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Functionally graded hardmetals offer a superior combination of fracture toughness and wear resistance and alleviate the compromise that conventional hardmetals must face between these two material properties. In tooling applications, they exhibit superior cutting performance compared to the conventionally employed hardmetals. Traditionally, graded tools are enabled by a surface treatment with nitrogen or carbon. This enables a tungsten carbide–cobalt (WC–Co) tool with a surface layer containing less cobalt (Co) than the core of the part. With this Co gradation, the wear properties can be improved due to the harder surface. If different loads act at different points in a tool and the geometric complexity of a tool increases, the requirements for a targeted positioning of the Co gradients become higher. A simple surface treatment does not allow a flexible distribution of the desired gradients. Binder jetting provides a solution to produce location-independent graded structures. In this work, the process was evaluated for the generation of Co gradients in WC–Co structures. Inks loaded with graphite particle contents of 2.5, 5, 7.5, and 10 m% were used to create differences in the carbon content in the green part. This induced a Co migration during the liquid phase sintering process. The sintering parameters were varied in time and temperature and studied regarding their effect on the microstructure and the porosity, the formation of the Co gradient, and the hardness. At low sintering times and temperatures, all carbon differences led to a Co gradient in the sintering part with a deviation of up to 10 m%. With an increase in sintering time and temperature, the Co distribution began to even out, and a deviation was observed only in the parts created with the inks containing 7.5 and 10 m% of particles. Hardness values of up to 1300 HV10 were obtained, which is comparable to conventionally produced WC–Co parts. The excess of carbon resulted in porosity in the parts leading to a reduced density. However, with inks containing 10 m% particles, densities of 94.26% were achieved at the longest sintering times and the highest temperature. [ABSTRACT FROM AUTHOR]

Objective: To determine the proportion of patients undergoing hysterectomy for a benign indication who have unexpected malignancy (UM) on postoperative pathology and characterize the nature of UMs. Methods: This was a multi-center, retrospective study of patients undergoing hysterectomy for a benign indication from July 2016 to December 2019 at 7 Ontario, Canada hospitals (4 academic, 3 community). Hysterectomies for invasive placentation, malignant, and premalignant indications were excluded. Primary outcome was rate of unexpected malignancy as defined by the number of patients with malignancy on final pathology divided by the total number of hysterectomy cases. Data was extracted from health records and electronic charts. Patient, surgical, and surgeon characteristics were compared between benign and UM groups using bivariate methods. Associations between UM status and perioperative variables were assessed using bivariate logistic regression. Results: In the study period, 2779 hysterectomies were performed. UM incidence was 1.8% (51 malignancies/2779 cases), with one patient having two malignancies (total UMs = 52). The most common UM types were endometrial (27/52, 51.9%) and sarcoma (13/52, 25%). Patients with UM were older (57.2 ± 11.4 years vs. 52.8 ± 12.5 years, p =.015), had more previous laparotomies (2 (1.25, 2.0) vs. 1 (1.0, 1.0), p <.001), and higher BMI (29.7 ± 7.2 kg/m2 vs. 28.0 ± 5.9 kg/m2, p =.049) and ASA class (p <.028). Regarding surgical factors, patients with UM had more adhesions (p =.001), transfusions (p =.020), and blood loss (p =.006) compared to those with benign pathology. Patient characteristics most strongly associated with UM were age (OR 2.57, 95% CI 1.78–3.72, p <.001) and preoperative diagnosis of pelvic mass (OR 2.76, 95% CI 1.11–6.20, p =.019). Conclusion: Incidence of UM at hysterectomy for benign indication was 1.8%. Several perioperative variables are associated with an increased chance of UM. [ABSTRACT FROM AUTHOR]

