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Summary The scale insects (Hemiptera: Coccomorpha) recorded on agricultural, ornamental and forest plant species in the wider area of Messenian Province (Peloponnese, Greece) during the years 2000 – 2020 are reviewed. Twenty species were recorded, which belong to four families: Diaspididae: Aonidiella aurantii (Maskell), Chrysomphalus aonidum (L.), Diaspis echinocacti (Bouché), Dynaspidiotus abieticola (Koroneos), D. abietis (Schrank), Lepidosaphes beckii (Newman), L. gloverii (Packard), Lineaspis striata (Newstead), Targionia vitis (Signoret); Coccidae: Ceroplastes rusci (L.), Eulecanium sericeum (Lindinger), Nemolecanium graniformis (Wünn), Parthenolecanium corni (Bouché), P. persicae (Fabricius), Physokermes hemicryphus (Dalman), P. inopinatus Danzig and Kozár, Protopulvinaria pyriformis (Cockerell); Pseudococcidae: Phenacoccus madeirensis Green, Planococcus vovae (Nasonov) and Kermesidae: Kermes echinatus Balachowsky. The biology, phenology and natural enemies in Messenia are discussed for fifteen of these scale species.

Background Community-acquired pleural infection (CAPI) is a growing health problem worldwide. Although most CAPI patients recover with antibiotics and pleural drainage, 20% require surgical intervention. The use of inappropriate antibiotics is a common cause of treatment failure. Awareness of the common causative bacteria along with their patterns of antibiotic resistance is critical in the selection of antibiotics in CAPI-patients. This study aimed to define CAPI bacteriology from the positive pleural fluid cultures, determine effective antibiotic regimens and investigate for associations between clinical features and risk for death or antibiotic-resistance, in order to advocate with more invasive techniques in the optimal timing. Methods We examined 158 patients with culture positive, CAPI collected both retrospectively (2012-2013) and prospectively (2014-2018). Culture-positive, CAPI patients hospitalized in six tertiary hospitals in Greece were prospectively recruited (N=113). Bacteriological data from retrospectively detected patients were also used (N=45). Logistic regression analysis was performed to identify clinical features related to mortality, presence of certain bacteria and antibiotic resistance. Results Streptococci, especially the non-pneumococcal ones, were the most common bacteria among the isolates, which were mostly sensitive to commonly used antibiotic combinations. RAPID score (i.e., clinical score for the stratification of mortality risk in patients with pleural infection; parameters: renal, age, purulence, infection source, and dietary factors), diabetes and CRP were independent predictors of mortality while several patient co-morbidities (e.g., diabetes, malignancy, chronic renal failure, etc.) were related to the presence of certain bacteria or antibiotic resistance. Conclusions The dominance of streptococci among pleural fluid isolates from culture-positive, CAPI patients was demonstrated. Common antibiotic regimens were found highly effective in CAPI treatment. The predictive strength of RAPID score for CAPI mortality was confirmed while additional risk factors for mortality and antibiotic resistance were detected.

Significance IL-1β is an immunomodulatory cytokine that is overexpressed in the brains of patients with Alzheimer’s disease (AD). The NLRP3 inflammasome is an intracellular complex that activates caspase-1, which processes the IL-1β and IL-18 precursors into active molecules. In this study, we used an APP/PS1 mouse model for AD, which confirms significant cognitive losses that are recovered in NLRP3-deficient mice, to evaluate the therapeutic potential of an orally bioavailable and safe NLRP3 inhibitor, OLT1177. OLT1177 ameliorated the phenotype in APP/PS1 mice, as evidenced by rescued spatial learning and memory in the Morris water maze test. Microglia were less activated, cortical plaques reduced, and plasma AD metabolic markers were normalized. OLT1177 is a potential therapeutic option for AD., Numerous studies demonstrate that neuroinflammation is a key player in the progression of Alzheimer’s disease (AD). Interleukin (IL)-1β is a main inducer of inflammation and therefore a prime target for therapeutic options. The inactive IL-1β precursor requires processing by the the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome into a mature and active form. Studies have shown that IL-1β is up-regulated in brains of patients with AD, and that genetic inactivation of the NLRP3 inflammasome improves behavioral tests and synaptic plasticity phenotypes in a murine model of the disease. In the present study, we analyzed the effect of pharmacological inhibition of the NLRP3 inflammasome using dapansutrile (OLT1177), an oral NLRP3-specific inhibitor that is safe in humans. Six-month-old WT and APP/PS1 mice were fed with standard mouse chow or OLT1177-enriched chow for 3 mo. The Morris water maze test revealed an impaired learning and memory ability of 9-mo-old APP/PS1 mice (P = 0.001), which was completely rescued by OLT1177 fed to mice (P = 0.008 to untreated APP/PS1). Furthermore, our findings revealed that 3 mo of OLT1177 diet can rescue synaptic plasticity in this mouse model of AD (P = 0.007 to untreated APP/PS1). In addition, microglia were less activated (P = 0.07) and the number of plaques was reduced in the cortex (P = 0.03) following NLRP3 inhibition with OLT1177 administration. We also observed an OLT1177 dose-dependent normalization of plasma metabolic markers of AD to those of WT mice. This study suggests the therapeutic potential of treating neuroinflammation with an oral inhibitor of the NLRP3 inflammasome.

Objectives This study aimed to assess the impact of polyethylene glycol (PEG) bowel cleansing on performance characteristics of small bowel capsule endoscopy (SBCE). Materials and Methods Data from consecutive patients undergoing SBCE in the period before and after the introduction of PEG 2 L bowel cleansing with PEG were collated retrospectively. The indication, diagnostic yield (DY), clinical outcome, small bowel transit time, gastric transit time, and completion rate were recorded for each procedure. Results Data from 286 patients were analyzed. PEG 2 L was not superior to 12-hour fasting for DY (66 [53%] vs. 76 [47%] patients [p = 0.348]), or DY for significant findings (findings requiring a further intervention or investigation; 29 [23%] vs. 52 [32%] patients [p = 0.090]).There was a trend toward an increased DY for significant findings in patients undergoing investigation for iron-deficiency anemia (IDA) receiving PEG 2 L that just failed to meet statistical significance (13 [31%] and 25 [21%] patients, respectively [p = 0.06]). Transit times and completion rates were unaffected by bowel cleansing. Conclusion Bowel cleansing with PEG 2 L is not superior to fasting for overall DY in SBCE. PEG 2 L may confer an advantage for the detection of significant lesions in patient with IDA. Further investigation of optimal modes of bowel preparation is indicated.

Zusammenfassung Einleitung In den letzten Jahrzehnten wurden Verletzungsmuster im Zusammenhang mit Trampolinspringen und Indoor-Trampolinparks (ITP) in mehreren Studien untersucht, jedoch zeigten diese unterschiedlichste Ergebnisse. Da in Deutschland bislang keine derartige Arbeit veröffentlicht wurde, war das Ziel der vorliegenden Studie, die spezifischen Trampolinpark-assoziierten Verletzungsmuster in unserer Bevölkerung zu analysieren. Methode Retrospektiv wurden alle Patienten, die zwischen dem 01.10.2016 und dem 30.04.2018 eine ITP-bedingte Verletzung erlitten hatten, in die Studie eingeschlossen. Die Patientendaten beinhalteten neben demografischen Angaben wie Alter und Geschlecht auch Angaben zur verletzten Körperregion, Verletzungsdiagnose, Dauer der Aufnahme und Behandlung (operativ/konservativ). Ergebnisse Im Betrachtungszeitraum von 19 Monaten erlitten 258 Patienten ITP-assoziierte Verletzungen. Bei 250 Patienten wurde eine ITP-bedingte Verletzung als Monoverletzung diagnostiziert. Das durchschnittliche Alter der Verletzten betrug 22 Jahre (IQR 15–28). 126 (50,4 %) der Verletzungen traten dabei bei Männern und 124 (49,6 %) bei Frauen auf. 168 (67,2 %) Verletzungen betrafen die untere Extremität (UE). Verstauchungen (n = 114; 45,6 %) und Frakturen ohne Luxation (n = 59; 23,6 %) waren die am häufigsten gestellten Diagnosen. Männer litten signifikant häufiger an Verletzungen der oberen Extremität (26,2 vs. 9,7 %; p = 0,010), während bei Frauen signifikant häufiger die UE betroffen war (79,8 vs. 54,8 %; p Schlussfolgerung ITP-bedingte Verletzungen traten in der zugrunde liegenden Studie bei Erwachsenen häufiger als bei Kindern auf. Die untere Extremität war in jedem Alter die am häufigsten betroffene Körperregion. Insgesamt gilt es festzustellen, dass Trampolinpark-assoziierte Verletzungen ein vielfältiges Bild zeigen und aufgrund dieses sehr heterotopen Verletzungsmusters die Behandlung moderne Unfallchirurgen vor große Herausforderungen stellen kann.

The increasing presence of advanced information and communication technologies (ICTs) across various fields of our lives has elevated the significance of individuals’ capability to utilize these ICTs substantially. Although scholars have underscored the importance of understanding such capabilities in terms of skills that are multidimensional, few empirical investigations are connected to sound theoretical backgrounds. Analyzing a survey administered to a random sample of adults in the City of Austin, this study empirically examines multiplicities of technological capabilities. Building on the literatures of Bourdieu’s theory of capital, digital literacy, field, and participatory culture, this study finds three sets of technological capabilities that constitute individuals’ “techno-capital.” Furthermore, we analyze the influences of cultural and economic/financial capital reflected by key socioeconomic predictors on the different levels of techno-capital. We find that acquiring basic technological capabilities is a key factor explaining advanced techno-capital, while effects of gender, race, education, and income also persist.

Objective: Acute Pancreatitis (AP) is sudden onset pancreas inflammation that causes systemic injury with a wide and markedly heterogeneous range of clinical consequences. Here, we hypothesised that this observed clinical diversity corresponds to diversity in molecular subtypes that can be identified in clinical and multi-omics data.Summary Background data: Observational cohort study. n=57 for the discovery cohort (clinical, transcriptomics, proteomics and metabolomics data) and n=312 for the validation cohort (clinical and metabolomics data).Methods: We integrated co-incident transcriptomics, proteomics, and metabolomics data at serial time points between admission to hospital and up to 48 hours after recruitment from a cohort of patients presenting with acute pancreatitis. We systematically evaluated four different metrics for patient similarity using unbiased mathematical, biological and clinical measures of internal and external validity. We next compared the AP molecular endotypes with previous descriptions of endotypes in a critically ill population with acute respiratory distress syndrome (ARDS).Results: Our results identify four distinct and stable AP molecular endotypes. We validated our findings in a second independent cohort of patients with AP.We observed that two endotypes in AP recapitulate disease endotypes previously reported in ARDS.Conclusions: Our results show that molecular endotypes exist in AP and reflect biological patterns that are also present in ARDS, suggesting that generalisable patterns exist in diverse presentations of critical illness.

IntroductionEndoscopic mucosal resection (EMR) is an invaluable technique, however it is associated with significant risks. In the elderly in particular, the long-term survival benefits of polyp resection with EMR are unknown. The aim of this study was to determine the long-term outcomes in elderly patients who had undergone EMR and to identify any adverse factors.MethodA retrospective observational study on patients of 75 years of age or greater, who underwent EMR of colorectal polyps, in a single tertiary centre, from 2005 to 2014. Demographics of the patients, including Charlson Comorbidity Index (CCI), endoscopic and histological data, were reviewed to identify potential factors predicting outcomes.ResultsThe patients’ median age was 80 years. In total 239 procedures were performed in 206 unique patients. The complication rate was 1.6%. Mean overall survival was 6.7 years with only one patient dying from metastatic colorectal cancer (0.5%) and 49 dying from non-colorectal cancer conditions (24%). Age more than 79 years and CCI more than 2 were independent predictors of significantly shorter survival (p=ConclusionEMR of colonic polyps is safe even for elderly patients. However, the decision to proceed to complex endoscopic therapy should be individualised considering the patients’ age and comorbidities. CCI can help to objectively assess the comorbid state of a patient prior to such decisions.

Research into hippocampal self-regulation abilities may help determine the clinical significance of hippocampal hyperactivity throughout the pathophysiological continuum of Alzheimer's disease. In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. We developed a closed-loop, real-time functional MRI neurofeedback task with virtual reality and tailored it for training downregulation of hippocampal subfield cornu ammonis 1 (CA1). Neurofeedback performance score, cognitive reserve score, hippocampal volume, number of apolipoprotein ε4 alleles and sex were controlled for as confounds in all cross-sectional analyses. First, using voxel-wise multiple regression analysis and controlling for CSF biomarkers, we identified the effect of healthy ageing on eigenvector centrality, a measure of each voxel's overall influence based on iterative whole-brain connectomics, during hippocampal CA1 downregulation. Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. Across subjects, our main findings during hippocampal downregulation were: (i) in the absence of abnormal biomarkers, age correlated with eigenvector centrality negatively in the insula and midcingulate cortex, and positively in the inferior temporal gyrus; (ii) abnormal CSF amyloid-β42 (19.2) correlated with eigenvector centrality positively in the ventral striatum, anterior cingulate and somatosensory cortex, and negatively in the precuneus and orbitofrontal cortex. During resting state functional MRI, similar eigenvector centrality patterns in the cingulate had previously been associated to CSF biomarkers in mild cognitive impairment and dementia patients. Using the developed closed-loop paradigm, we observed such patterns, which are characteristic of advanced disease stages, during a much earlier presymptomatic phase. In the absence of CSF biomarkers, our non-invasive, interactive, adaptive and gamified neuroimaging procedure may provide important information for clinical prognosis and monitoring of therapeutic efficacy. We have released the developed paradigm and analysis pipeline as open-source software to facilitate replication studies. This work has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie action grant agreement No 707730. The project leading to these results has received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004 and the Alzheimer s Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007). JDG is supported by the Spanish Ministry of Economy, and Competitiveness (RYC-2013-13054).

Spinal cord injury (SCI) leads to irreversible functional deficits due to the disruption of axons and the death of neurons and glial cells. The inflammatory response that occurs in the injured spinal cord results in tissue degeneration; thus, targeting inflammation after acute SCI is expected to ameliorate histopathological evidence indicative of damage and, consequently, reduce functional disabilities. Interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) are pro-inflammatory cytokines members of the IL-1 family that initiate and propagate inflammation. Here, we report that protein levels of IL-1β and IL-18 were increased in spinal cord parenchyma after SCI, but with different expression profiles. Whereas levels of IL-1β were rapidly increased reaching peak levels at 12 h after the injury, levels of IL-18 did not increase until 7 days after the injury. Since activation of the NLRP3 inflammasome is required for the processing and release of IL-1β and IL-18, we intraperitoneally administered OLT1177, a selective inhibitor of the NLRP3 inflammasome, to reduce the contribution of these cytokines to SCI. At a dose of 200 mg/kg, OLT1177 protected against neurological deficits and histological evidence of damage. OLT1177 also reduced the levels of IL-1β in the spinal cord after contusion injury and diminished the accumulation of neutrophils and macrophages at later time points. These data suggest that targeting the NLRP3 inflammasome with OLT1177 could be a novel therapeutic strategy to arrest neuroinflammation and reduce functional impairments after acute SCI in humans.

Background:. Live Surgery Meetings have been established as a vey effective means to demonstrate certain surgical techniques and intraoperative decision-making. However, many authors still question the ethics of this approach. We present our experience as organizers of the Live Makeover Aesthetic Surgery Symposium, an annual international live surgery meeting taking place in Athens, Greece. Methods:. Throughout the course of our meetings, 2 surveys were performed, 1 after Live Makeover Aesthetic Surgery Symposium 3, comparing the educational value between live surgery and pre-recorded videos, and the second after LMASS 6, re-evaluating the educational value of live surgery, as well as the ethics of this educational method and the patient safety. In addition, we studied the results of the patients operated on in all of our meetings, and their level of satisfaction. Results:. Based on the results of the first survey, the superior educational value of live surgery was obvious. The second survey confirmed those valuable educational benefits. In addition, the concerns on both surgical outcomes and patient safety were minimal. The patients showed a very high level of satisfaction through their answers. The complications encountered were only 2 of the 49 live surgical demonstrations and were not directly related to the live demonstration. Conclusions:. Based on our study, live surgery is an effective, safe educational tool. However, strict guidelines have to be followed to ensure high educational value and patient safety. Based on our 9-year experience with our live surgery meeting, we provide detailed guidelines for optimal outcomes.

Background:. Revision facelift is a very challenging operation. The goal of our study was to examine the most common problems that the facelift surgeon has to face in a revision case and to suggest ways of solving them. Methods:. A review of all patients from 2012 to 2017 in whom rhytidectomy was performed by the senior author was conducted. Results:. During the 5-year study period, the author performed 552 face lifts. After the review to confirm revision procedures, a total of 72 revision facelifts were found. On reviewing the most common problems encountered in our facelifts, we found that in addition to the stigmata of the primary facelift, which are thoroughly analyzed in our article, a new type of stigmata has been added nowadays to the revision facelift—that of the various noninvasive interventions that patients undergo after their first facelift, in their effort to postpone or avoid a second operation. In all the abovementioned cases, the surgeon has to modify his basic surgical plan accordingly, to be able to improve or solve all of those problems during the revision surgery. Conclusions:. The modern facelift surgeon often has to face much more than the stigmata of the primary facelift or the natural aging process. Thus, he/she should be appropriately trained to solve any problem we might encounter in a revision case.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments. With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in open science research practices and data sharing. publishedVersion

The goal of the study presented in this article is to provide a general overview of the various aspects related to electric vehicles (EVs), along with all associated emerging challenges and perspectives. In this context, the basic types of EVs and the corresponding charging technologies are analyzed. Since EVs are expected to be a key component of future smart electrical grids (SEG), connection to the grid issues, along with advanced charging techniques (i.e., wireless power transfer), are analyzed as well. To this end, the main features, the requirements of vehicle to grid (V2G) communications, as well as future developments and scenarios of electrification, are also presented and analyzed. Moreover, integration issues with currently deployed fifth generation (5G) mobile wireless networks are also outlined, in order to ensure optimum transmission and reception quality in V2G communications and improved user experience. This integration is also expanded in autonomous vehicles (AVs) technology (self-driving objects), since optimized information processing from various diverse sources is required in order to ensure advanced traffic management aspects.

International audience; We present an inverse design tool for fabric formwork - a process where flat panels are sewn together to form a fabric container for casting a plaster sculpture. Compared to 3D printing techniques, the benefit of fabric formwork is its properties of low-cost and easy transport. The process of fabric formwork is akin to molding and casting but having a soft boundary. Deformation of the fabric container is governed by force equilibrium between the pressure forces from liquid fill and tension in the stretched fabric. The final result of fabrication depends on the shapes of the flat panels, the fabrication orientation and the placement of external supports. Our computational framework generates optimized flat panels and fabrication orientation with reference to a target shape, and determines effective locations for external supports. We demonstrate the function of this design tool on a variety of models with different shapes and topology. Physical fabrication is also demonstrated to validate our approach.

To provide an updated summary of the pleurotoxic drugs and their manifestations. Novel antineoplastic agents for the treatment of hematologic and non-hematologic malignancies have been associated with the induction of pleural disorders. Moreover, the list of agents that have been associated with drug-induced lupus pleuritis is steadily increasing. Pleurotoxic medications are agents that may cause pleural disorders, most commonly pleural effusions. Connecting a pleural disorder to a specific drug requires the exclusion of other potential causes combined with resolution of the disorder after drug discontinuation while previous literature reports on similar cases may be of assistance. The incorporation of new therapies into clinical practice over the last few years has exposed medical professionals to areas devoid of a historic evidence base. Thus, drug-induced pleurotoxicity should be always included in the diagnostic approach to the patient with a pleural effusion.

Ultraviolet radiation exposure is the dominant environmental determinant of all major forms of skin cancer, and the main cause of prematurely aged skin that is referred to as photoaging. Collagen type I (COL I) is expressed differently along with the dermis between healthy and pathological skin tissues. The aim of this study was to understand the impact of solar radiation in the dermis and assess the impact of solar radiation to COL I. The hematoxylin and eosin staining protocol was performed in tissue paraffin blocks and then they were stained immunohistochemically with the rabbit monoclonal anti-COL I antibody. A total of 270 slides were studied with an Olympus BX 41 microscope, we scored positively the expression of COL I in dermis and statistically analyzed with IBM SPSS Statistics. Based on our results, we observed that solar elastosis changes the structure of the skin’s collagen. In healthy tissues, COL I had a uniform expression along with the dermis. In tissues with aging, COL I expression was weaker and lost homogeneity. In pathological tissues (non-melanoma skin cancers, NMSCs), precancerous lesions, and benign skin lesions), the expression of COL I was observed to be almost weaker than tissues with aging in all body parts and much weaker below the lesions. The most severe solar elastosis was observed in the extremities. The degree of severity of the solar elastosis in relation to age did not appear to be completely affected. Solar radiation divides the collagen more rapidly than normal biological aging and solar elastosis was observed into the skin tissues with photoaging, which replaces the collagen fibers of the skin. These results confirm previous studies, which have shown that skin COL I decreases during aging, more in photoaging and even more in skin cancers. We conclude that skin COL I expression is reduced as a result of ultraviolet radiation and leading to negative impacts on the skin.

Real-time fMRI neurofeedback is an increasingly popular neuroimaging technique that allows an individual to gain control over his/her own brain signals, which can lead to improvements in behavior in healthy participants as well as to improvements of clinical symptoms in patient populations. However, a considerably large ratio of participants undergoing neurofeedback training do not learn to control their own brain signals and, consequently, do not benefit from neurofeedback interventions, which limits clinical efficacy of neurofeedback interventions. As neurofeedback success varies between studies and participants, it is important to identify factors that might influence neurofeedback success. Here, for the first time, we employed a big data machine learning approach to investigate the influence of 20 different design-specific (e.g. activity vs. connectivity feedback), region of interest-specific (e.g. cortical vs. subcortical) and subject-specific factors (e.g. age) on neurofeedback performance and improvement in 608 participants from 28 independent experiments.With a classification accuracy of 60% (considerably different from chance level), we identified two factors that significantly influenced neurofeedback performance: Both the inclusion of a pre-training no-feedback run before neurofeedback training and neurofeedback training of patients as compared to healthy participants were associated with better neurofeedback performance. The positive effect of pre-training no-feedback runs on neurofeedback performance might be due to the familiarization of participants with the neurofeedback setup and the mental imagery task before neurofeedback training runs. Better performance of patients as compared to healthy participants might be driven by higher motivation of patients, higher ranges for the regulation of dysfunctional brain signals, or a more extensive piloting of clinical experimental paradigms. Due to the large heterogeneity of our dataset, these findings likely generalize across neurofeedback studies, thus providing guidance for designing more efficient neurofeedback studies specifically for improving clinical neurofeedback-based interventions. To facilitate the development of data-driven recommendations for specific design details and subpopulations the field would benefit from stronger engagement in Open Science and data sharing.

Aim: To evaluate the efficacy and safety of Flexible Bronchoscopy as first-line diagnosis and treatment modality in pediatric cases with Foreign body aspiration (FBA) Methods: We performed a retrospective study reviewing the clinical records of 219 children who underwent flexible bronchoscopy (FB) for suspected FBA, over a period of 26 years. We evaluated the success of FB in removal of foreign body using a retrieval basket at a referral tertiary hospital. Results: FBA was confirmed with bronchoscopy in 104 cases (47.5%), (mean age 3.13, range: 6 months-10 years, 68% males). The majority of the foreign bodies were nuts (52.5%), followed by other food particles (16%) and seeds (8%). The foreign body was located predominantly in the right bronchial tree (56%). The most common clinical signs and symptoms were cough (79.5%), reduced air entry (66.3%) and wheezing (29.4%). The most frequent radiological finding was unilateral hyperinflation (55.8%) followed by opacities (23%) and atelectasis (11.5%). Fifty-eight percent of the foreign bodies were removed with a rigid bronchoscope by ENT; over the last 7 years there has been an increasing trend to remove the inhaled foreign body with a basket through the FB. In 41% of the patients with FBA, foreign bodies were successfully removed during FB. Over the last 5 years, only in two patients, foreign body could not be removed with FB and they underwent rigid bronchoscopy. No serious complications were observed in these cases except cough. Conclusions: Flexible bronchoscopic extraction of a foreign body in the airway using a retrieval basket in children can be performed successfully with minimal complications.

Community acquired pleural infection (CAPI) is an increasingly common health problem worldwide, associated with high risk of fatal and non-fatal complications. The bacteriology and the ideal antibacterial treatment of CAPI differs among different countries. Aiming to unravel the microbiology and resistance patterns of CAPI and also identify clinical features that could predict risk of death or drug-resistance, we conducted a multicenter observational study of 158 CAPI patients in Greece. We collected a wide range of data, clinical/imaging findings, pleural fluid characteristics and bacteriological data, as well as survival rates. We found that the most common isolates in our study participants were the non-pneumococal streptococci (~40%). The bacterial isolates presented a high prevalence of sensitivity to commonly prescribed antibiotic combination, with highest the combination of aminopenicillin/lactamase inhibitor (92.9%). Moreover, we showed that mortality in these patients was strongly associated with the RAPID score (OR 102.12, p The results of our study could be of high clinical significance in both guiding antibiotic selection in CAPI patients and assisting the detection of patients resistant to antibiotics and therefore reducing the high morbidity and mortality associated with the disease.

SUMMARY: BACKGROUND: Gout flares are driven by interleukin (IL)-1β. Dapansutrile inhibits the NLRP3 inflammasome and subsequent activation of IL-1β. In this study we aimed to investigate the safety and efficacy of orally administered dapansutrile in patients with a gout flare. METHODS: In this open-label, proof-of-concept, phase 2a trial, adult patients (aged 18–80 years) with a monoarticular monosodium urate crystal-proven gout flare were enrolled at an outpatient clinic in the Netherlands and sequentially assigned using a dose-adaptive design to receive 100 mg/day, 300 mg/day, 1000 mg/day, or 2000 mg/day oral dapansutrile for 8 days. The coprimary outcomes were change in patient-reported target joint pain from baseline to day 3 and from baseline to day 7, assessed in the per-protocol population (all patients who received at least 80% of the study drug and had no major protocol deviations). Safety was assessed in the intention-to-treat population. This trial is registered with the EU Clinical Trials Register, EudraCT 2016-000943-14, and is completed. FINDINGS: Between May 18, 2017, and Jan 21, 2019, 144 patients were assessed for eligibility, of whom 34 were enrolled and 29 were included in the per-protocol population (three patients were excluded due to receiving

A new meshless numerical approach for studying heat conduction in particulate systems was developed that allows the efficient computation of the temperature distribution and the effective thermal conductivity in particle aggregates. The incorporation of the discretization-corrected particle strength exchange operator in meshless local Petrov&ndash, Galerkin calculations is suggested here, which was shown to perform better than previously tested trial functions, regarding the speed of convergence and accuracy. Moreover, an automated algorithm for node refinement was developed, which avoids the necessity for user intervention. This was quite important in the study of particle aggregates due to the appearance of multiple points of contact between particles. An alternative approach for interpolation is also presented, that increased the stability of the methods and reduced the computational cost. Test case models, commercial computational fluid dynamics software, and experimental data were used for validation. Heat transport in various aggregate morphologies was also studied using sophisticated aggregation models, in order to quantify the effect of aggregate fractal dimension on the nanofluid conductivity, targeting eventually the optimization of heat transfer applications. A trend of effective conductivity enhancement upon reduction of the fractal dimension of the aggregate was noted.

