Symbolic computation for mobile robot path planning

AbstractMotion planning for mobile robots is an arduous task. Among the various methods that have been proposed for the solution of this problem in its open loop version is the Lafferriere–Sussmann method, which is based on differential geometry and employs piecewise constant inputs. This paper gives a succinct description of the method and of a freely available software tool, called the Lie Algebraic Motion Planner—LAMP and written in Mathematica™, which automates motion planning based on this technique

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFα) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFα, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis ≤50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis ≤50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis ≤50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFα were higher in patients with monocyte apoptosis ≤50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis

Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia

Background. Because clarithromycin provided beneficiary nonantibiotic effects in experimental studies, its efficacy was tested in patients with sepsis and ventilator-associated pneumonia (VAP). Methods. Two hundred patients with sepsis and VAP were enrolled in a double-blind, randomized, multicenter trial from June 2004 until November 2005. Clarithromycin (1 g) was administered intravenously once daily for 3 consecutive days in 100 patients; another 100 patients were treated with placebo. Main outcomes were resolution of VAP, duration of mechanical ventilation, and sepsis-related mortality within 28 days. Results. The groups were well matched with regard to demographic characteristics, disease severity, pathogens, and adequacy of the administered antimicrobials. Analysis comprising 141 patients who survived revealed that the median time for resolution of VAP was 15.5 days and 10.0 days among placebo- and clarithromycin-treated patients, respectively (P=.011); median times for weaning from mechanical ventilation were 22.5 days and 16.0 days, respectively (P=.049). Analysis comprising all enrolled patients showed a more rapid decrease of the clinical pulmonary infection score and a delay for advent of multiple organ dysfunction in clarithromycin-treated patients, compared with those of placebo-treated patients (P=.047). Among the 45 patients who died of sepsis, time to death was significantly prolonged in clarithromycin-treated compared with placebo-treated patients (P=.004). Serious adverse events were observed in 0% and 3% of placebo- and clarithromycin-treated patients, respectively (P=.25). Conclusions. Clarithromycin accelerated the resolution of VAP and weaning from mechanical ventilation in surviving patients and delayed death in those who died of sepsis. The mortality rate at day 28 was not altered. Results are encouraging and render new perspectives on the management of sepsis and VA

Immunomodulatory intervention in sepsis by multidrug-resistant Pseudomonas aeruginosa with thalidomide: an experimental study

BACKGROUND: Thalidomide is an inhibitor of tumour necrosis factor-alpha (TNFα) that has been proven effective for the treatment of experimental sepsis by Escherichia coli. It was tested whether it might behave as an effective immunomodulator in experimental sepsis by multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: Sepsis was induced by the intraperitoneal injection of 1 × 10(8 )cfu/kg inoculum of the test isolate in a total of 109 Wistar rats divided in three groups as follows: group A controls; group B administered seed oil 30 minutes before bacterial challenge; and group C administered 50 mg/kg of thalidomide diluted in seed oil 30 minutes before bacterial challenge. Blood was sampled for estimation of endotoxins (LPS), TNFα, interferon-gamma (IFNγ), nitric oxide (NO) and malondialdehyde (MDA). LPS was measured by the QCL-1000 LAL assay, TNFα and IFNγ by ELISA, NO by a colorimetric assay and MDA by the thiobarbiturate assay. RESULTS: Mean (± SE) survival of groups A, B and C were 18.60 ± 1.84, 12.60 ± 0.60 and 30.50 ± 6.62 hours (p of comparisons A to C equal to 0.043 and B to C equal to 0.002). Decreased TNFα and NO levels were found in sera of animals of group C compared to group A. Plasma levels of LPS, MDA and IFNγ did not differ between groups. CONCLUSION: Intake of thalidomide considerably prolonged survival in experimental sepsis by MDR P.aeruginosa an effect probably attributed to decrease of serum TNFα

Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study

<p>Abstract</p> <p>Background</p> <p>Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections.</p> <p>Methods</p> <p>68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded.</p> <p>Results</p> <p>34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome.</p> <p>Conclusion</p> <p>TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.</p

Lower Risk of Recurrence with a Higher Induction Dose of Mesalazine and Longer Duration of Treatment in Ulcerative Colitis: Results from the Dutch, Non-Interventional, IMPACT Study

Background & Aims: The dose and duration of mesalazine treatment for ulcerative colitis (UC) is a potentially important determinant of effectiveness, with evidence suggesting that continuing the induction dose for 6-12 months may improve outcomes; however, real-world data are lacking. We assessed mesalazine use in Dutch clinical practice, including how differences in dose and duration affected UC outcomes.Methods: Adults with mild-to-moderate UC who received oral prolonged-release mesalazine de novo or had a dose escalation for an active episode were followed for 12 months in this non-interventional study (ClinicalTrials.gov identifier: NCT02261636). The primary endpoint was time from start of treatment to dose reduction (TDR). Secondary endpoints included recurrence rate, adherence, and work productivity.Results: In total, 151 patients were enrolled, of whom 108 (71.5%) were newly diagnosed with UC. The majority (120; 79.5%) received a dose of >= 4 g/day. Nearly one-third (48; 31.8%) underwent dose reduction, with mean TDR being 8.3 months. Disease extent and endoscopic appearance did not influence duration of induction therapy, while TDR increased with higher baseline UCDAI scores. TDR was longer in patients without (mean 8.8 months) than with (4.1 months) recurrence, although not significantly (p=0.09). Patients on >= 4 g/day had a significantly lower chance of recurrence versus those on 2-6 months vs 3-6 months: 0.19 (95%CI: 0.08-0.46); p= 4 g/day [0.15 (0.06-0.40) vs 0.26 (0.01-11.9) for 2-= 4 g/day) and longer duration of treatment (>6 months) was associated with a lower recurrence risk.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Neural mechanisms involved in enterotoxin- induced intestinal hypersecretion