Objective: We aimed to develop a system for people with amputation that non-invasively restores missing control and sensory information for an ankle-foot prosthesis. Methods: In our approach, a wrist exoskeleton allows people with amputation to control and receive feedback from their prosthetic ankle via teleoperation. We implemented two control schemes: position control with haptic feedback of ankle torque at the wrist; and torque control that allows the user to modify a baseline torque profile by moving their wrist against a virtual spring. We measured tracking error and frequency response for the ankle-foot prosthesis and the wrist exoskeleton. To demonstrate feasibility and evaluate system performance, we conducted an experiment in which one participant with a transtibial amputation tracked desired wrist trajectories during walking, while we measured wrist and ankle response. Results: Benchtop testing demonstrated that for relevant walking frequencies, system error was below human perceptual error. During the walking experiment, the participant was able to voluntarily follow different wrist trajectories with an average RMS error of 1.55° after training. The ankle was also able to track desired trajectories below human perceptual error for both position control (RMSE = 0.8°) and torque control (RMSE = 8.4%). Conclusion: We present a system that allows a user with amputation to control an ankle-foot prosthesis and receive feedback about its state using a wrist exoskeleton, with accuracy comparable to biological neuromotor control. Significance: This bilateral teleoperation system enables novel prosthesis control and feedback strategies that could improve prosthesis control and aid motor learning. [ABSTRACT FROM AUTHOR]

Human running is inefficient. For every 10 calories burned, less than 1 is needed to maintain a constant forward velocity - the remaining energy is, in a sense, wasted. The majority of this wasted energy is expended to support the bodyweight and redirect the center of mass during the stance phase of gait. An order of magnitude less energy is expended to brake and accelerate the swinging leg. Accordingly, most devices designed to increase running efficiency have targeted the costlier stance phase of gait. An alternative approach is seen in nature: spring-like tissues in some animals and humans are believed to assist leg swing. While it has been assumed that such a spring simply offloads the muscles that swing the legs, thus saving energy, this mechanism has not been experimentally investigated. Here, we show that a spring, or 'exotendon', connecting the legs of a human reduces the energy required for running by 6.4±2.8%, and does so through a complex mechanism that produces savings beyond those associated with leg swing. The exotendon applies assistive forces to the swinging legs, increasing the energy optimal stride frequency. Runners then adopt this frequency, taking faster and shorter strides, and reduce the joint mechanical work to redirect their center of mass. Our study shows how a simple spring improves running economy through a complex interaction between the changing dynamics of the body and the adaptive strategies of the runner, highlighting the importance of considering each when designing systems that couple human and machine. [ABSTRACT FROM AUTHOR]

This paper extends sublaminate-based variable kinematics plate finite elements towards the buckling analysis of composite structures. Robust locking-free 4-node and 8-node interpolations are used to build the finite element matrices in terms of fundamental nuclei, invariant with respect to the employed kinematic model of the composite plate. Geometric nonlinearities are accounted for in the von Kármán sense. The classical linearized stability analysis is mainly conducted for sandwich panels, for which different kinematic assumptions are employed for the skins and the core. Global buckling of the sandwich panel as well as short-wavelength wrinkling of the skins are investigated by referring to a variety of case studies, including homogeneous and laminated skins as well as isotropic and orthotropic cores. Convergence studies are performed to establish the minimum number of elements for the local instabilities to be grasped. The proposed computational framework requires a simple 2D mesh and is capable of providing quasi-3D response patterns. This is as demonstrated by numerous case studies that address the transition from global to local buckling, the onset of wrinkling in flat sandwich panels with anisotropic skins under various loading conditions as well as the local face sheet instability occurring in sandwich panels working in bending. It is concluded that he proposed FEM-based tool is computationally efficient and can be advantageously employed in pre-sizing design phases without resorting to full 3D models. • Global buckling and wrinkling of sandwich structures is investigated. • Robust locking-free finite plate elements are implemented. • Reduced-order modelling strategies are assessed against 3D solutions. • Guidelines for determining effective computational models for wrinkling are proposed. • Skew wrinkling and one-sided wrinkling under bending are successfully computed. [ABSTRACT FROM AUTHOR]

Abstract: The primary goal of this study was to determine the prevalence of bullying in children with epilepsy compared with their healthy peers and peers with chronic disease. Children with epilepsy were compared with healthy children and a cohort of children with chronic kidney disease (CKD). The following self-report questionnaires were completed: Revised Olweus Bully/Victim, Piers–Harris Self-Concept Scale, Revised Child Manifest Anxiety Scale, Child Depression Index, and Social Skills Rating System. Children with epilepsy were more frequently victims of bullying (42%) than were healthy controls (21%) or children with CKD (18%) (P = 0.01). Epilepsy factors such as early age at seizure onset, seizure type, and refractory epilepsy were not found to be predictors of victim status. Surprisingly, poor social skills, increased problem behaviors, poor self-concept, depression, and anxiety did not correlate with bully victim status. The relatively high prevalence of bullying behaviors in these children is concerning and, from a clinical standpoint, requires greater research specifically addressing peer relationships and consideration of the implementation of anti-bullying measures and coping strategies for children with epilepsy. [Copyright &y& Elsevier]

