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Ca isotope geochemistry has great potential for improving our understanding of magmatic systems and for tracing the deep Earth carbon cycle. There are still many open questions, however, regarding the proper application of this relatively novel proxy to the study of mantle-derived magmas, including (i) the possible effects of pressure on mineral-melt Ca isotope fractionation factors, and (ii) the potential for Ca isotopes to be used as tracers of recycled marine carbonates in mantle-derived magmas. Kimberlites are mantle-derived melts that are highly enriched in CO2 and are the deepest-sourced magmas (>200 km depth) known to erupt at Earth's surface, providing an excellent opportunity to explore these questions. We present Ca isotope data combined with detailed petrographic observations, bulk-carbonate C-O isotope data, and bulk-rock major element analyses, for a suite of 23 well-characterized kimberlite samples from their type-locality (Kimberley, South Africa). These kimberlites have abundant previous evidence for recycled surface materials in their mantle source, including low S isotope and moderately radiogenic Sr isotope compositions, yet display only limited variations in their Ca isotope compositions (δ44CaBSE of −0.08‰ to −0.27‰), with an average of −0.17 ± 0.02‰ (2SE, n = 21). This composition is indistinguishable from average carbonatites [−0.19 ± 0.03‰ (2SE, n = 106)] and OIB from recent studies [−0.16 ± 0.01‰ (2SE, n = 41)], and slightly lower than average MORB [−0.11 ± 0.02‰ (2SE, n = 31)]. Although our samples display a wide range of emplacement styles, alteration conditions, extents of magmatic differentiation, and degrees of mantle-cargo entrainment (i.e., xenocryst accumulation), we find no correlations between Ca isotopes and any of these factors. Instead, we find that low-degree partial melting of the likely kimberlite source lithology (i.e., carbon-bearing garnet lherzolite) yields modelled melt δ44CaBSE values ranging between −0.12‰ and −0.16‰ (at 1400–1500 °C), in agreement with the measured Ca isotope compositions of the Kimberley kimberlites. This observation, and the lack of heavy carbon isotope signatures in the examined samples, indicates that kimberlites do not require subducted carbonates in their mantle sources, despite their very high CO2 contents. Although several recent studies have suggested that equilibrium mineral-melt Ca isotope fractionation factors (e.g., 1000lnαgrt-melt) could be significantly different at higher pressures (i.e., due to pressure-induced changes in Ca[sbnd]O bond lengths and coordinations), our models successfully reproduce the kimberlite data using pressure-independent predictions for mineral-melt fractionations. It remains possible, however, that differences in isotopic fractionation due to the peculiar composition of kimberlite melts (e.g., high CO2, low SiO2) are effectively cancelled out by competing pressure effects, and future work independently targeting these factors will be especially important for our understanding of Ca isotope fractionation in mantle-derived melts and the Ca isotope systematics of Earth's mantle., Geochimica et Cosmochimica Acta, 348, ISSN:0016-7037, ISSN:1872-9533

SUMMARY This study derives the spatial variation of the elastic thickness (Te) and its implications for understanding the structure, geodynamic and seismicity of the lithosphere for the Zagros fold and thrust belt region of the Arabia–Eurasia collision zone. Te is calculated using the coherence function in the fan wavelet domain based on recent terrestrial Bouguer gravity and topography data as input signals. Utilizing the load deconvolution method and Brent's method of 1-D minimization, the final Te for the survey region is estimated for each grid node of the studied area. To illustrate the mass distribution in the studied area, the subsurface loading fraction (F) is calculated simultaneously with Te in the inversion. The crust thickness and density from three different global crustal models are tested and the results obtained for these input models do not yield substantially different Te patterns. The final results are in accord with the global Te models as well as previous rheological, geodynamical and flexural studies, however, this study establishes much more detailed regional information. The calculations yield a mean value of Te of 61 km for the Zagros, with a mean estimated error of about 5 km. The high-Te values (>70 km) are observed in the southeast of the studied area (some parts of the Sanandaj–Sirjan zone, Urumieh–Dokhtar magmatic arc and most of the Central Iranian blocks); while over most of the northwest of the studied area, the value of Te is about 58 km. The Te results are consistent with the lithospheric structure of the study area and also support the idea of the crust–mantle decoupling. Further, there is a positive and negative correlation between the surface wave velocity and surface heat flow, respectively. The mean value estimated for the internal loading friction (F) of 0.4 means in most of the studied areas we may consider that the surface loading is dominant, or at least the ratio of the surface and subsurface loading can be assumed equal. Based on earthquake distribution in the period 1900–2020, seismicity is more likely to occur in areas with a relatively low value of Te.

The purpose of this document is to highlight practical recommendations to assist acute-care hospitals in prioritization and implementation of strategies to prevent healthcare-associated infections through hand hygiene. This document updates the Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals through Hand Hygiene, published in 2014. This expert guidance document is sponsored by the Society for Healthcare Epidemiology (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America, the Association for Professionals in Infection Control and Epidemiology, the American Hospital Association, and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

Quantized vortices are a prototypical feature of superfluidity that have been observed in multiple quantum gas experiments. But the occurrence of vortices in dipolar quantum gases—a class of ultracold gases characterized by long-range anisotropic interactions—has not been reported yet. Here we exploit the anisotropic nature of the dipole–dipole interaction of a dysprosium Bose–Einstein condensate to induce angular symmetry breaking in an otherwise cylindrically symmetric pancake-shaped trap. Tilting the magnetic field towards the radial plane deforms the cloud into an ellipsoid, which is then set into rotation. At stirring frequencies approaching the radial trap frequency, we observe the generation of dynamically unstable surface excitations, which cause angular momentum to be pumped into the system through vortices. Under continuous rotation, the vortices arrange into a stripe configuration along the field, in close agreement with numerical simulations.

Inherited retinal degenerations (IRDs) are a heterogeneous group of predominantly monogenic disorders with over 300 causative genes identified. Short-read exome sequencing is commonly used to genotypically diagnose patients with clinical features of IRDs, however, in up to 30% of patients with autosomal recessive IRDs, one or no disease-causing variants are identified. Furthermore, chromosomal maps cannot be reconstructed for allelic variant discovery with short-reads. Long-read genome sequencing can provide complete coverage of disease loci and a targeted approach can focus sequencing bandwidth to a genomic region of interest to provide increased depth and haplotype reconstruction to uncover cases of missing heritability. We demonstrate that targeted adaptive long-read sequencing on the Oxford Nanopore Technologies (ONT) platform of the USH2A gene from three probands in a family with the most common cause of the syndromic IRD, Usher Syndrome, resulted in greater than 12-fold target gene sequencing enrichment on average. This focused depth of sequencing allowed for haplotype reconstruction and phased variant identification. We further show that variants obtained from the haplotype-aware genotyping pipeline can be heuristically ranked to focus on potential pathogenic candidates without a priori knowledge of the disease-causing variants. Moreover, consideration of the variants unique to targeted long-read sequencing that are not covered by short-read technology demonstrated higher precision and F1 scores for variant discovery by long-read sequencing. This work establishes that targeted adaptive long-read sequencing can generate targeted, chromosome-phased data sets for identification of coding and non-coding disease-causing alleles in IRDs and can be applicable to other Mendelian diseases.

Terranes are passengers within drifting oceanic plate, and ride with the plate to subduction plate boundaries. Although oceanic lithosphere readily subducts into the mantle at the plate boundary, terranes may resist sinking or not, depending on a variety of controlling factors that are not very well understood. Further, the tectonic development of terranes prior to their arrival at a subduction zone is not well documented. We performed numerical experiments to explore these unknowns of terrane geodynamics during the whole pre- to post-collisional period. Our analyses reveal that terranes can undergo considerable extension prior to their arrival to subduction plate boundaries owing to the pull force exerted by sinking oceanic slabs. Increasing terrane crustal thickness, decreasing terrane width or imposed convergence velocity, and an intra-oceanic subduction setting aggrandizes the pre-collisional terrane extension. The numerical models identify increasing terrane crustal thickness and width, and decreasing imposed convergence velocity as factors that promote terrane accretion. Additionally, having a continental overriding plate at the subduction boundary increases the propensity for terrane accretion. Some intra-oceanic subduction experiments demonstrate ablative subduction and subduction polarity reversal events in connection with terrane collisions/subduction. We compare our models to the evolution of a controversial Tethyan terrane, the Nilufer oceanic plateau. Our models suggest that the Nilufer terrane may have undergone pre-collisional extension owing to the pull of the sinking Tethys Ocean plate. Further, uninterrupted subduction of the Tethys Ocean, despite the accretion of the Nilufer terrane, is illustrated by our results which have implications on other regions along the Tethyan orogenic belt.

Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.

Uveitis encompasses a heterogeneous group of clinical entities with the common feature of intraocular inflammation. In addition to patient history and examination, a focused set of laboratory investigations is frequently necessary to establish a specific diagnosis. There is limited consensus among uveitis specialists regarding appropriate laboratory evaluation for many distinct patient presentations. The appropriateness of a laboratory test for a given case of uveitis will depend on patient-specific as well as epidemiologic factors. Bayesian analysis is a widely used framework for the interpretation of laboratory testing, but is seldom adhered to in clinical practice. Bayes theorem states that the predictive value of a particular laboratory test depends on the sensitivity and specificity of that test, as well as the prevalence of disease in the population being tested. In this review we will summarize the performance of commonly-utilized laboratory tests for uveitis, as well as the prevalence of uveitic diagnoses in different geographic practice settings. We will propose a logical framework for effective laboratory testing in uveitic disease through rigorous application of Bayesian analysis. Finally, we will demonstrate that while many highly sensitive laboratory tests offer an effective means to rule out associated systemic disease, limited test specificity and low pretest probability often preclude the diagnosis of systemic disease association with any high degree of certainty, even in the face of positive testing.

Background: Prostate size estimation is a valuable clinical measure widely utilized in urology. This study evaluated the accuracy of preoperative transabdominal ultrasound (TAUS) compared to radica...

To determine classification criteria for acute retinal necrosis (ARN).Machine learning of cases with ARN and 4 other infectious posterior uveitides / panuveitides.Cases of infectious posterior uveitides / panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set.Eight hundred three cases of infectious posterior uveitides / panuveitides, including 186 cases of ARN, were evaluated by machine learning. Key criteria for ARN included (1) peripheral necrotizing retinitis and either (2) polymerase chain reaction assay of an intraocular fluid specimen positive for either herpes simplex virus or varicella zoster virus or (3) a characteristic clinical appearance with circumferential or confluent retinitis, retinal vascular sheathing and/or occlusion, and more than minimal vitritis. Overall accuracy for infectious posterior uveitides / panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for ARN were 15% in the training set and 11.5% in the validation set.The criteria for ARN had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research.

PURPOSE: To determine classification criteria for cytomegalovirus (CMV) retinitis. DESIGN: Machine learning of cases with CMV retinitis and 4 other infectious posterior/panuveitides. METHODS: Cases of infectious posterior/panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior/panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: Eight hundred three cases of infectious posterior/panuveitides, including 211 cases of CMV retinitis, were evaluated by machine learning. Key criteria for CMV retinitis included: 1) necrotizing retinitis with indistinct borders due to numerous small satellites; 2) evidence of immune compromise; and either 3) a characteristic clinical appearance or 4) positive polymerase chain assay for CMV from an intraocular specimen. Characteristic appearances for CMV retinitis included: 1) wedge-shaped area of retinitis; 2) hemorrhagic retinitis; or 3) granular retinitis. Overall accuracy for infectious posterior/panuveitides was 92.1% in the training set and 93.3% (95% confidence interval 88.2, 96.3) in the validation set. The misclassification rates for CMV retinitis were 6.9% in the training set and 6.3% in the validation set. CONCLUSIONS: The criteria for CMV retinitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research.

