First prototype of a low-cost vacuum baffle with electrical feedthrough

En un trabajo previo, Conde Garrido y Silveyra propusieron una novedosa tecnología de trampa fría capaz de atrapar contaminantes en sistemas de vacío. La misma fue diseñada para ser aplicada en sistemas de deposición de películas delgadas de vidrios calcogenuros por ablación láser pulsada. Mientras que los sistemas tradicionales se enfrían por compresión de gases o baños fríos como nitrógeno líquido, la trampa reportada se enfría por efecto termoeléctrico. Esto permite reducir la inversión de capital, los costos operativos y los tiempos de puesta en marcha y mantenimiento. En el presente trabajo se presenta la construcción, puesta a punto y caracterización del primer prototipo físico de la trampa fría. La caracterización incluyó, en primer lugar, el control de la presión final alcanzada por el dispositivo. Para caracterizar el desempeño térmico del dispositivo, se diseñó y fabricó un sistema de medición temperaturas. Como parte de este sistema de medición, se destaca un pasante eléctrico para vacío de bajo costo. Los resultados indican que, con la trampa fabricada, se pueden alcanzar presiones menores a 2 × 10−5 mbar, mientras que las superficies frías alcanzan temperaturas de aproximadamente −12 ◦C. Los niveles de vacío y de temperatura cumplen las condiciones requeridas para el sistema de deposición de películas delgadas de vidrios calcogenuros por ablación láser pulsada. Sin embargo, no se logran temperaturas tan bajas como las estimadas para el prototipo virtual (de hasta −50◦C). Se identificaron entonces los puentes y resistencias térmicas presentes en el dispositivo fabricado, despreciados en el modelo, señalando oportunidades de mejora. Finalmente, se proponen revisiones al diseño actual que simplifican su proceso de manufactura, mejoran su robustez y eficacia, y facilitan su operación y mantenimiento.In a previous work, Conde Garrido and Silveyra proposed a novel cold trap (baffle) technology capable of trapping contaminants in vacuum systems. The baffle was designed to be applied in systems to synthesize chalcogenide glass thin films by pulsed laser deposition. While traditional baffles are cooled down with compression cooling systems or cooling solutions such as liquid nitrogen, the reported baffle is cooled down by the thermoelectric effect, which allows for reducing the capital investment, operating costs, as well as start-up and maintenance times. This paper presents the construction, tuning, and characterization of the first physical prototype of the baffle. The characterization included, first, the control of the final pressure reached by the device. To characterize the thermal performance of the baffle, a temperature measurement system was designed and manufactured. Within this measurement system, we highlight a low-cost electric vacuum feedthrough. The results indicate that the constructed baffle can reach pressures lower than 2 × 10−5 mbar, while the cold surfaces reach temperatures of approximately −12◦ C. The vacuum and cold temperature levels meet the required conditions for the pulsed laser deposition of chalcogenide glass thin films. However, temperatures are not as low as those estimated for the virtual prototype (down to −50◦ C). Thermal bridges and resistances present in the fabricated device, neglected in the model, were then identified, pointing out opportunities for improvement. Finally, revisions to the current design are proposed that simplify its manufacturing process, improve its robustness and efficiency, and facilitate its operation and maintenance.Fil: Conde Garrido, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Sólidos Amorfos; ArgentinaFil: Couselo, M. A.. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Sólidos Amorfos; ArgentinaFil: Silveyra, Josefina María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; Argentina. Universidad de Buenos Aires. Facultad de Ingeniería. Departamento de Física. Laboratorio de Sólidos Amorfos; Argentin

Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 degrees C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 degrees C, 25 degrees C, or vehicle at 21 degrees C, 25 degrees C and 32 degrees C for a week. Animals housed at 32 degrees C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 degrees C, body temperature of leptin infused animals housed at 21 degrees C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa

Case Report Catheter-Related Acremonium kiliense Fungemia in a Patient with Ulcerative Colitis under Treatment with Infliximab

is properly cited. Acremonium spp. are filamentous, cosmopolitan fungi commonly isolated from plant debris and soil. They are infrequent pathogens in humans. Acremonium fungemia has been reported in neutropenic patients associated with central venous catheters and in nonneutropenic patients receiving long-term total parenteral nutrition. TNF-α blockade is associated with fungal infections, but no Acremonium spp. infection had been reported up to the present. In this paper, we present a patient with ulcerative colitis who developed Acremonium kiliense fungemia associated with infliximab therapy while receiving total parenteral nutrition. The patient was successfully treated with voriconazole. Acremonium sp. infection must be suspected as another cause of fungal infection in patients under treatment with infliximab

SEOM clinical guideline for the management of cutaneous melanoma (2020)

Melanoma affects about 6000 patients a year in Spain. A group of medical oncologists from Spanish Society of Medical Oncology (SEOM) and Spanish Multidisciplinary Melanoma Group (GEM) has designed these guidelines to homogenize the management of these patients. The diagnosis must be histological and determination of BRAF status has to be performed in patients with stage ≥ III. Stage I-III resectable melanomas will be treated surgically. In patients with stage III melanoma, adjuvant treatment with immunotherapy or targeted therapy is also recommended. Patients with unresectable or metastatic melanoma will receive treatment with immunotherapy or targeted therapy, the optimal sequence of these treatments remains unclear. Brain metastases require a separate consideration, since, in addition to systemic treatment, they may require local treatment. Patients must be followed up closely to receive or change treatment as soon as their previous clinical condition changes, since multiple therapeutic options are available

Long-term field metal extraction by pelargonium:phytoextraction efficiency in relation to plant maturity

The long length of periods required for effective soil remediation via phytoextraction constitutes a weak point that reduces its industrial use. However, these calculated periods are mainly based on short-term and/or hydroponic controlled experiments. Moreover, only a few studies concern more than one metal, although soils are scarcely polluted by only one element.In this scientific context, the phytoextraction of metals and metalloids (Pb, Cd, Zn, Cu,and As) by Pelargonium was measured after a long-term field experiment. Both bulk and rhizosphere soils were analyzed in order to determine the mechanisms involved in soil-root transfer. First, a strong increase in lead phytoextraction was observed with plant maturity, significantly reducing the length of the period required for remediation. Rhizosphere Pb, Zn, Cu, Cd, and As accumulation was observed (compared to bulk soil), indicating metal mobilization by the plant, perhaps in relation to root activity. Moreover, metal phytoextraction and translocation were found to be a function of the metals’ nature. These results, taken altogether, suggest that Pelargonium could be used as a multi-metal hyperaccumulator under multi-metal soil contamination conditions, and they also provide an interesting insight for improving field phytoextraction remediation in terms of the length of time required, promoting this biological technique

Sex-related differences of fatty acid-binding protein 4 and leptin levels in atrial fibrillation

Aims: Adiposity plays a key role in the pathogenesis of atrial fibrillation (AF). Our aim was to study the sex differences in adipokines levels according to AF burden. Methods and results: Two independent cohorts of patients were studied: (i) consecutive patients with AF undergoing catheter ablation (n = 217) and (ii) a control group (n = 105). (i) Adipokines, oxidative stress, indirect autonomic markers, and leucocytes mRNA levels were analysed; (ii) correlation between biomarkers was explored with heatmaps and Kendall correlation coefficients; and (iii) logistic regression and random forest model were used to determine predictors of AF recurrence after ablation. Our results showed that: (i) fatty acid-binding protein 4 (FABP4) and leptin levels were higher in women than in men in both cohorts (P < 0.01). In women, FABP4 levels were higher on AF cohort (20 ± 14 control, 29 ± 18 paroxysmal AF and 31 ± 17 ng/mL persistent AF; P < 0.01). In men, leptin levels were lower on AF cohort (22 ± 15 control, 13 ± 16 paroxysmal AF and 13 ± 11 ng/mL persistent AF; P < 0.01). (ii) In female with paroxysmal AF, there was a lower acetylcholinesterase and higher carbonic anhydrase levels with respect to men (P < 0.05). (iii) Adipokines have an important role on discriminate AF recurrence after ablation. In persistent AF, FABP4 was the best predictor of recurrence after ablation (1.067, 95% confidence interval 1-1.14; P = 0.046). Conclusion: The major finding of the present study is the sex-based differences of FABP4 and leptin levels according to AF burden. These adipokines are associated with oxidative stress, inflammatory and autonomic indirect markers, indicating that they may play a role in AF perpetuation.This study was supported by projects (PI16/01282 and PI18/01584) integrated in the Plan Estatal de I+D+I 2016–2019 and cofounded by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación del Fondo Europeo de Desarrollo Regional (FEDER). J.N.L.-C. and M.R.-M. were a recipient of a Sociedade Galega de Cardioloxía (SOGACAR) research grant. D.d.G.-C. was a recipient of a Juan de la Cierva-Incorporación grant from the Ministry of Science Innovation and Universities (IJCI-2016-29393). CIBER Cardiovascular (CB16/11/00403 to V.Ll.-C. and D.d.G.-C.) is a project from Carlos III Health Institute.Peer reviewe

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A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study

[Purpose]: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L.[Materials and methods]: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L–T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed.[Results]: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1–43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%).[Conclusion]: The combination of L–T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L–T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.This work was supported by GlaxoSmithKline plc (GSK) through a contract with Medica Scientia Innovation Research (MedSIR), an academic research organization focused on independent clinical research development

Adjuvant Therapy of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Patients With Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915)

PURPOSE Ipilimumab and nivolumab have each shown treatment benefit for high-risk resected melanoma. The phase III CheckMate 915 trial evaluated adjuvant nivolumab plus ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or IV melanoma. PATIENTS AND METHODS In this randomized, double-blind, phase III trial, 1,833 patients received nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks (916 patients) or nivolumab 480 mg once every 4 weeks (917 patients) for &lt;= 1 year. After random assignment, patients were stratified by tumor programmed death ligand 1 (PD-L1) expression and stage. Dual primary end points were recurrence-free survival (RFS) in randomly assigned patients and in the tumor PD-L1 expression-level &lt; 1% subgroup. RESULTS At a minimum follow-up of approximately 23.7 months, there was no significant difference between treatment groups for RFS in the all-randomly assigned patient population (hazard ratio, 0.92; 95% CI, 0.77 to 1.09; P = .269) or in patients with PD-L1 expression &lt; 1% (hazard ratio, 0.91; 95% CI, 0.73 to 1.14). In all patients, 24-month RFS rates were 64.6% (combination) and 63.2% (nivolumab). Treatment-related grade 3 or 4 adverse events were reported in 32.6% of patients in the combination group and 12.8% in the nivolumab group. Treatment-related deaths were reported in 0.4% of patients in the combination group and in no nivolumab-treated patients. CONCLUSION Nivolumab 240 mg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks did not improve RFS versus nivolumab 480 mg once every 4 weeks in patients with stage IIIB-D or stage IV melanoma. Nivolumab showed efficacy consistent with previous adjuvant studies in a population resembling current practice using American Joint Committee on Cancer eighth edition, reaffirming nivolumab as a standard of care for melanoma adjuvant treatment

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery