Circulating tumor HPV DNA (ctHPV16) assessed in liquid biopsy may be used as a marker of cancer in patients with HPV-associated oropharyngeal cancer (HPV + OPC). Factors influencing the initial ...ctHPV16 quantity are not well recognized. In this study we aimed to establish what factors are related to the level of ctHPV16 at the time of diagnosis. 51 patients (37 men and 14 women, median age of 57 years old) with HPV + OPC prior to definitive treatment were included. ctHPV16 was measured by qPCR. Tumor and nodal staging were assessed according to AJCC8. Blood derived factors included squamous cell carcinoma antigen (SCC-Ag), serum soluble fragment of cytokeratin 19 (CYFRA 21-1), C-reactive protein (CRP), albumin level (Alb), neutrophils (Neut), thrombocytes (Plt) and lymphocyte (Lym) count, Neut/Lym ratio were assessed. The volumes of the primary tumor (TV) and involved lymph nodes (NV) were calculated using MRI, CT or PET-CT scans. Data were analysed using parametric and nonparametric methods. Variables for multivariable linear regression analysis were chosen based on the results from univariable analysis (correlation, univariable regression and difference). There were 9 (18%), 10 (19%) and 32 (63%) patients who had TV and NV assessed in MRI, CT or PET respectively. Primary tumor neither as T-stage nor TV was related to ctHPV16 level. Significant differences in the ctHPV16 between patients with high vs low pain (P = 0.038), NV (P = 0.023), TV + NV (P = 0.018), CYFRA 21-1 (P = 0.002), CRP (P = 0.019), and N1 vs N3 (P = 0.044) were observed. ctHPV16 was significantly associated with CYFRA 21-1 (P = 0.017), N stage (P = 0.005), NV (P = 0.009), TV + NV (P = 0.002), CRP (P = 0.019), and pain (P = 0.038). In univariable linear regression analysis the same variables predicted ctHPV16 level. In multivariable analyses, CYFRA 21-1 and CRP (both as categorical variables) were predictors of ctHPV16 level even above NV. ctHPV16 at presentation is driven by tumor volume measured mostly by N. CYFRA 21-1 and CRP are additional factors related to ctHPV16 prior to the treatment.
To examine trends in age-adjusted cigarette smoking prevalence among working adults by industry and occupation during 2004-2012, and to project those prevalences and compare them to the 2020 Healthy ...People objective (TU-1) to reduce cigarette smoking prevalence to ≤12%.
We analyzed the 2004-2012 National Health Interview Survey (NHIS) data. Respondents were aged ≥18 years working in the week prior to the interview. Temporal changes in cigarette smoking prevalence were assessed using logistic regression. We used the regression model to extrapolate to the period 2013-2020.
Overall, an estimated 19.0% of working adults smoked cigarettes: 22.4% in 2004 to 18.1% in 2012. The largest declines were among workers in the education services (6.5%) industry and in the life, physical, and social science (9.7%) occupations. The smallest declines were among workers in the real estate and rental and leasing (0.9%) industry and the legal (0.4%) occupations. The 2020 projected smoking prevalences in 15 of 21 industry groups and 13 of the 23 occupation groups were greater than the 2020 Healthy People goal.
During 2004-2012, smoking prevalence declined in the majority of industry and occupation groups. The decline rate varied by industry and occupation groups. Projections suggest that certain groups may not reach the 2020 Healthy People goal. Consequently, smoking cessation, prevention, and intervention efforts may need to be revised and strengthened, particularly in specific occupational groups.
In 2010, an estimated 8.2% of U.S. adults had current asthma, and among these persons, 49.1% had had an asthma attack during the past year (1). Workplace exposures can cause asthma in a previously ...healthy worker or can trigger asthma exacerbations in workers with current asthma* (2). To assess the industry- and occupation-specific prevalence of current asthma, asthma attacks, and asthma-related emergency department (ED) visits among working adults, CDC analyzed 2011-2016 National Health Interview Survey (NHIS) data for participants aged ≥18 years who, at the time of the survey, were employed at some time during the 12 months preceding the interview. During 2011-2016, 6.8% of adults (11 million) employed at any time in the past 12 months had current asthma; among those, 44.7% experienced an asthma attack, and 9.9% had an asthma-related ED visit in the previous year. Current asthma prevalence was highest among workers in the health care and social assistance industry (8.8%) and in health care support occupations (8.8%). The increased prevalence of current asthma, asthma attacks, and asthma-related ED visits in certain industries and occupations might indicate increased risks for these health outcomes associated with workplace exposures. These findings might assist health care and public health professionals in identifying workers in industries and occupations with a high prevalence of current asthma, asthma attacks, and asthma-related ED visits who should be evaluated for possible work-related asthma. Guidelines intended to promote effective management of work-related asthma are available (2,3).
