Miracle-dz/UniFAR-FTUs huggingface dataset:
Inequivalent quantizations and fundamentally perfect spaces.

We investigate the problem of inequivalent quantizations of a physical system with multiply connected configuration space X. For scalar quantum theory on X we show that state vectors must be single-valued if and only if the first homology group H/sub 1/(X) is trivial, or equivalently the fundamental group . pi. /sub 1/(X) is perfect. The theta-structure of quantum gauge and gravitational theories is discussed in light of this result.
Radioactive iodine in the treatment of medullary thyroid carcinoma: a controlled multicenter study.

OBJECTIVE Radioactive iodine (RAI) therapy in medullary thyroid carcinoma (MTC) is applied in some centers, based on the assumption that cross-irradiation from thyroid follicular cells may be beneficial. However, no systematic studies on the effect of RAI treatment in MTC have been performed. The aim of this study was to analyze the effect of RAI treatment on survival in MTC patients. DESIGN Retrospective multicenter study in eight University Medical Centers in The Netherlands. METHODS Two hundred and ninety three MTC patients without distant metastases who had undergone a total thyroidectomy were included between 1980 and 2007. Patients were stratified by clinical appearance, hereditary stage, screening status, and localization. All patients underwent regular surgical treatment with additional RAI treatment in 61 patients. Main outcome measures were disease-free survival (DFS) and disease-specific survival (DSS). Cure was defined as biochemical and radiological absence of disease. RESULTS In multivariate analysis, stratification according to clinical appearance (P=0.72), hereditary stage (P=0.96), localization (P=0.69), and screening status (P=0.31) revealed no significant effects of RAI treatment on DFS. Multivariate analysis showed no significant difference in DSS for the two groups stratified according to clinical appearance (P=0.14). Owing to limited number of events, multivariate analysis was not possible for DSS in the other groups of stratification. CONCLUSIONS Based on the results of the present analysis, we conclude that RAI has no place in the treatment of MTC.
Population Pharmacokinetics of Bedaquiline (TMC207), a Novel Antituberculosis Drug

ABSTRACT Bedaquiline is a novel agent for the treatment of pulmonary multidrug-resistant Mycobacterium tuberculosis infections, in combination with other agents. The objective of this study was to develop a population pharmacokinetic (PK) model for bedaquiline to describe the concentration-time data from phase I and II studies in healthy subjects and patients with drug-susceptible or multidrug-resistant tuberculosis (TB). A total of 5,222 PK observations from 480 subjects were used in a nonlinear mixed-effects modeling approach. The PK was described with a 4-compartment disposition model with dual zero-order input (to capture dual peaks observed during absorption) and long terminal half-life (t1/2). The model included between-subject variability on apparent clearance (CL/F), apparent central volume of distribution (Vc/F), the fraction of dose via the first input, and bioavailability (F). Bedaquiline was widely distributed, with apparent volume at steady state of >10,000 liters and low clearance. The long terminal t1/2 was likely due to redistribution from the tissue compartments. The final covariate model adequately described the data and had good simulation characteristics. The CL/F was found to be 52.0% higher for subjects of black race than that for subjects of other races, and Vc/F was 15.7% lower for females than that for males, although their effects on bedaquiline exposure were not considered to be clinically relevant. Small differences in F and CL/F were observed between the studies. The residual unexplained variability was 20.6% and was higher (27.7%) for long-term phase II studies.
Behavior problems in late childhood: the roles of early maternal attachment and teacher–child relationship trajectories

