Socioeconomic and geographic differences in ablation of atrial fibrillation in Norway - a national cohort study.

BACKGROUND: The aim of this study was to analyse whether there are patient related or geographic differences in the use of catheter ablation among atrial fibrillation patients in Norway. METHODS: National population-based data on individual level of all Norwegians aged 25 to 75 diagnosed with atrial fibrillation from 2008 to 2017 were used to study the proportion treated with catheter ablation. Survival analysis, by Cox regression with attained age as time scale, separately by gender, was applied to examine the associations between ablation probability and educational level, income level, place of residence, and follow-up time. RESULTS: Substantial socioeconomic and geographic variation was documented. Atrial fibrillation patients with high level of education and high income were more frequently treated with ablation, and the education effect increased with increasing age. Patients living in the referral area of St. Olavs Hospital Trust had around three times as high ablation rates as patients living in the referral area of Finnmark Hospital Trust. CONCLUSIONS: Differences in health literacy, patient preference and demands are probably important causes of socioeconomic variation, and studies on how socioeconomic status influences the choice of treatment are warranted. Some of the geographic variation may reflect differences in ablation capacity. However, geographic variation related to differences in clinical practice and provider preferences implies a need for clearer guidelines, both at the specialist level and at the referring level.

Optimized weak measurements of Goos-Hänchen and Imbert-Fedorov shifts in partial reflection.

The spatial and the angular variants of the Imbert-Federov (IF) beam shifts and the angular Goos-Hänchen (GH) shift contribute in a complex interrelated way to the resultant beam shift in partial reflection at planar dielectric interfaces. Here, we show that the two variants of the IF effects can be decoupled and separately observed by weak value amplification and subsequent conversion of spatial ↔angular nature of the beam shifts using appropriate pre and post selection of polarization states. Such optimized weak measurement schemes also enable one to nullify one effect (either the GH or the IF) and exclusively observe the other. We experimentally demonstrate this and illustrate various other intriguing manifestations of optimized weak measurements in elliptical and / or linear polarization basis. We also present a Poincare sphere based analysis on conversion / retention of the angular or spatial nature of the shifts with pre and post selection of states in weak measurement. The demonstrated ability to amplify, controllably decouple or combine the beam shifts via weak measurements may prove to be valuable for understanding the different physical contributions of the effects and for their applications in sensing and precision metrology.

Simultaneous weak value amplification of angular Goos-Hänchen and Imbert-Fedorov shifts in partial reflection.

The optical analogue of quantum weak measurements has shown considerable promise for the amplification and observation of tiny optical beam shifts, namely Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts. Here, we demonstrate simultaneous weak value amplification of both the angular GH and the IF shifts in partial reflection of a fundamental Gaussian beam at planar dielectric interfaces. We employ pre and postselection schemes with appropriate linear polarization basis states for simultaneous weak measurements and amplification of both of these shifts. The experimentally observed enhancement of the beam shifts and their dependence on the angle of incidence are analyzed/interpreted via theoretical treatment of weak measurements.

Mode-locked thulium bismuth codoped fiber laser using graphene saturable absorber in ring cavity: reply.

Jung and Lee have made comments [Appl. Opt.53, 553-554 (2014)] on "Mode-locked thulium bismuth codoped fiber laser using Graphene saturable absorber in ring cavity" [Appl. Opt.52, 1226-1229 (2013)]. The answer for the comment is provided in this report.

Has Oxidative Stress any Role on Mechanisms of Aminophylline-Induced Seizures? An Animal Study.

