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DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case–control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score. [ABSTRACT FROM AUTHOR]

The aim of this paper is to shed light on and critically evaluate the potential impact of evidential pluralism in the realm of pharmaceutical regulation. In the complex landscape of drug evaluation and approval, the role of evidence is pivotal. Firstly, we delve into the role of evidence of mechanisms within drug regulation, with a particular focus on the Accelerated Approval pathway administered by the US Food and Drug Administration. Our analysis reveals that this program, in practice, closely resembles a pluralistic approach to evidence. Secondly, we undertake a thorough examination of the reliability of evidential pluralism within the context of drug regulation. We dissect and discuss the open-cases approach recently put forth by Sung and Holman. While acknowledging its potential merits, we also identify and articulate significant limitations inherent in this approach. Finally, we propose an alternative empirical approach that centres on the real-world outcomes of regulatory programs. [ABSTRACT FROM AUTHOR]

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85–24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62–25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12–9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06–0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies. [ABSTRACT FROM AUTHOR]

Abstract Centrosome amplification, the presence of more than two centrosomes in a cell is a common feature of most human cancer cell lines. However, little is known about centrosome numbers in human cancers and whether amplification or other numerical aberrations are frequently present. To address this question, we have analyzed a large cohort of primary human epithelial ovarian cancers (EOCs) from 100 patients. We found that rigorous quantitation of centrosome number in tumor samples was extremely challenging due to tumor heterogeneity and extensive tissue disorganization. Interestingly, even if centrosome clusters could be identified, the incidence of centrosome amplification was not comparable to what has been described in cultured cancer cells. Surprisingly, centrosome loss events where a few or many nuclei were not associated with centrosomes were clearly noticed and overall more frequent than centrosome amplification. Our findings highlight the difficulty of characterizing centrosome numbers in human tumors, while revealing a novel paradigm of centrosome number defects in EOCs.

Background: The gonadotropins lutropin and follitropin stimulate steroid synthesis in the gonads during gonadal maturation by promoting oogenesis and spermatogenesis. Endocrine disruptors such as lindane (γHCH) can alter the reproductive stage so and could alter puberty by interfering with lutropin and follitropin signaling. γHCH was classified by World Health Organization as "moderately restricted", and in 2009 it is production and agricultural use was prohibited, under the Stockholm Convention, however, its use as a pharmaceutical treatment against lice and scabies is still allowed (and mainly, for use by the health sector). This study aimed to examine the effects of single-dose exposure to γHCH in young mice (Mus musculus) on lutropin and follitropin concentration, and to correlate gonadal maturity status and phenotypic characteristics. Methods: Young γHCH-treated mice (16 females and 16 males) received a single dose of 25, 10, 5, or 0 µg/ml γHCH per gram of body weight, ocular route. Once secondary sexual characteristics were observed, the gonads were dissected and examined using histological techniques and the ovarian follicles were classified as dependent and independent of gonadotropins; the testicles were classified as inactive, early and late spermatogenesis; and the blood was processed with the lutropin and follitropin ELISA kit. Results: The results indicate significant differences in the concentration of lutropin and follitropin between males and females (Fisher p < 0.05). The lutropin and follitropin levels showed a tendency to decrease in females, whereas, in males they tended to increase as the dose of γHCH increased. In females, it was observed that at the follitropin and lutropin decreased 42.3% and 83.7%, respectively at dose of 25 µg/ml; while in males, follitropin increased 51.9% at the dose of 25 µg/ml, and at the dose of 10 µg/ml lutropin increased by 242.5%. Contrary to that, gonadal maturity increased in females and decreased in males with increasing γHCH dose, disagreeing with the idea that gonadotropins coincide with the onset of puberty and gonadal maturity. Conclusions: The results allow us to infer that exposure to γHCH could promote non-monotonic responses; however, this does not seem to alter puberty in the doses and conditions of the present experiment. [ABSTRACT FROM AUTHOR]

Human disturbance has been shown to provoke physiological and behavioral responses in birds, so nature-based tourism might reduce bird abundance and diversity. The negative consequences of human disturbance might be expected to be maximized during eventual massive events in highly protected areas such as national parks. In this study, the consequences for soundscapes of human presence and disturbance of thousands of visitors during an ornithological fair (massive event) on the bird community of the Monfragüe National Park (Spain) were analyzed. We found that the number and diversity of bird vocalizations did not decrease during the massive event. In contrast, the presence of people in the Monfragüe National Park was associated with an increase in the number and diversity of vocalizations. The effect of human presence on the number of calls and songs differed: the number of calls mainly increased during the massive event when people were present, while the number of songs increased when people were present, particularly during the measurement campaign without the massive event. The human shield hypothesis, along with other behavioral and environmental factors, might potentially explain the results obtained. [ABSTRACT FROM AUTHOR]

