Left bundle branch pacing versus left ventricular septal pacing as a primary procedural endpoint during left bundle branch area pacing: Evaluation of two different implant strategies.

INTRODUCTION: Implant procedure features and clinical implications of left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) have not been yet fully described. We sought to compare two different left bundle branch area pacing (LBBAP) implant strategies: the first one accepting LVSP as a procedural endpoint and the second one aiming at achieving LBBP in every patient in spite of evidence of previous LVSP criteria. METHODS: LVSP was accepted as a procedural endpoint in 162 consecutive patients (LVSP strategy group). In a second phase, LBBP was attempted in every patient in spite of achieving previous LVSP criteria (n = 161, LBBP strategy group). Baseline patient characteristics, implant procedure, and follow-up data were compared. RESULTS: The final capture pattern was LBBP in 71.4% and LVSP in 24.2% in the LBBP strategy group compared to 42.7% and 50%, respectively, in the LVSP strategy group. One hundred and eighty-four patients (57%) had proven LBB capture criteria with a significantly shorter paced QRS duration than the 120 patients (37%) with LVSP criteria (115 ± 9 vs. 121 ± 13 ms, p < .001). Implant parameters were comparable between the two strategies but the LBBP strategy resulted in a higher rate of acute septal perforation (11.8% vs. 4.9%, p = .026) without any clinical sequelae. Patients with CRT indications significantly improved left ventricular ejection fraction (LVEF) during follow-up irrespective of the capture pattern (from 35 ± 11% to 45 ± 14% in proven LBBP, p = .024; and from 39 ± 13% to 47 ± 12% for LVSP, p = .003). The presence of structural heart disease and baseline LBBB independently predicted unsuccessful LBB capture. CONCLUSION: The LBBP strategy was associated with comparable implant parameters than the LVSP strategy but resulted in higher rates of septal perforation. Proven LBB capture and LVSP showed comparable effects on LVEF during follow-up.

Histological assessment of a novel de-epithelialization method for connective tissue grafts harvested from the palate. An experimental study in cadavers.

OBJECTIVES: This study aims to compare the histological outcomes of three distinct de-epithelialization methods used in (connective tissue grafts) CTG harvested from the palate. MATERIALS AND METHODS: An experimental study using nine cadaver head specimens was carried out to compare 3 different de-epithelialization techniques for CTG. Eighteen samples were randomly allocated to three study groups: bone scraper, diamond bur and extraoral removal with a scalpel. The main outcome variable was the graft surface percentage without epithelium remains. Additionally, the time employed, and the graft thickness were also measured. RESULTS: Sixteen CTGs were analyzed. The extraoral scalpel group presented a total surface area with no epithelium of 58.84% (22.68) and a mean de-epithelialization time of 3.7 min; the intraoral diamond bur group had 88.24% (41.3) of the surface with no epithelium and took 1.455 min, and the intraoral bone scraper showed 97.98% (5.99) of surface without epithelium and a mean time of 0.815 min (P < 0.05). Histological analysis showed significant differences between the bone scraper and the extraoral group (P = 0.009). CONCLUSION: The de-epithelialization technique with a bone scraper seems to be the most effective and fastest de-epithelialization technique for CTG. These findings need to be confirmed in future clinical studies with larger samples. CLINICAL RELEVANCE: The use of bone scrapers, could be a simple, effective and fast technique to de-epithelialize connective tissue grafts harvested from the palatal area for both novice and experienced surgeons.

Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice.

OBJECTIVE: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox-Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. METHODS: A multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. RESULTS: Eighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1-70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. CONCLUSION: This is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Non-infectious granulomatous disorders of the upper lip: clinicopathological analysis of 11 patients.

BACKGROUND: Non-infectious granulomatous disorders of the upper lip represent a special chapter of oral and maxillofacial pathology. In this work we report a case-series of this process, to analyse its main clinicopathological features and find differential data that allow us improve its diagnosis and understand its pathogenesis. METHODS: We present 11 cases of non-infectious granulomatous disorders of the upper lip, 8 women and 3 men with an age range of 29-84 years, who have been attended at the Oral Medicine Department of the IUCT (France) and the Oral Medicine Unit of the UPV/EHU (Spain). All clinicopathological data were collected in a specific protocol. RESULTS: We recognized 4 different subtypes of non-infectious granulomatous disorders of the upper lip: (1) associated with Crohn's disease (1 case), (2) associated with foreign body (2 cases), (3) associated with gingivitis lichenoid-like (4 cases), (4) idiopathic (4 cases). CONCLUSIONS: Clinicopathological differences were identified between these subtypes. A good differential diagnosis is necessary in all cases to rule out the presence of local or systemic etiopathogenic factors.

Pesticide Toxicity Hazard of Agriculture: Regional and Commodity Hotspots in Australia.

While the need to reduce the impacts of pesticide use on the environment is increasingly acknowledged, the existing data on the use of agricultural chemicals are hardly adequate to support this goal. This study presents a novel, spatially explicit, national-scale baseline analysis of pesticide toxicity hazard (the potential for chemicals to do harm). The results show an uneven contribution of land uses and growing regions toward the national aggregate toxicity hazard. A hectare of horticultural crops generates on average ten times more aquatic ecotoxicity hazard and five times more human toxicity hazard than a hectare of broadacre crops, but the higher yields and incomes in horticulture mean that both sectors are similar in terms of environmental efficiency. Livestock is the sector with the least contribution to overall hazard, even when the indirect hazard associated with feed is considered. Metrics such as pesticide use (kg/ha) or spray frequency (sprays/ha), commonly reported in highly aggregated forms, are not linearly related to toxicity hazard and are therefore less informative in driving reductions in impact. We propose toxicity hazard as a more suitable indicator for real-world risk than quantity of pesticide used, especially because actual risk can often be difficult to quantify. Our results will help broaden the discussion around pathways toward sustainability in the land-use sector and identify targeted priorities for action.

Osteosarcoma of the Trapezium.

Osteogenic sarcoma is a malignant tumor that rarely affects the hand. When it does, it most often involves the phalanges or metacarpal heads. We present the case of a 51-year-old woman with a low-grade osteosarcoma affecting the trapezium bone of her left hand. A total trapeziectomy with partial removal of the first metatarsal, scaphoid, trapezoid, and capitate bones was performed, and no adjuvant therapy was administered. Six years after the intervention, the patient is disease-free, with excellent functionality and yearly imaging tests showing no signs of recurrence.

Analysis of Playing Area Dimensions in Spanish Professional Soccer: Extrapolation to the Design of Small-Sided Games With Tactical Applications.

ABSTRACT: Caro, O, Zubillaga, A, Fradua, L, and Fernandez-Navarro, J. Analysis of playing area dimensions in Spanish professional soccer: Extrapolation to the design of small-sided games with tactical applications. J Strength Cond Res 35(10): 2795-2801, 2021-The aims of this study were to examine (a) the width and length dimensions of the playing area in 4v4 situations during competition, (b) the influence of the pitch zone where the ball is on 4v4 dimensions, and (c) the influence of match status on the dimensions of 4v4 situations. Data were collected from 25 matches from the Spanish La Liga of the 2007-2008 season using the Amisco system. Length, width, and individual playing area (IPA) of the rectangle that included the nearest 4 players to the ball from each team were collected in a total of 8,727 4v4 game situations. The pitch zone and match status were also considered for these 4v4 situations. To determine factors that affect 4v4 game situations, 1-way analysis of variance was used. The influence of the pitch zone where 4v4 situations took place showed significant differences (p < 0.001) between the zones where different principles of the game apply. The areas of the 4v4 situations ranged from 14.70 ± 4.69 × 17.18 ± 6 to 17.09 ± 5.16 × 20.34 ± 5.93 m, and the IPA of the 4v4 playing rectangle ranged from 46.33 ± 20 to 35.48 ± 16.95 m2, being larger in the central zones of the pitch. The length of the 4v4 rectangle showed a significant reduction in the closer zones to the goal. Match status did not affect the dimensions of these 4v4 game situations significantly. The findings of this study suggest that the size of 4v4 situations proposed for training should be designed according to the pitch zone where playing actions take place.

Personal Guides: Heterogeneous Robots Sharing Personal Tours in Multi-Floor Environments.

GidaBot is an application designed to setup and run a heterogeneous team of robots to act as tour guides in multi-floor buildings. Although the tours can go through several floors, the robots can only service a single floor, and thus, a guiding task may require collaboration among several robots. The designed system makes use of a robust inter-robot communication strategy to share goals and paths during the guiding tasks. Such tours work as personal services carried out by one or more robots. In this paper, a face re-identification/verification module based on state-of-the-art techniques is developed, evaluated offline, and integrated into GidaBot's real daily activities, to avoid new visitors interfering with those attended. It is a complex problem because, as users are casual visitors, no long-term information is stored, and consequently, faces are unknown in the training step. Initially, re-identification and verification are evaluated offline considering different face detectors and computing distances in a face embedding representation. To fulfil the goal online, several face detectors are fused in parallel to avoid face alignment bias produced by face detectors under certain circumstances, and the decision is made based on a minimum distance criterion. This fused approach outperforms any individual method and highly improves the real system's reliability, as the tests carried out using real robots at the Faculty of Informatics in San Sebastian show.

Fine-Tuning of GPCR-Chemokine Interactions. Design and Identification of Chemokine Analogues as Receptor Agonists, Biased Agonists, and Antagonists.

Chemokines play important roles in immune defense by directing migration of leukocytes and serve as key promoters of tumorigenesis and metastasis. This study explores the molecular mechanisms of recognition and activation of two homologous chemokine receptors, CXCR1 and CXCR2, using CXCL8 analogues with residue substitutions in the conserved Glu4Leu5Arg6 (ELR) triad. Analysis of the binding of CXCL8 analogues to CXCR1 is consistent with the two-site model for signal recognition of CXCR1, whereas analysis of the binding of CXCL8 analogues to CXCR2 supported a single-site model for signal recognition of CXCR2. The CXCL8-Arg6His analogue stimulated calcium release, phosphorylation of ERK1/2, and chemotaxis in cells expressing CXCR1. However, CXCL8-Arg6His failed to stimulate calcium release and chemotaxis in cells expressing CXCR2, although it stimulated phosphorylation of ERK1/2, indicating that CXCL8-Arg6His operated as a classical CXCR2 biased agonist. The CXCL8-Glu4AlaLeu5AlaArg6His analogue was inactive in cells expressing CXCR1 and CXCR2. These findings suggest that the Glu4Leu5 motif in CXCL8 is essential for activation of CXCR1 and CXCR2. Importantly, CXCL8-Glu4AlaLeu5AlaArg6His blocked specifically the calcium release and chemotaxis of cells expressing CXCR1 but not of cells expressing CXCR2. CXCL8-Glu4AlaLeu5AlaArg6His was identified as the first specific CXCR1 antagonist. The binding of CXCL8-ELR6H to CXCR1 created a Zn2+ coordination site at the receptor activation domain responsible for calcium release, as ZnCl2 specifically blocked CXCL8-Arg6His-induced calcium release without affecting CXCL8-induced calcium release. This work provides the basis for further exploration of the activation mechanisms of chemokine receptors and will assist in the design of the next generation of modulators of CXCR1 and CXCR2.

Dual-chambered membrane bioreactor for coculture of stratified cell populations.

We have developed a dual-chambered bioreactor (DCB) that incorporates a membrane to study stratified 3D cell populations for skin tissue engineering. The DCB provides adjacent flow lines within a common chamber; the inclusion of the membrane regulates flow layering or mixing, which can be exploited to produce layers or gradients of cell populations in the scaffolds. Computational modeling and experimental assays were used to study the transport phenomena within the bioreactor. Molecular transport across the membrane was defined by a balance of convection and diffusion; the symmetry of the system was proven by its bulk convection stability, while the movement of molecules from one flow line to the other is governed by coupled convection-diffusion. This balance allowed the perfusion of two different fluids, with the membrane defining the mixing degree between the two. The bioreactor sustained two adjacent cell populations for 28 days, and was used to induce indirect adipogenic differentiation of mesenchymal stem cells due to molecular cross-talk between the populations. We successfully developed a platform that can study the dermis-hypodermis complex to address limitations in skin tissue engineering. Furthermore, the DCB can be used for other multilayered tissues or the study of communication pathways between cell populations.

Diameter modulation of 3D nanostructures in focused electron beam induced deposition using local electric fields and beam defocus.

