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Liver; Pediatrics; Sarcoma Fetge; Pediatria; Sarcoma Hígado; Pediatría; Sarcoma Background To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. Methods This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. Results Out of 65 patients with a median age at diagnosis of 8.7 years (0.6–20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2–95.5) and 89.1% (95% CI: 78.4–94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. Conclusions Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

PURPOSE Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% ( P < .0001) and 3-year OS 60.0% versus 26.0% ( P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.

Background Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (18F-FDG-PET/CT (PET-CT)) use is increasing. The aim of this study was to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008. Methods Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared. Results Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0–5) with PET-CT and 1.72 (range 0–5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease. Conclusion PET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement.

The survival of patients with localized embryonal rhabdomyosarcoma (RMS) completely resected at diagnosis is greater than 90%. Most patients have paratesticular, uterine, or vaginal RMS, limiting specific analyses of RMS localized in other anatomic regions. This international study was conducted to define the outcome for completely resected embryonal RMS at sites other than paratesticular, uterine, or vaginal primary sites.A total of 113 patients aged 0-18 years were identified who were enrolled from January 1995 to December 2016 in Children's Oncology Group (COG) (64 patients) and European protocols (49). Genitourinary nonbladder and prostate RMS were excluded. The recommended chemotherapy was vincristine and actinomycin-D (VA) for 24 weeks or ifosfamide plus VA in the European protocols and VA for 48 weeks or VA plus cyclophosphamide in the COG protocols.The most common primary sites were nonparameningeal head and neck (40.7%), other (23.9%), and extremities (20.4%). In the COG studies, 42% of patients received VA and 58% VA plus cyclophosphamide. In Europe, 53% received VA and 47% ifosfamide plus VA. With a median follow-up of 97.5 months, the 5-year progression-free and overall survival was 80.0% (71.2%-86.4%) and 92.5% (85.6%-96.2%), respectively, without significant differences between chemotherapy regimens. Tumor size (or5 cm) significantly influenced overall survival: 96.2% (88.6%-98.8%) vs. 80.6% (59.5%-91.4%), respectively (p = .01).Survival of patients with nonalveolar RMS completely resected at diagnosis is excellent among tumors arising from nonparatesticular, uterine, and vaginal sites, and patients may be treated successfully with low-intensity chemotherapy. To reduce the burden of treatment, VA for 24 weeks may be considered in children with tumors5 cm.

Rhabdomyosarcoma is the commonest soft tissue sarcoma in children. Clinicians need vigilance to recognize the different signs and symptoms this tumor can present with because of variable sites of origin. Diagnosis requires a safe biopsy that obtains sufficient tissue for pathologic, genetic, and biological characterization of the tumor. Treatment depends on accurate staging with imaging and surgical sampling of draining lymph nodes. A multidisciplinary team assigns patients to risk-based therapy. Patients require chemotherapy and usually a combination of complex, site-specific surgery and/or radiotherapy. Outcomes for localized rhabdomyosarcoma continue to improve but new treatments are required for metastatic and relapsed disease.

Rhabdomyosarcoma (RMS) is the most common form of soft tissue sarcoma in children. We report the results of the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study, which prospectively evaluated the reduction of chemotherapy in patients with embryonal RMS (ERMS) after initial surgery.Between October 2005 and December 2016, all patients with localised ERMS with an initial microscopically complete resection (IRS group I) with lymph node-negative (N0) were prospectively enrolled in the low-risk (n = 70, subgroup A; age 10 years and tumour size ≤ 5 cm) or standard-risk group (n = 108, subgroup B; age ≥ 10 years or tumour size 5 cm. Subgroup A received 8 courses of vincristine and dactinomycin (VA) for 22 weeks; subgroup B received 4 courses of VA with ifosfamide (IVA) and 5 courses of VA for 25 weeks.The 5-year event-free survival (EFS) and overall survival (OS) were 90.8% (95% confidence interval [CI]: 85.0-94.4) and 95.7% (95% CI: 90.5-98.1), respectively (n = 178). The EFS and OS were 95.5% (95% CI: 86.8-98.5) and 100% (subgroupA), and 87.8% (95% CI: 79.3-93.0) and 93.0% (95% CI: 84.8-96.8)(subgroup B), respectively. Bearman stage 2 veno-occlusive disease (VOD) occurred in 4 very young patients.VA treatment for 8 courses was effective and well tolerated by the subgroup of patients with low-risk ERMS (group A). Four courses of IVA and 5 courses of VA instead of 9 courses of IVA also has very good results. Careful monitoring for liver toxicity is important in very young patients. European union drug regulating authorities clinical trials EUDRACT No. 2005-000217-35.