Abstract Climate change science has become an increasingly polarized site of controversy, where discussions on epistemological rigour are difficult to separate from debates on the impact that economic and political interests have on the production of evidence and the construction of knowledge. Little research has been conducted so far on the antagonistic discursive processes through which climate knowledge is being contested and traditional forms of expertise are being (de-)legitimized—whether by members of the scientific community or non-scientist actors. This corpus-based study contributes to previous scholarship on the climate science controversy in a number of respects. Unlike earlier studies based on the analysis of mainstream media articles, this paper interrogates a corpus of climate change blog posts published by scientists, journalists, researchers and lobbyists laying claim to core, contributory and interactional forms of expertise—as conceptualized within the third wave of science studies. Further, the corpus informing this study has been designed to reflect the complex and multivoiced nature of the climate knowledge production process. Drawn from five different blogs, the views represented are not confined to the two poles between which the entrenched dialectic of ‘alarmists’ versus ‘deniers’ is typically played out in the climate science debate. Following a systemic functional conceptualization of dialogic engagement as a means of positioning authorial voices vis-à-vis competing perspectives construed and referenced in a text, this paper reports on bloggers’ use of three lexical items (bias, dogma and peer review) to expose their reliance on (non-)epistemic values. Concordances and a range of visualization tools are used to gain systematic insights into the network of lexical choices that obtain around these items, and to gauge whether/how bloggers construct coherent authorial subjectivities in a bid to claim expert status and/or question the recognition of other players in the debate.

As dementia-induced impairments of daily functioning escalate, novel cognitive stimulation techniques utilizing technological advances, like social robots, have surfaced. This study examines the interaction level of the EBO social-care robot with day center patients in Cáceres, Extremadura, Spain. The study uses systematic video analysis as a method of interaction assessment. This observational pilot study was performed on patients above 65 with mild to moderate cognitive impairment (Minimental State Examination ≥ 21) receiving cognitive therapy at the AZTIDE social and health center. Two individualized 10–15 min sessions, replicating the Wizard of Oz technique, were conducted per participant, with the human operator's commands being unnoticeably executed by the EBO robot. Of the six participants involved, all maintained complete eye contact with the robot, with 83.3 % of the interactions recording maximum attention. Participants felt comfortable and calm, rating conversational factors such as attentiveness and naturalness as 'good' or 'excellent'. The high interaction level with the EBO robot suggests it as a promising tool for cognitive stimulation in patients with mild to moderate cognitive impairment. The systematic video evaluation also appears effective in assessing user–robot interaction, thus underscoring its potential utility in future social robotics research. [ABSTRACT FROM AUTHOR]

This work reports the studies conducted to characterize the microstructure and strength of Al–Cu alloys cast with various additions of Ti, V and Zr as these elements form stable particles of the Al3M type that are able to enhance their strength. The alloys were melted at 760 °C and poured into steel moulds. The solidification and cooling of the alloys was studied with the aid of a modified Scheil–Gulliver model. The volume fraction of D022 and D023 particles at the end of solidification was used to evaluate the strengthening by Orowan's mechanism. Microstructural studies revealed the presence of particles of the Al3M type made of Ti, V and Zr. The difference in strength of the different alloys is attributed to Al3M precipitates. [ABSTRACT FROM AUTHOR]

The high-temperature oxidation characteristics of Inconel 625 superalloy fabricated by additive manufacturing were studied at 900 and 1000 °C in a mixture of dry air and 12%vol water vapor. At 900 °C, oxidation in water vapor was slightly faster than oxidation in air (kpwv 900 = 3.4 × 10−3mg2cm−4 h−1 and kpa900 = 2.9 × 10−3mg2cm−4 h−1). At 1000 °C, oxidation in air (kpa1000 = 74 × 10−3mg2cm−4 h−1) occurred faster than oxidation in water vapor (kpwv1000 = 45 × 10−3mg2cm−4 h−1) although for the early oxidation up to ~ 14 h the opposite behavior was observed. Features like crack and pore formation accounted for increasing the ionic mobility through the oxide and the oxidation rate in water vapor at this temperature. Chromia Cr2O3 was the main oxide found on the surface of the alloy, but intergranular oxidation zones having Ti- and Al-rich oxides were also formed below the metal-oxide interface. Evidence of localized CrO2(OH)2 volatilization was also found. [ABSTRACT FROM AUTHOR]

Buena Pinta Cave (Pinilla del Valle, Madrid) has been interpreted as a hyena den with sporadic occupations of Homo neanderthalensis in the western part of the site (level 23). In order to identify the different formation processes in this area of the site, spatial analyses have been carried out with GIS and spatial statistics based on the taphonomic analysis of the faunal remains. Based on the vertical and sectional analyses of the assemblage, it has been possible to determine that level 23 actually corresponds to three archaeological levels with well-differentiated characteristics: a lower level with few faunal remains and fossil-diagenetic alterations related to humid environments associated with clays; an intermediate level with a high percentage of remains with water-related modifications and evidences of transport; and an upper level delimited mainly thanks to by a paraconformity evidenced by the concentration of weathered remains in this area and a significant reduction in remains with water-related alterations above. The results obtained show the necessity to redefine field layers and the usefulness of integrating taphonomic data and spatial studies. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate time-dependent administration of ibuprofen in a lower third molar extraction model. Methods: Eleven patients requiring bilateral surgical removal of lower third molars were recruited and randomized into a blinded crossover randomized controlled trial. For 3 days after surgery, the control group was prescribed ibuprofen 400 mg every 8 h. On the other hand, the experimental group received also ibuprofen 400 mg at breakfast and lunch, replacing the dinner intake with a placebo. Pain measurements (Visual Analog Scale from 0 to 10) were recorded at baseline, 24, 48, and 72 h postoperatively. Facial swelling and trismus were also measured at baseline, 24, and 72 h postoperatively. Results: Postoperative swelling and pain perception did not show significative difference between the control and experimental groups at 24, 48, and 72 h. Trismus was significantly lower in the control group than in the experimental group at 72 h postoperatively (p = 0.008). Rescue medication consumption seemed to be comparable between groups. Conclusion: Eliminating night time ibuprofen might be insignificant for pain control after third molar extraction. [ABSTRACT FROM AUTHOR]

