Measurement of the ν_{e}-Nucleus Charged-Current Double-Differential Cross Section at ⟨E_{ν}⟩=2.4 GeV Using NOvA.

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×10^{20} protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q^{2} (squared four-momentum transfer) and energy, in the range 1 GeV≤E_{ν}<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q^{2}.

Search for Active-Sterile Antineutrino Mixing Using Neutral-Current Interactions with the NOvA Experiment.

This Letter reports results from the first long-baseline search for sterile antineutrinos mixing in an accelerator-based antineutrino-dominated beam. The rate of neutral-current interactions in the two NOvA detectors, at distances of 1 and 810 km from the beam source, is analyzed using an exposure of 12.51×10^{20} protons-on-target from the NuMI beam at Fermilab running in antineutrino mode. A total of 121 of neutral-current candidates are observed at the far detector, compared to a prediction of 122±11(stat.)±15(syst.) assuming mixing only between three active flavors. No evidence for ν[over ¯]_{µ}→ν[over ¯]_{s} oscillation is observed. Interpreting this result within a 3+1 model, constraints are placed on the mixing angles θ_{24}<25° and θ_{34}<32° at the 90% C.L. for 0.05 eV^{2}≤Δm_{41}^{2}≤0.5 eV^{2}, the range of mass splittings that produces no significant oscillations at the near detector. These are the first 3+1 confidence limits set using long-baseline accelerator antineutrinos.

First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.

The NOvA experiment has seen a 4.4σ signal of ν[over ¯]_{e} appearance in a 2 GeV ν[over ¯]_{µ} beam at a distance of 810 km. Using 12.33×10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν[over ¯]_{µ}→ν[over ¯]_{e} candidates with a background of 10.3 and 102 ν[over ¯]_{µ}→ν[over ¯]_{µ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm_{32}^{2}|=2.48_{-0.06}^{+0.11}×10^{-3} eV^{2}/c^{4} and sin^{2}θ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δ_{CP}=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ_{23} values in the upper octant by 1.6σ.

Social anxiety and autism spectrum traits among adult FMR1 premutation carriers.

Behavioral symptoms and traits have been proposed as early markers in neurodegenerative diseases. The aim of this study was to evaluate social anxiety and autism in FMR1 premutation carriers using the Social Phobia Inventory (SPIN) and the Autism-Spectrum Quotient (AQ) questionnaires. Fifty-nine premutation carriers were compared with 50 controls. The SPIN test showed statistically significant differences between female but not male carriers. The AQ questionnaire found statistically significant differences between premutation carriers and controls in the total AQ as well as in the social skills and attention switching subdomains. A gender effect was only observed for the social skills subdomain. Spearman's correlation analysis revealed a moderately positive correlation with the total AQ scores as well as the social skills and communication subdomains. Our results show that fragile X-associated tremor/ataxia syndrome (FXTAS) patients have higher AQ scores. Moreover, this is the first study to find statistically significant differences between FXTAS and no-FXTAS premutation carriers in the communication and the imagination subdomains, suggesting that FXTAS patients present a broader autistic phenotype than premutation carriers without FXTAS. Based on our results, a wide range of behavioral/psychiatric traits should be included within the broader phenotypic presentation of individuals with the FMR1 premutation.

Measurement of the Neutrino Mixing Angle θ_{23} in NOvA.

This Letter reports new results on muon neutrino disappearance from NOvA, using a 14 kton detector equivalent exposure of 6.05×10^{20} protons on target from the NuMI beam at the Fermi National Accelerator Laboratory. The measurement probes the muon-tau symmetry hypothesis that requires maximal θ_{23} mixing (θ_{23}=π/4). Assuming the normal mass hierarchy, we find Δm_{32}^{2}=(2.67±0.11)×10^{-3} eV^{2} and sin^{2}θ_{23} at the two statistically degenerate values 0.404_{-0.022}^{+0.030} and 0.624_{-0.030}^{+0.022}, both at the 68% confidence level. Our data disfavor the maximal mixing scenario with 2.6σ significance.

Constraints on Oscillation Parameters from ν_{e} Appearance and ν_{µ} Disappearance in NOvA.

Results are reported from an improved measurement of ν_{µ}→ν_{e} transitions by the NOvA experiment. Using an exposure equivalent to 6.05×10^{20} protons on target, 33 ν_{e} candidates are observed with a background of 8.2±0.8 (syst.). Combined with the latest NOvA ν_{µ} disappearance data and external constraints from reactor experiments on sin^{2}2θ_{13}, the hypothesis of inverted mass hierarchy with θ_{23} in the lower octant is disfavored at greater than 93% C.L. for all values of δ_{CP}.