The current study aimed to assess the changes in physical and perceptual markers of health, fitness, and well-being over the first semester of university study in a New Zealand context. In a pre-post longitudinal design, 90 first-year university students (39 females, 51 males, mean ± SD age: 18 ± 2 years) studying in the field of health, sport and human performance underwent tests of body mass, height, body mass index (BMI), blood pressure, predicted VO2max, flexibility, countermovement jump height, handgrip strength, isometric mid-thigh pull strength, and well-being pre and post the first semester of university study (12 weeks). When evaluating the entire group, there was a significant increase in body mass (0.66 kg, P = 0.004) and BMI (0.2 kg/m2, P = 0.005) and decrease in the “engagement” construct of the well-being questionnaire (− 0.2, P = 0.03) over the first semester of university. In total, 73% of students living on-campus reported a decline in sleep and nutrition habits since starting university, in comparison to ~ 35%–40% of students living off-campus (P ≤ 0.03). Similar to results seen in other countries, and despite the field of study, the first semester of university in New Zealand is likely to be associated with increases in body mass and BMI; however, changes in physical fitness and overall well-being measures were less obvious in the current study.

Rhabdomyosarcoma of the extremities present with two main challenges: correct evaluation of initial regional nodal involvement and define adequate local treatment. Methods Pediatric patients with localized rhabdomyosarcoma of the extremity included in the EpSSG‐RMS2005 study between 2005 and 2014 were evaluated for staging, treatment, and survival. The outcome was compared to the preceding European SIOP‐MMT studies. Results Of the 162 patients included, histology was unfavorable in 113 (70%), 124 (77%) were younger than 10 years, 128 (79%) were IRS III, and 47 (29%) were node‐positive. A regional node biopsy was performed in 97 patients (60%) and modified the lymph node stage in 15/97 (16%). Primary and delayed surgery was performed in 155 (96%) and radiotherapy delivered in 118 (73%) patients. Relapse occurred in 61 cases (38%), local in 14 (23%), regional in 13 (21%), distant in 22 (36%), and combined relapse in 12 (20%) with five progressive diseases (8%) and four secondary tumors (7%). Five‐year event free (EFS) and overall survival (OS) were 58.4% (95%CI, 50.3‐65.7) and 71.7% (63.6‐78.4), respectively. In the previous studies MMT89 and MMT95, tumor surgery was performed in 32/53 (60%) and 74/82(90%), respectively, and radiotherapy delivered in 13/53 (25%) and 26/82 (30%), respectively. Five‐year EFS and OS were 35.6%, and 50.3% in MMT89 and 54.3% and 68.2% in the MMT95 study. Conclusions Even if the lymph node staging was not always complete according to the RMS2005 protocol, node sampling changed lymph node status in a significant number of patients. Despite the higher rate of patients treated with locoregional radiotherapy, survival in RMS2005 did not improve compared to the previous European SIOP‐MMT95 study., Adequate staging is important for the treatment of extremity RMS. Despite local therapy intensification, survival in RMS2005 did not improve compared to the previous European SIOP‐MMT95 study.

Control processes are critical for the generation of task-appropriate behaviour across cognitive domains, yet children have a long developmental period with reduced executive control. Traditionally, this is viewed as a negative but necessary consequence of the time taken to learn control processes and develop the prefrontal cortex. Here, we exploit a recent computational model of controlled semantic cognition to formally test an alternative (yet perhaps complementary) view that a developmental period without control promotes conceptual knowledge acquisition. Our simulations show that maturational delay and anatomical connectivity conspire to promote conceptual learning. Learning conceptual structure necessitates a connection from control to more peripheral regions rather than the deep multimodal hub. Delayed control speeds conceptual learning without compromising conceptual representations, particularly when control connects to intermediate layers. These results are counterintuitive as delayed control onset can produce overall faster mastery of controlled behaviours. To assess whether delayed semantic control is also observed over development, we conducted a meta-analysis of the classic triadic matching task where participants decide which of two options best matches a third. Matching can be based on taxonomic or thematic relations, and when these conflict, participants must use task context to determine which relation to choose—that is, they must exert semantic control. Children aged 2 have the representations to identify both relations when distractors are unrelated, but when relations conflict, they cannot use context to guide their choices. Context-sensitivity develops later than conceptual structure and shows large increases around 6, a critical time for executive function across domains.

Background: Adolescent and young adult patients with rhabdomyosarcoma often have poorer outcomes than do children. We aimed to compare the findings of adolescent and young adult patients with children enrolled in two prospective clinical protocols. Methods: This retrospective observational analysis was based on data from the European paediatric Soft tissue sarcoma Study Group (EpSSG) rhabdomyosarcoma 2005 trial (phase 3 randomised trial for localised rhabdomyosarcoma, open from April, 2006, to December, 2016) and the EpSSG MTS 2008 protocol (prospective, observational, single-arm study for metastatic rhabdomyosarcoma, open from June, 2010, to December, 2016), which involved 108 centres from 14 different countries in total. For this analysis, patients were categorised according to their age into children (age 0–14 years) and adolescents and young adults (age 15–21 years). For the analysis of adherence to treatment and toxicity, only patients with high-risk localised rhabdomyosarcoma included in the randomised part of the rhabdomyosarcoma 2005 study were considered. The primary outcome of event-free survival (assessed in all participants) was defined as the time from diagnosis to the first event (eg, tumour progression, relapse) or to the latest follow-up. Secondary outcomes were overall survival, response to chemotherapy, and toxicity. Findings: Our analysis included 1977 patients, 1720 children (median age 4·7 years; IQR 2·6–8·4) and 257 adolescents and young adults (16·6 years; 15·8–18·0). 1719 patients were from the EpSSG rhabdomyosarcoma 2005 study (1523 aged

The automated localisation of damage in structures is a challenging but critical ingredient in the path towards predictive or condition-based maintenance of high value structures. The use of acoustic emission time of arrival mapping is a promising approach to this challenge, but is severely hindered by the need to collect a dense set of artificial acoustic emission measurements across the structure, resulting in a lengthy and often impractical data acquisition process. In this paper, we consider the use of physics-informed Gaussian processes for learning these maps to alleviate this problem. In the approach, the Gaussian process is constrained to the physical domain such that information relating to the geometry and boundary conditions of the structure are embedded directly into the learning process, returning a model that guarantees that any predictions made satisfy physically-consistent behaviour at the boundary. A number of scenarios that arise when training measurement acquisition is limited, including where training data are sparse, and also of limited coverage over the structure of interest. Using a complex plate-like structure as an experimental case study, we show that our approach significantly reduces the burden of data collection, where it is seen that incorporation of boundary condition knowledge significantly improves predictive accuracy as training observations are reduced, particularly when training measurements are not available across all parts of the structure.

Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment.International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed.Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size5 cm impacting 5-year EFS and OS (p .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21.About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database.

Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes magnetic resonance imaging, chest computed tomography (CT) and bone scintigraphy, but 18 Fluorine-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared.Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118 of 121 patients, both PET-CT and radiological reports were available for review. PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% versus 78.5%, P value = 0.0013) and distant lymph node involvement (94.8% versus 79.3%, P value = 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% versus 100%, P value = 0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% versus 67.9%, P value = 0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively. The mean number of metastatic sites was 1.94 (range 0-5) with PET-CT and 1.72 (range 0-5) with SRW. In four patients (3.4%), PET-CT changed the staging from localised to metastatic disease.PET can identify metastatic disease not evident on SRW in a small number of patients. This is because of its higher ability to recognise lymph node and bone involvement. Chest CT remains essential to detect lesions in intrathoracic sites, which can be performed in a one stop-shot routine examination or on a dedicated chest CT scan. PET-CT could replace bone scintigraphy to study bone involvement.

