330 research outputs found
Far ultraviolet response of silicon P-N JUNCTION photodiodes
Silicon P-N junction photodiode resistivity in vacuum ultraviole
Development and Integration of Machine Learning Algorithm to Identify Peripheral Arterial Disease: Multistakeholder Qualitative Study
Association of chronic obstructive pulmonary disease with morbidity and mortality in patients with peripheral artery disease: insights from the EUCLID trial
Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD. Methods: EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model. Results: Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p< 0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p< 0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11β 1.52; p< 0.001; MI: aHR 1.45, 95% CI 1.18β 1.77; p< 0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12β 3.63; p< 0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p< 0.001; aHR 1.34, 95% CI 1.22β 1.47; p< 0.001). Conclusion: In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD. Registration: ClinicalTrials.gov: NCT01732822
Rapid clearance profile of plasma circulating tumor HPV type 16 DNA during chemoradiotherapy correlates with disease control in HPV-associated oropharyngeal cancer
Purpose: To identify a profile of circulating tumor human papilloma virus (HPV) DNA (ctHPVDNA) clearance kinetics that is associated with disease control after chemoradiotherapy (CRT) for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Experimental Design: A multi-institutional prospective biomarker trial was conducted in 103 patients with (i) p16- positive OPSCC, (ii) M0 disease, and (iii) receipt of definitive CRT. Blood specimens were collected at baseline, weekly during CRT, and at follow-up visits. Optimized multianalyte digital PCR assays were used to quantify ctHPVDNA (types 16/18/31/33/35) in plasma. A control cohort of 55 healthy volunteers and 60 patients with non-HPV-associated malignancy was also analyzed. Results: Baseline plasma ctHPVDNA had high specificity (97%) and high sensitivity (89%) for detecting newly diagnosed HPV-associated OPSCC. Pretreatment ctHPV16DNA copy number correlated with disease burden, tumor HPV copy number, and HPV integration status. We define a ctHPV16DNA favorable clearance profile as having high baseline copy number (>200 copies/mL) and >95% clearance of ctHPV16DNA by day 28 of CRT. Nineteen of 67 evaluable patients had a ctHPV16DNA favorable clearance profile, and none had persistent or recurrent regional disease after CRT. In contrast, patients with adverse clinical risk factors (T4 or >10 pack years) and an unfavorable ctHPV16DNA clearance profile had a 35% actuarial rate of persistent or recurrent regional disease after CRT (P = 0.0049). Conclusions: A rapid clearance profile of ctHPVDNA may predict likelihood of disease control in patients with HPVassociated OPSCC patients treated with definitive CRT and may be useful in selecting patients for deintensified therapy
Multipliers of Dirichlet series and monomial series expansions of holomorphic functions in infinitely many variables
[EN] Let H-infinity be the set of all ordinary Dirichlet series D = Sigma(n) a(n)(n-1) ann-s representing bounded holomorphic functions on the right half plane. A completely multiplicative sequence (b(n)) of complex numbers is said to be an l(1)-multiplier for H-infinity whenever Sigma(n vertical bar)a(n)b(n vertical bar) < infinity for every D is an element of H-infinity. We study the problem of describing such sequences (b(n)) in terms of the asymptotic decay of the subsequence (b(pj)), where p(j) denotes the j th prime number. Given a completely multiplicative sequence b = (b(n)) we prove (among other results): b is an l(1)-multiplier for H-infinity provided vertical bar b(pj)vertical bar < 1 for all j and (lim(n)) over bar 1/log(n) Sigma(n)(j=1) b(p j)*(2) < 1, and conversely, if b is an l(1)-multiplier for H-infinity, then vertical bar b(pj)vertical bar < 1 for all j and (lim(n)) over bar 1/log(n) Sigma(n)(j=1) b(p j)*(2) <= 1 (here b* stands for the decreasing rearrangement of b). Following an ingenious idea of Harald Bohr it turns out that this problem is intimately related with the question of characterizing those sequences z in the infinite dimensional polydisk