The purposes of the current study were: (1) to examine the roles of early maternal attachment relationships and teacher–child relationships during childhood for externalizing and internalizing behaviors in late childhood, and (2) to investigate teacher–child relationships, as well as externalizing and internalizing behaviors in early childhood as possible mechanisms linking early maternal attachment relationships to behavior problems in late childhood. Longitudinal data from the National Institute of Child Health and Human Development Early Child Care Research Network Study of Early Child Care and Youth Development (N = 1140 mothers and children) were used in this investigation. There were three main findings. First, insecure/other maternal attachment relationships in early childhood (i.e., 36 months) were associated with externalizing and internalizing behaviors in late childhood (Grade 5). Second, elevated levels of teacher–child conflict during childhood were associated with externalizing behaviors in late childhood whereas low levels of teacher–child closeness were associated with internalizing behaviors. Third, the effects of insecure/other attachment on externalizing and internalizing behaviors in late childhood were mediated through teacher–child relationships during childhood and early externalizing and internalizing behaviors. Implications for attachment theory are discussed.
BRCA-Mutation–Associated Fallopian Tube Carcinoma: A Distinct Clinical Phenotype?

OBJECTIVE: To compare clinical and histologic features between fallopian tube cancers in women with germline BRCA mutations and sporadic cases. METHODS: Twenty-eight patients with fallopian tube cancer had BRCA mutation testing using multiplex polymerase chain reaction and protein truncation testing. Histologic slides were reviewed by 2 pathologists, and immunohistochemical staining for p53, ki67, estrogen receptor, and progesterone receptor was performed on carcinomas and dysplastic and benign tubal epithelia. RESULTS: Twelve of 28 (43%) women had BRCA mutations: 11 BRCA1, 1 BRCA2. Excluding 4 cases found at prophylactic surgery, the median age of diagnosis of BRCA mutation carriers was 57 years compared with 65 years among sporadic cases (P = .09). Patients with BRCA-associated fallopian tube cancer had a median survival time of 68 months compared with 37 months when compared with sporadic cases (P = .14). Both groups had predominantly advanced stage, high grade, serous fallopian tube cancers. No patient had exclusively proximal disease. Occult fallopian tube cancer diagnosed at prophylactic surgery in BRCA mutation carriers was exclusively distal. “Skip” areas of high-grade dysplasia were only seen in 2 patients, both of whom were BRCA mutation carriers. There were no differences in the immunohistochemical staining for p53, ki67, estrogen receptor or progesterone receptor in carcinomas and dysplastic or benign epithelia of patients with or without BRCA mutations. Overexpression of p53 was commonly seen in fallopian tube cancers and dysplastic epithelium, but rarely noted in benign epithelium. CONCLUSION: Fallopian tube cancer is part of the BRCA mutation phenotype and seems to share many clinical features with sporadic fallopian tube cancers, including no exclusively proximal disease. The presentation of BRCA-associated fallopian tube cancers may, however, occur at a younger age and have an improved survival. LEVEL OF EVIDENCE: III
Gamma Knife Surgery of Vestibular Schwannomas: Volumetric Dosimetry Correlations to Hearing Loss Suggest Stria Vascularis Devascularization as the Mechanism of Early Hearing Loss

Objective: Determine which variables are correlated with early hearing changes after gamma knife surgery of vestibular schwannomas (VSs). Study Design: Prospective clinical study of hearing outcomes, radiation dosimetry, conformity, and tumor size of all sporadic unilateral VS patients treated between June 2000 and July 2009. Setting: Tertiary referral center. Patients: Fifty-nine VS patients with at least 6 months of follow-up data were studied. Interventions: Audiometry and imaging were performed to determine auditory thresholds, speech discrimination, and tumor size. Radiation doses to 5 volumes were measured. Main Outcome Measures: Pretreatment and posttreatment comparisons were performed with regard to change in tumor size; radiation dose to specific volumes including the internal auditory canal, cochlea, basal turn of the cochlea, and modiolus; and conformity of the treatment. Results: The mean follow-up was 63.76 months (standard deviation, ±29.02 mo; range, 9-109 mo). The median follow-up was 65.5 months. A statistically significant association between maximum radiation dose to the cochlea volume and 3-frequency pure-tone average in patients starting with 50 dB or lesser PTA3 was demonstrated using linear regression analysis. Conclusion: Longitudinal changes in hearing occur over time, with the largest changes seen in the first 12 months after treatment. With our study outcomes as basis, limiting the dose of radiation to the cochlea to no more than 4 Gy would likely reduce vascular injury to the stria vascularis and improve hearing outcomes. Shielding the cochlea during the treatment planning process would be one mechanism to accomplish this goal.
Spectrally coded optical nanosectioning (SpecON) with biocompatible metal–dielectric-coated substrates