Scanning ion conductance microscopy (SICM) is a scanned probe microscopy technique in which the probe is a fine glass pipet filled with a contact (reference) electrode and an electrolyte solution. The current flow between the reference electrode and a second reference electrode positioned in bulk solution when the two electrodes are biased externally can be used as a feedback signal to maintain a constant separation between the tip and a surface during imaging. In usual practice the tip position is modulated over a small amplitude perpendicular to the surface, and the resulting alternating current (AC) is used as the feedback signal, although the direct current can also be used. A comprehensive model for the current response is reported. Laplace's equation has been solved for the electrolyte solution for a range of tip geometries, enabling the factors controlling the tip current to be identified. The approach developed is shown to represent an improvement over earlier semiempirical treatments. To explore the influence of surface topography on the (AC) current response, various surfaces have been considered, including a tip moved toward a planar surface (in the nonnal direction) and tips scanned over a pit and a step in the surface. The results have allowed a critical assessment of the SICM response as a means of probing surface topography. Features identified through simulation have been found in experiments through studies of two model substrates for which imaging results are reported. In typical experimental practice, the response of the SICM tip to surface features occurs over much greater lateral distances than the size of the pipet aperture. [ABSTRACT FROM AUTHOR]

A scanning micropipet contact method (SMCM) is described which promises wide-ranging application in imaging and quantifying electrode activity at high spatial resolution. In SMCM, a moveable micropipet probe (diameter 300 nm to 1 μm) containing an electroactive species in electrolyte solution is brought to a sample electrode surface so that the liquid meniscus makes contact. The micropipet contains a reference-counter electrode, and the sample is connected as the working electrode to make a two-electrode voltammetric measurement. SMCM thus makes possible highly localized electrochemical experiments, and furthermore, heterogeneous electrode surfaces may be investigated without the substrate being completely immersed in solution. This opens up the possibility of making measurements on a wide range of electrode materials without having to encapsulate the electrode. Furthermore, the electrode! solution contact can be made rapidly and briefly, which is useful for situations where the electrode would be unstable for longer periods (e.g., due to corrosion or surface adsorption). For heterogeneously active surfaces the technique is particularly powerful as it allows defined areas to be targeted and individual sites to be probed. To exemplify the approach, the electroactivity of basal plane highly oriented pyrolytic graphite (HOPG) and two types of aluminum alloy were investigated. SMCM measurements indicate that basal plane HOPG shows much greater activity than present consensus. Measurements of chemically heterogeneous aluminum alloy surfaces with SMCM allow variations in redox activity to be mapped with high spatial resolution. [ABSTRACT FROM AUTHOR]