•The lowest mortality rate was found to be linked with Etanercept.•The highest mortality rate was observed in TPE and IVIG.•Cyclosporine treatment slows reepithelialisation time.•The shortest ...hospital stays were observed with steroid treatments.•There is a great need for randomized TEN trials.
Stevens-Johnson’s Syndrome (SJS) and Toxic Epidermal Necrolysis are rare, life-threatening dermatologic conditions with acute onset and not clearly established treatment protocol. A plethora of observational studies are present with lack of up-to-date consensus based on evaluation of objective endpoints, among others mortality. Thorough analysis of available databases (Pubmed, EMBASE, Cinahl, Web of Science, Clinical Trials) was conducted according to PRISMA guidelines. Authors initially identified 700 papers, with 82 of them potentially eligible according to adopted criteria. A total of 42 studies were included into pooled synthesis. For continuous outcomes we analyzed the pooled means for endpoint scores using observed cases data. Categorical outcomes were analyzed by calculating the pooled event rates. We conducted subgroup and exploratory maximum likelihood random effects meta-regression analyses regarding SCORTEN of all outcomes. Using random-effects model, the overall pooled Mortality Rate was 0.191 (95%CI, 0.132–0.269). The lowest mortality rate was found to be linked with Etanercept and highest in Total Plasma Exchange (TPE) and Intravenous Immunoglobulin (IVIG). Overall reepithelization was 13.278 days (95%CI, 8.773–17.784),The highest was found in cyclosporine treatment; 14.739 whilst the lowest for steroids. Length of hospital stay in overall analysis was 19.99 days (95%CI, 16.53–23.44),the highest was linked with TPE/TPE+IvIg treatment, the lowest with steroids. Risk of bias of assessed studies was estimated to be high (for observational studies mean STROBE score 12.44). High quality TEN and SJS studies are lacking. Almost all papers report observational data without randomization and double-blind control. Therefore, the pooled analysis cannot be presented with initial bias. In our meta-analysis the most successful regimen was Etanercept treatment. It was linked with the lowest mortality. The most negative treatment outcome was observed in studies reporting TPE and IVIG. Randomized trials of high quality are needed in SJS and TEN.
Aeolian coarse‐grained ripples have been found in all regions investigated by Mars rovers: Meridiani Planum, Gusev crater, Gale crater, and Jezero crater. Therefore, it can be assumed that ...coarse‐grained ripples are one of the most common landforms on Mars. Studying their formation and evolution gives us the opportunity to determine past and current wind patterns. They are also crucial for understanding the formation and evolution of larger aeolian bedforms. Of all locations studied in situ on Mars, coarse‐grained ripples in extensive (∼100 km2) ripple fields were found only on Meridiani Planum. As coarse‐grained ripples on Mars are not well characterized in the literature, in this work, the morphometry, morphology, spatial distribution, and orientation of coarse‐grained ripples investigated along the 45 km long traverse of the Opportunity rover were analyzed. The obtained results allowed for a more precise definition of coarse‐grained ripples and for distinguishing three classes of coarse‐grained ripples on Meridiani Planum: small, medium, and large. The coarse‐grained ripple activity on Meridiani Planum is now limited due to low material supply, and the relatively strong induration of the ripple surfaces. Even though most of the coarse‐grained ripples on Meridiani Planum were formed thousands of years ago, some smaller coarse‐grained ripples were formed by modern winds.
Plain Language Summary
Ripples are sand ridges formed by wind. As ripples are very common on Mars, understanding their formation and evolution is very crucial not only for understanding the Martian environment but also for future Mars missions. Meridiani Planum is an equatorial plain on Mars that is covered by sand ripples. These ripples range in size from centimeters to decimeters, and their surface is made up of coarse sand particles (1–2 mm in diameter). The western part of Meridiani Planum was investigated by the Opportunity rover. Based on the rover's data and high‐resolution orbital images, the properties of ripples, including their size, shape, composition, distribution, and orientation, were analyzed. Meridiani Planum coarse‐grained ripples occur in three different size classes: small, medium, and large. They change very slowly as coarse particles armor their surface and because smaller (and therefore easier to carry by wind) sand particles are available only in small amounts, even though some of these ripples were formed relatively recently. Coarse‐grained ripples on Meridiani Planum have morphometry and morphology very similar to ripples composed of coarse sand grains in other locations on Mars. Therefore, coarse‐grained ripples can be classified as a different class of ripples from fine sand ripples.
