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The complexity of flow conditions at junctions amplifies significantly with supercritical flow. It is a pronounced three-dimensional two-phased flow phenomenon, where standing waves with non-stationary water surface are formed. To analyse the hydrodynamic conditions at an asymmetric right-angled junction with incoming supercritical flows at Froude numbers between 2 and 12, an experimental approach was used. For a phenomenological determination of the relations between the integral parameters of incoming flows and the characteristics of standing waves at the junction area, water surface topographies for 168 scenarios at the junction were measured using non-intrusive measurement techniques. The new, phenomenologically derived equations allow for determination of location, height and extent of the main standing waves at the junction. Research results give important information on the processes and their magnitude for engineering applications.

This study investigates the effect of hydraulic shock waves on inactivation of MS-2 bacteriophage, a norovirus surrogate. A falling circular jet of water spiked with the MS-2 (∼1000 PFU/mL) was repeatedly impacted by a rotating blade, resulting in occurrence of hydraulic shock waves within the liquid region adjacent to the impact. The proof-of-concept rotational generator of hydraulic shock treating 9 L of water spiked with viruses was able to achieve 3 logs reduction of viral plaque count within 80-100 liquid passes at moderate blade impact velocities (namely, 70 and 88 m/s) despite the water temperature not exceeding 40 °C and no detectible cavitation. Within the first 20 liquid passes, most MS-2 capsid proteins were degraded, with their concentration reduced from 22 μg/mL to only 7.3 μg/mL. Due to the lack of further capsid protein destruction, additional reduction in MS-2 plaque count in subsequent 80 passes is indicative of damage inflicted to the viral recognition receptors. All this suggests that shockwaves of moderate amplitude (few tens of MPa) alone are sufficient for effective viral inactivation. Considering this and the device's good scalability potential, rotational hydraulic shock generators could prove effective in treating virus-contaminated waters., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The study investigated the methane production efficiency in a semi-continuous laboratory experiment with periodic feeding of wastewater sludge (WWS) as primary substrate and addition of whey (CW) and cow manure (CM). The short-term behavior of a real-scale anaerobic digester with WWS and the methane production improvements with different feeding mixtures of WWS, CW and CM were addressed. Gradual addition of CW to WWS (WWS:CW:CM = 70:20:0 to 70:55:0) increased the average daily methane production to 48.6 mL CH 4 /g COD/day and prevented reactor failure, but high VOA/TIC values showed that the reactors were conditionally stable evolution at an OLR of 8 g COD/L/day. Reactors that were additionally supplemented with CM (WWS:CW:CM = 70:55:10) achieved at least 12.3 % more methane than the reactors supplemented with WWS and CW alone. The highest methane production and process evolution in the reactors were achieved at OLRs between 7.5 and 8.7 g COD/L per day. After day 50, the addition of double the amount of CW further increased the methane production and VOA/TIC ratios. In this case, the OLR increased from 6.3 to 9.3 g COD/L/day. The concentration of propionic and acetic acid in all reactors increased above the recommended values and caused inhibition and instability. A strong positive Pearson correlation was found between the trace elements (Fe, Cu, Zn, Mn) detected by XRF. TE contributed to methane production, but to a lesser extent than TIC and NH4+-N. The simplified model successfully predicted methane production under a periodic feeding regime., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Slightly acidic (pH 5.1) waste sludge with 4.7 % Total Solids (TS) was treated on a laboratory scale pined disc rotary generator of hydrodynamic cavitation (PD RGHC). Influence of four rotor discs with different number of cavitation generation units (CGUs) was investigated: 8-pins, 12-pins, 16-pins and 8-prism elements. The effect of hydrodynamic cavitation (HC) was investigated by analyzing rheological properties, surface tension, dewaterability, and particle size distribution. After subjecting the sludge to 30 cavitation passes, the dewatering ability of the sludge significantly decreased, resulting in a more than two-fold increase in Capillary Suction Time (CST). All regimes were successful in disintegrating particles to smaller sizes. A slight increase of sludge surface tension was measured post cavitation. Cavitated samples displayed a zero-shear viscosity, in contrast to the untreated sample, where viscosity noticeably increased as shear stress decreased. HC did not improve methane yield. Statistically significant correlations between physio-chemical properties and apparent viscosity at low shear stress were identified. Although there were no discernible statistical differences in sludge characteristics, some trends are visible among investigated CGU designs and warrant further research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Turbulent free-surface flows are encountered in several engineering applications and are typically characterized by the entrainment of air bubbles due to intense mixing and surface deformation. The resulting complex multiphase structure of the air-water interface presents a challenge in precise and reliable measurements of the free-water-surface topography. Conventional methods by manometers, wave probes, point gauges or electromagnetic/ultrasonic devices are proven and reliable, but also time-consuming, with limited accuracy and are mostly intrusive. Accurate spatial and temporal measurements of complex three-dimensional free-surface flows in natural and man-made hydraulic structures are only viable by high-resolution non-contact methods, namely, LIDAR-based laser scanning, photogrammetric reconstruction from cameras with overlapping field of view, or laser triangulation that combines laser ranging with high-speed imaging data. In the absence of seeding particles and optical calibration targets, sufficient flow aeration is essential for the operation of both laser- and photogrammetry-based methods, with local aeration properties significantly affecting the measurement uncertainty of laser-based methods.

