Miracle-dz/UniFAR-FTUs huggingface dataset:
Omalizumab for asthma.

A 16-year-old boy with a history of severe persistent asthma despite treatment with inhaled corticosteroids presents for evaluation. Treatment with omalizumab, a monoclonal anti-IgE antibody, is recommended. This agent has been found to reduce the frequency of exacerbations of asthma in clinical trials. It is not known how the efficacy of omalizumab compares with that of other available therapies. The drug is more expensive than other agents.
Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody.

OBJECTIVE To analyze interactions between the thyroid-stimulating hormone receptor (TSHR) and a thyroid-stimulating human monoclonal autoantibody (M22) at the molecular level. DESIGN A complex of part of the TSHR extracellular domain (amino acids 1-260; TSHR260) bound to M22 Fab was prepared and purified. Crystals suitable for X-ray diffraction analysis were obtained and the structure solved at 2.55 A resolution. MAIN OUTCOME TSHR260 comprises of a curved helical tube and M22 Fab clasps its concave surface at 90 degrees to the tube length axis. The interface buried in the complex is large (2,500 A(2)) and an extensive network of ionic, polar, and hydrophobic bonding is involved in the interaction. There is virtually no movement in the atoms of M22 residues on the binding interface compared to unbound M22 consistent with "lock and key" binding. Mutation of residues showing strong interactions in the structure influenced M22 activity, indicating that the binding detail observed in the complex reflects interactions of M22 with intact, functionally active TSHR. The receptor-binding arrangements of the autoantibody are very similar to those reported for follicle-stimulating hormone (FSH) binding to the FSH receptor (amino acids 1-268) and consequently to those of TSH itself. CONCLUSIONS It is remarkable that the thyroid-stimulating autoantibody shows almost identical receptor-binding features to TSH although the structures and origins of these two ligands are very different. Furthermore, our structure of the TSHR and its complex with M22 provide foundations for developing new strategies to understand and control both glycoprotein hormone receptor activation and the autoimmune response to the TSHR.
Dietary intake and major sources of plant lignans in Latvian men and women

Higher intake of lignans, diphenolic plant compounds, may reduce the risk of certain types of cancer and cardiovascular diseases. We assessed the dietary intake of four lignans: matairesinol, secoisolariciresinol, lariciresinol and pinoresinol. Furthermore, for the breads we supplemented the data with two more lignans: syringaresinol and medioresinol. Study subjects were 172 men and 97 women aged 40–75 years, residing in Riga, the capital of Latvia, all living at home, eating habitual food. Median total lignan intake was 2259 (range 1169–5759) μg/day. Secoisolariciresinol contributed 58% and syringaresinol 22% of lignan intake. Bread was the major food source of lignans in men (86%), whereas in women it was bread (57%) and flaxseed (35%).
Isotopic fractionation indicates anaerobic monochlorobenzene biodegradation

The concentration and isotopic composition of monochlorobenzene (MCB) was monitored in the plume of an anaerobic, contaminated aquifer in Bitterfeld, Germany. An enrichment in the carbon isotopic composition of more than 4 δ units was found at the fringes of the plume relative to the center (‐26.5 ‰), suggesting the occurrence of in situ biodegradation of MCB. A similar enrichment was measured in a detailed cross‐section of the plume and in depth‐specific samples obtained in a multilevel sampling well. The latter samples gave a good correlation of MCB concentrations and respective isotopic composition according to the Rayleigh equation. On the other hand, batch experiments using the aerobic MCB‐degrading strains Ralstonia sp. DSM 8910, Acidovorax facilis UFZ B517, Rhodococcus erythropolis UFZ B528, and Pseudomonas veronii UFZ B547 showed that the known aerobic pathway initiated by dioxygenases does not result in a significant isotopic fractionation. Thus, a novel anaerobic pathway resulting in an isotopic fractionation appears to be the predominant process of MCB degradation in this aquifer. The study also clearly demonstrates the usefulness of isotopic fractionation analysis to prove biodegradation directly in the field, even when microcosm studies are not available and a metabolic pathway has not yet been elucidated.
Diagnosis of Engaging Bipolar Bone Defects in the Shoulder Using 2-Dimensional Computed Tomography

