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The compounds derived from Traditional Chinese Medicines have shown various pharmacological activities with unique advantages, especially in the aspect of anti-tumor. Neferine (Nef), a natural compound, extracted from green seed embryos of Lotus (Nelumbo nucifera Gaertn) also exerts antitumor effects on cancers. In this study, the effects and mechanisms of Nef on epithelial-to-mesenchymal transition (EMT) process in non-small cell lung cancer (NSCLC) were evaluated. The results showed that Nef had the antitumor effects in vivo and in vitro. Nef significantly suppressed cell viability and induced apoptosis in NSCLC cells, with elevated reactive oxygen species and reduced BCL-2 /BAX ratio. Nef was also demonstrated to inhibit the invasion, metastasis and EMT process of NSCLC cells, and attenuate EMT-related changes of E-cadherin, N-cadherin and Vimentin at both transcriptional and translational levels. Moreover, we concluded that the inhibitory effects of Nef on EMT was achieved by targeting Rho-associated protein kinase 1 (ROCK1), a protein mediating the process of EMT in various cancers. These results showed that Nef had a significant antitumor effect on NSCLC cells by inducing apoptosis and blocking EMT, providing the therapeutical prospect on NSCLC treatment.

Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomical likelihood estimate meta-analysis on structural magnetic imaging studies comparing patients with chronic pain and healthy controls. Specifically, we investigated a broad range of measures of brain structure as well as specific alterations in gray matter and cortical thickness. A total of 7849 abstracts of experiments published between January 1, 1990, and April 26, 2021, were identified from 8 databases and evaluated by 2 independent reviewers. Overall, 103 experiments with a total of 5075 participants met the preregistered inclusion criteria. After correction for multiple comparisons using the gold-standard family-wise error correction ( P < 0.05), no significant differences associated with chronic pain were found. However, exploratory analyses using threshold-free cluster enhancement revealed several spatially distributed clusters showing structural alterations in chronic pain. Most of the clusters coincided with regions implicated in nociceptive processing including the amygdala, thalamus, hippocampus, insula, anterior cingulate cortex, and inferior frontal gyrus. Taken together, these results suggest that chronic pain is associated with subtle, spatially distributed alterations of brain structure.

Fertigungsunternehmen, insbesondere kleine und mittelständische Unternehmen (KMU), können sich ihre Wettbewerbsfähigkeit über eine Industrie-4.0-gerechte Prozesslenkung sichern. Das Forschungsprojekt ToolProduction liefert eine Gesamtlösung für die digitale Prozesslenkung, die eine flexible Datenplattform für die einheitliche Integration von IT-Modulen und benutzerspezifische Datenbereitstellung bietet. Eine zentrale Datenbasis wurde über die gesamte Wertschöpfungskette geschaffen mit dem Ziel, eine webbasierte Kommerzialisierung digitaler Dienstleistungen zu ermöglichen. In diesem Beitrag wird eine datenbankbasierte Ausführungsumgebung zur Ausführung datengetriebener Mehrwertdienste vorgestellt, um nutzerspezifische Entscheidungsprozesse zu unterstützen. Für komplexere Anwendungen können zukünftig Methoden der Künstlichen Intelligenz (KI) und des Maschinellen Lernens (ML) genutzt werden.

Background: venous thromboembolism (VTE) is a well-known complication in adults with acute lymphoblastic leukemia (ALL), especially in patients treated with asparaginase (ASNase)-including regiments. However, VTE risk in adult Philadelphia-positive ALL (Ph+ve ALL) patients treated with non-hyperCVAD chemotherapy is unclear. In this study, we examined VTE incidence in adult Ph+ve ALL patients treated with imatinib plus a pediatric-inspired asparaginase (ASNase)-free regimen modified from the Dana Farber Cancer Institute (DFCI) ALL protocol. Methods: a single centre retrospective review of Ph+ve ALL patients treated at Princess Margaret Cancer Center (PMCC) from 2008&ndash, 2019 with imatinib plus modified DFCI protocol was conducted. Results: of the 123 patients included, 30 (24.3%) had at least 1 radiology confirmed VTE event from diagnosis to the end of maintenance therapy. 86.7% (26/30) of the VTE events occurred during active treatment. Of all VTE events, the majority (53.3%) were DVT and/or PE while another significant portion were catheter-related (40.0%). Major bleeding was observed in 1 patient on VTE treatment with low molecular weight heparin (LMWH). Conclusion: a high VTE incidence (24.3%) was observed in adults Ph+ve ALL patients treated with imatinib plus an ASNase-free modified DFCI pediatric ALL protocol, suggesting prophylactic anticoagulation should be considered for all adult Ph+ve ALL patients including those treated with ASNase-free regimens.

Deficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for an association between neural value signals and symptoms of amotivation and anhedonia across adults with major depression, bipolar disorder, schizophrenia, or no psychiatric diagnosis. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during intertemporal decision-making were dampened in individuals with greater motivational and hedonic deficits, after accounting for primary diagnosis. This relationship remained significant while controlling for diagnosis-specific symptoms of mood and psychosis, such as depression as well as positive and negative symptoms. Our results demonstrate that dysfunction in the vmPFC during value-based decision-making is specifically linked to motivational and hedonic impairments. These findings provide a quantitative neural target for the potential development of novel treatments for amotivation and anhedonia.

Deficits in motivation and pleasure are common across many psychiatric disorders, and manifest as symptoms of amotivation and anhedonia, which are prominent features of both mood and psychotic disorders. Here we provide evidence for a shared transdiagnostic mechanism underlying impairments in motivation and pleasure across major depression, bipolar disorder, and schizophrenia. We found that value signals in the ventromedial prefrontal cortex (vmPFC) during decision-making were dampened in individuals with greater motivational and hedonic deficits, regardless of the primary diagnosis. This relationship remained significant while controlling for diagnosis-specific symptoms of mood and psychosis, such as depression as well as positive and negative symptoms. Our results demonstrate that dysfunction in the vmPFC during value-based decision-making is specifically linked to motivational and hedonic impairments across various psychiatric conditions. These findings provide a quantitative neural target for the potential development of novel treatments for amotivation and anhedonia.

One assessment of embodiment is the rubber hand illusion (RHI), a visuo-tactile illusion in which individuals attribute a sense of ownership to a rubber hand and disownership to their real hand. Interestingly, interoception seems to influence RHI susceptibility. In this study, we administered the RHI and the Multidimensional Assessment of Interoceptive Awareness (MAIA) to examine embodiment experiences and interoceptive awareness in experienced meditators (n = 15) and non-meditators (n = 15). We found that meditators reported less intensity in rubber hand ownership, but there was no significant difference between groups with respect to disownership of their real hand or drift in finger proprioception. Moreover, we found, from our MAIA results, that disownership experiences were associated with a feeling of trusting one’s body in non-meditators and with the ability to maintain attention to unpleasant bodily sensations in meditators. These results suggest a unique relationship between interoceptive awareness and embodiment related to meditation.

Adventitious root formation is a critical step in micropropagation and genetic transformation. However, it is often a limiting factor for some crop species, particularly woody plants. In this report, we studied adventitious rooting using in vitro shoots of peach, a fruit tree species that is notoriously recalcitrant to genetic transformation and adventitious root induction. We found that culture age affected adventitious rooting efficiency. Hormone analysis revealed that the peach shoots maintained in vitro for 2 years (yr) with a higher rooting rate contained more endogenous indole-3-acetic acid (IAA) than those grown in vitro for 1yr under the same growth conditions. Treatment: of peach shoots with Aminoethoxyvinylglycine (AVG), a potent auxin biosynthesis inhibitor, inhibited adventitious rooting. To explore the association of gene expression with adventitious rooting, we performed a comparative transcriptome analysis. We found that genes encoding key enzymes in auxin biosynthesis were up-regulated in 2yr shoots. In contrast, genes involved in ethylene biosynthesis and its signaling pathway were down-regulated in 2yr shoots. Addition of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate metabolic precursor of ethylene, significantly inhibited adventitious rooting in a dose-dependent manner. Therefore, auxin and ethylene act antagonistically on adventitious rooting. Taken together, our results shed new insights into the mechanism regulating adventitious rooting of peach shoots, and may help develop novel rooting methods for peach and related woody plants.

Craton basins are the main sites where marine carbonate oil and gas reservoirs develop in China. However, the previous studies scarcely focused on the controlling effects of tectonic differentiation on the formation of large oil and gas fields in the ancient craton basins. In such circumstances, it is difficult to evaluate and select the favorable zones for exploring carbonate oil and gas. In this paper, based on the research results of the Sinian–Triassic prototype basin and lithofacies paleogeography of the Sichuan Basin, the tectonic differentiation pattern of craton basins and its controls on the accumulation elements and the distribution of hydrocarbons were analyzed with reference to the concept that structures control the sedimentation and distribution of oil and gas. The study reveals the results in three aspects. First, the intra-cratonic graben controls the high-quality source rocks and the hydrocarbon generation center, which forms good source-reservoir assemblage with the high-quality reservoir in the platform margin at the flank, showing excellent near-source accumulation conditions. Second, the three types of paleo-uplifts (i.e. differential denudation, syn-sedimentary, and folding) and the deep-large faults developed in the craton are favorable for the formation and distribution of large-scale carbonate reservoirs. Third, the superimposed areas with tectonic differentiation in multiple periods and multiple types are favorable for forming large oil and gas fields. It is concluded that the marine carbonate rocks show a huge oil and gas exploration potential in the Sichuan Basin. Attention should be paid to the new exploration targets of natural gas, such as the Sinian Dengying Fm. in the platform margin at the east flank of Deyang–Anyue graben, the Lower Cambrian Longwangmiao Fm. on the slope of paleo-uplift in central Sichuan Basin, and the Middle Permian Maokou Fm. in central–west Sichuan Basin, where oil and gas accumulation conditions are favorable.

Routine VTE prophylaxis is recommended for hospitalized patients, but its effectiveness and safety in cancer patients is unclear. By observation, larger patients seemed poorly covered by the prophylaxis policy. The effectiveness and safety of VTE prophylaxis policy in the hospitalized patients, their potential risk factors such as BMI were examined. A retrospective chart review was conducted to determine VTE incidences, risk factors for VTE and major bleeding events between 2007 and 2016 on the solid tumor units (STU). Patients were divided into pre-policy (Pre-2012) or post-policy implementation groups (Post-2012). Descriptive statistics were used to evaluate effectiveness and safety of prophylaxis, while propensity score matching (1:3, VTE:Non-VTE) was used to reduce selection bias. The VTE incidence per patient was 1.30% (57/4392) pre-policy and 0.56% (18/3210) post-policy (p value = 0.0013). After propensity score matching, a reduction (32.3%) of VTE cases was observed after policy implementation (OR = 0.677, p = 0.32). BMI was found to be a significant predictor of VTE (OR = 1.094, 95% CI 1.021–1.172, p = 0.011). Between July 2014 and July 2016, 1.7% (19/1091) patients who received anticoagulants had a documented bleeding event. The policy positively impacted VTE events on the STU. A significant predictor of VTE was BMI and patients with high BMI may pose a risk of breaking through standard VTE prophylaxis dosing. There was no reported major bleeding for patients who developed an VTE event despite receiving prophylaxis in either the pre-policy or post-policy phase of the study, although a low incidence of minor bleeding was documented in the post-phase.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute pain.HIGHLIGHTSPain stimulation recruits a core set of pain-related brain regions.This core set includes thalamus, SII, insula and mid-cingulate cortex.These regions were recruited regardless of stimulus modality and stimulus location.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p < 0.001, cluster p < 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute nociceptive pain.

