Reinforcement Learning-Based Tracking Control of USVs in Varying Operational Conditions.

We present a reinforcement learning-based (RL) control scheme for trajectory tracking of fully-actuated surface vessels. The proposed method learns online both a model-based feedforward controller, as well an optimizing feedback policy in order to follow a desired trajectory under the influence of environmental forces. The method's efficiency is evaluated via simulations and sea trials, with the unmanned surface vehicle (USV) ReVolt performing three different tracking tasks: The four corner DP test, straight-path tracking and curved-path tracking. The results demonstrate the method's ability to accomplish the control objectives and a good agreement between the performance achieved in the Revolt Digital Twin and the sea trials. Finally, we include an section with considerations about assurance for RL-based methods and where our approach stands in terms of the main challenges.

[Perioperative fluid therapy influences coagulation, blood loss and post-operative complications].

Literature on fluid therapy for surgery is updated in regard to coagulation, blood loss and post-operative complications. Haemorrhage depends on the surgical intervention but also on the chosen fluid therapy with artificial colloids affecting coagulation competence and in turn the blood loss. Furthermore, a stable central blood volume as indicated by plasma pro-atrial natriuretic peptide requires a calculated fluid surplus by approximately 2.5 l. Randomized controlled trials recommend haemorrhage to be treated by administration of a crystalloid; however, if the calculated excess of fluid approaches 2 l, albumin may be added.

Effect of perioperative crystalloid or colloid fluid therapy on hemorrhage, coagulation competence, and outcome: A systematic review and stratified meta-analysis.

BACKGROUND: A meta-analysis concerning perioperative coagulation competence, hemorrhage, and outcome was conducted including the use of hydroxyethyl starches (HESs), dextran, or albumin versus administration of a crystalloid as control to assess the efficacy and safety of colloids and crystalloids for fluid administration during major elective surgery. Surgery was restricted to cardiovascular and noncardiovascular surgery, and HESs were stratified to HES 130/0.4 and HES 200/0.5. METHODS: We searched Cochrane Central Register of Controlled Trials, MEDLINE, ISI Web of Science, EMBASE, conference proceedings, reference lists, and databases of ongoing trials. RESULTS: Thirty one primary clinical randomized controlled trials included 2287 patients undergoing major surgery from January 2000 to August 2015. The perioperative changes in coagulation competence were measured by thromboelastography (TEG) maximum amplitude (MA) in 9 studies administering crystalloids versus HES and in 4 studies administering albumin versus HES. All studies but 1 disclosed increased reduction in TEG-MA following HES administration (P = 0.0001 and 0.0002). The total loss of blood was reported in 17 studies in which crystalloids were compared to HES and 12 studies reported increased blood loss after administration of HES (P < 0.003). When administering albumin versus HES, 6 studies reported reduced hemorrhage associated with albumin administration (P = 0.005). Reoperation was not significantly reduced by the use of crystalloids, but may be more frequent after HESs compared to albumin (P < 0.03). In this analysis, more patients admitted to administration of HESs were exposed to decrease coagulation competence, compared to perioperative crystalloids and albumin administration. CONCLUSION: This stratified meta-analysis showed that increased blood loss was found in noncardiovascular surgery among patients receiving HES compared with crystalloids, followed by a marked reduction in TEG-MA, and infusion of 3rd-generation HES products did not influence the results significantly.

No association of tobacco use and disease activity in multiple sclerosis.

OBJECTIVE: To study whether tobacco use is associated with MRI and clinical disease activity in patients with multiple sclerosis (MS). METHODS: Prospective cohort study of 87 patients with relapsing-remitting MS originally included in a randomized placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS Study). Serum levels of cotinine (biomarker of tobacco use) were analyzed at baseline and every 6 months for 2 years. MRI activity was assessed at baseline and monthly for 9 months and after 12 and 24 months. RESULTS: Fifty-three patients (61%) had serum cotinine levels ≥85 nmol/L on ≥60% of the measurements and were considered tobacco users and 34 (39%) had cotinine levels <85 nmol/L, consistent with non-tobacco use. There was no association between tobacco use and the occurrence of new gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, or their aggregate (combined unique activity). Furthermore, there was no association between cotinine levels and MRI activity for the tobacco users, and tobacco users did not have more relapses or Expanded Disability Status Scale progression. CONCLUSION: Our results indicate that tobacco use does not directly influence MRI activity or relapse rate in MS. This may implicate that the reported association between smoking and MS disease progression could be mediated through other mechanisms.