Focused electron beam induced deposition (FEBID) is a leading nanolithography technique in terms of resolution and the capability for three-dimensional (3D) growth of functional nanostructures. However, FEBID still presents some limitations with respect to the precise control of the dimensions of the grown nano-objects as well as its use on insulating substrates. In the present work, we overcome both limitations by employing electrically-biased metal structures patterned on the surface of insulating substrates. Such patterned metal structures serve for charge dissipation and also allow the application of spatially-dependent electric fields. We demonstrate that such electric fields can dramatically change the dimensions of the growing 3D nanostructures by acting on the primary electron beam and the generated secondary electrons. In the performed experiments, the diameter of Pt-C and W-C vertical nanowires grown on quartz, MgO and amorphous SiO2 is tuned by application of moderate voltages (up to 200 V) on the patterned metal microstructures during growth, achieving diameters as small as 50 nm. We identify two competing effects arising from the generated electric fields: a slight change in the primary beam focus point and a strong action on the secondary electrons. Beam defocus is exploited to achieve the in situ modulation of the diameter of 3D FEBID structures during growth.

Applying Time-Dependent Attributes to Represent Demand in Road Mass Transit Systems.

The development of efficient mass transit systems that provide quality of service is a major challenge for modern societies. To meet this challenge, it is essential to understand user demand. This article proposes using new time-dependent attributes to represent demand, attributes that differ from those that have traditionally been used in the design and planning of this type of transit system. Data mining was used to obtain these new attributes; they were created using clustering techniques, and their quality evaluated with the Shannon entropy function and with neural networks. The methodology was implemented on an intercity public transport company and the results demonstrate that the attributes obtained offer a more precise understanding of demand and enable predictions to be made with acceptable precision.

Suspended tungsten-based nanowires with enhanced mechanical properties grown by focused ion beam induced deposition.

The implementation of three-dimensional (3D) nano-objects as building blocks for the next generation of electro-mechanical, memory and sensing nano-devices is at the forefront of technology. The direct writing of functional 3D nanostructures is made feasible by using a method based on focused ion beam induced deposition (FIBID). We use this technique to grow horizontally suspended tungsten nanowires and then study their nano-mechanical properties by three-point bending method with atomic force microscopy. These measurements reveal that these nanowires exhibit a yield strength up to 12 times higher than that of the bulk tungsten, and near the theoretical value of 0.1 times the Young's modulus (E). We find a size dependence of E that is adequately described by a core-shell model, which has been confirmed by transmission electron microscopy and compositional analysis at the nanoscale. Additionally, we show that experimental resonance frequencies of suspended nanowires (in the MHz range) are in good agreement with theoretical values. These extraordinary mechanical properties are key to designing electro-mechanically robust nanodevices based on FIBID tungsten nanowires.

Empowerment of Patients with Hypertension through BPM, IoT and Remote Sensing.

Hypertension affects one in five adults worldwide. Healthcare processes require interdisciplinary cooperation and coordination between medical teams, clinical processes, and patients. The lack of patients' empowerment and adherence to treatment makes necessary to integrate patients, data collecting devices and clinical processes. For this reason, in this paper we propose a model based on Business Process Management paradigm, together with a group of technologies, techniques and IT principles which increase the benefits of the paradigm. To achieve the proposed model, the clinical process of the hypertension is analyzed with the objective of detecting weaknesses and improving the process. Once the process is analyzed, an architecture that joins health devices and environmental sensors, together with an information system, has been developed. To test the architecture, a web system connected with health monitors and environment sensors, and with a mobile app have been implemented.

Three-dimensional core-shell ferromagnetic nanowires grown by focused electron beam induced deposition.

Functional nanostructured materials often rely on the combination of more than one material to confer the desired functionality or an enhanced performance of the device. Here we report the procedure to create nanoscale heterostructured materials in the form of core-shell nanowires by focused electron beam induced deposition (FEBID) technologies. In our case, three-dimensional (3D) nanowires (<100 nm in diameter) with metallic ferromagnetic cores of Co- and Fe-FEBID have been grown and coated with a protective Pt-FEBID shell (ranging 10-20 nm in thickness) aimed to minimize the degradation of magnetic properties caused by the surface oxidation of the core to a non-ferromagnetic material. The structure, chemistry and magnetism of nanowire cores of Co and Fe have been characterized in Pt-coated and uncoated nanostructures to demonstrate that the morphology of the shell is conserved during Pt coating, the surface oxidation is suppressed or confined to the Pt layer, and the average magnetization of the core is strengthened up to 30%. The proposed approach paves the way to the fabrication of 3D FEBID nanostructures based on the smart alternate deposition of two or more materials combining different physical properties or added functionalities.

