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Abstract The KM3NeT/ARCA neutrino detector is currently under construction at 3500 m depth offshore Capo Passero, Sicily, in the Mediterranean Sea. The main science objectives are the detection of high-energy cosmic neutrinos and the discovery of their sources. Simulations were conducted for the full KM3NeT/ARCA detector, instrumenting a volume of 1 km $$^3$$ 3 , to estimate the sensitivity and discovery potential to point-like neutrino sources. This paper covers the reconstruction of track- and shower-like signatures, as well as the criteria employed for neutrino event selection. With an angular resolution below 0.1 $$^\circ $$ ∘ for tracks and under 2 $$^\circ $$ ∘ for showers, the sensitivity to point-like neutrino sources surpasses existing observed limits across the entire sky.

Abstract The measurement of the flux of muons produced in cosmic ray air showers is essential for the study of primary cosmic rays. Such measurements are important in extensive air shower detectors to assess the energy spectrum and the chemical composition of the cosmic ray flux, complementary to the information provided by fluorescence detectors. Detailed simulations of the cosmic ray air showers are carried out, using codes such as CORSIKA, to estimate the muon flux at sea level. These simulations are based on the choice of hadronic interaction models, for which improvements have been implemented in the post-LHC era. In this work, a deficit in simulations that use state-of-the-art QCD models with respect to the measurement deep underwater with the KM3NeT neutrino detectors is reported. The KM3NeT/ARCA and KM3NeT/ORCA neutrino telescopes are sensitive to TeV muons originating mostly from primary cosmic rays with energies around 10 TeV. The predictions of state-of-the-art QCD models show that the deficit with respect to the data is constant in zenith angle; no dependency on the water overburden is observed. The observed deficit at a depth of several kilometres is compatible with the deficit seen in the comparison of the simulations and measurements at sea level.

Background Detailed visualization and precise measurements of aortic valve dimensions are critical for the success of transcatheter aortic valve implantation and for the prevention of complications. Currently, multislice computed tomography is the gold standard for assessment of the aortic annulus and surrounding structures to determine the prosthesis size. New technologies such as virtual reality (VR) not only enable 3‐dimensional (3D) visualization with the potential to improve understanding of anatomy and pathology but also allow measurements in 3D. This study aims to investigate the feasibility, accuracy, and reproducibility of VR for the visualization of the aortic valve, the surrounding structures, and its role in preprocedural sizing for transcatheter aortic valve implantation. Methods and Results Based on the preprocedural multislice computed tomography data, 3mensio measurements and 3D visualizations and measurements using VR software were performed retrospectively on 60 consecutive patients who underwent transcatheter aortic valve implantation at our heart center. There were no significant differences but strong correlations between the VR measurements compared with those performed with the 3mensio software. Furthermore, excellent or good intra‐ and interobserver reliability could be demonstrated for all values. In a structured questionnaire, users reported that VR simplified anatomical understanding, improved 3D comprehension of adjacent structures, and was associated with very good self‐perceived depth perception. Conclusions The use of VR for preprocedural transcatheter aortic valve implantation sizing is feasible and has precise and reproducible measurements. In addition, 3D visualization improves anatomical understanding and orientation. To evaluate the potential benefits of 3D visualization for planning further cardiovascular interventions, research in this field is needed.

Many authors have studied the effects of thyroid hormones and their diasteroisomers on mitochondrial activity. This topic is extensively debated because some authors have questioned the direct action of thyroid hormones on mitochondrial oxidative phosphorylation. […]

Reply to the discussion and comments of Azerêdo et al. (2023) and Schneider et al. (2023).

Abstract Background Patients undergoing cardiac surgery are prone to numerous complications. Increased vascular permeability may be associated with morbidity and mortality due to hemodynamic instability, fluid overload, and edema formation. We hypothesized that markers of endothelial injury and inflammation are associated with capillary leak, ultimately increasing the risk of postoperative complications. Methods In this prospective, observational, multidisciplinary cohort study at our tertiary academic medical center, we recruited 405 cardiac surgery patients. Patients were assessed daily using body impedance electrical analysis, ultrasound, sublingual intravital microscopy, and analysis of serum biomarkers. Multivariable models, as well as machine learning, were used to study the association of angiopoietin-2 with extracellular water as well as common complications after cardiac surgery. Results The majority of patients underwent coronary artery bypass grafting, valvular, or aortic surgeries. Across the groups, extracellular water increased postoperatively (20 ± 6 preoperatively to 29 ± 7L on postoperative day 2; P

Abstract This article reports the first observation of the Moon and the Sun shadows in the sky distribution of cosmic-ray induced muons measured by the KM3NeT/ORCA detector. The analysed data-taking period spans from February 2020 to November 2021, when the detector had 6 Detection Units deployed at the bottom of the Mediterranean Sea, each composed of 18 Digital Optical Modules. The shadows induced by the Moon and the Sun were detected at their nominal position with a statistical significance of 4.2 $$\sigma $$ σ and 6.2 $$\sigma $$ σ , and an angular resolution of $$\sigma _{res}=0.49^\circ $$ σ res = 0 . 49 ∘ and $$\sigma _{res}=0.66^\circ $$ σ res = 0 . 66 ∘ , respectively, consistent with the prediction of $$0.53^\circ $$ 0 . 53 ∘ from simulations. This early result confirms the effectiveness of the detector calibration, in time, position and orientation and the accuracy of the event direction reconstruction. This also demonstrates the performance and the competitiveness of the detector in terms of pointing accuracy and angular resolution.

