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Alan Townsend is renowned for his significant contributions to understanding turbulence. He began his research career studying nuclear physics but this was disrupted by the Second World War, after which his focus shifted to the study of turbulent fluid flow. Collaborating with George Batchelor (FRS 1957), Townsend conducted pioneering experiments that uncovered the spatially intermittent nature of small-scale turbulence, profoundly shaping subsequent theoretical advances. He further shaped the field by pioneering an approach highlighting the importance of eddies, localized regions of coherent or well-ordered motion within turbulent flows. His work distinguished the eddies underlying different classes of flow, particularly turbulence in open flows, free from solid boundaries, such as jets and wakes, and flows near such boundaries, such as flow over an aeroplane or ship or within a pipe or channel. A significant seminal contribution was his attached eddy hypothesis, which provides the basis of a model for how eddies in surface-bounded flows exert control over the transport of momentum, energy and other properties within the flow. The enduring relevance of this work resonates through contemporary research, challenging established paradigms and guiding ongoing research endeavours across the globe.

Objective: Stereoelectroencephalography (SEEG) is an established invasive diagnostic technique for use in patients with drug-resistant focal epilepsy evaluated before resective epilepsy surgery. The factors that influence the accuracy of electrode implantation are not fully understood. Adequate accuracy prevents the risk of major surgery complications. Precise knowledge of the anatomical positions of individual electrode contacts is crucial for the interpretation of SEEG recordings and subsequent surgery. Methods: We developed an image processing pipeline to localize implanted electrodes and detect individual contact positions using computed tomography (CT), as a substitute for time-consuming manual labeling. The algorithm automates measurement of parameters of the electrodes implanted in the skull (bone thickness, implantation angle and depth) for use in modeling of predictive factors that influence implantation accuracy. Results: Fifty-four patients evaluated by SEEG were analyzed. A total of 662 SEEG electrodes with 8,745 contacts were stereotactically inserted. The automated detector localized all contacts with better accuracy than manual labeling (p < 0.001). The retrospective implantation accuracy of the target point was 2.4 ± 1.1 mm. A multifactorial analysis determined that almost 58% of the total error was attributable to measurable factors. The remaining 42% was attributable to random error. Conclusion: SEEG contacts can be reliably marked by our proposed method. The trajectory of electrodes can be parametrically analyzed to predict and validate implantation accuracy using a multifactorial model. Significance: This novel, automated image processing technique is a potentially clinically important, assistive tool for increasing the yield, efficiency, and safety of SEEG.

Croatia’s accession to the EU in 2013 left a mark on the Croatian Copyright Act. This mark was in the form of several amendments which aimed to implement the EU copyright harmonising measures. This implementation led to an uneven approach to copyright and related rights protection by prioritising implementation of the acquis communautaireover internal coherence and balance of rights. The new Croatian Copyright Act, adopted in October 2021, restores the internal coherence by substantially improving the layout of the act. Nevertheless, the formulation of some of the provisions it contains are inconsistent with international law, EU law and the Croatian Constitution. This paper focuses on three problematic legislative choices in the new Croatian Copyright Act – the gold-plating provision of the press publishers’ right, the automatic transfer of copyright made within public or state-owned institutions, and the nationalisation of audio-visual works.

The diagnosis and treatment of sinonasal small round epithelial/neuroepithelial malignancies depend on the expression of conventional neuroendocrine markers (NEMs), such as synaptophysin, chromogranin A, INSM1, and CD56/NCAM1. However, these tumors remain diagnostically challenging because of overlapping histologic and immunohistochemical features. The transcriptional regulators ASCL1, NEUROD1, POU2F3, and YAP1 are novel NEM (nNEM) used for the subtyping of small-cell lung cancer (SCLC). Here, we assessed the immunoexpression of nNEM in 76 sinonasal malignancies, including 27 olfactory neuroblastomas (ONB), 14 small-cell neuroendocrine carcinomas (SCNEC), 2 large-cell neuroendocrine carcinomas, 12 sinonasal undifferentiated carcinomas (SNUC), 7 olfactory carcinomas (OC), 11 SWI/SNF-deficient carcinomas, and 3 neuroendocrine tumors. We correlated nNEM expression with the extent of neuroendocrine (NE) differentiation, as defined by averaged conventional NEM expression (NE-high: H-score, ≥150; NE-low: H-score, <150). Dominant NE subtypes were defined by the nNEM with the highest H-score. Coexpression of 2 nNEM with <100 H-score difference defined a codominant NE subtype. NE differentiation positively correlated with NEUROD1 and negatively with YAP1 expression (P< .0001). ONB were NE-high (96%), and all were NEUROD1-dominant/POU2F3-negative/ASCL1-negative (low)/YAP1-negative (low). In contrast to ONB, all OC were NE-low, mostly (71%) codominant subtypes, NEUROD1-low (negative) (100%, P = .0001), and YAP1 high (71%; P = .0001). Most notably, all SNUC were POU2F3-(co)dominant/NEUROD1-negative irrespective of the IDH2mutations. Sinonasal tumors with high POU2F3expression showed enrichment for “tuft cell carcinoma” and tuft cell signatures (P = .009). Similar to SCLC, SCNEC was heterogeneous in terms of nNEM expression comprising several molecular subtypes, including ASCL1-(co)dominant (43%) cases. All SWI/SNF-deficient carcinomas were consistently ASCL1/NEUROD1/POU2F3-negative and YAP1-positive. ASCL1/NEUROD1/POU2F3/YAP1 are useful markers in the differential diagnosis of ONB, SNUC, OC, and SWI/SNF-deficient carcinomas. Subsets of SNUC and large-cell neuroendocrine carcinomas may represent tuft cell–like carcinomas, suggesting that the tuft cell could be explored as the cell of origin for these tumors. The therapeutic vulnerabilities associated with POU2F3 expression in SCLC suggest that a similar approach might be considered for POU2F3-positive carcinomas of the sinonasal tract. Given their diagnostic and possible therapeutic relevance, nNEM have the potential to transform the way we approach the diagnosis and management of sinonasal small round epithelial/neuroepithelial malignancies.