To study the use of the self-expanding Covera covered stent for the treatment of stenotic lesions at the venous anastomosis of hemodialysis arteriovenous grafts (AVGs).A total of 110 patients with AVG venous anastomotic stenosis of ≥50% and access dysfunction were treated at 14 centers in the United States using percutaneous transluminal angioplasty followed by covered stent placement. The primary end points were 30-day safety and 6-month target lesion primary patency (TLPP). The secondary measures included access circuit primary patency, circuit cumulative patency, and the number of reinterventions through 24 months.Freedom from a primary safety event at 30 days was 96.4% while the 6-month TLPP rate was 70.3%. Seventy-five patients completed 24-month follow-up (68.2%). The TLPP rates were 54.2% at 365 days and 36.9% at 730 days while the access circuit primary patency rates were 16.7% at 365 days and 7.8% at 730 days (Kaplan-Meier analysis). The access circuit cumulative patency rates were 85.4% at 12 months and 73.6% at 24 months. The number of reinterventions to maintain the patency of the access circuit was 3.6 ± 3.1 at 24 months (1.6 ± 1.9 at the target lesion).Use of the Covera covered stent for hemodialysis graft-vein anastomotic stenosis provided a safe treatment option with a TLPP rate of 70.3% at 6 months and TLPP and cumulative access circuit patency rates of 36.9% and 73.6% at 2 years.

This workbook of "etudes" offers a collection of experimental texts for communal dialogue and discovery that crosses multiple academic disciplines, including: foundations of physics, metaphysics, theoretical biology, semiotics, cognitive science, linguistics, phenomenology, logic & mathematics, poetry and theology. Each etude probes limits, horizons and boundaries by implicitly bring into relation foundational issues that characterize different academic disciplines or systems of meaning formation. Some formal techniques are deployed the etudes. Most notable is the use of the “logic of three” to overcome falsely totalizing images and inexorable dualities. This technique involves a particular kind of attunement to the “betweenness” of mediation that is not common in modern science. The attunement draws on the formal and precise movements of analysis in concert with the metaphoric and singular movements of synthesis.

A deconstruction of the implicit notion of Absolute space that dominates modern physics. The deconstruction is enacted by juxtaposing the common notion of Absolute space abstracted from Newton’s Philosophiae Naturalis Principia Mathematica with Levinas’ particular present treatment of space in Otherwise than Being: Or Beyond Essence.

The treatment of paratesticular rhabdomyosarcoma (PT-RMS) has varied over time and by cooperative group. The International Soft Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group (COG) Soft Tissue Sarcoma Committee, European pediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS). The INSTRuCT surgical committee has been given charge of the development of internationally applicable consensus guidelines for the surgical treatment of rhabdomyosarcoma. This clinical consensus opinion document addresses accepted principles and areas of controversy, such as scrotal violation and retroperitoneal nodal evaluation, providing an evidence-based guideline for the surgical treatment for PT-RMS.

