This study is concerned with the mathematical modelling of the vibration response characteristic of a special dissimilar composite beam based on experimental modal analysis. Here, experimental modal ...analyses of three different dissimilar polyamide 6 composite beams, which are connected to each other by hot plate welding are performed. The measured natural frequencies are compared with finite element predictions for verification purposes. Modal information obtained by experiments is used to construct a mathematical model representing vibration response characteristic of beams by applying multi degree of freedom curve fitting method. The model showing modal characteristics of dissimilar beams is now ready to be used in different kinds of excitations to predict the frequency response of vibration.
Chronic exposure to ionizing radiation (IR) at low doses (<100 mGy) has been insufficiently studied to understand fully the risk to health. Relatively little knowledge exists regarding how species ...and healthy tissues respond at the protein level to chronic exposure to low doses of IR, and mass spectrometric-based profiling of protein expression is a powerful tool for studying changes in protein abundance.
SDS gel electrophoresis, LC-MS/MS mass spectrometry-based approaches and bioinformatic data analytics were used to detect proteomic changes following chronic exposure to moderate/low doses of radiation in adults and normally developed Medaka fish (Oryzias latipes).
Significant variations in the abundance of proteins involved in thyroid hormone signaling and lipid metabolism were detected, which could be related to the gonadal regression phenotype observed after 21.04 mGy and 204.3 mGy/day exposure. The global proteomic change was towards overexpression of proteins in muscle and skin, while the opposite effect was observed in internal organs.
The present study provides information on the impacts of biologically relevant low doses of IR, which will be useful in future research for the identification of potential biomarkers of IR exposure and allow for a better assessment of radiation biosafety regulations.
Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the ...50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was -1.43 log₁₀ c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).
Ionizing radiation is found naturally in the environment. Low doses of IR may have beneficial applications, yet there is also potential for detrimental long-term health effects. Impacts following ...exposure to low levels of IR have been refractory to identification and quantification. Glycoprotein glycosylation is vital to cell-cell communication and organismal function, and sensitive to changes in an organism's macro- and cellular environment. We investigated whether accumulated low doses of IR (LoDIR) affect the N-linked glycoprotein glycans using Medaka fish (Oryzias latipes).
State-of-the-art methods in radiation exposure and glycan analysis were applied to study N-glycan changes after 190 day exposure at three different rates of gamma irradiation (2.25, 21.01, and 204.3 mGy/day) in wild-type adult Medaka. Tissue N-glycans were analyzed following enzymatic release from extracted proteins.
N-linked glycan profiles are dominated by complex type N-glycans modified with terminal sialic acid and core fucose. Fucosylation and sialylation of N-linked glycoprotein glycans are affected by LoDIR and a subset of N-glycans are involved in the organismal radio-response.
This is the first indication that the glycome can be interrogated for biomarkers that report the impact of chronic exposure to environmental stressors, such as low-level IR.
To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) with an Eastern ...Cooperative Oncology Group (ECOG) performance status (PS) of 2.
In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m(2)) or CP (area under the curve of 5 and 500 mg/m(2), respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS).
A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio HR, 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm.
Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.
Background Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive ...impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown. Methods The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors. Results Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54–60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV. Conclusions HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs.
