Laboratory study of rotationally inelastic collisions of CO2 at low temperatures.

The rotational relaxation of CO2 by inelastic collisions has been studied in three supersonic jets. The jets were probed by means of Raman spectroscopy with high spectral and spatial resolutions, measuring the rotational populations and the total number density. The time evolution of the rotational populations was analyzed by means of a kinetic master equation, with the help of the energy-corrected sudden power law to relate the numerous state-to-state rate (STS rates) coefficients. In the thermal range investigated, 60-260 K, the STS rates decrease with increasing temperature and with increasing change in the rotational quantum number. Other quantities of interest for fluid dynamics, such as the rotational collision number, the relaxation cross section, and the bulk viscosity, have been derived from the STS rates.

Inter-group violence among early Holocene hunter-gatherers of West Turkana, Kenya.

The nature of inter-group relations among prehistoric hunter-gatherers remains disputed, with arguments in favour and against the existence of warfare before the development of sedentary societies. Here we report on a case of inter-group violence towards a group of hunter-gatherers from Nataruk, west of Lake Turkana, which during the late Pleistocene/early Holocene period extended about 30 km beyond its present-day shore. Ten of the twelve articulated skeletons found at Nataruk show evidence of having died violently at the edge of a lagoon, into which some of the bodies fell. The remains from Nataruk are unique, preserved by the particular conditions of the lagoon with no evidence of deliberate burial. They offer a rare glimpse into the life and death of past foraging people, and evidence that warfare was part of the repertoire of inter-group relations among prehistoric hunter-gatherers.

A process mining- deep learning approach to predict survival in a cohort of hospitalized COVID-19 patients.

BACKGROUND: Various machine learning and artificial intelligence methods have been used to predict outcomes of hospitalized COVID-19 patients. However, process mining has not yet been used for COVID-19 prediction. We developed a process mining/deep learning approach to predict mortality among COVID-19 patients and updated the prediction in 6-h intervals during the first 72 h after hospital admission. METHODS: The process mining/deep learning model produced temporal information related to the variables and incorporated demographic and clinical data to predict mortality. The mortality prediction was updated in 6-h intervals during the first 72 h after hospital admission. Moreover, the performance of the model was compared with published and self-developed traditional machine learning models that did not use time as a variable. The performance was compared using the Area Under the Receiver Operator Curve (AUROC), accuracy, sensitivity, and specificity. RESULTS: The proposed process mining/deep learning model outperformed the comparison models in almost all time intervals with a robust AUROC above 80% on a dataset that was imbalanced. CONCLUSIONS: Our proposed process mining/deep learning model performed significantly better than commonly used machine learning approaches that ignore time information. Thus, time information should be incorporated in models to predict outcomes more accurately.

[Usefulness of chest X-rays for detecting COVID 19 pneumonia during the SARS-CoV-2 pandemic]. / Utilidad de la radiografía de tórax para la detección de neumonía COVID 19 durante la pandemia por SARS-CoV-2.

Objective: To review the prognostic usefulness of chest X-rays in selecting patients with suspected SARS-CoV-2 infection. Material and methods: This cross-sectional descriptive observational study analyzed 978 patients with suspected SARS-CoV-2 infections who underwent chest X-ray examinations in the emergency department of a tertiary hospital in March 2020. We separately analyzed demographic, clinical, and prognostic variables in two groups of patients: those in whom reverse-transcriptase polymerase chain reaction (RT-PCR) was done (n = 535) and those in whom RT-PCR was not done because of low clinical suspicion (n = 443). Results: In the group of patients with RT-PCR, the prevalence of SARS-CoV-2 was 70.4%, and the sensitivity of chest X-rays was 62.8%. In the group of patients without RT-PCR, chest X-rays were negative in 97.5%, corroborating the low clinical suspicion; these patients were discharged, and 5.6% of them reconsulted with mild forms of the disease. In the group of patients with RT-PCR, we observed no statistically significant differences in the percentage of pathologic chest X-rays between patients hospitalized in the ICU (72.9%) and in those hospitalized in other wards (68.3%) (p = 0.22). Conclusion: In the context of the pandemic, patients with low clinical suspicion and negative chest X-rays can be discharged with a low probability of reconsultation or of developing severe COVID19. In patients with RT-PCR positive for SARS-CoV-2, chest X-rays have no prognostic usefulness.

Improved Magneto-Microfluidic Separation of Nanoparticles through Formation of the ß-Cyclodextrin-Curcumin Inclusion Complex.