Significance In this paper we describe a high-resolution light microscopy technique that translates spatial (position) information of fluorescent markers into spectral (color) information for improved biological imaging. By designing a thin biocompatible nanostructure on a microscope slide, we show how the distance-dependent spectral “fingerprint” of fluorophores can be used to monitor their relative distance from the nanostructure with an accuracy far beyond the resolution power of a conventional light microscope. We demonstrate the technique by studying the positions and dynamics of key proteins that play a role in cell motility. Fluorescence nanosectioning within a submicron region above an interface is desirable for many disciplines in the life sciences. A drawback, however, to most current approaches is the a priori need to physically scan a sculptured point spread function in the axial dimension, which can be undesirable for optically sensitive or highly dynamic samples. Here we demonstrate a fluorescence imaging approach that can overcome the need for scanning by exploiting the position-dependent emission spectrum of fluorophores above a simple biocompatible nanostructure. To achieve this we have designed a thin metal–dielectric-coated substrate, where the spectral modification to the total measured fluorescence can be used to estimate the axial fluorophore distribution within distances of 10–150 nm above the substrate with an accuracy of up to 5–10 nm. The modeling and feasibility of the approach are verified and successfully applied to elucidate nanoscale adhesion protein and filopodia dynamics in migrating cells. It is likely that the general principle can find broader applications in, for example, single-molecule studies, biosensing, and studying fast dynamic processes.
RELEASE OF CARBOHYDRATES AND PROTEINS BY A SUBTROPICAL STRAIN OF RAPHIDIOPSIS BROOKII (CYANOBACTERIA) ABLE TO PRODUCE SAXITOXIN AT THREE NITRATE CONCENTRATIONS 1

Raphidiopsis brookii P. J. Hill (cyanobacteria) was isolated from a small subtropical eutrophic pond (Biguá Pond) located in the grounds of Rio Grande University in the extreme south of Brazil, following a toxic bloom of this species. Growth, saxitoxin production, and release of carbohydrates and protein were monitored at three sodium nitrate concentrations (500, 1,000, and 1,500 μM), from inoculation up to the stationary growth phase. Growth was monitored by determining the biovolume, chl content, and trichome count. Growth was better described in terms of biovolume and chl measurements, because trichome fragmentation was observed to increase at the stationary growth phase. Carbohydrates and proteins were released in small amounts during most of the experiment, with a significant increase during the stationary phase. Extracellular polysaccharides were essentially composed of glucose, galactose, N‐acetyl‐glucosamine, mannose, xylose, rhamnose, arabinose, and fucose. The relative proportions of these units showed no significant variation during growth. Small quantities of extracellular free carbohydrates were also detected, and only fucose was released in significant amounts at the lowest nitrate concentration (500 μM). R. brookii produced both saxitoxin and dc‐saxitoxin, the former at four times the rate of the latter. This was the first study demonstrating saxitoxin production and the release of both carbohydrate and protein by R. brookii.
Formal and exact reduction for differential models of signalling pathways in rule-based languages. (Réduction formelle et exacte de modèles différentiels de voies de signalisation en Kappa)

Le comportement d'une cellule depend de sa capacite a recevoir, propager et integrer des signaux, constituant ainsi des voies de signalisations. Les proteines s'associent entre elles sur des sites de liaisons, puis modifient la structure spatiale des proteines voisines, ce qui a pour effet de cacher ou de decouvrir leurs autres sites de liaisons, et donc d'empecher ou de faciliter d'autres interactions. En raison du grand nombre de differents complexes bio-moleculaires, nous ne pouvons pas ecrire ou generer les systemes differentiels sous-jacents. Les langages de reecritures de graphes a sites offrent un bon moyen de decrire ces systemes complexes. Neanmoins la complexite combinatoire resurgit lorsque l'on cherche a calculer de maniere effective ce comportement. Ceci justifie l'utilisation d'abstractions. Nous proposons deux methodes pour reduire la taille des modeles de voies de signalisation, decrits en Kappa. Ces methodes utilisent respectivement la presence de symetries parmi certains sites et le fait que certaines correlations entre l'etat de differentes parties des complexes biomoleculaires n'ont pas d'impact sur la dynamique du systeme global. Des sites qui ont la meme capacite d'interaction sont lies par une relation de symetrie. Nous montrons que cette relation induit une bisimulation qui peut etre utilisee pour reduire la taille du modele initial. L'analyse du flot d'information detecte les parties du systeme qui influencent le comportement de chaque site. Ceci nous autorise a couper les especes moleculaires en petits morceaux pour ecrire un nouveau systeme. Enfin, nous montrons comment raffiner cette analyse pour tenir compte d'information contextuelle. Les deux methodes peuvent etre combinees. La solution analytique du modele reduit est la projection exacte de la solution originelle. Le calcul du modele reduit se fait au niveau des regles, en evitant l'execution du modele initial.
Investigation of Atopy in Primary Cutaneous CD30+ T-Cell Lymphoproliferative Disorders

Background: A link between atopy and primary cutaneous CD30+ lymphoproliferative disorders (CD30CLPD), which encompasses lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (pcALCL), has been suggested in the literature. Objective: Investigate whether patients with CD30CLPD have an atopic diathesis. Methods: We reviewed our experience with 157 patients with LyP and 23 patients with pcALCL for: (1) the patients’ personal history of seasonal allergic rhinitis, allergic asthma or atopic dermatitis/eczema, (2) a history of these conditions in a first degree family member, and (3) a serum total IgE level that exceeds 100 IU/mL which in adults has been used to signify “probable atopy”. Also recorded were a history of patients’ allergic reactions to medications and absolute peripheral blood eosinophil counts. Results: A personal history of at least one atopic disorder was noted for 38% and 17% of patients with LyP and pcALCL, respectively. Allergic rhinitis was the most frequent allergy in both LyP and pcALCL subsets (27% overall) with asthma and eczema reported in 10% or fewer cases. The prevalence of allergic rhinitis in these subsets was significantly lower than the 38.2% prevalence observed for healthy controls derived from the Interlymph project. However, recall bias and unstructured collection of data may contribute to these different results. The frequency of allergic drug reactions, most often to penicillin type drugs, were similar for both LyP and pcALCL subsets (28% overall). The frequency of penicillin reactions for patients with pcALCL was significantly higher than the 11.46% rate reported by Albin (P= 0.01). At least one atopic condition was recorded for a parent, sibling or child in about 20% of patients with either LyP or pcALCL. Multiple atopic conditions in first degree family members occurred in about a third of these cases, in particular for family members of patients with LyP-C. Mean total serum IgE values were significantly increased in patients with LyP and pcALCL compared to published reference values for non-atopic adults in the US and Europe. Between 30 to 36% of patients with LyP type A, LyP type C and pcALCL, but not LyP type B, had total IgE values that exceeded 100 IU/ml. Research Article
Theoretical Limitations on the Efficient Use of Parallel Memories

The effective utilization of single-instruction-multiple-data stream machines depends heavily on being able to arrange the data elements of arrays in parallel memory modules so that memory conflicts are avoided when the data are fetched. Several classes of storage algorithms are presented. Necessary and sufficient conditions are derived which can be used to determine if all conflict can be avoided. For the matrix subparts most often demanded in numerical analysis computations, whenever the class of storage algorithms called periodic skewing schemes provides conflict-free access, the subclass called linear skewing schemes also provides such access.
The Relationship Between Hospital Systems Load and Patient Harm