© 2017 Dr. Katerina KoussoulasExotoxins of the bacteria Vibrio cholerae (cholera toxin, CT) and Clostridium difficile (C. diff., TcdA) induce rampant disease in the form of irresolvable diarrhoea causing rapid dehydration and potential death if left untreated. Both bacterial toxins affect the nervous system of the gut, the enteric nervous system (ENS), but the types of enteric neurons involved are still indistinct. Additionally, preliminary work from a collaborator showed that specific bacterial metabolites, particularly GABA produced by the microorganisms residing in the gut, exacerbate pathophysiological effects of C. diff. GABA and its receptors are expressed in several parts of the gut wall, including enteric neurons. While studies have proposed GABA to be a putative neurotransmitter in the ENS, physiological roles of GABA in the gut remain unclear. It is unknown how enterotoxins and increased GABA at the level of the gut mucosa activate underlying enteric circuitry; my PhD aimed to elucidate these mechanisms. In Chapter 3, I investigated the enteric neural pathways underlying CT effects via in vitro incubations of CT in guinea pig jejunum. Previous work highlighted the impacts of CT on secretomotor neurons; I endeavoured to expand this by examining other key neuronal subtypes. I recorded neuronal activity in the myenteric plexus (MP) up to 6 hours after CT incubation via intracellular electrophysiology. A colleague undertook similar recordings in the submucosal plexus (SMP). We found that CT induced hyperexcitability in myenteric, but not submucosal, sensory neurons. The effect was neurally mediated and required activation of NK3 tachykinin receptors, but was independent of activation of 5-HT3 receptors or NK1 tachykinin receptors, suggesting that the effects of CT on myenteric sensory neurons are likely to be indirect and via a pathway independent of 5-HT release. In Chapter 4, I determined the effects of luminal incubations TcdA and GABA on myenteric sensory neurons via electrophysiology. I found that in vitro incubations of guinea pig jejuna with TcdA or GABA also increased the excitability of myenteric sensory neurons, highlighting the key role of these neurons as a common point through which enterotoxins and GABA operate. The GABA-induced effects were inhibited by GABAB and GABAC receptor antagonists, but enhanced by a GABAA antagonist, indicating involvement of at least two distinct GABA activated pathways. The GABAA antagonist enhanced excitability on its own suggesting that tonic release of endogenous GABA may play a role in suppressing the excitability of these neurons. In Chapter 5, I explored the role of endogenous GABA in the ENS of mouse small intestine. I employed Wnt1-Cre;R26R-GCaMP3 mice, which express a fluorescent calcium indicator in the ENS, for use in Ca2+ imaging. Neurons responded to GABA exposure via activation of GABAA, GABAB and GABAC receptors in myenteric ganglia. Further, I showed that the effects of GABA were neuronal subtype specific, for example neurons immunoreactive for neuronal nitric oxide synthase rarely responded to GABA. I also demonstrated that endogenous release of GABA may inhibit activation of myenteric neurons by activation of GABAC receptors, despite such receptors exciting myenteric neurons when activated by exogenous GABA. My data also suggest that neither GABAA nor GABAB receptors contribute to synaptic transmission in this system. Further I also demonstrated the expression of GABA in neurons and varicosities surrounding specific enteric neurons within the MP. This study clarifies the complex nature of GABAergic transmission in the ENS. In Chapter 6 to further examine the effects of enterotoxins on the enteric circuitry, I made intracellular recordings from myenteric neurons following in vivo incubations of CT in mouse ileal loops. A lab member previously showed that CT increases calcium responses in the submucosal but not myenteric, neurons. In undertaking electrophysiological recordings, a striking sampling bias was revealed with exclusion of largely descending interneurons and inhibitory motor neurons being markedly underrepresented in the data set and low sampling from sensory neurons meant that significant effects in excitability may have been missed. Nevertheless in concordance with the results from Ca2+ imaging, no significant changes in excitability of myenteric neurons were found at their resting membrane potential. However, CT induced spontaneous synaptic activity in specific myenteric neurons, but the sources of this input could not be identified due to the technical difficulty of maintaining impalements, the relative rarity of myenteric sensory neurons and the sampling bias. The data suggest a minor role for myenteric neurons in CT-induced hypersecretion in vivo. In Chapter 7 I employed the high throughput assay of Ca2+ imaging to perform a more extensive examination of the effects of TcdA on the ENS. I utilized the well-established ileal loop mouse model and incubated TcdA in vivo. Spontaneous and neurally-stimulated calcium responses were reduced in submucosal neurons, and myenteric neuronal activity was unchanged. However enteric neurons in regions of the gastrointestinal tract off-target from the site of acute toxin exposure were activated during the incubation as indicated by expression of activity dependent markers. This off target effect could possibly be due to release of inflammatory cytokines into the circulation or extrinsic neural pathways. In all, I have demonstrated a generality in the actions of enterotoxins and GABA as the pathways they activate converge to excite myenteric sensory neurons which may lead to activation of submucosal secretomotor neurons. I have extended our understanding of the role of GABA in the ENS as a means to elucidate the mechanisms through which microbial metabolites act and contribute to disease. Using the mouse ileal loop model, I further defined the effects of enterotoxins on the enteric circuitry. In this way, my thesis highlights neural elements involved in the mechanisms underlying enterotoxin-induced hypersecretion and identifies potential avenues for future research