BACKGROUND: Aminophylline can trigger seizures in patients without known underlying epilepsy or added risk factor for seizure exacerbation in epilepsy. Most of these seizures are difficult to control and are underappreciated compared to other drug toxicities. Despite a long clinical history of aminophylline-induced seizures, relatively little is known about the underlying molecular mechanisms that contribute to methylxanthine-induced seizure generation. OBJECTIVE: The present study evaluated the possible involvement of free radicals in aminophylline induced seizures in rat. METHOD: The rats were divided into two groups. The first group graded single doses of aminophylline from 100 to 300 mg/kg were administered intraperitoneally. On the basis of the results Aminophylline, a dose (300 mg/kg) producing tonic-clonic seizures and mortality in 100% animals was selected as control in the study. The second group were subjected to single antioxidant (Vitamin E or Vitamin C) or in combination for 45 days then single doses of aminophylline 300 mg/kg administered intraperitoneally to rats. RESULT: Aminophylline induced convulsions in rats in a dose-dependent manner, and both incidence of seizure and mortality were maximum at 300 mg/kg and there was significant increase of free radical generation. But though pre-treatment with antioxidants showed differential attenuating effects on aminophylline induced free radical generation as we all known but they were very much ineffective in antagonizing aminophylline induced seizures and post-seizure mortality by any appreciable extent. CONCLUSION: Though Aminophylline induces oxidative stress the results are suggestive that at least free radicals is not only cause of convulsiogenic effects and post-seizure mortality of aminophylline.

Deuterium labeling improves the therapeutic index of 3,3'-diselenodipropionic acid as an anticancer agent: insights from redox reactions.

3,3'-Diselenodipropionic acid (DSePA), a selenocystine derivative, has been previously reported as an oral supplement for anticancer/radio-modulation activities. The present study is focused on devising a strategy to synthesize and characterize the deuterated derivative of DSePA and on understanding the effect of deuteration on its therapeutic index by comparing its cytotoxicity in cancerous versus non-cancerous cell types. In this context, the synthesis of 3,3'-diselenodipropionic acid-D8 (D-DSePA) was accomplished in ∼42% yield. Further, the results clearly established that the deuteration of DSePA significantly reduced its cytotoxicity in non-cancerous cell types while retaining its cytotoxicity in cancerous cell lines. Together, D-DSePA displayed a ∼5-fold higher therapeutic index than the non-deuterated derivative for anticancer activity. The biochemical and NMR studies confirmed that the better biocompatibility of D-DSePA than its non-deuterated derivative in non-cancerous cells was due to its ability to undergo slower redox reactions and to cause lesser inhibition of intracellular redox enzymes.

A multi-tissue analysis identifies HLA complex group 9 gene methylation differences in bipolar disorder.

Epigenetic studies of DNA and histone modifications represent a new and important activity in molecular investigations of human disease. Our previous epigenome-wide scan identified numerous DNA methylation differences in post-mortem brain samples from individuals affected with major psychosis. In this article, we present the results of fine mapping DNA methylation differences at the human leukocyte antigen (HLA) complex group 9 gene (HCG9) in bipolar disorder (BPD). Sodium bisulfite conversion coupled with pyrosequencing was used to interrogate 28 CpGs spanning ∼700 bp region of HCG9 in 1402 DNA samples from post-mortem brains, peripheral blood cells and germline (sperm) of bipolar disease patients and controls. The analysis of nearly 40 000 CpGs revealed complex relationships between DNA methylation and age, medication as well as DNA sequence variation (rs1128306). Two brain tissue cohorts exhibited lower DNA methylation in bipolar disease patients compared with controls at an extended HCG9 region (P=0.026). Logistic regression modeling of BPD as a function of rs1128306 genotype, age and DNA methylation uncovered an independent effect of DNA methylation in white blood cells (odds ratio (OR)=1.08, P=0.0077) and the overall sample (OR=1.24, P=0.0011). Receiver operating characteristic curve A prime statistics estimated a 69-72% probability of correct BPD prediction from a case vs control pool. Finally, sperm DNA demonstrated a significant association (P=0.018) with BPD at one of the regions demonstrating epigenetic changes in the post-mortem brain and peripheral blood samples. The consistent multi-tissue epigenetic differences at HCG9 argue for a causal association with BPD.