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Existen dos grandes problemas a la hora de ver 𝐏elícula Avatar: El sentido del agua gratis en internet: Los continuos parones en la reproducción de la 𝐏elícula y la calidad en la que se reproduce. Seguramnte en más de una ocasión has buscado en Google “¿cómo puedo ver Avatar: El sentido del agua la 𝐏elícula 𝐂ompleta en 𝐄spañol?” o “¿dónde puedo ver Avatar: El sentido del agua la 𝐏elícula 𝐂ompleta?”. No lo niegues. No eres el único. Todos los días, millones de personas intentan ver 𝐏elícula online desde sus computadoras, laptops, smartphones, tablets o cual sea el dispositivo móvil de su preferencia. Sin embargo, la navegación muchas veces termina en páginas web que no cumplen lo prometido, que aseguran tener los últimos estrenos, pero que solo te derivan de un site a otro, que te obligan a dar clic tras clic mientras te llenan la pantalla de publicidad, para finalmente dirigirte hasta un enlace que no funciona o que demora mucho en cargar. Esto hace que sea imposible disfrutar de verdad de una tarde/noche de 𝐏elículas. Además existe una ley no escrita y es que este tipo de cosas suelen ocurrir los mejores momentos de la 𝐏elícula y acaba frustrando. Que esto ocurra se debe a muchos factores como: la conexión a Internet, la página desde la que estés viendo la 𝐏elícula gratis o la calidad de reproducción elegida. Todos estos problemas se pueden solucionar, salvo la velocidad de tu internet, por ello en este aqui encontrarás solo páginas para ver 𝐏elículas en Internet gratis en castellano y sin cortes de gran calidad dónde estás problemas no existen o son muy poco comunes. Por supuesto esta página están libres de virus y el listado se actualiza conforme a las nuevas páginas que van apareciendo y aquellas que se van cerrando. De las páginas más conocidas, cabe duda de que cumple su objetivo a la perfección ¡Ver 𝐏elícula Avatar: El sentido del agua online sin registrase en 𝐄spañol y otros idiomas! 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La ventaja es que puedes descargarlo si necesitas incluir subtítulos que probablemente puedas encontrar fácilmente en él. Una vez que sepas cómo funciona, hay miles de títulos disponibles y puedes filtrar por año, por tipo e incluso por directores o “creadores” de la 𝐏elícula. Etiqueta de Google Ver Avatar: El sentido del agua online Avatar: El sentido del agua online en 𝐄spañol Avatar: El sentido del agua pelicula 𝐂ompleta Ver Avatar: El sentido del agua online gratis Ver Avatar: El sentido del agua online latino Dónde ver Avatar: El sentido del agua en 𝐄spañol Avatar: El sentido del agua pelicula 𝐂ompleta en 𝐄spañol Avatar: El sentido del agua pelicula 𝐂ompleta en 𝐄spañ

Caves are important fossil repositories which provide records extending back over million-year timescales. While the physical processes of cave formation are well understood, the timing of initial cave development and opening—a more important parameter to studies of palaeontology, palaeoanthropology and archaeology—has proved more difficult to constrain. Here we investigate speleothems from the Naracoorte Cave Complex in southern Australia, with a rich record of Pleistocene vertebrate fossils (including extinct megafauna) and partly World Heritage-listed, using U-Th-Pb dating and analyses of their charcoal and pollen content. We find that, although speleothem formation began at least 1.34 million years ago, pollen and charcoal only began to be trapped within growing speleothems from 600,000 years ago. We interpret these two ages to represent the timing of initial cave development and the subsequent opening of the caves to the atmosphere respectively. These findings demonstrate the potential of U-Th-Pb dating combined with charcoal and pollen as proxies to assess the potential upper age limit of vertebrate fossil records found within caves.

This chapter considers colonial encounters in the vicinity of the Honduran city of San Pedro Sula between the sixteenth and eighteenth centuries and argues that ‘cultural contact’ lacks the sophistication required to grasp the tone of inequality that flows through contexts of imposition. Drawing upon De Certeau’s notion of ‘tactics’ as a means to occupy and navigate landscapes not under one’s control, the experience of colonial survival is approached as a shared project in which identities fluctuate, particularly in contexts of sexual reproduction. Emphasis on local and traceable ancestry as opposed to identity formation through migrant arrival is noted to be manifest in the materiality of everyday practice.

Identification or ID cards are used by many organizations nowadays to prove the person’s identity. Educational institution provides ID cards to their students, faculty, and staff to shows their connections to the institution. Several educational institutions have offices that will process the student’s ID cards. In this study, the researchers developed a web-based application that addressed the problem of restraining the students to on-site process their ID cards. This application allowed the student to process their ID cards thru the use of the online application. Using this application students will no longer go to the office of the school site to process their ID cards. The application also helped the students to save their time and effort in processing their ID. The newly developed system will be deployed on the web and it can access by many devices with the internet browser and connected to the world-wide-web.

Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and a series of germline mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provides a blueprint for the discovery of sex-dependent metabolites in other animals.

To report the clinical course of patients with ocular inflammatory disease treated with adalimumab in whom anti-adalimumab antibodies (AAA) were detected.Single center case series.Eight patients with initial response to adalimumab developed a disease flare associated with positive AAA testing after 5 to 76 months of therapy. Six patients were receiving no concurrent antimetabolite therapy at the time of AAA diagnosis and four had a temporary lapse in adalimumab therapy prior to AAA discovery. AAA resulted in undetectable drug levels in five of the seven patients for whom data were available, and adalimumab was discontinued in six of the eight patients. Of two patients continued on adalimumab, one maintained detectable serum adalimumab despite AAA and one had a low AAA titer.For patients receiving adalimumab for ocular inflammatory disease, a disease flare in the setting of previously well-controlled disease should prompt consideration of AAA testing.

We describe two complementary approaches based on a convergent [4+2] logic toward the synthesis of amorfrutins, cannabinoids, and related plant metabolites. An anionic cascade cyclization employing β-methoxycrotonates and β-chloro-α,β-unsaturated esters yielded amorfrutins in four linear steps and demonstrated utility of β-alkoxycrotonate-derived nucleophiles as functional equivalents of β-ketoester-derived dianions. Analogously, tandem Diels-Alder/retro-Diels-Alder cycloaddition of dimedone-derived bis(trimethylsiloxy)-dienes and α,β-alkynyl ester dienophiles provided facile access to resorcinol precursors of amorfrutins and cannabinoids, avoiding late-stage installation of prenyl or geranyl moieties as in previous approaches.

Unlike brick-and-mortar stores where consumers can use all of their senses to examine a product, online retailers must properly present products to shoppers via a computer-mediated interface. In this exploratory study, we investigate how the brain makes purchase decisions when it encounters different types of visual presentation strategies. Specifically, we use event-related fMRI to study brain activation preceding purchase decisions under three visual presentation strategies: (1) static picture, (2) image zooming, and (3) rotation video. Twenty-four (24) participants made 60 apparel purchase decisions. Utilizing machine learning, we study whether and how various neural circuits are engaged in purchase decision-making in regard to different types of visual sensory information. The functional neuroimaging results suggest high accuracy (highest: 95%, Rotation condition) in predicting purchase decisions using brain activity in the product evaluation process. Furthermore, cross-category validation reveals the activation patterns under the Rotation condition most successfully predict choices across the other two presentation conditions: this suggests a potential universal brain activity pattern in these apparel purchase decisions. Finally, we found some brain regions (such as the cerebellum) that are less likely to be associated with purchase decisions but are considered influential in predicting online apparel purchase decisions in the context of watching a rotation product video. The cerebellar activation may suggest association with spatial cognition and virtual navigation in addition to motor control. This study contributes to the research field of NeuroIS and online shopper study. The results provide empirical evidence to support the refined S-O-R theoretical model Jacoby (2002) and heuristic information process and inform the practical implications of sensory-engaging presentations in helping consumers to make online purchase decisions.

Angular oscillations can provide a useful probe of the superfluid properties of a system. Such measurements have recently been applied to dipolar supersolids, which exhibit both density modulation and phase coherence, and for which robust probes of superfluidity are particularly interesting. So far, these investigations have been confined to linear droplet arrays. Here, we explore angular oscillations in systems with 2D structure, which in principle have greater sensitivity to superfluidity. Surprisingly, in both experiment and simulation, we find that the frequency of angular oscillations remains nearly unchanged even when the superfluidity of the system is altered dramatically. This indicates that angular oscillation measurements do not always provide a robust experimental probe of superfluidity with typical experimental protocols., 4 pages, 4 figures

The basin and plateau regions of the Central Andes have undergone phases of rapid subsidence and uplift during the last ~20 Myr in addition to internal tectonic deformation. Paleoelevation data and the presence of high seismic wave speed anomalies beneath the Puna Plateau suggest that these tectonic events may be related to lithospheric foundering. Here, we study the geodynamic processes in the region using three dimensional, scaled, analogue models and high-resolution optical image correlation techniques. The analogue experiments show how a gravitational instability of the mantle lithosphere developing into a lithospheric drip may form a circular sedimentary basin in the crust that undergoes subsidence and subsequently reverses to uplift, while simultaneously undergoing internal crustal shortening. The model results reveal that drips may be “symptomatic” where the crust is well coupled to the sinking mantle lithosphere and manifests tectonic deformation at the surface, or poorly coupled “asymptomatic” drips with weak crustal surface manifestations. Overall, the physical models suggest that the formation of the Arizaro Basin and nearby Central Andean basins are caused by symptomatic lithospheric dripping events and highlight the significant role of non-subduction geodynamic mechanisms in driving surface tectonics.

The 8.2 ka event is regarded as the most prominent climate anomaly of the Holocene and is thought to have been triggered by a meltwater release to the North Atlantic that was of sufficient magnitude to disrupt the Atlantic Meridional Overturning Circulation (AMOC). It is most clearly captured in Greenland ice-core records, where it is reported as a cold and dry anomaly lasting ∼ 160 years, from 8.25 ± 0.05 until 8.09 ± 0.05 ka (Thomas et al., 2007). It is also recorded in several archives in the North Atlantic region; however, its interpreted timing, evolution and impacts vary significantly. This inconsistency is commonly attributed to poorly constrained chronologies and/or inadequately resolved time series. Here we present a high-resolution speleothem record of early Holocene palaeoclimate from El Soplao Cave in northern Spain, a region pertinent to studying the impacts of AMOC perturbations on south-western Europe. We explore the timing and impact of the 8.2 ka event on a decadal scale by coupling speleothem stable carbon and oxygen isotopic ratios, trace element ratios (Mg / Ca and Sr / Ca), and growth rate. Throughout the entire speleothem record, δ18O variability is related to changes in effective recharge. This is supported by the pattern of changes in δ13C, Mg / Ca and growth rate. The 8.2 ka event is marked as a centennial-scale negative excursion in El Soplao δ18O, starting at 8.19 ± 0.06 ka and lasting until 8.05 ± 0.05 ka, suggesting increased recharge at the time. Although this is supported by the other proxies, the amplitude of the changes is minor and largely within the realm of variability over the preceding 1000 years. Further, the shift to lower δ18O leads the other proxies, which we interpret as the imprint of the change in the isotopic composition of the moisture source, associated with the meltwater flux to the North Atlantic. A comparison with other well-dated records from south-western Europe reveals that the timing of the 8.2 ka event was synchronous, with an error-weighted mean age for the onset of 8.23 ± 0.03 and 8.10 ± 0.05 ka for the end of the event. This compares favourably with the North Greenland Ice Core Project (NGRIP) record. The comparison also reveals that the El Soplao δ18O is structurally similar to the other archives in south-western Europe and the NGRIP ice-core record.

All visual information in mammals is encoded in the aggregate pattern of retinal ganglion cell (RGC) firing. How this information is decoded to yield percepts remains incompletely understood. We have trained convolutional neural networks with multielectrode array-recorded murine RGC responses to projected images. The trained model accurately reconstructed novel facial images solely from RGC firing data. In this model, subpopulations of cells with faster firing rates are largely sufficient for accurate reconstruction, and ON- and OFF-cells contribute complementary and overlapping information to image reconstruction. Information content for reconstruction correlates with overall firing rate, and locality of information contributing to reconstruction varies substantially across the image and retina. This model demonstrates that artificial neural networks are capable of learning multicellular sensory neural encoding, and provides a viable model for understanding visual information encoding.Significance StatementConvolutional neural networks can be trained on high-density neuronal firing data from the optic nerve to reconstruct complicated images within a defined image space.

