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There are minimal data describing outcomes in ambulatory pediatric and young adult ventricular assist device (VAD)-supported patient populations. We performed a retrospective analysis of encounter-level data from 2006 to 2017 Nationwide Emergency Department Sample (NEDS) to compare emergency department (ED) resource utilization and outcomes for pediatric (≤18 years, n = 494) to young adult (19-29 years, n = 2,074) VAD-supported patient encounters. Pediatric encounters were more likely to have a history of congenital heart disease (11.3% vs. 4.8%). However, Pediatric encounters had lower admission/transfer rates (37.8% vs. 57.8%) and median charges ($3,334 (IQR $1,473-$19,818) vs. $13,673 ($3,331-$45,884)) (all p < 0.05). Multivariable logistic regression modeling revealed that age itself was not a predictor of admission, instead high acuity primary diagnoses and medical complexity were: (adjusted odds ratio; 95% confidence intervals): cardiac (3.0; 1.6-5.4), infection (3.4; 1.7-6.5), bleeding (3.9; 1.7-8.8), device complication (7.2; 2.7-18.9), and ≥1 chronic comorbidity (4.1; 2.5-6.7). In this largest study to date describing ED resource use and outcomes for pediatric and young adult VAD-supported patients, we found that, rather than age, high acuity presentations and comorbidities were primary drivers of clinical outcomes. Thus, reducing morbidity in this population should target comorbidities and early recognition of VAD-related complications.

Aims Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort. Methods and results A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1–16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48–2.78]. Model validation showed a Harrell’s C-index of 0.745 (95% CI 0.52–0.97) and Uno’s C-index 0.714 (95% 0.58–0.85) with a calibration slope of 1.15 (95% 0.51–1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60–0.81). Conclusions This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.

BACKGROUND: Measures of unhelpful thoughts and distress correlate with the intensity of pain and the magnitude of incapability among people seeking musculoskeletal specialty care. In this evolving knowledge area, we want to be sure we have not neglected other important mental health factors. This study addressed how measures of confidence in problem solving as well as past and current ability to achieve goals account for variation in symptoms and capability independent of unhelpful thoughts and distress. QUESTIONS/PURPOSES: (1) Are measures of confidence in problem solving ability and past and current ability to achieve goals regarding future outcomes associated with variation in capability, independent of measures of symptoms of depression and anxiety (distress) and measures of unhelpful thoughts (worst-case thinking, negative pain thoughts)? (2) Are these measures independently associated with variation in pain intensity? (3) Are these measures associated with measures of symptoms of depression, symptoms of anxiety, and unhelpful thoughts? METHODS: Over a 7-month period during the pandemic, we enrolled sporadically from the offices of four surgeons treating patients who sought care for various upper and lower extremity conditions. We invited approximately 200 adult new and returning patients to participate (the number of invitations was not formally tracked) and 187 accepted. Thirty-one were excluded due to markedly incomplete entries (related to a problematic attempt to use the patient’s cell phone to complete questionnaires as a pandemic work around), leaving 156 for analysis. Patients completed an 11-point ordinal rating of pain intensity, two measures of unhelpful thoughts (the Pain Catastrophizing Scale and the Negative Pain Thoughts Questionnaire), the Adult Hope Scale to measure past and current ability to achieve goals, the Personal Optimism and Self-Efficacy Optimism Scale to measure confidence in problem solving ability, the Patient-reported Outcomes Measurement Information System (PROMIS) computer adaptive test to measure symptoms of anxiety, the PROMIS computer adaptive test to measure symptoms of depression, and the PROMIS physical function computer adaptive test to assess the magnitude of capability. All questionnaires were validated in previous studies. We used bivariate analyses to identify factors associated with magnitude of capability, pain intensity, confidence in problem solving ability, and past and current ability to achieve goals. All factors with a p value of less than 0.1 were included in multivariable analyses to seek associations between these measures accounting for confounders. We reported partial η(2) as a measure of effect size for all multivariable regression models. The following rules of thumb are used to interpret values for partial η(2): a value of 0.01 = small, 0.06 = medium, and values of 0.14 and higher show large effect size. RESULTS: Greater capability was modestly associated with fewer negative pain thoughts (β = -0.63 [95% CI -1.0 to -0.22]; standard error = 0.20; partial η(2) = 0.06; p = 0.003) and no self-reported comorbidities (β = 2.6 [95% CI 0.02 to 5.3]; standard error = 1.3; partial η(2) = 0.03; p = 0.048) after controlling for education, symptoms of depression and anxiety, worst-case thinking, as well as past and current ability to achieve goals. In a similar multivariable model, greater pain intensity was modestly associated with greater worst-case thinking (β = 0.33 [95% CI 0.20 to 0.45]; standard error = 0.06; partial η(2) = 0.16; p < 0.001) and established patients (β = -1.1 [95% CI -1.8 to -0.31]; standard error = 0.38; partial η(2) = 0.05; p = 0.006). In another similar multivariable model, having more confidence in problem solving ability had a limited association with higher ratings of past and current ability to achieve goals (β = 0.15 [95% CI 0.09 to 0.21]; standard error = 0.03; partial η(2) = 0.13; p < 0.001). In a final multivariable model, lower past and current ability to achieve goals was independently associated with having greater symptoms of depression (β = -0.45 [95% CI -0.67 to -0.23]; standard error = 0.11; partial η(2) = 0.1; p < 0.001) and more negative pain thoughts (β = -0.49 [95% CI -0.89 to -0.09]; standard error = 0.20; partial η2 = 0.04; p = 0.02). CONCLUSION: The observation that unhelpful thoughts about symptoms are more strongly associated with symptom intensity than past and current ability to achieve goals and confidence in problem solving ability add to the evidence that attentiveness to unhelpful thinking is an important aspect of musculoskeletal health. Musculoskeletal specialists can prioritize communication strategies such as relationship building and motivational interviewing that develop trust and facilitate reorientation of common unhelpful thoughts. LEVEL OF EVIDENCE: Level II, prognostic study.

Aim This review article summarizes the current clinical practice guidelines around disease definitions and risk stratifications, and the treatment of non-muscle-invasive bladder cancer (NMIBC). Recently completed and ongoing clinical trials of novel and investigational therapies in Bacillus Calmette-Guerin (BCG)-naive, BCG-recurrent, and BCG-unresponsive patient populations are also described, e.g., those involving immune checkpoint inhibitors, targeted therapies, other chemotherapy regimens, vaccines, and viral- or bacterial-based treatments. Finally, a brief overview of enhanced cystoscopy and drug delivery systems for the diagnosis and treatment of NMIBC is provided. Background A global shortage of access to BCG is affecting the management of BCG-naive and BCG-recurrent/unresponsive NMIBC; hence, there is an urgent need to assist patients and urologists to enhance the treatment of this disease. Methods Searches of ClinicalTrials.gov, PubMed, and Google Scholar were conducted. Published guidance and conference proceedings from major congresses were reviewed. Conclusion Treatment strategies for NMIBC are generally consistent across guidelines. Several novel therapies have demonstrated promising antitumor activity in clinical trials, including in high-risk or BCG-unresponsive disease. The detection, diagnosis, surveillance, and treatment of NMIBC have also been improved through enhanced disease detection.

