Dynamic Nanoindentation and Short-Range Order in Equiatomic NiCoCr Medium-Entropy Alloy Lead to Novel Density Wave Ordering.

Chemical short-range order is believed to be a key contributor to the exceptional properties of multicomponent alloys. However, its direct validation and confirmation has been highly elusive in most compounds. Recent studies for equiatomic NiCoCr alloys have shown that thermal treatments (i.e., annealing and aging) may facilitate and manipulate such ordering. In this work, by using molecular simulations, we show that nanomechanical probes, such as nanoindentation, may be utilized toward further manipulation of chemical short-range order, providing explicit validation pathways. By using well established interatomic potentials, we perform hybrid molecular-dynamics-Monte Carlo at room temperature to demonstrate that particular dwell nanoindentation protocols can lead, through thermal Monte Carlo equilibration, to local reorganization under the indenter tip, toward a density-wave stripe pattern. We characterize the novel density-wave structures, which are highly anisotropic and dependent on local, nanoindentation-induced stress concentrations, and we show how they deeply originate from intrinsic features of interelemental interactions. Furthermore, we show that these novel patterns consistently scale with the incipient plastic zone, under the indenter tip, justifying their observation at experimentally feasible nanoindentation depths.

Green synthesis of gold nanoparticles via Moringa oleifera seed extract: antioxidant, antibacterial and anticarcinogenic activity on lung cancer.

Plant-mediated biosynthesis of nanoparticles is a green method that allows synthesis in one-pot process. Synthesis of gold nanoparticles with plant extracts has gained interest in the field of biomedicine due to its variety of applications. This study presents the synthesis via green chemistry of gold nanoparticles (AuNPs) using the methanol extract of Moringa oleifera seeds. The AuNPs were synthesized at room temperature. UV-Vis spectroscopy confirmed the formation of AuNPs by identifying the surface plasmon resonance located at 546 nm. TEM analysis shows spherical nanoparticles. FTIR analysis demonstrated the presence of specific bioactive molecules responsible for the Au3+ ion reduction process. The antioxidant activity of the nanoparticles was evaluated on the stabilization of the DPPH radical (1,1-diphenyl-2-picrylhydrazyl, 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl). The antimicrobial activity analysis was developed by broth microdilution method at different concentrations against Escherichia coli and Staphylococcus aureus. Minimum inhibitory concentration were 400 µg/mL and 200 µg/mL, respectively. A549 lung cancer cell proliferation was measured according to the MTT protocol, indicating a dose-dependent response and a IC50 of 163.9 ± 13.27 µg/mL. The AuNPs synthesized using M. oleifera seeds showed promise as active materials for antimicrobial or anticancer products.

Understanding Severe Asthma Through Small and Big Data in Spanish Hospitals: The PAGE Study.

BACKGROUND: Data on the prevalence of severe asthma (SA) are limited. Electronic health records (EHRs) offer a unique research opportunity to test machine learning (ML) tools in epidemiological studies. Our aim was to estimate the prevalence of SA among asthma patients seen in hospital asthma units, using both ML-based and traditional research methodologies. Our secondary objective was to describe patients with nonsevere asthma (NSA) and SA over a follow-up of 12 months. METHODS: PAGE is a multicenter, controlled, observational study conducted in 36 Spanish hospitals and split into 2 phases: a cross-sectional phase for estimation of the prevalence of SA and a prospective phase (3 visits in 12 months) for the follow-up and characterization of SA and NSA patients. A substudy with ML was performed in 6 hospitals. Our ML tool uses EHRead technology, which extracts clinical concepts from EHRs and standardizes them to SNOMED CT. RESULTS: The prevalence of SA among asthma patients in Spanish hospitals was 20.1%, compared with 9.7% using the ML tool. The proportion of SA phenotypes and the features of patients followed up were consistent with previous studies. The clinical predictions of patients' clinical course were unreliable, and ML found only 2 predictive models with discriminatory power to predict outcomes. CONCLUSION: This study is the first to estimate the prevalence of SA in hospitalized asthma patients and to predict patient outcomes using both standard and ML-based research techniques. Our findings offer relevant insights for further epidemiological and clinical research in SA.

PAGE Study: Summary of a Study Protocol to Estimate the Prevalence of Severe Asthma in Spain Using Big Data Methods.