BACKGROUND Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age

Timely presentation to care for people newly diagnosed with HIV is critical to optimize health outcomes and reduce onward HIV transmission. Studies describing presentation to care following diagnosis during a hospital admission are lacking. We sought to assess the timeliness of presentation to care and to identify factors associated with delayed presentation. We conducted a population-level study using health administrative databases. Participants were all individuals older than 16 and newly diagnosed with HIV during hospital admission in Ontario, Canada, between April 1, 2007 and March 31, 2015. We used modified Poisson regression models to derive relative risk ratios for the association between sociodemographic and clinical variables and the presentation to out-patient HIV care by 90 days following hospital discharge. Among 372 patients who received a primary HIV diagnosis in hospital, 83.6% presented to care by 90 days. Following multivariable analysis, we did not find associations between patient sociodemographic or clinical characteristics and presentation to care by 90 days. In a secondary analysis of 483 patients diagnosed during hospitalization but for whom HIV was not recorded as the principal reason for admission, 73.1% presented to care by 90 days. Following multivariable adjustment, we found immigrants from countries with generalized HIV epidemics (RR 1.265, 95% CI 1.133-1.413) were more likely to present to care, whereas timely presentation was less likely for people with a mental health diagnosis (RR 0.817, 95% CI 0.742-0.898) and women (RR 0.748, 95% CI 0.559-1.001). Future work should evaluate mechanisms to facilitate presentation to care among these populations.

An exploration of the hypothesis that quantum mechanics is the interpretative framework of relativity theory.

Experiential learning through active participation is thought to be a key benefit of simulation-based education. Recent research has challenged this assumption, suggesting that active participants learn just as well as observers. Studies report that active participants experience stress and anxiety during simulation, which may hamper learning by active participants. We undertook the current study to examine whether active participation results in different emotional arousal than observing during simulation. We hypothesized that participants in active roles experience higher levels of negative emotions than those observing and looked for evidence that this may impact learning.Pediatric residents participate in simulations, rotating through active and observer roles, as part of their standard curriculum. We assessed both positive and negative emotional arousal with the Positive and Negative Affect Scale immediately after each simulation and assessed learning through multiple-choice questions. We used repeated measures analysis of variance to examine potential interactions between Positive and Negative Affect Scale scores and role in simulation. To explore differences in learning, we examined whether knowledge retention differed between the groups.Residents had higher levels of both positive and negative emotional arousal in active roles compared with observing roles. We could not detect a difference in learning between the roles.The increase in both positive and negative emotions among active participants compared with observers may have important implications for simulation design and participant learning. Future studies should be powered to detect differences in learning and examine the impact of contributing factors such as learner level and context.

Background Risk factors for cause-specific mortality have not been widely studied among people with HIV infection. Our objectives were to estimate rates of and risk factors for all-cause and cause-specific mortality from 1995 to 2014 among HIV-infected people in Ontario. Methods We conducted a population-based retrospective cohort study using provincial health databases of people with HIV infection who were aged 16 years or more, were residents of Ontario between 1995 and 2014, and had HIV infection according to a previously validated algorithm. We used International Classification of Diseases codes to classify the underlying cause of death and estimated age-adjusted mortality rates per 100 person-years for 1995 to 2014. We used descriptive statistics to characterize the cohort at baseline and calculated adjusted mortality rate ratios (RRs) using generalized estimating equations. Results Among 23 043 people, the all-cause mortality rate declined from 6.69 to 1.53 per 100 person-years over the study period, and the rate of death from HIV/AIDS declined from 4.75 to 0.46 per 100 person-years. Concomitantly, the proportions of deaths due to cancer, cardiovascular disease and other noncommunicable diseases rose; however, rates remained constant or declined. Compared to males, females had higher mortality due to cardiovascular disease (adjusted RR 1.36, 95% confidence interval [CI] 1.04-1.77), noncommunicable causes (adjusted RR 1.75, 95% CI 1.39-2.20) and, by 2010-2014, any cause (adjusted RR 1.19, 95% CI 1.02-1.38). Residing in a low-income neighbourhood was associated with increased risk for most causes, including HIV/AIDS (adjusted RR in 2010-2014 1.86, 95% CI 1.49-2.31). Rural residence was associated with increased mortality due to malignant disease (adjusted RR 1.60, 95% CI 1.10-2.34) and noncommunicable disease (adjusted RR 1.86, 95% CI 1.25-2.77). Being an immigrant was associated with lower risk of death from all causes. Interpretation Over the study period, death was increasingly due to common chronic conditions rather than to HIV infection itself. Care should incorporate the prevention and management of these conditions, especially among females and those residing in rural and low-income areas.