Variable speed liquid chiller drop-in modeling for predicting energy performance of R1234yf as low-GWP refrigerant

This paper presents a model for a variable-speed liquid chiller integrating a compressor model based on Buckingham π-theorem to accurately predict the system performance when R134a is replaced with R1234yf, using a wide range of data obtained from an experimental setup. Relevant variables such as temperature, pressure, mass and volumetric flow rates, compressor power consumption and rotation speed were measured at several positions along the refrigeration and secondary circuits and were used to validate the developed model. Model results show that cooling capacity and power consumption predicted values are in good agreement with experimental data, within ±5%, being slightly higher for the deviation obtained for R134a than for R1234yf. Moreover, model results indicate that R1234yf has a reduction of coefficient of performance (COP) compared with R134a (between 2 and 11.3%), and that R1234yf COP reduction is diminished at intermediate volumetric flow rate and higher inlet temperature for the evaporator secondary fluid, respectively. On the other hand, an environmental analysis based on TEWI (total equivalent warming impact) method showed that direct emissions are almost negligible for R1234yf. However, there are no environmental benefits in terms of indirect greenhouse gas emissions using R1234yf without system modifications (as for instance the addition of internal heat exchanger or R1234yf new design components), which are required to reduce the liquid chiller climate change contribution using it as low GWP alternative in comparison with the typically used R134a refrigerant

Primary endometrial carcinoma with signet-ring cells. A case report and review of the literature

Endometrial adenocarcinoma with signet-ring cells is an infrequent histological type of carcinoma that usually corresponds to a metastasis of a primary carcinoma of another origin, mainly from the gastrointestinal tract or the breast. For this reason, in view of this histological finding, it is essential to carry out a thorough evaluation including mammography, gastroscopy, colonoscopy and thoracoabdominopelvic CT. To date, only six cases of primary endometrial carcinoma with signet-ring cells have been reported in the English literature. A 73-year-old patient was referred to the Gynecology Department with a 3-day history of postmenopausal bleeding. She was diagnosed with primary endometrial adenocarcinoma with signet-ring cells. The anatomopathological special features of the surgical specimen are presented, as well as the evolution of the patient, who remained asymptomatic and free of disease 28 months after surgery. A review of the literature is performed, emphasizing the peculiarities of this rare histological subtype. Despite the fact that primary endometrial carcinoma with signet-ring cells is an infrequent tumor, it must be considered in the differential diagnosis of malignant tumors of aforesaid origin. It is essential to carry out a correct and an extensive investigative study as well as an immunohistochemical analysis of the samples obtained for its confirmation diagnosis

Comparative evaluation of R1234yf, R1234ze(E) and R450A as alternatives to R134a in a variable speed reciprocating compressor

A comparative energetic evaluation of R1234yf, R1234ze(E) and R450A as alternatives to R134a in a variable speed compressor is carried out. A compressor model based on dimensionless numbers was obtained using the Buckingham p -theorem, which was validated with experimental data; showing that the prediction error of the model is lower than ± 10% and ± 2 K for temperature. The experimental data were obtained by testing R134a, R1234yf, R1234ze(E) and R450A for a wide range of operating condi- tions. Results obtained with the validated model, show that the dimensionless approach provides a similar estimation of energy parameters compared with the experimental results, such as power con- sumption, refrigerant mass fl ow rate, cooling capacity, COP, discharge temperature and compressor ef- fi ciencies for each refrigerant tested using the dimensionless approach proposed. The comparative evaluation of the compressor predictions shows a reduction in the cooling capacity obtained with R1234yf, R450A and R1234ze(E), in comparison with R134a. Also, COP values for R1234yf, R450A, and R1234ze(E) are lower than those obtained from R134a. Finally, results shows that the dimensionless correlation compressor model can be used to predict the performance of other reciprocating compres- sors, at similar operating conditions for a wide range of compressor rotation speed, with a reasonable accuracy.The authors thankfully acknowledge to the "Consejo Nacional deCiencia y Tecnología (CONACYT)” for their support to this study, and to the “Ministerio de Educación, Cultura y Deporte” (Grant number FPU12/02841) for sponsoring this work through “Becas y Contratosde Formación de Profesorado Universitario del Programa Nacional de Formación de Recursos Humanos de Investigación del ejercicio 2012”

Yield, quality, alternate bearing and long-term yield index in pecan, as a response to mineral and organic nutrition

