Amphibians are the most threatened group of vertebrates because they have certain biological and ecological characteristics that make them sensitive to environmental changes. The aim of this study ...was to evaluate the health status of field-collected adult frogs of Leptodactylus luctator (Amphibia, Anura) living in sites with different anthropogenic disturbances (florihorticulture, petrochemical industry and sewage discharges) and a reference site without any detectable influence of such activities. To this end, a battery of 21 biomarkers (hematological, biochemical and individual biomarkers) was studied using a multivariate approach that allows us to evaluate the relationship between them and provide information on their usefulness. The frogs at the florihorticulture, petrochemical and sewage discharges sites exhibited several biomarkers far from homeostasis. In addition, we identified 11 of 21 biomarkers that were useful indicators of the health status of the frogs and allowed discrimination between study sites in the following order: lymphocytes (98 %), neutrophils (45 %), hemoglobin (42 %), monocytes (41 %), fat body index (35 %), eosinophils (35 %), hepatosomatic index (33 %), mean corpuscular hemoglobin (32 %), thrombocytes (27 %), catalase in liver (26 %), and GST in liver (26 %). The results suggest that hematological biomarkers contribute the most to site separation, whereas biochemical biomarkers contribute the least. The integral interpretation of the results also allowed us to diagnose the different health status of L. luctator: The frogs from the petrochemical industry were the most negatively affected, followed by the frogs from the sewages discharges and finally the frogs from the florihorticulture and reference sites. This is the first field study with anurans in which so many biomarkers were examined.
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•Integral analysis of 21 biomarkers allowed diagnosing diverse frog health statuses.•Frogs in disturbed sites showed biomarkers far from homeostasis.•We identified 11 biomarkers indicative of frog health that distinguished each site.•We selected 9 sensitive biomarkers that require non-invasive methods.
The clinical course of COVID-19 critically ill patients, during their admission in the intensive care unit (UCI), including medical and infectious complications and support therapies, as well as ...their association with in-ICU mortality has not been fully reported.
This study aimed to describe clinical characteristics and clinical course of ICU COVID-19 patients, and to determine risk factors for ICU mortality of COVID-19 patients.
Prospective, multicentre, cohort study that enrolled critically ill COVID-19 patients admitted into 30 ICUs from Spain and Andorra. Consecutive patients from March 12
to May 26
, 2020 were enrolled if they had died or were discharged from ICU during the study period. Demographics, symptoms, vital signs, laboratory markers, supportive therapies, pharmacological treatments, medical and infectious complications were reported and compared between deceased and discharged patients.
A total of 663 patients were included. Overall ICU mortality was 31% (203 patients). At ICU admission non-survivors were more hypoxemic SpO
with non-rebreather mask, 90 (IQR 83 to 93) vs. 91 (IQR 87 to 94); P<.001 and with higher sequential organ failure assessment score SOFA, 7 (IQR 5 to 9) vs. 4 (IQR 3 to 7); P<.001. Complications were more frequent in non-survivors: acute respiratory distress syndrome (ARDS) (95% vs. 89%; P=.009), acute kidney injury (AKI) (58% vs. 24%; P<10
), shock (42% vs. 14%; P<10
), and arrhythmias (24% vs. 11%; P<10
). Respiratory super-infection, bloodstream infection and septic shock were higher in non-survivors (33% vs. 25%; P=.03, 33% vs. 23%; P=.01 and 15% vs. 3%, P=10
), respectively. The multivariable regression model showed that age was associated with mortality, with every year increasing risk-of-death by 1% (95%CI: 1 to 10, P=.014). Each 5-point increase in APACHE II independently predicted mortality OR: 1.508 (1.081, 2.104), P=.015. Patients with AKI OR: 2.468 (1.628, 3.741), P<10
), cardiac arrest OR: 11.099 (3.389, 36.353), P=.0001, and septic shock OR: 3.224 (1.486, 6.994), P=.002 had an increased risk-of-death.
Older COVID-19 patients with higher APACHE II scores on admission, those who developed AKI grades ii or iii and/or septic shock during ICU stay had an increased risk-of-death. ICU mortality was 31%.
► High rotation speed yielded intense onion ring-like mixing pattern in the stir zone. ► Limited material mixing at low rotation speeds. ► Pin tool threaded profile plays an important role in ...material flow and mixing pattern.