The causes promoting the formation of defects on the internal surface of two different copper alloys subjected to cold rolling to fabricate seamless copper tubes are described. Defects characterized by oxide formation and delaminated material were found in various zones along the length of the tubes, leading to crack formation. It was found that the alloy that presented severe failure included a considerable amount of Cu2O particles. These particles were responsible for incorrect material flow during manufacturing and acted as crack initiation sites. [ABSTRACT FROM AUTHOR]

During the first 500 million years of cosmic history, the first stars and galaxies formed, seeding the Universe with heavy elements and eventually reionizing the intergalactic medium1–3. Observations with the James Webb Space Telescope (JWST) have uncovered a surprisingly high abundance of candidates for early star-forming galaxies, with distances (redshifts, z), estimated from multiband photometry, as large as z ≈ 16, far beyond pre-JWST limits4–9. Although such photometric redshifts are generally robust, they can suffer from degeneracies and occasionally catastrophic errors. Spectroscopic measurements are required to validate these sources and to reliably quantify physical properties that can constrain galaxy formation models and cosmology10. Here we present JWST spectroscopy that confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9, with an unusual combination of nebular line emission and dust reddening that mimics the colours expected for much more distant objects. These results reinforce evidence for the early, rapid formation of remarkably luminous galaxies while also highlighting the necessity of spectroscopic verification. The large abundance of bright, early galaxies may indicate shortcomings in current galaxy formation models or deviations from physical properties (such as the stellar initial mass function) that are generally believed to hold at later times.JWST spectroscopy confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9. [ABSTRACT FROM AUTHOR]

The main objective of this study was to test a structural theoretical model of the effects of self-regulated learning on academic stress, subjective well-being, and academic achievement in Secondary Education, considering academic procrastination as a mediator. An additional aim was to explore whether these relationships were moderated by gender and educational level. Participants were 728 students in compulsory and post-compulsory secondary education in a large city in Eastern Spain. Path analysis results indicated that the proposed model showed satisfactory fit, with the three dimensions of self-regulated learning significantly predicting the educational outcomes considered, and that procrastination mediated these relationships. Overall, the model is able to predict 9.8% of the variance of academic stress, 23.1% of students wellbeing, and 14% of academic achievement. Moreover, the multi-group routine revealed no moderation effects due to gender, but educational level moderated two relationships, between self-efficacy and academic achievement and between metacognitive strategies and procrastination. Additionally, supplementary models were tested for three specific subjects (Spanish Language, Foreign Language and Mathematics), which showed an improvement in explained variance, being respectively: 29%, 28% and 27%. Results are discussed in light of previous research and in terms of their impact on educational practice. [ABSTRACT FROM AUTHOR]

The relative importance or saliency of sensory inputs depend on the animal's environmental context and the behavioural responses to these same inputs can vary over time. Here we show how freely moving rats, trained to discriminate between deviant tones embedded in a regular pattern of repeating stimuli and different variations of the classic oddball paradigm, can detect deviant tones, and this discriminability resembles the properties that are typical of neuronal adaptation described in previous studies. Moreover, the auditory brainstem response (ABR) latency decreases after training, a finding consistent with the notion that animals develop a type of plasticity to auditory stimuli. Our study suggests the existence of a form of long-term memory that may modulate the level of neuronal adaptation according to its behavioural relevance, and sets the ground for future experiments that will help to disentangle the functional mechanisms that govern behavioural habituation and its relation to neuronal adaptation. Rats can detect frequency deviant tones in a context-dependent manner, indicating a memory-based adaptation in auditory neurons that is shaped by stimuli saliency and behavioral relevance. [ABSTRACT FROM AUTHOR]

The global economy is increasingly focusing on the Oceans to meet its needs, for which maritime spatial planning is being fostered to promote this is done sustainably. Thus, assessing the current state and future development trends of the maritime sectors is key to evaluating the performance of the planning process. This is the aim of this study, in which the main maritime sectors related to the blue economy present in the archipelagos of the European Macaronesia Sea Basin, i.e. the Azores and Madeira (Portugal), and the Canary Islands (Spain), were identified and studied. The following maritime sectors were analysed: fisheries, marine aquaculture, marine biotechnology, coastal and maritime tourism, maritime transport, ship repair and maintenance, extraction of aggregates, deep-sea mining, offshore oil and gas, renewable ocean energies, and desalination. As part of the PLASMAR project, partners undertook in 2017–19 a literature review gathering scientific papers, official statistics and reports, which were complemented by interviews with experts from the economic sectors and public administration departments. Results show that while some maritime sectors are well established, others are emerging sectors with varying long-term growth potential. Besides, development patterns vary across the archipelagos. This study represents the first effort in the Macaronesia Sea Basin to set the basis of the current and future development conditions of the blue economy in applicability to maritime spatial planning processes at a regional level. The future post-pandemic context will provide a unique opportunity to promote the blue economy sectors and activities through the support provided by the EU Green Deal and Recovery and Resilience Plans, as well as with the actions envisioned under the United Nations Decade of Ocean Science for Sustainable Development (2021–2030). The European Macaronesia example –given its wide maritime territory, commitment, and capacities in terms of expertise and networking– presents a great potential to act as a good practice to extrapolate the new approach for a sustainable blue economy to other similar geographical settings such as island regions/states. [ABSTRACT FROM AUTHOR]

Antibiotics are among the most utilized drugs in pediatrics. Nonetheless, there is a lack in pharmacokinetics information for this population, and dosing criteria may vary between healthcare centers. Physiological variability associated with maturation in pediatrics makes it challenging to reach a consensus on adequate dosing, which is further accentuated in more vulnerable groups, such as critically ill or oncology patients. Model-informed precision dosing is a useful practice that allows dose optimization and attainment of antibiotic-specific pharmacokinetic/pharmacodynamic targets. The aim of this study was to evaluate the needs of model-informed precision dosing of antibiotics in a pediatrics unit, at a pilot scale. Pediatric patients under antibiotic treatment were monitored with either a pharmacokinetic/pharmacodynamic optimized sampling scheme or through opportunistic sampling. Clindamycin, fluconazole, linezolid, meropenem, metronidazole, piperacillin, and vancomycin plasma concentrations were quantified through a liquid chromatography coupled to mass spectrometry method. Pharmacokinetic parameters were estimated using a Bayesian approach to verify pharmacokinetic/pharmacodynamic target attainment. A total of 23 pediatric patients aged 2 to 16 years were included, and 43 dosing regimens were evaluated; 27 (63%) of them required adjustments as follows: 14 patients were underdosed, 4 were overdosed, and 9 patients needed infusion rate adjustments. Infusion rate adjustments were mostly recommended for piperacillin and meropenem; daily doses were augmented for vancomycin and metronidazole, meanwhile linezolid was adjusted for under- and overdosing. Clindamycin and fluconazole regimens were not adjusted at all. Conclusion: Results showcase a lack of antibiotic pharmacokinetic/pharmacodynamic target attainment (particularly for linezolid, vancomycin, meropenem, and piperacillin), and the need for model-informed precision dosing in pediatrics. This study provides pharmacokinetic evidence which can further improve antibiotic dosing practices. What is Known: • Model-informed precision dosing is performed in pediatrics to optimize the treatment of antimicrobial drugs such as vancomycin and aminoglycosides, while its usefulness is debated for other groups (beta-lactams, macrolides, etc.). What is New: • Vulnerable pediatric subpopulations, such as critically ill or oncology patients, can benefit the most from model-informed precision dosing of antibiotics. • Model-informed precision dosing of linezolid, meropenem, piperacillin, and vancomycin is particularly useful in pediatrics, and further research may improve dosing practices altogether. [ABSTRACT FROM AUTHOR]

In this paper, we present three estimators of the ROC curve when missing observations arise among the biomarkers. Two of the procedures assume that we have covariates that allow to estimate the propensity and and from this information, the estimators are obtained using an inverse probability weighting method or a smoothed version of it. The third one assumes that the covariates are related to the biomarkers through a regression model which enables us to construct convolution–based estimators of the distribution and quantile functions. Consistency results are obtained under mild conditions. Through a numerical study we evaluate the finite sample performance of the different proposals. A real data set is also analysed. [ABSTRACT FROM AUTHOR]

Kill/butchering sites are some of the most important places for understanding the subsistence strategies of hunter-gatherer groups. However, these sites are not common in the archaeological record, and they have not been sufficiently analysed in order to know all their possible variability for ancient periods of the human evolution. In the present study, we have carried out the spatial analysis of the Early Middle Palaeolithic (MIS 9–8) site of Cuesta de la Bajada site (Teruel, Spain), which has been previously identified as a kill/butchering site through the taphonomic analysis of the faunal remains. Our results show that the spatial properties of the faunal and lithic tools distribution in levels CB2 and CB3 are well-preserved although the site is an open-air location. Both levels show a similar segregated (i.e. regular) spatial point pattern (SPP) which is different from the SPP identified at other sites with similar nature from the ethnographic and the archaeological records. However, although the archaeological materials have a regular distribution pattern, the lithic and faunal remains are positively associated, which is indicating that most parts of both types of materials were accumulated during the same occupation episodes, which were probably sporadic and focused on getting only few animal carcasses at a time. [ABSTRACT FROM AUTHOR]

Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia. [ABSTRACT FROM AUTHOR]

The majority of massive disk galaxies in the local Universe show a stellar barred structure in their central regions, including our Milky Way1,2. Bars are supposed to develop in dynamically cold stellar disks at low redshift, as the strong gas turbulence typical of disk galaxies at high redshift suppresses or delays bar formation3,4. Moreover, simulations predict bars to be almost absent beyond z = 1.5 in the progenitors of Milky Way-like galaxies5,6. Here we report observations of ceers-2112, a barred spiral galaxy at redshift zphot ≈ 3, which was already mature when the Universe was only 2 Gyr old. The stellar mass (M★ = 3.9 × 109 M⊙) and barred morphology mean that ceers-2112 can be considered a progenitor of the Milky Way7–9, in terms of both structure and mass-assembly history in the first 2 Gyr of the Universe, and was the closest in mass in the first 4 Gyr. We infer that baryons in galaxies could have already dominated over dark matter at z ≈ 3, that high-redshift bars could form in approximately 400 Myr and that dynamically cold stellar disks could have been in place by redshift z = 4–5 (more than 12 Gyrs ago)10,11.We report observations of ceers-2112 that show that this galaxy, at a redshift of 3, unexpectedly has a barred spiral structure. [ABSTRACT FROM AUTHOR]