BACKGROUND AND OBJECTIVES: Background: The proposal and the initiative for the Prevalence of Severe Asthma in Hospital Units in Spain (PAGE) study came about because of the widespread implementation of electronic medical records and the limited data available on the prevalence of severe asthma in hospitals in our setting. Objectives: The primary objective was to determine the prevalence of severe asthma in the outpatient clinics of allergy and pulmonology departments in Spain. The secondary objectives were to describe the most prevalent characteristics and phenotypes of severe asthma, to evaluate the selection criteria for receiving approved biological treatments for this disease, and to estimate consumption of resources. Furthermore, digital technology and new data collection sources made it possible to reuse information stored in electronic medical records (Big Data). The study was performed using one such tool, Savana. METHODS: The PAGE study was a multicenter, nonexperimental, observational, cross-sectional study in the first phase and a prospective study in the second phase. The study was controlled and population-based, with 2-stage selection of patients by random sampling. The research was carried out in 40 hospitals selected using convenience sampling in order to ensure geographical representativeness in Spain. RESULTS: This manuscript describes the study design and protocol. CONCLUSIONS: Our study design was sufficiently robust to avoid bias and to establish the prevalence of patients with severe asthma in Spanish hospitals. It was also the first to incorporate new tools that can help in routine clinical practice and research, such as big data analysis software, and to evaluate the reliability and efficiency of these tools.

Role of the Interchangeable Cations on the Sorption of Fumaric and Succinic Acids on Montmorillonite and its Relevance in Prebiotic Chemistry.

It has been proposed that clays could have served as key factors in promoting the increase in complexity of organic matter in primitive terrestrial and extraterrestrial environments. The aim of this work is to study the adsorption-desorption of two dicarboxylic acids, fumaric and succinic acids, onto clay minerals (sodium and iron montmorillonite). These two acids may have played a role in prebiotic chemistry, and in extant biochemistry, they constitute an important redox couple (e.g. in Krebs cycle) in extant biochemistry. Smectite clays might have played a key role in the origins of life. The effect of pH on sorption has been tested; the analysis was performed by UV-vis and FTIR-ATR spectroscopy, X-ray diffraction and X-ray fluorescence. The results show that chemisorption is the main responsible of the adsorption processes among the dicarboxylic acids and clays. The role of the ion, present in the clay, is fundamental in the adsorption processes of dicarboxylic acids. These ions (sodium and iron) were selected due to their relevance on the geochemical environments that possibly existed into the primitive Earth. Different mechanisms are proposed to explain the sorption of dicarboxylic acids in the clay. In this work, we propose the formation of complexes among metal cations in the clays and dicarboxylic acids. The organic complexes were probably formed in the prebiotic environments enabling chemical processes, prior to the appearance of life. Thus, the data presented here are relevant to the origin of life studies.

Incubation period of COVID-19: A systematic review and meta-analysis. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial.

BACKGROUND: The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. PATIENTS AND METHODS: Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. RESULTS: CTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. CONCLUSION: We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00433563.

Referral Criteria for Asthma: Consensus Document.

Asthma is one of the most prevalent chronic diseases in Spain. Current treatments ensure that the disease is controlled in most cases. However, disease is often uncontrolled in daily clinical practice, mainly owing to underdiagnosis, loss to follow-up, and poor adherence to therapy. In order to improve this situation, we must coordinate all those health professionals who intervene in patient care. Therefore, the Spanish Society of Allergology and Clinical Immunology (SEAIC), the Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of Family and Community Medicine (semFYC), the Spanish Society of General and Family Physicians (SEMG), and the Spanish Society of Pneumology and Thoracic Surgery (SEPAR) have drawn up a consensus document in which they establish criteria for referral and guidelines for the diagnosis, control, and follow-up of patients with asthma. The document aims to facilitate continuing and improved care in this area.

Decreasing rates of acute myocardial infarction in people living with HIV: a nationwide cohort study in Spain, 2004-2015.