Abstract In the era of precision measurements of the neutrino oscillation parameters, upcoming neutrino experiments will also be sensitive to physics beyond the Standard Model. KM3NeT/ORCA is a neutrino detector optimised for measuring atmospheric neutrinos from a few GeV to around 100 GeV. In this paper, the sensitivity of the KM3NeT/ORCA detector to neutrino decay has been explored. A three-flavour neutrino oscillation scenario, where the third neutrino mass state ν 3 decays into an invisible state, e.g. a sterile neutrino, is considered. We find that KM3NeT/ORCA would be sensitive to invisible neutrino decays with 1/α 3 = τ 3 /m 3 < 180 ps/eV at 90% confidence level, assuming true normal ordering. Finally, the impact of neutrino decay on the precision of KM3NeT/ORCA measurements for θ 23, Δ m 31 2 $$ \Delta {m}_{31}^2 $$ and mass ordering have been studied. No significant effect of neutrino decay on the sensitivity to these measurements has been found.

Abstract Multi‐scale transgressive–regressive cycles from the mid‐Jurassic were recognised in the Central Lusitanian Basin, Portugal. These cycles allow the depositional evolution of the basin to be better understood and aid in the construction of stratigraphic sequences composed of three hierarchies. The stacking pattern of high‐frequency transgressive–regressive sequences forms larger clusters that define medium‐frequency transgressive–regressive sequences. Likewise, the stacking pattern of medium‐frequency transgressive–regressive sequences generates two Bathonian–early Callovian low‐frequency transgressive–regressive sequences. Integration of several methods supported the interpretation of facies associations representing clastic deposition in offshore to shoreface environments and carbonate sediments in outer to inner ramp settings. New data from calcareous nannofossils and dinoflagellate assemblages constrained the interval's Bathonian–early Callovian age, thus unveiling the Middle–Upper Jurassic disconformity and filling the Middle Jurassic stratigraphic record gap in the Central Lusitanian Basin. This study may be helpful for similar successions in Tethyan domains and comparable depositional settings elsewhere.

Automatic Milking System (AMS) installations are increasing in the USA despite the higher investment cost than conventional systems. Surveys on AMSs conducted outside the USA focused on small–medium herds, specific regions, or aspects of AMS milking. This study described farmers’ perceptions about the decision-making process of adopting an AMS in the USA’s large dairies (≥7 AMS boxes) regarding changes in technology, housing, management practices, labor, herd performance, and health. After being contacted, 27 of 55 farmers from large AMS herds completed the survey. The main reasons for adopting an AMS were labor costs, cows’ welfare, and herd performance. Most farms constructed new barns, used a free-flow traffic system, and changed their feed management. Increases in water and energy use were perceived by 42% and 62% of farmers, respectively. Farmers estimated decreases in labor costs of over 21%, and AMS employees worked 40–60 h/week. Milk production increases were reported by 58%, with 32% observing higher milk fat and protein content. Easier sick cow detection, better mastitis management, and improvements in pregnancy rates were reported. Thus, farmers transitioning to AMSs perceived altered resource utilization, labor cost savings, and improvements in employee quality of life, animal welfare, and farm management. While 54% of respondents would recommend an AMS to other farms, 38% suggested considering additional aspects prior to adoption.

Nowadays, in many fields and applications, such as mining engineering, environmental monitoring, soil science, natural resources and environmental topics, the potential of Remote Sensing have been exploited. Large amount of data, easy and fast accessibility, and time–space availability are the reasons of attractiveness of satellite data in many fields of geosciences. However, satellite images face the problems due to presence of shadows and clouds, which is a general and real challenge since the surface features are masked. In many cases, a dense cloud cover simply prevents any detailed study of the target area through Earth Observation techniques. Geostatistics is a science field properly developed to estimate the unknown values in two-dimensional or three-dimensional space; therefore, it can be a potential approach to solve cloud-cover issues in Remote Sensing investigations. This work applies the geostatistical tools over a sentinel-2 satellite image targeting land cover in Emilia Romagna (Italy). The three main spectrum bands (RGB-values) with 10-m spatial resolution have been selected as target variables. The objective is to estimate pixel values within an area which is covered by clouds. The spatial variability of pixels with available land cover information have been studied through the use of variogram tools. Different estimation neighborhoods have been tested for application of the Kriging interpolation method, in order to estimate the RGB values below the cloud-covered area. The estimation has been performed, by controlling the properties of the estimator, the varying sizes and shapes of the neighborhood, the available number of RGB data used for estimation and the spatial distribution of pixels in the image. An image with close time period, without clouds, has been used to validate the results. Moreover, the estimation variance of RGB values for each pixel has been mapped. Results have shown the advantages and limitations of the proposed geostatistical method for the specific application of cloud-covered areas.