Objectives The objective of this study was to describe the relationship between patient harm due to health-care errors and the stresses on the hospital systems that occur because of the patients in need of care. Methods Two California hospitals each provided 1 year of data to study the relationship between patient harm and Hospital Systems Load. This observational study used 2 metrics, Hospital Systems Load and patient harm. Hospital Systems Load was a composite measure consisting of the areas in the hospital most sensitive to intensity of service developed using factor analysis and clinical judgment to select the components. Patient harm was assessed using a weighted measure of all hospital incidents occurring during a single day and another controlling for census. Analyses were performed separately for each hospital, and each was broken up into weekdays and weekends. These 8 conditions were compared using a Pearson’s r and a trend analysis. Results Patient harm trended upward as the Hospital Systems Load increased. Six of the 8 analyses were statistically significant. Conclusions The results of this analysis are highly suggestive of a relationship between Hospital Systems Load and patient harm.
FUM2, a Cytosolic Fumarase, Is Essential for Acclimation to Low Temperature in Arabidopsis thaliana1[OPEN]

Accumulation of fumaric acid, catalyzed by a cytosolic fumarase, is essential for Arabidopsis thaliana to acclimate photosynthesis to low temperature. Although cold acclimation is a key process in plants from temperate climates, the mechanisms sensing low temperature remain obscure. Here, we show that the accumulation of the organic acid fumaric acid, mediated by the cytosolic fumarase FUM2, is essential for cold acclimation of metabolism in the cold-tolerant model species Arabidopsis (Arabidopsis thaliana). A nontargeted metabolomic approach, using gas chromatography-mass spectrometry, identifies fumarate as a key component of the cold response in this species. Plants of T-DNA insertion mutants, lacking FUM2, show marked differences in their response to cold, with contrasting responses both in terms of metabolite concentrations and gene expression. The fum2 plants accumulated higher concentrations of phosphorylated sugar intermediates and of starch and malate. Transcripts for proteins involved in photosynthesis were markedly down-regulated in fum2.2 but not in wild-type Columbia-0. Plants of fum2 show a complete loss of the ability to acclimate photosynthesis to low temperature. We conclude that fumarate accumulation plays an essential role in low temperature sensing in Arabidopsis, either indirectly modulating metabolic or redox signals or possibly being itself directly involved in cold sensing.
Maxillary sinus floor augmentation using biphasic calcium phosphate: a histologic and histomorphometric study.

PURPOSE The aim of this study was to analyze the histologic quality and histomorphometric quantity of newly formed bone and the biologic properties after maxillary sinus floor augmentation with biphasic tricalcium phosphate (BCP) prior to dental implant placement. MATERIALS AND METHODS The selected alloplastic bone substitute, a blend of 60% hydroxyapatite and 40% β-tricalcium phosphate, was placed into the sinus cavity and covered with a bioresorbable membrane. Ten bone samples were harvested from the grafted sinuses of eight patients at 6 months postsurgery for histologic and histomorphometric analysis during implant placement at stage-two surgery. RESULTS Histologic analysis of the 10 biopsy specimens showed remaining BCP particles in intimate contact with the newly formed bone. Several areas of bone substitute resorption and new bone remodeling were observed. The mean composition of the bone samples harvested from the grafted sinuses was 26.1% ± 6.3% newly formed bone, 29.3% ± 9.1% remaining BCP particles, and 44.7% ± 7.7% connective tissue/bone marrow. CONCLUSION BCP biomaterial was osteoconductive and biocompatible. This biomaterial scaffold promoted the formation of new bone, which was in intimate contact with the remaining bone substitute particles. Within the limits of this study, maxillary sinus floor augmentation using BCP bone substitute is a reliable procedure for dental implant placement.