Thermodynamics of conformal fields in topologically non-trivial space-time backgrounds

We analyze the finite temperature behaviour of massless conformally coupled scalar fields in homogeneous lens spaces $S^3/{\mathbb Z}_p$. High and low temperature expansions are explicitly computed and the behavior of thermodynamic quantities under thermal duality is scrutinized. The analysis of the entropy of the different lens spaces in the high-temperature limit points out the appearance of a topological nonextensive entropy, besides the standard Stefan-Boltzmann extensive term. The remaining terms are exponentially suppressed by the temperature. The topological entropy appears as a subleading correction to the free energy that can be obtained from the determinant of the lens space conformal Laplacian operator. In the low-temperature limit the leading term in the free energy is the Casimir energy and there is no trace of any power correction in any lens space. In fact, the remaining corrections are always exponentially suppressed by the inverse of the temperature. The duality between the results of both expansions is further analyzed in the paper.Comment: 21 pages, 2 figure

Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC). Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0. Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules. Conclusions. This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients

S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (s.d.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44-60) years, disease duration 6 (3-10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg × 2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5-9) months follow-up (n = 47, 18.2 + 10.9 vs 14.5 + 9.9, P = 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n = 26; 26.5 + 6.8 vs 20.4 + 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n = 10; 3.7 (2.6-6.4) vs 1.7 (0.9-2.5), P = 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n = 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months follow-up without reaching statistical significance [n = 8; 4.8 (2.5-7.5) vs 3.7 (2.6-6.6); p = 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 + 177 vs 184 + 139; n = 12, P = 0.03) and on digital ulcers [total number per patient 1 (1-3) vs 0 (0-1); n = 23; P = 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patient

Amiodarone-induced pulmonary toxicity with an excellent response to treatment

Amiodarone is an anti-arrhythmic drug widely used, but its administration can be associated with several adverse side-effects. Among these, amiodarone-induced pulmonary toxicity (APT) occurs in 4-17% of cases and, if not early diagnosed and treated, may evolve towards pulmonary fibrosis and respiratory failure. A 76 years-old-man went to the hospital for accidental trauma. The patient did not report respiratory symptoms but was suffering from atrial fibrillation treated with amiodarone 200 mg/day from three years (cumulative dose &gt;150 gr). HRCT showed ground-glass opacities and nodules in both lungs. The patient underwent fibreoptic bronchoscopy with BAL. Cytologic examination of BALF sediment put in evidence foamy macrophages. The electronic microscopy revealed into the alveolar macrophages "… the presence of multilamellar intracytoplasmic bodies and lysosomes, loads of lipid material". LFTs showed a restrictive syndrome and an impairment of DLCO. Amiodarone discontinuation and steroid administration led to the regression of radiological lesions and the recovery of lung function. Patients taking amiodarone can experience APT. They should perform a basal chest x-ray with LFTs before starting therapy. Monitoring could reveal early the pulmonary toxicity, and patients can respond favourably to the treatment

Topological entropy and renormalization group flow in 3-dimensional spherical spaces

We analyze the renormalization group (RG) flow of the temperature independent term of the entropy in the high temperature limit ß/a « 1 of a massive field theory in 3-dimensional spherical spaces, M 3, with constant curvature 6/a 2. For masses lower than 2p/ß , this term can be identified with the free energy of the same theory on M 3 considered as a 3-dimensional Euclidean space-time. The non-extensive part of this free energy, S hol, is generated by the holonomy of the spatial metric connection. We show that for homogeneous spherical spaces the holonomy entropy S hol decreases monotonically when the RG scale flows to the infrared. At the conformal fixed points the values of the holonomy entropy do coincide with the genuine topological entropies recently introduced. The monotonic behavior of the RG flow leads to an inequality between the topological entropies of the conformal field theories connected by such flow, i.e. S top UV¿>¿S top IR . From a 3-dimensional viewpoint the same term arises in the 3-dimensional Euclidean effective action and has the same monotonic behavior under the RG group flow. We conjecture that such monotonic behavior is generic, which would give rise to a 3-dimensional generalization of the c-theorem, along the lines of the 2-dimensional c-theorem and the 4-dimensional a-theorem. The conjecture is related to recent formulations of the F-theorem. In particular, the holonomy entropy on lens spaces is directly related to the topological Rényi entanglement entropy on disks of 2-dimensional flat spaces

Actigraphic sleep detection: an artificial intelligence approach

Objective: Polysomnography is the gold standard for sleep monitoring, despite its many drawbacks: it is complex, costly and rather invasive. Medical-grade actigraphy represents an acceptably accurate alternative for the estimation of sleep patterns in normal, healthy adult populations and in patients suspected of certain sleep disorders. An increasing number of consumer-grade accelerometric devices populate the “quantified-self” market but the lack of validation significantly limits their reliability. Our aim was to prototype and validate a platform-free artificial neural network (ANN) based algorithm applied to a high performance, open source device (Axivity AX3), to achieve accurate actigraphic sleep detection. Methods: 14 healthy subjects (29.35 14.40 yrs, 7 females) were equipped for 13.3 2.58 h with portable polysomnography (pPSG), while wearing the Axivity AX3. The AX3 was set to record 3D accelerations at 100 Hz, with a dynamic range of 8 g coded at 10 bit. For the automatic actigraphy-based sleep detection, a 4 layer artificial neural network has been trained, validated and tested against the pPSG-based expert visual sleep-wake scoring. Results: When compared to the pPSG gold standard scoring, the ANN-based algorithm reached high concordance (85.3 0.06%), specificity (87.3 0.04%) and sensitivity (84.6 0.1%) in the detection of sleep over 30-sec epochs. Moreover there were no statistical differences between pPSG and actigraphy-based Total Sleep Time and Sleep Efficiency measurements (Wilcoxon test). Conclusions: The high concordance rate between ANN-actigraphy scoring and the standard visual pPSG one suggests that this approach could represent a viable method for collecting objective sleep-wake data using a high performance, open source actigraph

Heart rate detection by Fitbit ChargeHR™: A validation study versus portable polysomnography

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66(0.04)beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r=0.85±0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r=0.9662; N1, r=0.9918; N2, r=0.9793; N3, r=0.9849) than in wakefulness (r=0.8432). Moreover, the correlation coefficient was lower for HRs of &gt;100bpm (r=0.374) than for HRs of &lt;100bpm (r=0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions