Boundary Graph Neural Networks for 3D Simulations

The abundance of data has given machine learning considerable momentum in natural sciences and engineering. However, the modeling of simulated physical processes remains difficult. A key problem is the correct handling of geometric boundaries. While triangularized geometric boundaries are very common in engineering applications, they are notoriously difficult to model by machine learning approaches due to their heterogeneity with respect to size and orientation. In this work, we introduce Boundary Graph Neural Networks (BGNNs), which dynamically modify graph structures to address boundary conditions. Boundary graph structures are constructed via modifying edges, augmenting node features, and dynamically inserting virtual nodes. The new BGNNs are tested on complex 3D granular flow processes of hoppers and rotating drums which are standard components of industrial machinery. Using precise simulations that are obtained by an expensive and complex discrete element method, BGNNs are evaluated in terms of computational efficiency as well as prediction accuracy of particle flows and mixing entropies. Even if complex boundaries are present, BGNNs are able to accurately reproduce 3D granular flows within simulation uncertainties over hundreds of thousands of simulation timesteps, and most notably particles completely stay within the geometric objects without using handcrafted conditions or restrictions

Association of analgosedation with psychiatric symptoms and health-related quality of life in ARDS survivors: post hoc analyses of the DACAPO study

Background The acute respiratory distress syndrome (ARDS) is a life-threatening condition with the risk of developing hypoxia and thus requires for invasive mechanical ventilation a long-term analgosedation. Yet, prolonged analgosedation may be a reason for declining health-related quality of life (HRQoL) and the development of psychiatric disorders. Methods We used data from the prospective observational nation‑wide ARDS study across Germany (DACAPO) to investigate the influence of sedation and analgesia on HRQoL and the risk of psychiatric symptoms in ARDS survivors 3, 6 and 12 months after their discharge from the intensive care unit (ICU). HRQoL was measured with the Physical and Mental Component Scale of the Short‑Form 12 Questionnaire (PCS‑12, MCS‑12). The prevalence of psychiatric symptoms (depression and post‑traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire‑9 and the Post‑Traumatic Stress Syndrome‑14. The associations of analgosedation with HRQoL and psychiatric symptoms were investigated by means of multivariable linear regression models. Results The data of 134 ARDS survivors (median age [IQR]: 55 [44–64], 67% men) did not show any significant association between analgosedation and physical or mental HRQoL up to 1 year after ICU discharge. Multivariable linear regression analysis (B [95%‑CI]) yielded a significant association between symptoms of psychiatric disorders and increased cumulative doses of ketamine up to 6 months after ICU discharge (after 3 months: depression: 0.15 [0.05, 0.25]; after 6 months: depression: 0.13 [0.03, 0.24] and PTSD: 0.42 [0.04, 0.80)]). Conclusions Up to 1 year after ICU discharge, analgosedation did not influence HRQoL of ARDS survivors. Prolonged administration of ketamine during ICU treatment, however, was positively associated with the risk of psychiatric symptoms. The administration of ketamine to ICU patients with ARDS should be with caution

protocol for a prospective, observational, multi-centre patient cohort study (DACAPO)

Background Health-related quality of life (HRQoL) and return to work are important outcomes in critical care medicine, reaching beyond mortality. Little is known on factors predictive of HRQoL and return to work in critical illness, including the acute respiratory distress syndrome (ARDS), and no evidence exists on the role of quality of care (QoC) for outcomes in survivors of ARDS. It is the aim of the DACAPO study (“Surviving ARDS: the influence of QoC and individual patient characteristics on quality of life”) to investigate the role of QoC and individual patient characteristics on quality of life and return to work. Methods/Design A prospective, observational, multi-centre patient cohort study will be performed in Germany, using hospitals from the “ARDS Network Germany” as the main recruiting centres. It is envisaged to recruit 2400 patients into the DACAPO study and to analyse a study population of 1500 survivors. They will be followed up until 12 months after discharge from hospital. QoC will be assessed as process quality, structural quality and volume at the institutional level. The main outcomes (HRQoL and return to work) will be assessed by self-report questionnaires. Further data collection includes general medical and ARDS-related characteristics of patients as well as sociodemographic and psycho-social parameters. Multilevel hierarchical modelling will be performed to analyse the effects of QoC and individual patient characteristics on outcomes, taking the cluster structure of the data into account. Discussion By obtaining comprehensive data at patient and hospital level using a prospective multi-centre design, the DACAPO-study is the first study investigating the influence of QoC on individual outcomes of ARDS survivors

Acceptability of a German multicentre healthcare research study: a survey of research personnels’ attitudes, experiences and work load

Objectives The DACAPO study as a multicentre nationwide observational healthcare research study investigates the influence of quality of care on the quality of life in patients with acute respiratory distress syndrome. The aim of this study was to investigate the acceptability to the participating research personnels by assessing attitudes, experiences and workload associated with the conduct of the DACAPO study. Design, setting and participants A prospective anonymous online survey was sent via email account to 169 participants in 65 study centres. The questionnaire included six different domains: (1) training for performing the study; (2) obtaining informed consent; (3) data collection; (4) data entry using the online documentation system; (5) opinion towards the study and (6) personal data. Descriptive data analysis was carried out. Results A total of 78 participants took part (46%) in the survey, 75 questionnaires (44%) could be evaluated. 51% were senior medical specialists. 95% considered the time frame of the training as appropriate and the presentation was rated by 93% as good or very good. Time effort for obtaining consent, data collection and entry was considered by 41% as a burden. Support from the coordinating study centre was rated as good or very good by more than 90% of respondents. While the DACAPO study was seen as scientifically relevant by 81%, only 45% considered the study results valuable for improving patient care significantly. Conclusion Collecting feedback on the acceptability of a large multicentre healthcare research study provided important insights. Recruitment and data acquisition was mainly performed by physicians and often regarded as additional time burden in clinical practice. Reducing the amount of data collection and simplifying data entry could facilitate the conduct of healthcare research studies and could improve motivation of researchers in intensive care medicine. Trial registration number NCT02637011; Pre-results