ObjectiveMRI is a cornerstone in presurgical evaluation of epilepsy. Despite guidelines, clinical practice varies. In light of the E‐PILEPSY pilot reference network, we conducted a systematic review and meta‐analysis on the diagnostic value of MRI in the presurgical evaluation of epilepsy patients. MethodsWe included original research articles on diagnostic value of higher MRI field strength and guideline‐recommended and additional MRI sequences in detecting an epileptogenic lesion in adult or paediatric epilepsy surgery candidates. Lesion detection rate was used as a metric in meta‐analysis. ResultsEighteen studies were included for MRI field strength and 25 for MRI sequences, none were free from bias. In patients with normal MRI at lower‐field strength, 3T improved lesion detection rate by 18% and 7T by 23%. Field strengths higher than 1.5T did not have higher lesion detection rates in patients with hippocampal sclerosis (HS). The lesion detection rate of epilepsy‐specific MRI protocols was 83% for temporal lobe epilepsy (TLE) patients. Dedicated MRI protocols and evaluation by an experienced epilepsy neuroradiologist increased lesion detection. For HS, 3DT1, T2, and FLAIR each had a lesion detection rate at around 90%. Apparent diffusion coefficient indices had a lateralizing value of 33% for TLE. DTI fractional anisotropy and mean diffusivity had a localizing value of 8% and 34%. SignificanceA dedicated MRI protocol and expert evaluation benefits lesion detection rate in epilepsy surgery candidates. If patients remain MRI negative, imaging at higher‐field strength may reveal lesions. In HS, apparent diffusion coefficient indices may aid lateralization and localization more than increasing field strength. DTI can add further diagnostic information. For other additional sequences, the quality and number of studies is insufficient to draw solid conclusions. Our findings may be used as evidence base for developing new high‐quality MRI studies and clinical guidelines.

Due to regional shortages some health services have proposed using surgical masks manufactured from sterilisation wrap. However, there has been little assessment of the safety of this practice. Therefore, we developed our own prototypes and evaluated whether they met regulatory standards.

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Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.

There is a need for scalable automated lab-on-chip systems incorporating precise hemodynamic control that can be applied to high-content screening of new more efficacious antiplatelet therapies. This paper reports on the development and characterization of a novel active micropump-mixer microfluidic to address this need. Using a novel reciprocating elastomeric micropump design, we take advantage of the flexible structural and actuation properties of this framework to manage the hemodynamics for on-chip platelet thrombosis assay on type 1 fibrillar collagen, using whole blood. By characterizing and harnessing the complex three-dimensional hemodynamics of the micropump operation in conjunction with a microvalve controlled reagent injection system we demonstrate that this prototype can act as a real-time assay of antiplatelet drug pharmacokinetics. In a proof-of-concept preclinical application, we utilize this system to investigate the way in which rapid dosing of human whole blood with isoform selective inhibitors of phosphatidylinositol 3-kinase dose dependently modulate platelet thrombus dynamics. This modular system exhibits utility as an automated multiplexable assay system with applications to high-content chemical library screening of new antiplatelet therapies.

ABSTRACTOriginal methodology for the calculation of island operation event occurrence possibility is proposed for the photovoltaic power plants connected to medium voltage grid. Within the methodology description, event fault tree with number of pairs of basic initial events is discussed, where probability for the basic events are defined and flow chart for the proposed calculation is given. The novelty in the approach for probability calculation includes also proposal for development of frequency distribution functions for concerned power generation and consumption variables which have to be modelled for the probability calculations, for which the triangular distributions curves have been chosen. Being boundary conditions for definition of non-detected island event, borders of non-detection zones are defined for the common island detection protection functions: over frequency and under frequency, over voltage and under voltage and rate of change of frequency functions. Comparison of the island event probability is presented on case study example, with conclusion that standard voltage and frequency protection alone are not satisfying, but ROCOF protection could be suitable, subject to particular local grid characteristic and calculative verification of probability.

Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications.