First Measurement of Electron Neutrino Appearance in NOvA.

We report results from the first search for ν_{µ}→ν_{e} transitions by the NOvA experiment. In an exposure equivalent to 2.74×10^{20} protons on target in the upgraded NuMI beam at Fermilab, we observe 6 events in the Far Detector, compared to a background expectation of 0.99±0.11(syst) events based on the Near Detector measurement. A secondary analysis observes 11 events with a background of 1.07±0.14(syst). The 3.3σ excess of events observed in the primary analysis disfavors 0.1π<δ_{CP}<0.5π in the inverted mass hierarchy at the 90% C.L.

Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis--subjective grading versus computer-aided objective quantification.

PURPOSE: To compare joint inflammation assessment using subjective grading of power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS) versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37 joints of 28 patients with arthritis of different etiologies underwent B-mode ultrasonography, PDUS, and CEUS using a second-generation contrast agent. Synovial thickness, extent of vascularized pannus and intensity of vascularization were included in a 4-point PDUS and CEUS grading system. Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS quantification using Qontrast® software for the calculation of the signal intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The interobserver agreement for subjective scoring was good to excellent (κ = 0.8 - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P < 0.05). The Qontrast® SI ratio correlated with subjective CEUS (P < 0.02) and PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or synovial thickening (P = N. S.) and no correlation between synovial thickening and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.). CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are valuable for assessing joint vascularity in arthritis and computer-aided CEUS quantification may be a suitable objective tool for therapy follow-up in arthritis.

Correction to: Curative radiation therapy for very elderly bladder cancer patients with localized disease.

In the original version of this article the figure captions of Figs. 1 and 2 were interchanged.

Curative radiation therapy for very elderly bladder cancer patients with localized disease.

PURPOSE: To report the outcomes of a cohort of very elderly muscle-invasive bladder cancer (MIBC) patients treated with contemporary 3D-conformal radiation therapy (3D-CRT) with or without concurrent chemotherapy, after transurethral resection of bladder tumor (TURBT). METHODS: From February 2010 to January 2014, a total of 41 patients older than 75 years, with T2-3 N0-1 high-grade MIBC, a Karnofsky index (KI) of at least 90% and/or a Barthel scale score of at least 95, were treated with TURBT followed by radiotherapy (RT) with or without chemotherapy, and were prospectively followed-up. RESULTS: The mean age of patients was 82 years (range 76-88). Median follow-up was 47 months for surviving patients. Mean Charlson Comorbidity Index (CCI) score was 5 points. 28 patients (68.29%) were T2N0. All received 3D-CRT to a mean dose of 60 Gy (range 48.6-66 Gy), and chemotherapy was delivered to 34 patients (83%). Cause-specific survival (CSS) was 86 and 78.8% at 1 and 5 years, respectively. Patients achieving a complete response lived longer (48 vs 14 m, p = 0.036) than those with a progressive disease, who were more likely to die from cancer than from other causes (HR 3.865, IC95% 1.562-9.562). Dead patients had a longest treatment time (mean 56.78 vs 48.91 days, p = 0.019) than survivors. CONCLUSION: RT with contemporary 3D-CRT techniques after TURBT for MIBC in elderly patients is feasible and well-tolerated. Achieving a maximal response and shortening the total radiation treatment time may improve outcomes and quality of life.

Inhibitory effects of leflunomide therapy on the activity of matrixmetalloproteinase-9 and the release of cartilage oligomeric matrix protein in patients with rheumatoid arthritis.