Attacking and defensive styles of play in soccer: analysis of Spanish and English elite teams.

The aim of this study was to define and categorise different styles of play in elite soccer and associated performance indicators by using factor analysis. Furthermore, the observed teams were categorised using all factor scores. Data were collected from 97 matches from the Spanish La Liga and the English Premier League from the seasons 2006-2007 and 2010-2011 using the Amisco® system. A total of 19 performance indicators, 14 describing aspects of attacking play and five describing aspects of defensive play, were included in the factor analysis. Six factors, representing 12 different styles of play (eight attacking and four defensive), had eigenvalues greater than 1 and explained 87.54% of the total variance. Direct and possession styles of play, defined by factor 1, were the most apparent styles. Factor analysis used the performance indicators to cluster each team's style of play. Findings showed that a team's style of play was defined by specific performance indicators and, consequently, teams can be classified to create a playing style profile. For practical implications, playing styles profiling can be used to compare different teams and prepare for opponents in competition. Moreover, teams could use specific training drills directed to improve their styles of play.

Land use efficiency: anticipating future demand for land-sector greenhouse gas emissions abatement and managing trade-offs with agriculture, water, and biodiversity.

Competition for land is increasing, and policy needs to ensure the efficient supply of multiple ecosystem services from land systems. We modelled the spatially explicit potential future supply of ecosystem services in Australia's intensive agricultural land in response to carbon markets under four global outlooks from 2013 to 2050. We assessed the productive efficiency of greenhouse gas emissions abatement, agricultural production, water resources, and biodiversity services and compared these to production possibility frontiers (PPFs). While interacting commodity markets and carbon markets produced efficient outcomes for agricultural production and emissions abatement, more efficient outcomes were possible for water resources and biodiversity services due to weak price signals. However, when only two objectives were considered as per typical efficiency assessments, efficiency improvements involved significant unintended trade-offs for the other objectives and incurred substantial opportunity costs. Considering multiple objectives simultaneously enabled the identification of land use arrangements that were efficient over multiple ecosystem services. Efficient land use arrangements could be selected that meet society's preferences for ecosystem service provision from land by adjusting the metric used to combine multiple services. To effectively manage competition for land via land use efficiency, market incentives are needed that effectively price multiple ecosystem services.

Chemokine CXCL1 dimer is a potent agonist for the CXCR2 receptor.

The CXCL1/CXCR2 axis plays a crucial role in recruiting neutrophils in response to microbial infection and tissue injury, and dysfunction in this process has been implicated in various inflammatory diseases. Chemokines exist as monomers and dimers, and compelling evidence now exists that both forms regulate in vivo function. Therefore, knowledge of the receptor activities of both CXCL1 monomer and dimer is essential to describe the molecular mechanisms by which they orchestrate neutrophil function. The monomer-dimer equilibrium constant (~20 µm) and the CXCR2 binding constant (1 nm) indicate that WT CXCL1 is active as a monomer. To characterize dimer activity, we generated a trapped dimer by introducing a disulfide across the dimer interface. This disulfide-linked CXCL1 dimer binds CXCR2 with nanomolar affinity and shows potent agonist activity in various cellular assays. We also compared the receptor binding mechanism of this dimer with that of a CXCL1 monomer, generated by deleting the C-terminal residues that stabilize the dimer interface. We observe that the binding interactions of the dimer and monomer to the CXCR2 N-terminal domain, which plays an important role in determining affinity and activity, are essentially conserved. The potent activity of the CXCL1 dimer is novel: dimers of the CC chemokines CCL2 and CCL4 are inactive, and the dimer of the CXC chemokine CXCL8 (which is closely related to CXCL1) is marginally active for CXCR1 but shows variable activity for CXCR2. We conclude that large differences in dimer activity among different chemokine-receptor pairs have evolved for fine-tuned leukocyte function.