Impact of Albumin on Coagulation Competence and Hemorrhage During Major Surgery: A Randomized Controlled Trial.

For patients exposed to a massive blood loss during surgery, maintained coagulation competence is important. It is less obvious whether coagulation competence influences bleeding during elective surgery where patients are exposed to infusion of a crystalloid or a colloid. This randomized controlled trial evaluates whether administration of 5% human albumin (HA) or lactated Ringer solution (LR) affects coagulation competence and in turn blood loss during cystectomy due to bladder cancer. Forty patients undergoing radical cystectomy were included to receive either 5% HA (n = 20) or LR (n = 20). Nineteen patients were analyzed in the HA group and 20 patients in the lactated Ringer group. Blinded determination of the blood loss was similar in the 2 groups of patients: 1658 (800-3300) mL with the use of HA and 1472 (700-4330) mL in the lactated Ringer group (P = 0.45). Yet, by thrombelastography (TEG) evaluated coagulation competence, albumin affected clot growth (TEG-angle 69 ±â€Š5 vs 74°â€Š±â€Š3°, P < 0.01) and strength (TEG-MA: 59 ±â€Š6 vs 67 ±â€Š6 mm, P < 0.001) more than LR. Furthermore, by multivariate linear regression analyses reduced TEG-MA was independently associated with the blood loss (P = 0.042) while administration of albumin was related to the changes in TEG-MA (P = 0.029), aPPT (P < 0.022), and INR (P < 0.033). This randomized controlled trial demonstrates that administration of HA does not affect the blood loss as compared to infusion of LR. Also the use of HA did not affect the need for blood transfusion, the incidence of postoperative complications, or the hospital in-stay. Yet, albumin decreases coagulation competence during major surgery and the blood loss is related to TEG-MA rather than to plasma coagulation variables.

Plasma pro-atrial natriuretic peptide to indicate fluid balance during cystectomy: a prospective observational study.

OBJECTIVES: During surgery the volume of administered fluid is debated. Pro-atrial natriuretic peptide (proANP) is released by atrial distension, and we evaluated the relationship between changes in proANP associated with perioperative fluid balance. DESIGN: Prospective observational study. SETTING: One university/tertiary centre. PARTICIPANTS: The study included patients who underwent radical cystectomy. Plasma for determination of proANP was obtained before surgery, after resection of the bladder, and at the end of surgery for 20 robotic-assisted radical cystectomy (RARC) and 20 open radical cystectomy (ORC) procedures. RESULTS: The blood loss was 1871 (95% CI 1267 to 2475) vs 589 mL (378 to 801) in the ORC and RARC groups (p=0.001), respectively, and fluid balance was positive by 1518 mL (1215 to 1821) during ORC, and by 1858 mL (1461 to 2255) during RARC (p=0.163). Yet, at the end of ORC, plasma proANP was reduced by 23% (14% to 32%, p=0.001), while plasma proANP did not change significantly during RARC. Thus, plasma proANP was associated both with the perioperative blood loss (r= -0.475 (0.632 to -0.101), p=0.002), and with fluid balance (r=0.561 (0.302 to 0.740), p=0.001), indicating that a stable plasma proANP required a fluid surplus by 2.4 L (2.0 to 2.7). CONCLUSIONS: There was a correlation between intraoperative haemorrhage and a decrease in plasma proANP and, taking plasma proANP to indicate filling of the heart, about 2.5 L surplus volume of lactated Ringer's solution appears to maintain cardiac preload during cystectomy. TRIAL REGISTRATION NUMBER: EudraCT (2012-005040-20), Results.

Coagulation competence for predicting perioperative hemorrhage in patients treated with lactated Ringer's vs. Dextran--a randomized controlled trial.

BACKGROUND: Perioperative hemorrhage may depend on coagulation competence and this study evaluated the influence of coagulation competence on blood loss during cystectomy due to bladder cancer. METHODS: Forty patients undergoing radical cystectomy were included in a randomized controlled trial to receive either lactated Ringer's solution or Dextran 70 (Macrodex ®) that affects coagulation competence. RESULTS: By thrombelastography evaluated coagulation competence, Dextran 70 reduced "maximal amplitude" (MA) by 25 % versus a 1 % reduction with the administration of lactated Ringer's solution (P <0.001). Blinded evaluation of the blood loss was similar in the two groups of patients - 2339 ml with the use of Dextran 70 and 1822 ml in the lactated Ringer's group (P = 0.27). Yet, the blood loss was related to the reduction in MA (r = -0.427, P = 0.008) and by multiple regression analysis independently associated with MA (P = 0.01). Thus, 11 patients in the dextran group (58 %) developed a clinical significant blood loss (>1500 ml) compared to only four patients (22 %) in the lactated Ringer's group (P = 0.04). CONCLUSIONS: With the use of Dextran 70 vs. lactated Ringer's solution during cystectomy, a relation between hemorrhage and coagulation competence is demonstrated. Significant bleeding develops based on an about 25 % reduction in thrombelastography determined maximal amplitude. A multivariable model including maximal amplitude discriminates patients with severe perioperative bleeding during cystectomy. TRIAL REGISTRATION: The study was accepted on January 7(th), 2013 at www.clinicaltrialsregister.eu EudraCT 2012-005040-20.

Body mass index influence interferon-beta treatment response in multiple sclerosis.

Obesity is a possible risk factor of multiple sclerosis (MS), but the association between obesity and MS disease activity has not been explored. In a cohort of 86 MS patients, 80% of overweight or obese patients (BMI≥25kg/m(2)) had MRI activity compared to 48% of the normal-weight patients (BMI<25kg/m(2)) (p=0.001) during interferon-beta treatment. NEDA-status (no evidence of disease activity) was defined as a composite that consisted of absence of any relapses, sustained disability-progression and MRI-activity. Among normal-weight patients 26% obtained NEDA-status compared to only 13% of patients with BMI >25 (p=0.05). This may indicate that BMI affects interferon-beta treatment response.

Vitamin D status and effect of interferon-ß1a treatment on MRI activity and serum inflammation markers in relapsing-remitting multiple sclerosis.

To explore if vitamin D modulates interferon-ß1a treatment effects in relapsing-remitting multiple sclerosis, we examined relationships between serum vitamin D and magnetic resonance imaging (MRI) activity and ten systemic inflammation markers in 88 patients, before and during treatment. Odds ratios for all MRI parameters were negatively associated with vitamin D levels before therapy, but converged to equally low values irrespective of vitamin D status during treatment. During therapy, similar alterations of MRI activity and inflammation markers were found across patients categorized by mean vitamin D values. This suggests that vitamin D status has no major influence on interferon-ß1a treatment effects.

Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis.

BACKGROUND: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. OBJECTIVES: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. METHODS: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. RESULTS: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07-8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12-0.84; p = 0.021) with CUA during IFNB treatment. CONCLUSIONS: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

Increasing serum levels of vitamin A, D and E are associated with alterations of different inflammation markers in patients with multiple sclerosis.

To explore the relationships between vitamin A, D and E and inflammation in relapsing remitting multiple sclerosis, we assessed their associations with 11 inflammation markers in 9 serial serum samples from 85 patients, before and during interferon-ß1a treatment. A negative association was found between vitamin A and pentraxin 3 independent of interferon-ß1a use, whereas positive associations between vitamin D and interleukin-1 receptor antagonist and secreted frizzled-related protein 3 were seen before, and between vitamin E and chemokine (C-X-C motif) ligand 16 during interferon-ß1a treatment. These findings suggest associations with diverse inflammatory pathways, which may be differentially influenced by interferon-ß1a treatment.

Undocumented water column sink for cadmium in open ocean oxygen-deficient zones.

Cadmium (Cd) is a micronutrient and a tracer of biological productivity and circulation in the ocean. The correlation between dissolved Cd and the major algal nutrients in seawater has led to the use of Cd preserved in microfossils to constrain past ocean nutrient distributions. However, linking Cd to marine biological processes requires constraints on marine sources and sinks of Cd. Here, we show a decoupling between Cd and major nutrients within oxygen-deficient zones (ODZs) in both the Northeast Pacific and North Atlantic Oceans, which we attribute to Cd sulfide (CdS) precipitation in euxinic microenvironments around sinking biological particles. We find that dissolved Cd correlates well with dissolved phosphate in oxygenated waters, but is depleted compared with phosphate in ODZs. Additionally, suspended particles from the North Atlantic show high Cd content and light Cd stable isotope ratios within the ODZ, indicative of CdS precipitation. Globally, we calculate that CdS precipitation in ODZs is an important, and to our knowledge a previously undocumented marine sink of Cd. Our results suggest that water column oxygen depletion has a substantial impact on Cd biogeochemical cycling, impacting the global relationship between Cd and major nutrients and suggesting that Cd may be a previously unidentified tracer for water column oxygen deficiency on geological timescales. Similar depletions of copper and zinc in the Northeast Pacific indicate that sulfide precipitation in ODZs may also have an influence on the global distribution of other trace metals.

Pulse oximetry for perioperative monitoring.

BACKGROUND: This is an update of a review last published in Issue 9, 2009, of The Cochrane Library. Pulse oximetry is used extensively in the perioperative period and might improve patient outcomes by enabling early diagnosis and, consequently, correction of perioperative events that might cause postoperative complications or even death. Only a few randomized clinical trials of pulse oximetry during anaesthesia and in the recovery room have been performed that describe perioperative hypoxaemic events, postoperative cardiopulmonary complications and cognitive dysfunction. OBJECTIVES: To study the use of perioperative monitoring with pulse oximetry to clearly identify adverse outcomes that might be prevented or improved by its use.The following hypotheses were tested.1. Use of pulse oximetry is associated with improvement in the detection and treatment of hypoxaemia.2. Early detection and treatment of hypoxaemia reduce morbidity and mortality in the perioperative period.3. Use of pulse oximetry per se reduces morbidity and mortality in the perioperative period.4. Use of pulse oximetry reduces unplanned respiratory admissions to the intensive care unit (ICU), decreases the length of ICU readmission or both. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 5), MEDLINE (1966 to June 2013), EMBASE (1980 to June 2013), CINAHL (1982 to June 2013), ISI Web of Science (1956 to June 2013), LILACS (1982 to June 2013) and databases of ongoing trials; we also checked the reference lists of trials and review articles. The original search was performed in January 2005, and a previous update was performed in May 2009. SELECTION CRITERIA: We included all controlled trials that randomly assigned participants to pulse oximetry or no pulse oximetry during the perioperative period. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed data in relation to events detectable by pulse oximetry, any serious complications that occurred during anaesthesia or in the postoperative period and intraoperative or postoperative mortality. MAIN RESULTS: The last update of the review identified five eligible studies. The updated search found one study that is awaiting assessment but no additional eligible studies. We considered studies with data from a total of 22,992 participants that were eligible for analysis. These studies gave insufficient detail on the methods used for randomization and allocation concealment. It was impossible for study personnel to be blinded to participant allocation in the study, as they needed to be able to respond to oximetry readings. Appropriate steps were taken to minimize detection bias for hypoxaemia and complication outcomes. Results indicated that hypoxaemia was reduced in the pulse oximetry group, both in the operating theatre and in the recovery room. During observation in the recovery room, the incidence of hypoxaemia in the pulse oximetry group was 1.5 to three times less. Postoperative cognitive function was independent of perioperative monitoring with pulse oximetry. A single study in general surgery showed that postoperative complications occurred in 10% of participants in the oximetry group and in 9.4% of those in the control group. No statistically significant differences in cardiovascular, respiratory, neurological or infectious complications were detected in the two groups. The duration of hospital stay was a median of five days in both groups, and equal numbers of in-hospital deaths were reported in the two groups. Continuous pulse oximetry has the potential to increase vigilance and decrease pulmonary complications after cardiothoracic surgery; however, routine continuous monitoring did not reduce transfer to an ICU and did not decrease overall mortality. AUTHORS' CONCLUSIONS: These studies confirmed that pulse oximetry can detect hypoxaemia and related events. However, we found no evidence that pulse oximetry affects the outcome of anaesthesia for patients. The conflicting subjective and objective study results, despite an intense methodical collection of data from a relatively large general surgery population, indicate that the value of perioperative monitoring with pulse oximetry is questionable in relation to improved reliable outcomes, effectiveness and efficiency. Routine continuous pulse oximetry monitoring did not reduce transfer to the ICU and did not decrease mortality, and it is unclear whether any real benefit was derived from the application of this technology for patients recovering from cardiothoracic surgery in a general care area.

Hydroxyethyl starch reduces coagulation competence and increases blood loss during major surgery: results from a randomized controlled trial.

OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch (HES) 130/0.4 affects coagulation competence and influences the perioperative blood loss. BACKGROUND: Artificial colloids substitute blood volume during surgery; with the administration of HES 130/0.4 (Voluven, Fresenius Kabi, Uppsala, Sweden) only a minor effect on coagulation competence is expected. METHODS: Eighty patients were scanned for enrollment in the study, and 40 patients fulfilled the inclusion criteria. Two patients withdrew their consent to participate in the study, and 5 patients were excluded. Thus, 16 patients were randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4. RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated reduced clot strength (P < 0.001) and blinded evaluation of the perioperative blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range 0.5 to 2.4) L in the patients who received HES 130/0.4 or lactated Ringer, respectively (P < 0.038). The patients in the lactated Ringer's group, however, received more fluid (P < 0.0001) than those in the HES 130/0.4 group. There was no significant difference between the 2 groups with regard to frequency of reoperations or the length of hospital stay, but use of HES 130/0.4 was both more expensive and less efficacious than the use of lactated Ringer. CONCLUSIONS: Administration of HES 130/0.4 reduced clot strength and perioperative hemorrhage increased by more than 50%, while administration of lactated Ringer's solution provoked an approximately 2.5 times greater positive volume balance at the end of surgery.

Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity.

BACKGROUND: Serum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers. METHODS: We performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation. RESULTS: After Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers. CONCLUSIONS: Serum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.

Alpha-tocopherol and MRI outcomes in multiple sclerosis--association and prediction.

OBJECTIVE: Alpha-tocopherol is the main vitamin E compound in humans, and has important antioxidative and immunomodulatory properties. The aim of this study was to study alpha-tocopherol concentrations and their relationship to disease activity in Norwegian multiple sclerosis (MS) patients. METHODS: Prospective cohort study in 88 relapsing-remitting MS (RRMS) patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids (the OFAMS study), before and during treatment with interferon beta. The patients were followed for two years with repeated 12 magnetic resonance imaging (MRI) scans and nine serum measurements of alpha-tocopherol. RESULTS: During interferon beta (IFNB) treatment, each 10 µmol/L increase in alpha-tocopherol reduced the odds (CI 95%) for simultaneous new T2 lesions by 36.8 (0.5-59.8) %, p = 0.048, and for combined unique activity by 35.4 (1.6-57.7) %, p = 0.042, in a hierarchical regression model. These associations were not significant prior to IFNB treatment, and were not noticeably changed by gender, age, body mass index, HLA-DRB1*15, treatment group, compliance, or the concentrations of 25-hydroxyvitamin D, retinol, neutralising antibodies against IFNB, or the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. The corresponding odds for having new T1 gadolinium enhancing lesions two months later was reduced by 65.4 (16.5-85.7) %, p = 0.019, and for new T2 lesions by 61.0 (12.4-82.6) %, p = 0.023. CONCLUSION: During treatment with IFNB, increasing serum concentrations of alpha-tocopherol were associated with reduced odds for simultaneous and subsequent MRI disease activity in RRMS patients.