This meta-analysis assesses differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging while adhering to current best practices for neuroimaging meta-analyses., Key Points Question Do the brains of patients with chronic pain respond differently to noxious stimuli? Findings This systematic review and meta-analysis of 37 experiments from 29 unique articles including 944 participants found that patients with chronic pain were not associated with significant differential responses to noxious stimuli that induce pain compared with healthy controls. Meaning Chronic pain does not appear to be associated with consistent marked alterations in the brain’s response to noxious stimuli., Importance Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies. Objective To identify differential brain responses to noxious stimuli in patients with chronic pain using functional magnetic resonance imaging (fMRI) while adhering to current best practices for neuroimaging meta-analyses. Data Sources All fMRI experiments published from January 1, 1990, to May 28, 2019, were identified in a literature search of PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library, PsycINFO, and SCOPUS. Study Selection Experiments comparing brain responses to noxious stimuli in fMRI between patients and controls were selected if they reported whole-brain results, included at least 10 patients and 10 healthy control participants, and used adequate statistical thresholding (voxel-height P

The Cambrian carbonate & evaporite paragenesis system in the Sichuan Basin is made up of the Longwangmiao, Gaotai and Xixiangchi Fms. So far, great breakthrough has been made only in the Longwangmiao Fm instead of the latter two, and the Anyue Gasfield was discovered in the center of this basin. In this paper, therefore, the Cambrian carbonate & evaporite paragenesis system in the Sichuan Basin was analyzed in terms of its structural–sedimentary setting, sequence stratigraphic framework, sedimentary facies and the distribution of evaporites by using various geologic, logging and seismic data. Then, the geological model of sedimentary facies was established and the distribution range of favorable reservoirs was predicted. Based on these studies, the following results are obtained. Firstly, the palaeotectonic framework is characterized by the style of “one depression between two uplifts” in the setting of a large SE dipping slope, and the stratigraphic filling is in the structure of “onlapping at the bottom and truncation at the top” which is thin in the west and thick in the east. Secondly, three third-order sequence cycles which, on the whole, become shallow upward are developed from bottom to top, and gypsum-salt rocks are mainly located at the high system tract (HST) of third-order sequences and concentrated in the Wanzhou–Yibin sag. Thirdly, the geological model of sedimentary facies is composed of three major sedimentary structural layers from bottom to top, namely the evaporative carbonate ramp, the evaporative diamictic restricted platform and the evaporative restricted platform. The sedimentary environment changes from the open to the closed and the penesaline for a long time, and then back to the open. The distribution of shoals changes from the pattern of “dual banks” in a large area to more scattered shoals and banded shoals, while the evaporative lagoon and tidal flat shrink. Fourthly, the reservoir distribution is complicated and mainly controlled by the sedimentary pattern of palaeotectonics, the grain shoals and the exposed surfaces of sequences with different orders. The favorable areas for reservoir development are located above the paleo-uplift and its surroundings, at the slope-break belt in the platform and in the periphery of platform margin.

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer's disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of

Cinnamon extract has been reported to have positive effects in fruit fly and mouse models for Alzheimer’s disease (AD). However, cinnamon contains numerous potential active compounds that have not been individually evaluated. The main objective of this study was to evaluate the impact of cinnamaldehyde, a known putative active compound in cinnamon, on the lifespan and healthspan of Drosophila melanogaster models for Alzheimer’s disease, which overexpress Aβ42 and MAPT (Tau). We found that cinnamaldehyde significantly improved the lifespan of both AD and non-AD flies. Cinnamaldehyde also improved the healthspan of AD flies overexpressing the Tau protein by improving climbing ability, evaluated by rapid iterative negative geotaxis (RING), and improving short-term memory, evaluated by a courtship conditioning assay. Cinnamaldehyde had no positive impact on the healthspan of AD flies overexpressing the Aβ42 protein.

