To demonstrate the safety and feasibility of the Urocross Expander System (formerly branded as XFLO Expander System), an implantable nitinol tissue expander to trea t patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).Men of 50 years or older were eligible to participate in the international, prospective, three-arm, open-label EXPANDER-1 trial if they had a prostate volume between 30 and 80 cc, prostatic urethra length between 20 and 60/80 mm, international prostate symptom score (IPSS) > 13, peak urinary flow (Qmax) < 12 mL/s, post-void residual (PVR) urine volume < 250 mL and quality of life (QoL) score ≥ 3. Patients had pre-assigned implant indwell times  with follow-up through 6 months (Arm-1) and 3 years (Arm-2 and Arm-3) post-retrieval.Outcome from treated subjects with their 6-month post-retrieval will be presented in this manuscript, as data collection from longer-term follow-up is ongoing. As of May 24, 2021, 39 and 22 men (mean age: 65), respectively, had implants successfully deployed and retrieved without any complications. No cases of implant encrustation were observed. Device- and procedure-related adverse events were predominantly mild to moderate in severity. Three SAEs were reported. Only one patient required catheterization post-implant for more than three days. Improvements in clinical parameters such as IPSS, QoL, PVR and Qmax as well as sexual function were observed.PRostatic Urethral Expansion (PURE) procedure. Negative features of earlier generations of prostatic implants such as biocompatibility, migrations and encrustation have possibly been overcome.Preliminary results demonstrate that the Urocross Expander System is a feasible and safe procedure for treating BPH/LUTS. A strong signal of efficacy justifies further evaluation of this  Benign Prostatic Hyperplasia (BPH) is a progressive condition commonly associated with bladder outflow obstruction and lower urinary tract symptoms (LUTS) .Surgery, specifically transurethral resection of the prostate (TURP), was once the cornerstone for the treatment of BPH/LUTS after drug therapy fails. However, because TURP has the potential for significant morbidity , a plethThe Expander System , Sunnyvale, California, USA) is a MIST that has been developed for use with a flexible cystoscope and includes an implantable tissue expander (the Expander implant or implant) and delivery system (handle and delivery catheter) designed for placement of the implant in the prostatic urethra and its retrieval after implantation for a minimum of one month and up to 12 months. The implant is a new nitinol device with a quadrant, strut-like design developed with the aim to expand and reshape the prostatic urethra, through gentle mechanical tissue retraction and relieve urinary outflow obstruction symptoms and LUTS. Early results from the first patients were promising with most patients reporting rapid symptom relief and minimal complications .The objective of the EXPANDER-1 trial was to demonstrate the safety and feasibility of the Expander System procedure to treat patients with BPH/LUTS.The Expander System consists of a sterile, single-use nitinol tissue expander implant preloaded in a delivery catheter. Each delivery catheter is designed to advance through the working channel of a flexible cystoscope. Using the handle of the delivery system, the controlled deployment of the implant in the prostatic urethra is performed under direct cystoscopic visualization.The implant has four arms connected by two hubs ; however, the second-generation Expander System included an additional option to use a larger implant.For implantation, a flexible cystoscope is used to measure the prostatic urethral length from bladder neck to the verumontanum. For second-generation-device patients, small and large implants are deployed for prostatic urethral lengths of 20–30 mm and >30 mm, respectively. The delivery catheter is first inserted through the port of the flexible cystoscope. Then the delivery handle is locked to the cystoscope. An irrigation line is connected to the handle to allow continuous irrigation during the procedure. Adjustments to the position of the tip of the delivery catheter can be made on the delivery handle. Using standard urology technique, the scope and catheter are inserted to the prostatic urethra. Once the catheter tip is positioned at the level of the verumontanum, the slider on the delivery handle is slowly advanced allowing the deployment of the implant between the verumontanum and bladder neck. The implant arms expand outwardly, retract the prostatic tissue and widen the prostatic urethra lumen  channel of the cystoscope and the implant hub is secured inside the jaws of the grasper. The Retrieval Sheath is carefully advanced to bring it within the cystoscope’s field of view in order to capture the implant hub. While holding the Retrieval Sheath, the cystoscope is withdrawn along with the grasper and implant into the Retrieval Sheath lumen. Once the collapsed implant is inside the Retrieval Sheath, all components  are removed from the urethra as one unit.Procedures were performed under topical anesthesia, mild intravenous sedation, or general anesthesia in a cystoscopy suite or operating room.This prospective, non-randomized, three-arm, multi-center, open-label, clinical trial evaluates the safety and feasibility of the Expander System in patients with LUTS due to BPH. This trial is being conducted at 4 centers in Taiwan, Canada and Australia.The protocol was approved by the ethics committees/institutional review boards at all enrolling centers  and all enrolled patients signed an informed consent.Inclusion and exclusion criteria are summarized in Supplementary Table In Arm 1, the implant indwell time was 1 month and post-retrieval follow-up at 6 months. Safety and effectiveness data were assessed at follow-up visits after 2 weeks and 1-month post-implantation, and up to 6 months following implant retrieval . In ArmsFor safety purposes, the trial design consisted of a staged approach in which 5 patients were initially enrolled and treated in Arm 1 with the shorter indwell time of 1 month. Once data from Arm 1 was reviewed and use of the device was assessed as safe by an independent data monitoring committee (DMC), Arm 2 was initiated, followed by Arm 3 with a longer indwell time of 6 and 12 months, respectively.The primary safety endpoint is the cumulative rate of device- and/or procedure-related adverse events from device implantation to 6 months following implant retrieval for each treatment arm. Other safety endpoints included incidence of repeat invasive treatment for LUTS (defined as any BPH-related serious adverse event (SAE) resulting in surgical intervention including minimally invasive procedures), and freedom from unanticipated adverse device effects. Acute and long-term implantation and post-retrieval effectiveness was evaluated using the following questionnaires and instruments: IPSS, uroflowmetry, post-void residual (PVR) urine volume, quality of life (QoL) score, Sexual Health Inventory for Men (SHIM), Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EjD), Michigan Incontinence Symptom Index (M-ISI) questionnaire. Additionally, safety and effectiveness were further assessed by the technical success of placement and retrieval. All safety and effectiveness assessments, including adverse events and medication review, were performed during the post-implant and post-retrieval follow-up period.Patients were also scheduled to undergo follow-up cystoscopies at 1-month post-retrieval (Arm 1), 9 (or 12) and 36 months post-retrieval (Arm 2), and 6 (or 9) months post-implant and 9 (or 12) and 36 months post-retrieval (Arm 3). Also, at 3 months post-implant, an ultrasound was to be performed to assess the location of the implant during the indwell period (Arm 3).Sample size was calculated using the simple asymptotic method. Data cut-off for this evaluation was on 24 May 2021. For continuous variables, data were expressed as mean and standard deviation (mean ± SD); for categorical variables, data were expressed as frequency counts and percentages. All endpoints were summarized by each treatment arm and overall treatment arms. Changes from baseline were calculated for each patient using their post-baseline value minus baseline value. Results were described for the full analysis population, consisting of enrolled patients who had met all eligibility criteria, had a successful implant procedure and had at least one follow-up assessment completed. SAS® software version 9.4 or higher was used for statistical analysis.A total of 39 men (mean age of 65 years) were treated between 09 November 2018 and 24 May 2021: 16 and 23 patients with the first- and second-generation Expander Systems, respectively . During the trial, 33.3% of patients received new BPH medication that included 5ARI, alpha blockers, and antimuscarinics after baseline due mainly to reported AEs.N = 5) under the first-in-human protocol. Upon review by an independent DMC, it was then decided to proceed with Arm 2 (N = 15) and Arm 3 (N = 19) under the revised feasibility protocol. Patient’s disposition can be found in Supplementary Fig. The initial patients were treated in Arm 1  without any complications or unanticipated SAEs. During retrieval, two device deficiencies, one for the implant and one for the retrieval sheath, both due to user error, were reported. No cases of implant encrustation were observed in any patient at the time of cystoscopic follow-up examinations or following any implant retrieval.A Clavien-Dindo Classification summary of adjudicated device- and procedure-related adverse events, predominantly mild to moderate in severity, is shown in Table Effectiveness data for IPSS is summarized in Table This is the first clinical report of the Expander System as a MIST for the treatment of BPH/LUTS. This technology is a novel treatment designed to be implanted using a flexible cystoscope. The implant is designed to reshape the prostatic tissue and to disobstruct the prostatic urethral lumen without heating, burning, ablating, cutting or removing any prostate tissue.To date, the Expander implant was associated with successful deployments and retrievals in the current clinical trial and has met the co-primary objective of safety and feasibility. The Expander System has also been confirmed as minimally invasive and meeting the co-primary objective for safety. The proposed mechanism of action by PURE using the new nitinol Expander implant appears concordant with the clinical effectiveness observed in these preliminary results.Numerous prostatic stent devices have been trialed over the past 40 years, but few remain in clinical use. Major problems with early generation stents included device migration and encrustation . These eOne patient experienced implant migration into the bladder, which was an unexpected finding due to the nature of the device expanding into the prostatic urethra with expected holding of its position. A careful review of device deployment videos confirmed that placement had been sub-optimally too proximal, potentially providing a reason for this implant migration. The solitary case of implant migration equates to an incidence of 2.6% and is not considered a major concern for the overall outcome of the trial.Reports of clinical parameters such as IPSS, QoL, PVR, Qmax and sexual function were not amongst the primary objectives of this trial, however, there were observed improvements similar to those of other MISTs  that wouTo date, increased indwell time is associated with having a higher risk of implant migration. Our current data showed a reduction of symptoms during the 6-month indwell time and this duration has been shown to have satisfactory outcome data with little risk of migration. As such, the 6-month indwell duration will be used in future studies.Potential benefits of using the Expander System include the ability to be deployed using a flexible cystoscope without the requirement for additional equipment.This trial is limited by the variations in treatment approaches reported in this trial including differing implant dwell times, changing from first- to second-generation delivery system and associated inclusion of a larger implant option and limited clinical outcomes data past 6-month post-implant retrieval. These limitations will largely be overcome in future reports as larger series are reported.Preliminary clinical results with a novel PURE procedure, using the Expander System, have met the trial objectives in terms of feasibility and safety.To date, the Expander System provides a signal of efficacy similar to that observed in other early-stage MIST trials , 15. ThiSupplementary LegendsSupplementary Figure 2Supplementary Figure 3Supplementary Figure 4Supplementary Table 3Supplementary Table 4


The Covid-19 pandemic brought enormous challenges for health professionals. As in past epidemics, the uncertainty, danger and fear of contamination and an excessive load of work under dramatic conditions may contribute to aggravate the mental health of health professionals.Explore how the Covid-19 crisis impacted the mental health of healthcare workers and how their mental status relates with perspectives on the recent past and near future.Depression, Anxiety and Stress Scale (DASS-21), the Impact of Event Scale – Revised (IES-R) and a questionnaire about the past and the future.A longitudinal study will be applied in two phases, Q1 and Q2, one year apart, to evaluate depression, anxiety and post-traumatic stress among health professionals from a healthcare center in Portugal. Phase Q1 is concluded and comprised the The IES-R scale revealed that nurses are at a higher risk of developing post-traumatic stress disorder (PTSD) than other professionals. The levels of depression and anxiety in the DASS-21 show no significant differences. Interestingly, professionals who worked almost exclusively at inpatient wards show higher levels of depression, anxiety and stress than those who worked at several hospital units . A positive correlation was found between depression and anxiety and negative perspectives about the past and the future.Covid-19 posed a terrible challenge for health professionals. Its impact on the mental health of healthcare workers may be significant even after the pandemic is under control.No significant relationships.


Hence, in this review, we provide the first-ever summary of various studies that used 2D and 3D in vitro co-culture models to assess the nature of aberrant immune cell-fibroblast interactions and their contributions to chronic inflammation and fibrotic mechanisms in asthma pathogenesis.Asthma is a chronic lung disease involving airway inflammation and fibrosis. Fibroblasts are the main effector cells important for lung tissue production which becomes abnormal in asthmatics and is one of the main contributors to airway fibrosis. Although fibroblasts were traditionally viewed solely as structural cells, they have been discovered to be highly active, and involved in lung inflammatory and fibrotic processes in asthma. In line with this, using 2D and 3D  Asthma is a chronic inflammatory lung disease that is a major global health burden with an estimated prevalence of 357.4 million as of 2019) (9 (1). AsH2 cells which then communicate with fibroblasts to add to the induction of various asthma features (The main effector cell involved in airway-fibrosis is the fibroblast which is mainly responsible for extracellular matrix (ECM) production in the lungs –9. In thfeatures –12. In afeatures –16. Myoffeatures –19.Lung fibroblasts were traditionally thought of as structural cells primarily responsible for ECM synthesis and organization –22. Howein vitro models. These in vitro models allow scientists to recreate and mimic the complex 3D spatial orientation of cells in the in vivo environment and examine the aberrant cell interactions that occur in chronic lung diseases such as asthma. The various models used range from simple co-culture experiments to more complex (3D) tricultures and microfluidic lung-on-a-chip systems. Co-culturing fibroblasts with various immune cells in these systems, allows the investigation of specific mechanisms involved in lung fibroblast-immune cell crosstalk. This in turn allows for the advancement of studies into targeted treatments and medications to reduce disease symptoms and ultimately aid in finding a cure for asthma.To assess how immune cells and fibroblasts interact, researchers have utilized a plethora of complex 3-dimensional (3D) in vitro co-culture models to assess lung immune cell-fibroblast interactions, and how these contribute to the various features of asthma.In this review, we will provide the first ever summary of studies that have used complex (3D) in vitro models have been developed in response to the demand for improved techniques that better mimic the complexity of the in vivo lung environment  exposure model  co-culture methods.via aberrant responses, which partly involves abnormal interactions between immune and structural cells   in the airways  , 30. Theoblasts) –33. Thesoblasts) , 35. Othoblasts) –39. In a airways . On the  airways . Below, To assess the interaction between fibroblasts and eosinophils and the role this plays in asthma pathogenesis, Esnault and colleagues exposed human lung fibroblasts (HLFs) to CM from eosinophils isolated from patients with and without asthma which had been treated with IL-5 and IL-3 to induce degranulation . EosinopMast cell-fibroblast crosstalk has also been demonstrated to be crucial for asthmatic airway inflammation. In line with this, Fitzgerald et al. directly and indirectly co-cultured the human mast cell line HMC-1 with NHLFs and found a transcription factor p38 mitogen-activated protein kinases (MAPK) activation with, subsequent IL-6 production by lung-fibroblasts . ThroughOther studies have looked at how the interaction between different T-cell subtypes and fibroblasts also contribute to inflammation in asthma. Here, Loubaki and colleagues co-cultured CD4+ T-cells with primary HBFs isolated from healthy controls and asthmatics . It was in vitro. There is currently a lack of studies assessing neutrophil-fibroblast interactions in asthma pathogenesis which may be due to inherent difficulties in the culturing and maintenance of neutrophils as these cells need to be freshly isolated from blood to be used for experiments  are key neutrophil chemoattractants, it would be beneficial to further assess the interactions between neutrophils and fibroblasts eriments . Nevertheriments . These mThe lungs of asthmatics undergo extensive remodeling that is partly characterized by airway fibrosis resulting in the thickening and narrowing of the airways , 56–58. α-smooth muscle actin (α-SMA), collagen I, and matrix metallopeptidases (MMPs) in HLFs. The increased production of ECM proteins was correlated with matrix turnover and degradation as well as increased ECM stiffness in the thickened asthmatic airways (α-SMA (α-SMA) and profibrotic cytokines such as TGF-β that are implicated in asthma fibrosis .in vitro co-culture models previously discussed, there are various applications using more advanced biological models. These include precision cut lung slices, microfluidic lung-on-a-chip systems (LOAC) and 3D lung bioprinted models, which are all being established to mimic the complex 3D in vivo environment of the lungs and allow for the study of more than two cell-types. Although, the addition of other cell types to these models may prevent the ability to isolate and study the specific communication between two cell types such as immune-fibroblast communication as examined in this review, triculture models such as these represent more wholistic mimics of the airway mucosa. This is because, addition of more cells, and other features of the in vivo environment, such as the airflow through microfluidics with these models further enable the discovery of (new) possible drug targets which hither-to were difficult to study with 2D-monolayer, animal model or (3D) co-culture systems as reviewed here.In this review, we provided an unbiased summary of studies that have examined the contribution of fibroblast-immune-cell crosstalk to the pathogenesis of asthma with specific emphasis on airway inflammation and fibrosis See Table 1.In conclusion, the studies reviewed here demonstrate that in asthmatic airway inflammation the interaction between immune cells and fibroblasts is significantly important for the release of inflammatory cytokines such as IL-6 and IL-8 that results in neutrophil activation and chemotaxis, even when the communication is between fibroblasts and classical allergic immune effector cells such as eosinophils, mast cells and T-cells. In addition to this, we found that various studies showed eosinophil and mast cell interaction with fibroblasts through the release of TGF-β and MMPs had critical implications for increased ECM deposition and abnormal ECM turnover. These findings are critical and requires further investigation as they have interesting consequences for asthma therapeutic research. It is already known that certain asthma subtypes which are resistant to treatment with underlying neutrophilia and aberrant airway fibrosis exist , 66. FroConceptualization ETO. Original draft preparation: TF, and ETO. Further writing and edits: TF, AS, PS, AA, and ETO. Preparation of Table, Figure, manuscript citations, references, and further edits: ETO, TF, FK, DE, and BJ. All authors contributed to the article and approved the submitted version.


Deciding whether to engage in strenuous mental activities requires trading-off the potential benefits against the costs of mental effort, but it is unknown which brain rhythms are causally involved in such cost-benefit calculations. We show that brain stimulation targeting midfrontal theta oscillations increases the engagement in goal-directed mental effort. Participants received transcranial alternating current stimulation over dorsomedial prefrontal cortex while deciding whether they are willing to perform a demanding working memory task for monetary rewards. Midfrontal theta tACS increased the willingness to exert mental effort for rewards while leaving working memory performance unchanged. Computational modelling using a hierarchical Bayesian drift diffusion model suggests that theta tACS shifts the starting bias before evidence accumulation towards high reward-high effort options without affecting the velocity of the evidence accumulation process. Our findings suggest that the motivation to engage in goal-directed mental effort can be increased via midfrontal tACS. When deciding whether to read a scientific article, we need to trade-off the benefits of reading a potentially interesting article against the mental effort required to read it. Because mental effort is perceived as costly, humans should engage in mentally demanding activities only if the potential benefits outweigh the costs of exerting effort  task for monetary rewards  were recruited from the student population in Munich. A power analysis assuming an effect size of Cohen’s d = 0.54 observed in a previous tACS study from our group  with a power of 80%. One participant erroneously performed the 1-back instead of the 2-back task during tACS (see below); the 2-back data of this participant were therefore excluded from the analysis. All volunteers were screened for possible contraindications of tDCS and gave voluntary informed consent prior to participation. They received a compensation of 10 euro/hour and additionally a bonus depending on their choices (see below). The study was approved by a local ethics committee.Thirty-five, healthy, young volunteers . The task was to decide via keypress whether the currently presented letter was identical with the letter presented N trials before. For illustration purpose, participants performed example blocks  for the 1-back, 2-back, 3-back, and 4-back conditions before receiving instructions for the decision task in order to familiarize them with the subjective effort demands. During stimulation, participants performed only the 2-back condition, because this difficulty level was shown to be sensitive to stimulation effects . To modulate midfrontal theta oscillations, we placed a 5×5 cm electrode over electrode position FCz according to the international 10-20 system as well as a 5×5 cm reference electrode under the chin Fig. . The eleTo assess which brain regions were affected by the electrode setup, we performed current flow simulations with the Simnibs 3.2 toolbox  within one experimental session Fig. . We admiEach miniblock started with a ramp-up period of 5 s for the tACS current. In the sham condition, the current was ramped-down directly after the ramp-up phase. In 15 s after the start of tACS, participants performed the decision and the 2-back tasks for 115 s. After task performance, the current was ramped-down over a period of 5 s. Starting with the ramp-down phase, participants had to indicate the perceived aversiveness of the stimulation and the tACS-induced flickering on rating scales from 0 to 20. The next block started after a stimulation-free interval of 40 s.theta-sham and tACSalpha-sham), the difference between high and low effort requirements (Effortdiff), the reward magnitude of the high effort option (Rewardhigh), and the interaction terms (MGLM-1). All predictors were also modelled as random slopes in addition to participant-specific random intercepts. To control for potential confounding effects of tACS-induced discomfort or flickering as well as of the order in which the experimental tasks and tACS conditions were administered, we added these variables as predictors of no interest (note that none of these control variables showed a significant result). We used noninformative flat priors (default in brms) and estimated the posterior distributions of the parameter estimates by computing two chains with 4,000 samples . For all parameter estimates, 95%).For the effort-based decision task, we conducted model-based and model-free analyses. For the model-free analysis, we computed a Bayesian mixed general linear model (MGLM) using the brms package in R Bürkner, . The titattribute, we assumed that the drift rate v depends on the comparisons of reward magnitudes and effort costs between the low effort and high effort options  using the JAGS software package Plummer, . JAGS utdiff and Effortdiff indicate the difference between the reward magnitudes and effort requirements of the high and low effort options, respectively. tACStheta and tACSalpha were dummy-coded variables that were set to 1 for theta tACS and alpha tACS, respectively, and to 0 for all other conditions. This allowed us to model tACS effects on DDM parameters relative to the baseline sham condition on a within-subject level, in analogy to the model-free MGLM analysis. To investigate stimulation effects on DDM parameters, we modelled individual and group-level effects of theta and alpha tACS on all DDM parameters in a hierarchical Bayesian approach. We excluded the trials with the 5% fastest and slowest response times to reduce the impact of outliers on parameter estimation. We used non-informative uniform priors over numerically plausible parameter ranges and estimated parameters by computing two chains with 50,000 samples . Again, Rewardattribute assumes that participants decide between the reward options by making attribute-wise comparisons between the reward magnitudes and the associated N-back demands of the low and the high effort options. In contrast, alternative accounts posit that decision makers compare the discounted subjective values of the reward options (“effort discounting”). In the literature, there is no agreement on the precise shape of the discount function .We estimated these model parameters  in three separate DDMs in the same way as for DDMFinally, we analyzed tACS effects on performance in the 2-back task. Again, we computed Bayesian MGLMs with the brms package in order to assess whether theta or alpha tACS, relative to sham tACS, affected mean reaction times (MGLM-2) on hit trials or d’ theta-sham, tACSalpha-sham, the difference between high and low effort demands (Effortdiff), and the reward magnitude of the high effort option (Rewardhigh). As expected, subjective values of high effort options decreased with increasing effort demands, HDImean = −0.06, HDI95% = . Consistent with our hypothesis, theta tACS significantly increased subjective values of high effort options relative to sham tACS, HDImean = 0.04, HDI95% =   or on option-wise comparisons of discounted subjective reward values as given via hyperbolic, parabolic, or linear discount functions. DDMattribute explained the data better than any other model, as indicated by a lower DIC . Posterior predictive checks for DDMattribute revealed strong overlap between simulated and empirically observed decision times, suggesting that the DDM parameters provide a reasonable explanation for the observed choices  theta tACS, relative to sham tACS, significantly increased the bias parameter. Thus, consistent with our model-free findings, midfrontal theta tACS increased the preference for high effort options via shifting the starting point of the evidence accumulation process.From the perspective of process models, this finding could be explained by two different mechanisms. First, theta tACS could modulate the influence of benefits and costs on the speed of the evidence accumulation process (drift rate parameter). Second, instead of affecting evidence accumulation per se, midfrontal tACS might shift the starting point of the accumulation process toward the high effort option. These alternatives can be distinguished via drift diffusion modelling (DDM). In DDMs, the decision process is modelled as evidence accumulation process with a drift rate v (starting after the nondecision time t and from the starting point b) until the threshold a is reached. We computed four separate DDMs assuming that the drift rate of the accumulation process depends either on attribute-wise comparisons of reward magnitudes and N-back levels  or sensitivity d’ . This does not support the possibility that tACS affected effort-based choice via changing the capacity to exert mental effort.To control for the possibility that  tACS-induced differences in working memory performance led to the observed tACS effects on decision making, we re-computed MGLM-1 on subjective values in the decision task and controlled for working memory performance either via mean reaction times or sensitivity d’. The main effects of theta and alpha tACS remained significant independently of whether we controlled for reaction times . We also did not directly assess whether blinding of participants was successful as we did not ask participants whether they currently received sham or active tACS in a given miniblock. However, tACS conditions did not significantly differ with regard to tACS-induced discomfort or flickering, suggesting that active and sham tACS were virtually indistinguishable to participants. As we moreover statistically controlled for such tACS-induced irritations in our statistical models, it seems unlikely that peripheral effects drove the observed stimulation effects on decision making.Taken together, our results provide insights into the neural mechanisms underlying the willingness to engage in rewarded mental effort. Deficits in the motivation to exert effort belong to the core deficits of several psychiatric disorders, including depression and schizophrenia (Hartmann et al.,


The intergroup comparison revealed statistical significance (p < 0.05) with respect to HRW and KTW (Keratinised tissue width) gains of 0.775 at the 6-month follow-up. Sticky-bone (Xenogenic-bone graft + i-PRF) served as a promising biomaterial in achieving better horizontal bone width gain.Guided bone regeneration (GBR) is a reliable technique used to treat ridge deficiencies prior or during implant placement. Injectable-platelet rich fibrin (i-PRF) laced with a bone substitute (sticky bone) has heralded the way for advancing the outcomes of bone regeneration. This study evaluated the efficacy of sticky bone in horizontal ridge augmentation with and without collagen membrane. A total of 20 partially edentulous patients  that indicated GBR were included, and the surgical procedure was carried out. In Group-I, the sticky bone and collagen membrane were placed in ridge-deficient sites and Group-II received only sticky bone. At the end of 6 months, 20 patients (Group-I (n = 10); Group-II (n = 10)) completed the follow-up period. A CBCT examination was performed to assess changes in the horizontal ridge width (HRW) and vertical bone height (VBH). A statistically significant increase in HRW ( Physiologic Alveolar ridge resorption following tooth loss leads to a range of ridge deficiencies. The majority of the dimensional alterations occur during the first three months and can persist up to 5 years ,2, with Bone substitutes are becoming more widely accepted as alternatives to autogenous bones for ridge augmentation procedures, minimising the morbidity associated with autogenous graft harvesting ,4,5,6. MSecond generation Autologous platelet concentrates such as Platelet-rich fibrin (PRF) and Concentrated growth factors (CGF) were proposed to be used as an autologous fibrin glue to create a bone graft matrix loaded with growth factors, known as "sticky bone" . In 2015, Mourao et al., stated that platelet-rich fibrin can be replaced by Injectable platelet-rich (i-PRF) fibrin, which has the ability to release a variety of growth factors with increased expression of Platelet-derived growth factor (PDGF), Transforming growth factor (TGF), Collagen 1, and Fibroblast migration for accelerating bone regeneration ,15. ThisThe sticky bone, according to Sohn et al., 2015 , may funVarious GBR membranes such as Type-1 Collagen, poly-lactic acid, polyglycolic acid, polyurethane, and dura mater are among the resorbable membranes available, with collagen membrane being the most popular and widely used with extensive documentation.The literature shows that collagen membrane exhibits 22 percent to 32 percent early membrane exposure, ,18,19 whSticky bone bypasses the need for a membrane, and the fibrin network drives platelets and leukocytes to release signalling molecules and drastically increase the regeneration of hard and soft tissue. The fibrin interconnectivity of the sticky bone also diminishes soft tissue and epithelial cell ingrowth . CordaroInclusion criteria: systemically healthy individuals within an age range of 21–60 years presenting with edentulous sites requiring a ridge width gain of 4–5 mm buccolingually and with a residual ridge width of 2–3 mm. The edentulous sites were required to be Kennedy’s Class III, with a post extraction healing of minimum of 6 months. Exclusion criteria: patients with debilitating systemic diseases or diseases that had a clinically significant effect on wound healing, had a history of intravenous bisphosphonate/oral bisphosphonate use for > 3 years or history of head and neck radiation therapy/chemotherapy, smokers, pregnant women or lactating mothers, and people possessing allergies to any of the materials or medications used in the current study were excluded.This randomised parallel arm clinical trial was conducted with approval of the institutional scientific and Ethical committee (SRMDC/IRB/2019/MDS/No.505A) before the commencement of the study and was registered with clinicaltrials.gov.in (CTRI/2020/06/025567). Sample size calculation was performed based on results obtained from a study by Mohammed Atef. et al in February 2020 . The tesTo establish the keratinised tissue width (KTW) and vestibular depth (VD), custom-made composite resin stents were prepared for each patient with a vertical groove created mid-buccally over the stent to guide consistent reorientation of the periodontal probe (UNC-15).For Groups I and II, a Cone Beam Computed Tomography (CBCT) scan was performed prior to surgery and 6 months post-surgery. Horizontal Ridge Widths (HRW) were measured at the crest, 3 mm, and 6 mm levels perpendicular to the longitudinal axis of the alveolar crest via tomographic sections. The Vertical Bone Height (VBH) of the ridge was measured from the crest to the mandibular canal.The Patients were randomly allocated using the lottery method. The investigator who evaluated the CBCT measurements was blinded in this study. A total of 20 ridge-deficient sites requiring ridge augmentation were randomized into 2 groups of 10 sites each.TM, Geistlich®, Zurich, Switzerland) . For both Group I and Group II, local anaesthesia was administered using 2% lignocaine with adrenaline. After performing a mid-crestal incision through the keratinized gingiva, a full-thickness flap was raised on the buccal and lingual side. To enable osteoprogenitor cell migration, multiple neo-angiogenetic cortical holes were made in the recipient bone bed. A total of 10 mL of venous blood obtained from the antecubital vein in non-coated plastic vacutainers was immediately spun in a centrifuge at a pre-programmed spin to obtain i-PRF (700 rpm for 3 min with 60 g force) (Dentifuge LC-100). The prepared i-PRF was mixed with ABBM (Bio-OSSzerland) ; polymerzerland) A–H and ozerland) A–H. TensPatients were administered with antibiotics  and analgesics (Ibuprofen+paracetamol) for up to five days after surgery. For the first four weeks after surgery, patients were told not to brush the surgical site and chlorhexidine mouth wash (0.12%) was prescribed as an adjunct to oral hygiene maintenance. All patients experienced uneventful wound healing. There was no wound dehiscence during the healing process. Patients had a stringent postoperative supportive care regimen and underwent reviews beginning one week after surgery, continuing every two weeks until eight weeks had passed post-surgery. Patients were then recalled once a month until six months as passed for assessment.p < 0.05.IBM SPSS was used to carry out the statistical analysis with 25.0 statistics programme. Using an independent samples T-test, the groups’ distributions of age and gender were compared. In order to compare and evaluate the relationship between the categories, the Chi-Square Test was employed. An unpaired t-test was developed to compare the values between the two groups; Values within the groups were compared using the paired sample t-test. The level of statistical significance was fixed at The primary outcome of our study was the assessment of the inter and intra group changes in the horizontal ridge width using Cone Beam Computed Tomography (CBCT). The secondary outcomes analysed were the changes in vertical bone height, changes in vestibular depth, and changes in the keratinized tissue width. A total of 20 patients  with a mean age of 36.1 years participated in the current investigation .The intragroup comparisons (Group I- Sticky Bone and Collagen Membrane) of the primary clinical parameters such as the HRW at various levels  showed a statistically significant difference at 6 months of healing compared to the baseline with the highest bone gain of 1.93 mm at the 6 mm level. There was a statistically significant improvement in the VD and KTW at 6 months compared to the baseline. The intragroup comparisons (Group II- Sticky Bone) of the primary clinical parameters such as the HRW at various levels  showed a statistically significant difference at 6 months of healing compared to the baseline, with the highest bone gain of 2.8 mm at the 6 mm level. There was a statistically significant improvement in the VBH and KTW at 6 months compared to the baseline .The intergroup comparisons between Group-I and Group-II for various clinical parameters such as the Horizontal ridge width (HRW), Vertical bone height (VBH), Vestibular depth (VD), and width of Keratinised tissue (KTW) at baseline showed no statistical significance between Group-I and Group-II. However, the results at 6 months showed a statistically significant improvement in Group-II. Even the KTW gain was statistically significant between the groups. Changes in the alveolar ridge dimensions post extraction have previously been reported ,26. AccoThe current study aimed at evaluating the outcomes of the use of sticky bone with and without a collagen membrane, following horizontal alveolar ridge augmentation, which was determined by using CBCT. The membrane employed in this investigation was a bilayer-cross-linked collagen membrane. TM, Geistlich®, Switzerland) used in this study was combined with i-PRF and used in the form of sticky bone, which could have led to the slow release of critical growth factors such as PDGF, VEGF , IGF (insulin like growth factor), and FGF (fibroblast growth factor), which have shown to favour new bone formation. With the additional use of a collagen barrier membrane, epithelial exclusion and space protection is expected, which in turn favours optimal treatment outcomes. In the intra group (Group-I: sticky bone + collagen membrane) comparison of various clinical parameters—such as the HRW at various levels , the VBH, the KTW in Group-I showed a statistically significant improvement in all the clinical parameters including the HRW gain, VD, and KTW. The results are comparable with those of Aboelela et al. (2021)  who evalThe intragroup comparisons (Group II- Sticky Bone) of various clinical parameters such as the HRW at various levels, the VBH, and the KTW showed a statistically significant improvement with a mean horizontal gain of 2.8 mm and a VBH gain of 1 mm.The results of the present study cannot be compared directly with any other study as this the first study of its kind using sticky bone alone for horizontal ridge augmentation. However, Staedt et al. (2020), using an animal model, histologically demonstrated significant new bone formations that were further reinforced using enzymatic assays such as Bone acid phosphatase (BAcPH) and total alkaline phosphatase (TAlPh) . Most ofTM  bone graft has been a very successful biomaterial used in the augmentation of resorbed ridges. It acts as a scaffold and favours new bone formation by osteoconduction; further, the addition of i-PRF to the sticky bone matrix may have led to the adherence of the grafted material to the recipient sites without micro and macro movements, and the PRF matrix prevents early epithelial ingress onto the defect site leading to significant new gains in both horizontal and vertical dimensions.The Bio-OSSTM  with and without a collagen membrane and concluded that though a bone graft with a membrane showed significantly earlier bone remodelling, there was no histological difference in the new bone formation between the groups [The intergroup comparisons showed an additional mean HRW gain of 0.9 mm in Group-II , which was statistically significant. Further, there was a statistically significant improvement in the KTW . To the best of our knowledge, this is a novel approach, wherein we have analysed and compared the efficacy of sticky bone with and without a collagen membrane. The results of the present study could not be directly compared with previous studies in the literature. However, Lee et al. (2013), in his study comparing a tooth bone graft with and without a membrane, determined a similar bone gain in both the groups and further carefully elucidated that the use of an additional membrane did not benefit the clinical outcomes . Furthere groups . In the In the introduction, we proposed that there would not be an additional benefit of using membranes, which has been proven from the results of our study. According to numerous studies, a GBR membrane is intended to protect and encapsulate the graft material during the sensitive bone-remodelling phase and its integration with the native bone . HoweverThe encouraging results obtained in both groups are due to the biological properties of i-PRF, which acts as biological glue by keeping the graft particles intact and at the same time allowing for neovascularisation during healing. Furthermore, the various growth factors released from the PRF such as PDGF, EGF , IGF, FGF, and VEGF help in promoting cellular proliferation, thereby increasing vascularity at the surgical site. The absence of a constrictive effect of the collagen membrane, the easy re-approximation of the flap, and the unjeopardized vascularity in group-II resulted in comparatively better outcomes. The CBCT analysis resulted in a reliable, non-invasive assessment of the changes in bone width and height.The study limitations include a small sample size, a longer follow-up, and a lack of histological evaluation of the new bone formed.Therefore, within the limits of the current study, we conclude that both the groups showed significant improvement in all the clinical parameters assessed, and we propose that a combination of ABBM+i-PRF (Sticky bone) can be predictably used without the need for a collagen barrier membrane as it did not provide any additional benefits regarding horizontal ridge augmentation in the current study.


This study examined the stock market response of the Japanese restaurant industry to the announcement of the self-restraint request and subsidy for restaurants by the Japanese government during the coronavirus outbreak. Using the event study approach, it was found that the market reacted negatively to the self-restraint request and positively to the subsidy for restaurants. Following the announcement of the self-restraint request, investors in the restaurant industry responded positively to the government’s stringent policy responses. Conversely, following the announcement on the “dining-out” subsidy, investors reacted negatively to the stringent government policies. Our findings provide useful information for policy makers and practitioners to mitigate losses in the hospitality industry during the pandemic. Go to Eat Campaign, which was intended to mitigate the damage of COVID-19 on the restaurant industry [The coronavirus disease 2019 (COVID-19) pandemic has had a massive and negative impact on the global economy [industry . This stThe WHO China Country Office first detected COVID-19 in China on December 31, 2019 . On JanuOn February 17, Prime Minister Abe announced the self-restraint request regarding going out in Japan. Growing fears over COVID-19 resulted in a shrinking domestic hospitality industry through government policies such as self-restraint requests and business trip warnings . A stateThis study focused on the effects of both the self-restraint request and the subsidy on the damage caused by COVID-19 by using the stock reactions of restaurant firms. Within the hospitality industry, the restaurant industry was regarded as having widely embedded and enormous business risks during the pandemic . In the This study aimed to analyze two major events regarding the Japanese government’s policy responses related to the hospitality industry by applying an event study methodology. We first analyzed whether self-restraint requests negatively affected stock responses to COVID-19 in the restaurant industry (Hypothesis 1). We regarded the first event (Event 1) as having occurred on February 17, 2020. Self-restraint was not considered a heavy-handed rule for the Japanese residents. The second event (Event 2) ensued on April 7, 2020, when the subsidy for dining out given to local restaurants was determined and announced by the government (Hypothesis 2). On the same day, the subsidy for domestic travel was also announced. The demand for local travel has increased post the domestic travel subsidy in Japan [Our study investigated whether government policy responses to COVID-19 were effective in mitigating the negative stock responses to self-restraint requests (Hypothesis 3a) and in mitigating the positive stock responses to the subsidy for dining out in the restaurant industry (Hypothesis 3b). Government interventions entail negative effects on market return of hospitality industry in the United States . In addiVarious countries’ COVID-19 market responses are an important research arena in the context of restaurant industry , which iIn addition, we focused on the effects of the subsidy for dining out on local restaurants. On April 7, 2020, the Japanese government announced the domestic subsidy to mitigate the negative effects of COVID-19. In fact, the domestic subsidy contributed to enhancing demand for local travel in Japan  pointed Using publicly listed restaurant firms in Japan, this study presents several findings by applying an event study methodology , 14. FirOur study contributes to the literature in several ways. First, it adds to the overall understanding of COVID-19 damages to the restaurant industry  by showiPrevious studies have investigated how COVID-19 affects the stock return in hospitability industry including restaurants, hotels, and tourism. The stock prices of listed hotels have been negatively affected by the COVID-19 outbreak . Jawed eThis study aimed to analyze whether the COVID-19 outbreak impacted stock returns in the restaurant industry in Japan. As mentioned, Prime Minister Abe encouraged Japanese residents to stay home voluntarily on February 17, 2020. On April 7, 2020, the Japanese government announced a dining-out discount campaign to minimize the damage COVID-19 inflicted on the restaurant industry. This campaign aimed to invigorate the restaurant industry.There are two reasons why we focused on these two events. To clarify this point, we use the additional table which shows the timeline of COVID-19 related news around the date of Events 1 and 2. Event 1 is thought of as the first negative news which directly implicated the Japanese restaurant industry. On January 30, WHO declared a “public health emergency.” However, there may have been no direct measures to affect Japanese corporations before the event 1 (February 14th). Next, we focus on Event 2 (“Go-to-campaign”) which entails the positive effects for the stock returns of restaurant industry. Certainly, other types of “negative event” have subsequently occurred post Events 1 and 2. We presumed that if the announcement effect of Event 2 was weak, its positive effects would not have persisted. The timeline is shown in A1 Appendix in Rit represents the daily closing stock return at time t, and Rmt is the daily stock return on a value-weighted market index for Japan. Thereafter, we defined AR as each firm’s stock return minus the expected return over a given day.Following Aharon et al.  and PoreWe estimated the parameters applied to market returns  and cumuThe high level of business risk during the pandemic crisis negatively affected the restaurant industry . The negSelf-restraint requests negatively affected stock responses to COVID-19 in the restaurant industry.Go to Eat Campaign, to mitigate the damage of COVID-19 on the restaurant industry [On April 7, 2020, Japanese government announced the subsidy for “dining-out” discount, named the industry . Owing tThe subsidy for dining out given to local restaurants positively affected stock responses to COVID-19 in the restaurant industry.Government responded to the COVID-19 outbreak by implementing several measures such as stringent distancing policies . The senStricter government policy responses to COVID-19 were effective in decreasing the negative stock responses to self-restraint requests in the restaurant industry.As for the announcement on “Go-to-Eat” campaign, the positive effect of this subsidy would be mitigated if government and social distancing policies are strengthened. During the COVID-19 outbreak, the sales of restaurants decreased due to strict government measures. In Chinese restaurants, the decrease of sales in regions with extensive shutdowns was greater than those with less strict ones . Thus, sGovernment policy responses to COVID-19 were effective in reducing the positive stock responses in the restaurant industry.OxCGRT database of several policy responses that governments have taken to respond to COVID-19 [We investigated how the government response to the COVID-19 outbreak influenced the announced domestic dining-out subsidy’s effect on Japanese restaurant stocks. To protect the lives and health of the people, the Japanese government implemented several measures to restrict the restaurant industry. Numerous measures were also reinforced to address the threat of the pandemic. Following Al-Awadhi et al.  and SakaCOVID-19 . The marCOVID-19 , 16. ThuCOVID-19  and the COVID-19  and finaCOVID-19 , 30. InsCOVID-19 .Astra Manager provided by Quick and NPM database provided by Financial Data Solutions, respectively. The number of our sample is 93. We excluded firms with missing data of institutional ownership during the event window. Next, we gathered data on the number of confirmed COVID-19 cases and deaths from the website of the Ministry of Health, Labour, and Welfare [OxCGRT website. The data definitions are summarized in A2 Appendix in We defined the restaurant industry as firms classified under the North American Industry Classification System codes (NAICS codes) 722511 and 722513 . We coll Welfare  and dataWe introduced descriptive statistics of the variables in We show the market responses on the two announcements to provide the average of AR (AAR) in By comparison, Panel A and Panel B of To compare the stock patterns of restaurant firms with other related industries affected by the “Go-to-Eat” campaign, we chose the entertainment industry whose NAICS code is 71. In addition, we also chose the manufacturing industry firms classified by NAICS codes 31 and 33, which were not affected by the campaign. To consider the difference within the restaurant industry, we additionally check the restaurants and other eating places whose NAICS code is 7225. From Panel A of th). After May 14, the state of emergency was lifted in 39 prefectures and the level of GMI and SI has decreased. Thus, these two indexes are connected to the COVID-19 situation in Japan.We also summarize the patterns of Stringency index (SI) and Government Response index (GRI) after two events in GRI (SI) was significantly positive for the AR in Columns (1) and (2). This suggests that the stringent government policy responses to the COVID-19 outbreak was effective in mitigating negative market reaction, consistent with non-pharmaceutical intervention effects [GRI (SI) and Case were significantly negative, which suggests that the positive announcement effects on GRI (SI) were negatively moderated by the increase in COVID-19 cases, supporting our Hypothesis 3a.We show the estimated results of Eq (2), which analyzed the government’s response to stock returns, in  effects . We alsoGRI (SI) is significantly negative for the AR in Columns (3) and (4). This implies that the stimulus effect for local restaurants was restricted to a great degree by the stringent government policy responses to the COVID-19 outbreak, supporting our Hypothesis 3b. In addition, we also found that the cross terms of GRI (SI) and Case were significant and positive. This implies that the negative announcement effects on GRI (SI) were positively moderated by the increase in COVID-19 cases.As for Event 2, we found that Case (Lag Case) in Columns (5), (6), (7), and (8) of Overall, these results prove that the mitigation of the outbreak through the implementation of social distancing policies was directly linked to stock returns, especially for the restaurant industry. Considering the fact that the previous day’s number of confirmed cases was reported by Japanese medias, we also check whether our results are robust when we adopted the lagged variables of LEVERAGE is significantly negative for the AR in Columns (1), (2), (5), and (6) suggesting that the higher COVID-19-related business risk resulted in higher investor anxiety for restaurant firms post the self-restraint request [Regarding the control variables,  request , 33. In This study evaluated the impact of the COVID-19 outbreak on Japanese restaurant stocks. First, we found that the Japanese government’s announcement of the self-restraint request had a negative effect on the restaurant stocks, implying that the request related to COVID-19 negatively affected the Japanese restaurant industry. To prevent the spread of COVID-19, Japanese government chose “Self-restraint-request”, different from strict lock-down in other countries such as U.S. and China. During the lockdown period of March to September, 2020, the negative stock returns were investigated in the U.S. restaurant industry , 15. We In addition, the study showed that the announcement of the domestic dining-out subsidy had a positive effect on restaurant stocks. We may infer that market investors understood that the domestic dining-out subsidy was an appropriate measure for the restaurant industry’s recovery in Japan, and this is consistent with the findings of previous studies , 34. We Furthermore, we analyzed whether the government’s response to the influence of the COVID-19 pandemic influenced stock returns. Our results revealed that social distancing and the government’s policy responses positively affected the AR post Event 1, consistent with the market responses to government intervention  and suppOverall, these results contributed to the stock market responses toward COVID-19 in the hospitality industry. We showed that the market responded negatively to the self-restraint request and positively to the dining-out subsidy for restaurant firms. These results suggest that the subsidy for local restaurants was effective in mitigating the negative impact of COVID-19 under the voluntary lockdown. Government stimulus, such as the dining-out subsidy, may be useful in supporting restaurants in the early stages of a pandemic. Furthermore, the social distancing policies negatively affected the market response following the announcement of the dining-out subsidy. We may interpret that the social distancing policies especially hurt the performance of the restaurant industry. Confirmed COVID-19 cases and deaths, as well as different stock market responses to the pandemic, are important for the restaurant industry.As for the limitations, first, since this study focused on short-term stock market responses, future studies should investigate the long-term effects of the pandemic on restaurant firms. Second, future studies should analyze the effect of stimulus packages provided by different governments during the peak of the COVID-19 crisis.This study opens new avenues for future research on the effects of pandemics on the restaurant industry. First, the level of lockdown have varied over time in many countries. It is possible that the effects of lockdown would be differently characterized in other countries. Second, government responses to COVID-19 might change. Thus, longer-term effects of government responses are unknown. Our study can form the basis of future research in these aspects. Future research could add to the knowledge of these varying effects.S1 File(DOCX)Click here for additional data file.