The pecan nut is produced in 57 countries in the world. Alternate bearing is one of the main biological problems that affect pecan cultivation. Mineral and organic fertilization is a good strategy to maintain and increase pecan nut production. In this study, several mineral and organic doses of fertilization were tested using a factorial arrangement 56 bounded to 25 treatments was used in structure Taguchi L25: nitrogen (N) 0 - 240 kg ha-1, phosphate (P2O5) 0 - 120 kg ha-1, potassium (K2O) 0 - 100 kg ha-1, calcium (CaO) 0 - 400 kg ha-1, liquid humus 0 - 3600 L ha-1 and solid humus 0 - 8000 kg ha-1. The study was carried out in Aldama city, Chihuahua (Mexico). An average yield of 2.4 t ha-1 was obtained, 157 nuts per kilogram and 58.9% of edible nut. The average alternate bearing intensity was 31.58%, and the long-term yield index (IRLP) was 9.59%. It is concluded that the factors whit the greatest impact on the analyzed variables were N and P2O5. In addition, it was found these mineral and organic fertilization systems help to reduce alternate bearing in pecan and simultaneously improve production and long-term productivity index. Optimal fertilization doses were defined: 181.4 kg ha-1 of N, 93.5 kg ha-1 of P2O5 and 3287.2 L ha-1 of liquid humus. Finally, the mineral fertilization complemented with organic fertilization is considered a good fertilization strategy for pecan trees, to increase production and with lower environmental impact

Fermented Dairy Foods: Impact on Intestinal Microbiota and Health-Linked Biomarkers

The intake of fermented foods is gaining increasing interest due to their health-promoting benefits. Among them, fermented dairy foods have been associated with obesity prevention, and reduction of the risk of metabolic disorders and immune-related pathologies. Fermented foods could lead to these health benefits by providing the consumer with both easily metabolizable nutrients and beneficial microorganisms. Our aim was to evaluate the relationship between the consumption of fermented dairy products and the intestinal microbiota, serum lipid profile, and the pro-oxidant/inflammatory status. 130 healthy adults were evaluated. Dietary fermented food intake was assessed by an annual food frequency questionnaire (FFQ), including 26 fermented dairy products. Levels of the major phylogenetic types of the intestinal microbiota were determined by qPCR, and concentration of fecal short chain fatty acids were assessed by gas chromatography. Serum glucose and lipid profile, as well as serum malondialdehyde (MDA), C-reactive protein (CRP), and leptin levels were determined by standardized protocols. Among fermented dairy foods, natural yogurt, sweetened yogurt and matured/semi-matured cheese were the most consumed. While natural yogurt consumers showed increased fecal levels of Akkermansia with respect to non-consumers, sweetened yogurt intake was associated to lower levels of Bacteroides. Serum levels of CRP were also significantly reduced in yogurt consumers. Our results underline the interest in exploring the potential effects of the different yogurt types and the role the microbiota may play in such effects

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.Ministry of Science and Innovation, Spain (MICINN) Spanish Government PID2020117979RB-I00Instituto de Salud Carlos III European Commission European Commission IMP/00019Junta de Andalucia COVID-0012-2020 PS-2020-342European Social Fund (ESF) 871075Carlos Loucera PAIDI2020-DOC_0035

A phase I trial of oncolytic adenovirus ICOVIR-5 administered intravenously to cutaneous and uveal melanoma patients

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplifcation of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly diferentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future

A Phase I/II Clinical Trial to evaluate the efficacy of baricitinib to prevent respiratory insufficiency progression in onco-hematological patients affected with COVID19: a structured summary of a study protocol for a randomised controlled trial

Objectives: Baricitinib is supposed to have a double effect on SARS-CoV2 infection. Firstly, it reduces the inflammatory response through the inhibition of the Januse-Kinase signalling transducer and activator of transcription (JAK-STAT) pathway. Moreover, it reduces the receptor mediated viral endocytosis by AP2-associated protein kinase 1 (AAK1) inhibition. We propose the use of baricinitib to prevent the progression of the respiratory insufficiency in SARS-CoV2 pneumonia in onco-haematological patients. In this phase Ib/II study, the primary objective in the safety cohort is to describe the incidence of severe adverse events associated with baricitinib administration. The primary objective of the randomized phase (baricitinib cohort versus standard of care cohort) is to evaluate the number of patients who did not require mechanical oxygen support since start of therapy until day +14 or discharge (whichever it comes first). The secondary objectives of the study (only randomized phase of the study) are represented by the comparison between the two arms of the study in terms of mortality and toxicity at day+30. Moreover, a description of the immunological related changes between the two arms of the study will be reported. Trial design: The trial is a phase I/II study with a safety run-in cohort (phase 1) followed by an open label phase II randomized controlled trial with an experimental arm compared to a standard of care arm

Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial

Background: Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. Patients and methods: This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Results: Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. Conclusions: High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations