Grey matter morphological anomalies in the caudate head in first-episode psychosis patients with delusions of reference.

PubMed

Tao, Haojuan; Wong, Gloria H Y; Zhang, Huiran; Zhou, Yuan; Xue, Zhimin; Shan, Baoci; Chen, Eric Y H; Liu, Zhening

2015-07-30

Delusions of reference (DOR) are theoretically linked with aberrant salience and associative learning. Previous studies have shown that the caudate nucleus plays a critical role in the cognitive circuits of coding prediction errors and associative learning. The current study aimed at testing the hypothesis that abnormalities in the caudate nucleus may be involved in the neuroanatomical substrate of DOR. Structural magnetic resonance imaging of the brain was performed in 44 first-episode psychosis patients (with diagnoses of schizophrenia or schizophreniform disorder) and 25 healthy controls. Patients were divided into three groups according to symptoms: patients with DOR as prominent positive symptom; patients with prominent positive symptoms other than DOR; and patients with minimal positive symptoms. All groups were age-, gender-, and education-matched, and patient groups were matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to identify group differences in grey matter density. Relationships were explored between grey matter density and DOR. Patients with DOR were found to have reduced grey matter density in the caudate compared with patients without DOR and healthy controls. Grey matter density values of the left and right caudate head were negatively correlated with DOR severity. Decreased grey matter density in the caudate nucleus may underlie DOR in early psychosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neuroprotection Against Hypoxic/Ischemic Injury: δ-Opioid Receptors and BDNF-TrkB Pathway.

PubMed

Sheng, Shiying; Huang, Jingzhong; Ren, Yi; Zhi, Feng; Tian, Xuansong; Wen, Guoqiang; Ding, Guanghong; Xia, Terry C; Hua, Fei; Xia, Ying

2018-05-11

The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR's role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR's specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect. Our serial studies have strongly demonstrated that DOR is a unique neuroprotector against hypoxic/ischemic injury in the brain, which has been well confirmed in current research. Moreover, mechanistic studies have shown that during acute phases of hypoxic/ischemic stress, DOR protects the neurons mainly by the stabilization of ionic homeostasis, inhibition of excitatory transmitter release, and attenuation of disrupted neuronal transmission. During prolonged hypoxia/ischemia, however, DOR neuroprotection involves a variety of signaling pathways. More recently, our data suggest that DOR may display its neuroprotective role via the BDNF-TrkB pathway. This review concisely summarizes the progress in this field. © 2018 The Author(s). Published by S. Karger AG, Basel.

Effect of action potential duration on Tpeak-Tend interval, T-wave area and T-wave amplitude as indices of dispersion of repolarization: Theoretical and simulation study in the rabbit heart.

PubMed

Arteyeva, Natalia V; Azarov, Jan E

The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area. T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted. Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value. Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account. Copyright © 2017 Elsevier Inc. All rights reserved.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study

PubMed Central

Testa, A; Kaijser, J; Wynants, L; Fischerova, D; Van Holsbeke, C; Franchi, D; Savelli, L; Epstein, E; Czekierdowski, A; Guerriero, S; Fruscio, R; Leone, F P G; Vergote, I; Bourne, T; Valentin, L; Van Calster, B; Timmerman, D

2014-01-01

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917–0.942), 0.918 (0.905–0.930), 0.914 (0.886–0.936) and 0.875 (0.853–0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90–96%, specificity 74–79% and diagnostic odds ratio (DOR) 32.8–50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6–75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference. PMID:24937676

DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex.

PubMed

Chao, Dongman; He, Xiaozhou; Yang, Yilin; Bazzy-Asaad, Alia; Lazarus, Lawrence H; Balboni, Gianfranco; Kim, Dong H; Xia, Ying

2012-08-01

Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na(+) influx through TTX-sensitive voltage-gated Na(+) channels may be a main mechanism for hypoxia-induced disruption of K(+) homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na(+) channels. In the present study we examined the role of DOR in the regulation of Na(+) influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na(+) influx induced by a Na(+) channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na(+) activity in mouse cortical slices with Na(+) selective electrodes and found that (1) anoxia-induced Na(+) influx occurred mainly through TTX-sensitive Na(+) channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na(+) influx; (3) veratridine, a Na(+) channel opener, enhanced the anoxia-induced Na(+) influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na(+) influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKCβII peptide inhibitor, and PKCθ pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na(+) influx through Na(+) channels via PKC (especially PKCβII and PKCθ isoforms) dependent mechanisms in the cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

Saprobe fungi decreased the sensitivity to the toxic effect of dry olive mill residue on arbuscular mycorrhizal plants.

PubMed

Sampedro, I; Aranda, E; Díaz, R; García-Sanchez, M; Ocampo, J A; García-Romera, I

2008-02-01

We studied the influence of olive mill dry residue (DOR) treated with saprobe fungi on growth of tomato and alfalfa colonized by Glomus deserticola. The application of 25g kg(-1) of dry DOR to soil decreased the shoot and root dry weight of tomato and alfalfa. Plants were more sensitive to the toxicity of DOR when colonized with the arbuscular mycorrhizal (AM) fungi. The sensitivity of both plants to the toxicity of DOR differed according to whether they were colonized by G. deserticola or by indigenous AM fungi. The phytotoxicity of DOR towards tomato and alfalfa was decreased by incubation the residue before planting with saprobe fungi for 20wk. The beneficial effects of AM fungi on plant growth added with DOR incubated with saprobe fungi depend of the type of the plant and AM fungi. The contribution of AM fungi to the beneficial effect of DOR incubated with saprobe fungi varied according to the type of the plant and AM fungi. G. deserticola increased the shoot and root dry weight of plants when they were grown in the presence of DOR incubated with saprobe fungi for 20wk. The beneficial effect of saprobe fungi on the dry weight and the level of AM mycorrhization of plants seem to be related to the decrease caused by these fungi in the phenol concentration in DOR. However, the toxicity of DOR due to substances other than phenols can not be ignored. The use of certain saprobe and AM fungi allows the possibility of using DOR as an organic fertilizer.

Delta Opioid Receptor (DOR) Ligands and Pharmacology: Development of Indolo- and Quinolinomorphinan Derivatives Based on the Message-Address Concept.

PubMed

Saitoh, Akiyoshi; Nagase, Hiroshi

2016-10-28

The pharmacology of the delta opioid receptor (DOR) has lagged, mainly due to the lack of an agonist with high potency and selectivity in vivo. The DOR is now receiving increasing attention, and there has been progress in the synthesis of better novel ligands. The discovery of a selective receptor DOR antagonist, naltrindole (NTI), stimulated the design and synthesis of (±)TAN-67, which was designed based on the message-address concept and the accessory site theory. Intensive studies using (±)TAN-67 determined the DOR-mediated various pharmacological effects, such as antinociceptive effects for painful diabetic neuropathy and cardiovascular protective effects. We improved the agonist activity of TAN-67 to afford SN-28, which was modified to KNT-127, a novel compound that improved the blood-brain barrier permeability. In addition, KNT-127 showed higher selectivity for the DOR and had potent agonist activity following systemic administration. Interestingly, KNT-127 produced no convulsive effects, unlike prototype DOR agonists. The KNT-127 type derivatives with a quinolinomorphinan structure are expected to be promising candidates for the development of therapeutic DOR agonists.

Risk element sorption/desorption characteristics of dry olive residue: a technique for the potential immobilization of risk elements in contaminated soils.

PubMed

Hovorka, Miloš; Száková, Jiřina; García-Sánchez, Mercedes; Acebal, Mercedes Blanc; García-Romera, Inmaculada; Tlustoš, Pavel

2016-11-01

Olive oil production is one of the most relevant agroindustrial activities in the Mediterranean region and generates a huge amount of both solid and semi-solid wastes, the uncontrolled disposal of which might lead to serious environmental problems. Due to its organic matter and mineral nutrient content, the waste material can be applied to agricultural soil as a fertilizer. However, due to its high organic matter content, dry olive residue (DOR), commonly called "alperujo," has the potential to immobilize risk elements in contaminated soils. The main objective of this study was to assess the possible effect of DOR on sorption of risk elements such as cadmium (Cd), lead (Pb), and zinc (Zn) in the soil. A set of batch sorption experiments were carried out to assess the ability of DOR to adsorb Cd, Pb, and Zn where the effect of the preceding biotransformation of DOR by four species of fungi: Penicillium chrysogenum, Coriolopsis floccosa, Bjerkhandera adusta, and Chondrostereum purpureum was compared. The Freundlich and Langmuir sorption isotherms were calculated to assess the sorption characteristics of both transformed and non-transformed DOR. The results showed good potential sorption capacity of DOR, especially for Pb and to a lesser extent for Cd and Zn. Better sorption characteristics were reported for the biotransformed DOR samples, which are expected to show higher humification of the organic matter. However, the desorption experiments showed weakness and instability of the DOR-bound elements, especially in the case of Zn. Thus, future research should aim to verify the DOR sorption pattern in contaminated soil as well as the potential stabilization of the DOR element bounds where the increase of the pH levels of the DOR samples needs to be taken into account.

Cortical delta-opioid receptors potentiate K+ homeostasis during anoxia and oxygen-glucose deprivation.

PubMed

Chao, Dongman; Donnelly, David F; Feng, Yin; Bazzy-Asaad, Alia; Xia, Ying

2007-02-01

Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that delta-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K(+), which plays a role in neuronal death, we asked whether DOR activation preserves K(+) homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K(+)-sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala(2), D-Leu(5)]-enkephalinamide attenuated the anoxia- and OGD-induced increase in extracellular K(+) and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K(+) and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K(+) homeostasis. These data suggest that activation of DOR protects the cortex against anoxia- or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K(+) homeostasis during anoxia or ischemia.

Impact of non-adherent Ibuprofen foam dressing in the lives of patients with venous ulcers.

PubMed

Salomé, Geraldo Magela; Ferreira, Lydia Masako

2017-01-01

to evaluate pain in patients with lower limb venous ulcer who used non-adherent Ibuprofen foam dressing (IFD). we conducted a prospective study of patients with lower limb venous ulcers treated from April 2013 to August 2014. We used the Numerical Scale and McGill Pain Questionnaire, performing the assessments at the moment of inclusion of the patient in the study and every eight days thereafter, totaling five consultations. We divided the patients into two groups: 40 in the Study Group (SG), who were treated with IFD, and 40 in the Control Group (CG), treated with primary dressing, according to tissue type and exudate. at the first consultation, patients from both groups reported intense pain. On the fifth day, SG patients reported no pain and the majority of CG reported moderate pain. Regarding the McGill Pain Questionnaire, most patients of both groups reported sensations related to sensory, affective, evaluative and miscellaneous descriptors at the beginning of data collection; after the second assessment, there was slight improvement among the patients in the SG. After the third consultation, they no longer reported the mentioned descriptors. CG patients displayed all the sensations of these descriptors until the fifth visit. non-adherent Ibuprofen foam dressing is effective in reducing the pain of patients with venous ulcers. avaliar a dor em pacientes portadores de úlcera venosa de membros inferiores que utilizaram curativo de espuma não aderente com Ibuprofeno (CEI). estudo prospectivo de pacientes portadores de úlceras venosas de membros inferiores tratados no período de abril de 2013 a agosto de 2014. Foram utilizados os questionários Escala Numérica e Questionário de Dor de McGille, as avaliações eram feitas no momento da inclusão do paciente no estudo e a cada oito dias, totalizando cinco consultas. Os pacientes foram divididos em dois grupos: 40 no Grupo Estudo (GE), que foram tratados com CEI, e 40 no Grupo Controle (GC), tratados com curativo primário, conforme o tipo de tecido e exsudato. na primeira consulta os pacientes de ambos os grupos relataram dor intensa. No quinto dia os pacientes do GE relataram ausência de dor e a maioria do GC relatou dor moderada. Com relação ao Questionário de Dor de McGill, a maioria dos pacientes de ambos os grupos, no início da coleta de dados, relataram sensações relacionadas aos descritores sensorial, afetivo, avaliativo e miscelânea, sendo que entre os pacientes do GE houve discreta melhora após a segunda consulta. Após a terceira consulta já não referiram os descritores citados. Os pacientes do GC manifestaram todas as sensações desses descritores até quinta a consulta. o curativo de espuma não aderente com Ibuprofeno é eficaz na redução da dor de pacientes portadores de úlceras venosas.

DOR(2)-selective but not DOR(1)-selective antagonist abolishes anxiolytic-like effects of the δ opioid receptor agonist KNT-127.

PubMed

Sugiyama, Azusa; Nagase, Hiroshi; Oka, Jun-Ichiro; Yamada, Mitsuhiko; Saitoh, Akiyoshi

2014-04-01

Recently, we reported that the δ opioid receptor (DOR) agonist KNT-127 produces anxiolytic-like effects in behaving rats. Here, we report on the roles of DOR subtypes ( DOR(1) and DOR(2)) play in mediating KNT-127-induced anxiolytic-like effects. Pretreatment with the DOR(2)-selective antagonist naltriben (NTB; 0.05mg/kg, s.c.) completely abolished KNT-127 (3.0mg/kg, s.c.)-induced anxiolytic-like effects in rats performing the elevated plus-maze task. By contrast, the DOR(1)-selective antagonist 7-benzylidenenaltrexone (BNTX; 0.5mg/kg, s.c.) produced no effect at a dose that completely blocked the antinociceptive effects of KNT-127. These findings were also supported by results from a light/dark test and open-field test. We clearly demonstrated that the DOR(2)-selective antagonist, but not the DOR(1)-selective antagonist, abolishes the anxiolytic-like effects of the DOR agonist KNT-127, suggesting different roles of these DOR subtypes in anxiety. We propose that DOR(2)-selective agonists would be good candidates for future development of anxiolytic drugs. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Diagnosis and Treatment of Diminished Ovarian Reserve in ART Cycles of Women Up to Age 40 Years: The Role of Insurance Mandates

PubMed Central

Butts, Samantha F.; Ratcliffe, Sarah; Dokras, Anuja; Seifer, David B.

2012-01-01

Summary Objective To explore correlates of diminished ovarian reserve (DOR) and predictors of ART treatment outcome in DOR cycles using the SART-CORS database. We hypothesized that state insurance coverage for ART is associated with the prevalence of DOR diagnosis in ART cycles and with treatment outcomes in DOR cycles. Design Cross sectional study using ART cycles between 2004–2007. Setting United States ART registry data. Patients 182,779 fresh, non-donor, initial ART cycles in women up to age 40. Interventions None. Main Outcome Measures Prevalence of DOR and elevated FSH, odds ratio of DOR and elevated FSH in ART mandated vs. non-mandated states, live birth rates. Results Compared to cycles performed in states with mandated ART coverage, cycles in states with no ART mandate were more likely to have DOR (AOR 1.43 95% CI 1.37–1.5, p<0.0001) or elevated FSH (AOR 1.69 95% CI 1.56–1.85, p<0.0001) as the sole reason for treatment. A relationship between lack of mandated ART coverage and increased live birth rates in some, but not all DOR cycles. Conclusions A significant association was observed between lack of mandated insurance for ART and the proportion of cycles treating DOR or elevated FSH. The presence or absence of state mandated ART coverage could impact access to care and the mix of patients that pursue and initiate ART cycles. Additional studies are needed that consider the coalescence of insurance mandates, patient and provider factors, and state level variables on the odds of specific infertility diagnoses and treatment prognosis. PMID:23102859

Src promotes delta opioid receptor (DOR) desensitization by interfering with receptor recycling.

PubMed

Archer-Lahlou, Elodie; Audet, Nicolas; Amraei, Mohammad Gholi; Huard, Karine; Paquin-Gobeil, Mélanie; Pineyro, Graciela

2009-01-01

Abstract An important limitation in the clinical use of opiates is progressive loss of analgesic efficacy over time. Development of analgesic tolerance is tightly linked to receptor desensitization. In the case of delta opioid receptors (DOR), desensitization is especially swift because receptors are rapidly internalized and are poorly recycled to the membrane. In the present study, we investigated whether Src activity contributed to this sorting pattern and to functional desensitization of DORs. A first series of experiments demonstrated that agonist binding activates Src and destabilizes a constitutive complex formed by the spontaneous association of DORs with the kinase. Src contribution to DOR desensitization was then established by showing that pre-treatment with Src inhibitor PP2 (20 microM; 1 hr) or transfection of a dominant negative Src mutant preserved DOR signalling following sustained exposure to an agonist. This protection was afforded without interfering with endocytosis, but suboptimal internalization interfered with PP2 ability to preserve DOR signalling, suggesting a post-endocytic site of action for the kinase. This assumption was confirmed by demonstrating that Src inhibition by PP2 or its silencing by siRNA increased membrane recovery of internalized DORs and was further corroborated by showing that inhibition of recycling by monensin or dominant negative Rab11 (Rab11S25N) abolished the ability of Src blockers to prevent desensitization. Finally, Src inhibitors accelerated recovery of DOR-Galphal3 coupling after desensitization. Taken together, these results indicate that Src dynamically regulates DOR recycling and by doing so contributes to desensitization of these receptors.

Dimerization with Cannabinoid Receptors Allosterically Modulates Delta Opioid Receptor Activity during Neuropathic Pain

PubMed Central

Stockton, Steven D.; Miller, Lydia K.; Devi, Lakshmi A.

2012-01-01

The diversity of receptor signaling is increased by receptor heteromerization leading to dynamic regulation of receptor function. While a number of studies have demonstrated that family A G-protein-coupled receptors are capable of forming heteromers in vitro, the role of these heteromers in normal physiology and disease has been poorly explored. In this study, direct interactions between CB1 cannabinoid and delta opioid receptors in the brain were examined. Additionally, regulation of heteromer levels and signaling in a rodent model of neuropathic pain was explored. First we examined changes in the expression, function and interaction of these receptors in the cerebral cortex of rats with a peripheral nerve lesion that resulted in neuropathic pain. We found that, following the peripheral nerve lesion, the expression of both cannabinoid type 1 receptor (CB1R) and the delta opioid receptor (DOR) are increased in select brain regions. Concomitantly, an increase in CB1R activity and decrease in DOR activity was observed. We hypothesize that this decrease in DOR activity could be due to heteromeric interactions between these two receptors. Using a CB1R-DOR heteromer-specific antibody, we found increased levels of CB1R-DOR heteromer protein in the cortex of neuropathic animals. We subsequently examined the functionality of these heteromers by testing whether low, non-signaling doses of CB1R ligands influenced DOR signaling in the cortex. We found that, in cortical membranes from animals that experienced neuropathic pain, non-signaling doses of CB1R ligands significantly enhanced DOR activity. Moreover, this activity is selectively blocked by a heteromer-specific antibody. Together, these results demonstrate an important role for CB1R-DOR heteromers in altered cortical function of DOR during neuropathic pain. Moreover, they suggest the possibility that a novel heteromer-directed therapeutic strategy for enhancing DOR activity, could potentially be employed to reduce anxiety associated with chronic pain. PMID:23272051

The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells.

PubMed

Mauvezin, Caroline; Orpinell, Meritxell; Francis, Víctor A; Mansilla, Francisco; Duran, Jordi; Ribas, Vicent; Palacín, Manuel; Boya, Patricia; Teleman, Aurelio A; Zorzano, Antonio

2010-01-01

The regulation of autophagy in metazoans is only partly understood, and there is a need to identify the proteins that control this process. The diabetes- and obesity-regulated gene (DOR), a recently reported nuclear cofactor of thyroid hormone receptors, is expressed abundantly in metabolically active tissues such as muscle. Here, we show that DOR shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. We demonstrate that DOR interacts physically with autophagic proteins Golgi-associated ATPase enhancer of 16 kDa (GATE16) and microtubule-associated protein 1A/1B-light chain 3. Gain-of-function and loss-of-function studies indicate that DOR stimulates autophagosome formation and accelerates the degradation of stable proteins. CG11347, the DOR Drosophila homologue, has been predicted to interact with the Drosophila Atg8 homologues, which suggests functional conservation in autophagy. Flies lacking CG11347 show reduced autophagy in the fat body during pupal development. All together, our data indicate that DOR regulates autophagosome formation and protein degradation in mammalian and Drosophila cells.

Inhibition of DOR prevents remifentanil induced postoperative hyperalgesia through regulating the trafficking and function of spinal NMDA receptors in vivo and in vitro.

PubMed

Wang, Chunyan; Li, Yize; Wang, Haiyun; Xie, Keliang; Shu, Ruichen; Zhang, Linlin; Hu, Nan; Yu, Yonghao; Wang, Guolin

2015-01-01

Several studies have demonstrated that intraoperative remifentanil infusions have been associated with opioid-induced hyperalgesia (OIH). Activation of delta opioid receptor (DOR) and augmentation of N-methyl-d-aspartate (NMDA) receptor expression and function may play an important role in the development of OIH. The aim of this study was to investigate whether DOR inhibition could prevent remifentanil-induced hyperalgesia via regulating spinal NMDA receptor expression and function in vivo and in vitro. A rat model of remifentanil-induced postoperative hyperalgesia was performed with the DOR agonist deltorphin-deltorphin II or the DOR antagonist naltrindole injected intrathecally 10 min before remifentanil infusion. Mechanical and thermal hyperalgesia were measured at -24h, 2, 6, 24 and 48 h after remifentanil infusion. Western blot was applied to detect the membrane and total expression of DOR and NMDA receptor subunits (NR1, NR2A and NR2B) in spinal cord L4-L6 segments. In addition, whole-cell patch-clamp recording was used to investigate the effect of DOR inhibition on NMDA receptor-induced current in spinal cord slices in vitro. We found that membrane trafficking of DOR, NR1 and NR2B subunits in the spinal cord increased after remifentanil administration and surgery. The DOR antagonist naltrindole could attenuate mechanical and thermal hyperalgesia without affecting baseline nociceptive threshold, reduce membrane expression of DOR and decrease the membrane and total expressions of NR1 and NR2B subunits. Furthermore, the amplitude and the frequency of NMDA receptor-induced current were significantly increased by remifentanil incubation in neurons of the dorsal horn, which was reversed by the application of naltrindole. The above results indicate that inhibition of DOR could significantly inhibit remifentanil-induced hyperalgesia via modulating the total protein level, membrane trafficking and function of NMDA receptors in the dorsal horn of spinal cord, suggesting that naltrindole could be a potential anti-hyperalgesic agent for treating OIH. Copyright © 2014. Published by Elsevier Inc.

Laparoscopic Heller myotomy can be used as primary therapy for esophageal achalasia regardless of age.

PubMed

Salvador, Renato; Costantini, Mario; Cavallin, Francesco; Zanatta, Lisa; Finotti, Elena; Longo, Cristina; Nicoletti, Loredana; Capovilla, Giovanni; Bardini, Romeo; Zaninotto, Giovanni

2014-01-01

Laparoscopic Heller-Dor surgery is the current treatment of choice for patients with esophageal achalasia, but elderly patients are generally referred for less invasive treatments (pneumatic dilations or botulinum toxin injections). To assess the effect of age on the surgical outcome of patients receiving laparoscopic Heller-Dor as primary treatment. Demographic and clinical findings were prospectively collected on patients undergoing laparoscopic Heller-Dor from 1992 to 2012. Patients were classified in three age brackets: group A (≤45 years), group B (45-70), and group C (≥70). Treatment was defined as a failure if the postoperative symptom score was >10th percentile of the preoperative score (i.e., >8). We consecutively performed the Heller-Dor in 571 achalasia patients, 305 (53.4 %) in group A, 226 (39.6 %) in group B, and 40 (7 %) in group C. The mortality was nil; the conversion and morbidity rates were both 1.1 %. Group C patients had higher preoperative symptom scores (p = 0.02), while the symptom duration was similar in all three groups. Mucosal tears occurred in 17 patients (3 %): 6 (2 %) in group A, 8 (3.5 %) in group B, and 3 (7.5 %) in group C (p = 0.09). The postoperative hospital stay was slightly longer for group C (p = 0.06). The treatment failure rate was quite similar: 31 failures in group A (10.1 %), 19 in group B (8.4 %), and 3 in group C (7.5 %; p = 0.80). These failures were seen more in manometric pattern III (22.2 %, p = 0.002). Laparoscopic Heller-Dor can be used as the first therapeutic approach to achalasia even in elderly patients with an acceptable surgical risk.

Anti-Analgesic Effect of the Mu/Delta Opioid Receptor Heteromer Revealed by Ligand-Biased Antagonism

PubMed Central

Milan-Lobo, Laura; Enquist, Johan; van Rijn, Richard M.; Whistler, Jennifer L.

2013-01-01

Delta (DOR) and mu opioid receptors (MOR) can complex as heteromers, conferring functional properties in agonist binding, signaling and trafficking that can differ markedly from their homomeric counterparts. Because of these differences, DOR/MOR heteromers may be a novel therapeutic target in the treatment of pain. However, there are currently no ligands selective for DOR/MOR heteromers, and, consequently, their role in nociception remains unknown. In this study, we used a pharmacological opioid cocktail that selectively activates and stabilizes the DOR/MOR heteromer at the cell surface by blocking its endocytosis to assess its role in antinociception. We found that mice treated chronically with this drug cocktail showed a significant right shift in the ED50 for opioid-mediated analgesia, while mice treated with a drug that promotes degradation of the heteromer did not. Furthermore, promoting degradation of the DOR/MOR heteromer after the right shift in the ED50 had occurred, or blocking signal transduction from the stabilized DOR/MOR heteromer, shifted the ED50 for analgesia back to the left. Taken together, these data suggest an anti-analgesic role for the DOR/MOR heteromer in pain. In conclusion, antagonists selective for DOR/MOR heteromer could provide an avenue for alleviating reduced analgesic response during chronic pain treatment. PMID:23554887

DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual regulators of autophagy and transcription.

PubMed

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A; Lamark, Trond; Macias, Maria J; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28-42; region 2, 66-112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription.

DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription

PubMed Central

Sancho, Ana; Duran, Jordi; García-España, Antonio; Mauvezin, Caroline; Alemu, Endalkachew A.; Lamark, Trond; Macias, Maria J.; DeSalle, Rob; Royo, Miriam; Sala, David; Chicote, Javier U.; Palacín, Manuel; Johansen, Terje; Zorzano, Antonio

2012-01-01

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription. PMID:22470510

Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

PubMed

Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

2016-10-01

As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The AB Doradus system revisited: The dynamical mass of AB Dor A/C

NASA Astrophysics Data System (ADS)

Azulay, R.; Guirado, J. C.; Marcaide, J. M.; Martí-Vidal, I.; Ros, E.; Tognelli, E.; Jauncey, D. L.; Lestrade, J.-F.; Reynolds, J. E.

2017-10-01

Context. The study of pre-main-sequence (PMS) stars with model-independent measurements of their masses is essential to check the validity of theoretical models of stellar evolution. The well-known PMS binary AB Dor A/C is an important benchmark for this task, since it displays intense and compact radio emission, which makes possible the application of high-precision astrometric techniques to this system. Aims: We aim to revisit the dynamical masses of the components of AB Dor A/C to refine earlier comparisons between the measurements of stellar parameters and the predictions of stellar models. Methods: We observed in phase-reference mode the binary AB Dor A/C, 0.2'' separation, with the Australian Long Baseline Array at 8.4 GHz. The astrometric information resulting from our observations was analyzed along with previously reported VLBI, optical (Hipparcos), and infrared measurements. Results: The main star AB Dor A is clearly detected in all the VLBI observations, which allowed us to analyze the orbital motion of the system and to obtain model-independent dynamical masses of 0.90 ± 0.08 M⊙ and 0.090 ± 0.008 M⊙, for AB Dor A and AB Dor C, respectively. Comparisons with PMS stellar evolution models favor and age of 40-50 Myr for AB Dor A and of 25-120 Myr for AB Dor C. Conclusions: We show that the orbital motion of the AB Dor A/C system is remarkably well determined, leading to precise estimates of the dynamical masses. Comparison of our results with the prediction of evolutionary models support the observational evidence that theoretical models tend to slightly underestimate the mass of the low-mass stars.

Role of DOR in neuronal plasticity changes promoted by food-seeking behaviour.

PubMed

Mancino, Samantha; Mendonça-Netto, Sueli; Martín-García, Elena; Maldonado, Rafael

2017-09-01

Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genotypes were revealed on operant behaviour acquisition in FR1. DOR knockout mice displayed lower number of active lever-presses than wild-type mice on FR5, and a similar decrease was revealed in DOR KO mice in the breaking point during the PR. This operant training to obtain palatable food increased dendritic spine density in the PFC, HCP and NAc shell of wild-type, but these plasticity changes were abolished in DOR KO mice. Our results support the hypothesis that DOR regulates the reinforcing effects and motivation for palatable food through neuroplastic changes in specific brain reward areas. © 2016 Society for the Study of Addiction.

Midterm follow-up evaluation after a novel approach to anterior fundoplication for achalasia.

PubMed

Richardson, W S; Kennedy, C I; Bolton, J S

2006-12-01

This study aimed to compare the outcomes for Heller myotomy alone and combined with different partial fundoplications. The authors retrospectively reviewed their experience with 69 laparoscopic myotomies and 14 Heller myotomies, 80% of which were performed with partial fundoplication including 20 Toupet, 18 Dor, and 17 modified Dor procedures, in which the fundoplication is sutured to both sides of the crura and not the myotomy. The mean age of the study patients was 69 years (range, 15-80 years). Four mucosal perforations were repaired intraoperatively. There was one small bowel fistula in an area of open hernia repair distant from the myotomy. One patient with severe chronic obstructive pulmonary disease died of pneumonia. Phone follow-up evaluation was achieved in 68% of the cases at a mean of 37 months (range, 2-97 months). The results for no dysphagia and for heartburn requiring proton pump inhibitors, respectively, were as follows: Heller myotomy (85.7%, 28.5%), Toupet (66.6%, 33.3%), Dor (83.3%, 20%), and modified Dor (84.6%, 15.3%). Two patients with reflux strictures required annual dilation (Toupet, Dor). Two patients required revisions: one redo Heller myotomy (Dor) and one esophageal replacement (Toupet). Heller myotomy provides excellent dysphagia relief with or without fundoplication. Heartburn is a significant problem for a minority of patients. In the authors' hands, Toupet had the worst results and modified Dor was most protective for heartburn.

Further Optimization and Evaluation of Bioavailable, Mixed-Efficacy μ-Opioid Receptor (MOR) Agonists/δ-Opioid Receptor (DOR) Antagonists: Balancing MOR and DOR Affinities.

PubMed

Harland, Aubrie A; Yeomans, Larisa; Griggs, Nicholas W; Anand, Jessica P; Pogozheva, Irina D; Jutkiewicz, Emily M; Traynor, John R; Mosberg, Henry I

2015-11-25

In a previously described peptidomimetic series, we reported the development of bifunctional μ-opioid receptor (MOR) agonist and δ-opioid receptor (DOR) antagonist ligands with a lead compound that produced antinociception for 1 h after intraperitoneal administration in mice. In this paper, we expand on our original series by presenting two modifications, both of which were designed with the following objectives: (1) probing bioavailability and improving metabolic stability, (2) balancing affinities between MOR and DOR while reducing affinity and efficacy at the κ-opioid receptor (KOR), and (3) improving in vivo efficacy. Here, we establish that, through N-acetylation of our original peptidomimetic series, we are able to improve DOR affinity and increase selectivity relative to KOR while maintaining the desired MOR agonist/DOR antagonist profile. From initial in vivo studies, one compound (14a) was found to produce dose-dependent antinociception after peripheral administration with an improved duration of action of longer than 3 h.

microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway.

PubMed

Zhang, Yi; Wei, Yangchao; Li, Xuan; Liang, Xingsi; Wang, Liming; Song, Jun; Zhang, Xiuzhong; Zhang, Chong; Niu, Jian; Zhang, Pengbo; Ren, Zeqiang; Tang, Bo

2018-01-26

The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3' untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator-epidermal growth factor (EGF)-can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.

Shifts in soil chemical properties and bacterial communities responding to biotransformed dry olive residue used as organic amendment.

PubMed

Siles, José A; Cajthaml, Tomas; Hernández, Paola; Pérez-Mendoza, Daniel; García-Romera, Inmaculada; Sampedro, Inmaculada

2015-07-01

Dry olive residue (DOR) is a waste product derived from olive oil extraction and has been proposed as an organic amendment. However, it has been demonstrated that a pre-treatment, such as its transformation by saprophytic fungi, is required before DOR soil application. A greenhouse experiment was designed where 0 and 50 g kg(-1) of raw DOR (DOR), Coriolopsis floccosa-transformed DOR (CORDOR) and Fusarium oxysporum-transformed DOR (FUSDOR) were added to soil. Analyses of the soil chemical properties as well as the structure and relative abundance of bacterial and actinobacterial communities were conducted after 0, 30 and 60 days following amendment. The different amendments produced a slight decrease in soil pH and significant increases in carbon fractions, C/N ratios, phenols and K, with these increases being more significant after DOR application. Quantitative PCR assays of the 16S rRNA gene and PLFA analyses showed that all amendments favoured bacterial growth at 30 and 60 days, although actinobacterial proliferation was more evident after CORDOR and FUSDOR application at 60 days. Bacterial and actinobacterial DGGE multivariate analyses showed that the amendments produced structural changes in both communities, especially after 60 days of amendment. PLFA data analysis identified changes in soil microbial communities according to the amendment considered, with FUSDOR and CORDOR being less disruptive than DOR. Finally, integrated analysis of all data monitored in the present study enabled us to conclude that the greatest impact on soil properties was caused by DOR at 30 days and that soil showed some degree of resilience after this time.

A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons

PubMed Central

Chung, Paul Chu Sin; Keyworth, Helen L.; Martin-Garcia, Elena; Charbogne, Pauline; Darcq, Emmanuel; Bailey, Alexis; Filliol, Dominique; Matifas, Audrey; Ouagazzal, Abdel-Mouttalib; Gaveriaux-Ruff, Claire; Befort, Katia; Maldonado, Rafael; Kitchen, Ian; Kieffer, Brigitte L.

2014-01-01

Background The delta opioid receptor (DOR) is broadly expressed throughout the nervous system and regulates chronic pain, emotional responses, motivation and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. Here we used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain. Methods We characterized DOR distribution in the brain of Dlx5/6-CreXOprd1fl/fl (Dlx-DOR) mice, and tested main central DOR functions through behavioral testing. Results DORs proteins were strongly deleted in olfactory bulb and striatum, and remained intact in cortex and basolateral amygdala. Olfactory perception, circadian activity and despair-like behaviors were unchanged. In contrast, locomotor stimulant effects of SNC80 (DOR agonist) and SKF81297 (D1 agonist) were abolished and increased, respectively. Furthermore, Dlx-DOR mice showed lower levels of anxiety in the elevated plus-maze, opposing the known high anxiety in constitutive DOR knockout animals. Also Dlx-DOR mice reached the food more rapidly in a novelty suppressed feeding (NSF) task, despite their lower motivation for food reward observed in an operant paradigm. Finally, c-fos staining after NSF was strongly reduced in amygdala, concordant with the low anxiety phenotype of Dlx-DOR mice. Conclusion Here we demonstrate that DORs expressed in the forebrain mediate the described locomotor effect of SNC80 and inhibit D1-stimulated hyperactivity. Our data also reveal an unanticipated anxiogenic role for this particular DOR subpopulation, with a potential novel adaptive role. DORs therefore exert dual anxiolytic/anxiogenic roles in emotional responses, which may both have implications in the area of anxiety disorders. PMID:25444168

The first comprehensive catalog of γ Dor pulsators and their characteristics

NASA Astrophysics Data System (ADS)

Ibanoglu, C.; Çakırlı, Ö.; Sipahi, E.

2018-07-01

We present the first comprehensive catalog of the γ Doradus type pulsating stars. This catalog covers observational properties of all γ Dor variables obtained until January 2017. The photometric and physical properties of 109 well - known γ Dor pulsators, 18 hybrid stars, 13 anomalous γ Dor stars, and 22 γ Dor stars in eclipsing plus 1 non-eclipsing SB2 binary systems are presented as separate tables. In addition, 291 candidate γ Dor variables discovered by CoRot, 307 candidate γ Dor, 205 hybrid and 11 candidate γ Dor in binaries discovered by Kepler were also presented. Distribution of the genuine single γ Dor pulsators in the Ppuls-Teff, Amplitude-Teff, Amplitude-Ppuls and L-Teff diagrams are presented and discussed. We find following correlations for the γ Dor pulsators in the eclipsing binaries: Ppuls ∝ Porb0.27, Ppuls ∝ Q0.45, and Ppuls ∝ r-0.44, where (Q) is the pulsation constant and r is the fractional radius of the pulsating component in the binary system. The correlation coefficients are not high enough due to limited sample and scattering in the data.

DOR undergoes nucleo-cytoplasmic shuttling, which involves passage through the nucleolus.

PubMed

Mauvezin, Caroline; Sancho, Ana; Ivanova, Saska; Palacin, Manuel; Zorzano, Antonio

2012-09-21

DOR is a bi-functional protein that regulates transcription and enhances starvation-induced autophagy. While autophagy has been mostly described as a stress-response mechanism, cells also need autophagy to maintain homeostasis in basal conditions. However, the mechanisms regulating basal autophagy still remain unknown. Our results show that DOR acts in basal autophagy. Indeed, DOR already undergoes nucleo-cytoplasmic shuttling in basal conditions and, surprisingly, DOR exits continuously the nucleus and traverses the nucleolus. However, the nucleolus integrity is not essential for both DOR nucleo-cytoplasmic shuttling and DOR function on basal autophagy. Taken together, we propose that DOR exit from the nucleus is essential for basal autophagy stimulation even under nucleolus disruption. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Activation of DOR attenuates anoxic K+ derangement via inhibition of Na+ entry in mouse cortex.

PubMed

Chao, Dongman; Bazzy-Asaad, Alia; Balboni, Gianfranco; Salvadori, Severo; Xia, Ying

2008-09-01

We have recently found that in the mouse cortex, activation of delta-opioid receptor (DOR) attenuates the disruption of K(+) homeostasis induced by hypoxia or oxygen-glucose deprivation. This novel observation suggests that DOR may protect neurons from hypoxic/ischemic insults via the regulation of K(+) homeostasis because the disruption of K(+) homeostasis plays a critical role in neuronal injury under hypoxic/ischemic stress. The present study was performed to explore the ionic mechanism underlying the DOR-induced neuroprotection. Because anoxia causes Na(+) influx and thus stimulates K(+) leakage, we investigated whether DOR protects the cortex from anoxic K(+) derangement by targeting the Na(+)-based K(+) leakage. By using K(+)-sensitive microelectrodes in mouse cortical slices, we showed that 1) lowering Na(+) concentration and substituting with impermeable N-methyl-D-glucamine caused a concentration-dependent attenuation of anoxic K(+) derangement; 2) lowering Na(+) concentration by substituting with permeable Li(+) tended to potentiate the anoxic K(+) derangement; and 3) the DOR-induced protection against the anoxic K(+) responses was largely abolished by low-Na(+) perfusion irrespective of the substituted cation. We conclude that external Na(+) concentration greatly influences anoxic K(+) derangement and that DOR activation likely attenuates anoxic K(+) derangement induced by the Na(+)-activated mechanisms in the cortex.

Value of circulating cell-free DNA analysis as a diagnostic tool for breast cancer: a meta-analysis

PubMed Central

Ma, Xuelei; Zhang, Jing; Hu, Xiuying

2017-01-01

Objectives The aim of this study was to systematically evaluate the diagnostic value of cell free DNA (cfDNA) for breast cancer. Results Among 308 candidate articles, 25 with relevant diagnostic screening qualified for final analysis. The mean sensitivity, specificity and area under the curve (AUC) of SROC plots for 24 studies that distinguished breast cancer patients from healthy controls were 0.70, 0.87, and 0.9314, yielding a DOR of 32.31. When analyzed in subgroups, the 14 quantitative studies produced sensitivity, specificity, AUC, and a DOR of 0.78, 0.83, 0.9116, and 24.40. The 10 qualitative studies produced 0.50, 0.98, 0.9919, and 68.45. For 8 studies that distinguished malignant breast cancer from benign diseases, the specificity, sensitivity, AUC and DOR were 0.75, 0.79, 0.8213, and 9.49. No covariate factors had a significant correlation with relative DOR. Deek's funnel plots indicated an absence of publication bias. Materials and Methods Databases were searched for studies involving the use of cfDNA to diagnose breast cancer. The studies were analyzed to determine sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the summary receiver operating characteristic (SROC). Covariates were evaluated for effect on relative DOR. Deek's Funnel plots were generated to measure publication bias. Conclusions Our analysis suggests a promising diagnostic potential of using cfDNA for breast cancer screening, but this diagnostic method is not yet independently sufficient. Further work refining qualitative cfDNA assays will improve the correct diagnosis of breast cancers. PMID:28460452

Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "Message-Address" Concept.

PubMed

Shen, Qing; Qian, Yuanyuan; Huang, Xiaoqin; Xu, Xuejun; Li, Wei; Liu, Jinggen; Fu, Wei

2016-04-14

The classic "message-address" concept was proposed to address the binding of endogenous peptides to the opioid receptors and was later successfully applied in the discovery of the first nonpeptide δ opioid receptor (DOR) antagonist naltrindole. By revisiting this concept, and based on the structure of tramadol, we designed a series of novel compounds that act as highly potent and selective agonists of DOR among which (-)-6j showed the highest affinity (K i = 2.7 nM), best agonistic activity (EC50 = 2.6 nM), and DOR selectivity (more than 1000-fold over the other two subtype opioid receptors). Molecular docking studies suggest that the "message" part of (-)-6j interacts with residue Asp128(3.32) and a neighboring water molecule, and the "address" part of (-)-6j packs with hydrophobic residues Leu300(7.35), Val281(6.55), and Trp284(6.58), rendering DOR selectivity. The discovery of novel compound (-)-6j, and the obtained insights into DOR-agonist binding will help us design more potent and selective DOR agonists.

F-box protein DOR functions as a novel inhibitory factor for abscisic acid-induced stomatal closure under drought stress in Arabidopsis,.

PubMed

Zhang, Yu'e; Xu, Wenying; Li, Zhonghui; Deng, Xing Wang; Wu, Weihua; Xue, Yongbiao

2008-12-01

Guard cells, which form stoma in leaf epidermis, sense and integrate environmental signals to modulate stomatal aperture in response to diverse conditions. Under drought stress, plants synthesize abscisic acid (ABA), which in turn induces a rapid closing of stoma, to prevent water loss by transpiration. However, many aspects of the molecular mechanism for ABA-mediated stomatal closure are still not understood. Here, we report a novel negative regulator of guard cell ABA signaling, DOR, in Arabidopsis (Arabidopsis thaliana). The DOR gene encodes a putative F-box protein, a member of the S-locus F-box-like family related to AhSLF-S(2) and specifically interacting with ASK14 and CUL1. A null mutation in DOR resulted in a hypersensitive ABA response of stomatal closing and a substantial increase of drought tolerance; in contrast, the transgenic plants overexpressing DOR were more susceptible to the drought stress. DOR is strongly expressed in guard cells and suppressed by ABA treatment, suggesting a negative feedback loop of DOR in ABA responses. Double-mutant analyses of dor with ABA-insensitive mutant abi1-1 showed that abi1-1 is epistatic to dor, but no apparent change of phospholipase Dalpha1 was detected between the wild type and dor. Affymetrix GeneChip analysis showed that DOR likely regulates ABA biosynthesis under drought stress. Taken together, our results demonstrate that DOR acts independent of phospholipase Dalpha1 in an ABA signaling pathway to inhibit the ABA-induced stomatal closure under drought stress.

Serum Anti-Glycan Antibody Biomarkers for Inflammatory Bowel Disease Diagnosis and Progression: A Systematic Review and Meta-analysis

PubMed Central

Kaul, Amit; Hutfless, Susan; Liu, Ling; Bayless, Theodore M.; Marohn, Michael R.; Li, Xuhang

2011-01-01

BACKGROUND Anti-glycan antibody serologic markers may serve as useful adjunct in the diagnosis/prognosis of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). This meta-analysis/systemic review was aimed to evaluate the diagnostic value, as well as the association of anti-glycan biomarkers with IBD susceptible gene variants, disease complications, and need for surgery in IBD. METHODS The diagnostic odds ratio (DOR), 95% confidence interval (CI), and sensitivity/specificity were used to compare the diagnostic value of individual and combinations of anti-glycan markers and their association with disease course (complication and/or need for surgery). RESULTS Fourteen studies were included in the systemic review and nine in the meta-analysis. Individually, ASCA had the highest DOR for differentiating IBD from healthy (DOR 21.1; 1.8-247.3; 2 studies), and CD from UC (DOR 10.2; CI 7.7-13.7; 7 studies). For combination of ≥2 markers, the DOR was 2.8 (CI 2.2-3.6; 2 studies) for CD-related surgery, higher than any individual marker, while the DOR for differentiating CD from UC was 10.2 (CI 5.6-18.5; 3 studies) and for complication was 2.8 (CI 2.2-3.7; 2 studies), similar to individual markers. CONCLUSIONS ASCA had the highest diagnostic value among individual anti-glycan markers. While ACCA had the highest association with complications, ASCA and ACCA associated equally with need for surgery. Although in most individual studies, combination of ≥2 markers had a better diagnostic value as well as higher association with complications and need for surgery, we found the combination performing slightly better than any individual marker in our meta-analysis. PMID:22294465

Heteromerization of the μ- and δ-Opioid Receptors Produces Ligand-Biased Antagonism and Alters μ-Receptor TraffickingS⃞

PubMed Central

Milan-Lobo, Laura

2011-01-01

Heteromerization of opioid receptors has been shown to alter opioid receptor pharmacology. However, how receptor heteromerization affects the processes of endocytosis and postendocytic sorting has not been closely examined. This question is of particular relevance for heteromers of the μ-opioid receptor (MOR) and δ-opioid receptor (DOR), because the MOR is recycled primarily after endocytosis and the DOR is degraded in the lysosome. Here, we examined the endocytic and postendocytic fate of MORs, DORs, and DOR/MOR heteromers in human embryonic kidney 293 cells stably expressing each receptor alone or coexpressing both receptors. We found that the clinically relevant MOR agonist methadone promotes endocytosis of MOR but also the DOR/MOR heteromer. Furthermore, we show that DOR/MOR heteromers that are endocytosed in response to methadone are targeted for degradation, whereas MORs in the same cell are significantly more stable. It is noteworthy that we found that the DOR-selective antagonist naltriben mesylate could block both methadone- and [d-Ala2,NMe-Phe4,Gly-ol5]-enkephalin-induced endocytosis of the DOR/MOR heteromers but did not block signaling from this heteromer. Together, our results suggest that the MOR adopts novel trafficking properties in the context of the DOR/MOR heteromer. In addition, they suggest that the heteromer shows “biased antagonism,” whereby DOR antagonist can inhibit trafficking but not signaling of the DOR/MOR heteromer. PMID:21422164

Physical examination tests of the shoulder: a systematic review and meta-analysis of diagnostic test performance.

PubMed

Gismervik, Sigmund Ø; Drogset, Jon O; Granviken, Fredrik; Rø, Magne; Leivseth, Gunnar

2017-01-25

Physical examination tests of the shoulder (PETS) are clinical examination maneuvers designed to aid the assessment of shoulder complaints. Despite more than 180 PETS described in the literature, evidence of their validity and usefulness in diagnosing the shoulder is questioned. This meta-analysis aims to use diagnostic odds ratio (DOR) to evaluate how much PETS shift overall probability and to rank the test performance of single PETS in order to aid the clinician's choice of which tests to use. This study adheres to the principles outlined in the Cochrane guidelines and the PRISMA statement. A fixed effect model was used to assess the overall diagnostic validity of PETS by pooling DOR for different PETS with similar biomechanical rationale when possible. Single PETS were assessed and ranked by DOR. Clinical performance was assessed by sensitivity, specificity, accuracy and likelihood ratio. Six thousand nine-hundred abstracts and 202 full-text articles were assessed for eligibility; 20 articles were eligible and data from 11 articles could be included in the meta-analysis. All PETS for SLAP (superior labral anterior posterior) lesions pooled gave a DOR of 1.38 [1.13, 1.69]. The Supraspinatus test for any full thickness rotator cuff tear obtained the highest DOR of 9.24 (sensitivity was 0.74, specificity 0.77). Compression-Rotation test obtained the highest DOR (6.36) among single PETS for SLAP lesions (sensitivity 0.43, specificity 0.89) and Hawkins test obtained the highest DOR (2.86) for impingement syndrome (sensitivity 0.58, specificity 0.67). No single PETS showed superior clinical test performance. The clinical performance of single PETS is limited. However, when the different PETS for SLAP lesions were pooled, we found a statistical significant change in post-test probability indicating an overall statistical validity. We suggest that clinicians choose their PETS among those with the highest pooled DOR and to assess validity to their own specific clinical settings, review the inclusion criteria of the included primary studies. We further propose that future studies on the validity of PETS use randomized research designs rather than the accuracy design relying less on well-established gold standard reference tests and efficient treatment options.

Angle of His Accentuation Is a Viable Alternative to Dor Fundoplication as an Adjunct to Laparoscopic Heller Cardiomyotomy: Results of a Randomized Clinical Study.

PubMed

Gupta, Prince; Parshad, Rajinder; Balakrishna, Pavithra; Saraya, Anoop; Makharia, Govind K; Sachdeva, Sanjeev; Sharma, Raju

2018-05-24

There is no consensus regarding the type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller cardiomyotomy (LHCM). The aim of this study was to compare Angle of His accentuation (AOH) with Dor Fundoplication (Dor) as an adjunct to LHCM. A total of 110 patients with achalasia cardia presenting for LHCM from March 2010 to July 2015 were randomized to Dor and AOH. Symptom severity, achalasia-specific quality of life (ASQOL), new onset heartburn, and patient satisfaction were assessed using standardized scores preoperatively, at 3, 6 months, and then yearly. The primary outcome was relief of esophageal symptoms while secondary outcomes were new onset heartburn and ASQOL. Both groups were comparable with respect to the baseline demographic characteristics. There was no conversion to open and no mortality in either group. Median operative time was 128 min in AOH and 144 min in Dor group (p < 0.01). Mean follow-up was 36 months and was available in 98% patients. There was significant improvement in esophageal symptoms in both groups with no statistically significant difference between the two groups (p > 0.05). There was no difference in cumulative symptom scores between the two groups over the period of follow-up. New onset heartburn was seen in 11% in AOH and 9% in Dor group. Mean ASQOL score improved in both groups with no difference between the two groups (p = 0.83). Patient satisfaction was similar in both groups. AOH is similar to Dor as an adjunct to LHCM in safety and efficacy and can be performed in shorter time. CTRI: REF/2014/06/007146.

Localization and Regulation of Fluorescence-Labeled Delta Opioid Receptor, Expressed in Enteric Neurons of Mice

PubMed Central

Scherrer, Gregory; Evans, Christopher J.; Kieffer, Brigitte L.; Bunnett, Nigel W.

2015-01-01

Background & Aims Opioids and opiates inhibit gastrointestinal functions via μ, δ, and κ receptors. Although agonists of the δ opioid receptor (DOR) suppress motility and secretion, little is known about the localization and regulation of DOR in the gastrointestinal tract. Methods We studied mice in which the gene that encodes the enhanced green fluorescent protein (eGFP) was inserted into Oprd1, which encodes DOR, to express an ~80 kDa product (DOReGFP). We used these mice to examine how agonists of DOR regulate the subcellular distribution of the DOR. Results DOReGFP was expressed in all regions but confined to enteric neurons and fibers within the muscularis externa. In the submucosal plexus, DOReGFP was detected in neuropeptide Y-positive secretomotor and vasodilator neurons of the small intestine, but was rarely observed in the large bowel. In the myenteric plexus of the small intestine, DOReGFP was present in similar proportions of excitatory motoneurons and interneurons that expressed choline acetyltransferase and substance P, and in inhibitory motoneurons and interneurons that contained nitric oxide synthase. DOReGFP was mostly present in nitrergic myenteric neurons of colon. DOReGFP and μ opioid receptors were often co-expressed. DOReGFP-expressing neurons were associated with enkephalin-containing varicosities and enkephalin-induced, clathrin- and dynamin-mediated endocytosis and lysosomal trafficking of DOReGFP. DOReGFP replenishment at the plasma membrane was slow, requiring de novo synthesis, rather than recycling. Conclusions DOR localizes specifically to submucosal and myenteric neurons, which might account for the ability of DOR agonists to inhibit gastrointestinal secretion and motility. Sustained down-regulation of DOReGFP at the plasma membrane of activated could induce long-lasting tolerance to DOR agonists. PMID:21699782

delta opioid receptors stimulate Akt-dependent phosphorylation of c-jun in T cells.

PubMed

Shahabi, Nahid A; McAllen, Kathy; Sharp, Burt M

2006-02-01

Activation of naive T cells markedly up-regulates the expression of delta opioid receptors (DORs). These receptors are bound by DOR peptides released by T cells, modulating T cell functions such as interleukin-2 production, cellular proliferation, and chemotaxis. Previous studies have shown that DOR agonists [e.g., [D-Ala(2)-D-Leu(5)]-enkephalin (DADLE)] modulate T cell antigen receptor signaling through mitogen-activated protein kinases (MAPKs; i.e., extracellular signal-regulated kinases 1 and 2) and that DORs directly induce phosphorylation of activating transcription factor-2 (implicated in cytokine gene transcription) and its association with the MAPK c-jun1 NH(2)-terminal kinase (JNK). Such observations suggest that DORs may induce the phosphorylation of c-jun. These experiments were performed to test this hypothesis and determine the potential roles of phosphoinositide 3-kinase (PI3K) and Akt (protein kinase B). DADLE (10(-10) to 10(-6) M) dose-dependently induced c-jun phosphorylation. This was blocked by pertussis toxin and the DOR-specific antagonist naltindole. Fluorescence flow cytometry showed that DADLE significantly stimulated c-jun phosphorylation by T cells. DADLE stimulated phosphorylation of membrane-associated Akt; wortmannin and LY294002 ([2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one]), specific inhibitors of PI3K, abolished the DADLE-induced phosphorylation of c-jun. Finally, inhibitors of Akt and JNK blocked DADLE-induced phosphorylation of c-jun. Thus, activated DORs directly stimulate c-jun phosphorylation through a PI3K-dependent pathway in T cells, apparently involving Akt. This implies that DORs activate JNK through a novel pathway dependent on PI3K and Akt, thereby regulating the function of activator protein-1 transcription complexes containing c-jun and other transcription partners.

Giant H II Regions in the Merging System NGC 3256: Are They the Birthplaces of Globular Clusters?

NASA Astrophysics Data System (ADS)

English, J.; Freeman, K. C.

2003-03-01

CCD images and spectra of ionized hydrogen in the merging system NGC 3256 were acquired as part of a kinematic study to investigate the formation of globular clusters (GCs) during the interactions and mergers of disk galaxies. This paper focuses on the proposition by Kennicutt & Chu that giant H II regions (GHRs), with an Hα luminosity greater than 1.5×1040 ergs s-1, are birthplaces of young populous clusters (YPCs). Although, compared with some other interacting systems, NGC 3256 has relatively few (seven) giant H II complexes, these regions are comparable in total flux to about 85 30 Doradus-like giant H II regions (GHRs). The bluest, massive YPCs (Zepf et al.) are located in the vicinity of observed 30 Dor GHRs, contributing to the notion that some fraction of 30 Dor GHRs do cradle massive YPCs, as 30 Dor harbors R136. If interactions induce the formation of 30 Dor GHRs, the observed luminosities indicate that almost 900 30 Dor GHRs would form in NGC 3256 throughout its merger epoch. In order for 30 Dor GHRs to be considered GC progenitors, this number must be consistent with the specific frequencies of globular clusters estimated for elliptical galaxies formed via mergers of spirals (Ashman & Zepf). This only requires that about 10% of NGC 3256's 900 30 Dor GHRs harbor YPCs, which survive several gigayears and have masses >=MR136.

Opioidergic mechanisms underlying the actions of Vitex agnus-castus L

PubMed Central

Webster, Donna E.; He, Ying; Chen, Shao.-Nong; Pauli, Guido F.; Farnsworth, Norman R.; Wang, Zaijie Jim

2010-01-01

Vitex agnus-castus (VAC) has been used since ancient Greek times and has been shown clinically to be effective for the treatment of pre-menstrual syndrome. However, its mechanism of action has only been partially determined. Compounds, fractions, and extracts isolated from VAC were used in this study to thoroughly investigate possible opioidergic activity. First, an extract of VAC was found to bind and activate μ- and δ-, but not κ- opioid receptor subtypes (MOR, DOR, and KOR respectively). The extract was then resuspended in 10% methanol and partitioned sequentially with petroleum ether, CHCl3, and EtOAc to form four fractions including a water fraction. The highest affinity for MOR was concentrated in the CHCl3 fraction, whereas the highest affinity for DOR was found in the CHCl3 and EtOAc fractions. However, the petroleum ether fraction had the highest agonist activity at MOR and DOR. Several flavonoids from VAC were found to bind to both MOR and DOR in a dose-dependent manner; however only casticin, a marker compound for genus Vitex, was found to have agonist activity selective for DOR at high concentrations. These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR. PMID:20854795

Opioidergic mechanisms underlying the actions of Vitex agnus-castus L.

PubMed

Webster, Donna E; He, Ying; Chen, Shao-Nong; Pauli, Guido F; Farnsworth, Norman R; Wang, Zaijie Jim

2011-01-01

Vitex agnus-castus (VAC) has been used since ancient Greek times and has been shown clinically to be effective for the treatment of pre-menstrual syndrome. However, its mechanism of action has only been partially determined. Compounds, fractions, and extracts isolated from VAC were used in this study to thoroughly investigate possible opioidergic activity. First, an extract of VAC was found to bind and activate μ- and δ-, but not κ-opioid receptor subtypes (MOR, DOR, and KOR respectively). The extract was then resuspended in 10% methanol and partitioned sequentially with petroleum ether, CHCl(3), and EtOAc to form four fractions including a water fraction. The highest affinity for MOR was concentrated in the CHCl(3) fraction, whereas the highest affinity for DOR was found in the CHCl(3) and EtOAc fractions. The petroleum ether fraction had the highest agonist activity at MOR and DOR. Several flavonoids from VAC were found to bind to both MOR and DOR in a dose-dependent manner; however only casticin, a marker compound for genus Vitex, was found to have agonist activity selective for DOR at high concentrations. These results suggest VAC may exert its therapeutic effects through the activation of MOR, DOR, but not KOR. Copyright © 2010 Elsevier Inc. All rights reserved.

Effects of N-Substitutions on the Tetrahydroquinoline (THQ) Core of Mixed-Efficacy μ-Opioid Receptor (MOR)/δ-Opioid Receptor (DOR) Ligands.

PubMed

Harland, Aubrie A; Bender, Aaron M; Griggs, Nicholas W; Gao, Chao; Anand, Jessica P; Pogozheva, Irina D; Traynor, John R; Jutkiewicz, Emily M; Mosberg, Henry I

2016-05-26

N-Acetylation of the tetrahydroquinoline (THQ) core of a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands increases DOR affinity, resulting in ligands with balanced MOR and DOR affinities. We report a series of N-substituted THQ analogues that incorporate various carbonyl-containing moieties to maintain DOR affinity and define the steric and electronic requirements of the binding pocket across the opioid receptors. 4h produced in vivo antinociception (ip) for 1 h at 10 mg/kg.

Beclometasone oral--DOR BioPharma.

PubMed

2007-01-01

orBec is an oral enteric-coated tablet formulation of the corticosteroid beclometasone, which has been developed by Enteron Pharmaceuticals, a subsidiary of Corporate Technology Development (now DOR BioPharma). orBec is being developed for the treatment of gastrointestinal graft-versus-host disease (GVHD) and an NDA has been filed in the US. DOR BioPharma has also filed an MAA in Europe for the same indication.orBec is designed to reduce the need for systemic immunosuppressive drugs, thereby improving the outcome of bone marrow and stem cell transplantation.DOR BioPharma may seek a marketing partner in the US and elsewhere for orBec in GVHD and will seek a partner for other potential indications of the drug.In December 2001, Corporate Technology Development was acquired by Endorex Corporation (now DOR BioPharma). In October 1998, Enteron Pharmaceuticals (DOR BioPharma) entered into an exclusive, worldwide, royalty bearing license agreement with George B. McDonald, MD, including the right to grant sublicenses, for the rights to the intellectual property and know-how relating to orBec. In January 2007, DOR BioPharma received $US3 million under a non-binding letter of intent from Sigma-Tau Pharmaceuticals. The agreement grants Sigma-Tau an exclusive right to negotiate terms and conditions for a possible business transaction or strategic alliance regarding orBec and potentially other DOR pipeline compounds until 1 March 2007. Under the terms of the agreement, Sigma-Tau purchased $US1 million of DOR's common stock, with an additional $US2 million paid in cash. If no agreement is reached by 1 March 2007, DOR will return the $US2 million to Sigma-Tau within 60 days. DOR BioPharma received an unsolicited proposal from Cell Therapeutics, Inc. to acquire DOR BioPharma in January 2007. Because of the non-binding agreement already signed with Sigma-Tau, DOR BioPharma's board of directors cannot consider Cell Therapeutics' merger proposal at this time. orBec has been filed for approval in the US for the treatment of gastrointestinal GVHD. The US FDA accepted the NDA filing and has established a target date of 21 July 2007 for completion of review of the NDA. In November 2006, the EMEA determined that the MAA for orBec for the treatment of gastrointestinal GVHD is complete and that the review process has begun. The data provided in the MAA and NDA submissions demonstrate that orBec safely provides a lower risk of mortality compared with the current standard of care. Both filings are supported by data from two randomised, double-blinded, placebo-controlled clinical trials. The first was a 129-patient pivotal phase III clinical trial for orBec conducted at 16 bone marrow/stem cell transplant centres in the US and France. The second trial was a 60-patient phase II clinical trial conducted at the Fred Hutchinson Cancer Research Centre. In the primary endpoint of its pivotal trial, time to treatment failure through day 50, orBec failed to achieve statistical significance (p-value 0.1177). However, orBec did achieve statistical significance in the secondary endpoints of time to treatment failure through day 80, and a reduction in mortality compared with placebo. In this trial, patient survival at the prespecified endpoint of 200 days post-transplant showed a statistically significant 66% reduction in mortality among patients randomised to orBec. DOR BioPharma believes the primary endpoint was not achieved due to a higher than expected rate of treatment failures during the initial 10 days in both treatment groups. The mortality benefit in favour of orBec was confirmed in a retrospective analysis of the phase II study, in which there was a 55% reduction in mortality at 200 days post-transplant. At 1 year after randomisation, there were relatively consistent 51% and 45% reductions in the risk of mortality among patients randomised to orBec in both the phase III and phase II studies, respectively.DOR BioPharma is also conducting a phase II clinical trial to investigate orBec in the prevention of gastrointestinal GVHD. DOR BioPharma has executed an exclusive licence agreement with the University of Texas Medical Branch at Galveston for the use of oral luminally active anti-inflammatory drugs, such as orBec, for the treatment of irritable bowel syndrome.

Microbial Diversity of a Mediterranean Soil and Its Changes after Biotransformed Dry Olive Residue Amendment

PubMed Central

Siles, José A.; Rachid, Caio T. C. C.; Sampedro, Inmaculada; García-Romera, Inmaculada; Tiedje, James M.

2014-01-01

The Mediterranean basin has been identified as a biodiversity hotspot, about whose soil microbial diversity little is known. Intensive land use and aggressive management practices are degrading the soil, with a consequent loss of fertility. The use of organic amendments such as dry olive residue (DOR), a waste produced by a two-phase olive-oil extraction system, has been proposed as an effective way to improve soil properties. However, before its application to soil, DOR needs a pre-treatment, such as by a ligninolytic fungal transformation, e.g. Coriolopsis floccosa. The present study aimed to describe the bacterial and fungal diversity in a Mediterranean soil and to assess the impact of raw DOR (DOR) and C. floccosa-transformed DOR (CORDOR) on function and phylogeny of soil microbial communities after 0, 30 and 60 days. Pyrosequencing of the 16S rRNA gene demonstrated that bacterial diversity was dominated by the phyla Proteobacteria, Acidobacteria, and Actinobacteria, while 28S-rRNA gene data revealed that Ascomycota and Basidiomycota accounted for the majority of phyla in the fungal community. A Biolog EcoPlate experiment showed that DOR and CORDOR amendments decreased functional diversity and altered microbial functional structures. These changes in soil functionality occurred in parallel with those in phylogenetic bacterial and fungal community structures. Some bacterial and fungal groups increased while others decreased depending on the relative abundance of beneficial and toxic substances incorporated with each amendment. In general, DOR was observed to be more disruptive than CORDOR. PMID:25058610

Attenuating Ischemic Disruption of K+ Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.

PubMed

Chao, Dongman; Wang, Qinyu; Balboni, Gianfranco; Ding, Guanghong; Xia, Ying

2016-12-01

Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K + homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K + homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K + homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K + homeostasis in the neonatal cortex. Since maintaining cellular K + homeostasis and inhibiting excessive K + fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K + homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.

Changes in gene expression of DOR and other thyroid hormone receptors in rat liver during acute-phase response

PubMed Central

Baumgartner, Bernhard G.; Naz, Naila; Sheikh, Nadeem; Moriconi, Federico; Ramadori, Giuliano

2010-01-01

Non-thyroidal illness is characterized by low tri-iodothyronine (T3) serum level under acute-phase conditions. We studied hepatic gene expression of the newly identified thyroid hormone receptor (TR) cofactor DOR/TP53INP2 together with TRs in a rat model of aseptic abscesses induced by injecting intramuscular turpentine-oil into each hind limb. A fast (4-6 h) decrease in the serum level of free thyroxine and free T3 was observed. By immunohistology, abundant DOR protein expression was detected in the nuclei of hepatocytes and ED-1+ (mononuclear phagocytes), CK-19+ (biliary cells), and SMA+ (mesenchymal cells of the portal tract) cells. DOR signal was reduced with a minimum at 6-12 h after the acute-phase reaction (APR). Immunohistology also showed a similar pattern of protein expression in TRα1 but without a significant change during APR. Transcripts specific for DOR, nuclear receptor co-repressor 1 (NCoR-1), and TRβ1 were down-regulated with a minimum at 6-12 h, whereas expression for TRα1 and TRα2 was slightly and significantly up-regulated, respectively, with a maximum at 24 h after APR was initiated. In cultured hepatocytes, acute-phase cytokines interleukin-1β (IL-1β) and IL-6 down-regulated DOR and TRβ1 at the mRNA level. Moreover, gene expression of DOR and TRs (TRα1, TRα2, and TRβ1) was up-regulated in hepatocytes by adding T3 to the culture medium; this up-regulation was almost completely blocked by treating the cells with IL-6. Thus, TRβ1, NCoR-1, and the recently identified DOR/TP53INP2 are abundantly expressed and down-regulated in liver cells during APR. Their down-regulation is attributable to the decreased serum level of thyroid hormones and most probably also to the direct action of the main acute-phase cytokines. PMID:20949361

Changes in gene expression of DOR and other thyroid hormone receptors in rat liver during acute-phase response.

PubMed

Malik, Ihtzaz Ahmed; Baumgartner, Bernhard G; Naz, Naila; Sheikh, Nadeem; Moriconi, Federico; Ramadori, Giuliano

2010-11-01

Non-thyroidal illness is characterized by low tri-iodothyronine (T3) serum level under acute-phase conditions. We studied hepatic gene expression of the newly identified thyroid hormone receptor (TR) cofactor DOR/TP53INP2 together with TRs in a rat model of aseptic abscesses induced by injecting intramuscular turpentine-oil into each hind limb. A fast (4-6 h) decrease in the serum level of free thyroxine and free T3 was observed. By immunohistology, abundant DOR protein expression was detected in the nuclei of hepatocytes and ED-1(+) (mononuclear phagocytes), CK-19(+) (biliary cells), and SMA(+) (mesenchymal cells of the portal tract) cells. DOR signal was reduced with a minimum at 6-12 h after the acute-phase reaction (APR). Immunohistology also showed a similar pattern of protein expression in TRα1 but without a significant change during APR. Transcripts specific for DOR, nuclear receptor co-repressor 1 (NCoR-1), and TRβ1 were down-regulated with a minimum at 6-12 h, whereas expression for TRα1 and TRα2 was slightly and significantly up-regulated, respectively, with a maximum at 24 h after APR was initiated. In cultured hepatocytes, acute-phase cytokines interleukin-1β (IL-1β) and IL-6 down-regulated DOR and TRβ1 at the mRNA level. Moreover, gene expression of DOR and TRs (TRα1, TRα2, and TRβ1) was up-regulated in hepatocytes by adding T3 to the culture medium; this up-regulation was almost completely blocked by treating the cells with IL-6. Thus, TRβ1, NCoR-1, and the recently identified DOR/TP53INP2 are abundantly expressed and down-regulated in liver cells during APR. Their down-regulation is attributable to the decreased serum level of thyroid hormones and most probably also to the direct action of the main acute-phase cytokines.

Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.

PubMed

Pastore, Lisa M; Christianson, Mindy S; Stelling, James; Kearns, William G; Segars, James H

2018-01-01

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.

Risk element immobilization/stabilization potential of fungal-transformed dry olive residue and arbuscular mycorrhizal fungi application in contaminated soils.

PubMed

García-Sánchez, Mercedes; Stejskalová, Tereza; García-Romera, Inmaculada; Száková, Jiřina; Tlustoš, Pavel

2017-10-01

The use of biotransformed dry olive residue (DOR) as organic soil amendment has recently been proposed due to its high contents of stabilized organic matter and nutrients. The potential of biotransformed DOR to immobilize risk elements in contaminated soils might qualify DOR as a potential risk element stabilization agent for in situ soil reclamation practices. In this experiment, the mobility of risk elements in response to Penicillium chrysogenum-10-transformed DOR, Funalia floccosa-transformed DOR, Bjerkandera adusta-transformed DOR, and Chondrostereum purpureum-transformed DOR as well as arbuscular mycorrhizal fungi (AMF), Funneliformis mosseae, inoculation was investigated. We evaluated the effect of these treatments on risk element uptake by wheat (Triticum aestivum L.) plants in a pot experiment with Cd, Pb, and Zn contaminated soil. The results showed a significant impact of the combined treatment (biotransformed DOR and AMF inoculation) on wheat plant growth and element mobility. The mobile proportions of elements in the treated soils were related to soil pH; with increasing pH levels, Cd, Cu, Fe, Mn, P, Pb, and Zn mobility decreased significantly (r values between -0.36 and -0.46), while Ca and Mg mobility increased (r = 0.63, and r = 0.51, respectively). The application of biotransformed DOR decreased risk element levels (Cd, Zn), and nutrient concentrations (Ca, Cu, Fe, Mg, Mn) in the aboveground biomass, where the elements were retained in the roots. Thus, biotransformed DOR in combination with AMF resulted in a higher capacity of wheat plants to grow under detrimental conditions, being able to accumulate high amounts of risk elements in the roots. However, risk element reduction was insufficient for safe crop production in the extremely contaminated soil. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluorescence spectroscopy studies of HEK293 cells expressing DOR-Gi1α fusion protein; the effect of cholesterol depletion.

PubMed

Brejchová, Jana; Sýkora, Jan; Dlouhá, Kateřina; Roubalová, Lenka; Ostašov, Pavel; Vošahlíková, Miroslava; Hof, Martin; Svoboda, Petr

2011-12-01

Biophysical studies of fluorescence anisotropy of DPH and Laurdan generalized polarization were performed in plasma membranes (PM) isolated from control and cholesterol-depleted HEK293 cells stably expressing pertussis toxin (PTX)-insensitive DOR-Gi1α (Cys351-Ile351) fusion protein. PM isolated from control, PTX-untreated, cells were compared with PM isolated from PTX-treated cells. Results from both types of PM indicated that i) hydrophobic membrane interior was made more accessible to water molecules and more chaotically organized in cholesterol-depleted samples, ii) cholesterol depletion resulted in an overall increase in surface area of membrane, membrane fluidity, and mobility of its constituents. Analysis of DOR-Gi1α coupling in PTX-treated and PTX-untreated cells indicated that cholesterol depletion did not alter the agonist binding site of DOR (Bmax and Kd) but the ability of DOR agonist DADLE to activate G proteins was markedly impaired. In PTX-untreated membranes, EC50 for DADLE-stimulated [35S]GTPγS binding was shifted by one order of magnitude to the right: from 4.3±1.2×10(-9) M to 2.2±1.3×10(-8) M in control and cholesterol-depleted membrane samples, respectively. In PTX-treated membranes, EC50 was shifted from 4.5±1.1×10(-9) M to 2.8±1.4×10(-8) M. In summary, the perturbation of optimum PM organization by cholesterol depletion deteriorates functional coupling of DOR to covalently bound Gi1α as well as endogenously expressed PTX-sensitive G proteins of Gi/Go family while receptor ligand binding site is unchanged. The biophysical state of hydrophobic plasma (cell) membrane interior should be regarded as regulatory factor of DOR-signaling cascade. Copyright © 2011 Elsevier B.V. All rights reserved.

Surgical diminished ovarian reserve after endometrioma cystectomy versus idiopathic DOR: comparison of in vitro fertilization outcome.

PubMed

Roustan, Audrey; Perrin, Jeanne; Debals-Gonthier, Mathias; Paulmyer-Lacroix, Odile; Agostini, Aubert; Courbiere, Blandine

2015-04-01

Does the live birth rate after IVF depend on the etiology of diminished ovarian reserve (DOR)? IVF outcome and live birth rate are significantly impaired in women with DOR caused by a previous cystectomy for endometrioma compared with women with idiopathic DOR. The safety of the surgical treatment of endometriomas is being discussed in terms of damage to ovarian reserve. Several studies have reported a poor response to controlled ovarian stimulation and a significantly impaired IVF outcome in women with DOR consecutive to an endometrioma cystectomy compared with women with tubal factor infertility. Retrospective case-control study conducted in women aged under 40 treated in our Reproductive Medicine Center between January 2010 and January 2014 for a DOR defined by anti-Müllerian hormone level <2 ng/ml. Two groups of patients were selected: group A included patients with a DOR diagnosed after cystectomy(s) for endometrioma(s), group B included patients with an idiopathic DOR. In each group, subgroups of patients 'poor ovarian responders', based on the ESHRE criteria ('Bologna criteria'), have been established. A total of 51 patients in group A were matched to 116 patients in group B, representing respectively 125 and 243 IVF cycles. Among them, 39 patients in group A and 78 patients in group B validated strictly by the Bologna criteria, representing 99 and 189 IVF cycles, respectively. Each patient underwent a controlled ovarian hyperstimulation and IVF with fresh embryo transfer. Primary end-point was the live birth rate. Secondary end-points were the number of retrieved oocytes, fertilization rate, implantation rate, clinical pregnancy rate, spontaneous abortion rate and cycle cancelation rate. Significantly lower pregnancy (11.2% in group A versus 20.6% in group B, P = 0.02) and live birth (7.2 versus 16.9% respectively, P = 0.01) rates per cycle were assessed in women in group A compared with women in group B. The same results were obtained in the Bologna criteria subgroup analysis with a significantly lower pregnancy (9.1 versus 20.1%, P = 0.016) and live birth (5.1 versus 15.3%, P = 0.001) rates per cycle in women in subgroup A compared with women in subgroup B. Patients in group A required significantly higher gonadotrophins doses (2881 IU ± 1111 versus 2526 IU ± 795, P = 0.005), longer ovarian stimulation (10.6 Days ± 2.8 versus 9.9 Days ± 2.4, P = 0.019) and higher cancelation rate for poor response (12 versus 6.2%, P = 0.05). Despite a mean number of retrieved oocytes similar with the group B (5.4 ± 3.1 and 5.1 ± 3.2, NS), and a significantly higher fertilization rate (65.7 versus 47.2%, P < 0.001), women in group A showed a significantly lower implantation rate (7.2 versus 13.5%, P = 0.03). Abortion rate, ectopic pregnancy rate and multiple pregnancy rate were similar in both groups. Data were collected retrospectively using the database of our Department. Sample size is relatively small but our study provides statistically significant evidence that the chances of IVF success are decreased in women with DOR after cystectomy for endometrioma. Further larger series are needed to confirm these findings. To our knowledge, this is the first study evaluating IVF outcome in patients with DOR after cystectomy(s) for endometrioma(s) versus in patients with an idiopathic DOR. In addition to the risk of damaging ovarian reserve, we hypothesize that endometrioma surgery would not have qualitative benefits on results in IVF in patients with DOR. The authors have no competing interests to declare. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Prospective External Validation of International Ovarian Tumor Analysis (IOTA) Simple Rules in the Hands of Level I and II Examiners.

PubMed

Knafel, A; Banas, T; Nocun, A; Wiechec, M; Jach, R; Ludwin, A; Kabzinska-Turek, M; Pietrus, M; Pitynski, K

2016-10-01

Objective: To externally validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) by examiners with different levels of sonographic experience defined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and to assess the morphological ultrasound features of the adnexal tumors classified as inconclusive based on IOTA SR. Materials and Methods: In the two-year prospective study adnexal tumors were assessed preoperatively with transvaginal ultrasound by examiners with different levels of experience (level 1- IOTA SR1, level 2-IOTA SR2). Additionally, an expert (level 3) evaluated all tumors by subjective assessment (SA). If the rules could not be applied, the tumors were considered inconclusive. The final diagnosis was based on the histopathological result of the removed mass. The diagnostic performance measures for the assessed model were sensitivity, specificity, negative (LR-) and positive(LR+) likelihood ratios, accuracy (ACC) and diagnostic odds ratio (DOR). Results: 226 women with adnexal tumors scheduled for surgery were included in the stutdy. The prevalence of malignancy was 36.3 % in the group of all studied tumors and was 52.5 % in the inconclusive group (n = 40) (p = 0.215). Fewer tumors were classified as inconclusive by level 2 examiners compared to level 1 examiners [20 (8.8 %) vs. 40 (17.7 %); p = 0.008], resulting from the discrepancy in the evaluation of acoustic shadows and the vascularization within the tumor. For level 1 examiners a diagnostic strategy using IOTA SR1 +MA (assuming malignancy when SR inconclusive) achieved a sensitivity, specificity and DOR of 96.3 %, 81.9 %, 13.624 respectively. For level 2 examiners the diagnostic strategy for IOTA SR2 +MA achieved a sensitivity, specificity and DOR of 95.1 %, 89.6 %, 137,143, respectively. Adding SA by an expert (or level 3 examiner) when IOTA SR were not applicable improved the specificity of the test and achieved a DOR of 505.137 (SR1 +SA) and 293.627 (SR2 +SA). The SA by an expert proved to have the best diagnostic performance with a DOR of 5768.857, and a sensitivity and specificity of 97.6 % and 99.3 % respectively. Within the inconclusive group the most common tumors were unilocular-solid (n-13), solid (n-8) and multilocular-solid (n-10) ones. All multilocular tumors were classified as inconclusive because of their size (≥ 100 mm) and were found to be benign by pathology. Most of the inconclusive tumors with cystic content presented low-level (43.75 %) echogenicity, followed by ground-glass (34.37 %), mixed (12.5 %) and anechoic (9.4 %). Conclusion: The study results show excellent diagnostic performance of IOTA Simple Rules followed by subjective expert assessment in inconclusive tumors irrespective of the level of experience, while subjective assessment by an expert still has the highest diagnostic odds ratio. The number of inconclusive cases seems to depend on the level of ultrasound expertise and less experienced examiners have a tendency to overestimate blood flow and a presence of acoustic shadows within the tumors. IOTA SR were not applicable either because no benign or malignant features were found or both were identified. Within inconclusive tumors the majority of cases comprise malignant masses that are either unilocular-solid, solid tumors or small multilocular-solid ones with a diameter of less than 100 mm. © Georg Thieme Verlag KG Stuttgart · New York.

The First Morphometric Study of the Horn Morphological Pattern in a Geotrupidae: The Case of the Dor Beetle Ceratophyus rossii Jekel, 1865.

PubMed

Pizzo, Astrid; Mazzone, Fabio; Palestrini, Claudia

2015-01-01

Among beetles, thousands of species develop horns, the size of which is often extraordinarily disproportionate with respect to body size. The Scarabaeidae is the family in which horned species are most predominant, but other families, such as the Geotrupidae (dor beetles), also show remarkable horns, although in a more limited number of species. Horn expression mechanisms are well documented in Scarabaeidae but, despite the wealth of studies on this family, the horn morphological pattern of the Geotrupidae, to our knowledge, has never been investigated. In this paper, we describe for the first time the horn expression pattern in a dor beetle. As a study species, we chose Ceratophyus rossii, an Italian endemic dor beetle of the protected Mediterranean maquis in Tuscany, which shows remarkable head and pronotal horns in males and a notable cephalic horn in females. We identified and modeled shape and size horn patterns combining traditional and geometric morphometric approaches. We discuss the results in the wider landscape of developmental models described for other, more well-characterized, scarab beetles.

deep-orange and carnation define distinct stages in late endosomal biogenesis in Drosophila melanogaster.

PubMed

Sriram, V; Krishnan, K S; Mayor, Satyajit

2003-05-12

Endosomal degradation is severely impaired in primary hemocytes from larvae of eye color mutants of Drosophila. Using high resolution imaging and immunofluorescence microscopy in these cells, products of eye color genes, deep-orange (dor) and carnation (car), are localized to large multivesicular Rab7-positive late endosomes containing Golgi-derived enzymes. These structures mature into small sized Dor-negative, Car-positive structures, which subsequently fuse to form tubular lysosomes. Defective endosomal degradation in mutant alleles of dor results from a failure of Golgi-derived vesicles to fuse with morphologically arrested Rab7-positive large sized endosomes, which are, however, normally acidified and mature with wild-type kinetics. This locates the site of Dor function to fusion of Golgi-derived vesicles with the large Rab7-positive endocytic compartments. In contrast, endosomal degradation is not considerably affected in car1 mutant; fusion of Golgi-derived vesicles and maturation of large sized endosomes is normal. However, removal of Dor from small sized Car-positive endosomes is slowed, and subsequent fusion with tubular lysosomes is abolished. Overexpression of Dor in car1 mutant aggravates this defect, implicating Car in the removal of Dor from endosomes. This suggests that, in addition to an independent role in fusion with tubular lysosomes, the Sec1p homologue, Car, regulates Dor function.

Molecular Perspectives for mu/delta Opioid Receptor Heteromers as Distinct, Functional Receptors

PubMed Central

Ong, Edmund W.; Cahill, Catherine M.

2014-01-01

Opioid receptors are the sites of action for morphine and the other opioid drugs. Abundant evidence now demonstrates that different opioid receptor types can physically associate to form heteromers. Understandings of the nature, behavior, and role of these opioid receptor heteromers are developing. Owing to their constituent monomers’ involvement in analgesia, mu/delta opioid receptor (M/DOR) heteromers have been a particular focus of attention. There is now considerable evidence demonstrating M/DOR to be an extant and physiologically relevant receptor species. Participating in the cellular environment as a distinct receptor type, M/DOR availability is complexly regulated and M/DOR exhibits unique pharmacology from that of other opioid receptors (ORs), including its constituents. M/DOR appears to have a range of actions that vary in a ligand- (or ligands-) dependent manner. These actions can meaningfully affect the clinical effects of opioid drugs: strategies targeting M/DOR may be therapeutically useful. This review presents and discusses developments in these understandings with a focus on the molecular nature and activity of M/DOR in the context of therapeutic potentials. PMID:24709907

Learning-Related Translocation of δ-Opioid Receptors on Ventral Striatal Cholinergic Interneurons Mediates Choice between Goal-Directed Actions

PubMed Central

Bertran-Gonzalez, Jesus; Laurent, Vincent; Chieng, Billy C.; Christie, MacDonald J.

2013-01-01

The ability of animals to extract predictive information from the environment to inform their future actions is a critical component of decision-making. This phenomenon is studied in the laboratory using the pavlovian–instrumental transfer protocol in which a stimulus predicting a specific pavlovian outcome biases choice toward those actions earning the predicted outcome. It is well established that this transfer effect is mediated by corticolimbic afferents on the nucleus accumbens shell (NAc-S), and recent evidence suggests that δ-opioid receptors (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show a persistent, learning-related plasticity in the translocation of DORs to the somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during the encoding of the specific stimulus–outcome associations essential for pavlovian–instrumental transfer. We found that increased membrane DOR expression reflected both stimulus-based predictions of reward and the degree to which these stimuli biased choice during the pavlovian–instrumental transfer test. Furthermore, this plasticity altered the firing pattern of CINs increasing the variance of action potential activity, an effect that was exaggerated by DOR stimulation. The relationship between the induction of membrane DOR expression in CINs and both pavlovian conditioning and pavlovian–instrumental transfer provides a highly specific function for DOR-related modulation in the NAc-S, and it is consistent with an emerging role for striatal CIN activity in the processing of predictive information. Therefore, our results reveal evidence of a long-term, experience-dependent plasticity in opioid receptor expression on striatal modulatory interneurons critical for the cognitive control of action. PMID:24107940

Quality of Life Comparing Dor and Toupet After Heller Myotomy for Achalasia

PubMed Central

Tomasko, Jonathan M.; Augustin, Toms; Tran, Tung T.; Haluck, Randy S.; Rogers, Ann M.

2014-01-01

Background: Laparoscopic Heller cardiomyotomy (LHC) is standard therapy for achalasia. Traditionally, an antireflux procedure has accompanied the myotomy. This study was undertaken to compare quality-of-life outcomes between patients undergoing myotomy with Toupet versus Dor fundoplication. In addition, we investigated overall patient satisfaction after LHC in the treatment of achalasia. Methods: One hundred thirty-five patients who underwent LHC over a 13-year period were identified for inclusion. Symptoms queried included dysphagia, heartburn, and bloating using the Gastroesophageal Reflux Disease–Health-Related Quality of Life Scale and a second published scale for the assessment of gastroesophageal reflux disease and dysphagia symptoms. The patients' overall satisfaction after surgery was also rated. Data were compared on the basis of type of fundoplication. Symptom scores were analyzed using chi-square tests and Fisher's exact tests. Results: Sixty-three patients completed the survey (47%). There were no perioperative deaths or reoperations. The mean length of stay was 2.8 days. The mean operative time for LHC with Toupet fundoplication was 137.3 ± 30.91 minutes and for LHC with Dor fundoplication was 111.5 ± 32.44 minutes (P = .006). There was no difference with respect to the incidence or severity of postoperative heartburn, dysphagia, or bloating. Overall satisfaction with Toupet fundoplication was 87.5% and with Dor fundoplication was 93.8% (P > .999). Conclusions: LHC with either Toupet or Dor fundoplication gave excellent patient satisfaction. Postoperative symptoms of heartburn and dysphagia were equivalent when comparing LHC with either antireflux procedure. Dor and Toupet fundoplication were found to have equivalent outcomes in the short term. We prefer Dor to Toupet fundoplication because of its decreased need for extensive dissection and better mucosal protection. PMID:25392612

Quality of life comparing dor and toupet after heller myotomy for achalasia.

PubMed

Tomasko, Jonathan M; Augustin, Toms; Tran, Tung T; Haluck, Randy S; Rogers, Ann M; Lyn-Sue, Jerome R

2014-01-01

Laparoscopic Heller cardiomyotomy (LHC) is standard therapy for achalasia. Traditionally, an antireflux procedure has accompanied the myotomy. This study was undertaken to compare quality-of-life outcomes between patients undergoing myotomy with Toupet versus Dor fundoplication. In addition, we investigated overall patient satisfaction after LHC in the treatment of achalasia. One hundred thirty-five patients who underwent LHC over a 13-year period were identified for inclusion. Symptoms queried included dysphagia, heartburn, and bloating using the Gastroesophageal Reflux Disease-Health-Related Quality of Life Scale and a second published scale for the assessment of gastroesophageal reflux disease and dysphagia symptoms. The patients' overall satisfaction after surgery was also rated. Data were compared on the basis of type of fundoplication. Symptom scores were analyzed using chi-square tests and Fisher's exact tests. Sixty-three patients completed the survey (47%). There were no perioperative deaths or reoperations. The mean length of stay was 2.8 days. The mean operative time for LHC with Toupet fundoplication was 137.3±30.91 minutes and for LHC with Dor fundoplication was 111.5±32.44 minutes (P=.006). There was no difference with respect to the incidence or severity of postoperative heartburn, dysphagia, or bloating. Overall satisfaction with Toupet fundoplication was 87.5% and with Dor fundoplication was 93.8% (P>.999). LHC with either Toupet or Dor fundoplication gave excellent patient satisfaction. Postoperative symptoms of heartburn and dysphagia were equivalent when comparing LHC with either antireflux procedure. Dor and Toupet fundoplication were found to have equivalent outcomes in the short term. We prefer Dor to Toupet fundoplication because of its decreased need for extensive dissection and better mucosal protection.

The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice.

PubMed

Hervera, Arnau; Leánez, Sergi; Negrete, Roger; Pol, Olga

2009-10-01

Several works reveal that nitric oxide could enhance the peripheral antinociception induced by opioids during acute inflammation. Nonetheless, the role of nitric oxide in the local antinociceptive effects of delta-opioid receptor (DOR) agonists during chronic peripheral inflammation is not known. The aim of this study is to evaluate whether nitric oxide would enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. Chronic inflammatory pain was induced by the subplantar administration of complete Freund's adjuvant (CFA; 30 microl) and thermal hyperalgesia assessed by plantar test. In C57BL/6J mice, we evaluated the local antinociceptive effects of a DOR agonist, [D-Pen2,5]-enkephalin (DPDPE) and a nitric oxide donor, DETA NONOate DETA/NO 2,2'-(hydroxynitrosohydrazino) Bis-Ethanamine (NOC-18) alone or combined (DPDPE plus NOC-18) at 1, 4, 7, and 10 days after CFA injection. The reversibility of the peripheral antinociceptive effects of DPDPE, alone or combined with NOC-18, was assessed with the local administration of selective (naltrindole) and non-selective (naloxone methiodide) DOR antagonists. The local administration of DPDPE or NOC-18 alone dose-dependently inhibited the thermal hyperalgesia induced by peripheral inflammation. Moreover, the co-administration of NOC-18 with DPDPE significantly increased the antinociceptive effects produced by DPDPE from 1 to 10 days of CFA-induced inflammatory pain (P < 0.05). These effects were completely blocked by naltrindole and naloxone methiodide. Our results demonstrate that nitric oxide might enhance the local antinociceptive effects of a DOR agonist during chronic inflammatory pain by interaction with peripheral DOR, representing a useful strategy for an efficient antinociceptive treatment of peripheral inflammatory pain.

A KINE-CHEMICAL INVESTIGATION OF THE AB DOR MOVING GROUP 'STREAM'

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barenfeld, Scott A.; Bubar, Eric J.; Mamajek, Eric E.

2013-03-20

The AB Dor Moving Group consists of a 'nucleus' of {approx}10 stars at d {approx_equal} 20 pc, along with dozens of purported 'stream' members distributed across the sky. We perform a chemical and kinematic analysis of a subsample of AB Dor stream stars to test whether they constitute a physical stellar group. We use the NEMO Galactic kinematic code to investigate the orbits of the stream members, and perform a chemical abundance analysis using high resolution spectra taken with the Magellan Clay 6.5 m telescope. Using a {chi}{sup 2} test with the measured abundances for 10 different elements, we findmore » that only half of the purported AB Dor stream members could possibly constitute a statistically chemically homogeneous sample. Some stream members with three-dimensional velocities were hundreds of parsecs from the AB Dor nucleus {approx}10{sup 8} yr ago, and hence were unlikely to share a common origin. We conclude that the published lists of AB Dor moving group stream members are unlikely to represent the dispersed remnant of a single star formation episode. A subsample of the stream stars appears to be both statistically chemically homogeneous and in the vicinity of the AB Dor nucleus at birth. Their mean metallicity is [Fe/H] = 0.02 {+-} 0.02 dex, which we consider representative for the AB Dor group. Finally, we report a strong lower limit on the age of the AB Dor nucleus of >110 Myr based on the pre-main sequence contraction times for K-type members which have reached the main sequence.« less

Results of a search for γ Dor and δ SCT stars with the Kepler spacecraft

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, P. A.; Miles, L. F.; Guzik, J. A.

2015-02-01

The light curves of 2768 stars with effective temperatures and surface gravities placing them near the gamma Doradus (γ Dor)/delta Scuti (δ Sct) instability region were observed as part of the Kepler Guest Observer program from Cycles 1 through 5. The light curves were analyzed in a uniform manner to search for γ Dor, δ Sct, and hybrid star pulsations. The γ Dor, δ Sct, and hybrid star pulsations extend asteroseismology to stars slightly more massive (1.4–2.5 M{sub ⊙}) than our Sun. We find 207 γ Dor, 84 δ Sct, and 32 hybrid candidate stars. Many of these stars aremore » cooler than the red edge of the γ Dor instability strip as determined from ground-based observations made before Kepler. A few of our γ Dor candidate stars lie on the hot side of the ground-based γ Dor instability strip. The hybrid candidate stars cover the entire region between 6200 K and the blue edge of the ground-based δ Sct instability strip. None of our candidate stars are hotter than the hot edge of the ground-based δ Sct instability strip. Our discoveries, coupled with the work of others, show that Kepler has discovered over 2000 γ Dor, δ Sct, and hybrid star candidates in the 116 square degree Kepler field of view. We found relatively few variable stars fainter than magnitude 15, which may be because they are far enough away to lie between spiral arms in our Galaxy, where there would be fewer stars.« less

A Kine-chemical Investigation of the AB Dor Moving Group "Stream"

NASA Astrophysics Data System (ADS)

Barenfeld, Scott A.; Bubar, Eric J.; Mamajek, Eric E.; Young, Patrick A.

2013-03-01

The AB Dor Moving Group consists of a "nucleus" of ~10 stars at d ~= 20 pc, along with dozens of purported "stream" members distributed across the sky. We perform a chemical and kinematic analysis of a subsample of AB Dor stream stars to test whether they constitute a physical stellar group. We use the NEMO Galactic kinematic code to investigate the orbits of the stream members, and perform a chemical abundance analysis using high resolution spectra taken with the Magellan Clay 6.5 m telescope. Using a χ2 test with the measured abundances for 10 different elements, we find that only half of the purported AB Dor stream members could possibly constitute a statistically chemically homogeneous sample. Some stream members with three-dimensional velocities were hundreds of parsecs from the AB Dor nucleus ~108 yr ago, and hence were unlikely to share a common origin. We conclude that the published lists of AB Dor moving group stream members are unlikely to represent the dispersed remnant of a single star formation episode. A subsample of the stream stars appears to be both statistically chemically homogeneous and in the vicinity of the AB Dor nucleus at birth. Their mean metallicity is [Fe/H] = 0.02 ± 0.02 dex, which we consider representative for the AB Dor group. Finally, we report a strong lower limit on the age of the AB Dor nucleus of >110 Myr based on the pre-main sequence contraction times for K-type members which have reached the main sequence.

The development and validation of the Dormitory Observation Report: a behavioral rating instrument for juvenile delinquents in residential care.

PubMed

Veneziano, Louis; Veneziano, Carol

2002-09-01

In order to provide an objective measure of problematic behavioral patterns among juvenile delinquents in residential facilities, the Dormitory Observation Report (DOR) was developed. The DOR assesses 11 dimensions of problematic behavioral patterns (e.g., physical assaultiveness, manipulativeness), as well as three dimensions of desirable behavioral patterns expected in an institutional setting (e.g., independent functioning, personal hygiene, care of surroundings). Empirical study regarding the reliability and validity of the DOR are reported, and the results are discussed in terms of the theoretical and practical implications of this instrument. Copyright 2002 Wiley Periodicals, Inc.

32 CFR 77.6 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Counselors shall update into the Defense Outplacement Referral System (DORS) database Service members..., Section 561. (2) Early retirees must provide a copy of their confirmation DORS mini-resume to their... confirmation DORS mini-resume is filed in the permanent document section of the Service record of Service...

Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study).

PubMed

Pastore, Lisa M; Young, Steven L; Manichaikul, Ani; Baker, Valerie L; Wang, Xin Q; Finkelstein, Joel S

2017-01-01

To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group. Case-control study. Academic and private fertility clinics. DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. None. FMR1 CGG repeat lengths. Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele. This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Studies at high frequencies of the 30 Doradus and RCW 57 regions.

NASA Astrophysics Data System (ADS)

Sabalisck, N. S. P.; Abraham, Z.

1990-11-01

The authors present maps of the 30 Dor region at 22 GHz and of the RCW 57 region at 43 GHz. The data are compared with maps at lower frequencies and similar resolutions. In the 30 Dor region 3 supernova remnants of plerionic type were detected: N 1578, MC 78 and MC 89.

A Global Approach to Delta Differential One-Way Range

NASA Technical Reports Server (NTRS)

Border, James S.

2006-01-01

Radio interferometric techniques for measuring spacecraft angular position play a role of increasing importance in today's missions of interplanetary exploration. Several national and international space agencies have or are developing operational systems to support spacecraft navigation using interferometric measurements. NASA's Deep Space Network has provided Delta Differential One-way Range ((Delta)DOR) for this purpose since 1980. Steady improvements in system performance and operability have taken place with accuracy today approaching the 1-nrad level. In this paper the current performance of NASA's (Delta)DOR system is presented. Recent data from the Mars Reconnaissance Orbiter cruise from Earth to Mars are used to illustrate system performance at 8.4 and 32 GHz. Technical feasibility and requirements for combining tracking stations from different agencies to support (Delta)DOR observations are discussed. The advantages of having additional stations to form baselines for measurements are presented. Results of a covariance study for encounter targeting are given for a candidate mission that may need (Delta)DOR data from additional baselines.

Spacecraft-spacecraft very long baseline interferometry for planetary approach navigation

NASA Technical Reports Server (NTRS)

Edwards, Charles D., Jr.; Folkner, William M.; Border, James S.; Wood, Lincoln J.

1991-01-01

The study presents an error budget for Delta differential one-way range (Delta-DOR) measurements between two spacecraft. Such observations, made between a planetary orbiter (or lander) and another spacecraft approaching that planet, would provide a powerful target-relative angular tracking data type for approach navigation. Accuracies of about 5 nrad should be possible for a pair of X-band spacecraft incorporating 40-MHz DOR tone spacings, while accuracies approaching 1 nrad will be possible if the spacecraft incorporate Ka-band downlinks with DOR tone spacings of order 250 MHz. Operational advantages of this data type are discussed, and ground system requirements needed to enable S/C-S/C Delta-DOR observations are outlined. A covariance analysis is presented to examine the potential navigation improvement for this scenario. The results show factors of 2-3 improvement in spacecraft targeting over conventional Doppler, range, and quasar-relative VLBI, along with reduced sensitivity to ephemeris uncertainty and other systematic errors.

A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing, sneezing and straining to assess nerve root compression on MRI.

PubMed

Verwoerd, Annemieke J H; Mens, Jan; El Barzouhi, Abdelilah; Peul, Wilco C; Koes, Bart W; Verhagen, Arianne P

2016-05-01

To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI. Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6-12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio's (DORs) were calculated for the various dichotomization options. The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option 'worsening of leg pain' with a DOR of 2.28 (95 % CI 1.28-4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27-4.90) for the presence of a herniated disc on MRI. Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking.

Results after laparoscopic Heller-Dor operation for esophageal achalasia in 100 consecutive patients.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2009-01-01

The laparoscopic Heller-Dor operation has been the procedure of choice for the treatment of achalasia. However, because the incidence of achalasia is low, reports on the outcome of surgical treatment for achalasia are limited. In this study, the therapeutic results after laparoscopic Heller-Dor operation for achalasia at a single university hospital were evaluated. Between August 1994 and July 2006, 100 consecutive patients underwent laparoscopic Heller-Dor operation. The therapeutic results after laparoscopic Heller-Dor operation were assessed based on complications, operation time, blood loss, postoperative hospital stay, and the standardized questionnaire for satisfaction by telephone or outpatient clinic interview. With respect to perioperative complications, lower esophageal mucosal perforation occurred in 14 patients, but all of them could be suture-obliterated laparoscopically. One patient was converted to laparotomy because of uncontrolled bleeding from the short gastric artery. The mean operative time was 169 minutes, and the mean perioperative blood loss was 22 mL. The median postoperative hospital stay was 7 days. Reflux esophagitis, which was seen in five patients, was treated successfully with a proton pump inhibitor. According to the standardized questionnaire for satisfaction, 77 patients rated their recovery as 'excellent', 17 as 'good', 4 as 'fair', and 2 as 'poor'; thus, the overall success rate was 94%. There were no significant differences in surgical outcomes by morphologic type and severity of esophageal dilatation; however, the success rate deteriorated significantly with progression of the morphologic type. Laparoscopic Heller-Dor operation is a safe and effective surgical treatment for achalasia.

WISEP J004701.06+680352.1: An Intermediate Surface Gravity, Dusty Brown Dwarf in the AB Dor Moving Group

DTIC Science & Technology

2015-02-01

reserved. WISEP J004701.06+680352.1: AN INTERMEDIATE SURFACE GRAVITY, DUSTY BROWN DWARF IN THE AB DOR MOVING GROUP John E. Gizis1,9, Katelyn N...pc. The three-dimensional space mo- tion identifies it as a member of the AB Dor Moving Group, an identification supported by our classification of...SUBTITLE WISEP J004701+680352.1: An Intermediate Surface Gravity, Dusty Brown Dwarf In The AB Dor Moving Group 5a. CONTRACT NUMBER 5b. GRANT NUMBER

Different amounts of ejaculatory activity, a natural rewarding behavior, induce differential mu and delta opioid receptor internalization in the rat's ventral tegmental area.

PubMed

Garduño-Gutiérrez, René; León-Olea, Martha; Rodríguez-Manzo, Gabriela

2013-12-06

Opioid receptors internalize upon specific agonist stimulation. The in vivo significance of receptor internalization is not well established, partly due to the limited in vivo models used to study this phenomenon. Ejaculation promotes endogenous opioid release which activates opioid receptors at the brain, including the mesolimbic system and medial preoptic area. The objective of the present work was to analyze if there was a correlation between the degree of in vivo mu (MOR) and delta opioid receptor (DOR) internalization in the ventral tegmental area and the execution of different amounts of ejaculatory behavior of male rats. To this aim, we analyzed the brains of rats that ejaculated once or six successive times and of sexually exhausted rats with an established sexual inhibition, using immunofluorescence and confocal microscopy. Results showed that MOR and DOR internalization increased as a consequence of ejaculation. There was a relationship between the amount of sexual activity executed and the degree of internalization for MOR, but not for DOR. MOR internalization was larger in rats that ejaculated repeatedly than in animals ejaculating only once. Significant DOR internalization was found only in animals ejaculating once. Changes in MOR, DOR and beta arrestin2 detection, associated to sexual activity, were also found. It is suggested that copulation to satiety might be useful as a model system to study the biological significance of receptor internalization. © 2013 Published by Elsevier B.V.

Receptor Heteromerization Expands the Repertoire of Cannabinoid Signaling in Rodent Neurons

PubMed Central

Rozenfeld, Raphael; Bushlin, Ittai; Gomes, Ivone; Tzavaras, Nikos; Gupta, Achla; Neves, Susana; Battini, Lorenzo; Gusella, G. Luca; Lachmann, Alexander; Ma'ayan, Avi; Blitzer, Robert D.; Devi, Lakshmi A.

2012-01-01

A fundamental question in G protein coupled receptor biology is how a single ligand acting at a specific receptor is able to induce a range of signaling that results in a variety of physiological responses. We focused on Type 1 cannabinoid receptor (CB1R) as a model GPCR involved in a variety of processes spanning from analgesia and euphoria to neuronal development, survival and differentiation. We examined receptor dimerization as a possible mechanism underlying expanded signaling responses by a single ligand and focused on interactions between CB1R and delta opioid receptor (DOR). Using co-immunoprecipitation assays as well as analysis of changes in receptor subcellular localization upon co-expression, we show that CB1R and DOR form receptor heteromers. We find that heteromerization affects receptor signaling since the potency of the CB1R ligand to stimulate G-protein activity is increased in the absence of DOR, suggesting that the decrease in CB1R activity in the presence of DOR could, at least in part, be due to heteromerization. We also find that the decrease in activity is associated with enhanced PLC-dependent recruitment of arrestin3 to the CB1R-DOR complex, suggesting that interaction with DOR enhances arrestin-mediated CB1R desensitization. Additionally, presence of DOR facilitates signaling via a new CB1R-mediated anti-apoptotic pathway leading to enhanced neuronal survival. Taken together, these results support a role for CB1R-DOR heteromerization in diversification of endocannabinoid signaling and highlight the importance of heteromer-directed signal trafficking in enhancing the repertoire of GPCR signaling. PMID:22235275

How a RING finger protein and a steroid hormone control autophagy.

PubMed

Lindmo, Karine; Stenmark, Harald

2006-01-01

Previous work in our laboratory has indicated that the steroid hormone ecdysone triggers programmed autophagy in the fat body of Drosophila larvae by downregulating the class I phosphoinositide 3-kinase (PI3K) pathway. We recently found evidence that Deep orange (Dor), a Drosophila RING finger protein implicated in late-endosomal trafficking, controls ecdysone signaling as well as autolysosome fusion, thus exerting a dual regulation of autophagy. We found that dor mutants are defective in programmed autophagy. The mutant larvae showed impaired upregulation of ecdysone signaling during development, accompanied by a failure to downregulate the PI3K pathway. Downregulation of the PI3K pathway could be restored by feeding the dor mutants with ecdysone. Even though ecdysone signaling and autophagy were impaired in the dor mutants, we detected an accumulation of autophagosomes in dor mutant fat bodies. This could probably be attributed to the failure of autophagosomes to fuse with lysosomes. In this Addendum we review these findings and provide some speculations about how Dor may control both ecdysone signalling and autolysosomal fusion.

Designing Delta-DOR acquisition strategies to determine highly elliptical earth orbits

NASA Technical Reports Server (NTRS)

Frauenholz, R. B.

1986-01-01

Delta-DOR acquisition strategies are designed for use in determining highly elliptical earth orbits. The requirements for a possible flight demonstration are evaluated for the Charged Composition Explorer spacecraft of the Active Magnetospheric Particle Tracer Explorers. The best-performing strategy uses data spanning the view periods of two orthogonal baselines near the same orbit periapse. The rapidly changing viewing geometry yields both angular position and velocity information, but each observation may require a different reference quasar. The Delta-DOR data noise is highly dependent on acquisition geometry, varying several orders of magnitude across the baseline view periods. Strategies are selected to minimize the measurement noise predicted by a theoretical model. Although the CCE transponder is limited by S-band and a small bandwidth, the addition of Delta-DOR to coherent Doppler and range improves the one-sigma apogee position accuracy by more than an order of magnitude. Additional Delta-DOR accuracy improvements possible using dual-frequency (S/X) calibration, increased spanned bandwidth, and water-vapor radiometry are presented for comparison. With these benefits, the residual Delta-DOR data noise is primarily due to quasar position uncertainties.