Spatial variations in the electrical and electrochemical activity of microarray electrodes, fabricated entirely from diamond, have been investigated. The arrays contain ∼50-μm-diameter boron-doped diamond (BDD) disks spaced 250 μm apart (center to center) in insulating intrinsic diamond supports, such that the BDD regions are coplanar with the intrinsic diamond. Atomic force microscopy (AFM) imaging of the surface reveals a roughness of no more than ±10 nm over the array. Each BDD microdisk within the array contains polycrystalline BDD with a variety of different grains exposed. Using conducting-AFM, the conductivity of the different grains was found to vary within a BDD microdisk. Electrochemical imaging of the electroactivity of the microdisk electrodes using scanning electrochemical microscopy operating in substrate generation-tip collection mode revealed that, under apparently diffusion-limited steady-state conditions, there was a small variation in the response between electrodes. However, the majority of electrodes in the array appeared to show predominantly metallic behavior. For the electrodes that showed a lower activity, all grains within the microdisk supported electron transfer, albeit at different rates, as evidenced by studies on the electrodeposition of metallic silver, at potentials far negative of the flat band potential of oxygen-terminated polycrystalline diamond. The possibility of using these array electrodes for steady-state diffusion-limited measurements in electroanalytical applications is far-reaching. However, caution should be exercised in the kinetic analysis of voltammetric measurements, since wide variations in the electroactivity of individual grains are apparent when the potential is below the diffusion-limited value. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polyvinylpyrrolidone is usable as a binder and simultaneously as a dispersant. • Formation and velocity of the drops are influenced by the particle mass fraction. • Increasing the particle load can lead to a deterioration of the printing behavior. • Inks with a particle load up to 5 m% show a drop formation without satellite drops. The use of particle loaded inks in binder jetting offers several advantages, such as the improved sintering ability or the adaption of material properties in a printed part. Various aspects have to be considered for the preparation and the printability. A high stability is necessary, therefore agglomeration and sedimentation of the particles must be avoided. It is also important that long filaments and thus satellite droplets are not formed during printing. In this study, inks loaded with graphite nanoparticles were investigated regarding their stability and drop formation behavior to qualify them for reliable processing in binder jetting. Polyvinylpyrrolidone (PVP) was used as a binder for the binder jetting process and simultaneously as a dispersing agent for the nanoparticles. The PVP mass fraction was investigated for its dispersion effect. To meet the print head requirements, the particle size distribution had to be below 1 μm. To destroy agglomerates with a diameter above this limit, ultrasonic treatment was used. The duration of the ultrasonic treatment was examined to identify the minimum time required to obtain a well dispersed ink. Particle loaded inks were then prepared and the fluid mechanical properties were determined for inks with different particle mass fractions. Monitoring of the drop formation provided information about a stable drop generation, the filament lengths, and the velocity of the drops. It was possible to qualify inks with a maximum particle mass fraction of 10 m% for the binder jetting process. [ABSTRACT FROM AUTHOR]

Adults spend the majority of their waking hours sedentary. Sedentary behaviour (SB) includes any waking behaviour with low energy expenditure while sitting, lying or reclining (e.g., watching television, sitting at a desk) and is associated with several chronic diseases and mortality. Social influence, namely SB norms may be a modifiable factor through which we can target and reduce SB. The objectives of this review were: 1) to create an inventory of measures assessing SB norms within the literature and population-based health surveys; and 2) identify measures of SB norms that are both reliable and valid in relation to SB for use in population-based health surveys. Four bibliographic databases and grey literature were searched to identify all studies and population-based health surveys which included participants from high-income countries. Studies were required to report measures of SB norms (descriptive or injunctive). Risk of bias within and across studies was assessed. Results were summarized using a narrative synthesis. This review identified 32 studies for review; no population-based health surveys with SB norm measures were identified. Of the studies, about half were conducted in children/youth (n = 17) where descriptive norms or a combination of both descriptive and injunctive norms were more frequently studied. In adult studies, injunctive norms were most frequently assessed. SBs were largely assessed via self-report, where the most common SB assessed was television viewing. Overall, the nature of the relationship between SB norms and SB was mixed; however, SB norms with friends as the referent group were more consistently associated with SB. No difference was observed in associations with SB between injunctive and descriptive norms. Based on the results, we suggest examples of SB norm measures for future validation and use in population-based health surveys. Future studies are needed to assess the validity of the proposed SB norm measures. PROSPERO #CRD42018106017. • No population health surveys contain a measure of sedentary behaviour social norms. • Norms with friends were more consistently associated with sedentary behaviour. • Future studies need to assess the validity of the proposed norm measures. [ABSTRACT FROM AUTHOR]

Background: With approximately 8 hours of one's waking day spent at work, occupational tasks and environments are important influencers on an individual's physical activity (PA) and sedentary behaviours. Little research has compared device-measured physical activity, sedentary behaviour and cardiometabolic outcomes between occupational groups. Objective: To compare device-measured movement (sedentary time [ST], light intensity physical activity [LPA], moderate-to-vigorous intensity physical activity [MVPA], and steps) across occupations. The secondary objective was to examine whether cardiometabolic and fitness outcomes differed by occupation. Methods: Five bibliographic databases were searched to identify all studies which included working age, employed adults from high-income countries, and reported on device-measured movement within occupations. Risk of bias within and across studies was assessed. Results were synthesized using meta-analyses and narrative syntheses. Results: The review includes 132 unique studies with data from 15,619 participants. Working adults spent ~ 60% of their working and waking time engaged in sedentary behaviour; a very small proportion (~ 4%) of the day included MVPA. On average, workers accumulated 8124 steps/day. Office and call center workers' steps/day were among the lowest, while those of postal delivery workers were highest. Office workers had the greatest ST and the lowest time in LPA both at work and during wakeful time. However, office workers had the greatest minutes sent in MVPA during wakeful hours. Laborers had the lowest ST and spent a significantly greater proportion of their work time in LPA and MVPA. Healthcare and protective services workers had higher levels of LPA at work compared to other occupations. Workers in driving-based occupations tended to have a higher body mass index and blood pressure. Conclusion: This review identifies that occupational and wakeful time PA and ST differed between occupations. Future studies are needed to assess whether patterns differ by age and sex, describe leisure-time movement and movement patterns, and the relationship with cardiometabolic health. Systematic review registration: PROSPERO CRD42017070448. [ABSTRACT FROM AUTHOR]

Pain experiences of youth with brain-based developmental disabilities are often overlooked and/or misinterpreted, increasing the risk for poor or inadequate pain assessment and management. Ample measures exist to assess acute and chronic pain, yet their utility and frequency of use in youth with brain-based developmental disabilities is unclear and available measures do not have strong measurement properties for this diverse group. This systematic review identified the scope of self-reported and observer-reported pain assessment in studies of youth (aged 3-24 years) with brain-based developmental disabilities (phase 1) and summarized other measures of pain-related functioning for acute and chronic pain (ie, physical, emotional, social, sleep, and quality of life, within the subset of quantitative studies focused primarily on pain, phase 2). A comprehensive search for English-language studies was conducted in August 2022 in Web of Science, CINAHL, MEDLINE, Cochrane CENTRAL, EMBASE, and APA PsychINFO (PROSPERO registration: CRD42021237444). A total of 17,029 unique records were screened. Of the 707 articles included in phase 1, most assessed chronic pain (n = 314; 62.0%) and primarily used observer-report (n = 155; 31%) over self-report (n = 67; 13%). Of the 137 articles included in phase 2, other outcomes assessed alongside pain intensity included motor ability (16.8%), adaptive functioning (11%), quality of life (8%), pain interference (6.6%), mental health (5.8%), and communication ability (2.9%). Cerebral palsy was the most common population in both phase 1 (n = 343; 48.5%) and phase 2 (n = 83; 59.7%). This review provides a foundational understanding of pain assessment in brain-based developmental disabilities and highlights continued inequities in holistic pain assessment for this population. [ABSTRACT FROM AUTHOR]

Background: Grass pollen is a major cause of allergy throughout the world. The only treatment targeting the causes and not only the symptoms of allergy is specific immunotherapy (IT). A number of controlled trials demonstrated the efficacy of IT in grass pollen allergic subjects, most using extracts of multiple grasses but some using extracts of a single grass. The optimal grass extract for IT has not yet been established. Methods: This study is aimed at investigating the IgE-binding pattern in sera from IT-naïve patients from central Italy with allergic rhinitis and/or asthma caused by grass pollen. A 5-grass extract was used (containing Dactylis glomerata, Poa pratensis, Lolium perenne, Antoxanthum odoratum and Phleum pratense) and compared to Phleum pratense alone, which is the most frequently used single grass extract, by the RAST-inhibition technique. Results: The 5-grass extract showed, by RAST-inhibition, a significantly higher binding compared to the Phleum pratense extract for Antoxanthum odoratum and Poa pratensis, while the two extracts for immunotherapy showed similar binding affinity for Phleum pratense and the non- Pooideae grass, Cynodon dactylon. Conclusions: The use of a mixed-grass pollen extract seems to be the optimal choice when applying specific IT in grass pollen-allergic subjects from the Mediterranean area. [ABSTRACT FROM AUTHOR]

Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4–16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657–62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic proten (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10–12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment. [ABSTRACT FROM AUTHOR]

