Abstract
Thermo‐cryogenic processes prepare and trigger rockfalls and rockslides in alpine environments. Temporal occurrence, controls, and applied stresses of Thermo‐cryogenic processes on rock ...masses are poorly understood. This paper reports annual crackmeter measurements with 3 h resolution across perennially ice‐filled fractures in an unstable rock permafrost crestline. Thermo‐cryogenic processes are controlled by snow cover onset and duration. Thermal changes in snow‐free periods control expansion and contraction coincident temperature gradients on a daily to seasonal scale. We can show how snow cover promotes sustained temperatures from −9 to −1°C and boosts ice segregation‐related fracture opening up to 1 cm in 8 months. During snowmelt, meltwater induces ice erosion and ice relaxation, which occur in the freeze‐thaw window close to the thawing point. We hypothesize that Thermo‐cryogenic processes and their cyclic repetition can lead to Thermo‐cryogenic fatigue preparing rock slope failure and can control type and location of rockfalls in a changing climate.
Key Points
Thermo‐cryogenic processes preparing and triggering rockfalls are controlled by snow cover
Thermal changes control temperature‐gradient‐dependent rockwall expansion in snow‐free periods
Snow cover boosts ice segregation‐related fracture opening
Interventional radiology provides a wide variety of vascular, nonvascular, musculoskeletal, and oncologic minimally invasive techniques aimed at therapy or palliation of a broad spectrum of ...pathologic conditions. Outcome data for these techniques are globally evaluated by hospitals, insurance companies, and government agencies targeting in a high-quality health care policy, including reimbursement strategies. To analyze effectively the outcome of a technique, accurate reporting of complications is necessary. Throughout the literature, numerous classification systems for complications grading and classification have been reported. Until now, there has been no method for uniform reporting of complications both in terms of definition and grading. The purpose of this CIRSE guideline is to provide a classification system of complications based on combining outcome and severity of sequelae. The ultimate challenge will be the adoption of this system by practitioners in different countries and health economies within the European Union and beyond.
In this study we report the identification of bicyclic imidazoles in aqueous aerosol mimics using HPLC-ESI-MS/MS. 2,2'-Biimidazole was identified to be a major contributor to the 280 nm absorbance ...band observed in mixtures of glyoxal and ammonium sulfate, despite the fact that its production rate is two orders of magnitude lower than the previously reported production rates of imidazole or imidazole-2-carboxaldehyde. The molar absorptivity of 2,2'-biimidazole was determined to be (36 690 ± 998) M−1 cm−1. This demonstrates the necessity of molecular product identification at trace levels to enable a better understanding of relevant absorbing species. Additionally, the formation of lower polarity products including formamides of imidazoles is proposed. The role of imidazoles and other light-absorbing species in the formation of SOA and optical properties of SOA is discussed and potentially interesting fields for future investigations are outlined.
The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance.
We searched four databases to July ...2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes.
Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants median 70% (IQR 50%-84%); n = 8 studies had heard of antibiotic resistance, but most median 88% (IQR 86%-89%); n = 2 studies believed it referred to changes in the human body. Many believed excessive antibiotic use median 70% (IQR 59%-77%); n = 11 studies and not completing antibiotic courses median 62% (IQR 47%-77%); n = 8 studies caused resistance. Most participants nominated reducing antibiotic use median 74% (IQR 72%-85%); n = 4 studies and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians.
The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.
Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have ...been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects' alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10
) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10
) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10
for drinker status and beta=-0.19, P=1.91 × 10
for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10
and beta=-0.21, P=2.58 × 10
, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10
for drinks/week and OR=0.96, P=4.08 × 10
for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10
for drinks/week and OR=1.04, P=5 × 10
for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.
Abstract
Making informed health decisions requires knowledge and skills in appraising health claims, and teaching adolescents these skills may prepare them for future decision-making. This cluster ...randomized trial evaluated the effectiveness of an educational intervention on students’ ability to identify and appraise health claims. Nine Australian high schools (4 control and 5 intervention) were recruited, comprising 974 students (382 control and 592 intervention) in Grades 7–10. Intervention impact was evaluated through baseline and follow-up evaluation. Follow-up mean scores on questions (maximum score of 25) from the Claim Evaluation Tools database (primary outcome) showed minimal between-group difference (intervention versus control: 14.4 versus 13.6; difference 0.8, 95% confidence interval CI −1.6 to 3.1; P = 0.52). Change scores were only slightly higher in the intervention group (difference 1.2 95% CI −0.7 to 3.1; P = 0.21). Between-group differences for secondary outcomes were also minimal. Most intervention group students ‘trusted’ and ‘liked’ the programme and found the content ‘easy’ and ‘helpful’. Most teacher feedback was positive, some noting challenges of covering content in allocated time and maintaining student engagement. It is unlikely that the assessed educational intervention had a large effect. Future research priorities are suggested.
