Evaluation of Haptic and Visual Cues for Repulsive or Attractive Guidance in Nonholonomic Steering Tasks.

Remote control of vehicles is a difficult task for operators. Support systems that present additional task information may assist operators, but their usefulness is expected to depend on several factors such as 1) the nature of conveyed information, 2) what modality it is conveyed through, and 3) the task difficulty. In an exploratory experiment, these three factors were manipulated to quantify their effects on operator behavior. Subjects ( $n = {{15}}$) used a haptic manipulator to steer a virtual nonholonomic vehicle through abstract environments, in which obstacles needed to be avoided. Both a simple support conveying near-future predictions of the trajectory of the vehicle and a more elaborate support that continuously suggests the path to be taken were designed (factor 1). These types of information were offered either with visual or haptic cues (factor 2). These four support systems were tested in four different abstracted environments with decreasing amount of allowed variability in realized trajectories (factor 3). The results show improvements for the simple support only when this information was presented visually, but not when offered haptically. For the elaborate support, equally large improvements for both modalities were found. This suggests that the elaborate support is better: additional information is key in improving performance in nonholonomic steering tasks

Post-migration stressors and their association with symptom reduction and non-completion during treatment for traumatic grief in refugees

Background: Resettled refugees exposed to trauma and loss are at risk to develop mental disorders such as posttraumatic stress disorder (PTSD) and persistent complex bereavement disorder (PCBD). Post-migration stressors have been linked to poor mental health and smaller treatment effects. Aim: Our aim was to evaluate reductions in PTSD and PCBD symptoms and to explore the presence of post-migration stressors and their associations with symptom change and non-completion in a traumatic grief focused treatment in a cohort of refugees. Methods: Paired sample t-tests were used to test the significance of the symptom reductions in PTSD and PCBD symptoms during treatment. The presence of post-migration stressors was derived from a qualitative analysis of the patient files. Associations between post-migration stressors and symptom reductions as well as non-completion were calculated. Results: In this uncontrolled study, 81 files of consecutive patients were included. Significant reductions in both PCBD and PTSD symptomatology with medium effect sizes were found. Patients experienced a mean of three different post-migration stressors during the treatment. Undocumented asylum seekers were more likely to be non-completers. Ongoing conflict in the country of origin was associated with smaller PTSD symptom reductions and the total number of post-migration stressors was associated with smaller PCBD symptom reductions. Conclusions: Treatment for resettled refugees for traumatic grief coincides with alleviations in both PCBD and PTSD symptomatology. Specific post-migration stressors were associated with reduced treatment effects and increased non-completion. This is a first step towards well-informed improvements of mental health interventions for resettled refugees

Leukocytosis and Enhanced Susceptibility to Endotoxemia but Not Atherosclerotic in Adrenalectomized APOE Knockout Mice

Hyperlipidemic apolipoprotein E (APOE) knockout mice show an enhanced level of adrenal-derived anti-inflammatory glucocorticoids. Here we determined in APOE knockout mice the impact of total removal of adrenal function through adrenalectomy (ADX) on two inflammation-associated pathologies, endotoxemia and atherosclerosis. ADX mice exhibited 91% decreased corticosterone levels (PBiopharmaceutic

On the geometrization of matter by exotic smoothness

In this paper we discuss the question how matter may emerge from space. For that purpose we consider the smoothness structure of spacetime as underlying structure for a geometrical model of matter. For a large class of compact 4-manifolds, the elliptic surfaces, one is able to apply the knot surgery of Fintushel and Stern to change the smoothness structure. The influence of this surgery to the Einstein-Hilbert action is discussed. Using the Weierstrass representation, we are able to show that the knotted torus used in knot surgery is represented by a spinor fulfilling the Dirac equation and leading to a mass-less Dirac term in the Einstein-Hilbert action. For sufficient complicated links and knots, there are "connecting tubes" (graph manifolds, torus bundles) which introduce an action term of a gauge field. Both terms are genuinely geometrical and characterized by the mean curvature of the components. We also discuss the gauge group of the theory to be U(1)xSU(2)xSU(3).Comment: 30 pages, 3 figures, svjour style, complete reworking now using Fintushel-Stern knot surgery of elliptic surfaces, discussion of Lorentz metric and global hyperbolicity for exotic 4-manifolds added, final version for publication in Gen. Rel. Grav, small typos errors fixe

Noncommutative Topological Theories of Gravity

The possibility of noncommutative topological gravity arising in the same manner as Yang-Mills theory is explored. We use the Seiberg-Witten map to construct such a theory based on a SL(2,C) complex connection, from which the Euler characteristic and the signature invariant are obtained. This gives us a way towards the description of noncommutative gravitational instantons as well as noncommutative local gravitational anomalies.Comment: 17+1 pages, LaTeX, no figures, some clarifications, comments and references added, style improve

The sublingual microcirculation throughout neonatal and pediatric extracorporeal membrane oxygenation treatment: Is it altered by systemic extracorporeal support?

Background: Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment. We hypothesized that the SMC improves after starting ECMO, that the SMC differs between venovenous (VV) and venoarterial (VA) ECMO, and that insufficient recovery of microcirculatory disturbances during ECMO predicts mortality. Methods: This single-center prospective longitudinal observational study included 34 consecutive children (April 2016-September 2018). The SMC was assessed daily with a handheld vital microscope (integrated with incident dark field illumination) before, during, and after ECMO. Validated parameters of vessel density, perfusion, and flow quality were assessed for all vessels (diameter 2.6) increased with higher MAP (OR: 1.050, 95%CI: 1.008-1.094). Microcirculatory parameters did not significantly differ between VV and VA ECMO or between survivors and non-survivors. None of the microcirculatory parameters could predict mortality on ECMO or overall mortality. Conclusion: In this heterogeneous study population, we were not able to demonstrate an effect of ECMO on the sublingual microcirculation. Microcirculatory parameters did not change throughout ECMO treatment and did not differ between VV and VA ECMO or between survivors and non-survivors. Future research should focus on determining which neonatal and pediatric ECMO patients wou

Coagulation complications after conversion from roller to centrifugal pump in neonatal and pediatric extracorporeal membrane oxygenation

Background/purpose: Coagulation complications are frequent, unwanted occurrences in extracorporeal membrane oxygenation (ECMO) treatment, possibly influenced by the pump in the ECMO-circuit. We hypothesized that fewer complications would occur with a smaller, heparin-coated ECMO system with a centrifugal pump (CP) than with one with a roller pump (RP) and that after conversion, complication rates would decrease over time. Methods: This single-center, retrospective chart study included all first neonatal and pediatric ECMO runs between 2009 and 2015. Differences between groups were assessed with Mann–Whitney U tests and Kruskal–Wallis tests. Determinants of complication rates were evaluated through Poisson regression models. The CP group was divided into three consecutive groups to assess whether complication rates decreased over time. Results: The RP group comprised 90 ECMO runs and the CP group 82. Hemorrhagic complication rates were significantly higher with the CP than with the RP, without serious therapeutic consequences, while thrombotic complications rates were unaffected. Intracranial hemorrhage rates and coagulation-related mortality rates were similar. Gained experience with the CP did not improve complication rates or su

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT):a multicentre, open-label, randomised, controlled trial

Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1–2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11–22) before surgery for intravenous iron and 19 days (IQR 13–27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55–2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87–4·58]; p&lt;0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). Interpretation: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. Funding: Vifor Pharma.</p

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care