We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.Five U.S. medical centers.Adults inpatients with severe COVID-19 disease and hyperinflammation.Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo.The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR1] 86.5% and OR = 2.53; p [OR1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR]1; 99.9%) and ICU admission (OR = 0.26; p [OR1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR]0.75; p [RR1]99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR1] 98.1%; OR = 3.36, p [OR1] 99.6%; and OR = 3.52, p [OR1] 99.8%, respectively).Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

In this review, we will discuss the state of the literature regarding Rezūm and opportunities for its application in the treatment of BPH. A comprehensive review of original research on convective water vapor thermal therapy (Rezūm) was conducted. Articles related to transurethral resection of the prostate, holmium laser enucleation of the prostate, Aquablation, and greenlight photoselective vaporization of the prostate were reviewed for discussion. Rezūm distinguishes itself from other treatment options by its durable improvement in objective clinical outcomes such as IPSS and BPH Impact Index, while being cost-effective and versatile in its ability to treat a variety of prostate gland morphologies. This treatment option shows good lower urinary tract symptom relief, especially in small-to-moderate prostate sizes (30–80 cc). The use of convective heat transfer is unique and allows for localized treatment, avoiding damage to surrounding structures, thus providing an excellent safety profile and sexual function preservation. The current evidence on Rezūm warrants its consideration as a therapeutic alternative to transurethral surgery in selected patients.

The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light1,2. In mice, OPN5 is a known photoreceptor in the retina3 and skin4 but is also expressed in the hypothalamic preoptic area (POA)5. Here we describe a light-sensing pathway in which POA neurons that express Opn5 regulate thermogenesis in brown adipose tissue (BAT). We show that Opn5 is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that Opn5 POA neurons project to BAT and decrease its activity under chemogenetic stimulation. Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not in Opn5-null mice. Direct measurements of intracellular cAMP ex vivo show that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis. Mice possess neurons in the preoptic area of the hypothalamus that are sensitive to violet light; these deep brain neurons sense light via OPN5 and regulate adaptive thermogenesis in brown fat.

In this review, we will discuss the state of the literature regarding Aquablation, its limitations, and opportunities for its application in the treatment of benign prostatic enlargement (BPE). A comprehensive review of original research on Aquablation was conducted. Articles related to transurethral resection of the prostate, holmium laser enucleation of the prostate, greenlight photoselective vaporization of the prostate, and simple prostatectomy were reviewed for discussion. For small–medium prostates (30–80 mL), Aquablation’s main advantages include better ejaculatory function and similar functional outcomes compared to TURP. For large prostates (80–150 mL), Aquablation demonstrates shorter operative time and superior ejaculatory function when compared to simple prostatectomy, HoLEP, and Greenlight PVP. In addition, Aquablation displays shorter hospital stays than simple prostatectomy. The integration of software programming and semi-automatic technology increases the reproducibility of the procedure and helps standardize overall outcomes, while also accelerating the learning curve. Its ability to preserve antegrade ejaculation makes Aquablation a very compelling option for sexually active patients. However cost and postoperative bleeding risks remain a concern. The current evidence suggests that Aquablation is a safe and effective alternative for BPE for small to large prostates. Further prospective clinical trials, with comparisons to other BPE modalities, and data from longer follow-up periods are still required.

In this article, we first compare adolescents’ responses to two formats (easily recognizable versus not easily recognizable) Internet ads. We find that Internet literacy and ad skepticism are neces...