Elemental mercury is a natural occurring trace component of fossil fuels, which poses significant health and safety risks during oil and gas processing due to its highly toxic and corrosive nature. In order to anticipate and control the distribution of mercury during industrial processes, there is a necessity for thermodynamic models, which can accurately predict its partitioning in the various phases. In this work, the UMR-PRU model is extended to systems that contain elemental mercury and is employed for predicting its solubility in hydrocarbons, compressed gases, water and methanol. A comparison is also made between UMR-PRU and the two most widely used equations of state, Soave-Redlich-Kwong and Peng-Robinson, with modified attractive terms. The results reveal that all three models can accurately describe the solubility of mercury in the aforementioned compounds, with UMR-PRU being the most accurate.

We provide detailed guidelines and code to derive high quality international equity data from Thomson Reuters Datastream (TDS) data. Our approach increases stock and country coverage (to 91 countries), improves data accuracy, filters problematic data and reduces survivorship bias and data staleness. We validate our approach by demonstrating that our U.S. TDS factors are statistically and economically indistinguishable to standard Fama-French CRSP factors. On the other hand, when we compare our international factors to other publicly available international factors, differences are significant, so we justify and detail every aspect of our proposed guidelines. Our guidelines and accompanying code and data should be especially useful for international research focused on wide coverage, equal weighted portfolios, small stocks and countries with a limited number of stocks and for researchers wishing to analyze the US market with access to only TDS but not CRSP-Compustat data.

The lattice-Boltzmann (LB) method is used in this work to reproduce the controlled addition of binder and hydrophobicity-promoting agents, like polytetrafluoroethylene (PTFE), into gas diffusion layers (GDLs) and to predict flow permeabilities in the through- and in-plane directions. The present simulator manages to reproduce spreading of binder and hydrophobic additives, sequentially, into the neat fibrous layer using a two-phase flow model. Gas flow simulation is achieved by the same code, sidestepping the need for a post-processing flow code and avoiding the usual input/output and data interface problems that arise in other techniques. Compression effects on flow anisotropy of the impregnated GDL are also studied. The permeability predictions for different compression levels and for different binder or PTFE loadings are found to compare well with experimental data for commercial GDL products and with computational fluid dynamics (CFD) predictions. Alternatively, the PTFE-impregnated structure is reproduced from Scanning Electron Microscopy (SEM) images using an independent, purely geometrical approach. A comparison of the two approaches is made regarding their adequacy to reproduce correctly the main structural features of the GDL and to predict anisotropic flow permeabilities at different volume fractions of binder and hydrophobic additives.

SETTING Data on the relationship between pleural tuberculosis (TB) and anti-tuberculosis drug resistance are scarce. OBJECTIVE To determine the patterns of drug resistance among pleural Mycobacterium tuberculosis isolates in Greece and the incidence of tuberculous pleural effusion (TPE) among patients with multidrug-resistant (MDR) or extensively drug-resistant (XDR) pulmonary TB. DESIGN Drug susceptibility testing (DST) results recorded in the database of the National Reference Centre for Tuberculosis in Athens, Greece, over a 9-year period (2003-2011) were reviewed. Chest X-rays from hospitalised patients with pulmonary MDR/XDR-TB during the same period were also reviewed for the presence of TPE. RESULTS Resistance to at least one first-line drug was observed in 11% of the cases (MDR-TB 3%, XDR-TB 1%), while 29% of the patients with pulmonary MDR/XDR-TB presented with TPE during the course of their disease, the majority ipsilateral to the lung lesions, which responded to guided anti-tuberculosis treatment. CONCLUSION The prevalence of drug resistance among pleural M. tuberculosis isolates in Greece highlights the importance of DST prior to treatment selection in TPE patients. In our study population, TPE that developed in one third of the patients with pulmonary MDR/XDR-TB usually resolved with DST-guided anti-tuberculosis treatment.

IL-1β and IL-18 are pro-inflammatory cytokines that are linked to inflammation. Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is involved in the maturation and secretion of IL-1β and IL-18 and, thus, plays a key role in the pathogenesis of many inflammatory conditions, including multiple sclerosis (MS). OLT1177™ (Dapansutrile) is a newly developed drug that is safe in humans and inhibits specifically the NLRP3 inflammasome. In the present study, we investigated whether OLT1177 exerts therapeutic effects in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We found that EAE mice fed an OLT1177-enriched diet prophylactically were significantly protected against functional deficits and demyelination in the spinal cord. We also demonstrated that prophylactic oral administration of OLT1177 led to marked reduction (~2- to 3-fold) in the protein levels of IL-1β and IL-18, as well as, IL-6 and TNFα, in the spinal cord of EAE mice. Moreover, prophylactic oral administration of OLT1177 significantly attenuated the infiltration of CD4 T cells and macrophages in the spinal cord. We also demonstrated that oral administration of OLT1177, starting at disease onset, resulted in significant amelioration of the clinical signs of EAE. Overall, these first data suggest that OLT1177 could have clinical benefit for the treatment of MS in humans.

Actuators of notable complexity are fabricated using multimaterial 3D printing coupled with automated design synthesis., Upcoming actuation systems will be required to perform multiple tightly coupled functions analogous to their natural counterparts; e.g., the ability to control displacements and high-resolution appearance simultaneously is necessary for mimicking the camouflage seen in cuttlefish. Creating integrated actuation systems is challenging owing to the combined complexity of generating high-dimensional designs and developing multifunctional materials and their associated fabrication processes. Here, we present a complete toolkit consisting of multiobjective topology optimization (for design synthesis) and multimaterial drop-on-demand three-dimensional printing for fabricating complex actuators (>106 design dimensions). The actuators consist of soft and rigid polymers and a magnetic nanoparticle/polymer composite that responds to a magnetic field. The topology optimizer assigns materials for individual voxels (volume elements) while simultaneously optimizing for physical deflection and high-resolution appearance. Unifying a topology optimization-based design strategy with a multimaterial fabrication process enables the creation of complex actuators and provides a promising route toward automated, goal-driven fabrication.

Virtual reality is a trending, widely accessible, and contemporary technology of increasing utility to biomedical and health applications. However, most implementations of virtual reality environments are tailored to specific applications. We describe the complete development of a novel, open-source virtual reality environment that is suitable for multipurpose biomedical and healthcare applications. This environment can be interfaced with different hardware and data sources, ranging from gyroscopes to fMRI scanners. The developed environment simulates an immersive (first-person perspective) run in the countryside, in a virtual landscape with various salient features. The utility of the developed VR environment has been validated via two test applications: an application in the context of motor rehabilitation following injury of the lower limbs and an application in the context of real-time functional magnetic resonance imaging neurofeedback, to regulate brain function in specific brain regions of interest. Both applications were tested by pilot subjects that unanimously provided very positive feedback, suggesting that appropriately designed VR environments can indeed be robustly and efficiently used for multiple biomedical purposes. We attribute the versatility of our approach on three principles implicit in the design: selectivity, immersiveness, and adaptability. The software, including both applications, is publicly available free of charge, via a GitHub repository, in support of the Open Science Initiative. Although using this software requires specialized hardware and engineering know-how, we anticipate our contribution to catalyze further progress, interdisciplinary collaborations and replicability, with regards to the usage of virtual reality in biomedical and health applications.

Hippocampal down-regulation is associated with genetic predisposition to Alzheimer’s disease (AD), neurodevelopmental processes and disease symptoms. Resting state eigenvector centrality (EC) patterns resemble those of FDG-PET in AD, they can predict self-regulation performance and they are related to functional compensation across the pathophysiological continuum of AD. We acquired cerebrospinal fluid (CSF) biomarkers from a cognitively unimpaired sample at risk for AD (N=48), to investigate the effect of β- amyloid peptide 42 (Aβ42) and phosphorylated tau (p-Tau) levels on EC during the down-regulation of hippocampal subfield cornu ammonis 1, with real-time fMRI closed-loop neurofeedback. Controlling the effects of confounding variables (age, sex, number of APOE ε4 alleles, cognitive reserve, brain reserve and hippocampal down-regulation performance), CSF Aβ42 levels correlated positively with EC in the anterior cingulate cortex (BA24, BA32) and primary motor cortex (BA4). CSF p-Tau levels correlated with EC positively in the ACC (BA32, BA10) ventral striatum (caudate, nucleus accumbens, putamen) and left primary somatosensory cortex (BA2), as well as negatively in the posterior cingulate cortex, precuneus, cuneus and left frontal pole (BA9). Controlling for CSF biomarkers and other prognosis variables, age correlated negatively with EC in the midcingulate cortex, insula, primary somatosensory cortex (BA2) and inferior parietal lobule (BA40), as well as positively with EC in the inferior temporal gyri. Taken together, we identified patterns of functional connectomics in individuals at risk of AD during hippocampal down-regulation, which resemble those found during resting state at advanced AD stages. Moreover, we provide a standard paradigm to replicate and extend this work on a global level. This opens new avenues for further research applications, which quantify and monitor disease progression, by identifying early alterations in the self-regulation of brain function, with potential for non-invasive prognostic screening.HighlightsACC centrality decreases with early Aβ42ACC centrality increases with p-TauPCC centrality decreases with p-TauMCC centrality decreases in healthy aging

INTRODUCTION:Antitumour necrosis factor (TNF) agents and vedolizumab are used to treat ulcerative colitis (UC) but the response is variable and there is little data on comparative effectiveness. Apart from previous exposure to anti-TNF agents, predictors of response have not been identified. We aimed to (i) compare the efficacy of anti-TNF agents and vedolizumab in UC and (ii) investigate the utility of clinical and biochemical parameters in predicting response. PATIENTS AND METHODS:Patients commencing any biological therapy for ambulant UC were included. Disease activity was monitored serially with the Simple Clinical Colitis Activity Index for up to 12 months. We compared the efficacy of anti-TNF agents and vedolizumab for induction and maintenance of response and remission on an intention-to-treat basis. We examined the utility of faecal calprotectin (FC) and early normalization of FC to predict response. RESULTS:Ninety-seven patients commencing anti-TNF and 42 commencing vedolizumab therapy were included. Vedolizumab-treated patients had significantly greater previous anti-TNF therapy exposure and a lower baseline FC. Response, remission and steroid-free remission rates were comparable between both groups at 6 weeks, 6 and 12 months. Clinical remission but not steroid-free remission at 12 months was higher in the vedolizumab group. There was a significant reduction in the Simple Clinical Colitis Activity Index and FC at 6 weeks, 6 and 12 months compared with baseline in both groups. Baseline FC and early normalization did not predict response at 6 and 12 months. CONCLUSION:The efficacy of anti-TNF and vedolizumab in UC appear comparable. We could not identify any predictors of response and remission.

Career situation of first and presenting author Young investigator. Introduction Acute gout is a severe debilitating type of arthritis that is treated in the acute phase with potent anti-inflammatory drugs. To date, prednisolone, colchicine and/or non-steroidal anti-inflammatory drugs are the standard of care despite serious side effects of chronic use, especially in the older population most often presenting with an acute gout attack. In addition, interleukin-1 (IL-1) biologics (e.g., canakinumab/rilonacept/ anakinra) have proven efficacy in RCTs, however, these biologics have not been broadly adopted due to barriers such as the requirement of parenteral administration, cost and risk of infection. There is an unmet need for a safe, oral, cost effective IL-1 inhibitor targeting the NLRP3 inflammasome pathway. Dapansutrile™ (OLT1177™) has been shown to inhibit IL-1β and IL-18 release in human macrophages and to prevent NLRP3 inflammasome activation, with no effect on the priming phase of the NLRP3 inflammasome formation or on TNF-alpha. Dapansutrile™ has no effect on the AIM2 or NLRC4 inflammasomes. In addition to acute gout, dapansutrile™ is under clinical development in heart failure and it has demonstrated positive results in numerous preclinical models. Dapansutrile’s™ Phase 1 dose escalation clinical trial demonstrated safety at doses up to 1000 mg/day for 8 days. Objectives The Phase 2a study is a dose ranging, proof-of-concept trial to demonstrate the clinical effectiveness, pharmacodynamics (e.g., cytokine levels and other relevant biomarkers), safety/tolerability and pharmacokinetics of dapansutrile™ in four cohorts at doses of 100 mg QD, 300 mg QD, 500 mg BID or 500 mg QID. Methods An adaptive dose design was used with planned enrollment of 8 patients per cohort to assess the efficacy of dapansutrile™ in treating the clinical signs and symptoms of acute gout over an 8 day treatment period. Clinical effect was targeted to be greater than 50% pain reduction from baseline at approximately 72 hours after the first dose. Cohorts 1, 2 and 3 were administered dapansutrile™ doses of 500 mg BID, 500 mg QID and 300 mg dapansutrile™ (200 mg at 08.00 hour and 100 mg at 20.00 hour), respectively. Cohort 4 is currently enrolling subjects given 100 mg dapansutrile™ QD. VAS pain, general disability and walking disability scores were measured by daily diary and blood sampling was conducted on study days 0 (baseline), 3, 7 and 14 to assess PK and PD (including plasma cytokine levels, hsCRP, inflammasome activity, etc). Safety was measured over the duration of the study with clinic visits on study days 0 (baseline), 3, 7, 14 and a follow-up telephonic visit on day 35. Results A significant clinical and inflammatory cytokine response at Day 3 was seen in all dose groups and will be elaborated upon once the final datasets become available. There were no metabolic, physiological or hematological changes and all doses were well tolerated. Conclusions On the basis of both the clinical response and the biomarkers, dapansutrile™ is a safe and effective anti-inflammatory oral NLRP3 inhibitor in the treatment of acute gout with a broad therapeutic range and promise for further clinical development in this indication. Acknowledgements We wish to acknowledge the gout patients willing to participate as well as Danielle Poeth and Dorine Baselmans for their commitment to the conduct of this study. Potential investigators conflicts of interest DS is founder and CEO of Olatec, CS is CMO of Olatec, RB is COO of Olatec, CD is CSO and SAB member of Olatec, LJ is SAB member of Olatec. Disclosure of Interest None declared.

