Giant Two-Level Systems in a Granular Superconductor.

Disordered thin films are a common choice of material for superconducting, high impedance circuits used in quantum information or particle detector physics. A wide selection of materials with different levels of granularity are available, but, despite low microwave losses being reported for some, the high degree of disorder always implies the presence of intrinsic defects. Prominently, quantum circuits are prone to interact with two-level systems (TLS), typically originating from solid state defects in the dielectric parts of the circuit, like surface oxides or tunneling barriers. We present an experimental investigation of TLS in granular aluminum thin films under applied mechanical strain and electric fields. The analysis reveals a class of strongly coupled TLS having electric dipole moments up to 30 eÅ, an order of magnitude larger than dipole moments commonly reported for solid state defects. Notably, these large dipole moments appear more often in films with a higher resistivity. Our observations shed new light on granular superconductors and may have implications for their usage as a quantum circuit material.

Imaging the Tight Orbit: Radiologic Manifestations of Orbital Compartment Syndrome.

BACKGROUND AND PURPOSE: Orbital compartment syndrome is a sight-threatening emergency caused by rising pressure inside the orbit. It is usually diagnosed clinically, but imaging might help when clinical findings are inconclusive. This study aimed to systematically evaluate imaging features of orbital compartment syndrome. MATERIALS AND METHODS: This retrospective study included patients from 2 trauma centers. Proptosis, optic nerve length, posterior globe angle, morphology of the extraocular muscles, fracture patterns, active bleeding, and superior ophthalmic vein caliber were assessed on pretreatment CT. Etiology, clinical findings, and visual outcome were obtained from patient records. RESULTS: Twenty-nine cases of orbital compartment syndrome were included; most were secondary to traumatic hematoma. Pathologies occurred in the extraconal space in all patients, whereas intraconal abnormalities occurred in 59% (17/29), and subperiosteal hematoma in 34% (10/29). We observed proptosis (affected orbit: mean, 24.4 [SD, 3.1] mm versus contralateral: 17.7 [SD, 3.1] mm; P < .01) as well as stretching of the optic nerve (mean, 32.0 [SD, 2.5] mm versus 25.8 [SD, 3.4] mm; P < .01). The posterior globe angle was decreased (mean, 128.7° [SD, 18.9°] versus 146.9° [SD, 6.4°]; P < .01). In 69% (20/29), the superior ophthalmic was vein smaller in the affected orbit. No significant differences were detected regarding the size and shape of extraocular muscles. CONCLUSIONS: Orbital compartment syndrome is characterized by proptosis and optic nerve stretching. In some cases, the posterior globe is deformed. Orbital compartment syndrome can be caused by an expanding pathology anywhere within the orbit with or without direct contact to the optic nerve, confirming the pathophysiologic concept of a compartment mechanism.

Intranasal orexin A modulates sympathetic vascular tone: a pilot study in healthy male humans.

Previous research suggests that the neuropeptide orexin A contributes to sympathetic blood pressure (BP) control inasmuch as hypothalamic injection of orexin A increases sympathetic vasomotor tone and arterial BP in rodents. In humans with narcolepsy, a disorder associated with loss of orexin-producing neurons, vasoconstrictive muscle sympathetic nerve activity (MSNA) is reduced. Since intranasally administered oligopeptides like orexin are known to modulate brain function, we investigated the effect of intranasal orexin A on vascular sympathetic baroreflex function in healthy humans. In a balanced, double-blind crossover study, orexin A (500 nmol) and placebo, respectively, were intranasally administered to 10 lean healthy males (age 25.8 ± 4.6 yr). MSNA was assessed microneurographically before and 30-45 min after either substance administration. Additionally, baroreflex was challenged via graded infusions of vasoactive drugs before and after substance administration. Baroreflex function was defined as the correlation of BP with MSNA and heart rate. Intranasal orexin A compared with placebo induced a significant increase in resting MSNA from pre-to postadministration [Δburst rate, orexin A vs. placebo: +5.8 ± 0.8 vs. +2.1 ± 0.6 bursts/min, P = 0.007; total activity 169 ± 11.5% vs. 115 ± 5.0%; P = 0.002]. BP, heart rate, and sympathovagal balance to the heart, as represented by heart rate variability (HRV), as well as baroreflex sensitivity during the vasoactive challenge were not altered. Intranasally administered orexin A acutely induced vasoconstrictory sympathoactivation in healthy male humans. This result suggests that orexin A mediates upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex feedback loop.NEW & NOTEWORTHY Our pilot study adds another important part to the complex network of neuroendocrine-sympathetic interaction. Our results demonstrate that intranasal orexin A elicits an excitatory effect on sympathetic vascular tone superordinate to mere baroreflex feedback regulation. This resetting of the baroreflex set point suggests an activation of hypothalamic core centers such as the paraventricular nucleus (PVN). The role of the orexinergic system in the development of neurogenic arterial hypertension warrants further investigations.