Background: Anatomic studies have demonstrated that bipolar glenoid and humeral bone loss have a cumulative effect on shoulder instability and that these defects may engage in functional positions depending on their size and location, potentially resulting in failure of stabilization procedures. Determining which lesions pose a risk for engagement remains challenging, with arthroscopic assessments and a 3-dimensional computed tomography (CT)–based glenoid track method being accepted approaches at this time. Purpose: The purpose was to investigate the interaction of humeral and glenoid bone defects on shoulder engagement in a cadaveric model. Two alternative approaches to predicting engagement were evaluated: (1) CT of the shoulder in abduction and external rotation (ABER) and (2) measurement of the glenoid lesion width and measurement of a novel parameter, the intact anterior articular angle (IAAA), on conventional 2-dimensional multiplane reformats. Study Design: Controlled laboratory study. Methods: Hill-Sachs and glenoid defects of varying sizes were created in 12 cadaveric upper limbs, producing 45 bipolar defect combinations. The defect characteristics were assessed using CT with the shoulder in a neutral position. ABER CT was performed with the shoulder positioned in 60° of glenohumeral abduction (corresponding to 90° of abduction relative to the trunk) and 90° of external rotation. The IAAA was measured as the cartilage arc angle anterior to the Hill-Sachs defect on the axial slice bisecting the humeral head. The performance of the ABER CT and IAAA approaches to predicting engagement were compared with the glenoid track method. Results: Of the 45 defect combinations, 24 (53%) were classified as engaging using the glenoid track method. ABER CT predicted engagement accurately in 43 of 45 (96%), with a sensitivity and specificity of 92% and 100%, respectively. A logistic model based on the glenoid defect width and IAAA provided a prediction accuracy of 87%, with a sensitivity and specificity of 92% and 81%, respectively. Conclusion/Clinical Relevance: Bipolar lesions at risk for engagement can be identified accurately using an ABER CT scan or by performing 2-dimensional measurements of the glenoid defect width and IAAA on conventional CT multiplane reformats. This information will be useful for surgical planning in the setting of bipolar bone defects before shoulder stabilization.
Development and Progression of Interstitial Lung Abnormalities in the Framingham Heart Study.

RATIONALE The relationship between the development and/or progression of interstitial lung abnormalities (ILA) and clinical outcomes has not been previously investigated. OBJECTIVES To determine the risk factors for, and the clinical consequences of, having ILA progression in participants from the Framingham Heart Study. METHODS ILA were assessed in 1,867 participants who had serial chest computed tomography (CT) scans approximately 6 years apart. Mixed effect regression (and Cox) models were used to assess the association between ILA progression and pulmonary function decline (and mortality). MEASUREMENTS AND MAIN RESULTS During the follow-up period 660 (35%) participants did not have ILA on either CT scan, 37 (2%) had stable to improving ILA, and 118 (6%) had ILA with progression (the remaining participants without ILA were noted to be indeterminate on at least one CT scan). Increasing age and increasing copies of the MUC5B promoter polymorphism were associated with ILA progression. After adjustment for covariates, ILA progression was associated with a greater FVC decline when compared with participants without ILA (20 ml; SE, ±6 ml; P = 0.0005) and with those with ILA without progression (25 ml; SE, ±11 ml; P = 0.03). Over a median follow-up time of approximately 4 years, after adjustment, ILA progression was associated with an increase in the risk of death (hazard ratio, 3.9; 95% confidence interval, 1.3-10.9; P = 0.01) when compared with those without ILA. CONCLUSIONS These findings demonstrate that ILA progression in the Framingham Heart Study is associated with an increased rate of pulmonary function decline and increased risk of death.
Pattern and impact of emerging resistance mutations in treatment experienced patients failing darunavir-containing regimen