Background:. This multicenter, retrospective study compared clinical outcomes and healthcare resource use in patients who underwent dual-plane (DP) or prepectoral (PP) implant-based breast reconstruction (IBR) after mastectomy in the United States. Methods:. Medical records were selected for patients at five sites undergoing immediate one-stage direct-to-implant (first hospitalization) or two-stage IBR (first and second hospitalization) using either DP or PP. Inverse probability of treatment weighting was used to adjust for potential confounders. Complications and healthcare resource use were assessed with logistic regression; pain severity was assessed with ordinary least-squares regression. Results:. After inverse probability of treatment weighting, data from 255 patients (DP = 130, PP = 125) and 441 breasts (DP = 226, PP = 215) were analyzed. Mean pain severity scores were lower with PP versus DP immediately after IBR for first (P = 0.0002) and second hospitalizations (P = 0.0145), and before discharge for first (P < 0.0001) and second hospitalizations (P = 0.0002). A greater proportion of PP versus DP patients had a shorter hospital length of stay (≤ 23 hours) for first hospitalization (P = 0.0052); proportions were similar for second hospitalization (P = 0.5499). Intravenous narcotics were prescribed less frequently to PP versus DP patients during first (61.1% versus 69.8%, respectively; P = 0.1486) and second (37.5% versus 55.3%, respectively; P = 0.0172) hospitalizations. Complication rates were low in both groups after first hospitalization discharge (DP: 13.6%, PP: 12.5%, P = 0.7225). Conclusion:. This retrospective study suggests that the PP technique in IBR may offer benefits related to clinical outcomes and health resource utilization; however, larger studies, including randomized controlled trials, are needed to confirm.

Abstract The KM3NeT research infrastructure is unconstruction in the Mediterranean Sea. KM3NeT will study atmospheric and astrophysical neutrinos with two multi-purpose neutrino detectors, ARCA and ORCA, primarily aimed at GeV–PeV neutrinos. Thanks to the multi-photomultiplier tube design of the digital optical modules, KM3NeT is capable of detecting the neutrino burst from a Galactic or near-Galactic core-collapse supernova. This potential is already exploitable with the first detection units deployed in the sea. This paper describes the real-time implementation of the supernova neutrino search, operating on the two KM3NeT detectors since the first months of 2019. A quasi-online astronomy analysis is introduced to study the time profile of the detected neutrinos for especially significant events. The mechanism of generation and distribution of alerts, as well as the integration into the SNEWS and SNEWS 2.0 global alert systems, are described. The approach for the follow-up of external alerts with a search for a neutrino excess in the archival data is defined. Finally, an overview of the current detector capabilities and a report after the first two years of operation are given.

Abstract This article presents the potential of a combined analysis of the JUNO and KM3NeT/ORCA experiments to determine the neutrino mass ordering. This combination is particularly interesting as it significantly boosts the potential of either detector, beyond simply adding their neutrino mass ordering sensitivities, by removing a degeneracy in the determination of ∆ m 31 2 $$ {m}_{31}^2 $$ between the two experiments when assuming the wrong ordering. The study is based on the latest projected performances for JUNO, and on simulation tools using a full Monte Carlo approach to the KM3NeT/ORCA response with a careful assessment of its energy systematics. From this analysis, a 5σ determination of the neutrino mass ordering is expected after 6 years of joint data taking for any value of the oscillation parameters. This sensitivity would be achieved after only 2 years of joint data taking assuming the current global best-fit values for those parameters for normal ordering.

Abstract The next generation of water Cherenkov neutrino telescopes in the Mediterranean Sea are under construction offshore France (KM3NeT/ORCA) and Sicily (KM3NeT/ARCA). The KM3NeT/ORCA detector features an energy detection threshold which allows to collect atmospheric neutrinos to study flavour oscillation. This paper reports the KM3NeT/ORCA sensitivity to this phenomenon. The event reconstruction, selection and classification are described. The sensitivity to determine the neutrino mass ordering was evaluated and found to be 4.4 $$\sigma $$ σ if the true ordering is normal and 2.3 $$\sigma $$ σ if inverted, after 3 years of data taking. The precision to measure $$\varDelta m^2_{32}$$ Δ m 32 2 and $$\theta _{23}$$ θ 23 were also estimated and found to be $$85 . 10^{-6}~{\mathrm{eV}^{2}}$$ 85 . 10 - 6 eV 2 and $$(^{+1.9}_{-3.1})^{\circ }$$ ( - 3.1 + 1.9 ) ∘ for normal neutrino mass ordering and, $$75 . 10^{-6}~{\mathrm{eV}^{2}}$$ 75 . 10 - 6 eV 2 and $$(^{+2.0}_{-7.0})^{\circ }$$ ( - 7.0 + 2.0 ) ∘ for inverted ordering. Finally, a unitarity test of the leptonic mixing matrix by measuring the rate of tau neutrinos is described. Three years of data taking were found to be sufficient to exclude event rate variations larger than 20% at $$3\sigma $$ 3 σ level.