Clinical characteristics and immunohistochemical analysis of p53, Ki-67 and cyclin D1 in 80 odontogenic keratocysts.

OBJECTIVE: The aim of this study was to evaluate clinical parameters and expression patterns of Ki-67, cyclin D1 and p53 in odontogenic keratocysts. MATERIAL AND METHODS: In this study, fifty-three patients with 80 odontogenic keratocysts were included. The medical records of these patients were reviewed retrospectively. To elucidate the molecular pathogenesis of the disease, the expression of p53, Ki-67 and cyclin D1 was analyzed using immunohistochemistry. RESULTS: A total of 53 patients (mean age 38 years) with a median follow-up of 4.2 years (ranging from 4 days to 14.4 years) were evaluated. The rates of recurrence and post-operative complications varied depending on the surgical approach: cystectomy and peripheral ostectomy led to manageable low rates of complications and recurrence frequency. Immunohistochemical evaluation revealed that all lesions were positive for Ki-67 and cyclin D1 expression. The expression of Ki-67 was associated with the degree of inflammation. Cyclin D1 was expressed significantly higher in syndrome-associated keratocystic lesions. In contrast to non-syndromal lesions, all syndromal lesions expressed p53. CONCLUSION: This investigation demonstrates that the pathogenesis of syndromal keratocysts appears to differ from sporadic odontogenic keratocysts. Additionally, the primary and recurrent non-syndromal keratocysts have a similar etiology, as no differences in the expression patterns of Ki-67, p53 and cyclin D1 were observed.

Phenotype diffusion and one health: A proposed framework for investigating the plurality of obesity epidemics across many species.

We propose the idea of "phenotype diffusion," which is a rapid convergence of an observed trait in some human and animal populations. The words phenotype and diffusion both imply observations independent of mechanism as phenotypes are observed traits with multiple possible genetic mechanisms and diffusion is an observed state of being widely distributed. Recognizing shared changes in phenotype in multiple species does not by itself reveal a particular mechanism such as a shared exposure, shared adaptive need, particular stochastic process or a transmission pathway. Instead, identifying phenotype diffusion suggests the mechanism should be explored to help illuminate the ways human and animal health are connected and new opportunities for optimizing these links. Using the plurality of obesity epidemics across multiple species as a prototype for shared changes in phenotype, the goal of this review was to explore eco-evolutionary theories that could inform further investigation. First, evolutionary changes described by hologenome evolution, pawnobe evolution, transposable element (TE) thrust and the drifty gene hypothesis will be discussed within the context of the selection asymmetries among human and animal populations. Secondly, the ecology of common source exposures (bovine milk, xenohormesis and "obesogens"), niche evolution and the hygiene hypothesis will be summarized. Finally, we synthesize these considerations. For example, many agricultural breeds have been aggressively selected for weight gain, microbiota (e.g., adenovirus 36, toxoplasmosis) associated with (or infecting) these breeds cause experimental weight gain in other animals, and these same microbes are associated with human obesity. We propose applications of phenotype diffusion could include zoonotic biosurveillance, biocontainment, antibiotic stewardship and environmental priorities. The One Health field is focused on the connections between the health of humans, animals and the environment, and so identification of phenotype diffusion is highly relevant for practitioners (public health officials, physicians and veterinarians) in this field.