Aims Risk stratification algorithms for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) and regional differences in clinical practice have evolved over time. We sought to compare primary prevention implantable cardioverter defibrillator (ICD) implantation rates and associated clinical outcomes in US vs. non-US tertiary HCM centres within the international Sarcomeric Human Cardiomyopathy Registry. Methods and results We included patients with HCM enrolled from eight US sites (n = 2650) and five non-US (n = 2660) sites and used multivariable Cox-proportional hazards models to compare outcomes between sites. Primary prevention ICD implantation rates in US sites were two-fold higher than non-US sites (hazard ratio (HR) 2.27 [1.89–2.74]), including in individuals deemed at high 5-year SCD risk (≥6%) based on the HCM risk-SCD score (HR 3.27 [1.76–6.05]). US ICD recipients also had fewer traditional SCD risk factors. Among ICD recipients, rates of appropriate ICD therapy were significantly lower in US vs. non-US sites (HR 0.52 [0.28–0.97]). No significant difference was identified in the incidence of SCD/resuscitated cardiac arrest among non-recipients of ICDs in US vs. non-US sites (HR 1.21 [0.74–1.97]). Conclusion Primary prevention ICDs are implanted more frequently in patients with HCM in US vs. non-US sites across the spectrum of SCD risk. There was a lower rate of appropriate ICD therapy in US sites, consistent with a lower-risk population, and no significant difference in SCD in US vs. non-US patients who did not receive an ICD. Further studies are needed to understand what drives malignant arrhythmias, optimize ICD allocation, and examine the impact of different ICD utilization strategies on long-term outcomes in HCM.

There are conflicting data regarding the benefit of compression-only bystander cardiopulmonary resuscitation (CO-CPR) compared with CPR with rescue breathing (RB-CPR) after pediatric out-of-hospital cardiac arrest (OHCA).This study sought to test the hypothesis that RB-CPR is associated with improved neurologically favorable survival compared with CO-CPR following pediatric OHCA, and to characterize age-stratified outcomes with CPR type compared with no bystander CPR (NO-CPR).Analysis of the CARES registry (Cardiac Arrest Registry to Enhance Survival) for nontraumatic pediatric OHCAs (patients aged ≤18 years) from 2013-2019 was performed. Age groups included infants (1 year), children (1 to 11 years), and adolescents (≥12 years). The primary outcome was neurologically favorable survival at hospital discharge.Of 13,060 pediatric OHCAs, 46.5% received bystander CPR. CO-CPR was the most common bystander CPR type. In the overall cohort, neurologically favorable survival was associated with RB-CPR (adjusted OR: 2.16; 95% CI: 1.78-2.62) and CO-CPR (adjusted OR: 1.61; 95% CI: 1.34-1.94) compared with NO-CPR. RB-CPR was associated with a higher odds of neurologically favorable survival compared with CO-CPR (adjusted OR: 1.36; 95% CI: 1.10-1.68). In age-stratified analysis, RB-CPR was associated with better neurologically favorable survival versus NO-CPR in all age groups. CO-CPR was associated with better neurologically favorable survival compared with NO-CPR in children and adolescents, but not in infants.CO-CPR was the most common type of bystander CPR in pediatric OHCA. RB-CPR was associated with better outcomes compared with CO-CPR. These results support present guidelines for RB-CPR as the preferred CPR modality for pediatric OHCA.

To date, no study has evaluated the effects of low center performance evaluations (CPE) on pediatric heart transplant center behavior. We sought to assess the impact of low CPE flags on pediatric heart transplant center listing and transplant volumes and center recipient and donor characteristics.We included centers performing at least 10 pediatric (age18 years) transplants during the Scientific Registry of Transplant Recipients reporting period January 2009-June 2011 and evaluated consecutive biannual program specific reports until the last reporting period January 2016-June 2018. We evaluated changes in center behavior at following time points: a year before flagging, a year and two years after the flag; and at last reporting period.During our study period, 24 pediatric centers were non-flagged and 6 were flagged. Compared to non-flagged centers, there was a decline in candidate listings in flagged centers at the last reporting period (mean increase of 5.5 ± 12.4 listings vs"?mean decrease of 14.0 ± 14.9 listings; p = .003). Similarly, the number of transplants declined in flagged centers (mean increase of 2.6 ± 9.6 transplants vs"?mean decrease of 10.0 ± 12.8 transplants; p = .012). Flagged centers had declines in listings for patients with restrictive cardiomyopathy, re-transplant, renal dysfunction, those on mechanical ventilation and extracorporeal membrane oxygenation. There was no significant change in donor characteristics between flagged and non-flagged centers.Low CPE may have unintended negative consequences on center behavior leading to declines in listing and transplant volumes and potentially leading to decreased listing for higher risk recipients.

To describe in detail the retinal phenotype of LAMP2-associated Danon disease.Three LAMP2-positive patients from two unrelated families were studied with spectral-domain optical coherence tomography and with short-wavelength and near-infrared fundus autofluorescence (FAF) imaging. Visual function was measured with full-field electroretinography and chromatic perimetry. A patient with choroideremia was also studied for comparison.A 45-year-old LAMP2-heterozygous woman, her 21-year-old hemizygous son, and an unrelated heterozygous 60-year-old woman had normal visual acuities. Central spectral-domain optical coherence tomographies were grossly normal in the younger two patients (mother and son). The oldest patient showed a tenuous interdigitation signal, interruptions of the inner segment ellipsoid zone band, and parafoveal outer nuclear layer thinning. Quantitatively, all patients had shorter than normal ellipsoid zone to retinal pigment epithelium distance in pericentral retina, normal at the foveola. A speckled hypoautofluorescence pattern on short-wavelength FAF contrasted with grossly abnormal near-infrared FAF in the heterozygous carriers. The oldest patient had reduced full-field electroretinography amplitudes (to ∼50% of normal) for rod- and cone-mediated responses and her perimetry showed severe rod dysfunction but substantial cone function. A disproportionate loss of the near-infrared FAF compared with the short-wavelength FAF, predominantly outer segment changes, and severe rod dysfunction with preserved cone function was similarly documented in a 9-year-old choroideremia hemizygous patient.A disproportionate loss of the near-infrared FAF signal compared with the short-wavelength FAF signal, outer segment abnormalities, and severe rod dysfunction but relatively preserved cone vision suggests a stereotypical pattern of primary retinal pigment epithelial or parallel retinal pigment epithelial + photoreceptor disease in Danon disease.

BACKGROUND Paracorporeal continuous-flow ventricular assist devices (PCF VAD) are increasingly used in pediatrics, yet PCF VAD resource utilization has not been reported to date. METHODS Pediatric Interagency Registry for Mechanically Assisted Circulatory Support (PediMACS), a national registry of VADs in children, and Pediatric Health Information System (PHIS), an administrative database of children's hospitals, were merged to assess VAD implants from 19 centers between 2012 and 2016. Resource utilization, including hospital and intensive care unit length of stay (LOS), and costs are analyzed for PCF VAD, durable VAD (DVAD), and combined PCF-DVAD support. RESULTS Of 177 children (20% PCF VAD, 14% PCF-DVAD, 66% DVAD), those with PCF VAD or PCF-DVAD are younger (median age 4 [IQR 0-10] years and 3 [IQR 0-9] years, respectively) and more often have congenital heart disease (44%; 28%, respectively) compared to DVAD (11 [IQR 3-17] years; 14% CHD); p < 0.01 for both. Median post-VAD LOS is prolonged ranging from 43 (IQR 15-82) days in PCF VAD to 72 (IQR 55-107) days in PCF-DVAD, with significant hospitalization costs (PCF VAD $450,000 [IQR $210,000-$780,000]; PCF-DVAD $770,000 [IQR $510,000-$1,000,000]). After adjusting for patient-level factors, greater post-VAD hospital costs are associated with LOS, ECMO pre-VAD, greater chronic complex conditions, and major adverse events (p < 0.05 for all). VAD strategy and underlying cardiac disease are not associated with LOS or overall costs, although PCF VAD is associated with higher daily-level costs driven by increased pharmacy, laboratory, imaging, and clinical services costs. CONCLUSION Pediatric PCF VAD resource utilization is staggeringly high with costs primarily driven by pre-implantation patient illness, hospital LOS, and clinical care costs.