Supplemental Digital Content is available in the text

Supplemental Digital Content is available in the text

Self-assembled molecules (SAMs) form layers on copper that have an advantage compared to traditional corrosion inhibitors because of the significant decrease of chemical application. The protective properties of such films can be improved by different procedures of application of the SAM layer. In this work, a SAM layer of elaidic acid, a monounsaturated long-chain fatty acid with trans geometrical configuration, was applied on copper surface. Gamma irradiation was used to improve the protective properties of the SAM layer toward corrosion in 3% NaCl. Influence of gamma irradiation on such layer's properties was studied by different electrochemical techniques (polarization measurements, EIS), contact angle measurements and FTIR analysis. The results have shown that gamma irradiation at doses 0.5-5 kGy improves the protective properties of the SAM. The surface film became thinner due to stronger adsorption and resulted in better ordering of molecules on the surface of the oxide film although the polymerization involving the participation of oxygen molecules has been initiated by irradiation.

Renal denervation (RDN) has been shown in several studies to reduce blood pressure (BP) in patients with resistant hypertension (RH). Data on potential biomarkers associated with BP changes remain scarce. We evaluated whether soluble vascular endothelial growth factor receptor (sVEGFR-1) is affected by the procedure. A total of 57 patients with RH participated in this study. BP and heart rate were recorded at baseline and at 3 months follow-up, at which time blood samples were collected to determine the levels of sVEGFR-1, VEGF-A, VEGF-C, nitric oxide (NO), soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1. None of the biomarkers had a predictive value that could identify responders vs non-responders to RDN. However, sVEGFR-1 concentration was dramatically reduced after RDN (5913±385 vs 280±57 pg ml−1, P<0.001). At the same time VEGF-A levels were significantly increased (10.0±3.0 vs 55.5±7.9 pg ml−1, P<0.001), without significant changes in VEGF-C. NO levels were significantly increased after RDN in the whole group (82.6±6.2 vs 106.9±7.8 μM, P=0.021). Interestingly, the elevation in NO levels at 3 months was only seen in patients who demonstrated a reduction in systolic BP of ⩾10 mm Hg (78.9±8.3 vs 111.6±11.7 μM, P=0.018). We report a significant reduction in sVEGFR-1 levels after RDN procedure, which was accompanied by a significant increase in VEGF-A concentration as well as NO. Changes in plasma cytokines were not quantitatively linked to magnitude of BP reduction. An RDN-induced reduction in sVEGFR-1 plasma levels and increase in VEGF-A would raise the VEGF-A/sVEGFR-1 ratio, thereby increasing VEGF-A bioavailability to act on its full-length receptor and may contribute to the BP-lowering effect potentially via NO-mediated pathways.

Bromodomain (BD) and extra-terminal domain containing proteins (BET) are chromatin adapters that bind acetylated histone marks via two tandem BDs, BD1 and BD2, to regulate gene transcription. BET proteins are involved in transcriptional reprogramming in response to inflammatory stimuli. BET BD inhibitors (BETis) that are nonselective for BD1 or BD2 have recognized anti-inflammatory properties in vitro and counter pathology in models of inflammation or autoimmune disease. Although both BD1 and BD2 bind acetylated histone residues, they may independently regulate the expression of BET-sensitive genes. Here we characterized the ability of RVX-297, a novel orally active BETi with selectivity for BD2, to modulate inflammatory processes in vitro, in vivo, and ex vivo. RVX-297 suppressed inflammatory gene expression in multiple immune cell types in culture. Mechanistically, RVX-297 displaced BET proteins from the promoters of sensitive genes and disrupted recruitment of active RNA polymerase II, a property shared with pan-BETis that nonselectively bind BET BDs. In the lipopolysaccharide model of inflammation, RVX-297 reduced proinflammatory mediators assessed in splenic gene expression and serum proteins. RVX-297 also countered pathology in three rodent models of polyarthritis: rat and mouse collagen-induced arthritis, and mouse collagen antibody–induced arthritis. Further, RVX-297 prevented murine experimental autoimmune encephalomyelitis (a model of human multiple sclerosis) disease development when administered prophylactically and reduced hallmarks of pathology when administered therapeutically. We show for the first time that a BD2-selective BETi maintains anti-inflammatory properties and is effective in preclinical models of acute inflammation and autoimmunity.

IT IS GENERALLY ACCEPTED THAT VOLUNTARY WEIGHT CUTTING BEFORE ENTERING A COMPETITION HAS BECOME A HABITUAL PRACTICE AMONG COMBAT SPORTS ATHLETES. APART FROM ANTIDOPING REGULATIONS BANNING THE USE OF DIURETICS, THE OLYMPIC GOVERNING BODY HAS NOT ESTABLISHED POLICIES AIMED TO MONITOR AGGRESSIVE WEIGHT CUTTING. IT IS EXTREMELY IMPORTANT FOR COMBAT SPORTS ATHLETES TO REDUCE ADVERSE AND HEALTH-THREATENING SIDE EFFECTS EVOKED BY DIFFERENT APPROACHES TO ACHIEVING COMPETITION WEIGHT. THEREFORE, DEVELOPMENT AND IMPLEMENTATION OF RELIABLE AND ACCURATE HYDRATION ASSESSMENT TOOLS ARE WARRANTED. THE OBJECTIVE OF THIS ARTICLE IS TO REVIEW CURRENT RESEARCH FINDINGS OF MEASUREMENT CHARACTERISTICS CURRENTLY DEPLOYED IN COMBAT SPORTS RESEARCH.