Scattering of energetic charge carriers and their coupling to lattice vibrations (phonons) in dielectric materials and semiconductors are crucial processes that determine the functional limits of optoelectronics, photovoltaics, and photocatalysts. The strength of these energy exchanges is often described by the electron-phonon coupling coefficient, which is difficult to measure due to the microscopic time- and length-scales involved. In the present study, we propose an alternate means to quantify the coupling parameter along with thermal boundary resistance and electron conductivity by performing a high angular-resolution time-resolved X-ray diffraction measurement of propagating lattice deformation following laser excitation of a nanoscale, polycrystalline metal film on a semiconductor substrate. Our data present direct experimental evidence for identifying the ballistic and diffusive transport components occurring at the interface, where only the latter participates in thermal diffusion. This approach provides a robust measurement that can be applied to investigate microscopic energy transport in various solid-state materials. In particular, the interaction between electronic states and the lattice in excited solids stands out as one of the dominant scattering processes that determine various material properties, ranging from charge carrier and thermal transport, high-temperature superconductivity4, and charge density waves5. Despite such importance, characterization of electron-phonon coupling (EPC) is challenging, especially when the system is driven out of thermodynamic equilibrium. The essence of EPC lies in the fact that perturbation of the electronic state leads to an exchange of energy and momentum between electrons and phonons, and therefore results in elastic stress. Ultrafast optical excitation can induce such transient states, in which a large population of hot carriers is generated and relaxes its excess energy to the cold lattice. Therefore, atomic-scale measurements of structural changes in relevant timescales potentially allow us to explore fine details of the coupling between the electronic states and the lattice.Light-matter interactions involving energetic electrons and quasiparticles are of fundamental interest in condensed matter physics9, where the sample’s surface reflectively is monitored after the incidence of femtosecond laser pulses. The time-dependent reflectance is compared with the two-step thermal relaxation model10 that assumes the linear relation between the reflectivity and temperature. However, the experimentally acquired values have often shown considerable variation likely due to the complex interplay between electrons and phonons as well as multiple scattering mechanisms. To mitigate such experimental challenges, first principle calculations have been conducted on metals and semiconductors to confirm the EPC coefficients11. Nevertheless, the availability of such results is still limited and their ability to account for discrepancies between the simulation and the experiments remains questionable12.The capability to deliver femtosecond laser pulses on metallic surfaces provides a systematic means to induce strong non-equilibrium between electron and phonon subsystems. Typically, the EPC coefficients can be measured by using time-domain thermo-reflectance methodsQ-range is especially important for modeling femtometer-scale lattice deformation in solids. The long material penetration depth of hard X-rays also enables probing propagation of impulsively driven strains from the thin metal surface to the bulk semiconductor, which contains information about athermal  contribution of phonons. In our X-ray measurement, the ballistic components appear in the form of transient interference fringes in reciprocal space or X-ray Brillouin scattering. In order to quantify the relevant physical parameters , we perform a time- and depth-dependent strain analysis by using dynamical X-ray diffraction theory15 and the heat transport model. By comparing the experimental result to the modeling, we determine the EPC coefficient G of 84 17. Furthermore, we find an effective thermal conductivity of the electrons 18. We attribute these apparent discrepancies to the effects of high electron temperatures following intense laser irradiation as well as multiple electron scattering events taking place at the grain boundaries in the metal film. Our structural measurement yields thermal conductivities of the substrates In this work, we conduct high angular resolution and large dynamic range time-resolved X-ray diffraction (TRXD) measurements of transient lattice displacement across buried layers of optically excited metal-to-semiconductor heterostructures, such as Cr/GaAs and Cr/Si. Obtaining the laser-induced changes in diffraction patterns from the substrates over a wide 19. The reflected acoustic wave makes multiple round trips between the film surface and the interface while its amplitude continuously decreases21. Consequently, we observe the emergence of a phonon-mediated real-space periodicity in the substrate crystal as evidenced by the strong sidebands at Temporal evolution of X-ray diffraction curves from the symmetric (0 0 4) Bragg reflection of a laser-excited GaAs substrate is shown in Fig. 22 as follows: S is given as F, R, and F = 8 mJ/cmR = 0.6, and 23. Here, we solve the partial differential equations numerically by using finite difference methods24. We assume that the electronic heat capacity carries a linear relationship with the electron temperature 6. Essentially, this equation describes the equilibration process, in which the electron subsystem continuously imparts its excess energy to the lattice until reaching the same temperature. Simultaneously, the electrons and phonons diffuse into a cold region.The phenomenological temperature relationship between the electrons 21. The effect of this strain profile is manifested in the diffracted X-ray intensity as a fringe pattern near the vicinity of the main Bragg peak, which is a characteristic feature of Brillouin scattering26. Figure 26, the fringe spacing in reciprocal space corresponds to the periodicity of the impulsive pulse train in real space in Fig. In our strain model, the impulsively generated acoustic phonon propagates into the depth direction with a speed of sound in Cr  of phonons, the thermal conductivity can be significantly altered due to the size effectsQ range. By modeling this experimental data, we successfully measure the electron-phonon coupling constant G and thermal conductivity of electron We investigate the laser-induced energy transport mechanism on a metal layered semiconductor system via high angular-resolution time-resolved X-ray diffraction. A careful transient diffraction peak analysis based on dynamical X-ray theory aided by the large dynamic range of our detection scheme enables modeling of the subtle features of scattering patterns over a wide 56 using 10 keV X-rays that were monochromatized by a water-cooled double-crystal diamond (111) monochromator. The X-rays were focused down to a spot size 57. In our experimental geometry, the 4-circle diffractometer allowed us to measure the high-resolution rocking curve with a 0.5 millidegrees angular resolution. The 80-nm thick chromium metal layer deposited on the semiconductor substrates acted as a heat transducer. Transient changes in the symmetric (0 0 4) Bragg diffraction peaks of the substrate semiconductors (Si and GaAs) were acquired as a function of delay times between optical laser and X-ray pulses. The diffracted X-ray photons were collected by the customized Avalanche Photodiode (APD), which is capable of resolving the 153 ns electron bunch separation of APS in 24-bunch filling mode58.Figure The 80 nm of Cr films are deposited on the substrates by D.C. magnetron sputtering of a high purity chromium target in a chamber with a base pressure of about 7 59f) and substrate (s) of the lattice displacement, mass density, total stress, speed of sound, bulk modulus, and lattice temperature, respectively. The second term in the right hand side of Eq.  despite the convolution effect from the instrumental broadening. The estimated mean crystalline domain sizes of 1.36 and 1.87


The integration of virtual reality into everyday life is changing sociocultural practices, including those related to cyberaggression, which causes negative consequences for mental health and well-being. Particular attention needs to be paid to the poorly researched but widespread roles of bystanders and defenders in cyberaggression .The aim is to study the behavioral witness strategies in cyberaggression in VR and their relation to personal and psychophysiological characteristics.50 adolescents aged 14-18 years old  witnessed cyberaggression in an experimental situation in the virtual space of VR-chat. Participants also filled Ten-Item Personality Inventory , I7-Impulsiveness , Prosocial Behaviour . To determine the functional state Heart rate variability  was measured before and after the experiment.Behavioral strategies in VR-aggression were divided into uninvolved bystanders (58%) and defenders (42%). All participants experienced stress and functional state decline when faced with cyberaggression, but the defenders were more affected . Defenders were more likely to have higher social responsibility  and lower neuroticism . There were no significant differences in impulsiveness.Cyberaggression in a virtual environment is stressful, especially for active defenders, who are more included in the situation compared to passive bystanders. The prosocial role of a defender rather than a passive bystander may be related to such characteristics as social responsibility and emotional stability, but not to impulsiveness. The research was supported by RSF (project No. 18-18-00365)This work was supported by the Russian Science Foundation, project # 18-18-00365.


The rapid spread of the deadly coronavirus disease 2019 (COVID-19) pandemic has fundamentally affected healthcare delivery globally. As governments struggled to preserve life, several approaches to healthcare delivery have emerged. Central to limiting viral transmission is the separation of patients based on their COVID-19 status. Studies have shown that a geographically separate dual-site service is preferable, contingent upon the local infrastructure and circumstances. Despite the restrictions on free movement, most studies indicate that low-energy hip fractures in elderly patients have remained relatively constant throughout the pandemic. Arguably these patients represent the most vulnerable subgroup in society and are susceptible to developing severe COVID-19 respiratory disease.In keeping with global recommendations, the government of Trinidad and Tobago devised a parallel healthcare system to limit the spread of disease. All regional health authorities under the Ministry of Health were at liberty to implement the system in a manner best suited for their particular infrastructure leading to highly variable practices among institutions. This report describes the clinical course of two hip fracture patients treated within the parallel healthcare system at different regional health authorities. Analysis of these cases provides an understanding of the potential risks to patients entering the parallel healthcare system and an insight into preventative measures to improve clinical outcomes. Previous studies have projected that the number of hip fractures occurring in the world each year will rise to 6.26 million by 2050 ,2. To daIn Trinidad and Tobago, a key containment strategy to reduce the spread of the virus was establishing a parallel healthcare system (PHCS), that is, a dual-site arrangement with specific hospitals designated for the treatment of confirmed COVID-19 cases separate from the routine public hospitals . To accoAs we reflect on the last two years with COVID-19, the overall success of the parallel healthcare system remains in question. For example, at the time of writing, there have been 4,195 deaths from COVID-19 in Trinidad and Tobago, the highest for any Caribbean territory . The parPatient 1 treated at Regional Health Authority 1 A 63-year-old man attended the Emergency Department two weeks after falling at home. His medical history was unremarkable, but he was a heavy smoker (43 pack years). Radiographs showed a displaced intracapsular fracture of his left hip (Garden IV) Figure .Under the hospital protocol, he was kept in a holding area within the Emergency Department while awaiting the results of his COVID-19 polymerase chain reaction (PCR) test. After receiving a negative result, he was admitted to a four-bed bay on a COVID-free ward and advised to wear a facemask. His surgery was delayed for two weeks and although he was asymptomatic, routine retesting within 48 hours of surgery returned a positive COVID-19 PCR test. The patient underwent a left hemiarthroplasty in a theatre reserved for COVID-19-positive patients Figure .Postoperatively, he remained afebrile without respiratory symptoms and was transferred to the PHCS for rehabilitation.The patient seemed to recover well and was ambulating comfortably with a walker; however, on day nine began experiencing breathlessness. His oxygen saturations were low on room air (93-95%) and he was tachycardic. Treatment was started with oxygen supplementation, dexamethasone and intravenous antibiotics.His chest radiograph demonstrated bilateral infiltrates throughout the lung fields, suggestive of acute respiratory distress syndrome (ARDS). A computed tomography pulmonary angiogram (CTPA) ruled out a pulmonary embolism and showed bilateral pleural effusions, pulmonary emphysema and atelectasis (Chest CT severity score 19/25: severe disease) Figure  18]..18].In light of these results, he was admitted to the Intensive Care Unit and placed on continuous passive air pressure (CPAP) using tiotropium bromide and salbutamol. Despite these measures, he continued to deteriorate and was prophylactically intubated on day 19. He returned a negative swab on day 25 but could not be taken off ventilatory support and eventually succumbed to COVID-19-related pulmonary complications 42 days after surgery.Patient 2 treated at Regional Health Authority 2 A 61-year-old fully vaccinated man presented to the Emergency Department with a displaced intertrochanteric fracture of his right hip. His past medical history was unremarkable, and he neither smoked cigarettes nor consumed alcohol. Although asymptomatic, his pre-admission COVID-19 PCR was positive, and the patient was transferred to the PHCS. While in the PHCS, he remained asymptomatic and was transferred back to the general hospital 28 days after a negative COVID-19 PCR test.A dynamic hip screw (DHS) was used to stabilise the fracture, and the patient recovered well. He was discharged home, where his rehabilitation was hampered by persistent severe hip pain and inability to walk. His fear of contracting COVID-19 resulted in a delay in seeking further medical attention; however, with no progress being made, he eventually returned to the hospital. At this presentation, his right lower limb was significantly shortened and externally rotated. Radiographs showed that the fracture had not been reduced satisfactorily, but there was no evidence of implant failure Figure .We agreed that revising the fixation to a total hip arthroplasty would be the best option to promote rapid mobilisation. At surgery, we encountered extensive fibrosis and marked chondrolysis within the hip joint with little hard callus. The hip was reconstructed using a porous-coated shell and a cemented calcar-replacement stem, while the greater trochanter and posteromedial calcar were reattached with cerclage wires Figure . Tissue After surgery, the patient reported significantly less pain and could mobilise comfortably with a walker. One week later, we noted a persistent wound discharge and took the patient back to the theatre. At surgery, we found marked osteonecrosis of the posteromedial calcar fragment and parts of the greater trochanter with loosening of the cerclage wires. All wires were removed, the soft tissues debrided, and the wound irrigated with copious dilute betadine solution. Despite losing the abductor muscle attachment, the hip remained stable, and the wound was closed over a suction drain. Culture reports were again negative, and the patient was discharged after seven days of intravenous antibiotics and placed on a three-month course of oral antibiotics. Six weeks after surgery, the incision is fully healed, the patient remains pain-free and has resumed rehabilitation Figure .Several reports have documented inferior clinical results in hip fracture patients during the pandemic compared with the pre-pandemic era -9. WhereNosocomial transmissionUsing one hospital to treat both COVID-19-positive and -negative patients increases the risk of cross-contamination. Despite efforts to limit contagion, transmission to hospitalised patients is common and nosocomial transmission is recognised as an important route of spread . Strict precautions within the hospital were enforced to reduce transmission, including limiting visitors, social distancing and frequent hand sanitisation. Nevertheless, patients remain vulnerable to contracting COVID-19 while awaiting surgery, as was the case with Patient 1. Additional protection could have been provided by, first, prioritising surgical stabilisation to minimise the time in the hospital, thereby reducing exposure. Second, divide the orthopaedic service into independent teams of two orthopaedic units. Teams treat either COVID-19-positive or -negative patients, and units rotate to allow adequate rest before returning to work . Third, Hip surgery in COVID-19-positive patients It is widely accepted that early surgery produces better outcomes in hip fracture patients . HoweverDual-site service During the pandemic, better clinical outcomes were seen in patients treated in a dual-site system compared with the traditional single-site model ,27. A duBoth RHAs implemented a dual-site service model but failed to duplicate orthopaedic services at each site, which contributed to the unfortunate outcomes for these two patients. Equality of service is critical for a dual-site arrangement but presents particular logistical challenges; orthopaedic staff would have to be divided between the two sites and the existing operating theatres opened. Despite the local limitations, successful dual-site services have been reported by Ramsingh et al. in a paper on urgent and emergency cardiac surgery in Trinidad .Trinidad and Tobago’s parallel healthcare system, a type of dual-site service, was initially successful at containing and limiting the spread of COVID-19 infection. However, an effective dual-site system separates patients based on their infection status without delaying treatment of concurrent illness. That arrangement requires the duplication of services at each site, which was not a feature of the parallel healthcare system and ultimately contributed to inferior clinical outcomes. With the end of the pandemic in sight, policymakers must use the lessons learnt over the last two years to restructure the health services to protect the most vulnerable in society from future pandemics.