Abstract KM3NeT/ORCA is a next-generation neutrino telescope optimised for atmospheric neutrino oscillations studies. In this paper, the sensitivity of ORCA to the presence of a light sterile neutrino in a 3+1 model is presented. After three years of data taking, ORCA will be able to probe the active-sterile mixing angles θ 14, θ 24, θ 34 and the effective angle θ μe , over a broad range of mass squared difference ∆ m 41 2 $$ \Delta {m}_{41}^2 $$ ∼ [10 −5 , 10] eV2, allowing to test the eV-mass sterile neutrino hypothesis as the origin of short baseline anomalies, as well as probing the hypothesis of a very light sterile neutrino, not yet constrained by cosmology. ORCA will be able to explore a relevant fraction of the parameter space not yet reached by present measurements.

Summary: Innate visually guided behaviors are thought to promote survival by guiding organisms to sources of food and safety and away from harm without requiring learning. Historically, innate behaviors have been considered hard-wired and invariable, but emerging evidence shows that many innate behaviors are flexible and complex due to modulation. Here, we investigate the modulation of the innate preference for light displayed by the Xenopus laevis tadpole, an exceptionally invasive and well-studied organism that is known to display several different innate visually guided behaviors. We found that tadpoles display a circadian-regulated oscillation in their preference for light over dark which can be altered by experimentally increasing or decreasing levels of serotonin transmission. We also found that endogenous levels of serotonin transmission during the day maintain a consistently moderate preference for light. Theoretically, a moderate preference for light, as opposed to a strong preference, optimizes survival by rendering tadpoles’ behavior less predictable.

The Aptian–Albian interval is characterized by significant paleoclimatic, paleoceanographic, and paleogeographic changes, which in turn affected the distribution and evolution of marine ecosystems. Despite the importance of such studies, there have been few correlations between Aptian–Albian sections of the Tethys Sea and those of the South Atlantic Ocean. This interval, including the Aptian–Albian transition, is preserved in the deposits of the Riachuelo Formation (Sergipe–Alagoas Basin, Brazil) located in the South Atlantic Ocean; therefore, this location was chosen for drilling four new cores. The goals of this paper are as follows: (1) to explain the drilling operation carried out in the deposits of the Riachuelo Formation and the methods used; (2) to present a brief lithostratigraphic characterization of the holes and the paleomagnetic data of core SER-03; and (3) to describe the high potential of the cores recovered for additional investigation in the future. The lithostratigraphic units of the SER-01 core consist mainly of coarse- to fine-grained sandstone, shales, marls, and mudstones; the SER-02 core was excluded due to low recovery; the SER-03 core is mainly composed of fine-grained sediments (shale, marls, and packstone) and bears some ammonite shells; the lithology of core SER-04 is mainly sandstones. Magnetic susceptibility values (χlf and χhf) and frequency-dependent susceptibility (χfd) data suggest that the section is located within the Cretaceous Normal Superchron. Future studies on these cores integrating micropaleontological, paleoichnological, geochemical, stratigraphic, and paleomagnetic (e.g., relative intensity) data will allow for a better understanding of paleoceanographic and paleogeographic events related to the early evolution of the South Atlantic Ocean and how these events correlate to similar events in Tethyan sections.

Objectives: The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods: A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results: Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

(1) Background: Mitral regurgitation (MR) is associated with increased mortality and frequent hospital admissions. Although mitral valve intervention offers improved clinical outcomes for MR, it is not feasible in many cases. Moreover, conservative therapeutic opportunities remain limited. The aim of this study was to evaluate the impact of ACE inhibitors and angiotensin receptor blockers (ACE-I/ARB) on elderly patients with moderate-to-severe MR and mildly reduced to preserved ejection fraction. (2) Methods: In total, 176 patients were included in our hypothesis-generating, single-center observational study. Hospitalization for heart failure and all-cause death have been defined as the combined 1-year primary endpoint. (3) Results: Patients treated with ACE-I/ARB showed a lower risk for the combined endpoint of death and heart failure-related readmission (HR 0.52 95%CI 0.27–0.99; p = 0.046), even after adjustment for EUROScoreII and frailty (HR 0.52 95%CI 0.27–0.99; p = 0.049) (4) Conclusions: The use of an ACE-I/ARB in patients with moderate-to-severe MR and preserved to mildly reduced left-ventricular ejection fraction (LVEF) significantly associates with improved clinical outcome and might be indicated as a valuable therapeutic option in conservatively treated patients.

CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.

Objective: To use Multi-Criteria Decision Analysis (MCDA) to determine weights for eleven criteria in order to prioritize COVID-19 non-critical patients for admission to hospital in healthcare settings with limited resources. Methods: The MCDA was applied in two main steps: specification of criteria for prioritizing COVID-19 patients (and levels within each criterion); and determination of weights for the criteria based on experts’ knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on low- and middle-income countries (LMICs). Results: The most important criteria (mean weights, summing to 100%) are: PaO2 (16.3%); peripheral O2 saturation (15.9%); chest X-ray (14.1%); Modified Early Warning Score-MEWS (11.4%); respiratory rate (9.5%); comorbidities (6.5%); living with vulnerable people (6.4%); body mass index (5.6%); duration of symptoms before hospital evaluation (5.4%); CRP (5.1%); and age (3.8%). Conclusions: At the beginning of a new pandemic, when evidence for disease predictors is limited or unavailable and effective national contingency plans are difficult to establish, the MCDA prioritization model could play a pivotal role in improving the response of health systems.

Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.

In Italy, use and production of asbestos and asbestos-containing materials (ACMs) were banned in 1992, however, the risk of exposure to asbestos still exists, because most ACMs are located in industrial and public buildings. A total of 111 Italian buildings with friable and non-friable ACMs were surveyed; 500 air samples were collected in the areas where contamination might have occurred. Airborne asbestos fiber concentration calculated from air samples was averaged for each building. Statistical analysis of the data showed no significant differences between the mean concentration measured in buildings with friable and non-friable ACMs (p = 0.258). The concentration values were below 2 f/L, the value stated by Italian regulation to ensure that the area is safe to reoccupy after asbestos removal. Samples of settled dust were also collected. The presence of asbestos fibers in the dust showed the occurrence of a release of asbestos from the material. Although the airborne asbestos fiber concentrations measured were low, current Italian regulation requires an asbestos management program. The Public Institution to which the authors of this work belong encourages asbestos removal as the preferred abatement method, in line with the asbestos-free future approach proposed by the European Commission.

Aging is associated with an increased reactive oxygen species that can decrease muscle strength. Thus, antioxidant substances could be positively associated with muscle strength in older adults. To investigate the association between serum antioxidants and muscle strength in older adults. A cross-sectional study evaluating 1172 individuals (627 men and 545 women), aged 50 to 85 years from NHANES 2001–2002, was performed. Carotenoids (α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, lutein/zeaxanthin combination, trans-lycopene), vitamin E, and retinol were analyzed via the high-performance liquid chromatography method. Muscle strength was evaluated by the isokinetic knee extension test. Linear regression was performed to evaluate the association between tertiles of serum antioxidant levels and strength, adjusted for confounders (energy and protein intake, body mass index, sex, age, C-reactive protein, uric acid, race/ethnicity, marital status, annual household income, educational level, physical activity, smoking, hypertension, arthritis, and diabetes). Alpha-carotene levels (p-trend = 0.027) were positively associated with muscle strength. However, serum vitamin E, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, carotenoids, and retinol levels were not associated with strength. Serum α-carotene, but not other antioxidants, was positively associated with muscle strength in older adults.

The solar wind is a highly turbulent medium exhibiting scalings of the fluctuations ranging over several decades of scales from the correlation length down to proton and electron gyroradii, thus suggesting a self-similar nature for these fluctuations. During its journey, the solar wind encounters the region of space surrounding Earth dominated by the geomagnetic field which is called magnetosphere. The latter is exposed to the continuous buffeting of the solar wind which determines its characteristic comet-like shape. The solar wind and the magnetosphere interact continously, thus constituting a coupled system, since perturbations in the interplanetary medium cause geomagnetic disturbances. However, strong variations in the geomagnetic field occur even in absence of large solar perturbations. In this case, a major role is attributed to solar wind turbulence as a driver of geomagnetic activity especially at high latitudes. In this review, we report about the state-of-art related to this topic. Since the solar wind and the magnetosphere are both high Reynolds number plasmas, both follow a scale-invariant dynamics and are in a state far from equilibrium. Moreover, the geomagnetic response, although closely related to the changes of the interplanetary magnetic field condition, is also strongly affected by the intrinsic dynamics of the magnetosphere generated by geomagnetic field variations caused by the internal conditions.

Influenza (IAV) neuraminidase (NA) is a glycoprotein required for the viral exit from the cell. NA requires disulfide bonds for proper function. We have recently demonstrated that protein disulfide isomerase (PDI)A3 is required for oxidative folding of IAV hemagglutinin (HA), and viral propagation. However, it not known whether PDIs are required for NA maturation or if these interactions represent a putative target for the treatment of influenza infection. We sought to determine whether PDIA3 is required for disulfide bonds of NA, its activity, and propagation of the virus. Requirement of disulfides for NA oligomerization and activity were determined using biotin switch and redox assays in WT and PDIA3−/− in A549 cells. A PDI specific inhibitor (LOC14) was utilized to determine the requirement of PDIs in NA activity, IAV burden, and inflammatory response in A549 and primary mouse tracheal epithelial cells. Mice were treated with the inhibitor LOC14 and subsequently examined for IAV burden, NA activity, cytokine, and immune response. IAV-NA interacts with PDIA3 and this interaction is required for NA activity. PDIA3 ablation or inhibition decreased NA activity, viral burden, and inflammatory response in lung epithelial cells. LOC14 treatment significantly attenuated the influenza-induced inflammatory response in mice including the overall viral burden. These results provide evidence for PDIA3 inhibition suppressing NA activity, potentially providing a novel platform for host-targeted antiviral therapies.

