Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images ...would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations.
New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined.
The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near
, which is implicated in mucin hypersecretion (p=1.1 ×10
). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome.
Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.
Content delivery service has become a major traffic load on today's Internet, and this has triggered the interest of ISPs in operating their own content delivery networks (CDNs) to optimize Internet ...traffic considering both content delivery caching and user-network proximity. ISPs, however, are typically regionally bound or network-domain-wise isolated; hence, their CDN gain is somewhat limited. In order to enhance the gain of ISP CDN services to the level of incumbent global CDNs, a CDN interconnection (CDNI) model is introduced by IETF, where local ISP CDN services can be extended among heterogeneous CDNs across network domains. However, despite the multiple benefits of a CDNI system, it is difficult to apply a CDNI service to the current CDN market due to the platform independence. Hence, we introduced a CDNI gateway model that is standard-capable and platform-independent. With the CDNI gateway model, we design and implement a complete CDNI system and conduct a CDNI service trial with three major ISPs in South Korea. To the best of our knowledge, this is the first CDNI service trial complying with the IETF standard achieved by a multi-ISP collaboration. According to the analysis of experimental results from the service trial, we observe that CDNI can reduce content traffic by about 40 percent at the Internet exchange link compared to a legacy CDN system.
In two large clinical trials (ZOE-50 NCT01165177 and ZOE-70 NCT01165229), two doses of the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy (VE) against herpes zoster (HZ) in ...adults ≥50 years of age (YOA). This post-hoc analysis assessed the VE against HZ and postherpetic neuralgia (PHN), in participants from Asian study sites enrolled in ZOE-50/70. Reactogenicity and safety were also assessed. Participants ≥50 YOA were randomized 1:1 to receive 2 doses of either RZV or placebo, 2 months apart. VE was evaluated for a median follow-up of 4 years post-vaccination overall and by age in the ZOE-50 Asian population ≥50 YOA and in the pooled ZOE-50/70 Asian population ≥70 YOA. Of the 2,729 participants included in the ZOE-50 Asian population ≥50 YOA, 3 RZV and 66 placebo recipients reported a confirmed HZ episode. Overall VE was 95.6% (95% confidence interval CI: 86.4-99.1) against HZ and 100% (95% CI: 35.44-100) against PHN. In the pooled ZOE-50/70 Asian population ≥70 YOA, 4 RZV and 75 placebo recipients out of the 2,723 participants reported a confirmed HZ episode. Overall VE was 94.7% (95% CI: 85.9-98.6) against HZ and 89.8% (95% CI: 28.39-99.77) against PHN. Pain and myalgia were the most frequent solicited local and general adverse events, respectively, in both populations. No safety concern was identified during the study periods. RZV is highly efficacious against HZ and PHN and has an acceptable safety profile in Asian populations ≥50 YOA, similar to what was observed in the general ZOE-50/70 populations.
Trademark statement: Shingrix is a trademark owned by or licensed to the GSK group of companies.
What is the context?
Herpes zoster (shingles) is a painful rash that affects worldwide around 30% of people aged 50 years and older. Postherpetic neuralgia, the most frequent complication characterized by chronic pain long after the rash has cleared, is debilitating and very challenging to treat.
Two previous trials involving around 30,000 people in 18 countries showed that Shingrix (GSK) significantly reduces the rate of shingles and postherpetic neuralgia in people aged 50 years and older and has an acceptable safety profile.
What is new?
We analysed the data of these studies to ascertain that the vaccine works as well and is equally safe for Asian people as compared to a diverse worldwide population.
We found:
That the vaccine is at least 90% effiicacious in preventing shingles and postherpetic neuralgia in Asian adults aged 50 years and above.
An acceptable reactogenicity and safety profile among Asian participants.
What is the impact?
Shingrix induced a high level of protection without safety concerns in Asian adults, in-line with the previous observations for adults aged 50 years and older across the globe.
Abstract
Background
This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted ...recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years mean post-vaccination) and includes partial data for year (Y) 8 post-vaccination.
Methods
Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD42+ T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination.
Results
Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval CI, 75.9–89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2–93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD42+ T cells reached a plateau at approximately 6-fold above pre-vaccination levels.
Conclusions
Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination.
Clinical Trials Registration. NCT02723773.
Efficacy against herpes zoster and immune responses to the adjuvanted recombinant zoster vaccine plateaued at high levels between 5.1 and 7.1 years (mean) post-vaccination, suggesting that its clinical benefit in older adults is sustained for at least 7 years post-vaccination.
Background & Aims The World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral ...hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop. Methods Twenty-eight representatives from local liver associations, patient organisations, and centres of excellence in Hong Kong, Japan, Korea, and Taiwan participated in the workshop. Findings Priority areas for action were described along the four axes of the WHO Framework: (1) awareness, advocacy and resources; (2) evidence and data; (3) prevention of transmission; and (4) screening and treatment. Priorities included: axis 1: greater public and professional awareness, particularly among primary care physicians and local advocacy networks. Axis 2: better economic data and identifying barriers to screening and treatment uptake. Axis 3: monitoring of vaccination outcomes and targeted harm reduction strategies. Axis 4: strengthening links between hospitals and primary care providers, and secure funding of screening and treatment, including for hepatocellular carcinoma. Conclusions The WHO Framework provides an opportunity to develop comprehensive and cohesive policies in North Asia and the broader region. A partnership between clinical specialists, primary care physicians, policy makers, and people with or at risk of viral hepatitis is essential in shaping future policies.
Silica coating of magnetite nanoparticles (MNPs) is of great importance because it offers stability to MNPs against oxidation, water dispersity, and a tailorable surface for functionalities, allowing ...a wide range of applications in areas such as water pollutant removal and targeted drug delivery. In this work, a simple and green procedure has been developed using water, instead of traditional alcohols, as the solvent in the Stober method to produce well-dispersed MNPs coated with ultrathin (<5 nm) silica outer shells. The resultant core–shell structures possess superparamagnetic properties, high magnetization value of 59 emu/g, and excellent resistance to oxidation when exposed to ultrasonic-accelerated oxidation. The oxidation stability of the coated MNPs is shown to extend to their functionalized product. All syntheses are carried out under ambient conditions using commonly available chemicals and equipment. The Fe3O4@SiO2 core–shell structures are characterized using Fourier transform infrared–attenuated total reflection spectroscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, and a vibrating sample magnetometer.
Pangasianodon hypophthalmus (striped catfish) is an important aquaculture species and intensification of farming has increased disease problems, particularly Edwardsiella ictaluri. The effects of ...feeding β-glucans on immune gene expression and resistance to E. ictaluri in P. hypophthalmus were explored. Fish were fed 0.1% fungal-derived β-glucan or 0.1% commercial yeast-derived β-glucan or a basal control diet without glucan. After 14 days of feeding, the mRNA expression of immune genes (transferrin, C-reactive protein, precerebellin-like protein, Complement C3 and factor B, 2a MHC class II and interleukin-1beta) in liver, kidney and spleen were determined. Following this fish from each of the three diet treatment groups were infected with E. ictaluri and further gene expression measured 24 h post-infection (h.p.i.), while the remaining fish were monitored over 2 weeks for mortalities. Cumulative percentage mortality at 14 days post-infection (d.p.i.) was less in β-glucan fed fish compared to controls. There was no difference in gene expression between dietary groups after feeding for 14 days, but there was a clear difference between infected and uninfected fish at 24 h.p.i., and based on principal component analysis β-glucans stimulated the overall expression of immune genes in the liver, kidney and spleen at 24 h.p.i.
•β-glucan enhanced resistance to Edwardsiella ictaluri in Pangasianodon hypophthalmus.•IL-1β, MHC-II, C3, Factor B, Transferrin, CRP and Precerebellin were evaluated.•β-glucan had no effect on immune genes after feeding.•Feeding β-glucan stimulated immune genes after infection.
Standard molecularly based strategies to predict and/or prevent oral cancer development in patients with oral premalignant lesions (OPLs) are lacking.