Summary The increasing global prevalence of SARS‐CoV‐2 and the resulting COVID‐19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS‐CoV‐2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS‐CoV‐2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self‐isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS‐CoV‐2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant‐specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS‐CoV‐2, and other infections are also reviewed.

Thyroid surgery is the primary treatment for substernal goiters, and iatrogenic injury to the recurrent laryngeal nerve (RNL) is always a risk. The literature suggests that iatrogenic lesions of the RNL post resection of substernal goiter are not equally distributed, being more frequent on the right recurrent laryngeal nerve (R-RLN) in comparison to the left recurrent laryngeal nerve (L-RLN). The relative paucity of basic anatomical and clinical reportages on R-RLN iatrogenic injuries and on the developmental factors that may help explain its higher incidence justifies this study's undertaking. Here we compare incidence of right versus left iatrogenic injuries to the RLN in surgical resections of substernal goiters and discuss the anatomical and embryological factors involved. This report is part of a larger retrospective observational cohort study of 239 patients surgically treated for substernal goiter in the Gaffrée and Guinle University Hospital, Rio de Janeiro, from 2006 to 2018. From 239 patients, 13 presented with iatrogenic RLN injury, one patient presented bilateral lesion, totalling 15 iatrogenic lesions. Our analysis showed that the R-RLN seems to be anatomically more vulnerable to injury due to the embryological underpinnings addressed in this review, R-RLN = 64.29% (n = 9) and L-RLN = 35.71% (n = 5). Pathological factors like malignancy and size of the mass are relevant issues to be considered. The knowledge of anatomical landmarks and embryological development of the thyroid and associated structures can improve our understanding and teaching of surgical anatomy, thus helping prevent and reduce the number of iatrogenic injuries on right RLNs.

Aims Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods and results We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36–4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16–2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03–1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23–3.23)]. Conclusion Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

OBJECTIVES We aimed to establish if in celiac disease (CD) with immunoglobulin A deficiency (IgAD) duodenal histopathology is influenced by human leukocyte antigen (HLA)-DQB1∗02 alleles dosage. Clinical differences between patients with CD and patients with CD and IgAD (CD-IgAD) were also evaluated. METHODS Five hundred and sixteen CD and 16 patients with CD-IgAD, enrolled over the time of 8 years, took part in this study. The severity of duodenal histopathology and frequency of CD at-risk HLA class II genes were compared in patients with CD versus patients with CD-IgAD. HLA class II genotypes were subdivided into two categories of genetic risk: high: HLA-DR3/DR7, -DR3/DR3, -DR4/DR4 -DR3/DR4 and low: HLA-DR5/DR7, -DR3/X, -DR4/X and X/X, where X means neither -DR3 nor -DR4. Then, they were compared with two types of duodenal histopathology: 0, 1, 2 and 3a of mild villous atrophy (MVA) and 3b and 3c of severe villous atrophy (SVA) according to the Marsh-Oberhuber classification. Clinical data concerning gender, number of esophagogastroduodenoscopies (EGDs) and association with other autoimmune diseases were obtained from medical records. RESULTS In comparison with CD, CD-IgAD showed an increased frequency of MVA (P

In this paper, we investigate the use of a social robot as an engaging interface of a serious game intended to make children more aware and well disposed towards waste recycle. The game has been designed as a competition between the robot Pepper and a child. During the game, the robot simultaneously challenges and teaches the child how to recycle waste materials. To endow the robot with the capability to play as a game opponent in a real-world context, it is equipped with an image recognition module based on a Convolutional Neural Network to detect and classify the waste material as a child would do, i.e. by simply looking at it. A formal experiment involving 51 primary school students is carried out to evaluate the effectiveness of the game in terms of different factors such as the interaction with the robot, the users’ cognitive and affective dimensions towards ecological sustainability, and the propensity to recycle. The obtained results are encouraging and draw promising scenarios for educational robotics in changing children’s attitudes toward recycling. Indeed Pepper turns out to be positively evaluated by children as a trustful and believable companion and this allows children to be concentrated on the “memorization” task during the game. Moreover, the use of real objects as waste items during the game turns out to be a successful approach not only for perceived learning effectiveness but also for the children’s engagement.

This retrospective cohort study compared the rates of virologically-confirmed SARS-CoV-2 infections, symptomatic or lethal COVID-19 among the residents of the Italian province of Pescara who received one or two doses of COVID-19 vaccines, versus the unvaccinated. The official data of the National Health System were used, and a total of 69,539 vaccinated adults were compared with 175,687 unvaccinated. Among the subjects who received at least one vaccine dose, 85 infections (0.12%), 18 severe and 3 lethal COVID-19 cases were recorded after an average follow-up of 38 days. Among the unvaccinated, the numbers were 6948 (4.00%), 933 (0.53%) and 241 (0.14%), respectively. The serious adverse event reports—yet unconfirmed—were 24 out of 102,394 administered doses. In a Cox model, adjusting for age, gender, and selected comorbidities, the effectiveness of either BNT162b2, ChAdOx1 nCoV-19 or mRNA-1273 vaccines was higher than 95% in preventing infections (mostly due to B.1.1.7 variant), symptomatic or lethal COVID-19. No differences were observed across genders, and among the 691 subjects who received the second dose of vaccine later than the recommended date. Although preliminary, these findings support current immunization policies and may help reducing vaccine hesitancy.

Computational fluid dynamics was employed to predict the early stages of the aerodynamic breakup of a cylindrical water column, due to the impact of a traveling plane shock wave. The unsteady Reynolds-averaged Navier–Stokes approach was used to simulate the mean turbulent flow in a virtual shock tube device. The compressible flow governing equations were solved by means of a finite volume-based numerical method, where the volume of fluid technique was employed to track the air–water interface on the fixed numerical mesh. The present computational modeling approach for industrial gas dynamics applications was verified by making a comparison with reference experimental and numerical results for the same flow configuration. The engineering analysis of the shock–column interaction was performed in the shear-stripping regime, where an acceptably accurate prediction of the interface deformation was achieved. Both column flattening and sheet shearing at the column equator were correctly reproduced, along with the water body drift.