The orogenic growth of the Domeyko Cordillera was induced by a positive tectonic inversion. In this work, we have validated this interpretation from new field data, which were combined with 2‐D reflection seismic profile interpretations obtained along the Central Andes forearc of northern Chile. To compare with this information, we performed a new series of Analog Models dealing with positive tectonic inversion. On the basis of this, we propose an integrated kinematic model that describes the relationships between extensional structures, inversion structures, and pure thrust faulting. The proposed model is developed with an initial syn‐rift phase related to the filling of half‐graben basins, followed by a positive tectonic inversion phase. Our models show two main structural styles: partially inverted normal faults and newly formed pure thrust faulting. The partial inversion of previous normal faults represents the initial stage of exhumation of the syn‐rift deposits. The pure thrusting consists of east‐verging faults, which decapitate early or partially inverted normal faults. The first type of structures are compared with west‐verging inverted, or partially inverted, normal faults, inversion anticlines, and buttressing structures, exposed on the western flank of the Domeyko Cordillera. The second type of structures are compared with the east‐verging thrust faults exposed on the eastern flank of the Domeyko Cordillera. Finally, we consider that the architecture of the Domeyko Fault System is associated with inversion structures and pure thrust faulting; being these faults first‐order structures that led to the orogenic growth of the Domeyko Cordillera from the Upper Cretaceous. Pure thrusting and inverted normal faults are described and interpretedAnalog models are performed to compare with the Domeyko Cordillera as a natural caseDecapitation of inverted normal faults by thrusting is proposed as first‐order structural mechanisms in the Domeyko Cordillera Pure thrusting and inverted normal faults are described and interpreted Analog models are performed to compare with the Domeyko Cordillera as a natural case Decapitation of inverted normal faults by thrusting is proposed as first‐order structural mechanisms in the Domeyko Cordillera

Objectives: Aim of the study was to investigate the effects of 1-year therapy by different proton pump inhibitors (PPIs) on epithelial tissue and surrounding inflammatory changes in Barrett’s oesophagus, in patients who have abandoned invasive therapy.Methods: A group of 120 patients (sampled in 60-month period, from 61201 upper gastrointestinal endoscopies) who were diagnosed both, endoscopically and pathohistologically with Barrett’s oesophagus, and who have abandoned invasive therapeutic approach were enrolled in study. Treatment with different PPIs was initiated and continued for a year. At the end of treatment, patients were reassessed by endoscopy with tissue biopsy and pathohistological analysis.Results: No difference in regenerating squamous epithelium or degree of dysplasia was seen between different treatment groups. Interestingly, most patients receiving pantoprazole (94%) ended up with thinner squamous epithel (P < 0.0001). The squamous epithel was consider thinner only if its total thickness, measured on histological specimen, was smaller for more than 50% of the thickness before therapy. Significantly less of difference (P < 0.0014) was seen with patients receiving lansoprazole (65%) and (P < 0.003) omeprazole (50%).Conclusion: Regeneration of the squamous epithel was the same for all PPIs but not good enough to stop the progression of the disease.

Objectives: Aim of the study was to investigate the effects of 1-year therapy by different proton pump inhibitors (PPIs) on epithelial tissue and surrounding inflammatory changes in Barrett’s oesophagus, in patients who have abandoned invasive therapy.Methods: A group of 120 patients (sampled in 60-month period, from 61201 upper gastrointestinal endoscopies) who were diagnosed both, endoscopically and pathohistologically with Barrett’s oesophagus, and who have abandoned invasive therapeutic approach were enrolled in study. Treatment with different PPIs was initiated and continued for a year. At the end of treatment, patients were reassessed by endoscopy with tissue biopsy and pathohistological analysis.Results: No difference in regenerating squamous epithelium or degree of dysplasia was seen between different treatment groups. Interestingly, most patients receiving pantoprazole (94%) ended up with thinner squamous epithel (P< 0.0001). The squamous epithel was consider thinner only if its total thickness, measured on histological specimen, was smaller for more than 50% of the thickness before therapy. Significantly less of difference (P< 0.0014) was seen with patients receiving lansoprazole (65%) and (P< 0.003) omeprazole (50%).Conclusion: Regeneration of the squamous epithel was the same for all PPIs but not good enough to stop the progression of the disease.

Spiradenocarcinoma is a rare skin adnexal neoplasm with potential for aggressive behavior, classified histologically into low- and high-grade tumors. Morphologically, low-grade tumors are thought to behave more favorably. Limited information is available, however, with only 18 published cases. To study their clinical behavior, histological features, and the diagnostic value of immunohistochemistry, 19 morphologically low-grade spiradenocarcinomas were retrieved and compared with 21 spiradenomas and cylindromas. H&E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB was performed. The tumors were solitary, measuring 0.8–7 cm (median: 2.7 cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53–92) without gender bias. Histologically, the tumors were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1–28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumors. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13–132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality. In this large study with long-term follow-up, we demonstrate that spiradenocarcinomas with low-grade morphology pursue an indolent course, characterized by local recurrence only. Metastases and disease-related mortality appear to be exceptional. Lack of MYB expression may be useful as an additional aid in the diagnosis of these challenging tumors.

Spiradenocarcinoma is a rare skin adnexal neoplasm with potential for aggressive behavior, classified histologically into low- and high-grade tumors. Morphologically, low-grade tumors are thought to behave more favorably. Limited information is available, however, with only 18 published cases. To study their clinical behavior, histological features, and the diagnostic value of immunohistochemistry, 19 morphologically low-grade spiradenocarcinomas were retrieved and compared with 21 spiradenomas and cylindromas. H&E-stained sections were reviewed, follow-up was obtained, and immunohistochemistry for Ki-67, p53 and, MYB was performed. The tumors were solitary, measuring 0.8–7 cm (median: 2.7 cm), with a predilection for the head and neck of elderly patients (median age: 72 years; range 53–92) without gender bias. Histologically, the tumors were multinodular and located in deep dermis and subcutis. A pre-existing spiradenoma was present in all cases. The malignant component was characterized by expansile growth with loss of the dual cell population, up to moderate cytological atypia and increased mitotic activity (median: 10/10 HPF; range 1–28). Additional findings included squamoid differentiation (n=9), necrosis (n=7), and ulceration (n=5). P53 expression was variable and no significant differences were noted in the benign compared with the malignant parts of the tumors. In contrast, in the malignant components the Ki-67 proliferative index was slightly increased, and MYB expression was lost. Follow-up (median: 67 months; range: 13–132) available for 16 patients (84%) revealed a local recurrence rate of 19% but no metastases or disease-related mortality. In this large study with long-term follow-up, we demonstrate that spiradenocarcinomas with low-grade morphology pursue an indolent course, characterized by local recurrence only. Metastases and disease-related mortality appear to be exceptional. Lack of MYB expression may be useful as an additional aid in the diagnosis of these challenging tumors.

Antigen (HSA) bound in immune complexes at equivalence with syngeneic anti-HSA antibodies elicit much stronger humoral immune response then soluble HSA. On the other hand, administration of immune complexes formed with xenogeneic (rabbit) anti-HSA antibodies suppressed humoral immune response against HSA, but not against rabbit IgG in mice. We suggest that immunization with antigen bound in immune complex might represent a powerful tool in enhancing humoral immune responses.

Biomaterials research for the discovery of new generation nanoparticles is one of the most active areas of nanotechnoloy. In the search of nature-made nanometer-sized objects, plant virus particles appear as symmetrically defined entities that can be formed by protein self-assembly. In particular, in the field of plant virology, there is plenty of literature available describing the exploitation of plant viral cages to produce safe vaccine vehicles and nanoparticles for drug delivery. In this context, we have investigated on the use of the artichoke mottled crinkle virus (AMCV) capsid both as a carrier of immunogenic epitopes and for the delivery of anticancer molecules. A dual approach that combines both in silicotools and experimental virology was applied for the rational design of immunologically active chimeric virus-like particles (VLPs) carrying immunogenic peptides. The atomic structures of wild type (wt) and chimeric VLPs were obtained by homology modeling. The effects of insertion of the HIV-1 2F5 neutralizing epitope on the structural stability of chimeric VLPs were predicted and assessed by detailed inspection of the nanoparticle intersubunit interactions at atomic level. Wt and chimeric VLPs, exposing on their surface the 2F5 epitope, were successfully produced in plants. In addition, we demonstrated that AMCV capsids could also function as drug delivery vehicles able to load the chemotherapeutic drug doxorubicin. To our knowledge, this is the first systematic predictive and empirical research addressing the question of how this icosahedral virus can be used for the production of both VLPs and viral nanoparticles for biomedical applications.

Renal denervation (RDN) has been demonstrated to reduce muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant hypertension. Whether alterations of arterial stiffness may contribute to BP-lowering effects of RDN is unknown.

To assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI. We retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome. Two patients underwent one-stage multimodal imageguided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. Nocorrelation between histopathological FCD subtype and seizure outcome was observed. Complete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.

Aims.To assess the practical localising value of subtraction ictal single‐photon emission computed tomography (SISCOM) coregistered with MRI and 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) in patients with extratemporal epilepsy and normal MRI. Methods.We retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome. Results.Two patients underwent one‐stage multimodal image‐guided surgery and the remaining 12 underwent long‐term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG‐PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. No correlation between histopathological FCD subtype and seizure outcome was observed. Conclusion.Complete resection of the dysplastic cortex localised by SISCOM, FDG‐PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non‐lesional extratemporal epilepsy.

The aim of this study was to investigate the efficiency of 1-H benzimidazole as a corrosion inhibitor in protection of cultural artifacts made of bronze. For that purpose1-H benzimidazole was studied on bare and patinated Cu-6Sn bronze, exposed to urban environments. Dissolution of bare and patinated bronze was investigated by potentiodynamic techniques and electrochemical impedance spectroscopy. The microstructure of the bronze surface exposed to the inhibitor was examined by SEM/EDS. 1-H benzimidazole showed a very good protective effect in sulfate/carbonate media which simulate urban acid rainfall. Benzimidazole protected the Cu-6Sn bronze covered by electrochemical patina by stabilizing the patina layer and by slowing down dissolution of bronze substrate.

A personal narrative is presented which explores the author's experience of shopping at Farmer's Market two days after the National Aeronautics and Space Administration (NASA) launched its biggest lunar probe to the moon.

Background:There is a well-known association between perception of poor physical health and higher rates of physical and psychological morbidity. However, little is known about the possible link between perception of health and suicidality. Aims:The study examines the relationship between perception of poor health and suicidal ideation and suicide attempt among adults in the community. Methods:Data were drawn from the National Comorbidity Survey (n= 5,877), a representative sample of individuals 15–54 years of age in the United States. Multiple logistic regression analyses were used to determine the relationship between perception of poor health and the likelihood of suicidal ideation and suicide attempt. Sociodemographic characteristics, comorbid mental disorders, and physical illnesses were adjusted for in the final model. Results:Perception of poor health was associated with a significantly increased likelihood of suicidal ideation (OR = 2.14 (1.36, 3.35) and suicide attempt (OR = 2.03 (1.06, 3.91)), which persisted after adjusting for differences in sociodemographic characteristics, mental disorders, and self-reported physical illnesses. Conclusions:Our findings provide initial evidence that perception of poor health is associated with a significantly increased likelihood of suicidal ideation and suicide attempt among adults in the community.

Sturge‐Weber syndrome is a neurocutaneous disorder classically characterized by the presence of facial port‐wine stain and ipsilateral leptomeningeal angiomatosis. It is often associated with refractory epilepsy which requires surgical treatment. We present a case of a patient who initially presented with partial seizures of temporo‐occipital origin, ipsilateral to the pial angiomatosis. During the course of the disease, the patient developed medically refractory epilepsy with partial seizures originating predominantly from the contralateral temporo‐occipital area as well as myoclonic and myoclonicastatic seizures. Resection of the occipital and temporal lobe affected by the pial angioma resulted in favourable outcome. Bilateral dysfunction observed in Sturge‐Weber syndrome may result in an increased capability of focal discharges to generate synchronous epileptiform activity leading to an increased incidence of generalised seizures, most probably via a mechanism of secondary bilateral synchrony. [Published with video sequences] Content available: Video

Sturge-Weber syndrome is a neurocutaneous disorder classically characterized by the presence of facial port-wine stain and ipsilateral leptomeningeal angiomatosis. It is often associated with refractory epilepsy which requires surgical treatment. We present a case of a patient who initially presented with partial seizures of temporo-occipital origin, ipsilateral to the pial angiomatosis. During the course of the disease, the patient developed medically refractory epilepsy with partial seizures originating predominantly from the contralateral temporo-occipital area as well as myoclonic and myoclonicastatic seizures. Resection of the occipital and temporal lobe affected by the pial angioma resulted in favourable outcome. Bilateral dysfunction observed in Sturge-Weber syndrome may result in an increased capability of focal discharges to generate synchronous epileptiform activity leading to an increased incidence of generalised seizures, most probably via a mechanism of secondary bilateral synchrony.

Mice lacking Tbk1 activity exhibit immune cell infiltrates in multiple tissues, altered circulating immune cell compartments, and increased susceptibility to LPS‐induced lethality. TBK1 is critical for immunity against microbial pathogens that activate TLR4‐ and TLR3‐dependent signaling pathways. To address the role of TBK1 in inflammation, mice were generated that harbor two copies of a mutant Tbk1allele. This Tbk1Δallele encodes a truncated Tbk1Δprotein that is catalytically inactive and expressed at very low levels. Upon LPS stimulation, macrophages from Tbk1Δ/Δmice produce normal levels of proinflammatory cytokines (e.g., TNF‐α), but IFN‐β and RANTES expression and IRF3 DNA‐binding activity are ablated. Three‐month‐old Tbk1Δ/Δmice exhibit mononuclear and granulomatous cell infiltrates in multiple organs and inflammatory cell infiltrates in their skin, and they harbor a 2‐fold greater amount of circulating monocytes than their Tbk1+/+and Tbk1+/Δlittermates. Skin from 2‐week‐old Tbk1Δ/Δmice is characterized by reactive changes, including hyperkeratosis, hyperplasia, necrosis, inflammatory cell infiltrates, and edema. In response to LPS challenge, 3‐month‐old Tbk1Δ/Δmice die more quickly and in greater numbers than their Tbk1+/+and Tbk1+/Δcounterparts. This lethality is accompanied by an overproduction of several proinflammatory cytokines in the serum of Tbk1Δ/Δmice, including TNF‐α, GM‐CSF, IL‐6, and KC. This overproduction of serum cytokines in Tbk1Δ/Δmice following LPS challenge and their increased susceptibility to LPS‐induced lethality may result from the reactions of their larger circulating monocyte compartment and their greater numbers of extravasated immune cells.

We have recently described an efficient transient expression system mediated by Agrobacterium tumefaciens for the production of HIV-1 Nef protein in Nicotiana benthamiana plants. In order to enhance the yield of recombinant protein we assayed the effect of three gene- silencing viral suppressor proteins (P25 of Potato Virus X, P19 of Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef expression levels. Results demonstrated that AMCV-P19 gave the highest Nef yield (1.3% of total soluble protein) and that this effect was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms. Here we report additional data on the production of different heterologous proteins including human immunoglobulin heavy and light chains and a virus coat protein that demonstrate the robustness of this co-agroinfiltration expression system boosted by the AMCV-P19 gene-silencing suppressor.

Importance of the field:Fas receptor is a mediator of the external apoptotic pathway in many cells and tissues. It is proposed that Fas receptor mediates osteoresorptive effects of estrogen deficiency and local/systemic inflammation.Areas covered in this review:This review covers the past two decades of research on the expression and function of the Fas–Fas ligand system on bone cells, involvement in the pathogenesis of osteoresorption and potential therapeutic modulation.What the reader will gain:We review the structure, biological function and intracellular signaling pathways of the Fas–Fas ligand system emphasizing the role of the non-apoptotic signaling pathways in bone cells, particularly osteoblast differentiation. We also present data on the in vitroexpression and function of the Fas–Fas ligand system on osteoblast/osteoclast lineage cells, animal and human studies confirming its involvement in osteoresorptive disorders and potential therapeutic approaches to modulate its function.Take home message:Tissue specific therapeutic approaches need to be established to modify the Fas–Fas ligand system in osteoresorptive disorders as systemic targeting has many side effects. The most promising approach would be to target Fas signaling molecules coupled with osteoblast/osteoclast differentiation pathways, but a precise definition of these targets is still needed.

High‐frequency activity has been described as having a role in the initiation of epileptic seizures. The case of a patient with refractory bitemporal epilepsy is presented. Extraoperative monitoring with depth and subdural electrodes revealed an ictal pattern with a build‐up of high‐frequency (> 80 Hz) activity originating in the cortex, with spread to both hippocampi. This observation was only revealed with the use of high‐pass filtering, and represented crucial information that significantly influenced the decision about the side, localization and extent of resection. Removal of the cortex generating high‐frequency activity, led to cessation of seizures in this patient. Current knowledge about the role of high‐frequency activity and the case presented here support the importance of recording with equipment capable of detecting fast activity during the presurgical invasive monitoring. An active search for a high‐frequency seizure onset zone in patients with structurally‐unaffected hippocampi may improve the outcome beyond that possible with conventional bandwidth, invasive EEG recordings. [Published with video sequences]

To determine the association between sleep, mental disorders, and suicidal ideation (SI) and suicide attempt (SA) among adults in the community.

Moderate alcohol intake lowers coronary heart disease risk. Because polymorphonuclear neutrophils (PMN) and monocytes (Mo) play a role in atherosclerotic plaque destabilization we investigated in vitro effects of clinically relevant concentrations of ethanol (0.05, 0.125, 0.25, and 0.5%) and its metabolite acetaldehyde (0.0625, 0.125, and 0.5 mM) on human PMN and Mo phagocytic functions. PMN and Mo from healthy volunteers were separated and purified according standard methods and the following parameters were determined: phagocytic activity (percent of phagocytes with at least one ingested particle), ingestion index (number of ingested particles per 100 phagocytic cells), and intracellular killing (percent of dead ingested particles per 100 phagocytes) using acridine orange method and living yeast cells as targets. Reactive oxygen species (ROS) formation of ethanol-treated PMN and Mo was evaluated using 2,7-dichlorofluorescin method and results were expressed as percent of fluorescence-positive cells. Ethanol and acetaldehyde significantly reduced PMN phagocytic functions, with the exception of phagocytic activity, starting at 0.125% for ethanol and 0.0625 mM for acetaldehyde. Mo ingestion and microbicidity were decreased at ethanol concentrations of 0.5% without effect on Mo phagocytic activity. Acetaldehyde impaired Mo ingestion ability starting at 0.0625 mM and phagocytic activity at 0.5 mM while was without effect on Mo microbicidity. ROS production was significantly increased at ethanol concentrations 0.25 and 0.5% in PMN and at 0.5% in Mo. These results might partly explain the benefitial role of moderate use of alcohol on cardiovascular disease.