Role of DOR-β-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis.

PubMed

Zhou, Pi-Qi; Fan, Heng; Hu, Hui; Tang, Qing; Liu, Xing-xing; Zhang, Li-juan; Zhong, Min; Shou, Zhe-xing

2014-12-01

This study was aimed to investigate the role of the delta-opioid receptor (DOR)-β-arrestin1-Bcl-2 signal transduction pathway in the pathogenesis of ulcerative colitis (UC) and the intervention effects of oxymatrine on UC. Forty Sprague-Dawley rats were divided into normal group, model group, oxymatrine-treated group and mesalazine-treated group (n=10 each) at random. The rat UC model was established by intra-colonic injection of trinitrobenzene sulfonic acid in the model group and two treatment groups. The rats in oxymatrine-treated group were subjected to intramuscular injection of oxymatrine [63 mg/(kg·day)] for 15 days, and those in mesalazine-treated group given mesalazine solution [0.5 g/(kg·day)] by gastric lavage for the same days. Animals in normal group and model group were administered 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the rats were sacrificed for the removal of colon tissues. The expression levels of DOR, β-arrestin1 and Bcl-2 were determined in colon tissues by immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR), respectively. It was found that the expression levels of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group as compared with the other groups (P<0.05). They were conspicuously decreased in both mesalazine-treated and oxymatrine-treated groups in contrast to the model group (P<0.05). No statistically significant difference was noted in these indices between mesalazine- and oxymatrinetreated groups (P>0.05). This study indicated that the DOR-β-arrestin1-Bcl-2 signal transduction pathway may participate in the pathogenesis of UC. Moreover, oxymatrine can attenuate the development of UC by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway.

Targeting delta opioid receptors for pain treatment: drugs in phase I and II clinical development.

PubMed

Spahn, Viola; Stein, Christoph

2017-02-01

Opioids are widely used to treat severe pain. Most clinically used opioids activate µ-opioid receptors (MOR). Their ligands induce potent analgesia but also adverse effects. The δ-opioid receptor (DOR) is another member of the opioid receptor family that has been under intense investigation with the aim to avoid MOR-induced side effects. Areas covered: This article reviews DOR ligands which appeared to be promising after preclinical evaluation. A literature search using Pubmed, Cochrane library, ClinicalTrials.gov, EudraCT, AdisInsight database and EBSCO Online Library was conducted. Out of numerous newly synthesized molecules, only few candidates entered phase I and/or II clinical investigation. The publicly accessible results are presented here. Expert opinion: Many compounds showed potent DOR-specific pain inhibition in preclinical studies. ADL5859 and ADL5747 entered clinical trials and successfully passed phase I. However, in phase II studies the primary endpoint (pain reduction) was not met and further investigation was terminated. A third compound, NP2, is in phase II clinical evaluation and results are pending. These findings suggest a potential of DOR ligands according to preclinical studies. Further clinical research and secondary analysis of unpublished data is needed to identify molecules which are useful in humans.

d-Alanine 2, Leucine 5 Enkephaline (DADLE)-mediated DOR activation augments human hUCB-BFs viability subjected to oxidative stress via attenuation of the UPR.

PubMed

Mullick, Madhubanti; Venkatesh, Katari; Sen, Dwaipayan

2017-07-01

Human mesenchymal stem cells (hMSCs) although being potent in repairing injured or ischemic tissues, their success regarding tissue-regenerative approaches are hindered by the paucity in their viability. The elevated levels of reactive oxygen species (ROS) in damaged sites provoke the pernicious effects of donor MSC survival. In the present study, the effect of delta-opioid receptor (DOR) activation on human umbilical cord-blood borne fibroblasts (hUCB-BFs) survival under oxidative stress (H 2 O 2 ) was evaluated. Oxidative stress which is known to trigger pathological conditions of the unfolded protein response (UPR) leads to endoplasmic reticulum stress. Upon its activation by D-Alanine 2, Leucine 5 Enkephaline (DADLE, selective DOR agonist) in hUCB-BFs under oxidative stress, a significant down regulation (~2 folds) of key UPR genes was observed as determined by qPCR, Thioflavin-T protein aggregation assay and western blot analysis. Concomitantly, the oxidative stress-mediated cell-death was ameliorated and the viable-cells' percentage was enhanced following DOR activation. The intracellular ROS production upon H 2 O 2 treatment as determined by CM-H 2 DCFDA staining was repressed, the anti-apoptotic marker Bcl-2 was upregulated along with a significant suppression in the expression levels of pro-apoptotic proteins Bax and Bad upon DOR activation. Upon subsequent treatment with naltrindole, the effects of DADLE-induced cytoprotection were reverted significantly. These results propound the role of DADLE-mediated DOR-activation on improvement of the viability, which might succour successful hUCB-BFs transplants and greatly absolve the inefficacy of tissue-specific engineered transplants. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Constraints on Metal Oxide and Metal Hydroxide Abundances in the Winds of AGB Stars: Potential Detection of FeO in R Dor

NASA Astrophysics Data System (ADS)

Decin, L.; Danilovich, T.; Gobrecht, D.; Plane, J. M. C.; Richards, A. M. S.; Gottlieb, C. A.; Lee, K. L. K.

2018-03-01

Using the Atacama Large Millimeter/submillimeter Array (ALMA), we observed the stellar wind of two oxygen-rich asymptotic giant branch stars, IK Tau and R Dor, between 335 and 362 GHz. One aim was to detect metal oxides and metal hydroxides (AlO, AlOH, FeO, MgO, and MgOH), some of which are thought to be direct precursors of dust nucleation and growth. We report on the potential first detection of FeO (v = 0, Ω = 4, J = 11–10) in R Dor (mass-loss rate \\dot{M} ∼ 1 × 10‑7 M ⊙ yr‑1). The presence of FeO in IK Tau (\\dot{M} ∼ 5 × 10‑6 M ⊙ yr‑1) cannot be confirmed, due to a blend with 29SiS, a molecule that is absent in R Dor. The detection of AlO in R Dor and of AlOH in IK Tau was reported earlier by Decin et al. All other metal oxides and hydroxides, as well as MgS, remain undetected. We derive a column density N(FeO) of 1.1 ± 0.9 × 1015 cm‑2 in R Dor, or a fractional abundance [FeO/H] ∼ 1.5 × 10‑8 accounting for non-local thermodynamic equilibrium effects. The derived fractional abundance [FeO/H] is a factor ∼20 larger than conventional gas-phase chemical-kinetic predictions. This discrepancy may be partly accounted for by the role of vibrationally excited OH in oxidizing Fe, or it may be evidence for other currently unrecognized chemical pathways producing FeO. Assuming a constant fractional abundance w.r.t. H2, the upper limits for the other metals are [MgO/H2] < 5.5 × 10‑10 (R Dor) and <7 × 10‑11 (IK Tau), [MgOH/H2] < 9 × 10‑9 (R Dor) and <1 × 10‑9 (IK Tau), [CaO/H2] < 2.5 × 10‑9 (R Dor) and <1 × 10‑10 (IK Tau), [CaOH/H2] < 6.5 × 10‑9 (R Dor) and <9 × 10‑10 (IK Tau), and [MgS/H2] < 4.5 × 10‑10 (R Dor) and <6 × 10‑11 (IK Tau). The retrieved upper-limit abundances for these latter molecules are in accord with the chemical model predictions.

Assisted Hatching and Intracytoplasmic Sperm Injection are not Associated with Improved Outcomes in ART Cycles for Diminished Ovarian Reserve: An Analysis of US Cycles from 2004–2011

PubMed Central

Butts, Samantha F.; Owen, Carter; Mainigi, Monica; Senapati, Suneeta; Seifer, David B.; Dokras, Anuja

2014-01-01

Objective To investigate the impact of intracytoplasmic sperm injection (ICSI) and assisted hatching (AH) on ART outcomes in cycles with diminished ovarian reserve (DOR) as the primary diagnosis. Design Retrospective cohort study of cycles from the SART-CORS database. Setting NA. Patient(s) A total of 422,949 fresh, non-donor, initial ART cycles of which 8,597 were diagnosed with only elevated FSH and 38,926 were diagnosed with only DOR according to the SART DOR categorization. Intervention(s) None. Main Outcome Measure(s) Live birth and clinical pregnancy rates. Result(s) ICSI and AH were associated with diminished odds of live birth in SART DOR only cycles (AOR, 95% CI 0.88, 0.81–0.96 for ICSI; AOR, 95% CI 0.77 0.71–0.84 for AH). No association between either ICSI or AH in Elevated FSH only cycles was observed. The combination of ICSI and AH resulted in significantly lower odds of live birth in SART DOR only cycles but not in Elevated FSH only cycles. Conclusion(s) In initial ART cycles for which the only indication relates to a diagnosis of diminished ovarian reserve, assisted hatching and ICSI are not associated with improved live birth rates. PMID:25086790

Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility.

PubMed

Nicoloro-SantaBarbara, Jennifer M; Lobel, Marci; Bocca, Silvina; Stelling, James R; Pastore, Lisa M

2017-07-01

To examine the magnitude and predictors of emotional reactions to an infertility diagnosis in two groups of women: those with diminished ovarian reserve (DOR), and those clinically diagnosed with an anatomical cause of infertility (ACI). Cross-sectional study. Academic and private fertility clinics. Women diagnosed with DOR (n = 51) and women diagnosed with ACI (n = 51). Not applicable. Fertility Problem Inventory (infertility distress), Rosenberg Self-Esteem Scale, Health Orientation Scale (emotional reactions to receiving a diagnosis). Women with DOR had statistically significantly higher infertility distress scores than women with ACI and higher scores on subscales assessing distress from social concerns, sexual concerns, and a need for parenthood. In both groups, higher self-esteem was associated with lower infertility distress. Hierarchical multiple regression analyses revealed that for women with DOR and those with ACI lower infertility distress but not self-esteem predicted a more positive emotional reaction toward receiving a fertility diagnosis. Women diagnosed with DOR have greater infertility distress but similar self-esteem and emotional reactions to their diagnosis compared with women who have an anatomical cause of infertility. These results suggest that for both groups distress surrounding infertility itself may influence the way women respond to learning the cause of their infertility. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The choice of optimal antireflux procedure after laparoscopic cardiomyotomy: two decades of clinical experience in one center

PubMed Central

Kiudelis, Mindaugas; Sakalys, Egidijus; Jonaitis, Laimas; Mickevicius, Antanas; Endzinas, Zilvinas

2017-01-01

Introduction Two types of partial wrap are commonly performed in achalasia patients after Heller myotomy: the posterior 270° fundoplication (Toupet) and the anterior 180° fundoplication (Dor). The optimal type of fundoplication (posterior vs. anterior) is still debated. Aim To compare the long-term rates of dysphagia, reflux symptoms and patient satisfaction with current postoperative condition between two fundoplication groups in achalasia treatment. Material and methods Our retrospective study included 97 consecutive patients with achalasia: 37 patients underwent laparoscopic posterior Toupet (270°) fundoplication followed by Heller myotomy (group I); 60 patients underwent laparoscopic anterior partial Dor fundoplication followed by Heller myotomy (group II). Long-term follow-up results included evaluation of dysphagia symptoms, intensity of heartburn and patient satisfaction with current condition. Results Patients in these two groups did not differ according to age, weight, height, postoperative stay or follow-up period. Laparoscopic myotomy with posterior Toupet fundoplication was effective in 89% of patients, while laparoscopic myotomy with anterior Dor was effective in 93% of patients (p > 0.05). 11% of patients after posterior Toupet fundoplication had clinically significant heartburn vs. 35% of patients after anterior Dor fundoplication (p < 0.05). Overall patient satisfaction with current condition was 88%, with no significant difference between the groups. Conclusions According to our study results, the two laparoscopic techniques were similarly effective in reducing achalasia symptoms, but postoperative clinical manifestation of heartburn is significantly more frequent after anterior Dor fundoplication (35% vs. 11%). The majority of patients (88%) were satisfied with operation outcomes. PMID:29062443

Ultrasound for Distal Forearm Fracture: A Systematic Review and Diagnostic Meta-Analysis

PubMed Central

Douma-den Hamer, Djoke; Blanker, Marco H.; Edens, Mireille A.; Buijteweg, Lonneke N.; Boomsma, Martijn F.; van Helden, Sven H.; Mauritz, Gert-Jan

2016-01-01

Study Objective To determine the diagnostic accuracy of ultrasound for detecting distal forearm fractures. Methods A systematic review and diagnostic meta-analysis was performed according to the PRISMA statement. We searched MEDLINE, Web of Science and the Cochrane Library from inception to September 2015. All prospective studies of the diagnostic accuracy of ultrasound versus radiography as the reference standard were included. We excluded studies with a retrospective design and those with evidence of verification bias. We assessed the methodological quality of the included studies with the QUADAS-2 tool. We performed a meta-analysis of studies evaluating ultrasound to calculate the pooled sensitivity and specificity with 95% confidence intervals (CI95%) using a bivariate model with random effects. Subgroup and sensitivity analysis were used to examine the effect of methodological differences and other study characteristics. Results Out of 867 publications we included 16 studies with 1,204 patients and 641 fractures. The pooled test characteristics for ultrasound were: sensitivity 97% (CI95% 93–99%), specificity 95% (CI95% 89–98%), positive likelihood ratio (LR) 20.0 (8.5–47.2) and negative LR 0.03 (0.01–0.08). The corresponding pooled diagnostic odds ratio (DOR) was 667 (142–3,133). Apparent differences were shown for method of viewing, with the 6-view method showing higher specificity, positive LR, and DOR, compared to the 4-view method. Conclusion The present meta-analysis showed that ultrasound has a high accuracy for the diagnosis of distal forearm fractures in children when used by proper viewing method. Based on this, ultrasound should be considered a reliable alternative, which has the advantages of being radiation free. PMID:27196439

The influence of monovalent cations on trimeric G protein G(i)1α activity in HEK293 cells stably expressing DOR-G(i)1α (Cys(351)-Ile(351)) fusion protein.

PubMed

Vošahlíková, M; Svoboda, P

2011-01-01

The effect of monovalent cations on trimeric G protein G(i)1α was measured at equimolar concentration of chloride anion in pertussis-toxin (PTX)-treated HEK293 cells stably expressing PTX-insensitive DOR- G(i)1α (Cys(351)-Ile(351)) fusion protein by high-affinity [(35)S]GTPgammaS binding assay. The high basal level of binding was detected in absence of DOR agonist and monovalent ions and this high level was inhibited with the order of: Na(+) > K(+) > Li(+). The first significant inhibition was detected at 1 mM NaCl. The inhibition by monovalent ions was reversed by increasing concentrations of DOR agonist DADLE. The maximum DADLE response was also highest for sodium and decreased in the order of: Na(+) > K(+) ~ Li(+). Our data indicate i) an inherently high activity of trimeric G protein G(i)1α when expressed within DOR- G(i)1α fusion protein and determined in the absence of monovalent cations, ii) preferential sensitivity of DOR- G(i)1alpha to sodium as far as maximum of agonist response is involved.

In vivo determination of the direction of rotation and moment-angle relationship of individual elbow muscles.

PubMed

Zhang, L; Butler, J; Nishida, T; Nuber, G; Huang, H; Rymer, W Z

1998-10-01

The direction of rotation (DOR) of individual elbow muscles, defined as the direction in which a muscle rotates the forearm relative to the upper arm in three-dimensional space, was studied in vivo as a function of elbow flexion and forearm rotation. Electrical stimulation was used to activate an individual muscle selectively, and the resultant flexion-extension, supination-pronation, and varus-valgus moments were used to determine the DOR. Furthermore, multi-axis moment-angle relationships of individual muscles were determined by stimulating the muscle at a constant submaximal level across different joint positions, which was assumed to result in a constant level of muscle activation. The muscles generate significant moments about axes other than flexion-extension, which is potentially important for actively controlling joint movement and maintaining stability about all axes. Both the muscle DOR and the multi axis moments vary with the joint position systematically. Variations of the DOR and moment-angle relationship across muscle twitches of different amplitudes in a subject were small, while there were considerable variations between subjects.

Dissecting Diffuse X-ray Emission in 30 Doradus with T-ReX

NASA Astrophysics Data System (ADS)

Townsley, Leisa K.; Broos, Patrick

2017-08-01

30 Doradus (the Tarantula Nebula) offers us a microscope on starburst astrophysics, having endured 25 Myrs of the birth and death of the most massive stars known. Across 30 Dor's 250-pc extent, stellar winds and supernovae have carved its ISM into an amazing display of arcs, pillars, and bubbles. For over 40 years, we have also known that 30 Dor is a bright X-ray emitter, so its familiar stars and cold ISM structures suffer irradiation by multi-million-degree plasmas. The 2-Ms Chandra X-ray Visionary Project ``The Tarantula -- Revealed by X-rays'' (T-ReX) exploits Chandra's fine spatial resolution and the ACIS-I field of view to study ISM interfaces on 1--10 pc scales across the entire 30 Dor complex. Here we give preliminary results from ongoing analyses of these data, focusing on the diffuse X-ray emission. Massive star winds and cavity supernovae over the millenia have contributed to a broad mix of X-ray-emitting plasmas and absorbing columns, showing that 30 Dor's hot ISM is just as complex and confusing as that seen at colder temperatures.

Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers.

PubMed

Carvalho, Ana Flávia Machado de; Feitosa, Maura Cristina Porto; Coelho, Nayana Pinheiro Machado de Freitas; Rebêlo, Veruska Cronemberger Nogueira; Castro, Juçara Gonçalves de; Sousa, Patrícia Regina Gomes de; Feitosa, Valrian Campos; Arisawa, Emilia Angela Lo Schiavo

2016-01-01

To evaluate the effects of low-level laser therapy isolated and associated with Calendula officinalis oil in treating diabetic foot ulcers. An experimental, randomized, controlled, prospective, interventional clinical case study using a quantitative approach. The sample consisted of 32 diabetic patients of both genders. Participants were randomly divided into four groups. Doppler Ultrasound evaluation of the Ankle-Brachial Index, brief pain inventory and analog pain scale were performed at baseline and after 30 days. Reduced pain was observed in the Low-level laser therapy and Low-level laser therapy associated with Essential Fatty Acids groups (p<0.01). Regarding the Ankle-Brachial Index and Doppler Ultrasound, all groups remained stable. By analyzing lesion area reduction, Low-level laser therapy associated with Essential fatty acids group showed a significance of p=0.0032, and the Low-level laser therapy group showed p=0.0428. Low-level laser therapy, performed alone or associated with the Calendula officinalis oil was effective in relieving pain and accelerating the tissue repair process of diabetic foot. Avaliar os efeitos da Terapia a Laser de Baixa Intensidade isolada e associada ao óleo de Calendula officinalis no reparo de úlceras em pé diabético. Estudo de caso clínico, experimental, controlado, randomizado, prospectivo, intervencional, de caráter quantitativo. A amostra foi composta de 32 pacientes diabéticos, de ambos os gêneros. Os participantes foram distribuídos aleatoriamente em quatro grupos. Ultrassom Doppler, avaliação do Índice Tornozelo-Braquial, Inventário breve de dor e escala de dor analógica foram realizados no início e após 30 dias. Houve redução da dor nos grupos Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa intensidade associada aos Ácidos Graxos Essenciais, com p<0,01. Quanto ao Índice Tornozelo-Braquial e Ultrassom Doppler, todos os grupos mantiveram-se estáveis. Na análise da redução de área da lesão, o grupo Terapia a Laser de Baixa Intensidade associada aos Ácidos Graxos Essenciais apresentou uma significância p=0,0032, e o grupo Terapia a Laser de Baixa Intensidade, p=0,0428. A Terapia a Laser de Baixa Intensidade, realizada tanto isoladamente quanto associada ao óleo de Calendula officinalis, foi eficaz no alívio da dor e na aceleração do processo de reparo tecidual de pé diabético.

A dual function for Deep orange in programmed autophagy in the Drosophila melanogaster fat body.

PubMed

Lindmo, Karine; Simonsen, Anne; Brech, Andreas; Finley, Kim; Rusten, Tor Erik; Stenmark, Harald

2006-07-01

Lysosomal degradation of cytoplasm by way of autophagy is essential for cellular amino acid homeostasis and for tissue remodeling. In insects such as Drosophila, autophagy is developmentally upregulated in the larval fat body prior to metamorphosis. Here, autophagy is induced by the hormone ecdysone through down-regulation of the autophagy-suppressive phosphoinositide 3-kinase (PI3K) signaling pathway. In yeast, Vps18 and other members of the HOPS complex have been found essential for autophagic degradation. In Drosophila, the Vps18 homologue Deep orange (Dor) has previously been shown to mediate fusion of multivesicular endosomes with lysosomes. A requirement of Dor for ecdysone-mediated chromosome puffing has also been reported. In the present report, we have tested the hypothesis that Dor may control programmed autophagy at the level of ecdysone signaling as well as by mediating autophagosome-to-lysosome fusion. We show that dor mutants are defective in programmed autophagy and provide evidence that autophagy is blocked at two levels. First, PI3K activity was not down-regulated correctly in dor larvae, which correlated with a decrease in ecdysone reporter activity. The down-regulation of PI3K activity was restored by feeding ecdysone to the mutant larvae. Second, neither exogenous ecdysone nor overexpression of PTEN, a silencer of PI3K signaling, restored fusion of autophagosomes with lysosomes in the fat body of dor mutants. These results indicate that Dor controls autophagy indirectly, via ecdysone signaling, as well as directly, via autolysosomal fusion.

Delta-opioid receptor expression in the ventral tegmental area protects against elevated alcohol consumption.

PubMed

Margolis, Elyssa B; Fields, Howard L; Hjelmstad, Gregory O; Mitchell, Jennifer M

2008-11-26

Alcoholism is a complex and debilitating syndrome affecting approximately 140 million people worldwide. However, not everyone who consumes ethanol develops abuse, raising the possibility that some individuals have a protective mechanism that inhibits elevated alcohol consumption. We tested the hypothesis that the delta-opioid receptor (DOR) plays such a protective role. Here we show that DOR activity in the ventral tegmental area (VTA) robustly decreases ethanol consumption in rats and that these effects depend on baseline ethanol consumption. Intra-VTA microinjection of the DOR agonist DPDPE decreases drinking, particularly in low-drinking animals. Furthermore, VTA microinjection of the DOR selective antagonist TIPP-Psi increases drinking in low, but not high, drinkers and this increase is blocked by comicroinjection of the GABA(A) antagonist bicuculline. Using electrophysiological techniques we found that in VTA brain slices from drinking rats DPDPE presynaptically inhibits GABA(A) receptor mediated IPSCs in low drinkers, but not in high drinkers or naive animals, most likely through activation of DORs on GABA terminals. This DOR-mediated inhibition of IPSCs also correlates inversely with behavioral correlates of anxiety measured in the elevated plus maze. In contrast, presynaptic inhibition of VTA GABA(A) IPSCs by the mu-opioid receptor agonist DAMGO is significantly reduced in both high- and low-drinking rats (<30%) compared with age-matched nondrinking controls (>70%). Together, our findings demonstrate the protective nature of VTA DORs and identify an important new target for therapeutic intervention for alcoholism.

Petrogenetic and geodynamic origin of the Neoarchean Doré Lake Complex, Abitibi subprovince, Superior Province, Canada

NASA Astrophysics Data System (ADS)

Polat, Ali; Frei, Robert; Longstaffe, Fred J.; Woods, Ryan

2018-04-01

The Neoarchean (ca. 2728 Ma) anorthosite-bearing Doré Lake Complex in the northeastern Abitibi subprovince, Quebec, was emplaced into an association of intra-oceanic tholeiitic basalts and gabbros known as the Obatogamau Formation. The Obatogamau Formation constitutes the lower part of the Roy Group, which is composed of two cycles of tholeiitic-to-calc-alkaline volcanic and volcaniclastic rocks, siliciclastic and chemical sedimentary rocks, and layered mafic-to-ultramafic sills. In this study, we report major and trace element results, and Nd, Sr, Pb and O isotope data for anorthosites, leucogabbros, gabbros and mafic dykes from the Doré Lake Complex and spatially associated basalts and gabbros of the Obatogamau Formation to assess their petrogenetic origin and geodynamic setting. Field and petrographic observations indicate that the Doré Lake Complex and associated volcanic rocks underwent extensive metamorphic alteration under greenschist facies conditions, resulting in widespread epidotization (20-40%) and chloritization (10-40%) of many rock types. Plagioclase recrystallized mainly to anorthite and albite endmembers, erasing intermediate compositions. Metamorphic alteration also led to the mobilization of many elements (e.g., LILE and transition metals) and to significant disturbance of the Rb-Sr and U-Pb isotope systems, resulting in 1935 ± 150 and 3326 ± 270 Ma errorchron ages, respectively. The Sm-Nd isotope system was less disturbed, yielding an errorchron age of 2624 ± 160 Ma. On many binary major and trace element diagrams, the least altered anorthosites and leucogabbros, and the gabbros and mafic dykes of the Doré Lake Complex plot in separate fields, signifying the presence of two distinct magma types in the complex. The gabbros and mafic dykes in the Doré Lake Complex share the geochemical characteristics of tholeiitic basalts and gabbros in the Obatogamau Formation, suggesting a possible genetic link between the two rock associations. Initial ɛNd (+2.6 to +5.0) and δ18O (+6.1 to +7.9‰) values for the Doré Lake Complex and gabbros of the Obatogamau Formation (ɛNd = +2.8 to +4.0; δ18O = +7.3 to 8.0‰) are consistent with depleted mantle sources. All rock types in the Doré Lake Complex and the Roy Group share the trace element characteristics of modern arc magmas, suggesting a suprasubduction zone setting for these two lithological associations. On the basis of regional geology and geochemical data, we suggest that the Doré Lake Complex and the Obatogamau Formation represent a dismembered fragment of a suture zone, like many Phanerozoic ophiolites, resulting from closure of a back-arc basin between 2703 and 2690 Ma.

Plan for the Future Direction of DORS' Schools: Illinois Children's School and Rehabilitation Center, Illinois School for the Deaf, and Illinois School for the Visually Impaired.

ERIC Educational Resources Information Center

Illinois State Dept. of Rehabilitation Services, Springfield.

The report is an outgrowth of a study of three residential schools operated by the Illinois Department of Rehabilitation Services (DORS). The schools are the Illinois Children's School and Rehabilitation Center (ICSRC), for severely physically handicapped or health-impaired, the Illinois School for the Deaf, and the Illinois School for the…

Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene.