Sublingual-swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen.Seventy-one patients with comparable age and symptoms were randomized to receive SLIT by the same grass pollen extract from Stallergénes (Antony, France), 40 of them with the 100 IR and 31 with the 300 IR extract. All patients recorded diary cards for symptoms, medications and side-effects of the treatment, and had measurements of specific IgE and IgG4 in serum by the CAP System FEIA (Pharmacia, Uppsala, Sweden) and in nasal secretion by anin situincubation method with the same reagents of CAP System FEIA.Symptom/medication scores during the pollen season were significantly higher in patients treated with the lower dosage compared with those treated with the 300 IR dosage. Side-effects occurred with a comparable rate (25.8%vs27.5%) in the two groups. Serum-specific IgE and IgG4 had no significant changes after 3 months of SLIT in both groups, while a significant seasonal increase of nasal IgE (P = 0.015) and IgG4 (P = 0.019) was found only in patients treated with the lower dosage.A rise of specific IgG4 and a blunting of seasonal increase of specific IgE in serum was repeatedly reported during subcutaneous immunotherapy (SCIT) with pollen extracts. Our findings show such blunting of specific nasal IgE along with a low symptom/medication score in patients treated with SLIT with the higher dosage, but not a concomitant rise of specific nasal IgG4. This suggests a local immunological effect of SLIT, different from systemic mechanisms of SCIT. [ABSTRACT FROM AUTHOR]

Clinical trials have long established the long-term safety of omitting axillary lymph node dissection (ALND) after sentinel lymph node dissection (SLND) in patients with clinically node-negative early stage breast cancer. The variations in utilization of SLND and ALND in this patient population, however, are currently unknown. Adult female patients (40 years and older) within the National Cancer Database diagnosed with breast cancer between January 2013 and December 2015, who had clinical T1-T2 and N0 disease, and who underwent either SLND (with or without subsequent ALND) or ALND were included. Differences in utilization across race, ethnicity, insurance type, facility, and residential characteristics were assessed using multivariable logistic regression. Overall, 271,689 patients were included, of which 26,527 (10%) received ALND and 245,162 (90%) underwent SLND. After adjusting for demographics and cancer characteristics, black (odds ratio [OR], 1.11; 95% confidence interval [95% CI], 1.06-1.17) and Hispanic women (OR, 1.16; 95% CI, 1.10-1.24) were more likely to receive ALND. Patients without health insurance (OR, 1.33; 95% CI, 1.19-1.47), compared with private health insurance, and those receiving treatment at community cancer centers (OR, 1.60; 95% CI, 1.53-1.67), compared with academic/research centers, were also more likely to receive ALND. Although the vast majority of women undergo SLND, significant disparities exist in its utilization for early stage breast cancer, with traditionally underserved patients receiving unwarranted extensive axillary surgery. Increased patient and surgeon education is needed to decrease variations in care that can affect patient's quality of life. [ABSTRACT FROM AUTHOR]

Purpose Human or animal thin corneal lenticules (L) have been used as biological carrier to experimentally reconstitute tissue‐engineered grafts. Decellularization of the stroma proved to reduce immune rejection after allografts in animals. Aim: to assess different decellularization methods of human corneal L. Methods Stromal L were prepared with a Moria microkeratome on human organ cultured corneas mounted on an artificial anterior chamber. After desepithelialization, an anterior L was obtained with a 90 μm head and a posterior one with a 110 μm head. Four physical methods (sonification at 37 kHz for 45 minutes (min), 3 freeze/thaw cycles in liquid nitrogen, heating at 50°C for 60 min, and hypoxia) and four chemical methods (75% ethanol for 2x10 min, 0,1% sodium Dodecyl sulphate for 24 hours (h), 4M urea for 4h, and 29% NaCl for 24h) were tested. Efficiency and safety were assessed by determining: 1/mortality of the keratocytes using the Hoechst‐Ethidium‐Calcein triple labelling (Pipparelli, IOVS2011;52:6018), 2/alteration of the stroma using transparency measurement (analysis of modulation and contrast transfer functions), and collagen fibres analysis by transmitted electron microscopy (TEM), and 3/elimination of the cell debris using a staining of cell cytoplasm (Dioc 6) and TEM. Results 75% ethanol and hypoxia triggered complete keratocytes mortality with minimal alterations of the stroma. None of the methods eliminated dead cells debris. Combination with the sonification helped fragmenting cells Conclusion Two simple and rapid methods allow complete decellularization of human corneal L. The ability of these Lt to promote endothelial cells adhesion and proliferation is under investigation. [ABSTRACT FROM AUTHOR]