D-infinity (the open unit ball of l(infinity)) for which every bounded and holomorphic function f on D-infinity has an absolutely convergent monomial series expansion Sigma(alpha) partial derivative alpha f (0)/alpha! z alpha. Moreover, we study analogous problems in Hardy spaces of Dirichlet series and Hardy spaces of functions on the infinite dimensional polytorus T-infinity.The second, fourth and fifth authors were supported by MINECO and FEDER Project MTM2014-57838-C2-2-P. The fourth author was also supported by PrometeoII/2013/013. The fifth author was also supported by project SP-UPV20120700.Bayart, F.; Defant, A.; Frerick, L.; Maestre, M.; Sevilla Peris, P. (2017). Multipliers of Dirichlet series and monomial series expansions of holomorphic functions in infinitely many variables. Mathematische Annalen. 368(1-2):837-876. https://doi.org/10.1007/s00208-016-1511-1S8378763681-2Aleman, A., Olsen, J.-F., Saksman, E.: Fatou and brother Riesz theorems in the infinite-dimensional polydisc. arXiv:1512.01509Balasubramanian, R., Calado, B., QueffΓ©lec, H.: The Bohr inequality for ordinary Dirichlet series. 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Pre-ejection period by radial artery tonometry supplements echo doppler findings during biventricular pacemaker optimization
<p>Abstract</p> <p>Background</p> <p>Biventricular (Biv) pacemaker echo optimization has been shown to improve cardiac output however is not routinely used due to its complexity. We investigated the role of a simple method involving computerized pre-ejection time (PEP) assessment by radial artery tonometry in guiding Biv pacemaker optimization.</p> <p>Methods</p> <p>Blinded echo and radial artery tonometry were performed simultaneously in 37 patients, age 69.1 Β± 12.8 years, left ventricular (LV) ejection fraction (EF) 33 Β± 10%, during Biv pacemaker optimization. Effect of optimization on echo derived velocity time integral (VTI), ejection time (ET), myocardial performance index (MPI), radial artery tonometry derived PEP and echo-radial artery tonometry derived PEP/VTI and PEP/ET indices was evaluated.</p> <p>Results</p> <p>Significant improvement post optimization was achieved in LV ET (286.9 Β± 37.3 to 299 Β± 34.6 ms, p < 0.001), LV VTI (15.9 Β± 4.8 cm to 18.4 Β± 5.1 cm, p < 0.001) and MPI (0.57 Β± 0.2 to 0.45 Β± 0.13, p < 0.001) and in PEP (246.7 Β± 36.1 ms to 234.7 Β± 35.5 ms, p = 0.003), PEP/ET (0.88 Β± 0.21 to 0.79 Β± 0.17, p < 0.001), and PEP/VTI (17.3 Β± 7 to 13.78 Β± 4.7, p < 0.001). The correlation between comprehensive echo Doppler and radial artery tonometry-PEP guided optimal atrioventricular delay (AVD) and optimal interventricular delay (VVD) was 0.75 (p < 0.001) and 0.69 (p < 0.001) respectively. In 29 patients with follow up assessment, New York Heart Association (NYHA) class reduced from 2.5 Β± 0.8 to 2.0 Β± 0.9 (p = 0.004) at 1.8 Β± 1.4 months.</p> <p>Conclusion</p> <p>An acute shortening of PEP by radial artery tonometry occurs post Biv pacemaker optimization and correlates with improvement in hemodynamics by echo Doppler and may provide a cost-efficient approach to assist with Biv pacemaker echo optimization.</p
A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck
BACKGROUND: Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. METHODS: Randomised trials testing curatively intended RT (β₯60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. RESULTS: Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). CONCLUSION: RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival
Different cellular p16INK4a localisation may signal different survival outcomes in head and neck cancer
Background:Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status.Methods:Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS).Results:A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20β82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status.Conclusion:Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status
Mice with Asthma Are More Resistant to Influenza Virus Infection and NK Cells Activated by the Induction of Asthma Have Potentially Protective Effects
Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression
The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC
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