Career situation of first and presenting author Young investigator. Introduction Gout flares are characteristically mediated by the pro-inflammatory cytokine interleukin (IL)-1β.1 Uptake of monosodium urate (MSU) crystals by macrophages activates the nucleotide-binding domain and leucine-rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome, which converts intracellular pro-interleukin-1β (pro-IL-1β) to mature bioactive IL-1β by proteolytic cleavage. Deposition of MSU crystals alone is not sufficient to trigger a gout flare. In the presence of concomitant pro-inflammatory stimuli, i.e. Toll-Like Receptor (TLR) agonists, transcription of il-1β gene is induced and pro-IL-1β is rapidly converted into its active form. IL-1β binds to its receptor (IL-1R1) and induces a cascade of secondary inflammatory mediators including prostaglandins, cytokines and chemokines. Recently, OLT1177™, a β-sulfonyl nitrile compound, safe in humans, was shown to inhibit the NLRP3 inflammasome, reverse the metabolic cost of inflammation and inhibit joint inflammation in murine models of acute arthritis.2 3 Objectives To explore the mechanism by which oral OLT1177™ inhibits joint inflammation in humans with gout flares. Methods 29 patients with a gout flare were treated within 4 days after the start of the symptoms with three different doses of OLT1177™ for 7 days (EudraCT: 2016-000943-14). Blood was drawn at baseline, days 3, 7 and 14 (7 days after finishing treatment). Haematology, hsCRP and SAA were measured as markers for systemic inflammation. Plasma was collected for assessment of circulating cytokines. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured under unstimulated or stimulated conditions with a TLR ligands (Pam3Cys and LPS) in combination with MSU crystals after which intra- and extracellular cytokine production was assessed. Results Plasma IL-1β are increased in samples from intercritical gout patients and individuals with gout flares when compared to healthy controls (healthy controlshsCRP and SAA and acute phase proteins of individuals treated with OLT1177™ during a gout flare show a dose-dependent reduction during course of treatment. Circulating IL–1β and IL–6, but not TNFα, was reduced and stimulated cytokine production of PBMCs declined during treatment. In unstimulated PBMCs on day 3, ratio of intracellular pro-IL-1β and IL-1β revealed inhibition of the NLRP3 inflammasome by oral OLT1177™. Moreover, in vitro and ex vivo data show OLT1177™ spontaneously increases the level of IL-1 receptor antagonist (IL-1Ra). Conclusions Oral OLT1177™, safe in humans, inhibits inflammation and increases systemic IL-1Ra concentrations in patients with an acute gout flare by inhibiting the NLRP3 inflammasome product, IL–1b. References Dinarello CA. How interleukin-1beta induces gouty arthritis. Arthritis Rheum 2010;62(11):3140–4. Marchetti C, et al. OLT1177, a beta-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc Natl Acad Sci USA 2018;115(7):E1530–E1539. Marchetti C, et al. NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. Arthritis Res Ther 2018;20(1):169. Acknowledgements We wish to acknowledge the gout patients who participated as well as Danielle Poeth and Dorine Baselmans for their commitment to the conduct of this study. Potential investigators conflict of interest DS is Founder and CEO of Olatec, CD is CSO and SAB member of Olatec, LJ is SAB member of Olatec. Disclosure of Interest None declared.

Acute pancreatitis (AP) is sudden onset pancreas inflammation that causes multiple organ dysfunction syndrome (MODS) and death in certain individuals who develop AP yet minimal systemic inflammation in others. Here, we show that this observed diversity in systemic response and outcome is accompagnied by diversity in molecular subtypes that can be identified using computational analysis of clinical and multiomic data. We integrated co-incident whole blood transcriptomic, plasma proteomic, and serum metabolomic data at serial time points from a cohort of patients presenting with AP and systematically evaluated four different metrics for patient similarity, using unbiased mathematical, biological and clinical measures of internal and external validity. Our results identify four distinct and stable AP endotypes that are characterized by pathway and biomarker combination stereotypes into hypermetabolic, hepatopancreaticobiliary, catabolic and innate immune endotypes. The catabolic endotype in AP strikingly recapitulates a disease endotype previously reported in acute respiratory distress syndrome, a recognized complication of AP. Our findings demonstrate that clinically-relevant and generalizable endotypes exist in AP.

Combination therapy with infliximab and immunomodulators is superior to monotherapy, resulting in better outcomes and higher trough levels of infliximab. The role of concurrent immunomodulatory therapy on adalimumab trough levels has not been adequately investigated. We evaluated the impact of concomitant immunomodulation on adalimumab trough levels in patients on scheduled maintenance therapy.We conducted a prospective observational, cross-sectional study of all inflammatory bowel disease patients on maintenance therapy who had adalimumab trough levels measured between January 2013 and January 2016. Drug level and anti-drug antibody measurements were performed on sera using a solid phase assay. Pairwise comparison of means was used to compare trough levels in patients with and without concomitant immune modulator therapy.In total, 79 patients were included. Twenty-three patients (29.1%) were on weekly dosing whereas 56 (70.9%) were on alternate weeks. Median adalimumab trough levels were comparable in patients with and without clinical remission (6.8 μg/ml (IQR 5.6-8.1) versus 6.7 μg/ml (IQR 3.9-8.1), respectively. Patients with an elevated faecal calprotectin 250 μg/g had lower adalimumab trough levels (median 6.7, IQR 3.9-8) compared to patients with faecal calprotectin 250 μg/g (median 7.7, IQR 6.1-8.1) though this did not achieve statistical significance (p = .062). Median adalimumab trough levels among patients on concurrent immunomodulators was 7.2 μg/ml (IQR 5.7-8.1) compared to those not on concurrent immunomodulator, 6.1 μg/ml (IQR 2.7-7.7, p = .0297).Adalimumab trough levels were significantly higher in patients on concurrent immunomodulators during maintenance therapy. There was a trend towards a lower adalimumab trough level in patients with elevated calprotectin.

Chemotherapy has reached a plateau in the efforts for survival improvement in non-small cell lung cancer (NSCLC). The growing knowledge of NSCLC molecular pathobiology has led to the development of new treatments that target specific tumor functions. Angiogenesis is a tumor function leading to the formation of new tumor vessels that are crucial for its survival. Although vascular endothelial growth factor (VEGF) plays a primary role in angiogenesis, the inhibition of the VEGF pathway with VEGF-receptor (VEGFR) tyrosine kinase inhibitors (TKIs) is associated with a modest survival benefit due to the development of resistance by the tumor that has been mainly attributed to the up-regulation of other stimulators of angiogenesis. Thus, the use of multitargeted antiangiogenesis TKIs (MATKIs) for simultaneous inhibition of multiple angiogenic pathways has been proposed. This review summarizes data about novel treatment strategies incorporating the inhibition of angiogenesis with MATKIs in NSCLC. The data from all relevant studies shows that MATKIs do not offer additional survival benefit to currently available chemotherapeutic options in unselected NSCLC patients. However, the diversity in disease response to MATKI-containing regimens implies that specific patient subgroups may benefit from or be harmed by these agents. In this context, most studies agree that the VEGFR-targeting MATKIs are harmful in squamous NSCLC while specific MATKIs (i.e., motesanib, vandetanib and nintedanib) are associated with improved progression free survival in non-squamous NSCLC. However, overall survival benefit was found only in adenocarcinoma and Asian non-squamous NSCLC patients with the use of nintedanib and motesanib, respectively.