Experimental dual plane particle image velocimetry (PIV) data are assessed using direct numerical simulation (DNS) data of a similar flow with the aim of studying the effect of averaging within the interrogation window. The primary reason for the use of dual plane PIV is that the entire velocity gradient tensor and hence the full vorticity vector can be obtained. One limitation of PIV is the limit on dynamic range, while DNS is typically limited by the Reynolds number of the flow. In this study, the DNS data are resolved more finely than the PIV data, and an averaging scheme is implemented on the DNS data of similar Reynolds number to compare the effects of averaging inherent to the present PIV technique. The effects of averaging on the RMS values of the velocity and vorticity are analyzed in order to estimate the percentage of turbulence intensity and enstrophy captured for a given PIV resolution in turbulent boundary layers. The focus is also to identify vortex core angle distributions, for which the two-dimensional and three-dimensional swirl strengths are used. The studies are performed in the logarithmic region of a turbulent boundary layer at z+= 110 from the wall. The dual plane PIV data are measured in a zero pressure gradient flow over a flat plate at Reτ= 1,160, while the DNS data are extracted from a channel flow at Reτ= 934. Representative plots at various wall-normal locations for the RMS values of velocity and vorticity indicate the attenuation of the variance with increasing filter size. Further, the effect of averaging on the vortex core angle statistics is negligible when compared with the raw DNS data. These results indicate that the present PIV technique is an accurate and reliable method for the purposes of statistical analysis and identification of vortex structures.Experimental dual plane particle image velocimetry (PIV) data are assessed using direct numerical simulation (DNS) data of a similar flow with the aim of studying the effect of averaging within the interrogation window. The primary reason for the use of dual plane PIV is that the entire velocity gradient tensor and hence the full vorticity vector can be obtained. One limitation of PIV is the limit on dynamic range, while DNS is typically limited by the Reynolds number of the flow. In this study, the DNS data are resolved more finely than the PIV data, and an averaging scheme is implemented on the DNS data of similar Reynolds number to compare the effects of averaging inherent to the present PIV technique. The effects of averaging on the RMS values of the velocity and vorticity are analyzed in order to estimate the percentage of turbulence intensity and enstrophy captured for a given PIV resolution in turbulent boundary layers. The focus is also to identify vortex core angle distributions, for which the two-dimensional and three-dimensional swirl strengths are used. The studies are performed in the logarithmic region of a turbulent boundary layer at z+= 110 from the wall. The dual plane PIV data are measured in a zero pressure gradient flow over a flat plate at Reτ= 1,160, while the DNS data are extracted from a channel flow at Reτ= 934. Representative plots at various wall-normal locations for the RMS values of velocity and vorticity indicate the attenuation of the variance with increasing filter size. Further, the effect of averaging on the vortex core angle statistics is negligible when compared with the raw DNS data. These results indicate that the present PIV technique is an accurate and reliable method for the purposes of statistical analysis and identification of vortex structures.

Symmetry properties of a class of toroidal molecular graphs, arising as covers of certain bipartite cubic Cayley graphs of dihedral groups, are studied. Although these symmetries make all vertices and all edges indistinguishable, they imply intrinsic chirality.

Simultaneous dual-plane PIV experiments, which utilized three cameras to measure velocity components in two differentially separated planes, were performed in streamwise-spanwise planes in the log region of a turbulent boundary layer at a moderate Reynolds number (Reτ ∼ 1100). Stereoscopic data were obtained in one plane with two cameras, and standard PIV data were obtained in the other with a single camera. The scattered light from the two planes was separated onto respective cameras by using orthogonal polarizations. The acquired datasets were used in tandem with continuity to compute all 9 velocity gradients, the complete vorticity vector and other invariant quantities. These derived quantities were employed to analyze and interpret the structural characteristics and features of the boundary layer. Sample results of the vorticity vector are consistent with the presence of hairpin-shaped vortices inclined downstream along the streamwise direction. These vortices envelop low speed zones and generate Reynolds shear stress that enhances turbulence production. Computation of inclination angles of individual eddy cores using the vorticity vector suggests that the most probable inclination angle is 35° to the streamwise-spanwise plane with a resulting projected eddy inclination of 43° in the streamwise-wall-normal plane.Simultaneous dual-plane PIV experiments, which utilized three cameras to measure velocity components in two differentially separated planes, were performed in streamwise-spanwise planes in the log region of a turbulent boundary layer at a moderate Reynolds number (Reτ ∼ 1100). Stereoscopic data were obtained in one plane with two cameras, and standard PIV data were obtained in the other with a single camera. The scattered light from the two planes was separated onto respective cameras by using orthogonal polarizations. The acquired datasets were used in tandem with continuity to compute all 9 velocity gradients, the complete vorticity vector and other invariant quantities. These derived quantities were employed to analyze and interpret the structural characteristics and features of the boundary layer. Sample results of the vorticity vector are consistent with the presence of hairpin-shaped vortices inclined downstream along the streamwise direction. These vortices envelop low speed zones and generate Reynolds shear stress that enhances turbulence production. Computation of inclination angles of individual eddy cores using the vorticity vector suggests that the most probable inclination angle is 35° to the streamwise-spanwise plane with a resulting projected eddy inclination of 43° in the streamwise-wall-normal plane.