Molecular adsorption to the nanoparticle surface may switch the colloidal interactions from repulsive to attractive and promote nanoparticle agglomeration. If the nanoparticles are magnetic, then their agglomerates exhibit a much stronger response to external magnetic fields than individual nanoparticles. Coupling between adsorption, agglomeration, and magnetism allows a synergy between the high specific area of nanoparticles (∼100 m2/g) and their easy guidance or separation by magnetic fields. This yet poorly explored concept is believed to overcome severe restrictions for several biomedical applications of magnetic nanoparticles related to their poor magnetic remote control. In this paper, we test this concept using curcumin (CUR) binding (adsorption) to ß-cyclodextrin (ßCD)-coated iron oxide nanoparticles (IONP). CUR adsorption is governed by host-guest hydrophobic interactions with ßCD through the formation of 1:1 and, possibly, 2:1 ßCD:CUR inclusion complexes on the IONP surface. A 2:1 stoichiometry is supposed to promote IONP primary agglomeration, facilitating the formation of the secondary needle-like agglomerates under external magnetic fields and their magneto-microfluidic separation. The efficiency of these field-induced processes increases with CUR concentration and ßCD surface density, while their relatively short timescale (<5 min) is compatible with magnetic drug delivery application.

FGF2/EGF contributes to brain neuroepithelial precursor proliferation and neurogenesis in rat embryos: the involvement of embryonic cerebrospinal fluid.

BACKGROUND: At the earliest stages of brain development, the neuroepithelium works as an interdependent functional entity together with cerebrospinal fluid, which plays a key regulatory role in neuroepithelial cell survival, replication and neurogenesis; however, the underlying mechanism remains unknown in mammals. RESULTS: We show the presence of fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), in 13.5-day rat embryo cerebrospinal fluid (eCSF). Immunohistochemical detection of FGF2 expression localized this factor inside neuroepithelial precursors close to the neuroepithelial-CSF interface, suggesting that FGF2 from eCSF could originate in the neuroepithelium by apical secretion. The colocalization of FGFR1 and FGF2 in some neuroepithelial cells close to the ventricular surface suggests they are target cells for eCSF FGF2. Brain neuroepithelium EGF expression was negative. By using a neuroepithelial organotypic culture, we demonstrate that FGF2 and EGF from eCSF plays a specific role in triggering the self-renewal and are involved in neurogenetic induction of mesencephalic neuroepithelial precursor cells during rat development. CONCLUSIONS: We propose eCSF as an intercommunication medium for neuroepithelial precursor behavior control during early rat brain development, and the neuroepithelial regulation of FGF2 and EGF presence in eCSF, as a regulative mechanism controlling precursor proliferation and neurogenesis.

Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain.

BACKGROUND: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. METHODS: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. RESULTS: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). CONCLUSIONS: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Inelastic Collisions of O2 with He at Low Temperatures.

Rotationally inelastic collisions of O2 with He in the 10-34 K thermal range are investigated by means of an experimental procedure based on supersonic gas jets probed by Raman spectroscopy. The procedure employs a kinetic master equation (MEQ) that describes the time evolution of the rotational populations of O2 along supersonic jets of O2 and He mixtures. The MEQ is expressed in terms of experimental quantities (number density and rotational populations) measured here, and state-to-state rate coefficients for the O2:He inelastic collisions calculated here, plus those for O2:O2 collisions from the literature. An agreement with the experiments is accomplished for temperatures between 10 and 34 K. Within this thermal range, the role of the fine structure due to electron spin in the collision dynamics of O2 is discussed.

Biophysics and protein corona analysis of Janus cyclodextrin-DNA nanocomplexes. Efficient cellular transfection on cancer cells.

The self-assembling processes underlining the capabilities of facially differentiated ("Janus") polycationic amphiphilic cyclodextrins (paCDs) as non-viral gene nanocarriers have been investigated by a pluridisciplinary approach. Three representative Janus paCDs bearing a common tetradecahexanoyl multitail domain at the secondary face and differing in the topology of the cluster of amino groups at the primary side were selected for this study. All of them compact pEGFP-C3 plasmid DNA and promote transfection in HeLa and MCF-7 cells, both in absence and in presence of human serum. The electrochemical and structural characteristics of the paCD-pDNA complexes (CDplexes) have been studied by using zeta potential, DLS, SAXS, and cryo-TEM. paCDs and pDNA, when assembled in CDplexes, render effective charges that are lower than the nominal ones. The CDplexes show a self-assembling pattern corresponding to multilamellar lyotropic liquid crystal phases, characterized by a lamellar stacking of bilayers of the CD-based vectors with anionic pDNA sandwiched among them. When exposed to human serum, either in the absence or in the presence of pDNA, the surface of the cationic CD-based vector becomes coated by a protein corona (PC) whose composition has been analyzed by nanoLC-MS/MS. Some of the CDplexes herein studied showed moderate-to-high transfection levels in HeLa and MCF-7 cancer cells combined with moderate-to-high cell viabilities, as determined by FACS and MTT reduction assays. The ensemble of data provides a detail picture of the paCD-pDNA-PC association processes and a rational base to exploit the protein corona for targeted gene delivery on future in vivo applications.

Lymphomagenesis-related gene expression in B cells from sustained virological responders with occult hepatitis C virus infection.

The expression of activation-induced cytidine deaminase, B-aggressive lymphoma, cyclin D1 and serine/threonine kinase 15 genes, among others, is increased in B cells from patients with chronic hepatitis C virus (HCV) infection. It is unknown whether the level of expression of these genes in B cells is increased in patients with hepatitis C who have achieved a sustained virological response (SVR) but who have persistent, detectable HCV RNA, so-called occult infection. Eighty-three patients who achieved and SVR, 27 with detectable HCV and 56 without detectable HCV RNA, 28 chronic hepatitis C patients and 32 healthy controls were studied. RNA was extracted from B cells, and gene expression levels were measured by RT-PCR. Patients with chronic HCV and those who achieved an SVR (with and without persistent low-level HCV RNA) showed a statistically significant higher expression compared to healthy controls, of activation-induced cytidine deaminase (P = 0.004, P < 0.001 and P = 0.002, respectively), B-aggressive lymphoma (P < 0.001, P = 0.001 and P = 0.006) and cyclin D1 (P = 0.026, P = 0.001; P = 0.038). For activation-induced cytidine deaminase patients with an SVR and 'occult infection' had a statistically significantly higher expression level than patients with and SVR without 'occult infection' (P = 0.014). The higher expression levels found for activation-induced cytidine deaminase, together with other genes indicates that these B lymphomagenesis-related genes are upregulated following HCV therapy and this is more marked when HCV can be detected in PBMCs.

Conformationally-locked C-glycosides: tuning aglycone interactions for optimal chaperone behaviour in Gaucher fibroblasts.

A series of conformationally locked C-glycosides based on the 3-aminopyrano[3,2-b]pyrrol-2(1H)-one (APP) scaffold has been synthesized. The key step involved a totally stereocontrolled C-Michael addition of a serine-equivalent C-nucleophile to tri-O-benzyl-2-nitro-D-galactal, previously published by the authors. Stereoselective transformations of the Michael adduct allowed us the synthesis of compounds with mono- or diantennated aglycone moieties and different topologies. In vitro screening showed highly selective inhibition of bovine liver ß-glucosidase/ß-galactosidase and specific inhibition of human ß-glucocerebrosidase among lysosomal glycosidases for compounds bearing palmitoyl chains in the aglycone, with a marked dependence of the inhibition potency upon their number and location. Molecular dynamics simulations highlighted the paramount importance of an optimal orientation of the hydrophobic substituent to warrant efficient non-glycone interactions, which are critical for the binding affinity. The results provide a rationale for the strong decrease of the inhibition potency of APP compounds on going from neutral to acidic pH. The best candidate was found to behave as pharmacological chaperone in Gaucher fibroblasts with homozygous N370S and F213I mutations, with enzyme activity enhancements similar to those encountered for the reference compound Ambroxol.

Staff lens doses in interventional urology. A comparison with interventional radiology, cardiology and vascular surgery values.

The purpose of this work is to evaluate radiation doses to the lens of urologists during interventional procedures and to compare them with values measured during interventional radiology, cardiology and vascular surgery. The measurements were carried out in a surgical theatre using a mobile C-arm system and electronic occupational dosimeters (worn over the lead apron). Patient and staff dose measurements were collected in a sample of 34 urology interventions (nephrolithotomies). The same dosimetry system was used in other medical specialties for comparison purposes. Median and 3rd quartile values for urology procedures were: patient doses 30 and 40 Gy cm(2); personal dose equivalent Hp(10) over the apron (µSv/procedure): 393 and 848 (for urologists); 21 and 39 (for nurses). Median values of over apron dose per procedure for urologists resulted 18.7 times higher than those measured for radiologists and cardiologists working with proper protection (using ceiling suspended screens) in catheterisation laboratories, and 4.2 times higher than the values measured for vascular surgeons at the same hospital. Comparison with passive dosimeters worn near the eyes suggests that dosimeters worn over the apron could be a reasonable conservative estimate for ocular doses for interventional urology. Authors recommend that at least the main surgeon uses protective eyewear during interventional urology procedures.

Occupational eye lens doses in interventional cardiology. A multicentric study.

New European regulation regarding radiological protection of workers and more specifically the new occupational dose limit for the eye lens recently reduced to 20 mSv yr(-1) may affect interventional cardiologists. This paper presents a set of measurements of occupational doses performed in five interventional cardiology centres and then compared with the new dose limit. The measurement of occupational doses was performed over the apron at chest level using electronic dosemeters recording H p(10). In one of the centres, scatter dose at goggles was also measured with optically stimulated luminescence dosemeters calibrated in terms of H p(0.07). An average H p(10) over the apron of 46 µSv/procedure was measured for cardiologists. Lower doses were noted in other professionals like second cardiologists, nurses or anaesthetists. Procedures for valvular and other structural heart diseases involved the highest occupational doses, averaging over 100 µSv/procedure. Important differences in occupational doses among centres may be indicative of different radiation protection habits. The new occupational dose limit for the eye lens is likely to be exceeded by those among the interventionalists who do not use protection tools (ceiling suspended screen and/or goggles) even with standard workloads.

Mixing effects in the crystallization of supercooled quantum binary liquids.

By means of Raman spectroscopy of liquid microjets, we have investigated the crystallization process of supercooled quantum liquid mixtures composed of parahydrogen (pH2) or orthodeuterium (oD2) diluted with small amounts of neon. We show that the introduction of the Ne impurities affects the crystallization kinetics in terms of a significant reduction of the measured pH2 and oD2 crystal growth rates, similarly to what found in our previous work on supercooled pH2-oD2 liquid mixtures [Kühnel et al., Phys. Rev. B 89, 180201(R) (2014)]. Our experimental results, in combination with path-integral simulations of the supercooled liquid mixtures, suggest in particular a correlation between the measured growth rates and the ratio of the effective particle sizes originating from quantum delocalization effects. We further show that the crystalline structure of the mixtures is also affected to a large extent by the presence of the Ne impurities, which likely initiate the freezing process through the formation of Ne-rich crystallites.

A safer disposal of hazardous phosphate coating sludge by formation of an amorphous calcium phosphate matrix.

Phosphate coating hazardous wastes originated from the automotive industry were efficiently encapsulated by an acid-base reaction between phosphates present in the sludge and calcium aluminate cement, yielding very inert and stable monolithic blocks of amorphous calcium phosphate (ACP). Two different compositions of industrial sludge were characterized and loaded in ratios ranging from 10 to 50 wt.%. Setting times and compressive strengths were recorded to establish the feasibility of this method to achieve a good handling and a safe landfilling of these samples. Short solidification periods were found and leaching tests showed an excellent retention for toxic metals (Zn, Ni, Cu, Cr and Mn) and for organic matter. Retentions over 99.9% for Zn and Mn were observed even for loadings as high as 50 wt.% of the wastes. The formation of ACP phase of low porosity and high stability accounted for the effective immobilization of the hazardous components of the wastes.

Correlations between changes in intestinal microbiota composition and performance parameters in broiler chickens.

Growing male Cobb broiler chickens were fed on diets supplemented with additives reported as able to influence intestinal microbiota composition. The diets used were a balanced commercial diet (no additive), inulin (20 g/kg), fructose caramel (FC, 20 g/kg) and the garlic derivative PTS-O (propyl propane thiosulfonate, 45 and 90 mg/kg diet). The composition of the intestinal microbiota was analysed by qPCR at different points of the intestinal tract, and a number of nutritional parameters were also determined. The relative amounts of bacteroides (bacteroides/total bacteria) in the ileal contents correlated (p < 0.05) positively with faecal NDF, ADF, hemicellulose and cellulose digestibility. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the crop contents correlated (p = 0.05) negatively with weight gain of broilers. Faecal N digestibility correlated (p < 0.05) negatively with total bacteria in the ileal contents of chickens. The relative amounts of Escherichia-Shigella (Escherichia-Shigella/total bacteria) in the caecal contents correlated (p = 0.05) negatively with faecal fat digestibility of broilers. Total bacteria in ileal or caecal contents of growing chickens correlated (p < 0.05) negatively with ileal N digestibility. The results here reported suggest that positive or negative correlations can be found between performance parameters and changes in intestinal microbiota composition of growing broiler chickens.