Production of recombinant human tektin 1, 2, and 4 and in vitro assembly of human tektin 1.

Proteins predicted to be composed of large stretches of coiled-coil structure have often proven difficult to crystallize for structural determination. We have successfully applied EPR spectroscopic techniques to the study of the structure and assembly of full-length human vimentin assembled into native 11 nm filaments, in physiologic solution, circumventing the limitations of crystallizing shorter peptide sequences. Tektins are a small family of highly alpha helical filamentous proteins found in the doublet microtubules of cilia and related structures. Tektins exhibit several similarities to intermediate filaments (IFs): moderate molecular weight, highly alpha helical, hypothesized to be coiled-coil, and homo- and heteromeric assembly into long smooth filaments. In this report, we show the application of IF research methodologies to the study of tektin structure and assembly. To begin in vitro studies, expression constructs for human tektins 1, 2, and 4 were synthesized. Recombinant tektins were produced in E. coli and purified by chromatography. Preparations of tektin 1 successfully formed filaments. The recombinant human tektin 1 was used to produce antibodies which recognized an antigen in mouse testes, most likely present in sperm flagella. Finally, we report the creation of seven mutants to analyze predictions of coiled-coil structure in the rod 1A domain of tektin 1. Although this region is predicted to be coiled-coil, our EPR analysis does not reflect the parallel, in register, coiled-coil structure as demonstrated in vimentin and kinesin. These results document that tektin can be successfully expressed and assembled in vitro, and that SDSL EPR techniques can be used for structural analysis.

Glycemic Control in US Immigrant and Nonimmigrant Black Youth with Type 1 Diabetes.

Differences in glycemic control based on race have been reported in pediatric populations with type 1 diabetes (T1D). It is unknown if differences exist between pediatric populations within the same race classification. This retrospective study identified all immigrant and nonimmigrant Black youth diagnosed with T1D and treated at Seattle Children's Hospital from 2001 to 2011. Demographic characteristics and hemoglobin A1c (HbA1c) levels at 12, 24, and 36 months post diagnosis were obtained from existing medical records. Immigrant youth had lower mean HbA1c levels at all three time points. The ethnicity effect on mean HbA1c levels approached significance at 36 months. When comparing 12 and 36 months, the time effect was significant; the ethnicity effect approached significance. Clinically important differences may exist in glycemic control between pediatric populations with T1D from the same race classification. Additional work is needed to confirm these findings and determine potential causes.

Fluorescence in situ hybridization identifies high risk Barrett's patients likely to develop esophageal adenocarcinoma.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) defines a group of individuals at high risk of progression to esophageal adenocarcinoma (EA). Fluorescence in situ hybridization (FISH) has been shown to be useful for the detection of dysplasia and EA in endoscopic brushing specimens from BE patients. The aim of this study was to determine whether FISH in combination with histological findings would further identify more rapid progressors to EA. This is a retrospective cohort study of high-risk patients, having a history of biopsy-confirmed HGD without EA, with an endoscopic brushing specimen analyzed by FISH while undergoing endoscopic surveillance and treatment between April 2003 and October 2010. Brushing specimens were assessed by FISH probes targeting 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) and evaluated for the presence of polysomy, defined as multiple chromosomal gains (displaying ≥ 3 signals for ≥ 2 probes). Specimens containing ≥ 4 cells exhibiting polysomy were considered polysomic. HGD was confirmed by at least two experienced gastrointestinal pathologists. Of 245 patients in this study, 93 (38.0%) had a polysomic FISH result and 152 (62.0%) had a non-polysomic FISH result. Median follow-up was 3.6 years (interquartile range [IQR] 2-5 years). Patients with a polysomic FISH result had a significantly higher risk of developing EA within 2 years (14.2%) compared with patients with a non-polysomic FISH result (1.4%, P < 0.001). These findings suggest that a polysomic FISH result in BE patients with simultaneous HGD identifies patients at a higher risk for developing EA compared with those with non-polysomy.