PubMed

Ansonoff, Michael A; Wen, Ting; Pintar, John E

2010-01-01

Over the past several years substantial evidence has documented that opioid receptor homo- and heterodimers form in cell lines expressing one or more of the opioid receptors. We used opioid receptor knockout mice to determine whether in vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors changed following knockout of specific opioid receptors. Using displacement of the general opioid ligand diprenorphine, we observed that occupancy or knockout of the DOR-1 gene increases the binding density of kappa1 receptors and eliminates kappa2 receptors in crude membrane preparations while the total density of kappa opioid binding sites is unchanged. Further, the analgesic potency of U69,593 in cumulative dose response curves is enhanced in mice lacking the DOR-1 gene. These results demonstrate that the DOR-1 gene is required for the expression of the kappa2 opioid receptor subtype and are consistent with the possibility that a KOR-1/DOR-1 heterodimer mediates kappa2 pharmacology.

The γ Dor stars as revealed by Kepler: A key to reveal deep-layer rotation in A and F stars

NASA Astrophysics Data System (ADS)

Salmon, S. J. A. J.; Ouazzani, R.-M.; Antoci, V.; Bedding, T. R.; Murphy, S. J.

2017-09-01

The γ Dor pulsating stars present high-order gravity modes, which make them important targets in the intermediate-and low-mass main-sequence region of the Hertzsprung-Russell diagram. Whilst we have only access to rotation in the envelope of the Sun, the g modes of γ Dor stars can in principle deliver us constraints on the inner layers. With the puzzling discovery of unexpectedly low rotation rates in the core of red giants, the γ Dor stars appear now as unique targets to explore internal angular momentum transport in the progenitors of red giants. Yet, the γ Dor pulsations remain hard to detect from the ground for their periods are close to 1 day. While the CoRoT space mission first revealed intriguing frequency spectra, the almost uninterrupted 4-year photometry from the Kepler mission eventually shed a new light on them. It revealed regularities in the spectra, expected to bear signature of physical processes, including rotation, in the shear layers close to the convective core. We present here the first results of our effort to derive exploitable seismic diagnosis for mid- to fast rotators among γ Dor stars. We confirm their potential to explore the rotation history of this early phase of stellar evolution.

Improving healthy eating in families with a toddler at risk for overweight: A cluster randomized controlled trial

PubMed Central

Hammer, Lawrence D.; Huffman, Lynne C.; Mascola, Anthony; Bryson, Susan W.; Danaher, Carol

2012-01-01

Objective To ascertain whether a parent education program based on Satter’s division of responsibility in feeding children (DOR) is effective in enhancing parent/child feeding interactions for children with an overweight/obese parent. The primary hypothesis was that the intervention would decrease parental pressure to eat. Methods Sixty-two families with a child aged 2–4 years with at least one overweight/obese parent were randomly allocated using a cluster design to either the DOR intervention or a control group. The control group focused on increasing family consumption of healthy foods and activity levels, and enhancing child sleep duration. The primary outcome was parent pressure on their child to eat. Results The DOR intervention was superior to the control group in reducing pressure to eat. Two moderators of pressure to eat were found: disinhibition of eating and hunger. DOR group parents irrespective of disinhibition levels lowered pressure to eat whereas control group parents with low disinhibition increased pressure to eat. There were similar findings for hunger. Gender moderated restrictive feeding with DOR parents lowering restriction more than the control group in girls only. Conclusion The DOR intervention was more effective in reducing parent pressure to eat and food restriction (in girls only) than the control group. PMID:22947882

Opiate antagonist prevents μ- and δ-opiate receptor dimerization to facilitate ability of agonist to control ethanol-altered natural killer cell functions and mammary tumor growth.

PubMed

Sarkar, Dipak K; Sengupta, Amitabha; Zhang, Changqing; Boyadjieva, Nadka; Murugan, Sengottuvelan

2012-05-11

In the natural killer (NK) cells, δ-opiate receptor (DOR) and μ-opioid receptor (MOR) interact in a feedback manner to regulate cytolytic function with an unknown mechanism. Using RNK16 cells, a rat NK cell line, we show that MOR and DOR monomer and dimer proteins existed in these cells and that chronic treatment with a receptor antagonist reduced protein levels of the targeted receptor but increased levels of opposing receptor monomer and homodimer. The opposing receptor-enhancing effects of MOR and DOR antagonists were abolished following receptor gene knockdown by siRNA. Ethanol treatment increased MOR and DOR heterodimers while it decreased the cellular levels of MOR and DOR monomers and homodimers. The opioid receptor homodimerization was associated with an increased receptor binding, and heterodimerization was associated with a decreased receptor binding and the production of cytotoxic factors. Similarly, in vivo, opioid receptor dimerization, ligand binding of receptors, and cell function in immune cells were promoted by chronic treatment with an opiate antagonist but suppressed by chronic ethanol feeding. Additionally, a combined treatment of an MOR antagonist and a DOR agonist was able to reverse the immune suppressive effect of ethanol and reduce the growth and progression of mammary tumors in rats. These data identify a role of receptor dimerization in the mechanism of DOR and MOR feedback interaction in NK cells, and they further elucidate the potential for the use of a combined opioid antagonist and agonist therapy for the treatment of immune incompetence and cancer and alcohol-related diseases.

A dual function for Deep orange in programmed autophagy in the Drosophila melanogaster fat body

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindmo, Karine; Simonsen, Anne; Brech, Andreas

2006-07-01

Lysosomal degradation of cytoplasm by way of autophagy is essential for cellular amino acid homeostasis and for tissue remodeling. In insects such as Drosophila, autophagy is developmentally upregulated in the larval fat body prior to metamorphosis. Here, autophagy is induced by the hormone ecdysone through down-regulation of the autophagy-suppressive phosphoinositide 3-kinase (PI3K) signaling pathway. In yeast, Vps18 and other members of the HOPS complex have been found essential for autophagic degradation. In Drosophila, the Vps18 homologue Deep orange (Dor) has previously been shown to mediate fusion of multivesicular endosomes with lysosomes. A requirement of Dor for ecdysone-mediated chromosome puffing hasmore » also been reported. In the present report, we have tested the hypothesis that Dor may control programmed autophagy at the level of ecdysone signaling as well as by mediating autophagosome-to-lysosome fusion. We show that dor mutants are defective in programmed autophagy and provide evidence that autophagy is blocked at two levels. First, PI3K activity was not down-regulated correctly in dor larvae, which correlated with a decrease in ecdysone reporter activity. The down-regulation of PI3K activity was restored by feeding ecdysone to the mutant larvae. Second, neither exogenous ecdysone nor overexpression of PTEN, a silencer of PI3K signaling, restored fusion of autophagosomes with lysosomes in the fat body of dor mutants. These results indicate that Dor controls autophagy indirectly, via ecdysone signaling, as well as directly, via autolysosomal fusion.« less

Symptomatic outcome following laparoscopic Heller's cardiomyotomy with Dor fundoplication versus laparoscopic Heller's cardiomyotomy with angle of His accentuation: results of a randomized controlled trial.

PubMed

Balakrishna, Pavithra; Parshad, Rajinder; Rohila, Jitender; Saraya, Anoop; Makharia, Govind; Sharma, Raju

2015-08-01

The type of anti-reflux procedure to be used as an adjunct to laparoscopic Heller's cardiomyotomy (LHCM) in Achalasia cardia is controversial. We compared Angle of His accentuation and Dor fundoplication in a randomized controlled trial. From May 2010 to October 2013, 62 patients undergoing LHCM were randomized to receive either Dor fundoplication (Dor group) or Angle of His accentuation (AOH group) as an anti-reflux procedure. Symptomatic outcome was evaluated using modified Mellow and Pinkas scale for dysphagia and modified DeMeester's score for regurgitation and heartburn. Achalasia-specific quality-of-life (QOL) questionnaire was used to assess quality of life. The primary outcome was symptomatic relief and the secondary outcome was postoperative heartburn. Statistical analysis was done using SPSS software. All the procedures were completed laparoscopically with no mortality. Morbidity was similar in the two groups (6.4 %). Median operative time was higher in Dor group (170 vs 130 min). At a median follow-up of 21 months relief of dysphagia, regurgitation, and heartburn was seen in 87, 90.3, and 90.3 % patients in Dor group versus 93.5, 96.7, and 77.4 % in AOH group patients with significant improvement in symptom scores. Improvement was similar in both groups with no statistically significant difference in the symptom scores (p = 0.48 for dysphagia, p = 0.37 for regurgitation, and p = 0.19 for heartburn). The QOL improved in both groups [62.3 to 12.3 (p = 0.02) in Dor group and 63.9-13 (p = 0.02) in AOH group] with no statistically significant difference between the two groups (p = 0.96). There was no statistically significant difference in the postoperative heartburn between the two groups (p = 0.19). Laparoscopic Heller's cardiomyotomy with either Angle of His accentuation or Dor fundoplication leads to similar improvement in symptoms and quality of life.

Malaria rapid diagnostic test evaluation at private retail pharmacies in Kumasi, Ghana.

PubMed

Audu, Rauf; Anto, Berko Panyin; Koffuor, George Asumeng; Abruquah, Akua Afriyie; Buabeng, Kwame Ohene

2016-01-01

Malaria rapid diagnostic test (MRDT) provides a good alternative to malaria microscopy diagnosis, particularly in resource-constrained settings. This study therefore evaluated MRDT in private retail pharmacies (PRPs) as a critical step in community case malaria management. In a prospective, cross-over, validation survey at six PRPs in the Ashanti Region of Ghana, 1200 patients presenting with fever in the preceding 48 h were sampled. Fingerstick blood samples were collected for preparation of thick and thin blood films for malaria microscopy. Categorized patients (600 each) went through the processes of MRDT or presumptive diagnosis (PD) of malaria. The malaria disease prevalence of the study area was established. Selectivity (Se), specificity (Sp), positive predictive value (PPV) along with false discovery rate (FDR), and negative predictive value (NPV) along with the false omission rate (FOR), and diagnostic odds ratio (DOR) of MRDT were then calculated. While 43.0% tested positive using the MRDT, 57.0% tested negative. However, 62.0% MRDT-negative patients in addition to all the MRDT positives were given artemether-lumefantrine. Of those diagnosed by PD, 98.2% were prescribed with an antimalarial (microscopy however confirmed only 70.3% as positive). Se and Sp of the MRDT were 90.68 ± 11.18% and 98.68 ± 1.19%, respectively. Malaria prevalence was estimated to be 43.3%. PPV was 98.0%, FDR was 2.0%, NPV was 98.0%, FOR was 2.0%, and DOR was 2366.43. Results highlighted good performance of MRDTs at PRPs which could inform decision toward its implementation.

Ability of King's College Criteria and Model for End-Stage Liver Disease Scores to Predict Mortality of Patients With Acute Liver Failure: A Meta-analysis.

PubMed

McPhail, Mark J W; Farne, Hugo; Senvar, Naz; Wendon, Julia A; Bernal, William

2016-04-01

Several prognostic factors are used to identify patients with acute liver failure (ALF) who require emergency liver transplantation. We performed a meta-analysis to determine the accuracy of King's College criteria (KCC) versus the model for end-stage liver disease (MELD) scores in predicting hospital mortality among patients with ALF. We performed a systematic search of the literature for articles published from 2001 through 2015 that compared the accuracy of the KCC with MELD scores in predicting hospital mortality in patients with ALF. We identified 23 studies (comprising 2153 patients) and assessed the quality of data, and then performed a meta-analysis of pooled sensitivity and specificity values, diagnostic odds ratios (DORs), and summary receiver operating characteristic curves. Subgroups analyzed included study quality, era, location (Europe vs non-Europe), and size; ALF etiology (acetaminophen-associated ALF [AALF] vs nonassociated [NAALF]); and whether or not the study included patients who underwent liver transplantation and if the study center was also a transplant center. The DOR for the KCC was 5.3 (95% confidence interval [CI], 3.7-7.6; 57% heterogeneity) and the DOR for MELD score was 7.0 (95% CI, 5.1-9.7; 48% heterogeneity), so the MELD score and KCC are comparable in overall accuracy. The summary area under the receiver operating characteristic curve values was 0.76 for the KCC and 0.78 for MELD scores. The KCC identified patients with AALF who died with 58% sensitivity (95% CI, 51%-65%) and 89% specificity (95% CI, 85%-93%), whereas MELD scores identified patients with AALF who died with 80% sensitivity (95% CI, 74%-86%) and 53% specificity (95% CI, 47%-59%). The KCC predicted hospital mortality in patients with NAALF with 58% sensitivity (95% CI, 54%-63%) and 74% specificity (95% CI, 69%-78%), whereas MELD scores predicted hospital mortality in patients with NAALF with 76% sensitivity (95% CI, 72%-80%) and 73% specificity (95% CI, 69%-78%). In patients with AALF, the KCC's DOR was 10.4 (95% CI, 4.9-22.1) and the MELD score's DOR was 6.6 (95% CI, 2.1-20.2). In patients with NAALF, the KCC's DOR was 4.16 (95% CI, 2.34-7.40) and the MELD score's DOR was 8.42 (95% CI, 5.98-11.88). Based on a meta-analysis of studies, the KCC more accurately predicts hospital mortality among patients with AALF, whereas MELD scores more accurately predict mortality among patients with NAALF. However, there is significant heterogeneity among studies and neither system is optimal for all patients. Given the importance of specificity in decision making for listing for emergency liver transplantation, MELD scores should not replace the KCC in predicting hospital mortality of patients with AALF, but could have a role for NAALF. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

The criterion and discriminant validity of the Referential Thinking (REF) scale.

PubMed

Startup, Mike; Sakrouge, Rebecca; Mason, Oliver J

2010-03-01

The Referential Thinking (REF) scale was designed to be a comprehensive self-report measure of both simple and guilty ideas of reference in the general population. One aim of the present study was to test the proposed interpretations of REF scores by comparing REF scores with ratings of delusions among psychotic patients. A 2nd aim was to test whether REF scores are better predicted by the severity of patients' delusions of reference (DoRs) than by the severity of their auditory verbal hallucinations (AVHs), thus supporting the scores' ability to discriminate between proneness to the 2 different symptoms. The REF scale was completed by 56 healthy controls and 53 acutely psychotic patients. The severity of the patients' DoRs and AVHs were assessed in structured clinical interviews. REF scores differed significantly not only between the patients and controls but also between patients with versus without DoRs. REF scores correlated significantly with the severity of the patients' DoRs but not their AVHs. The interpretation of REF scores as a measure of proneness to simple and guilty ideas of reference was supported. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Current Research on Opioid Receptor Function

PubMed Central

Feng, Yuan; He, Xiaozhou; Yang, Yilin; Chao, Dongman; Lazarus, Lawrence H.; Xia, Ying

2012-01-01

The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes is still unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of membrane ionic homeostasis, cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders. In some species, they play an essential role in hibernation. One of the most exciting findings of the past decade is the opioid-receptor, especially DOR, mediated neuroprotection and cardioprotection. The up-regulation of DOR expression and DOR activation increase the neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers (depending on stress duration and severity) different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of homeostasis and increased pro-survival signaling (e.g., PKC-ERK-Bcl 2) and anti-oxidative capacity. In the heart, PKC and KATP channels are involved in the opioid receptor-mediated cardioprotection. The DOR-mediated neuroprotection and cardioprotection have the potential to significantly alter the clinical pharmacology in terms of prevention and treatment of life-threatening conditions like stroke and myocardial infarction. The main purpose of this article is to review the recent work done on opioids and their receptor functions. It shall provide an informative reference for better understanding the opioid system and further elucidation of the opioid receptor function from a physiological and pharmacological point of view. PMID:22204322

The ultraviolet extinction properties of the 30 Dor Nebula

NASA Astrophysics Data System (ADS)

De Marchi, Guido; Panagia, Nino

2018-01-01

Recent investigation of the extinction law in 30 Dor and the Tarantula Nebula, at optical and near infrared wavelengths, has revealed a ratio of total to selective extinction RV=AV/E(B-V) of about 4.5. This indicates a larger proportion of large grains than in the Galactic diffuse interstellar medium. Possible origins include coalescence of small grains, grain growth, selective destruction of small grains, and fresh injection of large grains. From a study of the ultraviolet extinction properties of three Wolf-Rayet stars in 30 Dor (R 139, R 140, R 145), observed with the International Ultraviolet Explorer, we show that the excess of large grains does not come at the expense of small grains, which are still present. Fresh injection of large grains by supernova explosions appears to be the dominant mechanism.

Enhanced dispersion of repolarization explains increased arrhythmogenesis in severe versus therapeutic hypothermia.

PubMed

Piktel, Joseph S; Jeyaraj, Darwin; Said, Tamer H; Rosenbaum, David S; Wilson, Lance D

2011-02-01

Hypothermia is proarrhythmic, and, as the use of therapeutic hypothermia (TH) increases, it is critically important to understand the electrophysiological effects of hypothermia on cardiac myocytes and arrhythmia substrates. We tested the hypothesis that hypothermia-enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrhythmogenesis in hypothermia. In addition, we investigated whether the degree of hypothermia, the rate of temperature change, and cooling versus rewarming would alter hypothermia-induced arrhythmia substrates. Optical action potentials were recorded from cells spanning the transmural wall of canine left ventricular wedge preparations at baseline (36°C), during cooling and during rewarming. Electrophysiological parameters were examined while varying the depth of hypothermia. On cooling to 26°C, DOR increased from 26±4 ms to 93±18 ms (P=0.021); conduction velocity decreased from 35±5 cm/s to 22±5 cm/s (P=0.010). On rewarming to 36°C, DOR remained prolonged, whereas conduction velocity returned to baseline. Conduction block and reentry was observed in all severe hypothermia preparations. Ventricular fibrillation/ventricular tachycardia was seen more during rewarming (4/5) versus cooling (2/6). In TH (n=7), cooling to 32°C mildly increased DOR (31±6 to 50±9, P=0.012), with return to baseline on rewarming and was associated with decreased arrhythmia susceptibility. Increased rate of cooling did not further enhance DOR or arrhythmogenesis. Hypothermia amplifies DOR and is a mechanism for arrhythmogenesis. DOR is directly dependent on the depth of cooling and rewarming. This provides insight into the clinical observation of a low incidence of arrhythmias in TH and has implications for protocols for the clinical application of TH.

Fundoplication After Heller Myotomy: A Retrospective Comparison Between Nissen and Dor

PubMed Central

Cuttitta, Antonello; Tancredi, Antonio; Andriulli, Angelo; De Santo, Ermelinda; Fontana, Andrea; Pellegrini, Fabio; Scaramuzzi, Roberto; Scaramuzzi, Gerardo

2011-01-01

Objective: A retrospective comparison between Nissen and Dor fundoplication after laparoscopic Heller myotomy for achalasia. Materials and Methods: From 1998 to 2004 a first group of 48 patients underwent Heller myotomy and Nissen fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D group). Some patients received a previous endoscopic treatment with pneumatic dilatation or endoscopic injection of botulinum toxin that provided them only a temporary clinical benefit. Changes in clinical and instrumental examinations from before to after surgery were evaluated in all patients. Clinical evaluation was carried out using a modified DeMeester symptom score system. Results: Dor fundoplication treatment reduced both dysphagia and regurgitation severity scores significantly more than Nissen fundoplication (p<0.0001). Indeed, the incidence of dysphagia was significantly higher in patients treated with floppy-Nissen than in those treated with Dor fundoplication: by defining dysphagia as a DeMeester score equal to 3 (arbitrary cut-off), at the end of follow-up dysphagia occurred in 17.65% and 0% (p=0.037) of patients belonging to the H+N and H+D groups, respectively. Conclusion: Heller myotomy followed by Dor fundoplication is a safe and valuable treatment. The procedure showed a lower incidence of postoperative dysphagia versus Nissen fundoplication and a negligible incidence of postoperative GERD in a long-term postoperative follow-up. PMID:25610181

Fundoplication after heller myotomy: a retrospective comparison between nissen and dor.

PubMed

Cuttitta, Antonello; Tancredi, Antonio; Andriulli, Angelo; De Santo, Ermelinda; Fontana, Andrea; Pellegrini, Fabio; Scaramuzzi, Roberto; Scaramuzzi, Gerardo

2011-12-01

A retrospective comparison between Nissen and Dor fundoplication after laparoscopic Heller myotomy for achalasia. From 1998 to 2004 a first group of 48 patients underwent Heller myotomy and Nissen fundoplication for idiopathic achalasia (H+N group). From 2004 to 2010 a second group of 40 patients underwent Heller myotomy followed by Dor fundoplication (H+D group). Some patients received a previous endoscopic treatment with pneumatic dilatation or endoscopic injection of botulinum toxin that provided them only a temporary clinical benefit. Changes in clinical and instrumental examinations from before to after surgery were evaluated in all patients. Clinical evaluation was carried out using a modified DeMeester symptom score system. Dor fundoplication treatment reduced both dysphagia and regurgitation severity scores significantly more than Nissen fundoplication (p<0.0001). Indeed, the incidence of dysphagia was significantly higher in patients treated with floppy-Nissen than in those treated with Dor fundoplication: by defining dysphagia as a DeMeester score equal to 3 (arbitrary cut-off), at the end of follow-up dysphagia occurred in 17.65% and 0% (p=0.037) of patients belonging to the H+N and H+D groups, respectively. Heller myotomy followed by Dor fundoplication is a safe and valuable treatment. The procedure showed a lower incidence of postoperative dysphagia versus Nissen fundoplication and a negligible incidence of postoperative GERD in a long-term postoperative follow-up.

CCDS concept paper: Delta-DOR

NASA Technical Reports Server (NTRS)

Berry, David S.; Broder, James S.

2005-01-01

This Concept Paper proposes the development of Consultative Committee for Space Data Systemes (CCSDS) standards for the deep space navigation technique known as 'delta-DOR' (Delta Differential One-Way Ranging).

CCSDS concept paper: Delta-DOR

NASA Technical Reports Server (NTRS)

Berry, David S.; Border, James S.

2005-01-01

This Concept Paper proposes the development of Consultative Committee for Space Data Systems (CCSDS) standards for the deep space navigation technique known as 'delta-DOR' (Delta Differential One-Way Ranging).

The DNA Data Bank of Japan launches a new resource, the DDBJ Omics Archive of functional genomics experiments.

PubMed

Kodama, Yuichi; Mashima, Jun; Kaminuma, Eli; Gojobori, Takashi; Ogasawara, Osamu; Takagi, Toshihisa; Okubo, Kousaku; Nakamura, Yasukazu

2012-01-01

The DNA Data Bank of Japan (DDBJ; http://www.ddbj.nig.ac.jp) maintains and provides archival, retrieval and analytical resources for biological information. The central DDBJ resource consists of public, open-access nucleotide sequence databases including raw sequence reads, assembly information and functional annotation. Database content is exchanged with EBI and NCBI within the framework of the International Nucleotide Sequence Database Collaboration (INSDC). In 2011, DDBJ launched two new resources: the 'DDBJ Omics Archive' (DOR; http://trace.ddbj.nig.ac.jp/dor) and BioProject (http://trace.ddbj.nig.ac.jp/bioproject). DOR is an archival database of functional genomics data generated by microarray and highly parallel new generation sequencers. Data are exchanged between the ArrayExpress at EBI and DOR in the common MAGE-TAB format. BioProject provides an organizational framework to access metadata about research projects and the data from the projects that are deposited into different databases. In this article, we describe major changes and improvements introduced to the DDBJ services, and the launch of two new resources: DOR and BioProject.

Influence of gold content on copper oxidation from silver-gold-copper alloys

NASA Astrophysics Data System (ADS)

Swinbourne, D. R.; Barbante, G. G.; Strahan, A.

1996-10-01

In the final stages of the smelting of copper anode slimes, a silver alloy, known as “doré,” is produced. Oxidation refining is used to remove copper since this element interferes with subsequent electroparting of the small amounts of gold and platinum group metals in the doré. The gold content of doré can be greatly increased by gold scrap additions and this may affect the minimum achievable copper content of doré. In this work, silver-gold-copper alloys were oxidized by injecting pure oxygen at 1100 °C in the absence of any slag cover. For the gold contents expected in practice, the equilibrium copper content of the doré did not increase significantly as the gold content increased. However, at the other extreme of composition, the equilibrium copper content was a very strong function of the silver content of the gold bullion. The activity coefficient of copper in silver-gold alloys was calculated and compared to those predicted from a ternary subregular solution model of the system Ag-Au-Cu. Satisfactory agreement was found.

Laparoscopic heller myotomy for achalasia cardia-initial experience in a teaching institute.

PubMed

Kaman, Lileswar; Iqbal, Javid; Kochhar, Rakesh; Sinha, Saroj

2013-10-01

Laparoscopic Heller cardiomyotomy and Dor fundoplication is the surgical procedure of choice for esophageal achalasia. The aim of our study was to investigate the clinical outcome and safety of laparoscopic Heller-Dor procedure performed by using Hook electrocautery and as a teaching module for advanced laparoscopic surgery. Between January 2005 and December 2010, 25 consecutive patients with achalasia underwent laparoscopic Heller-Dor operation by a single surgeon. All the patients received upper gastrointestinal series (barium swallow), esophagogastroscopy, and esophageal manometry to exclude esophageal carcinoma and to confirm the diagnosis. All the patients were operated by laparoscopic modified Heller myotomy with Dor fundoplication by using hook electrocautery. Among 25 operated patients, 14 were male and 11 were female with a median age of 43 years (range 18-72 years). The mean operative time was 93.3 min (range 50-50 min), the mean operative blood loss was 90 ml (range 40-200 ml), the median time to oral feeding was 2 days (2-4 days), and the median hospital stay was 4 days (4-7 days). There was no conversion to open surgery. Intraoperative mucosal perforation was encountered in three patients and was repaired in all of them by laparoscopic suture. All the patients had an uneventful recovery without postoperative complication and had excellent clinical response (96 %) during follow-up. Laparoscopic Heller-Dor operation using hook electrocautery is safe, inexpensive, and effective treatment for achalasia which is useful for teaching and training surgical residents in advanced laparoscopic surgery.

Prolonged duration of response in lenvatinib responders with thyroid cancer.

PubMed

Gianoukakis, Andrew G; Dutcus, Corina E; Batty, Nicolas; Guo, Matthew; Baig, Mahadi

2018-06-01

We present an updated analysis of lenvatinib in radioiodine-refractory differentiated thyroid cancer (RR-DTC) with new duration of response (DOR) data unavailable for the primary analysis. In this randomized, double-blind, multicenter, placebo-controlled phase 3 study, patients ≥18 years old with measurable, pathologically confirmed RR-DTC with independent radiologic confirmation of disease progression within the previous 13 months were randomized 2:1 to oral lenvatinib 24 mg/day or placebo. The main outcome measures for this analysis are DOR and progression-free survival (PFS). The median DOR for all lenvatinib responders (patients with complete or partial responses; objective response rate: 60.2%; 95% confidence interval (CI) 54.2-66.1) was 30.0 months (95% CI 18.4-36.7) and was generally similar across subgroups. DOR was shorter in patients with greater disease burden and with brain and liver metastases. Updated median PFS was longer in the overall lenvatinib group vs placebo (19.4 vs 3.7 months; hazard ratio (HR) 0.24; 99% CI 0.17-0.35; nominal P  < 0.0001). In lenvatinib responders, median PFS was 33.1 months (95% CI 27.8-44.6) vs 7.9 months (95% CI 5.8-10.7) in non-responders. The median DOR of 30.0 months seen with patients who achieved complete or partial responses with lenvatinib (60.2%) demonstrates that lenvatinib responders can have prolonged, durable and clinically meaningful responses. Prolonged PFS (33.1 months) was also observed in these lenvatinib responders. © 2018 The authors.