The population structure of Jujubinus striatus and Jujubinus exasperatus (Trochidae), common gastropod grazers of Posidonia oceanica leaves, was investigated in the seagrass bed off Lacco Ameno of Ischia (Gulf of Naples). Sampling was performed monthly, from July 1981 to June 1982, at five stations along a depth gradient (1, 3, 10, 15 and 25 m), using a hand-towed net. Throughout the study period, both populations were characterised by seasonal fluctuations in abundance, with a total of 550 individuals counted and measured. The two populations analysed showed different distributional trends along the depth gradient. Jujubinus striatus settled and occurred mainly at shallower stands (1–3 m depth), while J. exasperatus was found deeper (10–15 m). Both species are semelparous. Juveniles and small individuals (shell height < 4 mm) were mainly found during the late winter and early spring months. The survivorship curves of both Jujubinus species showed a very low mortality rate in the first few months after settlement. Demographic analysis suggests an indeterminate growth rate after sexual maturity, with a lifespan of about 22 months for J. striatus and 17 months for J. exasperatus. For both species the growth rate is fast during the first couple of months after settlement. The findings of this study, compared with earlier work, reveal a certain number of shared traits in the life cycle of the most common gastropod species living on the leaves of P. oceanica seagrass: semelparous reproduction, spring settlement, fast early growth and short lifespan (2 years maximum).

Mitochondria regulate a myriad of cellular functions. Dysregulation of mitochondrial control within airway epithelial cells has been implicated in the pro-inflammatory response to allergens in asthma patients. Because of their multifaceted nature, mitochondrial structure must be tightly regulated through fission and fusion. Dynamin Related Protein 1 (DRP1) is a key driver of mitochondrial fission. During allergic asthma, airway epithelial mitochondria appear smaller and structurally altered. The role of DRP1-mediated mitochondrial fission, however, has not been fully elucidated in epithelial response to allergens. We used a Human Bronchial Epithelial Cell line (HBECs), primary Mouse Tracheal Epithelial Cells (MTECs), and conditional DRP1 ablation in lung epithelial cells to investigate the impact of mitochondrial fission on the pro-inflammatory response to house dust mite (HDM) in vitro and in vivo. Our data suggest that, following HDM challenge, mitochondrial fission is rapidly upregulated in airway epithelial cells and precedes production of pro-inflammatory cytokines and chemokines. Further, deletion of Drp1 in lung epithelial cells leads to decreased fission and enhanced pro-inflammatory signaling in response to HDM in vitro, as well as enhanced airway hyper-responsiveness (AHR), inflammation, differential mucin transcription, and epithelial cell death in vivo. Mitochondrial fission, therefore, regulates the lung epithelial pro-inflammatory response to HDM.

Protein disulfide isomerases (PDI) are a family of redox chaperones that catalyze formation or isomerization of disulfide bonds in proteins. Previous studies have shown that one member, PDIA3, interacts with influenza A virus (IAV) hemagglutinin (HA), and this interaction is required for efficient oxidative folding of HA in vitro. However, it is unknown whether these host-viral protein interactions occur during active infection and whether such interactions represent a putative target for the treatment of influenza infection. Here we show that PDIA3 is specifically upregulated in IAV-infected mouse or human lung epithelial cells and PDIA3 directly interacts with IAV-HA. Treatment with a PDI inhibitor, LOC14 inhibited PDIA3 activity in lung epithelial cells, decreased intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in both H1N1 (A/PR8/34) and H3N2 (X31, A/Aichi/68) infected lung epithelial cells. These reduced disulfide bond formation significantly decreased viral burden, and also pro-inflammatory responses from lung epithelial cells. Lung epithelial-specific deletion of PDIA3 in mice resulted in a significant decrease in viral burden and lung inflammatory-immune markers upon IAV infection, as well as significantly improved airway mechanics. Taken together, these results indicate that PDIA3 is required for effective influenza pathogenesis in vivo, and pharmacological inhibition of PDIs represents a promising new anti-influenza therapeutic strategy during pandemic and severe influenza seasons.

To simulate clinical trials to assess overall survival (OS) benefit of bevacizumab in combination with chemotherapy in selected patients with gastric cancer (GC), a modeling framework linking OS with tumor growth inhibition (TGI) metrics and baseline patient characteristics was developed. Various TGI metrics were estimated using TGI models and data from two phase III studies comparing bevacizumab plus chemotherapy vs. chemotherapy as first‐line therapy in 976 GC patients. Time‐to‐tumor‐growth (TTG) was the best TGI metric to predict OS. TTG, Eastern Cooperative Oncology Group (ECOG) score, albumin level, and Asian ethnicity were significant covariates in the final OS model. The model correctly predicted a decreased hazard ratio favorable to bevacizumab in patients with high baseline plasma VEGF‐A above the median of 113.4 ng/L. Based on trial simulations, in trials enrolling patients with elevated baseline plasma VEGF‐A (500 patients per arm), the expected hazard ratio was 0.82 (95% prediction interval: 0.70–0.95), independent of ethnicity.

The solar energetic particle (SEP) events from impulsive solar flares are often characterized by short-timescale modulations affecting, at the same time, particles with different energies. Several models and simulations suggest that these modulations are observed when SEPs propagate through magnetic structures with a different connection with the flare site. However, in situ observations rarely showed clear magnetic signatures associated with these modulations. In this paper we used the Grad–Shafranov reconstruction to perform a detailed analysis of the local magnetic field topology during the SEP event of 9–10 January 1999, characterized by several SEP dropouts. An optimization procedure is used to identify, during this SEP event, the magnetic structures which better satisfy the Grad–Shafranov assumptions and to evaluate the direction of their invariant axis. We found that these two-dimensional structures, which are flux ropes or current sheets with a more complex field topology, are generally associated with the maxima in the SEP counts. This association suggests that the SEPs propagate within these structures and, since their gyration radii is much smaller than the transverse dimension of these structure, cannot escape from them.