Novel therapeutic approaches combining immune-checkpoint inhibitors are needed to improve clinical outcomes for patients with cancer. Lymphocyte-activation gene 3 (LAG-3) is an immune-checkpoint molecule that inhibits T-cell activity and antitumor immune responses, acting through an independent mechanism from that of programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Here, we describe the development and preclinical characterization of relatlimab, a human antibody that binds to human LAG-3 with high affinity and specificity to block the interaction of LAG-3 with the ligands MHC II and fibrinogen-like protein-1, and to reverse LAG-3-mediated inhibition of T-cell function in vitro. Consistent with previous reports, in mouse models, the combined blockade of LAG-3 and PD-1 with surrogate antibodies resulted in enhanced antitumor activity greater than the individual blockade of either receptor. In toxicity studies in cynomolgus monkeys, relatlimab was generally well tolerated when combined with nivolumab. These results are consistent with findings from the RELATIVITY-047 phase II/III trial showing that relatlimab combined with nivolumab is a well-tolerated regimen that demonstrates superior progression-free survival compared with nivolumab monotherapy in patients with unresectable or metastatic melanoma., (©2022 The Authors; Published by the American Association for Cancer Research.)

Wastewater treatment plants, the last barrier between ever-increasing human activities and the environment, produce huge amounts, of unwanted semi-solid by-product - waste activated sludge. Anaerobic digestion can be used to reduce the amount of sludge. However, the process needs extensive modernisation and refinement to realize its full potential. This can be achieved by using efficient pre-treatment processes that result in high sludge disintegration and solubilization. To this end, we investigated the efficiency of a novel pinned disc rotational generator of hydrodynamic cavitation. The results of physical and chemical evaluation showed a reduction in mean particle size up to 88%, an increase in specific surface area up to 300% and an increase in soluble COD, NH 4 -N, NO 3 -N, PO 4 -P up to 155.8, 126.3, 250 and 29.7%, respectively. Microscopic images confirmed flocs disruption and damage to yeast cells and Epistilys species due to mechanical effects of cavitation such as microjets and shear forces. The observed cell ruptures and cracks were sufficient for the release of small soluble biologically relevant dissolved organic molecules into the bulk liquid, but not for the release of microbial DNA. Cavitation treatment also decreased total Pb concentrations by 70%, which was attributed to the reactions triggered by the chemical effects of cavitation. Additionally, the study confirmed the presence of microplastic particles and fibers of polyethylene, polyethylene terephthalate, polypropylene, and nylon 6 in the waste activated sludge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The Adriatic Sea, a semi-enclosed and vulnerable environment, deserves special attention regarding the risk of introducing Harmful Aquatic Organisms and Pathogens via ships' ballast water as new species findings occur at an alarming rate. This species introduction vector was addressed with the 2004 International Convention for the Control and Management of Ships' Ballast Water and Sediments, which entered into force in 2017. The efficient implementation of this convention calls for Adriatic States' cooperation on environmental specifics that have not been dealt with neither by national nor by international measures yet. Based on legal and institutional data gathered, and considering the regional maritime traffic and environmental specifics, this paper reveals that the integration of current environmental law commitments as well as a better dialogue between public institutions from shipping and environmental sectors may foster the implementation of ballast water management obligations through appropriate Adriatic States' cooperation., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Our aim was to compare the structure and management of conditions mimicking acute cerebrovascular events (ACE) defined as stroke or transient ischaemic attack between patients referred directly to a neurological emergency department (ED) by non-ambulance physicians, ambulance physicians and paramedics., Methods: This is a retrospective study of 802 consecutive patients referred to a Polish urban neurological ED with a prehospital suspicion of ACE between January and December 2014., Results: After proper neurological assessment, ACE was excluded in 258 (32.2%) patients. The ratios of neurological to non--neurological ACE mimics were similar across all groups (35:93 for non-ambulance physicians, 22:39 for ambulance physicians, and 28:39 for paramedics). The most frequent conditions mimicking ACE were vertigo (14.0%), headache (9.7%), seizures (7.0%), blood hypertension (7.0%), electrolyte and metabolic disturbances (5.4%), infections (4.7%) and syncope (4.3%). There were no major differences between patients with ACE-mimics referred by ambulance physicians and referred by paramedics in terms of demographic, previous medical history, extent of diagnostic workup, final diagnosis or further management (neurological admission in 42.6% and 28.4% of cases). However, the characteristics and management of ACE mimics referred by non-ambulance physicians were slightly different, including a lower need for hospital admission (neurological admission in 21.5% of cases)., Conclusions: There seem to be no major differences in the structure, early diagnostic approach or management of ACE mimics between referrals from ambulance physicians and ambulance paramedics, which provides reassurance to healthcare systems that rely solely on paramedics. Mimics referred by non ambulance physicians appear different in structure and are less resource-consuming.