This study was designed to evaluate the use of a novel imaging technique, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), for detecting mesenteric peritoneal metastases. Thirty-four patients underwent preoperative conventional MRI, including T1, T2, diffusion-weighted (DWI), and delayed gadolinium MRI, as well as DCE MRI. DCE MRI involved imaging the peritoneal cavity every 9 s for 6 min. DCE images were processed to generate parametric maps of tumor vascularity. Two oncologic surgeons and a radiologist reviewed conventional MRI for all tumor and then later reviewed the conventional MRI plus the DCE parametric maps. Images were reviewed for tumor of the parietal peritoneum, porta hepatis, bowel serosa, upper small bowel mesentery, lower small bowel mesentery, and pelvis. Conventional MRI and DCE + MRI findings were compared to operative and histopathologic reports for tumor detection. PCI scores were calculated for surgery, MRI, and DCE. Upper mesenteric tumor was present in 21 patients. DCE images showed a sensitivity of 100%, specificity of 92%, and accuracy of 97% compared with conventional MRI sensitivity of 24%, specificity of 93%, and accuracy of 50% (p = 0.006). Lower mesenteric tumor was present in 22 patients. DCE images showed a sensitivity of 100%, specificity of 92%, and accuracy of 97% compared with conventional MRI sensitivity of 45%, specificity of 92%, and accuracy of 62% (p = 0.008). The mean surgical PCI for all 34 patients was 23.4 compared with MRI 20.0 (p = 0.003) and DCE MRI 24.1 (p = 0.26). The addition of the DCE images improved the accuracy of total PCI by > 10% in 16 (0.46) patients. For PCI regions 9–12, the mean surgical PCI was 6.0 compared with MRI 4.8 (p = 0.08) and DCE 6.6 (p = 0.02). The addition of DCE images improved the accuracy of the regional PCI > 10% in 15 (0.43) patients. DCE MRI provides a novel contrast tool that improves detection of mesenteric tumor. Depicting small-volume mesenteric tumor is better on DCE MRI compared with conventional MRI.

This chapter discusses the process Broward College in Fort Lauderdale, Florida used to embed certifications from the Council of Supply Chain Management Professionals into its associate and bachelor degree programs. Included is an overview of the process followed as well as challenges encountered. The chapter concludes with recommendations for institutions that are looking to embed third‐party industry certifications into their academic programs.

Post-infectious uveitis describes the condition of chronic immune mediated ocular inflammation associated with pathogens such as Mycobacterium tuberculosis (Mtb). Mtb associated post-infectious uveitis can be modeled in mice by intravitreal injection of heat-killed Mtb (HKMtb). To better understand how prior systemic exposure to the pathogen alters the local immune response to Mtb, we used flow cytometry and multiplex ELISAs to compare ocular responses to intravitreal HKMtb in the presence or absence of a systemic "prime" of HKMtb. Priming resulted in exacerbation of local inflammation with significantly increased clinical and histologic inflammation scores and increased vitreous cytokines concentrations one day after intravitreal injection of HKMtb. Seven days after injection, uveitis in unprimed animals had largely resolved. In contrast in primed animals, clinical signs of chronic inflammation were associated with a significant increase in the number of ocular T cells, NK cells, and Ly6C

Earth's carbon cycle is strongly influenced by subduction of sedimentary material into the mantle. The composition of the sedimentary subduction flux has changed considerably over Earth's history, but the impact of these changes on the mantle carbon cycle is unclear. Here, we show that the carbon isotopes of kimberlite magmas record a fundamental change in their deep-mantle source compositions during the Phanerozoic Eon. The

Causes of blindness differ across the globe; in higher-income countries, most blindness results from the degeneration of specific classes of cells in the retina, including retinal pigment epithelium (RPE), photoreceptors, and retinal ganglion cells. Advances over the past decade in retinal regenerative medicine have allowed each of these cell types to be produced ex vivo from progenitor stem cells. Here, we review progress in applying these technologies to cell replacement - with the goal of vision restoration in degenerative disease. We discuss the landscape of human clinical trials for RPE transplantation and advanced preclinical studies for other cell types. We also review progress toward in situ repair of retinal degeneration using endogenous progenitor cells. Finally, we provide a high-level overview of progress toward prosthetic ocular vision restoration, including advanced photovoltaic devices, opsin-based gene therapy, and small-molecule photoswitches. Progress in each of these domains is at or near the human clinical-trial stage, bringing the audacious goal of vision restoration within sight.