Depressive symptoms, self-esteem, HIV symptom management self-efficacy and self-compassion in people living with HIV.

The aims of this study were to examine differences in self-schemas between persons living with HIV/AIDS with and without depressive symptoms, and the degree to which these self-schemas predict depressive symptoms in this population. Self-schemas are beliefs about oneself and include self-esteem, HIV symptom management self-efficacy, and self-compassion. Beck's cognitive theory of depression guided the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico. Sixty-five percent of the sample reported depressive symptoms. These symptoms were significantly (p ≤ 0.05), negatively correlated with age (r = -0.154), education (r = -0.106), work status (r = -0.132), income adequacy (r = -0.204, self-esteem (r = -0.617), HIV symptom self-efficacy (r = - 0.408), and self-kindness (r = - 0.284); they were significantly, positively correlated with gender (female/transgender) (r = 0.061), white or Hispanic race/ethnicity (r = 0.047) and self-judgment (r = 0.600). Fifty-one percent of the variance (F = 177.530 (df = 1524); p < 0.001) in depressive symptoms was predicted by the combination of age, education, work status, income adequacy, self-esteem, HIV symptom self-efficacy, and self-judgment. The strongest predictor of depressive symptoms was self-judgment. Results lend support to Beck's theory that those with negative self-schemas are more vulnerable to depression and suggest that clinicians should evaluate PLHIV for negative self-schemas. Tailored interventions for the treatment of depressive symptoms in PLHIV should be tested and future studies should evaluate whether alterations in negative self-schemas are the mechanism of action of these interventions and establish causality in the treatment of depressive symptoms in PLHIV.

A multinational study of self-compassion and human immunodeficiency virus-related anxiety.

AIM: This study represents an initial effort at examining the association between the construct of self-compassion and human immunodeficiency virus (HIV)-related anxiety in a multinational population with HIV disease. BACKGROUND: Previous studies have found that self-compassion is a powerful predictor of mental health, demonstrating positive and consistent linkages with various measures of affect, psychopathology and well-being, including anxiety. METHODS: Cross-sectional data from a multinational study conducted by the members of the International Nursing Network for HIV Research (n = 1986) were used. The diverse sample included participants from Canada, China, Namibia, the United States of America and the territory of Puerto Rico. Study measures included the anxiety subscale of the Symptom Checklist-90 instrument, the Brief Version Self-Compassion Inventory and a single item on anxiety from the Revised Sign and Symptom Checklist. FINDINGS: Study findings show that anxiety was significantly and inversely related to self-compassion across participants in all countries. We examined gender differences in self-compassion and anxiety, controlling for country. Levels of anxiety remained significantly and inversely related to self-compassion for both males (P = 0.000) and females (P = 0.000). Levels of self-compassion and anxiety varied across countries. CONCLUSIONS: Self-compassion is a robust construct with cross-cultural relevance. A culturally based brief treatment approach aimed at increasing self-compassion may lend itself to the development of a cost effective adjunct treatment in HIV disease, including the management of anxiety symptoms.

[Nursing Home Care Index. Development and validation of a new instrument to evaluate care quality in nursing homes]. / Betreuungsindex in Pflegeheimen : Entwicklung und Validierung eines neuen Instruments zur Beurteilung von Betreuungsqualität in Pflegeheimen.

BACKGROUND: There is currently no adequate tool in the literature for assessing the quality of care in nursing homes. Therefore, we developed and tested a new instrument the Nursing Home Care Index (NCI). METHODS: Quality of care is defined in the literature by 8 dimensions. An instrument with 42 questions of 12 validated scales was implemented. The new instrument was tested on 320 staff members in 15 nursing homes. The data were examined with the help of factor analysis and Cronbach's α, which reduced the factors to 3 and the questions to 16. Finally the revised scale was tested in a further pilot study with 136 staff members. RESULTS: The revised scale consists of 16 items. Based on the factor analysis, a 3-factor structure, namely social relationships, personal well-being, and self-determination were identified. These 3 factors explained 51.2% of total variance. Overall Cronbach's α was 0.87. The α reliability for the subscales was 0.86 (self-determination), 71 personal well-being, and 0.78 social relationship, respectively. Based on the NCI score, quality of care can be categorized into 3 classes: good, adequate, and urgent need for action. CONCLUSIONS: The NCI has a double function. Nursing staff and management can now use the NCI to conduct internal quality assurance regarding their caring efforts. In the future, the NCI can become a useful tool for families and residents to compare the quality of care in different nursing homes.

Association of elevation, urbanization and ambient temperature with obesity prevalence in the United States.

BACKGROUND: The macrogeographic distribution of obesity in the United States, including the association between elevation and body mass index (BMI), is largely unexplained. This study examines the relationship between obesity and elevation, ambient temperature and urbanization. METHODS AND FINDINGS: Data from a cross-sectional, nationally representative sample of 422603 US adults containing BMI, behavioral (diet, physical activity, smoking) and demographic (age, sex, race/ethnicity, education, employment, income) variables from the 2011 Behavioral Risk Factor Surveillance System were merged with elevation and temperature data from WorldClim and with urbanization data from the US Department of Agriculture. There was an approximately parabolic relationship between mean annual temperature and obesity, with maximum prevalence in counties with average temperatures near 18 °C. Urbanization and obesity prevalence exhibited an inverse relationship (30.9% in rural or nonmetro counties, 29.2% in metro counties with <250000 people, 28.1% in counties with population from 250000 to 1 million and 26.2% in counties with >1 million). After controlling for urbanization, temperature category and behavioral and demographic factors, male and female Americans living <500 m above sea level had 5.1 (95% confidence interval (CI) 2.7-9.5) and 3.9 (95% CI 1.6-9.3) times the odds of obesity, respectively, as compared with counterparts living ≥ 3000 m above sea level. CONCLUSIONS: Obesity prevalence in the United States is inversely associated with elevation and urbanization, after adjusting for temperature, diet, physical activity, smoking and demographic factors.

Mediators of antiretroviral adherence: a multisite international study.

The purpose of this study was to investigate the effects of stressful life events (SLE) on medication adherence (3 days, 30 days) as mediated by sense of coherence (SOC), self-compassion (SCS), and engagement with the healthcare provider (eHCP) and whether this differed by international site. Data were obtained from a cross-sectional sample of 2082 HIV positive adults between September 2009 and January 2011 from sites in Canada, China, Namibia, Puerto Rico, Thailand, and US. Statistical tests to explore the effects of stressful life events on antiretroviral medication adherence included descriptive statistics, multivariate analysis of variance, analysis of variance with Bonferroni post-hoc analysis, and path analysis. An examination by international site of the relationships between SLE, SCS, SOC, and eHCP with adherence (3 days and 30 days) indicated these combined variables were related to adherence whether 3 days or 30 days to different degrees at the various sites. SLE, SCS, SOC, and eHCP were significant predictors of adherence past 3 days for the United States (p = < 0.001), Canada (p = 0.006), and Namibia (p = 0.019). The combined independent variables were significant predictors of adherence past 30 days only in the United States and Canada. Engagement with the provider was a significant correlate for antiretroviral adherence in most, but not all, of these countries. Thus, the importance of eHCP cannot be overstated. Nonetheless, our findings need to be accompanied by the caveat that research on variables of interest, while enriched by a sample obtained from international sites, may not have the same relationships in each country.

Facile production of minor metabolites for drug development using a CYP3A shuffled library.

Metabolic profiling of new drugs is limited by the difficulty in obtaining sufficient quantities of minor metabolites for definitive structural identification. Biocatalytic methods offer the potential to produce metabolites that are difficult to synthesize by traditional medicinal chemistry. We hypothesized that the regioselectivity of the drug metabolizing cytochrome P450s could be altered by directed evolution to produce minor metabolites of drugs in development. A biocatalyst library was constructed by DNA shuffling of four CYP3A forms. The library contained 11 ± 4 (mean ± SD) recombinations and 1 ± 1 spontaneous mutations per mutant. On expression in Escherichia coli, 96% of mutants showed detectable activity to at least one probe substrate. Using testosterone as a model drug-like substrate, mutants were found that preferentially formed metabolites produced in only trace amounts by parental forms. A single 1.6L batch culture of one such mutant enabled the facile isolation of 0.3mg of the minor metabolite 1ß-hydroxytestosterone and its ab initio structural determination by 1D- and 2D-NMR spectroscopy.

Impact of brain tumor location on morbidity and mortality: a retrospective functional MR imaging study.

BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to preoperatively identify areas of eloquent cortex. Our study evaluated the efficacy of clinical fMRI by analyzing the relationship between the distance from the tumor border to the area of functional activation (LAD) and patient pre- and postoperative morbidity and mortality. MATERIALS AND METHODS: The study included patients with diagnosis of primary or metastatic brain tumor who underwent preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The impact of LAD and other variables collected from patient records was analyzed with respect to functional deficits in terms of morbidity (paresis and aphasia) and mortality. RESULTS: Significant relationships were found between motor and language LAD and the existence of either pre- or postoperative motor (P < .001) and language deficits (P=.009). Increasing age was associated with motor and language deficits (P=.02 and P=.04 respectively). Right-handedness was related to language deficits (P=.05). Survival analysis revealed that pre- and postoperative deficits, grade, tumor location, and LAD predicted mortality. Motor deficits increased linearly as the distance from the tumor to the primary sensorimotor cortex decreased. Language deficits increased exponentially as the distance from the tumor to the language areas decreased below 1 cm. Postoperative mortality analysis showed an interaction effect between motor or language LAD and mortality predictors (grade and tumor location, respectively). CONCLUSIONS: These findings indicate that tumors may affect language and motor function differently depending on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate patient prognosis and are directly applicable to neurosurgical planning.

A new dipteran forensic indicator in buried bodies.

The first breeding records of miltogrammine fleshflies in buried vertebrate carrion are presented. First instars of Eumacronychia persolla Reinhard (Nearctic) (Diptera: Sarcophagidae) and Phylloteles pictipennis Loew (Palaearctic) (Diptera: Sarcophagidae) are able to penetrate dry, loose soil and reach deeply buried animal remains, an ability which distinguishes is unique to necrophagous Calyptratae. Their broad geographical distribution, fast location and colonization of carrion, complete development on buried food resources and easy identification make these species useful forensic indicators in buried bodies in dry habitats.

CD11c as a transcriptional biomarker to predict response to anti-TNF monotherapy with adalimumab in patients with rheumatoid arthritis.

We performed transcription profiling using monocytes to identify predictive markers of response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). Several potential predictors of response were identified, including CD11c. Validation in samples from independent cohorts (total of n = 27 patients) using reverse transcription-PCR confirmed increased expression of CD11c in responders to adalimumab (100% sensitivity; 91.7% specificity, power 99.6%; alpha = 0.01). Pretherapy CD11c levels significantly correlated with the response criteria as defined by the American College of Rheumatology (ACR) (r = 0.656, P < 0.0001). However, CD11c was neither predictive of response to methotrexate (MTX) alone (n = 34) nor to MTX in combination with adalimumab (n = 16). Clinical responders revealed a reset to a normal expression pattern of resident/inflammatory monocyte markers, which was absent in nonresponders. Therefore, an analysis of key cell types identifies potentially predictive biomarkers that may help to restrict the use of adalimumab to therapy responders. Larger studies, including studies of monotherapy with other drugs, are now needed to confirm and validate the specificity of CD11c for anti-TNF biologics.