Objective: The purpose of this prospective observational study was to describe the prevalence and adverse outcomes associated with seizure clusters (defined as ≥2 seizures in a 6-hour period) in a large sample of adult patients with a range of epilepsy severities and to identify clinical characteristics predictive of clustering., Methods: Patients maintained a seizure diary and were contacted monthly to verify compliance and data accuracy. Logistic regression models were utilized to test associations between individual patient demographic/clinical characteristics and seizure clustering. Fisher's exact test was utilized to test associations between rescue medication use and adverse seizure-related outcomes., Results: A total of 300 patients were followed prospectively for one year; 247 patients qualified for final analysis. Six-hour seizure clusters occurred in 45.8% of patients with active epilepsy at enrollment, including 62.7% of those with prior day-clusters and 30.0% of those without prior day-clusters. The odds of clustering were markedly greater among patients who reported a higher seizure frequency (>4 seizures per year vs. 1-4 seizures per year) (adjusted odds ratio (OR): 8.9; 95% confidence interval (CI): 3.2-24.6; p < 0.0001) and among patients with prior day-clusters (adjusted OR: 11.0; 95% CI: 1.2-104.2; p = 0.036). Rescue medication use was associated with significantly fewer injuries and emergency department visits, but rescue medication was underutilized., Conclusions: Seizure clusters are common, occurring in nearly half of adult patients with active epilepsy followed prospectively over one year, and are more frequent in those with higher seizure frequencies and prior day-clusters. Although underutilized, rescue medication was associated with fewer injuries and emergency department visit., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Peripartum cardiomyopathy, a type of dilated cardiomyopathy of unknown origin, occurs in previously healthy women in the final month of pregnancy and up to 5 months after delivery. Although the incidence is low--less than 0.1% of pregnancies--morbidity and mortality rates are high at 5% to 32%. The etiology of left ventricular dysfunction is unknown. Diagnosis of peripartum cardiomyopathy requires heightened awareness among multidisciplinary patient care teams and a high degree of suspicion. Confirmation involves the echocardiography reveals severe left ventricular failure. The outcome of peripartum cardiomyopathy is also highly variable. For some women, the clinical and echocardiographic status improves and sometimes returns to normal, whereas for others, the disease progresses to severe cardiac failure and even sudden cardiac death. Management of peripartum cardiomyopathy should aim first at improving heart-failure symptoms through conventional therapies, and then at administering targeted therapies.The prognosis is best when peripartum cardiomyopathy is diagnosed and treated early. Fortunately, despite a high risk of recurrence in subsequent pregnancies, many patients with peripartum cardiomyopathy recover within 3 to 6 months of disease onset. Future pregnancy is not recommended especially in patients with persistent left ventricular dysfunction because of the risk of dangerous complications.

Signaling pathways leading to natural killer (NK)-cell effector function are complex and incompletely understood. Here, we investigated the proximal signaling pathways downstream of the immunotyrosine-based activation motif (ITAM) bearing activating receptors. We found that the adaptor molecule SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is recruited to microclusters at the plasma membrane in activated NK cells and that this is required for initiation of downstream signaling and multiple NK-cell effector functions in vitro and in vivo. Surprisingly, we found that 2 types of proximal signaling complexes involving SLP-76 were formed. In addition to the canonical membrane complex formed between SLP-76 and linker for activation of T cells (LAT) family members, a novel LAT family-independent SLP-76-dependent signaling pathway was identified. The LAT family-independent pathway involved the SH2 domain of SLP-76 and adhesion and degranulation-promoting adaptor protein (ADAP). Both the LAT family-dependent and ADAP-dependent pathway contributed to interferon-gamma production and cytotoxicity; however, they were not essential for other SLP-76-dependent events, including phosphorylation of AKT and extracellular signal-related kinase and cellular proliferation. These results demonstrate that NK cells possess an unexpected bifurcation of proximal ITAM-mediated signaling, each involving SLP-76 and contributing to optimal NK-cell function.