The scope of this investigation is to evaluate the effect of joining parameters on the mechanical properties, microstructural features and material flow of dissimilar aluminium alloys (3mm-thick AA2024-T3 and AA7075-T6 sheets) joints produced by friction stir welding. Mechanical performance has been investigated in terms of hardness and tensile testing. Material flow using the stop action technique has also been investigated in order to understand the main features of the mixing process. No onion ring formation has been observed; the boundary between both base materials at the stir zone is clearly delineated, i.e., no material mixing is observed. A non-stable rotational flow inside the threads has been identified due to the formation of a cavity on the rear of the pin. Microstructural observation has revealed the development of a recrystallised fine-grained stir zone, with two different grain sizes resulting from the two different base materials.
Friction stir lap welds in AA 7075-T6 aluminium alloy were produced using tools with and without geometrical imperfections and varying welding pitch. Geometrical imperfections, resulting from the ...damage of the tool during the welding of the hard aluminium alloy, were simulated by machining small flats in the pin threads. Material adhesion to the worn tool was simulated by increasing the welding pitch. The welds produced were characterised, in the as-welded and heat-treated conditions, by performing monotonic and cyclic tensile-shear tests, micro-hardness measurements and metallography. The peak temperatures reached during welding were calculated using the spindle torque. No important differences in heat generation were registered when varying the welding conditions. The morphology and size of the lap weld defects were analysed in order to assess the influence of tool damage on welds properties. Material adhesion to the tool, simulated by increasing the welding pitch, showed to have a stronger influence on defect size than the thread imperfections. The small changes in welds defect size had no important effect on the monotonic strength of the welds, but had important influence on the fatigue behaviour. An increase of around 10% in the effective sheet thickness of the CL joints resulted in an increase of 500% in the fatigue life. Improved fatigue performance was also registered for the welds performed with the tool with pin imperfections indicating that sensitive tool damage will have no negative influence on the performance of the lap welds.
The use of a multipass welding strategy for increasing the bonding area in the dissimilar friction stir lap welding (FSLW) of aluminium to steel is analysed in current work. In order to minimize tool ...wear, the pin penetration into the lower plate, the steel plate, was set to a minimum. By performing partially overlapped welding passes it was possible to analyse the quality of the bonding across the multipass weld. The microstructural analysis of the bonding interface, after weld collapse in tensile-shear testing, enabled to conclude that by minimizing the pin penetration in the steel plate, the formation of intermetallics in the bonding interface is supressed and base materials joining results from mechanical bonding and solid state solution. However, for each welding pass, the bonding is not uniform/continuous across the pin trajectory. The deleterious effect of the bonding discontinuities on the monotonic weld strength may be limited by overlapping the successive weld passes, in order to maximize the bonding area. Improving the fatigue strength requires optimizing the welding parameters and/or pin positioning relative to the lower plate in order to avoid the occurrence of micro-cavities at the bonding interface.
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•Multipass friction stir lap welding of aluminium to steel•Mechanical bonding by a wavy interface and diffusion/solid solution•Interfacial failure in monotonic tensile-shear loading•Small discontinuities work as fatigue crack nucleation sites
Non-syndromic pediatric cataracts are defined as opacification of the crystalline lens that occurs during the first years of life without affecting other organs. Given that this disease is one of the ...most frequent causes of reversible blindness in childhood, the main objective of this study was to propose new responsible gene candidates that would allow a more targeted genetic approach and expand our genetic knowledge about the disease. We present a whole exome sequencing (WES) study of 20 Spanish families with non-syndromic pediatric cataracts and a previous negative result on an ophthalmology next-generation sequencing panel. After ophthalmological evaluation and collection of peripheral blood samples from these families, WES was performed. We were able to reach a genetic diagnosis in 10% of the families analyzed and found genes that could cause pediatric cataracts in 35% of the cohort. Of the variants found, 18.2% were classified as pathogenic, 9% as likely pathogenic, and 72.8% as variants of uncertain significance. However, we did not find conclusive results in 55% of the families studied, which suggests further studies are needed. The results of this WES study allow us to propose
,
,
,
,
,
,
, and
as potential candidates to further investigate for their role in pediatric cataracts, and
and locus 2q37 as causal genes.
Lung cancer remains the leading cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents 85 % of all lung cancer cases and it is classified into three major subtypes: ...adenocarcinoma, squamous cell carcinoma and large-cell carcinoma. In the past years, molecular-targeted therapies have been developed in order to improve response, survival and quality of life in patients with advanced NSCLC. Lung cancers harboring mutations in the epidermal growth factor receptor (EGFR) respond to EGFR tyrosine-kinase inhibitors (TKIs). However, virtually all patients with initial response relapse due to acquired resistance. Better understanding the biology of these tumors and mechanisms of EGFR TKIs resistance could shed some light on research of new therapeutic options in this setting. This review aims to emphasize on EGFR involved lung cancer pathway, primary and acquired mechanisms of TKIs resistance, and discuss agents currently used in clinical development in this emerging scenario.
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