Background:Ritonavir-boosted darunavir (DRV/r) has proven potent efficacy when used in heavily pretreated patients, harboring protease inhibitor-associated resistance mutations. Limited data are available on resistance pattern emerging in patients failing DRV/r and on subsequent remaining protease inhibitor options. Methods:Analysis of baseline and failure resistance genotypes were performed in patients experiencing virologic failure (>200 copies/ml) after at least 3 months on a DRV/r (600/100 mg twice daily)-containing regimen. Results:Twenty-five highly protease inhibitor-experienced patients were included. Baseline median human immunodeficiency virus type 1 RNA was 5 log10 copies/ml and number of total-protease inhibitor, major-protease inhibitor and DRV-associated-resistance mutations was 13, 4 and 3, respectively. Median viral replication duration on DRV/r selective pressure was 34 weeks. Emergence of DRV-associated-resistance mutations was observed in 72% (18/25) of patients, at codons L89I/M/V (32%), V32I (28%), V11I (20%), I47V/A (20%), I54L/M (20%), L33F/I (16%) and I50V (16%). A high risk of DRV resistance was observed in patients with 2 and 3 baseline DRV-associated-resistance mutations and in patients with more than 24 weeks of ongoing viral replication. According to 2007 ANRS algorithm, isolates classified as susceptible to ritonavir-boosted tipranavir decreased from baseline to failure from 76 to 60% and susceptible to DRV/r from 32 to 12%. Conclusion:Emerging mutations observed after DRV/r failure were those already described to impact the DRV efficacy. Our study provided recommendations to firstly, reconsider lowering the cutoff number of DRV mutations to two; secondly, avoid keeping patients on a DRV-failing regimen for more than 24 weeks and thirdly, to examine the efficacy of using tipranavir after DRV failure.
Teachers’ perceptions of students’ additional support needs: in the eye of the beholder?

Nowadays, teachers are regarded as key players in the process of identifying and catering to students’ additional support needs within mainstream primary classrooms. However, teachers’ professional judgements regarding students with special needs have been found to be contextually influenced (e.g. by school context, student population, level of achievement). It is unclear whether teachers’ perceptions of their students’ actual support needs are also influenced by their personal and professional characteristics. Hence, a better understanding of the value of teachers’ perceptions regarding students’ needs is needed. Therefore, this study explored perceptions of 109 Dutch mainstream primary teachers regarding four dimensions of students’ additional support. It addressed whether these teacher-perceived students’ needs are affected by teachers’ years of experience, level of training, personality traits and self-efficacy beliefs. It was found that teachers’ perceptions of students’ needs were relatively unbiased by their personal and professional characteristics.
Anatomy and physiology of a neural mechanism defining depth order and contrast polarity at illusory contours

We studied the anatomy and physiology of neurons in monkey visual cortex, which contribute to mechanisms segregating figure and ground at contours based on information provided by occlusion cues. First, we defined the location of neurons sensitive to occluding (illusory) contours. These neurons were found most frequently in the pale cytochrome oxidase stripes of area V2 but rarely in V1. In area V2, they were found in all laminae and with similar frequencies. The few neurons recorded in area V1 concentrated in the upper laminae. Second, we studied the properties and anatomical location of neurons sensitive to occlusion cues (dark and light line‐ends, corners). These neurons had end‐stopped receptive fields and were found with similar frequencies in both areas. In area V1, they concentrated in the upper laminae. In area V2, they were found in all laminae and cytochrome oxidase stripes. These neurons responded to short stimuli of optimal length (bars, edges) and to stimuli terminating in their receptive field (line‐ends, corners). Overall, about half of these neurons detected the direction of such terminations and about 60% were selective for certain types of termination. In summary, our results suggest that in monkey visual cortex, occlusion cues are represented in areas V1 and V2, whereas grouping mechanisms detecting occluding contours concentrate in area V2.
nxiety and spatial attention moderate the electrocortical response o aversive pictures

Aversive stimuli capture attention and elicit increased neural activity, as indexed by behavioral, electrocortical and hemodynamic measures; moreover, individual differences in anxiety relate to a further increased sensitivity to threatening stimuli. Evidence has been mixed, however, as to whether aversive pictures elicit increased neural response when presented in unattended spatial locations. In the current study, ERP and behavioral data were recorded from 49 participants as aversive and neutral pictures were
Risk factors associated with lymphoedema among Chinese women after breast cancer surgery