Among the outstanding questions about the emergence of human-controlled fire is the systematic recurrence between the geochemical remains of fire and its preservation in the archaeological record, as the use of fire is considered a technological landmark, especially for its importance in food cooking, defensive strategies, and heating. Here we report fossil lipid biomarkers associated with incomplete combustion of organic matter at the Valdocarros II site, one of the largest European Acheulean sites in Spain dated to marine isotopic stage (MIS) 8/7 (~ 245 kya) allowing a multiproxy analysis of human-controlled fire use. Our results reveal isolated cases of highly concentrated and diverse polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs (APAHs), along with diagnostic conifer-derived triterpenoids in two hearth-like archaeological structures. The presence of combustion byproducts suggests the presence of anthropogenic (controlled) fires at Valdocarros—one of the oldest evidence of fire use in Europe-in association with Acheulean tools and bones. Hominins possibly used fire for two main activities, as a means of defense against predators and cooking. Our results help to better delineate major gaps in our current knowledge of human-controlled fire in the context of the Middle-Pleistocene in Europe and suggest that human ancestors were able to control fire before at least 250 kya. [ABSTRACT FROM AUTHOR]

Spatial analysis has been much used to examine the distribution of archaeological remains at Pleistocene sites. However, little is known about the distribution patterns at sites identified as hunting camps, i.e., places occupied over multiple short periods for the capture of animals later transported to a base camp. The present work examines a Neanderthal hunting camp (the Navalmaíllo Rock Shelter in Pinilla del Valle, Madrid, Spain) to determine whether different activities were undertaken in different areas of the site. A spatial pattern was detected with a main cluster of materials (lithic tools, faunal remains, and coprolites) clearly related to the presence of nearby hearths—the backbone of the utilised space. This main cluster appears to have been related to collaborative and repetitive activities undertaken by the hunting parties that used the site. Spatial analysis also detected a small, isolated area perhaps related to carcasses processing at some point in time and another slightly altered by water. [ABSTRACT FROM AUTHOR]

The statistical inference of multi-component reliability stress–strength system with nonidentical-component strengths is considered for the modified Weibull extension distribution in the presence of progressive censoring samples. For this aim, we study the estimation of multi-component reliability parameter in classical and Bayesian inference. So we derive some point and interval estimates such as maximum likelihood estimation, asymptotic confidence intervals, uniformly minimum variance unbiased estimation, approximate and exact Bayes estimation and highest posterior density intervals. Comparing of different estimates is provided by employing the Monte Carlo simulation, the mean squared error and coverage probabilities. Finally, one real data is utilized to illustrate the applicability of this new model. [ABSTRACT FROM AUTHOR]

We studied the effect of prior learning of symmetrical intraverbals on the emergence of complex intraverbals after reading a text. In Experiment 1, eighteen 7- and 8-year-old children read a text with sentences in which A and B stimuli and B and C stimuli were related (e.g., "The Alps" to "Mont Blanc," and to "Falcon"). Thereafter, all ABC intraverbals (e.g., C–A—"Name the mountain range of the falcon") were probed without reinforcement with written stimuli and written responses. In Condition 1, six children learned before intraverbals that relate the categories to the exemplars that served as stimuli in the text (e.g., "Name a mountain"—"Mont Blanc"—Exemplars) and learned intraverbals that relate the exemplars to the categories (e.g., "What is the Mont Blanc?"—"A mountain"—Categories.) In Conditions 2 and 3, 12 children did not learn Categories or neither Exemplars and Categories. All children in Condition 1 demonstrated the emergence of all ABC intraverbals, but not all children in Conditions 2–3 demonstrated emergence. Experiment 2 controlled that text presentations and teaching trials did not affect the results and replicated the effect. Therefore, learning simple discriminations symmetrical to one another facilitates further emergence with more complex discriminations—intraverbals—which evidence reading comprehension. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis (Nm) is asymptomatically carried in the nasopharynx of 5–10% adults, although certain populations, such as men who have sex with men (MSM), exhibit a higher colonisation rate. Interest in Nm carriage has been renewed, owed to meningitis outbreaks within populations of MSM. The aim of this study was to characterise Nm isolates and risk factors for its carriage among MSM attending a sexual health unit. A retrospective cross-sectional study was undertaken between June 2018 and December 2021. We took anal, oropharyngeal, urethral, and blood samples as part of the sexually transmitted infection screening procedures routinely implemented. Nm isolates were subjected to antimicrobial susceptibility testing; the serogroup and genogroup were determined by multi-locus sequence typing. A total of 399 subjects were recruited, and the Nm oropharyngeal carriage rate was 29%, similar among both people living with HIV (PLWH) and uninfected individuals. Nm carriage was less common in vaccinated individuals, especially those who had received the tetravalent vaccine (2.6% vs. 10.6%, p = 0.008). The most frequent serogroups were B (40%) and non-groupable (45%). Most of the isolates were susceptible to ciprofloxacin (96%) and ceftriaxone (100%). However, we identified 21 strains (20%) belonging to hyperinvasive lineages (CC11, CC4821, CC32, CC41/44, CC213, and CC269), most of which belonged to serogroup B. Given that vaccination with MenACWY was associated with a low Nm carriage, we encourage routine vaccination of all MSM. Moreover, the administration of the meningitis B vaccine should also be assessed considering that several invasive lines included in serogroup B are circulating among MSM. [ABSTRACT FROM AUTHOR]

