We report a comparative study of a single plasma and a colliding laser produced plasma, investigated using a Faraday cup. An enhancement in ion emission and stagnation is observed in colliding plasma ...plume compared to single plasma plume. We observed that fast ion generation in laser ablated plasma can be achieved at large laser intensity on to the target. As laser intensity increases ionic yield increases for both colliding and single plume and at a fixed laser intensity ionic yield decreases with increase in ambient pressure. The double peak structure is observed in the ion signal at large fluence where the peaks correspond to fast and slow species. A Faraday cup composed of nine collectors is used to measure the spatial/angular distribution of ion of expanding plasma plume. Ionic yield is found to be larger in the colliding plasma plume than the single plasma plume at all spatial/angular positions.
Faraday cup; Laser-produced plasma; Colliding plasma; Carbon plasma.
•The limiter based ADITYA tokamak has been upgraded in the divertor configured ADITYA-U tokamak.•The main modification in ADITYA is the replacement of old rectangular cross section vacuum vessel by ...new circular cross section vacuum vessel to accommodate divertor coils.•The ADITYA-U vessel has been designed with 111 port openings including 4 tangential ports.•The final acceptable tests had been carried out with local leak rate <5×10−10mbarl/s and UHV test as <10−9mbar.•The vessel had been installed in ADITYA-U tokamak structure.
Limiter based ADITYA tokamak has been upgraded in the divertor configured ADITYA-U tokamak. The ADITYA tokamak upgradation includes the replacement of rectangular cross section vacuum vessel by circular cross section vacuum vessel to accommodate additional poloidal (divertor) coils in space between the new vessel and toroidal field coils. The major radius (0.75m) and minor radius (0.25m) has been kept same as of old torus so as to accommodate the new torus inside the toroidal field coils. In order to accommodate as many numbers of diagnostics as possible, the ADITYA-U vessel is designed to have 111 port openings directly on the vessel. The leak proof, UHV condition, precise dimensions and lots of weld and demountable joints in the new vessel made the fabrication job very challenging. The ADITYA-U vacuum vessel of SS304L has been precisely fabricated as per IPR design by Godrej & Boyce Mfg. Co. Ltd. under the supervision of IPR scientists. The factory and IPR site acceptance tests of new vessel had been completed successfully, such as dimensional measurement, leak test, pressure, baking. The final acceptable tests had been carried out successfully as results of local leak rate <5×10−10mbarl/s and global leak rate <5×10−8mbar.l/s, UHV test as <10−9mbar, vessel baking >150°C. After external testing, the vessel has been installed successfully in ADITYA-U tokamak structure. In this paper, we present the all details of ADITYA-U vacuum vessel like design, analysis, fabrication, acceptance, installation and operation to ascertain its suitability for the plasma experiments.
Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based ...on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017–2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models.
In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.
In the ORIOLES study, 77% of opioid pain medication prescribed after radical prostatectomy was unused, with 84% of patients using less than half their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.
Literature comparing the use of isoflurane and sevoflurane inhalation anesthetic agents in birds is scarce. This study aimed to evaluate the comparison of isoflurane and sevoflurane during induction, ...maintenance, and recovery of anesthesia in avian patients.
In this study, 24 injured avian patients (n=24) were selected randomly and divided into four groups during kite flying festival. In the present study, isoflurane and sevoflurane were used as induction and maintenance anesthetic agents, with and without butorphanol tartrate premedication agent in all the birds. Different physiological parameters were evaluated, namely, cloacal temperature (°F), heart rate (beats/min), respiratory rate (breaths/min), and SpO
(%) were recorded at 0, 10, 20 min, and at recovery time. The quality of anesthesia was assessed on the basis of induction time, quality of induction, production of analgesia, muscle relaxation, body reflexes, recovery time, quality of recovery, sitting, standing, and complete recovery time (CRT).
The mean±standard error value of induction time was 230.00±32.55, 280.00±25.29, 180.00±21.90, and 260.00±36.87 s, respectively, in Groups I, II, III, and IV. The feather plucking, pharyngeal, and toe pinching reflexes were noticed, when the birds were passing through the light plane of anesthesia during induction. Comparison of cloacal temperature at the time of recovery between Group-I versus Group-III revealed a significant difference (p<0.05). Comparison of mean respiratory rates at the time of recovery between Group-II versus Group-IV revealed a significant difference (p<0.05). Excellent quality of recovery was observed in all the groups of anesthetic protocols. Sitting, standing, and CRT were observed shortest in avian patients maintained with sevoflurane as compared to isoflurane.
The quality of induction of anesthesia was rapid in avian patients when induced with sevoflurane as compared to isoflurane. Rapid onset of induction and recovery of anesthesia were found with sevoflurane followed by isoflurane. Induction and maintenance of anesthesia in avian patients with sevoflurane resulted in the lowest time required for sitting, standing, and CRT.
To determine whether recommended amounts of leisure-time physical activity (ie, 7.5-15 metabolic equivalent task MET hours/week) are associated with lower cancer risk, describe the shape of the ...dose-response relationship, and explore associations with moderate- and vigorous-intensity physical activity.