Fibrosis in systemic sclerosis (SSc), a complex polygenic disease associated with autoimmunity and proliferative/ obliterative vasculopathy, shares pathobiologic features in common with other fibrosing illnesses, but also has distinguishing characteristics. Fibroblast activation induced by transforming growth factor-β (TGF-β), Wnts and innate immune receptors, along with oxidative stress and reactive oxygen species (ROS) are implicated in pathogenesis. On the other hand, the roles of endothelial-mesenchymal differentiation and bone marrow-derived fibrocytes remain to be established. Fibrotic responses are modulated by transcriptional activators and cofactors, epigenetic factors, and microRNAs that can amplify or inhibit ligand-induced signaling. The nuclear orphan receptor PPAR-g appears to be important in governing the duration and intensity of fibroblast activation and mesenchymal progenitor cell differentiation, and defects in PPAR-g expression or function in SSc may underlie the uncontrolled progression of fibrosis. Identifying the perturbations in signaling pathways and cellular differentiation programs responsible for tissue damage and fibrosis in SSc allows their selective targeting using novel compounds, or by innovative uses of already-approved drugs (drug repurposing). [ABSTRACT FROM AUTHOR]

The steadily increasing luminosity of the LHC requires an upgrade with high-rate and high-resolution detector technology for the inner end cap of the ATLAS muon spectrometer: the New Small Wheels (NSW). In order to achieve the goal of precision tracking at a hit rate of about 15 kHz/cm 2 at the inner radius of the NSW, large area Micromegas quadruplets with 100 µm spatial resolution per plane have been produced. IRFU, from the CEA research center of Saclay, is responsible for the production and validation of LM1 Micromegas modules. The construction, production, qualification and validation of the largest Micromegas detectors ever built are reported here. Performance results under cosmic muon characterization will also be discussed. [ABSTRACT FROM AUTHOR]

The gastrointestinal system plays a central role in immune system homeostasis. It is the main route of contact with the external environment and is overloaded every day with external stimuli, sometimes dangerous as pathogens (bacteria, protozoa, fungi, viruses) or toxic substances, in other cases very useful as food or commensal flora. The crucial position of the gastrointestinal system is testified by the huge amount of immune cells that reside within it. Indeed, gut-associated lymphoid tissue (GALT) is the prominent part of mucosal-associated lymphoid tissue (MALT) and represents almost 70% of the entire immune system; moreover, about 80% of plasma cells [mainly immunoglobulin A (IgA)-bearing cells] reside in GALT. GALT interacts strictly with gastrointestinal functions in a dynamic manner; for instance, by increasing intestinal permeability in replay to particular stimulations, or orientating the immune response towards luminal content, allowing either tolerance or elimination/degradation of luminal antigens, or sometimes provoking damage to the intestinal mucosa, such as in coeliac disease or food allergy. The immune mechanisms implicated in these actions are very complex and belong to both innate and adaptive immunity; innate immunity supplies an immediate non-specific response that is indispensable before specific adaptive immunity, which needs 7–10 days to be efficacious, takes place. The results of their interactions depend upon different contexts in which contact with external agents occurs and may change according to different genetic settings of the hosts. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical TH-immunoreactive neurons were first observed 2 weeks postnatally and peaked in number 3 weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggest that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in non-overlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence. [Copyright &y& Elsevier]

Scanning electrochemical microscopy (SECM) has been employed in the feedback mode to assess the electrochemical behavior of two-dimensional networks of single-walled carbon nanotubes (SWNTs). It is shown that, even though the network comprises both metallic and semi-conducting SWNTs, at high density (well above the percolation threshold for metallic SWNTs) and with approximately millimolar concentrations of redox species the network behaves as a thin metallic film, irrespective of the formal potential of the redox couple. This result is particularly striking since the fractional surface coverage of SWNTs is only ∼1% and SECM delivers high mass transport rates to the network. Finite element simulations demonstrate that under these conditions diffusional overlap between neighboring SWNTs is significant so that planar diffusion prevails in the gap between the SECM tip and the underlying SWNT substrate. The SECM feedback response diminishes at higher concentrations of the redox species. However, wet gate measurements show that at the solution potentials of interest the conductivity is sufficiently high that lateral conductivity is not expected to be limiting. This suggests that reaction kinetics may be a limiting factor, especially since the low surface coverage of the SWNT network results in large fluxes to the SWNTs, which are characterized by a low density of electronic states. For electroanalytical purposes, significantly, two-dimensional SWNT networks can be considered as metallic films for typical millimolar concentrations employed in amperometry and voltammetry. Moreover, SWNT networks can be inexpensively and easily formed over large scales, opening up the possibility of further electroanalytical applications. [ABSTRACT FROM AUTHOR]