Three years after the first report of Lutzomyia longipalpis in Clorinda, Argentina, a border city near Asunción, Paraguay, the city was surveyed again. Lu. longipalpis was found clustered in the same neighbourhoods in 2007 as in 2004, even though the scattered distribution of canine visceral leishmaniasis was more related to the traffic of dogs through the border.

The polar solar wind is a fast, tenuous and steady flow that, with the exception of a relatively short phase around the Sun's activity maximum, fills the high-latitude heliosphere. The polar wind properties have been extensively investigated by Ulysses, the first spacecraft able to perform in-situ measurements in the high-latitude heliosphere. The out-of-ecliptic phases of Ulysses cover about seventeen years. This makes possible to study heliospheric properties at high latitudes in different solar cycles. In the present investigation we focus on hourly- to daily-scale fluctuations of the polar wind velocity. Though the polar wind is a quite uniform flow, fluctuations in its velocity do not appear negligible. A simple way to characterize wind velocity variations is that of performing a multi-scale statistical analysis of the wind velocity differences. Our analysis is based on the computation of velocity differences at different time lags and the evaluation of statistical quantities (mean, standard deviation, skewness, and kurtosis) for the different ensembles. The results clearly show that, though differences exist in the three-dimensional structure of the heliosphere between the investigated solar cycles, the velocity fluctuations in the core of polar coronal holes exhibit essentially unchanged statistical properties.

This study focuses on the role that magnetically dominated fluctuations have within the solar wind MHD turbulence. It is well known that, as the wind expands, magnetic energy starts to dominate over kinetic energy but we lack of a statistical study apt to estimate the relevance of these fluctuations depending on wind speed, radial distance from the sun and heliographic latitude. Our results suggest that this kind of fluctuations can be interpreted as non-propagating structures, advected by the wind during its expansion. In particular, observations performed in the ecliptic revealed a clear radial dependence of these magnetic structures within fast wind, but not within slow wind. At short heliocentric distances (~0.3 AU) the turbulent population is largely dominated by Alfvénic fluctuations characterized by high values of normalized cross-helicity and a remarkable level of energy equipartition. However, as the wind expands, a new-born population, characterized by lower values of Alfvénicity and a clear imbalance in favor of magnetic energy becomes visible and clearly distinguishable from the Alfvénic population largely characterized by an outward sense of propagation. We estimate that more than 20% of all the analyzed intervals of hourly scale within fast wind are characterized by normalized cross-helicity close to zero and magnetic energy largely dominating over kinetic energy. Most of these advected magnetic structures result to be non-compressive and might represent the crossing of the border between adjacent flux tubes forming, as suggested in literature, the advected background structure of the interplanetary magnetic field. On the other hand, their features are also well fitted by the Magnetic Field Directional Turnings paradigm as proposed in literature.

Previous analyses have shown that polar wind fluctuations at MHD scales appear as a mixture of Alfvénic fluctuations and variations with an energy imbalance in favour of the magnetic term. In the present study, by separately examining the behaviour of kinetic and magnetic energies versus the Alfvénic correlation level, we unambiguously confirm that the second population is essentially related to a large increase of the magnetic energy with respect to that of the Alfvénic population. The relevant new result is that this magnetic population, though of secondary importance in terms of occurrence frequency, corresponds to a primary peak in the distribution of total energy. The fact that this holds in the case of polar wind, which is the least structured type of interplanetary plasma flow and with the slowest evolving Alfvénic turbulence, strongly suggests the general conclusion that magnetic structures cannot be neglected when modeling fluctuations for all kinds of wind regime.

Statistics associated with the fluctuations in solar wind parameters show a remarkable dependence on the solar activity phase. In particular, we focus our attention on the waiting-time statistics governing the MHD fluctuations of the z-component of the interplanetary magnetic field, which are important within the framework of the Sun-Earth connections, and briefly discuss the preliminary results. Data from several spacecrafts, covering different phases of the solar cycle and different radial distances, are used. We found that propagating Alfvénic fluctuations and convected structures strongly influence the statistics which vary from quasi-Poissonian to power law.

The mid-latitude phases of the Ulysses mission offer an excellent opportunity to investigate the solar wind originating near the coronal hole boundaries. Here we report on Alfvénic turbulence features, revealing a relevant presence of in-situ generated fluctuations, observed during the wind rarefaction phase that charaterizes the transition from fast to slow wind. Heavy-ion composition and magnetic field measurements indicate a strict time correspondence of the locally generated fluctuations with 1) the crossing of the interface between fast and slow wind and 2) the presence of strongly underwound magnetic field lines (with respect to the Parker spiral). Recent studies suggest that such underwound magnetic configurations correspond to fast wind magnetic lines that, due to footpoint motions at the Sun, have their inner leg transferred to slow wind and are stretched out by the velocity gradient. If this is a valid scenario, the existence of a magnetic connection across the fast-slow wind interface is a condition that, given the different state of the two kinds of wind, may favour the development of processes acting as local sources of turbulence. We suggest that heavy-ion effects could be responsible of the observed turbulence features.