The TNM system is an established tool for classification of solid tumors by means of tumor size and extent, the involvement of local lymph nodes, and the presence of distant metastases. The ...classification was established in order to visualize prognostic implications and to allow establishment of systematic therapeutic algorithms. Since the beginning of 2017 a revised version of the classification has applied. Particularly the classification of otorhinolaryngologic tumors has been thoroughly revised in the 8th edition, partly on the basis of new prognostically relevant parameters, such as infection with oncogenic human papillomavirus (HPV) subtypes.
The 8th edition of the American Joint Committee on Cancer (AJCC) served as a basis for the review. The highlighted changes were supplemented by a literature review and the most important elements were summarized.
Substantial changes were made for oropharyngeal carcinomas caused by HPV, for the classification of lymph node metastases under consideration of extranodal extension, and for classification of tumors of the oral cavity. Due to their frequency and special biology, skin tumors in the head and neck area are now described in a separate chapter.
The new classification is a challenge for all specialties involved in tumor staging and therapy. The advantage for the patient lies in a more accurately adjustable treatment modality through more precise classification of tumors. Good collaboration and rapid implementation of the new classification is required in all disciplines involved in head neck tumor diagnostics and therapy.
The first‐line treatment of hyperuricemia, which causes gout, is allopurinol. The allopurinol response is highly variable, with many users failing to achieve target serum uric acid (SUA) levels. No ...genome‐wide association study (GWAS) has examined the genetic factors affecting allopurinol effectiveness. Using 2,027 subjects in Kaiser Permanente's Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort, we conducted a GWAS of allopurinol‐related SUA reduction, first in the largest ethnic group, non‐Hispanic white (NHW) subjects, and then in a stratified transethnic meta‐analysis. ABCG2, encoding the efflux pump BCRP, was associated with SUA reduction in NHW subjects (P = 2 × 10−8), and a missense allele (rs2231142) was associated with a reduced response (P = 3 × 10−7) in the meta‐analysis. Isotopic uptake studies in cells demonstrated that BCRP transports allopurinol and genetic variants in ABCG2 affect this transport. Collectively, this first GWAS of allopurinol response demonstrates that ABCG2 is a key determinant of response to the drug.
Summary
Head and neck squamous cell carcinoma (HNSCC) is a highly immunosuppressive malignancy. Exosomes in HNSCC patients' plasma are enriched in inhibitory cargo and mediate immunosuppression. As ...these exosomes are products of various cells, the cellular origin of immunoregulatory proteins they carry is unknown. To test whether tumour‐ or T cell‐derived exosomes in patients' plasma are immunosuppressive and impact upon disease activity, we separated CD3(–) from CD3(+) exosomes by immunocapture using anti‐CD3 antibodies. The exosome protein cargo was evaluated for immunoregulatory proteins using on‐bead flow cytometry. Tumour protein‐enriched CD3(–) exosomes were CD44v3(+). Surprisingly, mean levels of programmed death ligand 1 (PD‐L1), cytotoxic T lymphocyte antigen 4 (CTLA‐4) and cyclooxygenase‐2 (COX‐2) were similar in CD3(+) and CD3(–) exosomes, although the latter induced higher (P < 0·0025) ex‐vivo apoptosis of CD8(+) T cells and greater (P < 0·005) conversion of CD4+ T cells to CD4(+)CD39(+) regulatory T cells (Treg). CD3(+) and CD3(–) exosomes carrying high levels of immunosuppressive proteins were highly effective in mediating these functions. Exosomes of patients with Union for International Cancer Control (UICC) stages III/IV disease had higher levels of PD‐L1 and COX‐2 than stages I/II patients (P < 0·005). Patients with nodal involvement had exosomes with the higher inhibitory protein content than N0 patients (P < 0·03). CD3(+) and CD3(–) exosomes of HNSCC patients had higher PD‐L1, COX‐2 and CD15s levels than healthy donors' exosomes (P < 0·009), although levels of immunostimulatory OX40 or OX40L were not different. By isolating CD3(–)/CD44v3‐enriched and CD3(+) exosomes from plasma, the cellular origins of immunoregulatory proteins they carry were identified. Association of exosome molecular profiles with disease progression supports the exosome potential as future cancer biomarkers.
Exosomes from plasma of patients with HNSCC were separated by immunocapture with anti‐CD3 Abs into CD3+ and CD3(‐) fractions. Each fraction was evaluated for the content of immunoregulatory proteins by on‐bead flow cytometry. The levels of immunoregulatory proteins carried by exosomes were correlated to disease activity and stage and lymph node positivity. CD3(‐) CD44v3+ tumor‐derived exosomes were more immunosuppressive than CD3(+) T cell‐derived exosomes.
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