The efficacy of specific immunotherapy and particularly of sublingual immunotherapy (SLIT) in subjects allergic to Cupressaceae pollen is well defined, but no study assessed its effects on quality of life (QoL). We evaluated the effectiveness of SLIT with a standardized, high-dose extract of Juniperus ashei in patients with cypress-induced rhinitis, using QoL as the major outcome measure. Thirty-four patients, 20 males and 14 females, mean age 33.8 years, with allergic rhinitis (AR) from cypress pollen were randomly assigned to receive an allergen extract standardized in index of reactivity (IR) of J. ashei (19 patients) or a placebo (15 patients). The schedule was pre-coseasonal, with a build-up phase in 12 days and a maintenance treatment with 300 IR a day up to the end of the cypress pollen season. All patients registered in diary cards their symptoms, drug consumption and side-effects. The QoL was measured before and after SLIT by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) by Juniper during the peak of the cypress pollen season. QoL significantly improved in respect to baseline in actively ( P=0.017) but not in placebo-treated patients, and there was a significant difference in favour of actively treated patients during the pollen season ( P=0.02). Actively and placebo-treated patients had comparable symptom–medication scores in the period from 15 February to 15 March, corresponding to the peak pollen season, but placebo-treated patients showed an uneven drug consumption compared with actively treated patients. Side-effects were relatively common, but mostly with local short-lasting symptoms, and no systemic reaction was reported. These findings show that SLIT with high doses of J. ashei in subjects with cypress-induced rhinitis significantly improves QoL and confirm previous observations on the disagreement between QoL – which assesses patient's perception – and medical parameters used in trials. [ABSTRACT FROM AUTHOR]

Oral allergy syndrome (OAS) is often associated with pollen-induced rhinitis, and there are preferential associations between causative substances. If OAS and rhinitis are both immunoglobulin (Ig)E-mediated and there are cross-reacting proteins, it is expected that similar reactions can be elicited in the nose and mouth. In order to test this hypothesis we performed a series of‘cross-challenges’ with foods and pollens in both the nose and the mouth.Nine patients with ascertained OAS due to vegetables and rhinitis due to pollens were studied. On the first day a nasal challenge with pollen extracts and an oral challenge with fresh food was carried out. After a week, washout nasal challenge with food and an oral challenge with pollens were performed. Immediate symptoms, mucosal tryptase and soluble eosinophil cationic protein (ECP) were assessed after each challenge.The administration of pollen into the nose and food into the mouth elicited symptoms as expected, but the cross-challenge had no clinical effect. In parallel, tryptase and ECP increased after nasal challenge with pollens, whereas foods did not elicit a measurable response.The cross-reactivity between foods and pollens, when evaluated at the shock organ, was not clinically evident. This data can be explained with a low concentration of cross-reagent epitopes in pollen extracts and food homogenized because of degradation. The different behaviour upon challenge suggests that different immunological mechanisms may act in the nose and mouth. [ABSTRACT FROM AUTHOR]

The article offers a bioptic study on oral reactions to sublingual immunotherapy (SLIT). It is stated that although sublingual immunotherapy (SLIT) is currently considered a feasible option to traditional subcutaneous immunotherapy (SCIT) for treating allergic rhinitis caused by sensitization to seasonal or perennial allergens with a significant advantage in terms of safety, but mast cells and eosinophils are not the elicitors of local reactions to SLIT.

Reports on a patient in whom Nonne-Milroy lymphedema was prenatally diagnosed during a routine sonographic examination. Description of the disease; Features of the patient; Other dysmorphic syndromes that must be considered in prenatal diagnosis.

Focuses on the likely association between a new type of Ehlers-Danlos syndrome and tortuous systemic arteries. Overview of various types of Ehlers-Danlos syndrome; Linkage analysis of the disease; Assessment of genotypes of linked markers; Information on multiple screening of affected patients.