Dew point measurements for six natural gases, originating from different gas fields of the Norwegian Continental Shelf, were performed using a custom made chilled mirror apparatus. The natural gas samples were taken from different points of the Norwegian pipeline network and their composition was determined by gas chromatography. The experimental dew point data cover a temperature range from 259 to 297 K and a pressure range from 12 to 110 bar. The performance of SRK, PR, PC-SAFT and UMR-PRU models has been evaluated against the experimental data. The results indicate that the best model for hydrocarbon dew point predictions, especially at high pressures and the cricondenbar pressure, is the UMR-PRU model.

This article summarizes current data regarding the accuracy of pleural fluid tests assisting the diagnosis of tuberculous pleuritis (TBP).No pleural fluid test reliably rules-in TBP in settings with low TBP prevalence. Interferon-γ) alone or in combination with adenosine deaminase (ADA) is more reliable than ADA for this purpose in nonlow prevalences. ADA can reliably rule-out TBP in prevalences of less than 40% although in higher prevalences the product of interleukin-27 and ADA is the most accurate rule-out test.The definite diagnosis of TBP requires the isolation of Mycobacterium tuberculosis from pleural fluid or biopsies. Because of the low sensitivity of pleural fluid cultures and the invasiveness of pleural biopsy techniques, the concept of a pleural fluid test that accurately establishes or excludes TBP diagnosis has been proposed. Numerous pleural fluid tests have been evaluated for this purpose with ADA being the most widely accepted one. During the last years, it has been demonstrated that the ability of ADA to rule-in or rule-out TBP is affected by the prevalence of TBP in the setting where the test is used. The complementary use of interferon-γ or interleukin-27 increases the ability of ADA to rule-in or rule-out the disease, respectively.

“Asbestos” is a term used to characterise a number of natural mineral fibres of silica that can be categorised according to their structure in the serpentine-type fibres, mainly represented by chrysotile, and the amphibole-type fibres, which include crocidolite, amosite, anthophyllite, actinolite and tremolite [1]. Due to its remarkable durability and fire resistance, asbestos has been used in pottery and clothing since for at least 4500 years. However, modern commercial production of asbestos began during the second half of the 19th century when industry started to exploit its unique chemical characteristics for manufacturing various products, such as pipe insulation, brake linings, cement pipes, protective clothing, etc. With the increasing use of such materials, individuals working in the construction (e.g. builders, plumbers, etc.) and ship building (e.g. dockyard workers) industries began to be exposed to high concentrations of inhaled asbestos fibres. Approximately 50–70 years after the introduction of asbestos in commercial use, the first reports of asbestos-related diseases emerged [1]. Since then, multiple studies have connected asbestos exposure with a variety of malignant and non-malignant lung disorders., Novel aspects of the pathogenesis of asbestos-related diseases are still coming to light http://ow.ly/EPDa30e8JqK

We propose an inverse strategy for modeling thin elastic shells physically, just from the observation of their geometry. Our algorithm takes as input an arbitrary target mesh, and interprets this configuration automatically as a stable equilibrium of a shell simulator under gravity and frictional contact constraints with a given external object. Unknowns are the natural shape of the shell (i.e., its shape without external forces) and the frictional contact forces at play, while the material properties (mass density, stiffness, friction coefficients) can be freely chosen by the user. Such an inverse problem formulates as an ill-posed nonlinear system subject to conical constraints. To select and compute a plausible solution, our inverse solver proceeds in two steps. In a first step, contacts are reduced to frictionless bilateral constraints and a natural shape is retrieved using the adjoint method. The second step uses this result as an initial guess and adjusts each bilateral force so that it projects onto the admissible Coulomb friction cone, while preserving global equilibrium. To better guide minimization towards the target, these two steps are applied iteratively using a degressive regularization of the shell energy. We validate our approach on simulated examples with reference material parameters, and show that our method still converges well for material parameters lying within a reasonable range around the reference, and even in the case of arbitrary meshes that are not issued from a simulation. We finally demonstrate practical inversion results on complex shell geometries freely modeled by an artist or automatically captured from real objects, such as posed garments or soft accessories.

Aim: To investigate epidemiological data of foreign body aspiration (FBA) over a 25 year period and define the sensitivity and specificity of clinical and radiological findings on diagnosis. Methods: We performed a retrospective study reviewing the clinical records of 176 children (mean age: 3.03 years, 60.8% male) who underwent flexible bronchoscopy for suspected FBA, over a period of 25 years. Results: FBA was confirmed with bronchoscopy in 78 cases (44.3%), (mean age 2.74, range: 6 months-10 years, 61.5% males). The majority of the foreign bodies were nuts (52.0%), followed by other food particles (16%) and seeds (14%). The foreign body was located predominantly in the right bronchial tree (56%). The average time between aspiration and diagnosis was 16 days (range: 1 day – 4 years), with the most common clinical signs and symptoms being cough (76.5%), reduced air entry (62.9%) and wheezing (28.6%). This triad was present in 20.6% of the patients. The most frequent radiological finding was unilateral hyperinflation (56.5%) followed by opacities (20.3%) and atelectasis (10.1%). Eighteen patients (23%) presented with normal X-rays. Most of the foreign bodies were removed with a rigid bronchoscope by ENT; over the last 5 years there has been an increasing trend to remove the inhaled foreign body with a basket through the flexible bronchoscope (15 cases). Conclusions: The clinical symptoms and the radiological findings alone are not sufficiently specific and sensitive in the diagnosis of FBA; children who present with a history of suspected FBA, should undergo diagnostic flexible endoscopy.

Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn’s disease (CD) patients with ileal resection. BAM is usually diagnosed by selenium-labelled homotaurocholic acid test (75SeHCAT) but its availability is limited. Consequently, a large proportion of patients either remain undiagnosed or subject to empirical therapy. There is a paucity of studies examining the correlation between length of ileal resection and severity of BAM, which will be of use to clinicians with no recourse to diagnostic testing for BAM. We tested the correlation between length of resected ileum and percentage retention on 75SeHCAT of all CD patients with a prior surgical resection who underwent 75SeHCAT testing. Response to treatment with bile salt sequestrant and 75SeHCAT retention values was tested using Fisher’s exact test. A total of 91 patients were identified with a median age of 47 (IQR 21-80). The median length of resected ileum was 24 cm (range 15–165 cm) with a median of 1 resection (range 1–4). Overall, 88 patients (97%) had 75SeHCAT retention values of