OBJECTIVE: To determine the effects of the disease modifying antirheumatic drug (DMARD) leflunomide on the expression of the matrix metalloproteinase MMP-1 (collagenase) and the activity of MMP-9 that are believed to play a major role in cartilage destruction associated with inflammation in patients with rheumatoid arthritis (RA). Serum concentrations of cartilage oligomeric matrix protein (COMP) should offer promise for monitoring tissue degradation in the RA joints during a 6-month therapy with leflunomide. METHODS: Thirty-six patients with RA meeting the ACR-criteria were recruited for the study in a multicentre trial. A dose of 20 mg leflunomide/day (after a 3-day 100 mg/day loading dose), an isoxazole derivate and inhibitor of the "de novo" pyrimidine synthesis, was administered for a study period of 6 months. MMP-1, the activity of MMP-9 and COMP values were measured in serum by enzyme immuno assay. The very sensitive acute phase protein serum amyloid A (SAA) was also determined by EIA. The measurements were performed before and after 3 and 6 months of leflunomide therapy. RESULTS: High levels of active MMP-9, COMP and SAA were detected in the sera of the patients with RA prior to the start of the leflunomide therapy compared to normal control sera. A significant reduction of the MMP-9 activity levels was seen after 3 months immunomodulation with leflunomide and was maintained after 6 months (p < 0.01). The degradation marker COMP and the inflammation marker SAA decreased significantly after 6 months (p < 0.04, respectively p < 0.01). There was also an insignificant tendency of MMP-1 reduction in serum after 6 months. CONCLUSION: This study demonstrated that a DMARD therapy with leflunomide can cause positive effects on cartilage degradation and inflammation achieving reductions in the acute phase protein SAA, the enzymatic attack of MMPs and the loss of the cartilage matrix component COMP.

Cosmetic outcome of breast conservative treatment for early stage breast cancer.

PURPOSE: To evaluate the cosmetic outcome of breast conservative therapy and to examine the degree of agreement between the patients' and oncologists' ratings. We also analyze the influence of several factors on cosmesis. METHODS AND MATERIALS: We retrospectively evaluated 145 patients with primary breast cancer treated by local excision and radiotherapy between January 2000 and May 2001. Cosmetic outcome was evaluated by doctors and patients and was scored as excellent, good, fair or poor. RESULTS: 73% of patients rated cosmesis as excellent or good while the percentage was 71% when rated by radiation oncologists. The degree of cosmesis concordance evaluated by oncologists and patients was low (kappa = 0.3). In our study the variables which significantly influence on the cosmetic outcome were concomitant adjuvant chemotherapy (p = 0.04) and radiation therapy boost, either by electron beam or brachytherapy (p = 0.013). CONCLUSION: The cosmetic outcome of breast conserving therapy was good. There was a similar rating by the patient and radiation oncologist, but the level of concordance between patients and doctors was low. Factors that significantly influence the cosmesis appear to be concomitant adjuvant chemotherapy and radiation therapy boost.

Impact of Whole Body Cryotherapy at -110 °C on Subjects with Arterial Hypertension.

Whole body cryotherapy (WBC) in a cryo-chamber as a medical treatment was first established in Japan in the 1980s, later in Central Europe, and is now becoming more popular also in the United States. The exposure to extreme, non-physiological environmental conditions in a cryo-chamber at -110 °C may exceed the normal adaption capacity. The aim of this study was to investigate the effects of WBC on blood pressure (BP) readings in adult subjects with rheumatic disorders and normal or moderately elevated BP. A sample of 23 subjects (8 female, 15 male) which were recruited according to their pathology between the age of 35 and 69 years undergoing 21 WBC applications was divided into three groups: a group of subjects with anti-hypertensive therapy, a group of subjects with mild arterial hypertension without medical treatment, and a normotensive control-group. A total of 483 BP readings were taken immediately before and after each WBC application. The systolic and diastolic BP were recorded, and the mean arterial pressure, and the amplitude of BP were calculated. A statistically significant rise of BP after WBC was found in the whole sample and in the normotensive group. Over the course of time, no significant change of BP behavior was observed, except for normotensive subjects, who showed a wider range in their systolic BP values. Generally accepted exclusion criteria were applied, and in our sample group WBC was safe with respect to unwanted BP alterations for adult subjects under 70 years-regardless of a pre-existing untreated mild or pharmacologically treated arterial hypertension. Greater changes of BP values might infrequently occur, so an individual monitoring of subjects is necessary.

The presence of secretoneurin in human synovium and synovial fluid.

Secretoneurin is a neuropeptide formed from the proprotein secretogranin II. It is found in afferent nerve fibres and has chemotactic activity for monocytes, neutrophils and fibroblasts. We investigated the presence of secretoneurin in synovial fluid and synovium from patients with osteoarthritis and rheumatoid arthritis. The secretoneurin immunoreactive material found in synovial fluid was identified by high performance liquid chromatography as the free peptide secretoneurin. Its level in hip joints was 15.6, in knee joints of osteoarthritis patients 17.3 and in rheumatoid patients significantly lower (8.6 fmol/ml). Immunocytochemistry provided evidence for the presence of sub-intimal secretoneurin-immunoreactive nerve fibres in knee synovium in osteoarthritic patients. In rheumatoid synovium, only very few immunoreactive fibres were found these being mostly localised in deep stroma. The results show that secretoneurin is present in osteoarthritic joint and suggest that secretoneurin levels are down-regulated in rheumatoid joint. Therefore, secretoneurin may participate in acute or mild phases of inflammation but is unlikely to have a major role when more severe inflammation is present such as that seen in rheumatoid joint.