Analyzing plant phenology and plant–animal interaction networks can provide sensitive mechanistic indicators to understand the response of alpine plant communities to climate change. However, ...monitoring data to analyze these processes is scarce in alpine ecosystems, particularly in the highland tropics. The Andean páramos constitute the coldest biodiversity hotspot on Earth, and their species and ecosystems are among the most exposed and vulnerable to the effects of climate change. Here, we analyze for the first time baseline data for monitoring plant phenological dynamics and plant–pollinator networks along an elevation gradient between 4,200 and 4,600 m asl in three mountain summits of the Venezuelan Andes, which are part of the GLORIA monitoring network. We estimated the presence and density of plants with flowers in all the summits and in permanent plots, every month for 1 year. Additionally, we identified pollinators. We calculated a phenological overlap index between species. We summarized the plant–pollinator interactions as a bipartite matrix and represented a quantitative plant–pollinator network, calculating structural properties (grade, connectance, nestedness, and specialization). We also evaluated whether the overall network structure was influenced by differences in sampling effort, changes in species composition between summits, and phenology of the plant species. Finally, we characterized the pollination syndrome of all species. Flowering showed a marked seasonality, with a peak toward the end of the wet season. The overall phenological overlap index was low (0.32), suggesting little synchrony in flowering among species. Species richness of both plants and pollinators decreased along the elevation gradient. Flies, bumblebees, and hummingbirds were the most frequent pollinators in the network, while entomophily and anemophily were the prevailing pollination syndromes. The interaction network in all summits showed high connectance values, significant specialization (H2), and low nestedness. We did not find a significant effect of sampling effort, summit plant species composition, or plant phenology on network structure. Our results indicate that these high tropical alpine plant communities and their plant-pollination networks could be particularly vulnerable to the loss of species in climate change scenarios, given their low species richness and functional redundancy coupled with a high degree of specialization and endemism.
Background: Intravesical bacillus Calmette-Guerin (BCG) therapy is an effective and widely used treatment for superficial bladder carcinoma. Local complications are frequent whereas systemic ...complications are rare but can be serious, and their management is not well known. Methods: We describe retrospectively the records of 22 patients treated in 3 infectious disease departments, for complications related to intravesical BCG therapy as treatment of bladder cancer. Results: All the patients were male, with a median age of 68 years (range 56-88). Complications occurred after a median of 5 instillations (range 1-11) and were observed within 24 h following BCG instillation for 14 patients. Common symptoms were fever (n = 20), impaired general condition (n = 14), and shortness of breath (n = 7). Six patients had a systemic septic reaction leading to transfer into the intensive care unit for five of them. Lung infiltration was the most frequent presentation (n = 11). Mycobacterium bovis was isolated from only two patients, but histology showed the presence of a granuloma in nine patients. Antimycobacterial treatment was initialized in 17 patients; the outcome was favorable in 16 patients, with a median length of symptoms resolution of 22.5 days (range 5-425 days). Eleven patients received corticosteroids in addition to specific treatment and had a more rapid improvement. One patient died with disseminated BCGitis proved by biopsy. Conclusions: Complications following intravesical BCG therapy are rare but can be severe and fatal. Histology seems to be the method that contributes most in confirmation of the diagnosis. Antimycobacterial therapy is effective, and probably more efficient when combined with corticosteroids, but the regimen and duration of the treatment are not standardized.
Aim
Anal screening is recommended in HIV‐positive patients, especially men who have sex with men (MSM), due to an increased incidence of anal cancer. The optimal screening methods are not generally ...agreed.
Method
Screening for anal lesions by anorectal examination, including anoscopy, was offered to HIV‐positive outpatients in a tertiary care university hospital regardless of gender or sexual orientation.
Results
Among the 1206 screened patients (701 MSM, 247 heterosexual men, 258 women), 311 (26%) had histologically proven lesions related to human papilloma virus (HPV) (34% MSM, 14% heterosexual men, 14% women); 123 (10%) had low‐grade dysplasia and 70 (6%) high‐grade dysplasia. Seven anal cancers were also diagnosed. Determinants of any lesion were age < 45 years OR = 1.56 (95% CI, 1.16–2.11), a CD4 count of < 200/mm3 OR = 2.54 (1.71–3.78), receptive anal intercourse OR =3.03 (2.06–4.47), sub‐Saharan African origin OR = 0.53 (0.33–0.85), and history of HPV‐related lesion OR = 1.84 (1.35–2.51). These determinants were similar for all different grades of dysplasia. In patient subgroup analysis, receptive anal intercourse, the CD4 cell count and a history of HPV lesions were determinants of HPV‐positivity in all patients, whereas age was only a determinant in men.
Conclusion
Anoscopy is an alternative method for anal screening in an HIV‐positive population. This screening has to be compared with other tools in populations at high risk of anal cancer.
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