Mode-locked thulium-bismuth codoped fiber laser using graphene saturable absorber in ring cavity.

We demonstrate mode locking of a thulium-bismuth codoped fiber laser (TBFL) operating at 1901.6 nm, using a graphene-based saturable absorber (SA). In this work, a single layer graphene is mechanically exfoliated using the scotch tape method and directly transferred onto the surface of a fiber pigtail to fabricate the SA. The obtained Raman spectrum characteristic indicates that the graphene on the core surface has a single layer. At 1552 nm pump power of 869 mW, the mode-locked TBFL self starts to generate an optical pulse train with a repetition rate of 16.7 MHz and pulse width of 0.37 ps. This is a simple, low-cost, stable, and convenient laser oscillator for applications where eye-safe and low-photon-energy light sources are required, such as sensing and biomedical diagnostics.

Study Protocol of the Bladder Adjuvant RadioTherapy (BART) Trial: A Randomised Phase III Trial of Adjuvant Radiotherapy Following Cystectomy in Bladder Cancer.

AIMS: To assess the efficacy and safety of adjuvant radiotherapy in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) and chemotherapy. MATERIALS AND METHODS: The BART (Bladder Adjuvant RadioTherapy) trial is an ongoing multicentric, randomised, phase III trial comparing the efficacy and safety of adjuvant radiotherapy versus observation in patients with high-risk MIBC. The key eligibility criteria include ≥pT3, node-positive (pN+), positive margins and/or nodal yield <10, or, neoadjuvant chemotherapy for cT3/T4/N+ disease. In total, 153 patients will be accrued and randomised, in a 1:1 ratio, to either observation (standard arm) or adjuvant radiotherapy (test arm) following surgery and chemotherapy. Stratification parameters include nodal status (N+ versus N0) and chemotherapy (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy). For patients in the test arm, adjuvant radiotherapy to cystectomy bed and pelvic nodes is planned with intensity-modulated radiotherapy to a dose of 50.4 Gy in 28 fractions using daily image guidance. All patients will follow-up with 3-monthly clinical review and urine cytology for 2 years and subsequently 6 monthly until 5 years, with contrast-enhanced computed tomography abdomen pelvis 6 monthly for 2 years and annually until 5 years. Physician-scored toxicity using Common Terminology Criteria for Adverse Events version 5.0 and patient-reported quality of life using the Functional Assessment of Cancer Therapy - Colorectal questionnaire is recorded pre-treatment and at follow-up. ENDPOINTS AND STATISTICS: The primary endpoint is 2-year locoregional recurrence-free survival. The sample size calculation was based on the estimated improvement in 2-year locoregional recurrence-free survival from 70% in the standard arm to 85% in the test arm (hazard ratio 0.45) using 80% statistical power and a two-sided alpha error of 0.05. Secondary endpoints include disease-free survival, overall survival, acute and late toxicity, patterns of failure and quality of life. CONCLUSION: The BART trial aims to evaluate whether contemporary radiotherapy after standard-of-care surgery and chemotherapy reduces pelvic recurrences safely and also potentially affects survival in high-risk MIBC.

Quantification of physiological and mental workloads of faster and slower finishers of a long-distance military training activity.