Tracheostomy in patients with acute respiratory distress syndrome is not related to quality of life, symptoms of psychiatric disorders or return-to-work: the prospective DACAPO cohort study

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors. Methods Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive-compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models. Results Primary 877 ARDS patients (mean +/- standard deviation: 54 +/- 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: - 0.73 [- 3.96, 2.51]; MCS-12: - 0.71 [- 4.92, 3.49]), symptoms of psychiatric disorders (depression: 0.10 [- 1.43, 1.64]; PTSD: 3.31 [- 1.81, 8.43]; anxiety: 1.26 [0.41, 3.86]; obsessive-compulsive disorder: 0.59 [0.05, 6.68]) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI]). Conclusions Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered

Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma

Background Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. Methods We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. Results Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. Conclusion TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastom

Short pulse generation and high power emission of Quantum Cascade lasers

The final publication is available via https://doi.org/10.1109/IRMMW-THz.2017.8067124.A unique feature of Quantum Cascade lasers is the possibility to stack active regions. Using a three stack heterogeneous Quantum Cascade laser ultra broadband amplification and short pulse generation is demonstrated. High power output is achieved by two stacked symmetric active regions

Influence of quality of intensive care on quality of life/return to work in survivors of the acute respiratory distress syndrome: prospective observational patient cohort study (DACAPO)

BackgroundSignificant long-term reduction in health-related quality of life (HRQoL) is often observed in survivors of the acute respiratory distress syndrome (ARDS), and return to work (RtW) is limited. There is a paucity of data regarding the relationship between the quality of care (QoC) in the intensive care unit (ICU) and both HRQoL and RtW in ARDS survivors. Therefore, the aim of our study was to investigate associations between indicators of QoC and HRQoL and RtW in a cohort of survivors of ARDS.MethodsTo determine the influence of QoC on HRQoL and RtW 1 year after ICU-discharge, ARDS patients were recruited into a prospective multi-centre patient cohort study and followed up regularly after discharge. Patients were asked to complete self-report questionnaires on HRQoL (Short Form 12 physical component scale (PCS) and mental component scale (MCS)) and RtW. Indicators of QoC pertaining to volume, structural and process quality, and general characteristics were recorded on ICU level. Associations between QoC indicators and HrQoL and RtW were investigated by multivariable linear and Cox regression modelling, respectively. B values and hazard ratios (HRs) are reported with corresponding 95% confidence intervals (CIs).Results877 (of initially 1225 enrolled) people with ARDS formed the DACAPO survivor cohort, 396 were finally followed up to 1 year after discharge. The twelve-month survivors were characterized by a reduced HRQoL with a greater impairment in the physical component (Md 41.2 IQR [34-52]) compared to the mental component (Md 47.3 IQR [33-57]). Overall, 50% of the patients returned to work. The proportion of ventilated ICU patients showed significant negative associations with both 12months PCS (B=-11.22, CI -20.71; -1,74) and RtW (HR=0,18, CI 0,04;0,80). All other QoC indicators were not significantly related to outcome.ConclusionsAssociations between ICU QoC and long-term HrQoL and RtW were weak and largely non-significant. Residual confounding by case mix, treatment variables before or during ICU stay and variables pertaining to the post intensive care period (e.g. rehabilitation) cannot be ruled out.Trial registrationClinicaltrials.govNCT02637011.(December 22, 2015, retrospectively registered

Characteristics and provision of care of patients with the acute respiratory distress syndrome: descriptive findings from the DACAPO cohort baseline and comparison with international findings: a cross-sectional study

Background: Little is known about the characteristics and real world life circumstances of ARDS (acute respiratory distress syndrome) patient populations. This knowledge is essential for transferring evidence-based therapy into routine healthcare. The aim of this study was to report socio-demographic and clinical characteristics in an unselected population of ARDS patients and to compare these results to findings from other large ARDS cohorts. Methods: A German based cross-sectional observational study was carried out. A total of 700 ARDS patients were recruited in 59 study sites between September 2014 and January 2016. Socio-demographic, disease and care related variables were recorded. Additionally, characteristics of other large ARDS cohorts identified by a systematic literature search were extracted into evidence tables. Results: Median age of ARDS patients was 58 years, 69% were male. Sixty percent had no employment, predominantly due to retirement. Seventy-one percent lived with a partner. The main cause of ARDS was a pulmonary 'direct' origin (79%). The distribution of severity was as follows: mild (14%), moderate (48%), severe (38%). Overall ICU mortality was calculated to be 34%. The observed prevalence of critical events (hypoxemia, hypoglycemia, re-intubation) was 47%. Supportive measures during ICU-treatment were applied to 60% of the patients. Other ARDS cohorts revealed a high heterogeneity in reported concomitant diseases, but sepsis and pneumonia were most frequently reported. Mean age ranged from 54 to 71 years and most patients were male. Other socio-demographic factors have been almost neglected. Conclusions: The proportion of patients suffering of mild ARDS was lower compared to the only study identified, which also applied the Berlin definition. The frequency of critical events during ICU treatment was high and the implementation of evidence-based therapy (prone positioning, neuro-muscular blockers) was limited. More evidence on socio-demographic characteristics and further studies applying the current diagnostic criteria are desirable