The causes for the formation of defects of different characteristics on an electrical-grade cold-rolled steel strip surface are presented. Inspection of material taken from coils that presented failure was conducted using field emission scanning electron microscopy (FEGSEM), energy-dispersive x-ray analyses (EDX), and confocal microscopy (CM). The surface and cross section analyses of selected specimens suggested that the formation of holes and scale-like defects during cold rolling could be related to a considerable number of non-metallic inclusions dispersed within the metallic matrix, the presence of both small MnS particles and silicon-rich oxides in the alloy. [ABSTRACT FROM AUTHOR]

The effects of emerging contaminants on environmental health are of high concern, especially those potentially induced by mixtures. We assessed single and composite mixtures of triclosan (T), 17β-estradiol (E2), sulfamethoxazole (SMX), and nicotine (N) at various concentrations, on neonates of Daphnia magna. When used in single exposure, T and N induced high toxicity (100% immobility, each one), compared to SMX and E2 (2.5% and 10% immobility, respectively). When T, E2, SMX and N were in mixture, T had the highest contribution to the overall toxicity in mixture exposures. The N toxicity lowered when in a fourfold exposure (85% immobility in fourfold exposure). Due to the high toxicity of T and N, both alone and in the mixtures, our results can serve as a warning about the use of these substances and their release in the aquatic ecosystem. [ABSTRACT FROM AUTHOR]

We explored the emergence of relations between stimuli learned as discriminative, responses, and consequences with intraverbals. In Experiment 1, five 9- and 10-year-old children learned intraverbals that related a country (A) with a city (B)—e.g., "Name a city of Switzerland"; "Davos"—and that country with a predator animal (C). Correct responses were followed by saying the name of a feature of the city (T) or saying an animal preyed by the predator (U), respectively. The emergence of BC and CB intraverbals that relate the cities and the predators and that of intraverbals that relate the specific consequences to the cities (T-B and U-B) and to the prey animals (T-C and U-C) was probed with no differential consequences. All five children demonstrated the emergence of BC, CB, U-B, and U-C and four children also demonstrated the emergence of T-B and T-C. In Experiment 2, a simpler procedure that controlled a possible extraneous factor, was used with seven 7- and 8-year old children and they also demonstrated emergence. Thus, the emergence of verbal relations with elements taught as discriminative stimuli, responses, and consequences was demonstrated. [ABSTRACT FROM AUTHOR]

Purpose: Huntington's disease (HD) is a monogenic neurodegenerative disease with no effective treatment currently available. The pathological hallmark of HD is the aggregation of mutant huntingtin in the medium spiny neurons of the striatum, leading to severe subcortical atrophy. Cortical degeneration also occurs in HD from its very early stages, although its biological origin is poorly understood. Among the possible pathological mechanisms that could promote cortical damage in HD, the in vivo study of TDP-43 pathology remains to be explored, which was the main objective of this work. Methods: We investigated the clinical and structural brain correlates of plasma TDP-43 levels in a sample of 36 HD patients. Neuroimaging alterations were assessed both at the macrostructural (cortical thickness) and microstructural (intracortical diffusivity) levels. Importantly, we controlled for mutant huntingtin and tau biomarkers in order to assess the independent role of TDP-43 in HD neurodegeneration. Results: Plasma TDP-43 levels in HD specifically correlated with the presence and severity of apathy (p = 0.003). The TDP-43 levels also reflected cortical thinning and microstructural degeneration, especially in frontal and anterior-temporal regions (p < 0.05 corrected). These TDP-43-related brain alterations correlated, in turn, with the severity of cognitive, motor and behavioral symptoms. Conclusion: Our results suggest that the presence of TDP-43 pathology in HD has an independent contribution to the severity of neuropsychiatric symptoms and frontotemporal degeneration. These findings point out the importance of TDP-43 as an additional pathological process to be taken into consideration in this devastating disorder. [ABSTRACT FROM AUTHOR]

Ambient intelligence (AmI) focuses on supporting people by designing sensitive and responsive environments to context through implicit and explicit interactions. Explicit interactions in AmI systems have requirements specific to making interactions robust, smooth, intuitive, and reliable. Based on requirements, the designers can detect and eliminate faults from the beginning of the design process and understand the users' needs and demands. This work presents a UIPatternM model for predicting interaction design patterns from processing text-based requirements through machine learning algorithms. We evaluate the predictions of our proposal. We also present a case study with professional designers who evaluated the UIPatternM recommender predictions according to a set of design-level requirements that emulate everyday needs. Our participants performed a set of tasks based on scenarios, and we evaluated the participants' using effectiveness, efficiency, and satisfaction as performance metrics. Applying the UIPatternM model helped to endorse the conception and refinement of user interface design for explicit interaction in AmI systems. [ABSTRACT FROM AUTHOR]