The 3-D structure of the solar wind varies dramatically along the Sun's activity cycle. In the present paper we focus on some properties of the polar solar wind. This is a fast, teneous, and steady flow (as compared to low-latitude conditions) that fills the high-latitude heliosphere at low solar activity. The polar wind has been extensively investigated by Ulysses, the first spacecraft to perform in-situ measurements in the high-latitude heliosphere. Though the polar wind is quite a uniform flow, fluctuations in its velocity do not appear negligible. A simple way to characterize the solar wind structure is that of performing a multi-scale statistical analysis of the wind velocity differences. The occurrence frequency distributions of velocity differences at time lags from 1 to 1024h and the corresponding values of mean, standard deviation, skewness, and kurtosis have been obtained. A comparison with previous results in ecliptic wind at both low and high solar activity has been performed. It comes out that the kind of trend observed in the distributions for changing scale is the same for the different solar wind regimes. Differences between different flows just have an effect on the values of the distribution moments and the scales at which the transition from non-Gaussian to Gaussian-like behaviours occurs. This is typical of systems in which random fluctuations are mixed to coherent structures of some characteristic size, in other words, systems where long-range correlations cannot be neglected.

In spite of a large number of papers dedicated to the study of MHD turbulence in the solar wind there are still some simple questions which have never been sufficiently addressed, such as: a) Do we really know how the magnetic field vector orientation fluctuates in space? b) What are the statistics followed by the orientation of the vector itself? c) Do the statistics change as the wind expands into the interplanetary space? A better understanding of these points can help us to better characterize the nature of interplanetary fluctuations and can provide useful hints to investigators who try to numerically simulate MHD turbulence. This work follows a recent paper presented by some of the authors which shows that these fluctuations might resemble a sort of random walk governed by Truncated Lévy Flight statistics. However, the limited statistics used in that paper did not allow for final conclusions but only speculative hypotheses. In this work we aim to address the same problem using more robust statistics which, on the one hand, forces us not to consider velocity fluctuations but, on the other hand, allows us to establish the nature of the governing statistics of magnetic fluctuations with more confidence. In addition, we show how features similar to those found in the present statistical analysis for the fast speed streams of solar wind are qualitatively recovered in numerical simulations of the parametric instability. This might offer an alternative viewpoint for interpreting the questions raised above.

Observations by Ulysses during its second out-of-ecliptic orbit have shown that near the solar activity maximum the solar wind appears as a highly variable flow at all heliolatitudes. In the present study Ulysses data from polar latitudes are compared to contemporary ACE data in the ecliptic plane to search for the presence of latitudinal effects in the large-scale structure of the solar wind velocity. The investigated period roughly covers the Sun's magnetic polarity reversal. The Ulysses-ACE comparison is performed through a multi-scale statistical analysis of the velocity fluctuations at scales from 1 to 64 days. The results indicate that, from a statistical point of view, the character of the wind velocity structure does not appear to change remarkably with latitude. It is likely that this result is characteristic of the particular phase of the solar magnetic cycle.

Solar wind compressive fluctuations at MHD scales have been extensively studied in the past using data from spacecraft on the ecliptic plane. In the present study, based on plasma and magnetic field measurements by Ulysses, a statistical analysis of the compressive fluctuations observed in the high-latitude solar wind is performed. Data are from the first out-of-ecliptic orbit of Ulysses, when the Sun's activity is low and the high-latitude heliosphere is characterized by the presence of a fast and relatively steady solar wind, the polar wind. Our analysis is based on the computation of hourly-scale correlation coefficients for several pairs of solar wind parameters such as velocity, density, temperature, magnetic field magnitude, and plasma pressures (thermal, magnetic, and total). The behaviour of the fluctuations in terms of their amplitude has been examined, too, and comparisons with the predictions of existing models have been performed. The results support the view that the compressive fluctuations in the polar solar wind are mainly a superposition of MHD compressive modes and of pressure-balanced structures. Nearly-incompressible effects do not seem to play a relevant role. In conclusion, our results about compressive fluctuations in the polar wind do not appear as a break with respect to previous low-latitude observations. However, our study clearly indicates that in a homogeneous environment, as the polar wind, the pressure-balanced fluctuations tend to play a major role. Key words. Interplanetary physics (MHD waves and turbulence; solar wind plasma) – Space plasma physics (turbulence)

Launched on an elliptical high inclination orbit (apogee: 19.6 RE) since January 2001 the Cluster satellites have been conducting the first detailed three-dimensional studies of the high-latitude dayside magnetosphere, including the exterior cusp, neighbouring boundary layers and magnetopause regions. Cluster satellites carry the CIS ion spectrometers that provide high-precision, 3D distributions of low-energy (RE from the reconnection site.Key words. Magnetospheric physics (magnetopause, cusp, and boundary layers; magnetosheath) Space plasma physics (magnetic reconnection)