Abstract Lymphoedema is recognized as a major sequela after breast cancer treatment. This study aims to estimate the risk factors of lymphoedema development after breast cancer treatment in Chinese women. A case-control study including 100 women with lymphoedema and 130 without lymphoedema, matched on the type of surgery. Lymphoedema was defined as breast cancer patients who complained of sensations such as swelling or heaviness. The logistic regression analysis was used to examine the relationship between lymphoedema and various factors. Findings from this study show that age, overweight or obesity and radiotherapy were associated with lymphoedema development. Oncologists and nurses should provide adequate information for breast cancer survivors, especially for those who are at high-risk of developing lymphoedema.
Selective prophylactic transfusion in sickle cell disease

Objective. To record feto‐maternal complications following the use of selective prophylactic transfusions in women with major sickle cell disease (SCD) and determine whether selective prophylactic transfusion reduces these complications, through a comparison with a population of women who received transfusions for complications only. Design. A retrospective cohort study. Setting. Public regional referral hospital in western French Guyana. Population. Between 1992 and 2004, in all 29 women, 55 pregnancies, and 56 neonates. Methods. Close obstetric follow‐up and selective prophylactic transfusions after 26 weeks. Main outcome measures. Adverse obstetric outcome (pre‐eclampsia, preterm delivery, intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), cesarean delivery, neonatal and maternal mortality) and end‐points for SCD outcome (vaso‐occlusive crisis (VOC), acute chest syndrome, and infections). Results. Complications involved the different major SCD types to an equal extent. Comparison with the control group showed that women who had received prophylactic transfusions had lower rates of VOC (p = 0.002) and preterm deliveries (p = 0.036), but a significant increase in IUGR cases (p = 0.048). Conclusion. Selective prophylactic transfusion seems to reduce certain maternal and fetal complications in women with severe forms of SCD. These results can only be confirmed through a randomized prospective study.
Are neonatal morbidities associated with no prenatal care different from those associated with inadequate prenatal care

Objective: Compare neonatal morbidities in women with no prenatal care, and women with inadequate prenatal care, to those with adequate prenatal care. Methods: Retrospective cohort study of neonatal morbidities of 3 exposure groups. Group 1: No prenatal care; Group 2: Inadequate prenatal care; Group 3: Intermediate/adequate prenatal care. Results: 2.5%, 23.3% and 74.1% of subjects (N = 264,138) were in Groups 1, 2 and 3 respectively. Severe neonatal morbidity was more common in Group 1, followed by Group 2, and least common in Group 3. After controlling for gestational age and birth weight, most of these differences were attenuated and not significant except for the following Group 1 vs Group 3 comparisons: meconium aspiration, odds ratio (OR) 2.15 and 95% confidence interval (CI) 1.39 - 3.33; suspected sepsis, OR 1.30 and CI 1.13 - 1.49; proven viral sepsis, OR 2.23 and CI 1.24 - 4.00. Conclusions: Severe neonatal morbidity was most common in those with no prenatal care followed by those with inadequate prenatal care. For most neonatal morbidities, this could largely be explained by gestational age and birth weight differences, but for some neonatal morbidities (meconium aspirations, viral sepsis and dysmorphic features) the impact of no prenatal care persisted after adjustment for these factors.
Diagnosing ocean feedbacks to the MJO: SST‐modulated surface fluxes and the moist static energy budget

The composite effect of intraseasonal sea surface temperature (SST) variability on the Madden‐Julian Oscillation (MJO) is studied in the context of the column‐integrated moist static energy (〈m〉) budget using data from the European Centre for Medium‐Range Weather Forecasts Interim Reanalysis (ERA‐I). SST fluctuations influence the Δq and ΔT parts of the bulk surface latent and sensible heat flux calculations, respectively, each of which influence column 〈m〉. Reynolds decomposition of latent and sensible heat fluxes (LH and SH) reveal that the thermodynamic perturbations (e.g., Δq′|V|¯ for LH) modestly offset the equatorial wind‐driven perturbations ( Δq¯|V|′ ) and 〈m〉, but strongly offset the subtropical Δq¯|V|′ and 〈m〉. Column moistening east of MJO convection is opposed by Δq¯|V|′ and supported by Δq′|V|¯ . Impacts of intraseasonal SST fluctuations are analyzed by recomputing surface flux component terms using 61 day running‐mean SST. Differences between “full SST” and “smoothed SST” projections onto 〈m〉 and its tendency (∂〈m〉/∂t) yield the “SST effect” on the MJO 〈m〉 budget. Particularly in the Indian Ocean, intraseasonal SST fluctuations maintain equatorial 〈m〉 anomalies at a rate of 1%–2% d−1 and damp subtropical 〈m〉 anomalies at a similar rate. Vertical advection (−〈ω∂m/∂p〉) exports 10%–20% of 〈m〉 per day, implying that the SST modulation of surface fluxes offsets roughly 10% of equatorial 〈m〉 export and amplifies by 10% the subtropical 〈m〉 export by −〈ω∂m/∂p〉. SST fluctuations support MJO propagation by encouraging on‐equator convection and the circulation anomalies that drive MJO propagation, and by contributing up to 10% of ∂〈m〉/∂t across the Warm Pool.
Business Ethics as Practice

In this article we develop a conceptualization of business ethics as practice. Starting from the view that the ethics that organizations display in practice will have been forged through an ongoing process of debate and contestation over moral choices, we examine ethics in relation to the ambiguous, unpredictable, and subjective contexts of managerial action. Furthermore, we examine how discursively constituted practice relates to managerial subjectivity and the possibilities of managers being moral agents. The article concludes by discussing how the ‘ethics as practice’ approach that we expound provides theoretical resources for studying the different ways that ethics manifest themselves in organizations as well as providing a practical application of ethics in organizations that goes beyond moralistic and legalistic approaches.
1 LOCUS COERULEUS NORADRENERGIC INNERVATION OF THE AMYGDALA 1 FACILITATES ALERTING-INDUCED CONSTRICTION OF THE RAT TAIL ARTERY 2 3

17 The amygdala, innervated by the noradrenergic locus coeruleus, processes salient 18 environmental events. Alpha-2 adrenoceptor-stimulating drugs (clonidine-like agents) 19 suppress the behavioral and physiological components of the response to salient events. 20 Activation of sympathetic outflow to the cutaneous vascular bed is part of the physiological 21 response to salience-mediated activation of the amygdala. We have determined whether 22 acute systemic and intra-amygdala administration of clonidine, and chronic immunotoxin23 mediated destruction of the noradrenergic innervation of the amygdala, impairs salience24 related vasoconstrictor episodes in the tail artery of conscious freely-moving Sprague25 Dawley rats. After acute i.p. clonidine (10, 50, 100 μg/kg) there was a dose-related decrease 26 in the reduction in tail blood flow elicited by alerting stimuli, an effect prevented by prior 27 administration of the alpha-2 adrenergic blocking drug idazoxan (1 mg/kg i.p. or 75 nmol 28 bilateral intra-amygdala). A dose-related decrease in alerting-induced tail artery 29 vasoconstriction was also observed after bilateral intra-amygdala injection of clonidine (5, 30 10, 20 nmol in 200 nl), an effect substantially prevented by prior bilateral intra-amygdala 31 injection of idazoxan. Intra-amygdala injection of idazoxan by itself did not alter tail artery 32 vasoconstriction elicited by alerting stimuli. Intra-amygdala injection of saporin coupled to 33 antibodies to dopamine-β-hydroxylase (immunotoxin) destroyed the noradrenergic 34 innervation of the amygdala and the parent noradrenergic neurons in the locus coeruleus. The 35 reduction in tail blood flow elicited by standardized alerting stimuli was substantially 36 reduced in immunotoxin-treated rats. Thus inhibiting the release of noradrenaline within the 37 amygdala reduces activation of the sympathetic outflow to the vascular beds elicited by 38 salient events. 39 40
Kinetics of bile salt binding to liposomes revealed by carboxyfluorescein release and mathematical modeling

We propose a mathematical model for the release of carboxyfluorescein from liposomes whose membrane permeability is modified by the binding of different bile salts to the leaflets of the lipid bilayer. We find that the permeability of the liposomal bilayer depends on the difference in the concentrations of bile salt in the inner and outer leaflets and is only minimally influenced by the total concentration of bile salt in the bilayer. Deoxycholate and cholate are found to behave similarly in enhancing permeability for limited times, whereas the novel bile salt, 12-monoketocholate, flips from the outer to inner leaflet slowly, thereby enhancing membrane permeability for a prolonged time.