Synthesis and evaluation of 4-substituted piperidines and piperazines as balanced affinity μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist ligands.

PubMed

Bender, Aaron M; Clark, Mary J; Agius, Michael P; Traynor, John R; Mosberg, Henry I

2014-01-15

In this letter, we describe a series of 4-substituted piperidine and piperazine compounds based on tetrahydroquinoline 1, a compound that shows balanced, low nanomolar binding affinity for the mu opioid receptor (MOR) and the delta opioid receptor (DOR). We have shown that by changing the length and flexibility profile of the side chain in this position, binding affinity is improved at both receptors by a significant degree. Furthermore, several of the compounds described herein display good efficacy at MOR, while simultaneously displaying DOR antagonism. The MOR agonist/DOR antagonist has shown promise in the reduction of negative side effects displayed by selective MOR agonists, namely the development of dependence and tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diaphragm and Lung Ultrasound to Predict Weaning Outcome: Systematic Review and Meta-Analysis.

PubMed

Llamas-Álvarez, Ana M; Tenza-Lozano, Eva M; Latour-Pérez, Jaime

2017-12-01

Deciding the optimal timing for extubation in patients who are mechanically ventilated can be challenging, and traditional weaning predictor tools are not very accurate. The aim of this systematic review and meta-analysis was to assess the accuracy of lung and diaphragm ultrasound for predicting weaning outcomes in critically ill adults. MEDLINE, the Cochrane Library, Web of Science, Scopus, LILACS, Teseo, Tesis Doctorales en Red, and OpenGrey were searched, and the bibliographies of relevant studies were reviewed. Two researchers independently selected studies that met the inclusion criteria and assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The summary receiver-operating characteristic curve and pooled diagnostic OR (DOR) were estimated by using a bivariate random effects analysis. Sources of heterogeneity were explored by using predefined subgroup analyses and bivariate meta-regression. Nineteen studies involving 1,071 people were included in the study. For diaphragm thickening fraction, the area under the summary receiver-operating characteristic curve was 0.87, and DOR was 21 (95% CI, 11-40). Regarding diaphragmatic excursion, pooled sensitivity was 75% (95% CI, 65-85); pooled specificity, 75% (95% CI, 60-85); and DOR, 10 (95% CI, 4-24). For lung ultrasound, the area under the summary receiver-operating characteristic curve was 0.77, and DOR was 38 (95% CI, 7-198). Based on bivariate meta-regression analysis, a significantly higher specificity for diaphragm thickening fraction and higher sensitivity for diaphragmatic excursion was detected in studies with applicability concerns. Lung and diaphragm ultrasound can help predict weaning outcome, but its accuracy may vary depending on the patient subpopulation. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Endogenous opioids regulate moment-to-moment neuronal communication and excitability.

PubMed

Winters, Bryony L; Gregoriou, Gabrielle C; Kissiwaa, Sarah A; Wells, Oliver A; Medagoda, Danashi I; Hermes, Sam M; Burford, Neil T; Alt, Andrew; Aicher, Sue A; Bagley, Elena E

2017-03-22

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear.

Patients with endometriosis using positive coping strategies have less depression, stress and pelvic pain.

PubMed

Donatti, Lilian; Ramos, Denise Gimenez; Andres, Marina de Paula; Passman, Leigh Jonathan; Podgaec, Sérgio

2017-01-01

To determine the correlations between coping strategies, depression, stress levels and pain perception in patients with endometriosis. This prospective and exploratory study included 171 women undergoing treatment for endometriosis between April and August 2014. The questionnaires used were Brief COPE, Beck Depression Inventory, Lipp's Stress Symptom Inventory for Adults and Visual Analogue Scale. Clinical data were collected from electronic medical records. Patients with endometriosis who used positive coping strategies had better adaptation to stress (p<0.004) and less depression (p<0.004). The presence and intensity of depression, stress and acyclic pelvic pain were directly associated (p<0.05). The intensity of dysmenorrhea was associated with the degree of depression (p<0.001), whereas acyclic pelvic pain was associated with the degree of depression (p<0.001), stress level (p<0.001) and stress type (p<0.001). We found a positive association between coping, depression levels, type and levels of stress and pain intensity in patients with endometriosis. The use of maladaptive coping strategies focused on emotion is correlated with increase in depression and stress. Observar a correlação entre estratégias de enfrentamento, depressão, níveis de estresse e percepção de dor em pacientes com endometriose. Estudo prospectivo e exploratório, que incluiu 171 mulheres em tratamento por endometriose entre abril e agosto de 2014. Foram utilizadas as escalas: COPE Breve, Inventário de Depressão de Beck, Inventário de Sintomas de Stress para Adultos de Lipp e a Escala Visual Analógica. Os dados clínicos foram coletados do prontuário eletrônico. Pacientes com endometriose que utilizaram estratégias positivas de enfrentamento apresentaram melhor adaptação ao estresse (p<0,004) e menos depressão (p<0,004). A presença e a intensidade da depressão, do estresse e da dor pélvica estiveram diretamente associadas (p<0,05). A intensidade da dismenorreia foi associada com o grau de depressão (p<0,001), enquanto a intensidade da dor pélvica acíclica esteve associada com o grau de depressão (p<0,001), nível de estresse (p<0,001) e tipo de estresse (p<0,001). Houve associação positiva entre coping, níveis de depressão, tipo e níveis de estresse e intensidade da dor nas pacientes com endometriose. A utilização de estratégias de coping desadaptativa focada na emoção está correlacionada com o aumento da depressão e do estresse.

30 Dor B - A supernova remnant in a star formation region

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Kennicutt, Robert C., Jr.; Schommer, Robert A.; Laff, Joshua

1992-01-01

The supernova remnant 30 Dor B is embedded in an H II region around the OB association LH 99, and has been suggested to be a Crab-type remnant. To determine the spatial extent and kinematic properties of this supernova remnant, long-slit echelle observations were obtained in the H-alpha and forbidden N II lines, along with imaging Fabry-Perot observations in the H-alpha line. It is found that 30 Dor B is partially obscured by a dark cloud with which the supernova remnant also interacts. The size of 30 Dor B is much larger than previously thought, making it much older than the Crab Nebula. If the progenitor of the supernova was formed coevally with LH 99, then it would have been more massive than the O3 members of the OB association.

Making structural sense of dimerization interfaces of delta opioid receptor homodimers.

PubMed

Johnston, Jennifer M; Aburi, Mahalaxmi; Provasi, Davide; Bortolato, Andrea; Urizar, Eneko; Lambert, Nevin A; Javitch, Jonathan A; Filizola, Marta

2011-03-15

Opioid receptors, like other members of the G protein-coupled receptor (GPCR) family, have been shown to associate to form dimers and/or oligomers at the plasma membrane. Whether this association is stable or transient is not known. Recent compelling evidence suggests that at least some GPCRs rapidly associate and dissociate. We have recently calculated binding affinities from free energy estimates to predict transient association between mouse delta opioid receptor (DOR) protomers at a symmetric interface involving the fourth transmembrane (TM4) helix (herein termed "4" dimer). Here we present disulfide cross-linking experiments with DOR constructs with cysteines substituted at the extracellular ends of TM4 or TM5 that confirm the formation of DOR complexes involving these helices. Our results are consistent with the involvement of TM4 and/or TM5 at the DOR homodimer interface, but possibly with differing association propensities. Coarse-grained (CG) well-tempered metadynamics simulations of two different dimeric arrangements of DOR involving TM4 alone or with TM5 (herein termed "4/5" dimer) in an explicit lipid-water environment confirmed the presence of two structurally and energetically similar configurations of the 4 dimer, as previously assessed by umbrella sampling calculations, and revealed a single energetic minimum of the 4/5 dimer. Additional CG umbrella sampling simulations of the 4/5 dimer indicated that the strength of association between DOR protomers varies depending on the protein region at the interface, with the 4 dimer being more stable than the 4/5 dimer.

The role of δ-opioid receptors in learning and memory underlying the development of addiction.

PubMed

Klenowski, Paul; Morgan, Michael; Bartlett, Selena E

2015-01-01

Opioids are important endogenous ligands that exist in both invertebrates and vertebrates and signal by activation of opioid receptors to produce analgesia and reward or pleasure. The μ-opioid receptor is the best known of the opioid receptors and mediates the acute analgesic effects of opiates, while the δ-opioid receptor (DOR) has been less well studied and has been linked to effects that follow from chronic use of opiates such as stress, inflammation and anxiety. Recently, DORs have been shown to play an essential role in emotions and increasing evidence points to a role in learning actions and outcomes. The process of learning and memory in addiction has been proposed to involve strengthening of specific brain circuits when a drug is paired with a context or environment. The DOR is highly expressed in the hippocampus, amygdala, striatum and other basal ganglia structures known to participate in learning and memory. In this review, we will focus on the role of the DOR and its potential role in learning and memory underlying the development of addiction. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

Supraspinal inhibitory effects of chimeric peptide MCRT on gastrointestinal motility in mice.

PubMed

He, Chunbo; Li, Hailan; Zhang, Jing; Kang, Yanping; Jia, Fang; Dong, Shouliang; Zhou, Lanxia

2017-09-01

Chimeric peptide MCRT, based on morphiceptin and PFRTic-NH 2 , was a bifunctional ligand of μ- and δ-opioid receptors (MOR-DOR) and produced potent analgesia in tail-withdrawal test. The study focused on the supraspinal effects of morphiceptin, PFRTic-NH 2 and MCRT on gastrointestinal motility. Moreover, opioid receptor antagonists, naloxone (non-selective), cyprodime (MOR selective) and naltrindole (DOR selective) were utilized to explore the mechanisms. Intracerebroventricular administration was achieved via the implanted cannula. Gastric emptying and intestinal transit were measured to evaluate gastrointestinal motility. (1) At supraspinal level, morphiceptin, PFRTic-NH 2 and MCRT significantly decreased gastric emptying and intestinal transit; (2) MCRT at 1 nmol/mouse, far higher than its analgesic dose (ED 50  = 29.8 pmol/mouse), failed to regulate the gastrointestinal motility; (3) MCRT-induced gastrointestinal dysfunction could be completely blocked by naloxone and naltrindole, but not affected by cyprodime. (1) Morphiceptin and PFRTic-NH 2 played important roles in the regulation of gastrointestinal motility; (2) MCRT possessed higher bioactivity of pain relief than gastrointestinal regulation, suggesting its promising analgesic property; (3) MCRT-induced motility disorders were sensitive to DOR but not to MOR blockade, indicating the pain-relieving specificity of speculated MOR subtype or splice variant or MOR-DOR heterodimer. © 2017 Royal Pharmaceutical Society.

The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy

PubMed Central

Devillé, Walter LJM; Yzermans, Joris C; van Duijn, Nico P; Bezemer, P Dick; van der Windt, Daniëlle AWM; Bouter, Lex M

2004-01-01

Background Many studies have evaluated the accuracy of dipstick tests as rapid detectors of bacteriuria and urinary tract infections (UTI). The lack of an adequate explanation for the heterogeneity of the dipstick accuracy stimulates an ongoing debate. The objective of the present meta-analysis was to summarise the available evidence on the diagnostic accuracy of the urine dipstick test, taking into account various pre-defined potential sources of heterogeneity. Methods Literature from 1990 through 1999 was searched in Medline and Embase, and by reference tracking. Selected publications should be concerned with the diagnosis of bacteriuria or urinary tract infections, investigate the use of dipstick tests for nitrites and/or leukocyte esterase, and present empirical data. A checklist was used to assess methodological quality. Results 70 publications were included. Accuracy of nitrites was high in pregnant women (Diagnostic Odds Ratio = 165) and elderly people (DOR = 108). Positive predictive values were ≥80% in elderly and in family medicine. Accuracy of leukocyte-esterase was high in studies in urology patients (DOR = 276). Sensitivities were highest in family medicine (86%). Negative predictive values were high in both tests in all patient groups and settings, except for in family medicine. The combination of both test results showed an important increase in sensitivity. Accuracy was high in studies in urology patients (DOR = 52), in children (DOR = 46), and if clinical information was present (DOR = 28). Sensitivity was highest in studies carried out in family medicine (90%). Predictive values of combinations of positive test results were low in all other situations. Conclusions Overall, this review demonstrates that the urine dipstick test alone seems to be useful in all populations to exclude the presence of infection if the results of both nitrites and leukocyte-esterase are negative. Sensitivities of the combination of both tests vary between 68 and 88% in different patient groups, but positive test results have to be confirmed. Although the combination of positive test results is very sensitive in family practice, the usefulness of the dipstick test alone to rule in infection remains doubtful, even with high pre-test probabilities. PMID:15175113

Masses and activity of AB Doradus B a/b. The age of the AB Dor quadruple system revisited

NASA Astrophysics Data System (ADS)

Wolter, U.; Czesla, S.; Fuhrmeister, B.; Robrade, J.; Engels, D.; Wieringa, M.; Schmitt, J. H. M. M.

2014-10-01

We present a multiwavelength study of the close binary AB Dor Ba/b (Rst137B). Our study comprises astrometric orbit measurements, optical spectroscopy, X-ray and radio observations. Using all available adaptive optics images of AB Dor B taken with VLT/NACO from 2004 to 2009, we tightly constrain its orbital period to 360.6 ± 1.5 days. We present the first orbital solution of Rst 137B and estimate the combined mass of AB Dor Ba+b as 0.69+0.02-0.24 M⊙, slightly exceeding previous estimates based on IR photometry. Our determined orbital inclination of Rst 137B is close to the axial inclination of AB Dor A inferred from Doppler imaging. Our VLT/UVES spectra yield high rotational velocities of ≥30 km s-1 for both components Ba and Bb, in accord with previous measurements, which corresponds to rotation periods significantly shorter than one day. Our combined spectral model, using PHOENIX spectra, yields an effective temperature of 3310 ± 50 K for the primary and approximately 60 K less for the secondary. The optical spectra presumably cover a chromospheric flare and show that at least one component of Rst 137B is significantly active. Activity and weak variations are also found in our simultaneous XMM-Newton observations, while our ATCA radio data yield constant fluxes at the level of previous measurements. Using evolutionary models, our newly determined stellar parameters confirm that the age of Rst 137B is between 50 and 100 Myr. Based on observations collected at the European Southern Observatory, Paranal, Chile, 383.D-1002(A) and the ESO Science Archive Facility. Using data obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member states and NASA. Using data obtained with the Australia Telescope Compact Array (ATCA) operated by the Commonwealth Scientific and Industrial Research Organisation (CSIRO).

Spacecraft-spacecraft very long baseline interferometry. Part 1: Error modeling and observable accuracy

NASA Technical Reports Server (NTRS)

Edwards, C. D., Jr.; Border, J. S.

1992-01-01

In Part 1 of this two-part article, an error budget is presented for Earth-based delta differential one-way range (delta DOR) measurements between two spacecraft. Such observations, made between a planetary orbiter (or lander) and another spacecraft approaching that planet, would provide a powerful target-relative angular tracking data type for approach navigation. Accuracies of better than 5 nrad should be possible for a pair of spacecraft with 8.4-GHz downlinks, incorporating 40-MHz DOR tone spacings, while accuracies approaching 1 nrad will be possible if the spacecraft incorporate 32-GHz downlinks with DOR tone spacing on the order of 250 MHz; these accuracies will be available for the last few weeks or months of planetary approach for typical Earth-Mars trajectories. Operational advantages of this data type are discussed, and ground system requirements needed to enable spacecraft-spacecraft delta DOR observations are outlined. This tracking technique could be demonstrated during the final approach phase of the Mars '94 mission, using Mars Observer as the in-orbit reference spacecraft, if the Russian spacecraft includes an 8.4-GHz downlink incorporating DOR tones. Part 2 of this article will present an analysis of predicted targeting accuracy for this scenario.

Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

PubMed

Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

2015-05-01

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Predictors of hope among women with breast cancer during chemotherapy.

PubMed

Balsanelli, Alessandra Cristina Sartore; Grossi, Sonia Aurora Alves

2016-01-01

Identifying the predictors of hope in patients with breast cancer during chemotherapy treatment. A prospective longitudinal study. The sample was composed of 122 women who responded to the instruments of hope, anxiety and depression, coping, fatigue, religiosity and self-esteem in the first and last cycle of chemotherapy. These variables were used in adjusting the logistic regression model that characterized multivariate statistics, allowing identification of predictor variables. The increase of hope at the end of chemotherapy treatment was statistically significant (p = 0.012). The delay in undergoing treatment from the onset of breast cancer symptoms, Karnofsky Performance Status, depression, self-esteem and pain were characterized as factors being associated to hope by univariate analysis. Among the variables analyzed, pain was the only predicting factor of hope. Pain was the predicting factor in this sample. Hope increased during treatment and revealed the following associated factors: Karnofsky Performance Status, delay in starting the treatment, depression, self-esteem and pain. This study brought forth a multidisciplinary contribution, allowing for understanding the factors that can influence hope and presenting support to nursing care. The data evidenced conditions of improvement or worsening of hope, which requires interdisciplinary attention in Oncology. Identificar os fatores preditores da esperança nas pacientes com câncer de mama em tratamento quimioterápico. Estudo prospectivo longitudinal. A amostra foi de 122 mulheres que responderam aos instrumentos de esperança, ansiedade e depressão, coping, fadiga, religiosidade e autoestima no primeiro e no último ciclo de quimioterapia. Essas variáveis foram utilizadas no ajuste do modelo de regressão logística que caracterizou a estatística multivariada permitindo a identificação das variáveis preditoras. O aumento da esperança ao final do tratamento quimioterápico foi estatisticamente significante (p = 0,012). A demora na realização do tratamento desde o início dos sintomas do câncer de mama, o Karnofsky Performance Status, a depressão, a autoestima e a dor foram caracterizadas como fatores associados à esperança pela análise univariada. Dentre as variáveis analisadas, a dor apresentou-se como o único fator preditor da esperança. A dor foi o fator preditor nesta amostra. A esperança aumentou durante o tratamento e revelou os fatores associados: Karnofsky Performance Status, demora no início do tratamento, depressão, autoestima e dor. Este estudo trouxe uma contribuição multidisciplinar, permitiu compreender os fatores que podem influenciar a esperança e apresentou subsídios à assistência de enfermagem. Os dados evidenciaram condições de melhora ou agravamento da esperança, o que requer atenção interdisciplinar em Oncologia.

Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis.

PubMed

Chalco, Juan P; Huicho, Luis; Alamo, Carlos; Carreazo, Nilton Y; Bada, Carlos A

2005-12-08

Anaemia is highly prevalent in children of developing countries. It is associated with impaired physical growth and mental development. Palmar pallor is recommended at primary level for diagnosing it, on the basis of few studies. The objective of the study was to systematically assess the accuracy of clinical signs in the diagnosis of anaemia in children. A systematic review on the accuracy of clinical signs of anaemia in children. We performed an Internet search in various databases and an additional reference tracking. Studies had to be on performance of clinical signs in the diagnosis of anaemia, using haemoglobin as the gold standard. We calculated pooled diagnostic likelihood ratios (LR's) and odds ratios (DOR's) for each clinical sign at different haemoglobin thresholds. Eleven articles met the inclusion criteria. Most studies were performed in Africa, in children underfive. Chi-square test for proportions and Cochran Q for DOR's and for LR's showed heterogeneity. Type of observer and haemoglobin technique influenced the results. Pooling was done using the random effects model. Pooled DOR at haemoglobin <11 g/dL was 4.3 (95% CI 2.6-7.2) for palmar pallor, 3.7 (2.3-5.9) for conjunctival pallor, and 3.4 (1.8-6.3) for nailbed pallor. DOR's and LR's were slightly better for nailbed pallor at all other haemoglobin thresholds. The accuracy did not vary substantially after excluding outliers. This meta-analysis did not document a highly accurate clinical sign of anaemia. In view of poor performance of clinical signs, universal iron supplementation may be an adequate control strategy in high prevalence areas. Further well-designed studies are needed in settings other than Africa. They should assess inter-observer variation, performance of combined clinical signs, phenotypic differences, and different degrees of anaemia.

Toupet versus Dor as a procedure to prevent reflux after cardiomyotomy for achalasia: results of a randomised clinical trial.

PubMed

Kumagai, Koshi; Kjellin, Ann; Tsai, Jon A; Thorell, Anders; Granqvist, Staffan; Lundell, Lars; Håkanson, Bengt

2014-01-01

The optimal anti-reflux procedure after Heller cardiomyotomy for oesophageal achalasia remains unclear. The most commonly used procedure is the anterior partial fundoplication according to Dor, although during recent years the posterior counterpart (Toupet) has become popular. Patients with newly diagnosed achalasia and referred for cardiomyotomy were randomised to receive either an anterior or partial posterior fundoplication following a classical cardiomyotomy. The effect of surgery was assessed during the first postoperative year by Eckardt scores, EORTC QLQ-OES18 scores and HRQL questionnaires. Timed barium oesophagogram (TBO) and ambulatory 24-h pH monitoring were performed to determine oesophageal emptying and the degree of reflux control, respectively. Forty-two patients were randomised into Dor (n = 20) and Toupet (n = 22) groups. Eckardt scores improved dramatically with both procedures, but the EORTC QLQ-OES18 (functional scales) scores revealed significantly better relative improvements in the Toupet group compared to the Dor repair (P = 0.044). Corresponding advantages in favour of Toupet were observed postoperatively in the percentage of oesophageal emptying at TBO (P = 0.011 in height and P = 0.018 in area), an effect not observed in the Dor group. There were no other significant differences recorded between the study groups concerning HRQL evaluations and objective assessment of gastro-oesophageal acid reflux. A partial posterior fundoplication after cardiomyotomy seems to achieve more improvement in oesophageal emptying and EORTC QLQ-OES18 functional scale scores than the anterior fundoplication. Otherwise no differences between the two anti-reflux repairs were noted. ClinicalTrials.gov Identifier: NCT01933373. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Signs and symptoms of Group A versus Non-Group A strep throat: A meta-analysis.

PubMed

Thai, Thuy N; Dale, Ariella P; Ebell, Mark H

2017-10-13

Both non-Group A streptococcal (non-GAS) pharyngitis and Group A streptococcal (GAS) pharyngitis are commonly found in patients with sore throat. It is not known whether or not they present with similar signs and symptoms compared to patients with non-streptococcal pharyngitis. MEDLINE was searched for prospective studies that reported throat culture for both GAS and non-GAS as a reference standard, and reported at least one sign, symptom, or the Centor score. Summary estimates of sensitivity, specificity, likelihood ratios (LR+ and LR-), and diagnostic odds ratios (DOR) were calculated using a bivariate random effects model. Summary receiver operating characteristic (ROC) curves were created for key signs and symptoms. Eight studies met our inclusion criteria. Tonsillar exudate had the highest LR+ for both GAS and non-GAS pharyngitis (1.53 versus 1.71). The confidence intervals of sensitivity, LR+, LR-, and DOR for all signs, symptoms, and the Centor score between two groups overlapped, with the relative difference between sensitivities within 15% for arthralgia or myalgia, fever, injected throat, tonsillar enlargement, and tonsillar exudate. Larger differences in sensitivities were observed for sore throat, cervical adenopathy, and lack of a cough, although the difference for lack of a cough largely due to a single outlier. Signs and symptoms of patients with GAS and non-GAS pharyngitis are generally similar. No signs or symptoms clearly distinguish GAS from non-GAS infection. Further work is needed to determine whether Group C streptococcus is a pathogen that should be treated. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Selection of radio sources for Venus balloon-Pathfinder Delta-DOR navigation at 1.7 GHz

NASA Technical Reports Server (NTRS)

Liewer, K. M

1986-01-01

In order to increase the success rate of the Delta-DOR (Delta-Differential One-way Range) VLBI navigational support for the French-Soviet Venus Balloon and Halley Pathfinder projects, forty-four extragalactic radio sources were observed in advance of these projects to determine which were suitable for use as reference sources. Of these forty-four radio sources taken from the existing JPL radio source catalogue, thirty-six were determined to be of sufficient strength for use in Delta-DOR VLBI navigation.

Secret Lives of Cepheids: beta Dor as a Test of Cepheid X-ray Heating Mechanisms

NASA Astrophysics Data System (ADS)

Engle, Scott

2017-09-01

We propose two 40 ksec phase-constrained ACIS-I observations of the 9.8 day Cepheid beta Dor. This will fill its uncharted 0.9-0.2 phase gap to confirm and define (Lx, kT) its pulsation-driven X-ray variations and help identify the mechanism (shocks, magnetic fields, turbulent dynamos) responsible, in complement to our recent confirmation of pulsation-induced X-ray variations from delta Cep (Engle et al. 2017). Beta Dor has different properties than delta Cep (P = 9.8/5.4d; R = 61/44Rsun), and the proposed visits are crucial to combine with existing X-ray and FUV data and test the X-ray heating mechanisms. This program is the culmination of several years of work, and the resulting nearly complete phase coverage of beta Dor makes this Cepheid the timeliest and most promising target.

[Efficacy comparison of laparoscopic Nissen, Toupet and Dor fundoplication in the treatment of hiatal hernia complicated with gastroesophageal reflux disease].