BACKGROUND: Long-distance runs with equipment are practised in military training establishments to develop physical stamina and prepare for battles. A study was planned to quantify and compare the physiological and mental workloads of the early and late finishers of a military endurance run through the jungle terrain of north-eastern India in hot and humid conditions. METHODS: Twenty-five soldiers of the Indian Army completed a 15 km run through a rural and jungle track with 6.5 kg of equipment. Twelve participants who finished the race before 130 min were categorised as 'early finishers', and 13 were categorised as 'late finishers' who finished the race after 130 min. Physiological parameters, viz., heart rate (HR), breathing rate (BR), estimated core temperature (ECT), peak acceleration (PAC), and physiological intensity (PHYI) and mechanical intensity (MECHI) were recorded using BioHarness V.3 (Zephyr Technologies, USA) and NASA Task Load Index scores were obtained to assess mental workload. Mann-Whitney U test was applied to assess the level of significance at a p value of <0.05. RESULTS: HR, ECT and PAC were significantly higher (167.9 and 156.0 beats/min, 39.0℃ and 38.4℃, and 1.1 and 1.0 g, respectively) for the first group compared with the second group. The second group expressed higher BR and subjective responses ('total scores' were 76.5 and 82.5, respectively) than the first. The PHYI was significantly higher (from 7.2 to 6.3) for the first group, whereas the MECHI was similar in both groups. CONCLUSION: The successful completion by the first group can be attributed to their motivation to continue heavy work in an adverse environment, and their ability to negotiate with natural obstacles was reflected through controlled subjective responses. Adoption of a possible safe and stable approach to the same task might have led the second group to take a longer duration, exert higher mental effort and demand lower physiological cost.

Impact of Adjuvant Treatment in pN3 Penile Cancer.

AIMS: Due to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. PATIENTS AND METHODS: All consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan-Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). RESULTS: Of 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3-4], P = 0.027 and 2.2 [1.3-4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5-5.5], P < 0.001; multimodality: 3.1 [1.6-6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4-0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07-1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1-1], P = 0.05). CONCLUSION: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.

Fabrication and characterization of new Yb-doped zirconia-germano-alumino silicate phase-separated nano-particles based fibers.

New zirconia-germano-alumino silicate, nano-particles based, Ytterbium doped fibers are obtained through the conventional modified chemical vapour deposition and solution doping techniques. The start fiber preforms are characterized by means of electron micro probe, energy dispersive x-ray, and electron diffraction analyses, revealing the presence of phase-separated nano-sized Ytterbium-rich areas in the core, while the final fibers are inspected in the sense of spectroscopy and laser properties.

Radiotherapy for Post-Chemotherapy Residual Mass in Advanced Seminoma: A Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography-Based Risk-adapted Approach.

AIMS: There is a lack of consensus regarding the management of post-chemotherapy residual mass in classical seminoma. The use of fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) may aid the detection of residual masses harbouring viable disease and help to tailor therapy. The aim of this study was to evaluate if PET-CT could identify patients who will benefit from locoregional radiotherapy. MATERIALS AND METHODS: This ethics-approved study included patients with advanced classical seminoma primarily treated with standard platinum-based first-line chemotherapy. Patients were either observed or given adjuvant radiotherapy based on the clinician's preference and followed up. For this study, patients were stratified into two groups based on FDG PET-CT residual nodal maximum standardised uptake value (SUVmax): low risk (SUVmax <3) and high risk (SUVmax ≥3). Further subgroup analysis was carried out for patients with residual nodal size ≥3 cm and SUVmax ≥3, and this was considered as the very high risk group. The diagnostic accuracy of FDG PET-CT was assessed and survival was compared between the different groups. RESULTS: Sixty-nine patients were included in the study: 48 patients were observed and 21 received radiotherapy. The low and high risk groups contained 50.7% and 49.3% of the patients, respectively. The very high risk subgroup had 24 patients. At a median follow-up of 44 months, locoregional failures in the radiotherapy and observation cohorts were 0% and 30% (P = 0.059) in the very high risk subgroup and 5.8% and 29.4% (P = 0.078) in the high risk group. The positive predictive value for the very high risk and high risk groups was 30% and 17.1%, respectively. The benefit of locoregional control failed to translate into overall survival benefit. CONCLUSION: A tailored, FDG PET-based risk-adapted treatment approach can refine the management of post-chemotherapy residual masses in seminoma. In this study, with the largest cohort of advanced seminoma patients treated with radiotherapy reported to date, radiotherapy seems to benefit patients with post-chemotherapy residual mass SUVmax ≥3.

Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway in rats.

The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.

Performance comparison of Zr-based and Bi-based erbium-doped fiber amplifiers.

In this Letter, we present a comprehensive comparison of the performance of a zirconia-based erbium-doped fiber amplifier (Zr-EDFA) and a bismuth-based erbium-doped fiber amplifier (Bi-EDFA). The experimental results reveal that a Zr-EDFA can achieve comparable performance to the conventional Bi-EDFA for C-band and L-band operations. With a combination of both Zr and Al, we could achieve a high erbium-doping concentration of about 2800 ppm (parts per million) in the glass host without any phase separations of rare earths. The Zr-based erbium-doped fiber (Zr-EDF) was fabricated using in a ternary glass host, zirconia-yttria-aluminum codoped silica fiber through a solution-doping technique along with modified chemical vapor deposition. At a high input signal of 0 dBm, a flat gain at average value of 13 dB is obtained with a gain variation of less than 2 dB within the wavelength region of 1530-1575 nm and using 2 m of Zr-EDF and 120 mW pump power. The noise figures are less than 9.2 at this wavelength region. It was found that a Zr-EDFA can achieve even better flat-gain value and bandwidth as well as lower noise figure than the conventional Bi-EDFA.

Near-atomic resolution analysis of BipD, a component of the type III secretion system of Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, possesses a type III protein secretion apparatus that is similar to those found in Salmonella and Shigella. A major function of these secretion systems is to inject virulence-associated proteins into target cells of the host organism. The bipD gene of B. pseudomallei encodes a secreted virulence factor that is similar in sequence and is most likely to be functionally analogous to IpaD from Shigella and SipD from Salmonella. Proteins in this family are thought to act as extracellular chaperones at the tip of the secretion needle to help the hydrophobic translocator proteins enter the target cell membrane, where they form a pore and may also link the translocon pore with the secretion needle. BipD has been crystallized in a monoclinic crystal form that diffracted X-rays to 1.5 A resolution and the structure was refined to an R factor of 16.1% and an Rfree of 19.8% at this resolution. The putative dimer interface that was observed in previous crystal structures was retained and a larger surface area was buried in the new crystal form.

Thermoluminescence and optically stimulated luminescence properties of beta-irradiated TiO2:Yb nanoparticles.

The thermoluminescence (TL) and optically stimulated luminescenece (OSL) response of TiO2:Yb nanoparticles are studied. After beta irradiation, the materials developed a significant TL/OSL signal associated to several localized trapping states around 360-620 K. The OSL signal is mainly due to the releasing of trapped charges in the low temperature (360 and 460 K) trapping states. A computer glow curve deconvolution procedure was used to determine the activation energies and kinetic order of the TL processes.

Human sperm DNA integrity in normal and abnormal semen samples and its correlation with sperm characteristics.

Reports indicate an increase in the incidence of DNA fragmentation in male factor infertility and its role in the outcome of assisted reproductive techniques (ART). However, reports are conflicting between the relationships of sperm DNA integrity with conventional semen parameters. We examined the relationship between conventional sperm parameters and DNA integrity using acridine orange (AO) test. The study included 373 patients and 28 fertile volunteers. DNA normality was compared with semen parameters between the patient and donor populations. Significant correlations were noted between DNA normality and sperm concentration (r = 0.18, P = 0.000), motility (r = 0.21, P = 0.0001), rapid motility (0.19, P = 0.000), normal morphology by World Health Organization (r = 0.15, P = 0.019) and head defects (r = -0.15, P = 0.023). A significant difference was noted in AO levels between donors and patients with asthenozoospermia (P = 0.002) and oligoasthenozoospermia (P = 0.001). A significant difference in DNA integrity was noted in samples having <30% and >30% normal morphology. A wide range of % DNA normality was observed in the patient group. Sperm assessment for DNA status using AO is reliable and shows good correlation with sperm count, motility and morphology. Assessment of sperm DNA status with AO staining may be helpful prior to ART.