The impact of life events on patients with rheumatoid arthritis: a psychological myth?

OBJECTIVE AND METHODS: A large number of studies from the field of "psychorheumatology" have investigated the relationship between critical life events and disease parameters with varying results. In the present study 48 patients with rheumatoid arthritis (RA) (mean age 57.8; range 32-78 years) were questioned about life events within the past two years using an "inventory for assessing life change events"-ILE (1). In contrast to previous studies, this inventory not only assesses the number of life events, but also captures the extent of subjectively experienced stress caused by these events. Since psychosocial factors such as social support and coping strategies influence subjectively experienced stress, these factors were taken into consideration for the definition of "life event". Furthermore, a series of objective medical parameters as well as the patient's and the physician's subjective impression of disease activity were assessed. RESULTS: The results show that patients with RA in the earlier stages of the disease cannot be differentiated from severely affected patients in later stages on the basis of life event parameters. In addition, no differences in the life event data could be observed between patients with and those without subjectively experienced episodes of illness in the two years immediately preceding the study. CONCLUSION: Our results suggest that the course of RA is influenced neither by the number of life events nor by the extent of stress caused by these life events. Therefore, the role of life events should not be overemphasized, at least as far as the disease parameters in RA is concerned.

Body image of women with rheumatoid arthritis.

OBJECTIVE: Physical disabilities generally cause severe disturbances in a patient's body image perception. The aim of the present study was to investigate different aspects of body image, including sexual dissatisfaction, in women with rheumatoid arthritis (RA) in relation to their subjective impression of handicap. METHODS: Forty women with RA were investigated using a series of instruments: Strauss and Appelt's questionnaire for assessing one's body (1), the body perception scale of Paulus (2), and an interview focusing on appearance, worries about health and sickness, and sexual dissatisfaction. In addition, clinical parameters and the subjective extent of morning stiffness were documented, and patients with a high degree of morning stiffness were compared to patients with a low degree of morning stiffness. RESULTS: In contrast to patients with a low degree of morning stiffness, patients with a high degree of morning stiffness worried significantly more about their bodies (p < or = 0.05) and reported significantly more problems in sexuality (p < or = 0.05). CONCLUSION: Our results suggest that morning stiffness plays a very important role in how severely a woman feels herself to be handicapped. Severely handicapped women have to deal with anxieties about health and have sexual problems. Physicians should not shy away from addressing these issues and in severe cases psychological therapy should be initiated.

Stable pattern of stress coping in patients with rheumatoid arthritis.

The stress coping mechanisms of patients with rheumatoid arthritis (74 women and 27 men) were compared to those of healthy controls (17 women and 16 men) using the Stress Coping Questionnaire of Janke et al. (1). Based on the duration of illness, male and female patients were divided into three groups, those with a duration of illness of less than 5 years, those with 5-15 years and a third group with 15 or more years of illness. From a comparison of these groups with healthy controls, the following conclusions can be drawn: (1) RA patients can be characterized by a coping pattern which is determined by significantly more cognitive mechanisms, e.g. trivialization, more attempts at controlling their reactions and less self-accusation. (2) The patient groups with different disease durations do not differ in their coping patterns. The stress coping behaviour of RA patients seems to be stable and does not appear to be influenced by the duration of illness.

Efficacy of an EMG-biofeedback therapy in fibromyalgia patients. A comparative study of patients with and without abnormality in (MMPI) psychological scales.