Background: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixaforvials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use.Objective: To determine whether the portion of plerixafor remaining in an opened vial of the Mozobil product after administration of a single dose is chemically stable, by comparison with the original product.Methods: Stability testing of partial drug contents of an opened vial, stored at room temperature or under refrigeration (4°C), was conducted using liquid chromatography–tandem mass spectrometry analysis. The mean concentration of plerixafor (μmol/L), standard deviation, coefficient of variation, and bias were determined on days 2, 3, 11, 17, 24, and 31. Method validation included determination of precision, sensitivity, recovery, dilution linearity, and carryover.Results: Throughout the 4-week testing period, measured plerixafor concentration in aliquots stored at room temperature and under refrigeration, tested in series over time, appeared similar. The mean residual drug concentration after initial opening was slightly, but not significantly, higher for the sample designated for storage at room temperature than the one designated for refrigerated storage (40.4 versus 39.9 μmol/L; p = 0.37).Conclusions: Residual plerixafor after initial opening of a vial of the Mozobil product remained chemically stable for at least 2 weeks both at room temperature and under refrigeration. The results of this study provide in vitro evidence to support multiple uses, instead of single use, of vials of this drug in an aseptic, controlled environment.RÉSUMÉContexte : L’ajout de l’immunostimulant plérixafor aux traitements reconnus comme la norme de soins actuelle quant au facteur de stimulation des colonies de granulocytes, accompagné ou non de chimiothérapie, a amélioré les résultats cliniques de mobilisation des cellules souches et les résultats de greffe de cellules souches dans différents contextes. Cela dit, avec cette innovation médicale vient un poids financier supplémentaire pour les établissements où l’on exécute couramment des greffes de cellules souches. En outre, comme les fioles de plérixafor (Mozobil, Sanofi-Aventis Canada Inc.) sont présentement jugées adéquates pour un usage unique seulement, l’excédent de médicament gaspillé peut représenter une dépense additionnelle.Objectif : Déterminer si ce qui reste de Mozobil dans une fiole ouverte après l’administration d’une dose unique est chimiquement stable comparativement au produit de départ.Méthodes : Une étude de stabilité du contenu partiel d’une fiole de médicament ouverte, entreposé à température ambiante ou conservé au réfrigérateur (4°C), a été réalisée par chromatographie en phase liquide couplée à la spectrométrie de masse en tandem. La concentration moyenne de plérixafor (μmol/L), l’écart-type, le coefficient de variation et le biais ont été établis aux jours 2, 3, 11, 17, 24 et 31. La méthode de validation comprenait la détermination de : la précision, la sensibilité, la récupération, la limite de linéarité et la contamination inter-échantillons.Résultats : Tout au long des quatre semaines d’analyse, les concentrations mesurées des aliquotes de plérixafor, entreposées à température ambiante ou conservées au réfrigérateur et analysées en séries chronologiques, semblaient similaires. Les concentrations moyennes de médicament restant après l’ouverture initiale étaient légèrement plus élevées lorsqu’entreposées à température ambiante (40,4 μmol/L) que lorsque réfrigérées (39,9 μmol/L) (p = 0,37), mais pas de façon significative.Conclusions : Le plérixafor résiduel, après l’ouverture initiale des fioles de Mozobil, demeurait chimiquement stable pendant au moins deux semaines, qu’il soit entreposé à température ambiante ou conservé au réfrigérateur. Les résultats de la présente étude offrent des données in vitro qui soutiennent une utilisation multiple, plutôt qu’un usage unique, des fioles de ce médicament en milieu aseptique contrôlé.

Background Low adherence to prescribed medications leads to serious negative health consequences in older adults. Effective interventions that improve adherence are often labor-intensive and complex. However, most studies do not analyze the separate effects of the components. Objective Persuasive System Design (PSD) is framework that analyzes the motivations that change behavior. In this paper, we aim to apply the model to changing the pill-taking behaviors of the aging population and determine which persuasive elements in interventions drive improvement in medication adherence. Methods Systematic review using the databases Medline (1977 to February 2012), Cochrane library (2000 to June 2013); Cinahl (1975 to June 2013), and Psycinfo (2002 to June 2012). Inclusion criteria were experimental trials with participants' mean age ⩾ 60 years and had medication adherence as a primary or secondary measure. Results Meta-analysis (40 studies) demonstrated a significant association of tailoring, or one-on-one counseling, with medication adherence. Interventions with simulation (showing the causal relationship between non-adherence and negative effects) and rehearsal (miming medication-taking behavior) also showed evidence for improved adherence. Conclusions Future medication adherence interventions might be more effective if they were based on persuasive technology.

