this technique in the management of exsanguinating injuries and resultant physiologic decompensation in other body cavities is ill defined. Concerns over potential cardiac and pulmonary compromise secondary to packing along with the lethal nature of penetrating injuries to the thorax has limited extension of these practices to the management of this body region. Many patients with central vascular injuries secondary to penetrating trauma either expire prior to hospital arrival or arrive haemodynamically unstable and require emergency department thoracotomy. To our knowledge, there are no reports of the use of damage control sternotomy with temporary substernal and intrathoracic packing for traumatic thoracic injuries. We report our experience treating an adolescent patient who sustained a central venous injury and bilateral lung lacerations with a damage control sternotomy approach. A 15-year-old girl presented to the emergency department after sustaining multiple stab wounds to the neck, chest and back. On arrival to the emergency department, she was tachycardic (HR = 120) and hypothermic (T = 34.5 8C) but normotensive (SBP = 113) and neurologically intact (GCS = 15). Exam findings included a 3 cm laceration extending from zone 2 to zone 1 of her right neck, a 2 cm infraclavicular sucking wound to the left chest with associated crepitus and a 5 cm laceration to the posterior left shoulder. Standard ATLS resuscitation was performed and a left tube thoracostomy was placed with resultant rush of air and 500 ml of bloody drainage. A subsequent chest X-ray demonstrated a large right haemothorax. After placement of a right tube thoracostomy and immediate drainage of over 1000 ml of blood, the patient began to cough, resulting in massive bleeding from her neck wound and haemodynamic instability. Direct pressure was applied to the neck to temporarily control bleeding. Subsequent Accepted 1 March 2010