OBJECTIVES: Contemporary data from country-wide cohorts are needed to reveal trends in the occurrence of acute myocardial infarction (AMI) in people living with HIV (PLWH). We analysed time trends in the standardized incidence rate (sIR) of AMI in PLWH in Spain from 2004 to 2015, and compared them with trends in the general population. METHODS: A longitudinal study in a nationwide contemporary multicentre HIV-infected cohort was carried out. Data on all incident AMI events were collected, and age- and sex-standardized IRs calculated. To analyse the IR of AMI in the general population, the national rates of hospital discharges for AMI per 100 000 inhabitants stratified for age and sex from 2004 to 2015 were obtained using the morbidity report data from the National Statistics Institute. A Poisson regression model was fitted to assess the effect of covariates of interest on AMI occurrence. RESULTS: The sIRs of AMI in 2004-2015 were 237.92 [95% confidence interval (CI) 225.95-249.90] and 66.75 (95% CI: 23.49-110.01) per 100 000 patient-years in male and female PLWH, respectively. There was a decrease in the sIR of AMI in male PLWH from 279.02 (95% CI: 265.46-292.59) per 100 000 person-years in 2004-2009 to 222.13 (95% CI: 210.83-233.42) per 100 000 person-years in 2010-2015. Compared with the general population, the sIR ratio was 1.41 (95% CI: 1.26-1.55) in 2004-2009, and 1.28 (95% CI: 1.15-1.43) in 2010-2014. AMI occurrence was associated with older age (P < 0.066 for each 10-year age stratum ≥ 35-years compared with the 25-34 year stratum), higher plasma HIV RNA (P < 0.001), lower CD4 count (P < 0.04 for CD4 strata > 350 cells/µL compared with the 0-100 cells/µL stratum), and the period 2004-2009 (P < 0.001). CONCLUSIONS: There has been a decreasing incidence of AMI in PLWH in Spain, associated with improving immune and virological status, but the incidence of AMI has remained higher than in the general population.

Peripheral levels of brain-derived neurotrophic factor and S100B in neuropsychiatric systemic lupus erythematous.

BACKGROUND: The aim of this study was to investigate serum S100B and brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE) patients, with and without neuropsychiatric (NP) manifestation activity. METHODS: We assessed 47 SLE patients and 20 selected healthy individuals. Disease activity was assessed according to the SLE disease activity index (SLEDAI). Serum BDNF and S100B were measured by enzyme-linked immunosorbent assay. RESULTS: Serum S100B protein was significantly higher in SLE patients. BDNF levels were significantly decreased in active SLE, when compared with inactive SLE, but not when compared with controls. S100B was clearly higher in the NPSLE group, when compared with the non-NPSLE or control groups. Receiver operating characteristic analysis of S100B revealed an area under the curve of 0.706 that discriminated NPSLE patients with peripheral polyneuropathy. CONCLUSIONS: Our findings reinforce the use of serum S100B as a biomarker in SLE, particularly for NPSLE. Moreover, we found a strong association between serum S100B and peripheral neuropathy, indicating a specific utility for this biomarker in SLE that warrants clinical investigation.

Pleural tumours and tumour-like lesions.

There are various neoplasms and tumour-like conditions of the pleura. Mesothelioma is perhaps the most widely recognised; however, there are many others that are more common and should be considered. Understanding the similarities and differences can be helpful in managing the patient with a newly found pleural lesion. We will discuss clinical symptoms at presentation and describe the imaging findings associated with these tumours, starting with conventional radiology, and correlating with computed tomography and combined positron-emission tomography (PET)/computed tomography (CT). Finally, imaging characteristics that help differentiation between the benign and malignant varieties will be reviewed.

Measurement of optical fiber parameters and thermal core diffusion characteristics by digital image processing.

The simultaneous measurement of the numerical aperture (NA) and mode field diameter (MFD) of single-mode fibers was performed on several commercial fibers by means of digital image processing of the output light projected into a screen. In addition, the changes induced by core diffusion in an ultra-high (UH) NA fiber at several heat depositions from a CO2 laser source were measured. The measurement method was demonstrated to be useful to monitor the adiabaticity of this process, by taking the product of the NA and MFD to verify if it remains constant. The method provides a cheap alternative to measure these optical fiber parameters by using simple optomechanical elements and a readily available smartphone camera, and it can be easily implemented in the laboratory.

Teledermatology-driven topical therapy of actinic keratosis: a comparative study of clinical effectiveness and compliance.