OBJECTIVE: The aim of the present study was to investigate the efficacy of EMG-biofeedback in female fibromyalgia patients with and without abnormality in the MMPI. METHODS: According to their MMPI profile out of a total of 24 patients, 12 patients were classified as 'psychologically abnormal' (at least one scale with a T-score higher than 70) and 12 as 'normal'. In a quasi-experimental setting, all patients underwent EMG-biofeedback therapy (12 sessions, twice weekly), after a waiting period of six weeks. Clinical symptoms (pressure point sensitivity, secondary symptoms), subjective pain dimensions as well as quality of life were assessed before and after the waiting period, immediately after the biofeedback training and at a three month follow up. RESULTS: Within the 'psychologically abnormal' patients primarily depressive, hypochondriacal and hysterical symptoms were found. Statistical evaluation showed that 'psychologically normal' patients experience long-term relief from pain measured in terms of pressure point sensitivity; vitality and mental health. 'Psychologically abnormal' patients, on the other hand, showed improvements in all the measured parameters (clinical symptoms, sensory and affective pain components, quality of life) after EMG-biofeedback. Long-term improvement, however, was observed only in pressure point sensitivity and the sensory pain dimension. CONCLUSION: The results suggest, that assessment of FM-patients should not only consist of commonly used ACR diagnostic criteria but should also include psychodiagnostic criteria, as these may co-determine treatment outcome. One approach to treating FM patients with additional psychological abnormality might be combining EMG-biofeedback that enhances self-efficacy with psychotherapy that helps patients to become aware of their basic psychological problems.

Oxidative burst of neutrophils in patients with rheumatoid arthritis: influence of various cytokines and medication.

OBJECTIVE: Toxic oxygen products are believed to be implicated in tissue damage in some complex-mediated diseases such as rheumatoid arthritis. In the present study we compared the superoxide (O2) production of polymorphonuclear leukocytes (PMNs) in 21 patients with rheumatoid arthritis (RA) with that of 9 healthy controls, examining the effect of different stimulants and cytokines on the oxidative burst (OB). Since many drugs used in the treatment of RA may alter O2 metabolism, the effects of antirheumatic medication were also studied. METHODS: Generation of superoxide anions was analysed by a flow cytometric method, using the fluorochrome dihydro-rhodamine. As stimulants for OB, we used N-formyl-methionyl-leucyl-phenylalanine (fMLP), which acts via a membrane receptor, and phorbol-myristate acetate (PMA), which acts in a membrane receptor-independent manner. As preactivating substances, TNF-alpha, G-CSF and GM-CSF were applied. RESULTS: In RA patients under treatment with antirheumatic medication, fMLP-induced OB (+/- cytokines) was significantly reduced, while O2 production after stimulation with PMA was similar compared to controls. GM-CSF showed the highest level of preactivation in controls, whereas in RA patients TNF-alpha proved to be most potent. In both controls and RA patients, a combination of GM-CSF or G-CSF with TNF-alpha further enhanced OB. No correlation between OB and clinical data or treatment could be established in RA patients. CONCLUSIONS: There is a reduced cytokine priming capacity for OB in RA patients under antirheumatic medication in spite of the presence of an intact enzyme system of OB. Antirheumatic medication combining multiple drugs capable of decreasing OB might effectively modulate oxidative metabolism.

Decrease of respiratory burst in neutrophils of patients with ankylosing spondylitis by combined radon-hyperthermia treatment.

OBJECTIVE: To define the respiratory burst activity of neutrophils, the total anti-oxidative status of plasma, and the parameters of systemic inflammation in patients with ankylosing spondylitis (AS) before and after a combined radon-hyperthermia treatment in the thermal tunnels of Böckstein-Bad Gastein in Austria. METHODS: In 20 patients with AS the effects of a total of 15 hours of radon-hyperthermia-treatment spread over a period of three weeks were studied. The respiratory burst activity of neutrophils was measured fluorometrically using dichlorofluorescein diacetate, the total anti-oxidant status was measured using azinodiethyl-benzthiazoline-sulphonate, and inflammation parameters were determined by routine laboratory assays. RESULTS: Before treatment, the basal neutrophil respiratory burst in patients (n = 20) was 409 +/- 62 fluorescence arbitrary units (AU; mean +/- SEM) and 359 +/- 37 AU in controls (n = 9; p > 0.5); the stimulated respiratory burst (fMet-Leu-Phe, 10(-6) M) was 1,027 +/- 133 AU in patients and 1,152 +/- 218 AU in controls (p > 0.5). After treatment, the basal neutrophil respiratory burst in patients (n = 19) was 137 +/- 16 and in controls it was 174 +/- 35 AU (n = 8; p > 0.1); the stimulated respiratory burst was 670 +/- 66 and 1,305 +/- 82 AU, in patients and controls respectively (p < 0.001). No effects of treatment on the total anti-oxidant status of the plasma or on the parameters of inflammation were detected. CONCLUSION: Combined radon-hyperthermia treatment reduces the respiratory burst activity of the blood circulating neutrophils in patients with AS. If respiratory burst activity from the neutrophils plays a role in the pathophysiology of ankylosing spondylitis, the observed reduction may be related to the beneficial effects of radon-hyperthermia treatment.