To test if the epidermal growth factor receptor ...inhibitor erlotinib would reduce oral cancer development in patients with high-risk OPLs defined by specific loss of heterozygosity (LOH) profiles. Secondary objectives included prospective determination of LOH as a prognostic marker in OPLs.
The Erlotinib Prevention of Oral Cancer (EPOC) study was a randomized, placebo-controlled, double-bind trial. Accrual occurred from November 2006 through July 2012, with a median follow-up time of 35 months in an ambulatory care setting in 5 US academic referral institutions. Patients with OPLs were enrolled in the protocol, and each underwent LOH profiling (N = 379); they were classified as high-risk (LOH-positive) or low-risk (LOH-negative) patients based on their LOH profiles and oral cancer history. The randomized sample consisted of 150 LOH-positive patients.
Oral erlotinib treatment (150 mg/d) or placebo for 12 months.
Oral cancer-free survival (CFS).
A total of 395 participants were classified with LOH profiles, and 254 were classified LOH positive. Of these, 150 (59%) were randomized, 75 each to the placebo and erlotinib groups. The 3-year CFS rates in placebo- and erlotinib-treated patients were 74% and 70%, respectively (hazard ratio HR, 1.27; 95% CI, 0.68-2.38; P = .45). The 3-year CFS was significantly lower for LOH-positive compared with LOH-negative groups (74% vs 87%, HR, 2.19; 95% CI, 1.25-3.83; P = .01). Increased EGFR gene copy number correlated with LOH-positive status (P < .001) and lower CFS (P = .01). The EGFR gene copy number was not predictive of erlotinib efficacy. Erlotinib-induced skin rash was associated with improved CFS (P = .01).
In this trial, LOH was validated as a marker of oral cancer risk and found to be associated with increased EGFR copy number (the target of the intervention). Erlotinib did not, however, improve CFS in high-risk patients with LOH-positive or high-EGFR-gene-copy-number OPLs. These results support incorporation of LOH testing as a prognostic tool in routine clinical practice but do not support erlotinib use in this setting.
clinicaltrials.gov Identifier: NCT00402779.
The physical composition and intensities of solar particle event exposures of sensitive astronaut tissues are examined under conditions approximating an astronaut in deep space. Response functions ...for conversion of particle fluence into dose and dose equivalent averaged over organ tissues are used to establish significant fluence levels and the expected dose and dose rates of the most important events from past observations. The BRYNTRN transport code is used to evaluate the local environment experienced by sensitive tissues and used to evaluate bioresponse models developed for use in tactical nuclear warfare. The present results will help to clarify the biophysical aspects of such exposure in the assessment of RBE and dose rate effects and their impact on design of protection systems for the astronauts. The use of polymers as shielding material in place of an equal mass of aluminum would provide a large safety factor without increasing the vehicle mass. This safety factor is sufficient to provide adequate protection if a factor of two larger event than has ever been observed in fact occurs during the mission.
Somatic genetic alterations including copy number and point mutations in the androgen receptor (AR) are associated with resistance to therapies targeting the androgen/AR axis in patients with ...metastatic castration resistant prostate cancer (mCRPC). Due to limitations associated with biopsying metastatic lesions, plasma derived cell-free DNA (cfDNA) is increasingly being used as substrate for genetic testing. AR mutations detected by deep next generation sequencing (NGS) of cfDNA from patients with mCRPC have been reported at allelic fractions ranging from over 25% to below 1%. The lower bound threshold for accurate mutation detection by deep sequencing of cfDNA has not been comprehensively determined and may have locus specific variability. Herein, we used NGS for AR mutation discovery in plasma-derived cfDNA from patients with mCRPC and then used droplet digital polymerase chain reaction (ddPCR) for validation. Our findings show the AR (tTC>cTC) F877L hotspot was prone to false positive mutations during NGS. The rate of error at AR (tTC>cTC) F877L during amplification prior to ddPCR was variable among high fidelity polymerases. These results highlight the importance of validating low-abundant mutations detected by NGS and optimizing and controlling for amplification conditions prior to ddPCR.
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