The differences between the isothermal oxidation behavior of the Inconel 625® superalloy fabricated by additive manufacturing and wrought conditions are presented. At 900 and 1000 °C, the oxidation kinetics of polished specimens exposed to synthetic dry air followed the parabolic rate law. The values of the oxidation rate constant kp were similar to values obtained for the same alloy and similar oxidation conditions in different investigations and depended on both, oxidation temperature and alloy condition being kpW = 1.2 × 10–3 mg2cm−4 h−1 and kpAM = 2.9 × 10–3 mg2cm−4 h−1 for the alloys in wrought and additive manufacturing conditions, respectively, at 900 °C and kpW = 16 × 10–3 mg2cm−4 h−1 and kpAM = 74 × 10–3 mg2cm−4 h−1 for the alloys in wrought and additive manufacturing conditions, respectively, at 1000 °C. For both alloys, chromia Cr2O3 was the primary oxide found on the surface of the alloy, together with nodules of NiCr2O4 spinel. Metallographic cross sections of the specimens revealed the formation of Al- and Ti-rich intergranular oxides below the metal–oxide interface. The amount of surface and subsurface oxidation of the alloys depended on their microstructures and their porosity. [ABSTRACT FROM AUTHOR]

The study investigated the joint contribution of the self-regulated learning (SRL) and individual differences approaches to the prediction of university students' grade point average (GPA) obtained at three separate time points throughout their degree (3 years). We assessed cognitive (i.e., previous academic performance, cognitive ability, and cognitive SRL strategies) and non-cognitive variables (i.e., personality, trait emotional intelligence, motivation, and non-cognitive SRL strategies) in a sample of Spanish undergraduates. Results showed that GPA correlated with previous academic performance (i.e., combination of high school's GPA and college admission test score), academic self-efficacy, academic engagement, SRL strategies, and conscientiousness. Hierarchical regression analyses indicated that non-cognitive factors (i.e., academic engagement, academic self-efficacy, regulation of behavior and context, and conscientiousness) alone explained 17–25% of the variance in GPA across three years, and previous academic performance accounted up to an additional 25% of the variance, jointly reaching an explained variance of up to 50% in GPA. Specifically, academic engagement and regulation of behavior and context demonstrated incremental validity over and above cognitive predictors such as previous academic performance, inductive reasoning and regulation of cognition and metacognition. The role of intelligence, whether cognitive or emotional, was not as obvious as a predictor. Two nested structural equation models explained about 27–29% of the variance in a latent GPA factor exclusively from a proxy of a global variable of non-cognitive factors as a latent predictor, which is a novel and promising proof of its robust criterion validity. Implications and recommendations for future studies are discussed. [ABSTRACT FROM AUTHOR]

The Navachiste complex (NAV) is impacted by neighbored human activities and is located in the southwestern coastal zone of the Gulf of California. The study determines the trace metal (TM) and organochlorine pesticides (OCP) health risk content in the edible tissue of Sphoeroides spp. from NAV. The daily intakes (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic and non-carcinogenic risks were calculated. Twenty OCP and seven TM were detected. Cd, Cu, Fe, Mn, Pb, and Zn were above MRLs. The γ‒Chlordane was the most frequent OCP. The highest average concentration was for α‒HCH, followed by γ‒chlordane. With the high ratios of γ‒HCH, p, p′‒ DDD and p, p′‒DDD, and the absence of p, p′‒ DDT, the higher ratios for dieldrin and endrin than for aldrin, α‒ chlordane, γ‒chlordane, heptachlor, and heptachlor epoxide indicates historical contamination. In contrast, the residual products of methoxychlor, endosulfan, and its isomers indicate endosulfan's recent use. The TM EDI, THQ > 1 (at 120 g day−1), and the ILCR (> 1 × 10–6) were above minimum levels, showing a high-risk potential for cancer development in the long term. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) in the brain play a role in neuronal homeostasis by removing intracellular material and regulating cell-to-cell communication. Given that sex and aging differentially modulate brain networks, we investigated sex-dependent differences in EV levels and content in the brain during aging. EVs were isolated from the brains of 3, 6, 12, 18, and 24 month-old female and male C57BL/6 J mice, and the levels of different EV species determined. While the number of plasma membrane-derived microvesicles and a subset of late endosomes-derived exosomes increased with age in the brain of female mice, no significant changes were seen in males. Mitochondria-derived mitovesicles in the brain increased during aging in both sexes, a change that may reflect aging-dependent alterations in mitochondrial function. These findings reveal enhanced turnover during aging in female brains, suggesting a mechanism for advantageous successful female brain aging and sex-depending different susceptibility to age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Companies face the challenge of managing customer relationships (CRM) in a context marked by a drastic digital transformation and unbridled evolution of consumer behavior, exacerbated by the COVID-19 pandemic. The customer is more demanding, has access to the global market and interacts with companies through multiple digital channels, such as email, social networks, mobile apps or instant messaging. In this situation, the success of a CRM implementation highly depends on information technology and the applications used. To harmonize this new business context with the development of information systems (IS), a suitable CRM ontology and enterprise architecture (EA) is needed. While an ontology-based conceptual model provides a unifying framework, aids sharing and reusing knowledge, and facilitates communication within a domain, an EA-based model unequivocally describes, analyzes, and visualizes how an organization should operate from the perspective of business, application, and technology. The purpose of the paper is the proposal of CURIE-O, a CRM OntoUML UFO-based ontology, together with CURIE-EA, a CRM ArchiMate-based EA to serve business managers and IS specialists an updated unifying framework of reference in the CRM domain as well as a highly efficient tool to support application development and maintenance in this changing and increasingly digital context. Modeling has proven to be an essential element to achieve high-performance information systems. In order to apply the ontology and the EA proposed here, the authors developed a CRM task management application prototype that was implemented as a case study in a consulting company. The methodology followed was design science research (DSR), in order to design and validate the artifacts. Within the DSR framework, other complementary research methods have been used, in particular literature research, interviews and focus groups carried out with several hotel chains in Tenerife (Canary Islands). The main existing CRM models in the scientific literature have also been analyzed together with the leading CRM market solutions. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic is giving rise to a wide range of clinical manifestations, which can affect all organs and systems. Due to the enormous and constantly growing number of infected people, even the rarest complications will be observed in a very high number of patients. Late periprosthetic seroma of the breast has gained importance since the description of Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), but this entity is not the only cause. Among the causes of non-BIA-ALCL late seroma, we can include those of mechanical origin and those of non-mechanical origin. Within the latter, the common denominator is the triggering of an aberrant immune reaction that generates an inflammatory exudate from the periprosthetic capsule that gives rise to the seroma. We present two cases of late breast seroma as a manifestation of SARS-CoV-2 infection. Level of evidence: Level V, diagnostic study. [ABSTRACT FROM AUTHOR]