Background: Venous thromboembolism (VTE) is a well-known complication in adults with acute lymphoblastic leukemia (ALL) receiving asparaginase (ASNase) based therapy. The MD Anderson Cancer Centre reported an overall VTE incidence of 29% (14/49) in patients with Philadelphia positive ALL (Ph+ ALL) treated with Hyper-CVAD and in the absence of ASNase (Vu et al. Cancer Medicine. 2015;4(1):27-35. doi:10.1002/cam4.332). The VTE incidence in adult Ph+ ALL patients treated with tyrosine kinase inhibitor plus the pediatric-inspired regimen modified from the Dana Farber Cancer Institute (DFCI) ALL protocol remains unclear. We have previously compared the incidence of VTE in adults with Ph+ ALL treated with or without ASNase during the intensification phase of the modified DFCI treatment. This study suggested that patients with Ph+ve ALL experience high incidence of VTE, even in the absence of ASNase, and that this risk is not restricted to the intensification phase. As ASNase was omitted from the protocol due to toxicity since 2008, in this report, we provide further insight into the risk of VTE in adults with Ph+ ALL during the entire ASNase-free DFCI treatment course. Methods: A single-institution retrospective review of sequential Ph+ ALL patients treated at Princess Margaret Cancer Center (PMCC) from 2008-2018 with an imatinib-containing DFCI protocol-based regimen that omitted ASNase. VTE events were recorded from the time of diagnosis to the end of modified DFCI treatment, including at the time of allogenic bone marrow transplantation. Co-variants of age, sex, weight, BMI, Padua score, white blood cell count, and platelet count were also collected. Statistical analyses were performed using the 2-tailed t test. Results: Overall, 130 patients were included for analysis; none received prophylactic anticoagulation. Among the 130 Ph+ ALL patients treated with the modified DFCI protocol, 28 (21.5%) patients had at least 1 VTE events from diagnosis to the end of treatment. The mean age of patients with and without VTE were 56.8 and 49.0 years, respectively (p=0.014) (Table 1). The majority of the VTE events occurred during active treatment, with 9 (7.0%), 11 (8.5%), and 4 (3.1%) occurring during induction, intensification, and maintenance, respectively (Figure 1). Only four patients (3.1%) presented with VTE at the time of diagnosis. Of all VTE events, 14 (50%) were DVT and/or PE, 12 (43%) were line-related, and 2 (7%) involved a cardiac thrombus (Table 2). The average Padua score for these patients was 5.4 with a range of 3-10. All VTE events were treated with low weight molecular heparin (LMWH), with 2 patients experiencing a recurrent episode within a year while on LMWH treatment. Bleeding following anticoagulation was rare. One patient experienced a major bleeding into the psoas muscle while on LMWH plus platelet transfusion for a right atrial clot during the induction phase in ICU. No other significant bleeding event was observed. Conclusion: VTE was observed in more than 20% of adults with Ph+ ALL patients treated with imatinib plus a modified DFCI pediatric ALL protocol. The majority of VTE events occurred during active treatment (induction and intensification), and DVT/PE incidence was similar to that of line-related thrombosis. The high observed VTE incidence suggests that prophylactic anticoagulation should be considered for adult patients with Ph+ ALL even in ASNase-free regimens, especially if additional thromboembolic risk factors are present. Disclosures Maze: Pfizer Inc: Consultancy; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chan:Celgene: Honoraria, Research Funding; Agios: Honoraria; AbbVie Pharmaceuticals: Research Funding. Gupta:Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding. Yee:Novartis, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas, Celgene, Otsuka, Shire, Takeda: Membership on an entity's Board of Directors or advisory committees; Agensys, Astex, Hoffman La Roche, MedImmune, Merck, Millenium, Roche/Genentech: Research Funding. Minden:Trillium Therapetuics: Other: licensing agreement. Schimmer:Novartis Pharmaceuticals: Consultancy; Otsuka Pharmaceuticals: Consultancy; Medivir Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy. Schuh:Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Teva Canada Innovation: Honoraria, Membership on an entity's Board of Directors or advisory committees. McNamara:Novartis Pharmaceutical Canada Inc.: Consultancy.