Data from 9 prospective cohorts with self-reported leisure-time physical activity and follow-up for cancer incidence were pooled. Multivariable Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% CIs of the relationships between physical activity with incidence of 15 types of cancer. Dose-response relationships were modeled with restricted cubic spline functions that compared 7.5, 15.0, 22.5, and 30.0 MET hours/week to no leisure-time physical activity, and statistically significant associations were determined using tests for trend (
< .05) and 95% CIs (< 1.0).
A total of 755,459 participants (median age, 62 years range, 32-91 years; 53% female) were followed for 10.1 years, and 50,620 incident cancers accrued. Engagement in recommended amounts of activity (7.5-15 MET hours/week) was associated with a statistically significant lower risk of 7 of the 15 cancer types studied, including colon (8%-14% lower risk in men), breast (6%-10% lower risk), endometrial (10%-18% lower risk), kidney (11%-17% lower risk), myeloma (14%-19% lower risk), liver (18%-27% lower risk), and non-Hodgkin lymphoma (11%-18% lower risk in women). The dose response was linear in shape for half of the associations and nonlinear for the others. Results for moderate- and vigorous-intensity leisure-time physical activity were mixed. Adjustment for body mass index eliminated the association with endometrial cancer but had limited effect on other cancer types.
Health care providers, fitness professionals, and public health practitioners should encourage adults to adopt and maintain physical activity at recommended levels to lower risks of multiple cancers.
The druggability of the tyrosyl-DNA phosphodiesterase 1 (Tdp1) enzyme was investigated in conjunction with topoisomerase 1 inhibition. A novel class of thiazole, aminothiazole and hydrazonothiazole ...usnic acid derivatives was synthesized and evaluated as Tdp1 inhibitors and their ability to sensitize tumors to topotecan, a topoisomerase inhibitor in clinical use. Of all the compounds tested, four hydrazinothiazole derivatives, 20c, 20d, 20h and 20i, inhibited the enzyme in the nanomolar range. The activity of the compounds was verified by affinity experiments as well as supported by molecular modelling. The most effective Tdp1 inhibitor, 20d, was ton-toxic and increased the effect of topotecan both in vitro and in vivo in the Lewis lung carcinoma model. Furthermore, 20d showed significant increase in the antitumor and antimetastatic effect of topotecan in mice. The results presented here justify compound 20d to be considered as a drug lead for antitumor therapy.
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•Hydrazinothiazole derivatives of usnic acid are excellent inhibitors of Tdp1.•The most effective Tdp1 inhibitor showed significant increase in the antitumor activity of topotecan in mice.•The most effective Tdp1 inhibitor showed significant increase in the antimetastatic effect of topotecan in mice.•The inhibitor proved to have no own acute toxicity at the concentration used.
Coconut coir (a lignin-rich, organic material) is widely used for its commercial and economic benefits. In this study, crossbred (exotic) and Kankrej (indigenous) breeds of cattle were fed diets ...containing 7 or 14% coconut coir. Metagenomic analyses (16S rRNA gene amplicon and shotgun sequencing) were used to characterize the microbial community in the rumen and fecal samples along with their functional capabilities. Both amplicon and shotgun analyses revealed the predominance of bacterial phyla, Bacteroidetes, Firmicutes, Actinobacteria and Fibrobacter in ruminal liquid, ruminal solid and fecal samples. 16S rRNA gene amplicon sequencing revealed a total of 18 different bacterial taxa were found to be enriched exclusively in the animals fed with 14% coir. The shotgun analysis revealed abundance of bacterial genera, Fibrobacter, Clostridium, Prevotella, Butyrivibrio, and Ruminococcus in both liquid and solid fractions of ruminal contents, while in the fecal sample, Bacteroides, Alistipes, Plaudibacter, Parabacteroides, Porphyromonas, and Victivallis and archaeal genus, Methanocorpusculum were abundant. The functional analysis based on dbCAN database suggested that among the Glycoside hydrolase family, genes that encode oligosaccharide degrading enzymes, GH3, GH13 (p-value < 0.05), and GH43 were abundant in the feces. In ruminal solid, cellulase encoding the GH5 family was abundant. Also, lignocellulosic binding modules encoded by the CBM family, including cellulose (CBM3) and hemicellulose binding modules (CBM32 and CBM67) were abundant. Thus, the study indicated the enrichment of lignocellulosic enzymes in ruminal contents in response to feeding the coconut coir, which could be mined for potential biofuel production and other biotechnological applications.
•Coconut coir was used as a feed supplement for cattle to analyze gut microbial changes.•Significant differences were observed between the animals fed 7 or 14% of coconut coir.•Bacteroides, Fibrobacter, Clostridium, Prevotella, Porphyromonas, Plaudibacter, and Ruminococcusare predominated bacteria.•GH5 was the highest among the other CAZy families, encoding cellulase enzyme in the ruminal solids of acttle fed 14% coir.•The genes related to cellulose and hemicellulose deconstruction were found in the highest abundance in all the metagenomes.
In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab ...before surgery. Data from a phase 2 study are needed to confirm these findings.
We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events.
A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval CI, 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%).
Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).
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