Key Points
There are at least two classes of ripples on Mars: fine‐grained ripples and coarse‐grained ripples
Coarse‐grained ripples on Meridiani Planum can be statistically distinguished into small, medium, and large ripples
These ripples are at various stages of development and the youngest are small ripples and rim ripples, the latter formed near obstacles
Health care providers should ask workers with new or worsening asthma for occupational exposures and be alert to potential associations between workplace exposures and asthma symptoms.
Abstract Drugs that selectively inhibit the serotonin transporter (SERT) are widely prescribed for treatment of depression and a range of anxiety disorders. We studied the time course of changes in ...tryptophan hydroxylase (TPH) in four raphe nuclei after initiation of two different SERT inhibitors, citalopram and fluoxetine. In the first experiment, groups of Sprague–Dawley rats received daily meals of rice pudding either alone ( n=9 ) or mixed with citalopram 5 mg/kg/day ( n=27 ). Rats were sacrificed after 24 h, 7 days or 28 days of treatment. Sections of dorsal raphe nucleus (DRN), median raphe nucleus (MRN), raphe magnus nucleus (RMN) and caudal linear nucleus (CLN) were processed for TPH immunohistochemistry. Citalopram induced a significant reduction in DRN TPH-positive cell counts at 24 h (41%), 7 days (38%) and 28 days (52%). Similar reductions in TPH-positive cell counts were also observed at each timepoint in the MRN and in the RMN. In the MRN, citalopram resulted in significant reductions at 24 h (26%), 7 days (16%) and 28 days (23%). In the RMN, citalopram induced significant reductions of TPH-positive cell counts at 24 h (45%), 7 days (34%) and 28 days (43%). By contrast, no significant differences between control and treatment groups were observed in the CLN at any of the time points that we studied. To investigate whether these changes would occur with other SERT inhibitors, we conducted a second experiment, this time with a 28-day course of fluoxetine. As was observed with citalopram, fluoxetine induced significant reductions of TPH cell counts in the DRN (39%), MRN (38%) and RMN (41%), with no significant differences in the CLN. These results indicate that SERT inhibition can alter the regulation of TPH, the rate limiting enzyme for serotonin biosynthesis. This persistent and regionally specific downregulation of serotonin biosynthesis may account for some of the clinical withdrawal symptoms associated with drugs that inhibit SERT.
The effect of confining pressure (CP) on the diffusion of tritiated-water (HTO) and iodide (I−) tracers through Ordovician rocks from the Michigan Basin, southwestern Ontario, Canada, and Opalinus ...Clay from Schlattingen, Switzerland was investigated in laboratory experiments. Four samples representing different formations and lithologies in the Michigan Basin were studied: Queenston Formation shale, Georgian Bay Formation shale, Cobourg Formation limestone and Cobourg Formation argillaceous limestone. Estimated in situ vertical stresses at the depths from which the samples were retrieved range from 12.0 to 17.4MPa (Michigan Basin) and from 21 to 23MPa (Opalinus Clay). Effective diffusion coefficients (De) were determined in through-diffusion experiments. With HTO tracer, applying CP resulted in decreases in De of 12.5% for the Queenston Formation shale (CPmax=12MPa), 30% for the Georgian Bay Formation shale (15MPa), 34% for the Cobourg Formation limestone (17.4MPa), 31% for the Cobourg Formation argillaceous limestone (17.4MPa) and 43–46% for the Opalinus Clay (15MPa). Decreases in De were larger for the I− tracer: 13.8% for the Queenston shale, 42% for the Georgian Bay shale, 50% for the Cobourg Formation limestone, 55% for the Cobourg Formation argillaceous limestone and 63–68% for the Opalinus Clay. The tracer-specific nature of the response is attributed to an increasing influence of anion exclusion as the pore size decreases at higher CP.
Results from the shales (including Opalinus Clay) indicate that the pressure effect on De can be represented by a linear relationship between De and ln(CP), which provides valuable predictive capability. The nonlinearity results in a relatively small change in De at high CP, suggesting that it is not necessary to apply the exact in situ pressure conditions in order to obtain a good estimate of the in situ diffusion coefficient. Most importantly, the CP effect on shale is reversible (±12%) suggesting that, for argillaceous rocks, it is possible to obtain De values that are representative of the in-situ condition by conducting measurements on re-pressurized samples that were obtained with standard drilling practices. This may not be the case for brittle rock samples as the results from limestone suggest that irreversible damage occurred during the pressure cycling.
•Effect of confining pressure (CP) on diffusion was investigated for sedimentary rocks.•Decreases in De and accessible porosity (ϕ) were observed as pressure increased.•For clay-rich rocks, the pressure dependence of De on CP is reversible.•Anion exclusion increases with confining pressure.
PDF