The Carboniferous reservoir in KJ oilfield is a carbonate reservoir with extremely low porosity and permeability and high-pressure. The reservoir has severe heterogeneity, is deeply buried, has complex master control factors, is covered with thick salt, all of which result in the serious distortion of reflection time and amplitudes under the salt, the poor seismic imaging, and the low S/N ratio and resolution. The key to developing this kind of reservoir is to correctly predict the distribution of highly profitable oil zones. In this paper we start by analyzing the master control factors, perform seismic-log calibration, optimize the seismic attributes indicating the lithofacies, karst, petrophysical properties, and fractures, and combine these results with the seismic, geology, log, oil reservoir engineering, and well data. We decompose the seismic prediction into six key areas: structural interpretation, prediction of lithofacies, karst, petrophysical properties, fractures, and then perform an integrated assessment. First, based on building the models of faults and fractures, sedimentary facies, and karst, we predict the distribution of the most favorable reservoir zones qualitatively. Then, using multi-parameter inversion and integrated multi-attribute analysis, we predict the favorable reservoir distribution quantitatively and setni-quantitatively to clarify the distribution of high-yield zones. We finally have a reliable basis for optimal selection of exploration and development targets.

Social media is an interesting, relatively new topic in health and self-management, which is generating enormous amounts of data, but little is yet known about its effect on the health of participants. The goal of this study is to determine online interaction behaviours that predict weight loss performance. The problem is modelled as a binomial classification task for predicting whether a patient would lose significant weight, based on analysis of two obesity online communities. An expansion-reduction method was developed for the patient feature vector, where the expansion is based on concatenating network structure features and the reduction is based on feature subset selection. Further, empirical evaluation of classifiers was done on the datasets, before and after the expansion. Based on feature subset selection, centrality measures such as degree and between ness were more predictive than basic demographic features. Top performers, compared with bottom performers, were significantly more active online and connected to more than one sub-community (at 95% CI and p

In this systematic review of weight loss interventions, we reviewed interventions aimed at maintaining weight loss, and identify persuasive elements that drive weight maintenance. Methods: We searched the Medline database for long-term obesity interventions, and targeted randomized control trials that aimed to reduce weight among adults for over 12 months, and extracted outcomes related to body weight change. Results: Seventeen publications were in the final review. Tailoring, or group counseling led by a health care professional, was shown to have a significant effect on long-term weight loss. Positive effects were also obtained by personalization one-on-one counseling, competition competing against other people trying to lose weight, and reminders. Conclusion: Maintaining weight loss long-term as so far eluded researchers, but results suggest that that some elements of the interventions are more greatly associated with weight maintenance than others. Future interventions might be more effective if they were based on persuasive technology.

Background Statins are effective for primary prevention of cardiovascular (CV) disease, the leading cause of death in the world. Multinational guidelines emphasize CV risk as an important factor for optimal statin prescribing. However, it’s not clear how primary care providers (PCPs) use this information. The objective of this study was to determine how primary care providers use information about global CV risk for primary prevention of CV disease. Methods A double-blinded, randomized experiment using clinical vignettes mailed to office-based PCPs in the United States who were identified through the American Medical Association Physician Masterfile in June 2012. PCPs in the control group received clinical vignettes with all information on the risk factors needed to calculate CV risk. The experimental group received the same vignettes in addition to the subject’s 10-year calculated CV risk (Framingham risk score). The primary study outcome was the decision to prescribe a statin. Results Providing calculated CV risk to providers increased statin prescribing in the two high-risk cases (CV risk > 20%) by 32 percentage points (41% v. 73%; 95% CI = 23-40, p

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants and children worldwide. We wished to determine whether intratracheal administration of beta-agonists improved alveolar fluid clearance (AFC) across the distal respiratory epithelium of RSV-infected mice. Following intranasal infection with RSV strain A2, AFC was measured in anesthetized, ventilated BALB/c mice by instillation of 5% BSA into the dependent lung. We found that direct activation of protein kinase A by forskolin or 8-bromo-cAMP increased AFC at day 2 after infection with RSV. In contrast, short- and long-acting beta-agonists had no effect at either day 2 or day 4. Insensitivity to beta-agonists was not a result of elevated plasma catecholamines or lung epithelial cell beta-adrenergic receptor degradation. Instead, RSV-infected mice had significantly higher levels of phosphorylated PKCzeta in the membrane fractions of their lung epithelial cells. In addition, insensitivity to beta-agonists was mediated in a paracrine fashion by KC (the murine homolog of CXCL8) and reversed by inhibition of either PKCzeta or G protein-coupled receptor kinase 2 (GRK2). These results indicate that insufficient response to beta-agonists in RSV may be caused, at least in part, by impaired beta-adrenergic receptor signaling, as a consequence of GRK2-mediated uncoupling of beta-adrenergic receptors from adenylyl cyclase.

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na + transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A 1 R), 2a (A 2a R), 2b (A 2b R), and 3 (A 3 R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2). Rat AT2 cells generated and produced cAMP in response to adenosine, and micromolar concentrations of adenosine were measured in bronchoalveolar lavage fluid from mice. Ussing chamber studies of rat AT2 cells indicated that adenosine affects ion transport through engagement of A 1 R, A 2a R, and/or A 3 R through a mechanism that increases CFTR and amiloride-sensitive channel function. Intratracheal instillation of low concentrations of adenosine (≤10 −8 M) or either A 2a R- or A 3 R-specific agonists increased alveolar fluid clearance (AFC), whereas physiologic concentrations of adenosine (≥10 −6 M) reduced AFC in mice and rats via an A 1 R-dependent pathway. Instillation of a CFTR inhibitor (CFTR inh-172 ) attenuated adenosine-mediated down-regulation of AFC, suggesting that adenosine causes Cl − efflux by means of CFTR. These studies report a role for adenosine in regulation of alveolar ion transport and fluid clearance. These findings suggest that physiologic concentrations of adenosine allow the alveolar epithelium to counterbalance active Na + absorption with Cl − efflux through engagement of the A 1 R and raise the possibility that adenosine receptor ligands can be used to treat pulmonary edema.

Background Examining deaths caused by anaphylaxis may help identify factors that may decrease the risk of these unfortunate events. However, information on fatal anaphylaxis is limited. The objectives of our study were to examine all cases of fatal anaphylaxis in Ontario to determine cause of death, associated features, co factors and trends in mortality. The identification of these factors is important for developing effective strategies to overcome gaps in monitoring and treatment of patients with food allergies and risk for anaphylaxis. Methods This was a retrospective case-series analysis of all causes of anaphylaxis-related deaths using data from the Ontario Coroner’s database between 1986 and 2011. Quantitative data (e.g. demographic) were analyzed using descriptive statistics and frequency analysis using SPSS. Qualitative data were analyzed using content analysis of grounded theory methodology. Results We found 92 deaths in the last 26 years related to anaphylaxis. Causes of death, in order of decreasing frequency, included food (40 cases), insect venom (30 cases), iatrogenic (16 cases), and idiopathic (6 cases). Overall, there appears to be a decline in the frequency of food related deaths, but an increase in iatrogenic causes of fatalities. We found factors associated with fatal anaphylaxis included: delayed epinephrine administration, asthma, allergy to peanut, food ingestion outside the home, and teenagers with food allergies. Conclusions Our findings indicate the need to improve epinephrine auto-injector use in acute reactions, particularly for teens and asthmatics with food allergies. In addition, education can be improved among food service workers and food industry in order to help food allergic patients avoid potentially fatal allergens. The increasing trend in iatrogenic related anaphylaxis is concerning, and requires monitoring and more investigation.