BACKGROUND: Teledermatology (TD) provides efficient care for skin cancer patients. OBJECTIVE: To compare the clinical effectiveness of imiquimod 5% for the treatment of AK with in-person care and through TD. METHODS: Longitudinal prospective controlled study including patients with single AK diagnosed and treated at face-to-face visits (FTF group) or through teledermatology (TD group) with imiquimod 5% cream. The main outcome measures assessed were the complete and global response percentage (CR and GR) under per-protocol (PP) and intention-to-treat (ITT) analysis. RESULTS: A total of 157 patients were enrolled (FTF = 75, TD = 82). PP analysis showed CR in 66.7% of FTF patients and 65.6% in TD patients (P > 0.05). The ITT yielded CR in 64.0% and 51.2% in FTF visits and TD, respectively (P = 0.073). The analysis showed an advantage of FTF care against TD in achieving GR (84.0% vs. 70.7%; P = 0.036). Facial location and local adverse reactions were the only explanatory factors of complete response in the ITT approach. Treatment completion was found in 90.7% and 72.0% in the FTF and TD groups, respectively (P = 0.004). CONCLUSIONS: Improvements in patient counselling at the primary care centre are needed before the implementation of TD as a routine methodology for the management of AK.

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48-week analysis of results from the PROTEST study.

OBJECTIVES: Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue. METHODS: PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL. RESULTS: Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure. CONCLUSIONS: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Impact of the implementation of a Sepsis Code hospital protocol in antibiotic prescription and clinical outcomes in an intensive care unit. / Impacto de la implantación de un Código Sepsis intrahospitalario en la prescripción de antibióticos y los resultados clínicos en una unidad de cuidados intensivos.

INTRODUCTION: A study was performed to analyze the impact of an in-hospital Sepsis Code (SC) program on use of antibiotic and clinical outcomes. DESIGN: Quasi-experimental observational retrospective study. SETTING: Polyvalent 11 beds ICU belonging to a tertiary Universitary hospital. PATIENTS: Patients admitted consecutively to the ICU with diagnosis of severe sepsis or septic shock. INTERVENTIONS: A post intervention group (POST-SC) (September 2012-August 2013) was compared with a historical group (PRE-SC) used as control (January-December 2010). VARIABLES: Antibiotic treatment, therapeutic antibiotic strategy, mortality and length of stay. Antibiotic consumption was expressed as defined daily doses (DDD)/ 100 stays. RESULTS: 42 patients with SS/SS in POST-SC group and 50 patients in PRE-SC group were consecutively recluted and further analyzed. Total antibiotic consumption (DDD) was similar in both groups. Rate of de-escalation therapy was significantly higher in POST-SC group (75% vs 30,8%, p<0,005) while prescription of restricted antibiotics was significantly lower (74% vs 52%, p=0,031). Finally POST-SC patients showed a significantly decrease in hospital and 28 days mortality rates [23% vs 44%, (p=0,035) and 31% vs 56% (p=0,014) respectively] as well as a reduction in ICU length of stay compared to PRE-SC cohort (5 days vs 10,5 days, p=0,05). CONCLUSION: The implementation of a Sepsis Code-hospital protocol is associated to an improvement in the management of antibiotic therapy with a significant increase in de-escalation therapy and lesser utilization of restricted use antibiotics, as well as a significant reduction in mortality, and a tendency towards shorter ICU length stay.

Prognostic and therapeutic factors of gliosarcoma from a multi-institutional series.

The aims of this multicentre retrospective study were to identify prognostic or therapeutic factors impacting on overall survival in patients with gliosarcoma. The analysis included all patients treated for gliosarcoma between 1998 and 2014 in seven French academic centres. Seventy-five patients with a median age of 60 years (range from 23 to 79 years) were treated with a combination of surgery (n = 66), radiotherapy (adjuvant for 64 patients and exclusive for 8 patients) and temozolomide based chemotherapy (n = 58). Median follow-up was 12 months (range from 2 to 71 months). Two-year overall survival (OS) and disease free survival rates were 12 % (95 % CI 4-20 %) and 2 % (95 % CI 0-6 %), respectively. The median OS was 13 months. Treatment at recurrence consisted of chemotherapy (n = 38) (bevazicumab for 18 patients, repeat temozolomide for 10 patients), salvage surgery (n = 8) and radiochemotherapy (n = 1). In univariate analysis, younger age, higher total dose of radiotherapy, longer time to recurrence and treatment at recurrence significantly increased OS. In multivariate analysis, high total dose of radiotherapy (HR = 0.97, p = 0.007) and treatment at recurrence (HR = 0.28, p < 0.001) were favourable prognostic factors of OS. Radiotherapy at a minimum dose of 54 Gy and salvage treatment increased OS of gliosarcoma. Unlike glioblastoma, in our analysis, TMZ based chemotherapy was not associated with an improvement in OS compared to patients who received radiation therapy only.

Toward a comprehensive care of HIV patients: finding a strategy to detect depression in a Spanish HIV cohort.

Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.