Previous works that have analysed the efficiency of the management of professional football clubs have not paid much attention to the interaction between the sporting, social and economic dimensions of their activity. To bridge this research gap, a DEA model is developed and applied to determine the relative efficiency of clubs participating in one of the main football leagues while taking into account their multiplicity of objectives. The proposed two-stage relational network DEA model assumes that the financial resources of the clubs are distributed between social and sporting dimensions, contributing to generate results in both areas that, in the second stage, determine the business performance of the clubs. As the actual distributions of the primary inputs are unknown, two complementary approaches are used. First, the model is solved by assuming a parameterization of the distribution. Then, a simulation model is used to study the effect of the different distributions on the efficiency by means of contour charts. A final cluster analysis completes the study. The sample consists of the 20 clubs that played in Spain's First Division in the 2016–17 season. The evidence shows that the efficiency of the clubs increases when a higher proportion of the primary inputs is allocated to the social dimension. In addition, the clubs are more efficient in converting their sporting and social results into income, than when turning their economic resources into sporting successes and social support. As a result, the model makes it possible to extend efficiency analysis to professional sports organisations which have multiple objectives. [ABSTRACT FROM AUTHOR]

Introduction: Budd-Chiari syndrome (BCS) is a rare vascular disease of the liver, characterised by occlusion of the venous outflow tract. Cancer, pyogenic liver infection, and prothrombotic haematological conditions are the most frequent causes of BCS. The treatment and prognosis of the disease are closely related to the underlying cause. Methods: This is a retrospective case-series study performed in Spain, in a health area of around 523,000 inhabitants. Cases were identified in the discharge database of the hospital between 2000 and 2020. Epidemiological, clinical, therapeutic, and prognosis data were obtained from the patient medical records. Results: A total of 15 cases were identified. Most of them were male patients (n = 8, 53.3%) with a median age of 52 years. The most common cause of BCS was cancer (n = 6, 40.0%) followed by liver abscesses (n = 4, 26.7%). The most frequent clinical course was subacute hepatitis (n = 8, 53.3%); 12 of the 15 patients (80%) received anticoagulant treatment, and interventional treatment was carried out in 4 patients (26.7%). Seven patients died within 6 months (46.7%), 6 of them due to progression of the underlying disease, most often cancer; 2 patients (13.3%) developed liver cirrhosis after BCS. Discussion: The incidence of BCS was low but higher than in other European studies. In addition, this current research showed a different aetiology than previously described. The mortality rate was extremely high and closely related to the underlying disease. The involvement of classic prothrombotic haematological factors was less common than previously described. [ABSTRACT FROM AUTHOR]

In this research work, the effect of the change in the surface area of silicon dioxide nanoparticles of the same size on mechanical properties of poly(lactic acid) nanocomposites (PLA) was studied, as well as the role of coupling agent amount in the compatibility of these nanomaterials. We consider a spherical silicon dioxide with a surface area of 170–200 m2/g (labeled as S–SiO2) and another considered amorphous with a surface area of 180–600 m2/g (labeled as P-SiO2). This surface areas difference plays an important role in modifying of nanoparticles polarity by incorporating a coupling agent and its integration into partially polar polymers. According to obtained results, for nanomaterials with high surface area, it was observed while increasing coupling agent amount, the elasticity of the composite was observed to increase. In contrast, in nanomaterials with spherical nanoparticles, it was observed that as the amount of coupling agent decreases, the resistance of the material increases, reaching a maximum when a 10:2 ratio is used. It was observed that behaviors for both nanoparticles were different, which gives an idea that the incorporation of nanoparticles in polymers is not an issue of coupling agent or quantity only, it is more important as it is arranged on the surface. This kind of couplings does not only affect mechanical properties, since the thermal behavior of the material was also influenced, where it was observed that particles with low surface area modify the crystallization rate when they have different percentages of coupling agent on the surface. Furthermore, it is observed that the incorporation of nanoparticles with high surface areas area does not modify the crystallization rate significantly. Besides, in both cases, it was observed that the highest crystallization rate is reached when a 10:2 ratio is used. However, the energy required to form crystals remains unchanged. Therefore, it is considered that the incorporation of nanoparticles only affects the crystal formation rate without disturbing the energy requirement for crystal formation. Finally, a maximum in the 10:2 ratio was observed for the compatibility in both particles, which was manifested in an increase in the storage module through a dynamic mechanical analysis. The rate of crystal formation as well as the number of formed crystals have a considerable effect on mechanical properties of nanocomposites when the surface area is modified. [ABSTRACT FROM AUTHOR]