Introdução. A ansiedade é um dos importantes achados no curso do HIV/AIDS e em outras condições neuropsiquiátricas. A incidência de efeitos colaterais com medicamentos tradicionais, desperta o interesse acerca dos fitoterápicos. Assim, o objetivo desta revisão, é identificar a eficácia da Valeriana officinalis no controle da ansiedade e suas manifestações. Método. Foi realizada uma busca em bases de dados: Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS), Medline, Scientific Electronic Library Online (Scielo) e Cochrane, nos idiomas: português, espanhol, inglês e francês, publicados de 2000 a 2020. Resultados. Os resultados apresentaram um total de 11 estudos, incluindo revisões, estudos clínicos e experimentais. A Valeriana officinalis teve ação ansiolítica e modulou a qualidade do sono sendo efetiva em diferentes grupos de indivíduos, inclusive os portadores de HIV/AIDS. Os mecanismos de ação propostos foram: ligação aos Receptores GABA tipo A, 5- Hidroxitriptamina e Adenosina, e redução do turnover de monoaminas. Achados também revelaram facilitação da conectividade cerebral. Conclusão. O conjunto de evidências sugere que esta planta pode ser uma estratégia alternativa no tratamento da ansiedade, inclusive para portadores de HIV. Unitermos: HIV; Aids; Valeriana officinalis; Ansiedade

The recent explosive increase in the number of works on gut microbiota has been accompanied by the spread of rather vague or improper definitions, chosen more for common use than for experimental evidence. Among them are those defining the human gut microbiota as an organ of our body or as a commensal. But, is the human gut microbiota an organ or a commensal? Here, we address this issue to spearhead a reflection on the real roles of the human gut microbiota in our life. Actually, the misuse of the vocabulary used to describe the properties and functions of the gut microbiota may generate confusion and cause misunderstandings both in the scientific community and among the general public.

Objective to investigate the reliability of laryngeal reflux finding score (RFS) and symptom index (RSI) in assessing gastroesophageal reflux (GER) in children and infants. Methods patients with laryngeal or respiratory symptoms, who underwent laryngoscopy and esophageal pH-impedance (MII-pH) were recruited. RSI and RFS were correlated to MII-pH results. A RSI>13, RFS>7, acid exposure index>7%, total reflux episodes>100/24 h in infants or>70/24 h in children, or a positive symptom index or association probability, were considered pathological. Analysis considering age ( 12 months) was performed. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the laryngeal scores were calculated. Results 197 children (median 53 months, 61 infants) were enrolled. MII-pH was pathological in 5/10 patients with RFS>7, and in 17/31 with RSI>13. RFS>7 had 3.9% sensitivity, 93% specificity, a PPV of 50 and a NPV of 34 in predicting GER disease. RFS was inversely associated to weakly acidic and proximal GER. RSI>13 had 13% sensitivity, 83% specificity, and a PPV and NPV similar to RFS. RSI was significantly associated with the number of acid reflux episodes, and, in infants, with bolus exposure index. Conclusions RSI and RFS aren't accurate in predicting GER in infants and children. Acid reflux relates to laryngeal symptoms, but neither acid, nor proximal and weakly acidic GER relate to laryngeal alterations.

Objective To describe the characteristics and rates of child psychiatric hospitalizations in the Brazilian public health system, as well as their variation according to the country’s macro-regions. Methods This was a descriptive study focusing on year 2017, having as main source the Brazilian Ministry of Health’s hospital information system. Child hospitalizations were considered to encompass those of individuals under 13 years of age whose main diagnosis was included in Chapter V of the International Classification of Diseases, 10th edition (ICD-10). Results The most prevalent diagnostic group was F10-F19, with 24.1% (21.8-26.3), followed by groups F30-39, F80-F89, F90-F99, F20-F29, with no statistical difference among them. Hospitalizations occurred more frequently in non-psychiatric hospitals, with 93.1% (91.7-94.4); most hospitalizations lasted for up to one week – 75.5% (73.2-77.8). The national hospitalization rate was 4.3 (4.1-4.5)/100,000, showing variations according to macro-regions. The highest rate was found in the South macro-region and the lowest in the Northeast, with values of 10.9 (9.9-12.0)/100,000 and 1.9 (1.6-2.2)/100,000, respectively. Intermediate values were found in the other macro-regions. Conclusion Some specificities of the characteristics of hospitalizations for psychiatric reasons in this age group could be attested, as well as important variations in their occurrence among the different macro-regions of the country.

Background The present study performed a systematic review and meta-analysis of clinical trials using bisphosphonates for bone demineralization in human immunodeficiency virus (HIV) patients. Methods A comprehensive literature search was performed from January 2004 to January 2020 considering the bone mineral density (BMD) of the lumbar spine (LS) as the main outcome. Out of 214 titles that met criteria, 9 studies fulfilled the selection criteria. Results A total of 394 patients were identified, and they were allocated into 2 groups: the intervention group (200 patients), to whom a combination of alendronate or zoledronate with calcium and vitamin D was administered; and control group (194 patients), to whom only calcium and vitamin D was administered. Clinical profile and indicators of bone metabolism of the participants were evaluated regarding effect size, homogeneity, and consistency. No substantial heterogeneity between the groups was found for the baseline variables, and there was high consistency to the main outcome. The meta-analysis shows a significant difference in post-treatment BMD, favoring the intervention over the control treatment. The intervention improved LS density up to 0.227 g/cm², raising the average to the levels of general population. Adverse effects related to intervention were fever immediately after zoledronate administration and gastrointestinal complaints during alendronate usage. Other adverse effects were barely reported and poorly connected to intervention by studies' authors, despite all of them have been successfully resolved. Conclusions This study provides evidence that BMD post-treatment is better in HIV patients who used bisphosphonates combined with calcium and vitamin D.

Kidney transplantation (KT) is an effective treatment for end-stage renal disease. Despite their rate has reduced over time, post-transplant complications still represent a major clinical problem because of the associated risk of graft failure and loss. Thus, post-KT complications should be diagnosed and treated promptly. Imaging plays a pivotal role in this setting. Grayscale ultrasound (US) with color Doppler analysis is the first-line imaging modality for assessing complications, although many findings lack specificity. When performed by experienced operators, contrast-enhanced US (CEUS) has been advocated as a safe and fast tool to improve the accuracy of US. Also, when performing CEUS there is potentially no need for further imaging, such as contrast-enhanced computed tomography or magnetic resonance imaging, which are often contraindicated in recipients with impaired renal function. This technique is also portable to patients' bedside, thus having the potential of maximizing the cost-effectiveness of the whole diagnostic process. Finally, the use of blood-pool contrast agents allows translating information on graft microvasculature into time-intensity curves, and in turn quantitative perfusion indexes. Quantitative analysis is under evaluation as a tool to diagnose rejection or other causes of graft dysfunction. In this paper, we review and illustrate the indications to CEUS in the post-KT setting, as well as the main CEUS findings that can help establishing the diagnosis and planning the most adequate treatment.

Coronavirus disease of 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has rapidly spread to a global pandemic in March 2020. This emergency condition has been putting a severe strain on healthcare systems worldwide, and a prompt, dynamic response is instrumental in its management. While a definite diagnosis is based on microbiological evidence, the relationship between lung ultrasound (LU) and high-resolution computed tomography (HRCT) in the diagnosis and management of COVID-19 is less clear. Lung ultrasound is a point-of-care imaging tool that proved to be useful in the identification and severity assessment of different pulmonary conditions, particularly in the setting of emergency and critical care patients in intensive care units; HRCT of the thorax is regarded as the mainstay of imaging evaluation of lung disorders, enabling characterization and quantification of pulmonary involvement. Aims of this review are to describe LU and chest HRCT main imaging features of COVID-19 pneumonia, and to provide state-of-the-art insights regarding the integrated role of these techniques in the clinical decision-making process of patients affected by this infectious disease.

Objective: To analyze the prevalence and impact of asthma in schoolchildren from the city of Caxias do Sul, RS, Brazil. Methods: Cross-sectional observational and case-control study with children and adolescents between 7 and 15 years old, from public schools in Caxias do Sul, RS. The study is composed of two phases: Phase I analyzed the prevalence of asthma in the delimited population, investigating 1915 schoolchildren; Phase II quality of life questionnaires, asthma control and classification (for the asthmatic group), physical activity, school performance, pulmonary function tests and anthropometric measures were applied to 266 asthmatics and 288 controls. Results: The estimated prevalence of asthma was 16.1%. In the comparison between asthmatics and nonasthmatics premature birth (p < 0.001) and diagnosis of another chronic disease at birth (p < 0.001) were found. Regarding pulmonary function, significant differences were found in the values between groups in FEV1, FEV1/FVC and forced expiratory flow in the 25 and 75% (FEF25-75%), being that asthmatics presented lower values. Among asthmatics, 133 (50.8%) did not have the disease controlled. In the anthropometric variables, significant differences were observed, with higher values in controls, in the the waist-to-height ratio (p = 0.009) and in the perception of health (p < 0.001). Quality of life is lower in asthmatics in the physical well-being domain (p = 0.001) and in the total score (p = 0.016). The total school performance score did not present a statistically significant difference between the groups. Conclusion: The prevalence of asthma is similar to that of other industrialized urban centers and may negatively affect some areas of the development of schoolchildren. Resumo Objetivo: Analisar a prevalência e o impacto da asma em escolares do município de Caxias do Sul-RS. Métodos: Estudo analítico observacional transversal e caso-controle, com crianças e adolescentes entre sete e 15 anos, de escolas da rede pública de Caxias do Sul-RS. O estudo é composto por duas fases: Fase I analisou a prevalência da asma na população delimitada e investigou 1.915 escolares; Fase II foram aplicados a 266 asmáticos e 288 controles, questionários de qualidade de vida, classificação e controle da asma (para o grupo asmático), atividade física, desempenho escolar, espirometria e antropometria. Resultados: A prevalência de asma estimada foi de 16,1%. Na comparação entre asmáticos e não asmáticos foram encontradas diferenças na prematuridade (p< 0,001) e ter diagnóstico de outra doença crônica ao nascer (p< 0,001). Na espirometria foram encontradas diferenças significativas entre os grupos nos valores de VEF1, VEF1/CVF e fluxo expiratório forçado nos momentos 25 e 75% (FEF25-75%); os asmáticos apresentaram valores inferiores. Entre os asmáticos, 133 (50,8%) não tem a doença controlada. Nas variáveis antropométricas foram observadas diferenças significativas, com valores superiores entre os controles, na classificação razão cintura/estatura (p = 0,009) e na percepção da própria saúde (p< 0,001). A qualidade de vida é menor nos asmáticos no domínio bem estar físico (p = 0,001) e no escore total (p = 0,016). O escore total do desempenho escolar não apresentou diferença estatisticamente significativa entre os grupos de estudo. Conclusão: A prevalência de asma se assemelha à de outros centros urbanos industrializados e pode impactar negativamente alguns domínios do desenvolvimento dos escolares.

LocWeb 2020 was the tenth workshop in the LocWeb workshop series at the intersection of location-based analytics and Web architecture and was held at The Web Conference, WWW 2020, on 21 st April 2020. The focus was on Web-scale services and systems facilitating location-aware information access as well as on Spatial Social Computing on the Web. The LocWeb 2019 workshop had contributions ranging from urban location data analysis over geospatial open data access to worldwide media consumption patterns. The workshop and conference was intended to be held in Taipei, Taiwan, but was instead held as a virtual workshop since also The Web Conference itself moved to be an online-only event, due to the current pandemic. That also gave rise to a number of discussions around spatial models, online work modes, and current mitigation efforts. This report presents an overview of these discussions, after an introduction to the workshop theme and the individual contributions.

Postoperative analgesia after corrective surgery of pediatric craniosynostosis is crucial in terms of short- and long-term outcomes. The objective of this observational study was to evaluate the effectiveness of an analgesic technique based on the scalp block versus traditional pharmacological approach. Thirteen patients, aged between 3 months and 2 years, undergoing surgical correction of craniosynostosis, received scalp nerve block before awakening (scalp block group). This group of patients was compared to a second group of 13 patients, retrieved from our database, treated with the traditional pharmacological approach (control group). Pain scores, need of rescue therapy, resumption of oral nutrition, degree of parent satisfaction at discharge, and length of stay in the Pediatric Intensive Care Unit (PICU) and in the hospital were compared between the two groups. Objective Pain Score values were significantly lower in patients treated with scalp block at 30 min and at 8 h after extubation. The number of pharmacological interventions for the treatment of pain in PICU was significantly higher in Control group. Children in Scalp block group started earlier oral feeding than in Control group, both for clear fluids and milk. Length of stay in PICU was longer in Scalp block group than in Control group, though the difference between the mean data in the two groups is about 3 . This difference does not seem significant from a clinical standpoint, since it seems more related to logistic issues (e.g., availability of bed in the Pediatric Neurosurgery Unit, presence of a parent), rather than clinical problems contraindicating the discharge from PICU. Indeed, the overall hospital length of stay was similar between the two groups. Scalp nerve block was effective for immediate postoperative pain control in patients younger than 2 years who underwent cranioplasty for craniosynostosis. The best pain control compared to conventional therapy allowed to limit the need for rescue analgesics in PICU and an earlier recovery time. ClinicalTrials.gov Identification: NCT04133467

Finite element analysis (FEA) and computational fluid dynamics (CFD) are generally insufficient independently to model the physics of the cardiovascular system. Individually, they are unable to resolve the interplay between the solid and fluid domains, and the interplay is integral to the functioning of the system. The use of fluid-structure interaction (FSI) methods overcomes these shortcomings by providing the means to couple the fluid and structural domains. In the last decade, the utilization of FSI has greatly increased in cardiovascular engineering. In this study, we conducted a systematic review process of more than 1000 journal articles to investigate the implementation of One-Way and Two-Way FSI for cardiovascular applications. We explored the utility of FSI to study aneurysms, the hemodynamics of patient anatomies, native and prosthetic heart valve dynamics, flow and hemodynamics of blood pumps, and atherosclerosis. Computational resource requirements, implementation strategies and future directions of FSI for cardiovascular applications are also discussed.

Requesting plays a key role in human communication. One can request the same thing in multiple ways (e.g., “Pass the salt” vs. “Could you pass the salt?”). How do speakers determine which request f...

Background: Avelumab, a human IgG1 anti–PD-L1 monoclonal antibody, has shown antitumor activity and a manageable safety profile in several tumor types. Talazoparib, an orally available PARP inhibitor, is approved for the treatment of patients with deleterious or suspected deleterious germline BRCA1/2-mutated HER2− locally advanced (LA) or metastatic (M) breast cancer (BC). Preclinical data suggest that PARP inhibitors may have synergistic activity when administered in combination with immune checkpoint inhibitors. We report results from patients with LA/MBC enrolled in the phase 1b/2, multicohort JAVELIN PARP Medley study (NCT03330405). Methods: In phase 1b (cohort 1), patients with advanced solid tumors who had received ≥1 prior standard of care chemotherapy (CT) regimen were treated with avelumab 800 mg IV every 2 weeks (Q2W) in combination with talazoparib 1.0 mg orally once daily (QD) (dose de-escalation to 0.75 or 0.5 mg permitted following toxicity). In 2 phase 2 cohorts, eligible patients had either LA/M triple-negative BC (TNBC, cohort 2A) or LA/M hormone receptor positive (HR+), HER2−, DNA damage repair defect-positive BC (cohort 2B). Patients in cohort 2A had received 0 to 2 prior CT regimens (no progression on prior platinum-based CT) and patients in cohort 2B had received prior standard of care hormone therapy in either the adjuvant and/or LA/M setting followed by 0 to 2 prior CT regimens (no progression on prior platinum-based CT). The primary endpoint for phase 1b was first-cycle dose-limiting toxicities (DLTs) and for phase 2 was objective response (investigator assessed per RECIST v1.1). Adverse events (AEs) were characterized using National Cancer Institute Common Terminology Criteria for AEs v4.03. Results: By the data cutoff on December 24, 2018, 34 patients had been treated in cohorts 1 and 2. Twelve patients with advanced solid tumors were treated in cohort 1 (including 2 patients with TNBC); 3 patients (25.0%) had a first-cycle DLT: grade 3 neutropenia, (n=1) and grade 3 thrombocytopenia, (n=2). Best overall response (BOR) was partial response (PR) in 1 patient, stable disease (SD) in 3, progressive disease (PD) in 6, and non-complete response/non-PD in 1 patient with metastatic castration-resistant prostate cancer and non-measurable disease at baseline; 1 patient was not evaluable for response. Both patients with TNBC had a BOR of SD and remained on treatment for ≥9 months. Objective response rate in this pre-treated and heterogenous population was 8.3% (95% CI, 0.2, 38.5). Based on the phase 1b data, the recommended phase 2 dose was avelumab 800 mg Q2W and talazoparib 1 mg QD. By data cutoff, 22 patients had been treated in cohorts 2A (n=19) and 2B (n=3); median age was 56 and 50 years, respectively. In cohort 2A, 12 patients were evaluable for disease assessment; BOR was PR in 1, SD in 6, and PD in 5. All 3 patients in cohort 2B were non-evaluable for response at data cutoff. Treatment-related AEs (TRAEs) of any grade occurred in 11 patients (91.7%) in cohort 1, and 18 (94.7%) patients in cohort 2A. In cohort 2A, the most common TRAEs were anemia (57.9%), nausea (26.3%), fatigue (21.1%) and thrombocytopenia (21.1%); 9 patients (47.4%) had grade ≥3 TRAEs. There were no treatment-related deaths. Safety data from cohort 2B are not reported owing to low patient numbers. Observed pharmacokinetic (PK) data for avelumab 800 mg Q2W were similar to simulated data derived from a population PK model developed using 10 mg/kg dosing. Conclusions: Avelumab 800 mg Q2W administered in combination with talazoparib 1 mg QD in patients with advanced solid tumors, showed preliminary antitumor activity and a manageable safety profile, which was comparable to the safety profiles of the single agents. The study is ongoing; updated safety and efficacy data, and biomarker data will be presented. Citation Format: Timothy A Yap, Panagiotis Konstantinopoulos, Melinda L. Telli, Smita Saraykar, J Thaddeus Beck, Matthew D. Galsky, Jame Abraham, David R. Wise, Mustafa Khasraw, Gabor Rubovszky, Mikhail Dvorkin, Anil A Joy, Mateusz Opyrchal, Daria Stypinski, Colombe Chappey, Ross Stewart, Rossano Cesari, Anita Scheuber, Aditya Bardia. JAVELIN PARP Medley, a phase 1b/2 study of avelumab plus talazoparib: Results from advanced breast cancer cohorts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-03.

Multi-parametric prostate MRI (mpMRI) plays a critical role in the diagnosis, staging, and evaluation of treatment response in patients with prostate cancer. Radiologists, through an accurate and standardized interpretation of mpMRI, can clinically stage prostate cancer and help to risk stratify patients who may benefit from more invasive treatment or exclude patients who may be harmed by overtreatment. The purpose of this article is to describe key findings to accurately stage prostate cancer with mpMRI and to describe the contexts in which mpMRI is best applied.

Purpose To compare the sensitivity for breast cancer (BC) and BC size estimation of preoperative contrast-enhanced magnetic resonance imaging (CEMRI) versus combined unenhanced magnetic resonance imaging (UMRI) and digital breast tomosynthesis (DBT). Patients and methods We retrospectively included 56 women who underwent DBT and preoperative 1.5 T CEMRI between January 2016–February 2017. Three readers with 2–10 years of experience in CEMRI and DBT, blinded to pathology, independently reviewed CEMRI (diffusion-weighted imaging [DWI], T2-weighted imaging, pre- and post-contrast T1-weighted imaging) and a combination of UMRI (DWI and pre-contrast T1-weighted imaging) and DBT. We calculated per-lesion sensitivity of CEMRI and UMRI + DBT, and the agreement between CEMRI, UMRI and DBT versus pathology in assessing cancer size (Bland-Altman analysis). Logistic regression was performed to assess features predictive of cancer missing. Results We included 70 lesions (64% invasive BC, 36% ductal carcinoma in situ or invasive BC with in situ component). UMRI + DBT showed lower sensitivity (86–89%) than CEMRI (94–100%), with a significant difference for the most experienced reader only (p = 0.008). False-positives were fewer with UMRI + DBT (4–5) than with CEMRI (18–25), regardless of the reader (p = 0.001–0.005). For lesion size, UMRI showed closer limits of agreement with pathology than CEMRI or DBT. Cancer size ≤1 cm was the only independent predictor for cancer missing for both imaging strategies (Odds ratio 8.62 for CEMRI and 19.16 for UMRI + DBT). Conclusions UMRI + DBT showed comparable sensitivity and less false-positives than CEMRI in the preoperative assessment of BC. UMRI was the most accurate tool to assess cancer size., Highlights • Combined UMRI + DBT shows high sensitivity in the preoperative assessment of breast cancer. • UMRI + DBT avoids most false-positives induced by CEMRI. • In combined imaging, UMRI is the better predictor of cancer size at pathology. • UMRI + DBT is a potential alternative to CEMRI in the preoperative assessment of breast cancer.

Introduction:The concept of compressions only cardiopulmonary resuscitation (CO-CPR) evolved from a perception that lay rescuers may be less likely to perform mouth-to-mouth ventilations during an emergency. This study hopes to describe the efficacy of bystander compressions and ventilations cardiopulmonary resuscitation (CV-CPR) in cardiac arrest following drowning.Hypothesis/Problem:The aim of this investigation is to test the hypothesis that bystander cardiopulmonary resuscitation (CPR) utilizing compressions and ventilations results in improved survival for cases of cardiac arrest following drowning compared to CPR involving compressions only.Methods:The Cardiac Arrest Registry for Enhanced Survival (CARES) was queried for patients who suffered cardiac arrest following drowning from January 1, 2013 through December 31, 2017, and in whom data were available on type of bystander CPR delivered (ie, CV-CPR CO-CPR). The primary outcome of interest was neurologically favorable survival, as defined by cerebral performance category (CPC).Results:Neurologically favorable survival was statistically significantly associated with CV-CPR in pediatric patients aged five to 15 years (aOR = 2.68; 95% CI, 1.10–6.77; P = .03), as well as all age group survival to hospital discharge (aOR = 1.54; 95% CI, 1.01–2.36; P = .046). There was a trend with CV-CPR toward neurologically favorable survival in all age groups (aOR = 1.35; 95% CI, 0.86–2.10; P = .19) and all age group survival to hospital admission (aOR = 1.29; 95% CI, 0.91–1.84; P = .157).Conclusion:In cases of cardiac arrest following drowning, bystander CV-CPR was statistically significantly associated with neurologically favorable survival in children aged five to 15 years and survival to hospital discharge.

In the environmental sector, in recent years, policies and governance of marine issues have seen greater enhancement of participatory and community-based processes (for example the Blue Growth Actions of the Interreg Med Program of the European Union). The greater involvement of citizens in the processes and policies of the sea can greatly benefit the survival of the marine environment and support reforms, since most environmental problems are caused by human behavior. Changes in individual behaviors are desirable to ensure sustainable use of the ocean and its resources. These changes are possible only if there is an improvement in people’s knowledge and awareness since the childhood. Ocean literacy interventions will allow people to understand their responsibilities towards the oceans and their health. For this reason, it is necessary to promote sustainable behavior changes using new educational approaches that can be effective with young pupils. The research presents a serious game and an explainer video, used in order to introduce the problem of marine litter, one of the main dangers for the marine species. The aim of the serious game was to enhance ocean literacy with a particular attention to the biodiversity of the Apulian and Mediterranean sea to raise children’s awareness of the issue of caring for life in the sea. The measure of learning effectiveness confirmed that the knowledge gained can be actually acquired by children using new technologies, in general, and serious games in particular.

Currently digital educational applications are employed in education, since technological tools are very interesting and engaging for pupils. Augmented Reality (AR) is one of the most explored and successfully used technology. Thanks to the AR, the situated learning can occur; it suggests that people easily acquire new knowledge if learning occurs in a specific context and is embedded in a physical environment. This paper presents an AR application, called Geo+, for supporting primary school students in the acquisition of knowledge on the solid geometry. Geo+ has been developed by following a Human-Centered Design approach, thus several formative evaluation studies were performed to enhance the quality of the resulting application. A user study involving 96 pupils of the 3rd grade of primary school was performed in order to investigate the learning effectiveness, the engagement and the perceived workload of Geo+ at school. The results showed that Geo+ is effective in terms of student learning gain. In addition, pupils really appreciated the ease of use of the game; they were satisfied and felt engaging and comfortable during the interaction, none of them ask for help during the execution of the learning activities.

Supplemental Digital Content is available in the text., Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Objectives: To compare the effect of different PSA density (PSAD) thresholds on the accuracy for clinically significant prostate cancer (csPCa) of the Prostate Imaging Reporting And Data System v.2.1 (PI-RADSv2.1). Methods: We retrospectively included 123 biopsy-naïve men who underwent multiparametric magnetic resonance imaging (mpMRI) and transperineal mpMRI-targeted and systematic prostate biopsy between April 2019 and October 2020. mpMRI, obtained on a 3.0T magnet with a PI-RADSv2.1-compliant protocol, was read by two radiologists (>1500/>500 mpMRI examinations). csPCa was defined as International Society of Urogenital Pathology grading group ≥2. Receiver operating characteristic analysis was used to calculate per-index lesion sensitivity, specificity, and area under the curve (AUC) of PI-RADSv.2.1 categories after adjusting for PSAD ≥0.10,≥0.15, and ≥0.20 ng/mL ml−1. Per-adjusted category cancer detection rate (CDR) was calculated, and decision analysis performed to compare PSAD-adjusted PI-RADSv.2.1 categories as a biopsy trigger. Results: csPCa prevalence was 43.9%. PSAD-adjustment increased the CDR of PI-RADSv2.1 category 4. Sensitivity/specificity/AUC were 92.6%/53.6%/0.82 for unadjusted PI-RADS, and 85.2%/72.4%/0.84, 62.9%/85.5%/0.83, and 92.4%/53.6%/0.82 when adjusting PI-RADS categories for a 0.10, 0.15, and 0.20 ng/ml ml−1 PSAD threshold, respectively. Triggering biopsy for PI-RADS four lesions and PSAD ≥0.10 ng/mL ml−1 was the strategy with greatest net benefit at 30 and 40% risk probability (0.307 and 0.271, respectively). Conclusions: PI-RADSv2.1 category four with PSAD ≥0.10 ng/mL ml−1 was the biopsy-triggering cut-off with the highest net benefit in the range of expected prevalence for csPCa. Advances in knowledge: 0.10 ng/mL ml−1 is the PSAD threshold with higher clinical utility in stratifying the risk for prostate cancer of PI-RADSv.2.1 categories.

Fontan-associated protein losing enteropathy is a challenge to treat and is a major contributor to morbidity and mortality in patients with palliated single ventricle. Numerous strategies for management have been proposed, with confusion as to how best to stratify and implement care among the many treatments available. Medical management can be helpful in some, while novel lymphatic interventions hold potential for remission with good results. We review our institutional approach to protein losing enteropathy after Fontan operation and provide a suggested algorithm and pathway for effective care.

Objectives Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality. Methods A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation. Results All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells. Conclusions This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial.

BACKGROUND Desensitization, the process of reducing anti-human leukocyte antigen (HLA) antibodies in sensitized patients awaiting heart transplantation (HT), has unclear efficacy in pediatric HT candidates. METHODS Pediatric HT candidates listed at our institution between January 1, 2013 and June 30, 2018 were retrospectively evaluated. Sensitization was defined as the calculated panel reactive antibody (cPRA) ≥ 10% with ≥ 1 a strong positive antibody. The desensitization response was defined as a ≥ 25% reduction in the mean fluorescence intensity (MFI) for ≥ 90% of the strong positive antibodies on follow-up panel reactive antibody (PRA) testing before waitlist removal, HT, or death (data available for 13 patients). RESULTS The HT candidates were categorized as sensitized receiving desensitization therapy (ST, n = 14), sensitized not receiving therapy (SNT, n = 18), or non-sensitized (n = 55). A desensitization response was observed in 8 (62%) of the ST upon repeat PRA testing, with the ST responders receiving more doses of intravenous immunoglobulin (IVIG) (8 vs 2, p < 0.05). The anti-HLA class I antibodies were particularly resistant for non-responders (p = 1.9 × 10-4). The combination of homograft and ventricular assist device was more sensitizing than either alone (p = 3.1 × 10-4). However, these sensitization risk factors did not impact the desensitization response. The ST was associated with a higher likelihood of remaining listed and a longer waitlist time without substantially impacting the HT rate, waitlist mortality, or early post-HT outcomes. CONCLUSIONS Most ST patients had a favorable response to desensitization, with a dose-dependent response observed for IVIG. The anti-HLA class likely impacts the ST response, whereas traditional sensitization risk factors had no impact on the response.

Background Patients with single‐ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight–adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post‐Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2‐part, open‐label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single‐arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open‐label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov . Identifier: NCT02846532.

This paper reports the results of a simulation study with the aim of evaluating the capability of two portions of a hybrid AC/DC MV/LV network of maintaining their operation in off-grid mode during the loss of the main AC grid due to a failure. In particular, the study aims to verify, in the case of islanded operation of the two microgrids, the continuity of the electricity service by exploiting the local generation plants, Energy Storage Systems (ESSs), and other flexible resources managed by suitable algorithms in different energy scenarios. The analysis was carried out considering two microgrids: an underground station and a car parking with Electric Vehicles (EVs). For assessing the performance of the network, specific indicators have been defined and calculated.

Patients with chronic disorders, like chronic kidney disease (CKD), are considered at greater risk of COVID-19 infection, with higher morbidity and mortality. To date, specific instructions have been developed for managing COVID-19 outbreaks for patients on haemodialysis and peritoneal dialysis, and with kidney transplants; however, the proper management of patients with non-dialysis CKD is still being evaluated. The rapid spread of COVID-19 and the consequent lockdown, required many changes in our CKD center organization to avoid unnecessary exposure of staff and patients to infection, while still continuing to provide care and support to our patients. Therefore, elective treatments and procedures, routine laboratory testing and non-urgent outpatient clinics were deferred, and patients were divided in 2 main priority groups: 1)Non urgent, deferrable patients, for whom we adopted telemedicine follow-up; 2)Urgent, undeferrable outpatients, for whom an effort has been made to arrange for specific appointment times for blood drawing and for ambulatory visits. Specific recommendations have been provided to our staff office to respond to patient questions about a possible COVID-19 exposure. Elective procedures, as kidney biopsies and access creation for dialysis, have been defereed in most cases, except for urgent patients. For patients receiving intravenous treatments, we organized home therapy services; new enrolment into clinical trials has been paused during the COVID-19 crisis, but CKD patients enrolled in therapeutic clinical trials should continue the study drug.

Computational fluid dynamics (CFD) analysis is carried out to evaluate the early stages of the aerobreakup of a cylindrical water column due to the impact of a travelling plane shock wave. The mean flow in a shock tube is simulated by adopting the compressible unsteady Reynolds-averaged Navier-Stokes modelling approach, where the governing equations are solved by means of a finite volume-based numerical technique. The volume of fluid method is employed to track the transient interface between air and water on the fixed numerical mesh. The present computational modelling approach for industrial gas dynamics applications is verified to have significant practical potential by making a comparison with reference experiments and numerical simulations.

Agreement measures are useful metrics to both compare different evaluations of the same diagnostic outcomes and validate new rating systems or devices. While many of them have been proposed in the literature so far, Cohen’s n is still the de facto standard in gauging the agreement. Information Agreement (IA) is a novel two-observers information-theoretic-based metric introduced to overcome all the limitations and alleged pitfalls of Cohen’s n. It offers an operative meaning to the agreement since it measures – in both dichotomous and multi-value ordered-categorical cases-the information shared between two raters through the virtual diagnostic channel connecting them: the more information exchanged between the raters, the higher their agreement. Unfortunately, this measure is only able to deal with agreement matrices whose values are all strictly positive numbers. This work extends IA by admitting also 0 as a possible value for the entries of an agreement matrix. Moreover, a Python software library to compute the extended version of IA, together with some of the most used agreement measures, is presented and tested.

Diabetes is a complex pathology both for the affected patients and for the medical specialists who follow them. Furthermore, since diabetes is a pathology with a high prevalence and incidence, it is essential to intervene effectively in therapeutic actions through the application of common guidelines. Therefore, in order to improve the management of the diabetic patient, the aim of the work is to define a Diagnostic Therapeutic Assistance Pathway (PDTA). A questionnaire-based approach is adopted for data collection from 136 patients at the Clinical Dermatology Unit of the University Hospital “Federico II”. In most cases (64%) the diagnosis was made by the General Practitioner, 15% of patients obtained the diagnosis at the ASL and 12% at the Polyclinic of Naples AOU “Federico II” and the remaining part from the diabetologist specialist. The second access is generally carried out at the “Federico II” AOU (66%), followed by the ASL (17%), by a doctor specialized in diabetology (12%) while no patient has turned to the General Practitioner for the treatment of diabetes. The final visit is carried out at the “Federico II” AOU in almost cases. The data obtained follow the Italian guidelines: the patients get the diagnosis from the Family Doctor and then they are addressed either to ASL or to diabetologists specialists. For the subsequent visits, most of them prefer to turn to the “Federico II” AOU, especially when they have complications associated with the diseases as they are followed in a more careful and satisfying manner.

The energy transition and climate neutrality are a short time scenario as climate concerns are rising fast. Small islands are natural microgrids in which the energy transition is subjected to economic and regulatory constraints and highly challenged by technical issues. As a first step, the Mediterranean island of Favignana has been considered in this study, to assess how electric mobility could impact the power system. According to the plans from the local decision makers, the island is moving towards a full public electric mobility in the near term, also due to the participation in the BloRin project. For this reason, a feasibility study about the technical and environmental impact of electric mobility is highly needed. What appears is that the network is ready for such a transition even if carried out in massive terms, while the current electric mix makes the shift to electric mobility more polluting. Therefore, the assessment of the environmental impact, quantified comparing the emissions of the current scenario with those of a future condition with a 20% penetration of EVs on the island, highlights the need of a simultaneous shift to zero emission power production. The simulations are carried out using the NEPLAN software and considering various operating scenarios. In most cases, the substations are charged two times the current power flows, but never going beyond the rated capacity.

We present a case of a chronic mass-forming pancreatitis (CMFP) detected by 18F-choline (FCH) PET/CT in a male affected by prostate cancer. FCH PET/CT scan showed a focal uptake in the uncinate process of the pancreas, later diagnosed as a CMFP at biopsy. Although the physiological distribution of FCH in the pancreas, a careful interpretation of the images in this area is warranted.

This work examines the operation of the autonomous power system of a geographical island assuming the integration of significant generation shares from renewable energy sources and the installation of the required storage systems. The frequency stability of the system is investigated considering different operating conditions, in terms of load demand and renewable power generation. The main focus of the work is an original control strategy specifically designed for power converters interfacing storage units to the grid. The proposed strategy is based on an extended frequency droop control, which selects specific droop settings depending on the operating mode—charge or discharge—of the storage unit. A simulation model of the whole electrical system is developed for dynamic analysis. The model also implements the possibility of including specific auxiliary frequency controls for synthetic inertia and primary reserve. The results of the simulation and analysis indicate that the proposed control strategy has a significant positive effect, making the storage units able to provide a fundamental and more effective support to the frequency stability of the system. The application of the proposed control strategy to storage units also reduces the need for a contribution to the frequency control from intermittent and variable sources, making the whole system more robust, stable and reliable.

Severe acute respiratory coronavirus-2 syndrome (SARS-CoV-2) is a well-known pandemic infectious disease caused by an RNA virus belonging to the coronaviridae family. The most important involvement during the acute phase of infection concerns the respiratory tract and may be fatal. However, COVID-19 may become a systemic disease with a wide spectrum of manifestations. Herein, we report the natural history of sacroiliac inflammatory involvement in two females who developed COVID-19 infection with mild flu-like symptoms. After the infection they reported inflammatory back pain, with magnetic resonance imaging (MRI) studies showing typical aspects of sacroiliitis. Symptoms improved with NSAIDs therapy over the following months while MRI remained positive. A literature review was performed on this emerging topic. To our knowledge, this is the first MRI longitudinal study of post-COVID-19 sacroiliitis with almost one year of follow-up. Predisposing factors for the development of articular involvement are unclear but a long-lasting persistence of the virus, demonstrated by nasopharyngeal swab, may enhance the probability of altering the immune system in a favourable background.