PubMed

Su, Fuzeng; Zhang, Cheng; Ke, Limu; Wang, Zhi; Li, Yiliang; Li, Huiling; Du, Zhi

2016-09-25

To compare the efficacy and safety among laparoscopic Nissen, Toupet and Dor fundoplication in the treatment of hiatal hernia complicated with gastroesophageal reflux disease (GERD). Clinical data of 276 patients of hiatal hernia complicated with GERD undergoing operation in our hospital from December 2012 to January 2015 were retrospectively analyzed, including 149 patients of laparoscopic Nissen fundoplication (Nissen group), 41 of laparoscopic Toupet fundoplication (Toupet group), and 86 patients of laparoscopic Dor fundoplication (Dor group). Esophageal reflux status, esophageal manometry, GERD Q rating scale, and postoperative recovery were compare among the three groups. Reflux status was improved significantly in the three groups after operation(all P<0.05),except that the efficacy in reducing reflux episodes and reflux longest time was not obvious in Toupet group(P>0.05). There were no significant differences in postoperative reflux time, acid reflux time ratio, reflux longest time ratio, DeMeester score among the three groups (all P>0.05). Pairwise comparison showed that Dor group was significantly better than Toupet group in reducing the number of reflux episode(14.36±10.58 vs. 29.83±19.71) and long-reflux (0.64±0.21 vs. 6.20±3.48)(both P<0.05), but Nissen group was better than these two groups in reducing the number of long-reflux (0.38±0.16, P<0.05). As compared to pre-operation, the postoperative esophageal sphincter pressure and residual pressure increased significantly, and the relaxation rate reduced significantly (all P<0.05), while the episode of ineffective swallowing increased significantly in Toupet group (11.25±2.04 vs. 6.36±3.26, P<0.05). The contrast in esophageal manometry between Toupet and Dor group showed that Dor group was better than Toupet group in the recovery of lower esophageal sphincter pressure (mean resting breathing) [(20.69±13.95) mmHg vs.(12.91±6.89) mmHg] and the decrease of ineffective swallowing [9.15±6.44 vs. 11.25±2.04](both P<0.05), while such results of Dor group were similar to Nissen group[(19.87±10.40) mmHg, 6.15±2.95, all P>0.05]. The GERD Q scores were significantly decreased after operation in 3 groups(Nissen group:10.94±2.20 vs.7.41±1.43, t=11.667, P=0.001; Toupet group: 10.91±2.02 vs.7.18±1.33, t=5.109, P=0.005; Dor group: 10.69±1.69 vs. 7.10±1.30, t=7.610, P=0.002). There was no significant difference in GERD Q scores among three groups (F=1.465, P=0.207). The operative time, blood loss, hospital stay and complications were not significantly different among 3 groups (all P>0.05). Follow-up period was 12-51 months (median 19 months), and no significant difference in recurrence was found [Nissen group: 2 cases (1.3%), Toupet group: 1 case (2.4%), Dor group: 1 case (1.2%), χ 2 =0.363, P=0.834]. It is safe and feasible for these three laparoscopic fundoplications to the treatment of hiatal hernia complicated with GERD. But laparoscopic Nissen and Dor fundoplication are better than Toupet fundoplication in reducing the number of reflux episodes, suppressing long reflux, increasing lower esophageal sphincter pressure (mean resting respiration) and decreasing the incidence of postoperative dysphagia.

Prediction of the severity of acute pancreatitis on admission by urinary trypsinogen activation peptide: A meta-analysis

PubMed Central

Huang, Wei; Altaf, Kiran; Jin, Tao; Xiong, Jun-Jie; Wen, Li; Javed, Muhammad A; Johnstone, Marianne; Xue, Ping; Halloran, Christopher M; Xia, Qing

2013-01-01

AIM: To undertake a meta-analysis on the value of urinary trypsinogen activation peptide (uTAP) in predicting severity of acute pancreatitis on admission. METHODS: Major databases including Medline, Embase, Science Citation Index Expanded and the Cochrane Central Register of Controlled Trials in the Cochrane Library were searched to identify all relevant studies from January 1990 to January 2013. Pooled sensitivity, specificity and the diagnostic odds ratios (DORs) with 95%CI were calculated for each study and were compared to other systems/biomarkers if mentioned within the same study. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated. RESULTS: In total, six studies of uTAP with a cut-off value of 35 nmol/L were included in this meta-analysis. Overall, the pooled sensitivity and specificity of uTAP for predicting severity of acute pancreatitis, at time of admission, was 71% and 75%, respectively (AUC = 0.83, DOR = 8.67, 95%CI: 3.70-20.33). When uTAP was compared with plasma C-reactive protein, the pooled sensitivity, specificity, AUC and DOR were 0.64 vs 0.67, 0.77 vs 0.75, 0.82 vs 0.79 and 6.27 vs 6.32, respectively. Similarly, the pooled sensitivity, specificity, AUC and DOR of uTAP vs Acute Physiology and Chronic Health Evaluation II within the first 48 h of admission were found to be 0.64 vs 0.69, 0.77 vs 0.61, 0.82 vs 0.73 and 6.27 vs 4.61, respectively. CONCLUSION: uTAP has the potential to act as a stratification marker on admission for differentiating disease severity of acute pancreatitis. PMID:23901239

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis.

PubMed

Kedia, Saurabh; Sharma, Raju; Sreenivas, Vishnubhatla; Madhusudhan, Kumble Seetharama; Sharma, Vishal; Bopanna, Sawan; Pratap Mouli, Venigalla; Dhingra, Rajan; Yadav, Dawesh Prakash; Makharia, Govind; Ahuja, Vineet

2017-04-01

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

Making Structural Sense of Dimerization Interfaces of Delta Opioid Receptor Homodimers†

PubMed Central

2011-01-01

Opioid receptors, like other members of the G protein-coupled receptor (GPCR) family, have been shown to associate to form dimers and/or oligomers at the plasma membrane. Whether this association is stable or transient is not known. Recent compelling evidence suggests that at least some GPCRs rapidly associate and dissociate. We have recently calculated binding affinities from free energy estimates to predict transient association between mouse delta opioid receptor (DOR) protomers at a symmetric interface involving the fourth transmembrane (TM4) helix (herein termed “4” dimer). Here we present disulfide cross-linking experiments with DOR constructs with cysteines substituted at the extracellular ends of TM4 or TM5 that confirm the formation of DOR complexes involving these helices. Our results are consistent with the involvement of TM4 and/or TM5 at the DOR homodimer interface, but possibly with differing association propensities. Coarse-grained (CG) well-tempered metadynamics simulations of two different dimeric arrangements of DOR involving TM4 alone or with TM5 (herein termed “4/5” dimer) in an explicit lipid−water environment confirmed the presence of two structurally and energetically similar configurations of the 4 dimer, as previously assessed by umbrella sampling calculations, and revealed a single energetic minimum of the 4/5 dimer. Additional CG umbrella sampling simulations of the 4/5 dimer indicated that the strength of association between DOR protomers varies depending on the protein region at the interface, with the 4 dimer being more stable than the 4/5 dimer. PMID:21261298

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis.

PubMed

Pashaiasl, Maryam; Ebrahimi, Mansour; Ebrahimie, Esmaeil

2016-09-01

Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses.

Real-time Continuous Esophageal High-resolution Manometry (HRM) During Laparoscopic Heller Myotomy and Dor Fundoplication for the Treatment of Achalasia. A Promising Novelty in Regards of Perfecting Surgical Technique: Could It Guide Surgical Technique Toward Excellent Results?

PubMed

Triantafyllou, Tania; Doulami, Georgia; Papailiou, Joanna; Mantides, Apostolos; Zografos, Georgios; Theodorou, Dimitrios

2016-12-01

High-resolution manometry (HRM) is the gold-standard diagnostic tool for achalasia of the esophagus. Laparoscopic Heller-Dor technique is the preferred surgical approach with success rate estimated 90%. The use of intraoperative HRM provides real-time estimation of intraluminal esophageal pressures and identifies the exact points of esophageal luminal pressure during laparoscopy. Ten patients with achalasia underwent surgery. All patients preoperatively completed 1 manometric study and Quality of Life questionnaires (EORTC QLQ-C30 version 3.0) with Eckardt scores. We collected intraoperative manometry data and repeated manometric studies, EORTC QLQ-C30, and Eckardt scores postoperatively. Median Eckardt score was decreased from 7.5 to 0.5, mean resting pressure decreased from 51.4 to 11.9 mm Hg, whereas mean residual pressure diminished from 45.9 to 9.5 mm Hg postoperatively. The simultaneous use of HRM during the Heller-Dor technique may lead to an individualized management of the disease.

Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: a systematic review and a meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Prior, John O; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

DORS: DDC Online Retrieval System.

ERIC Educational Resources Information Center

Liu, Songqiao; Svenonius, Elaine

1991-01-01

Describes the Dewey Online Retrieval System (DORS), which was developed at the University of California, Los Angeles (UCLA), to experiment with classification-based search strategies in online catalogs. Classification structures in automated information retrieval are discussed; and specifications for a classification retrieval interface are…

Transvaginal ultrasound vs magnetic resonance imaging for diagnosing deep infiltrating endometriosis: systematic review and meta-analysis.

PubMed

Guerriero, S; Saba, L; Pascual, M A; Ajossa, S; Rodriguez, I; Mais, V; Alcazar, J L

2018-05-01

To perform a systematic review of studies comparing the accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in diagnosing deep infiltrating endometriosis (DIE) including only studies in which patients underwent both techniques. An extensive search was carried out in PubMed/MEDLINE and Web of Science for papers from January 1989 to October 2016 comparing TVS and MRI in DIE. Studies were considered eligible for inclusion if they reported on the use of TVS and MRI in the same set of patients for the preoperative detection of endometriosis in pelvic locations in women with clinical suspicion of DIE and using surgical data as a reference standard. Quality was assessed using the QUADAS-2 tool. A random-effects model was used to determine pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR). Of 375 citations identified, six studies (n = 424) were considered eligible. For MRI in the detection of DIE in the rectosigmoid, pooled sensitivity was 0.85 (95% CI, 0.78-0.90), specificity was 0.95 (95% CI, 0.83-0.99), LR+ was 18.4 (95% CI, 4.7-72.4), LR- was 0.16 (95% CI, 0.11-0.24) and DOR was 116 (95% CI, 23-585). For TVS in the detection of DIE in the rectosigmoid, pooled sensitivity was 0.85 (95% CI, 0.68-0.94), specificity was 0.96 (95% CI, 0.85-0.99), LR+ was 20.4 (95% CI, 4.7-88.5), LR- was 0.16 (95% CI, 0.07-0.38) and DOR was 127 (95% CI, 14-1126). For MRI in the detection of DIE in the rectovaginal septum, pooled sensitivity was 0.66 (95% CI, 0.51-0.79), specificity was 0.97 (95% CI, 0.89-0.99), LR+ was 22.5 (95% CI, 6.7-76.2), LR- was 0.38 (95% CI, 0.23-0.52) and DOR was 65 (95% CI, 21-204). For TVS in the detection of DIE in the rectovaginal septum, pooled sensitivity was 0.59 (95% CI, 0.26-0.86), specificity was 0.97 (95% CI, 0.94-0.99), LR+ was 23.5 (95% CI, 9.1-60.5), LR- was 0.42 (95% CI, 0.18-0.97) and DOR was 56 (95% CI, 11-275). For MRI in the detection of DIE in the uterosacral ligaments, pooled sensitivity was 0.70 (95% CI, 0.55-0.82), specificity was 0.93 (95% CI, 0.87-0.97), LR+ was 10.4 (95% CI, 5.1-21.2), LR- was 0.32 (95% CI, 0.20-0.51) and DOR was 32 (95% CI, 12-85). For TVS in the detection of DIE in the uterosacral ligaments, pooled sensitivity was 0.67 (95% CI, 0.55-0.77), specificity was 0.86 (95% CI, 0.73-0.93), LR+ was 4.8 (95% CI, 2.6-9.0), LR- was 0.38 (95% CI, 0.29-0.50) and DOR was 12 (95% CI, 7-24). Confidence intervals of pooled sensitivities, specificities and DOR were wide for both techniques in all the locations considered. Heterogeneity was moderate or high for sensitivity and specificity for both TVS and MRI in most locations assessed. According to QUADAS-2, the quality of the included studies was considered good for most domains. The diagnostic performance of TVS and MRI is similar for detecting DIE involving rectosigmoid, uterosacral ligaments and rectovaginal septum. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Dor Vs Toupet Fundoplication After Laparoscopic Heller Myotomy: Long-Term Randomized Controlled Trial Evaluated by High-Resolution Manometry.

PubMed

Torres-Villalobos, Gonzalo; Coss-Adame, Enrique; Furuzawa-Carballeda, Janette; Romero-Hernández, Fernanda; Blancas-Breña, Blanca; Torres-Landa, Samuel; Palacios-Ramírez, Axel; Alejandro-Medrano, Edgar; Hernández-Ávila, Axel; Flores-Najera, Athenea; Ávila Escobedo, Lourdes Margarita; Ramírez Angulo, Cecilia; Rodríguez-Garcés, Angélica; Valdovinos, Miguel Ángel

2018-01-01

Laparoscopic Heller myotomy (LHM) with partial fundoplication is an effective treatment for achalasia. However, the type of fundoplication is still a subject of debate. The aim of the study is to identify which partial fundoplication leads to better control of acid exposure, manometric parameters, and symptoms scores. A randomized controlled trial was performed to compare Dor vs Toupet fundoplication after LHM. The preoperative diagnosis was made by high-resolution manometry (HRM), upper endoscopy, and barium esophagogram. Preoperative and postoperative symptoms were evaluated with Eckardt, GERD-HRQL, and EAT-10 questionnaires. Seventy-three patients were randomized, 38 underwent Dor and 35 Toupet. Baseline characteristics were similar between groups. Postoperative HRM showed that the integrated relaxation pressure (IRP) and basal lower esophageal sphincter (LES) pressure were similar at 6 and 24 months. The number of patients with abnormal acid exposure was significantly lower for Dor (6.9%) than that of Toupet (34.0%) at 6 months, but it was not different at 12 or 24 months. No differences were found in postoperative symptom scores at 1, 6, or 24 months. There were no differences in symptom scores or HRM between fundoplications in the long term. A higher percentage of abnormal 24-h pH test were found for the Toupet group, with no difference in the long term.

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Curcuma longa on CYP2D6- and CYP3A4-mediated metabolism of dextromethorphan in human liver microsomes and healthy human subjects.

PubMed

Al-Jenoobi, Fahad Ibrahim; Al-Thukair, Areej A; Alam, Mohd Aftab; Abbas, Fawkeya A; Al-Mohizea, Abdullah M; Alkharfy, Khalid M; Al-Suwayeh, Saleh A

2015-03-01

Effect of Curcuma longa rhizome powder and its ethanolic extract on CYP2D6 and CYP3A4 metabolic activity was investigated in vitro using human liver microsomes and clinically in healthy human subjects. Dextromethorphan (DEX) was used as common probe for CYP2D6 and CYP3A4 enzymes. Metabolic activity of CYP2D6 and CYP3A4 was evaluated through in vitro study; where microsomes were incubated with NADPH in presence and absence of Curcuma extract. In clinical study phase-I, six healthy human subjects received a single dose (30 mg) of DEX syrup, and in phase-II DEX syrup was administered with Curcuma powder. The enzyme CYP2D6 and CYP3A4 mediated O- and N-demethylation of dextromethorphan into dextrorphan (DOR) and 3-methoxymorphinan (3-MM), respectively. Curcuma extract significantly inhibited the formation of DOR and 3-MM, in a dose-dependent and linear fashion. The 100 μg/ml dose of curcuma extract produced highest inhibition, which was about 70 % for DOR and 80 % for 3-MM. Curcuma significantly increases the urine metabolic ratio of DEX/DOR but the change in DEX/3-MM ratio was statistically insignificant. Present findings suggested that curcuma significantly inhibits the activity of CYP2D6 in in vitro as well as in vivo; which indicates that curcuma has potential to interact with CYP2D6 substrates.

How well can the observed Arctic sea ice summer retreat and winter advance be represented in the NCEP Climate Forecast System version 2?

NASA Astrophysics Data System (ADS)

Collow, Thomas W.; Wang, Wanqiu; Kumar, Arun; Zhang, Jinlun

2017-09-01

The capability of a numerical model to simulate the statistical characteristics of the summer sea ice date of retreat (DOR) and the winter date of advance (DOA) is investigated using sea ice concentration output from the Climate Forecast System Version 2 model (CFSv2). Two model configurations are tested, the operational setting (CFSv2CFSR) which uses initial data from the Climate Forecast System Reanalysis, and a modified version (CFSv2PIOMp) which ingests sea ice thickness initialization data from the Pan-Arctic Ice Ocean Modeling and Assimilation System (PIOMAS) and includes physics modifications for a more realistic representation of heat fluxes at the sea ice top and bottom. First, a method to define DOR and DOA is presented. Then, DOR and DOA are determined from the model simulations and observational sea ice concentration from the National Aeronautics and Space Administration (NASA). Means, trends, and detrended standard deviations of DOR and DOA are compared, along with DOR/DOA rates in the Arctic Ocean. It is found that the statistics are generally similar between the model and observations, although some regional biases exist. In addition, regions of new ice retreat in recent years are represented well in CFSv2PIOMp over the Arctic Ocean, in terms of both spatial extent and timing. Overall, CFSv2PIOMp shows a reduction in error throughout the Arctic. Based on results, it is concluded that the model produces a reasonable representation of the climatology and variability statistics of DOR and DOA in most regions. This assessment serves as a prerequisite for future predictability experiments.

The benzomorphan-based LP1 ligand is a suitable MOR/DOR agonist for chronic pain treatment.

PubMed

Pasquinucci, Lorella; Parenti, Carmela; Turnaturi, Rita; Aricò, Giuseppina; Marrazzo, Agostino; Prezzavento, Orazio; Ronsisvalle, Simone; Georgoussi, Zafiroula; Fourla, Danai-Dionysia; Scoto, Giovanna M; Ronsisvalle, Giuseppe

2012-01-02

Powerful analgesics relieve pain primarily through activating mu opioid receptor (MOR), but the long-term use of MOR agonists, such as morphine, is limited by the rapid development of tolerance. Recently, it has been observed that simultaneous stimulation of the delta opioid receptor (DOR) and MOR limits the incidence of tolerance induced by MOR agonists. 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2H)-yl]-N-phenylpropanamide (LP1) is a centrally acting agent with antinociceptive activity comparable to morphine and is able to bind and activate MOR and DOR. The aim of this work was to evaluate and compare the induction of tolerance to antinociceptive effects from treatment with LP1 and morphine. Here, we evaluated the pharmacological effects of LP1 administered at a dose of 4 mg/kg subcutaneously (s.c.) twice per day for 9 days to male Sprague-Dawley rats. In addition, the LP1 mechanism of action was assessed by measurement of LP1-induced [(35)S]GTPγS binding to the MOR and DOR. Data obtained from the radiant heat tail flick test showed that LP1 maintained its antinociceptive profile until the ninth day, while tolerance to morphine (10mg/kg s.c. twice per day) was observed on day 3. Moreover, LP1 significantly enhanced [(35)S]GTPγS binding in the membranes of HEK293 cells expressing either the MOR or the DOR. LP1 is a novel analgesic agent for chronic pain treatment, and its low tolerance-inducing capability may be correlated with its ability to bind both the MOR and DOR. Copyright © 2011 Elsevier Inc. All rights reserved.

Instruments for assessing the risk of falls in acute hospitalized patients: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Falls are a serious problem for hospitalized patients, reducing the duration and quality of life. It is estimated that over 84% of all adverse events in hospitalized patients are related to falls. Some fall risk assessment tools have been developed and tested in environments other than those for which they were developed with serious validity discrepancies. The aim of this review is to determine the accuracy of instruments for detecting fall risk and predicting falls in acute hospitalized patients. Methods Systematic review and meta-analysis. Main databases, related websites and grey literature were searched. Two blinded reviewers evaluated title and abstracts of the selected articles and, if they met inclusion criteria, methodological quality was assessed in a new blinded process. Meta-analyses of diagnostic ORs (DOR) and likelihood (LH) coefficients were performed with the random effects method. Forest plots were calculated for sensitivity and specificity, DOR and LH. Additionally, summary ROC (SROC) curves were calculated for every analysis. Results Fourteen studies were selected for the review. The meta-analysis was performed with the Morse (MFS), STRATIFY and Hendrich II Fall Risk Model scales. The STRATIFY tool provided greater diagnostic validity, with a DOR value of 7.64 (4.86 - 12.00). A meta-regression was performed to assess the effect of average patient age over 65 years and the performance or otherwise of risk reassessments during the patient’s stay. The reassessment showed a significant reduction in the DOR on the MFS (rDOR 0.75, 95% CI: 0.64 - 0.89, p = 0.017). Conclusions The STRATIFY scale was found to be the best tool for assessing the risk of falls by hospitalized acutely-ill adults. However, the behaviour of these instruments varies considerably depending on the population and the environment, and so their operation should be tested prior to implementation. Further studies are needed to investigate the effect of the reassessment of these instruments with respect to hospitalized adult patients, and to consider the real compliance by healthcare personnel with procedures related to patient safety, and in particular concerning the prevention of falls. PMID:23547708

High-resolution 17O double-rotation NMR characterization of ring and non-ring oxygen in vitreous B2O3.

PubMed

Wong, Alan; Howes, Andy P; Parkinson, Ben; Anupõld, Tiit; Samoson, Ago; Holland, Diane; Dupree, Ray

2009-08-28

The application of double rotation (DOR) NMR to crystalline materials (both inorganic and organic) has made tremendous strides in providing site-specific information about materials in recent years. However (17)O DOR has yet to demonstrate its potential in disordered materials such as glasses. In the present study, we have successfully recorded high resolution (17)O DOR spectra of vitreous B(2)O(3) (v-B(2)O(3)), a highly effective glass-forming oxide of considerable technological importance. Two distinct oxygen sites are resolved and a complete set of (17)O NMR parameters were determined from the DOR spectra. These were assigned to oxygen atoms in the planar boroxol ring [B(3)O(6)] and in the non-boroxol [BO(3)] groups which share oxygen with the ring boron atoms. This assignment was based on the similarity of all of their (17)O parameters with those found by DFT calculation for caesium enneaborate, Cs(2)O.9B(2)O(3), which has two boroxol rings in its structure. The boroxol ring oxygens have a more positive chemical shift, a larger shift anisotropy and a smaller electric field gradient than non ring oxygens (O(R): delta(iso) = 100 +/- 1 ppm, span = 180 +/- 20 ppm, skew = -0.4 +/- 0.1, P(q) = 5.0 +/- 0.2 MHz; O(NR): delta(iso) = 86 +/- 1 ppm, span = 100 +/- 20 ppm, skew = 0.1 +/- 0.1, P(q) = 5.7 +/- 0.2 MHz). The relative proportions of the two sites in v-B(2)O(3) are approximately 1 : 1, as expected if all three boron atoms in the boroxol ring are each connected to one oxygen in a linking [BO(3)] group and there are very few [BO(3)]-[BO(3)] linkages. We see no evidence for a third oxygen site such as has been reported in an earlier study of v-B(2)O(3). This work demonstrates the potential of (17)O DOR to provide site-specific information in disordered materials.

Voyager flight engineering - Preparing for Uranus

NASA Technical Reports Server (NTRS)

Mclaughlin, W. I.; Wolff, D. M.

1985-01-01

Two Voyager spacecraft are currently engaged in exploration of the outer solar system with Voyager 2 scheduled to conduct the first close-up investigation of the planet Uranus during the period November 4, 1985 through March 3, 1986. Flight engineering for the Voyager project has the objectives of delivering a functioning spacecraft containing observing sequences to the right places at the right times. Due to the changing environment as the mission has progressed outward from Jupiter to Saturn to Uranus (and on to Neptune), this engineering task has included the development of significant new capabilities. The paper utilizes the case-study method to examine some new spacecraft capabilities in three subsystems: data, attitude and articulation control, and power. The implementation of a new navigational data-type, delta DOR, is also reviewed. An overview is given of the Voyager sequencing process for the cruise and encounter phases with a case study focusing on late updating of part of the near encounter sequence. The prospective mission to Neptune is previewed.

Intervention effects of QRZSLXF, a Chinese medicinal herb recipe, on the DOR-β-arrestin1-Bcl2 signal transduction pathway in a rat model of ulcerative colitis.

PubMed

Fan, Heng; Liu, Xing-xing; Zhang, Li-juan; Hu, Hui; Tang, Qing; Duan, Xue-yun; Zhong, Min; Shou, Zhe-xing

2014-05-28

Qingre Zaoshi Liangxue Fang (QRZSLXF) is a Chinese medicinal herb recipe that is commonly prescribed for the treatment of ulcerative colitis. It includes 5 quality assured herbs: Sophora flavescens Aiton., Baphicacanthus cusia (Nees) Bremek., Bletilla striata Rchb.f., Glycyrrhiza uralensis Fisch. and Coptis chinensis Franch. The main phytochemical ingredient of QRZSLXF includes ammothamnine, sophocarpidine, liquiritin, berberine and indirubin. QRZSLXF has been clinically proven for use in the treatment of ulcerative colitis for over twenty years. In the past ten years, research has confirmed the therapeutic effect of QRZSLXF in ulcerative colitis and partially revealed its mechanism of action. Here, we further reveal the therapeutic mechanism of QRZSLXF in ulcerative colitis. To investigate the role of the DOR-β-arrestin1-Bcl-2 signal transduction pathway in ulcerative colitis and to determine the effects of QRZSLXF on this signal transduction pathway. Eighty-four Sprague-Dawley rats were randomly divided into six groups: normal control group, model group, mesalazine group, and QRZSLXF high-dose, medium-dose group and low-dose groups (n=14). Experimental colitis was induced by trinitrobenzenesulfonic acid (TNBS) in each group, except the normal control group. After modeling, bloody stool, mental state and diarrhea were observed and recorded. Two rats were randomly selected from the model groups adfnd sacrificed on day 3 to observe pathological changes in the colon tissue by microscopy. The rats in the QRZSLXF-treated groups received intramuscular injections of different concentrations of QRZSLXF for 15 days. The rats in the mesalazine group were treated with mesalazine solution (0.5 g/kg/day) by gastric lavage for 15 days. The rats in the normal control group and the model group were treated with 3 mL water by gastric lavage for 15 days. On the 16th day, after fasting for 24 h, the remaining rats were sacrificed and their colon tissues were used to detect the mRNA and protein expressions of DOR, β-arrestin1 and Bcl-2 by Real-time PCR and immunohistochemistry, respectively. Histological changes in the colon tissues were also examined. The expressions of DOR, β-arrestin1 and Bcl-2 were significantly different among the four groups. The expressions of DOR, β-arrestin1 and Bcl-2 protein and mRNA were significantly increased in the model group compared with the other groups (P<0.05). In contrast to the model group, the expressions of DOR, β-arrestin1 and Bcl-2 were significantly decreased in the mesalazine group and the groups that received different doses of QRZSLXF (P<0.05), and there were no statistically significant differences among the mesalazine and QRZSLXF-treated groups (P>0.05). This study indicates that the DOR-beta-arrestin1-Bcl-2 signal transduction pathway may participate in the pathologic course of ulcerative colitis. Moreover, QRZSLXF could attenuate ulcerative colitis by regulating the DOR-β-arrestin1-Bcl-2 signal transduction pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

BROWN DWARFS IN YOUNG MOVING GROUPS FROM PAN-STARRS1. I. AB DORADUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aller, Kimberly M.; Liu, Michael C.; Magnier, Eugene A.

Substellar members of young (≲150 Myr) moving groups are valuable benchmarks to empirically define brown dwarf evolution with age and to study the low-mass end of the initial mass function. We have combined Pan-STARRS1 (PS1) proper motions with optical–IR photometry from PS1, Two Micron All Sky Survey (2MASS), and WISE to search for substellar members of the AB Dor Moving Group within ≈50 pc and with spectral types of late M to early L, corresponding to masses down to ≈30 M {sub Jup} at the age of the group (≈125 Myr). Including both photometry and proper motions allows us tomore » better select candidates by excluding field dwarfs whose colors are similar to young AB Dor Moving Group members. Our near-IR spectroscopy has identified six ultracool dwarfs (M6–L4; ≈30–100 M {sub Jup}) with intermediate surface gravities (int-g) as candidate members of the AB Dor Moving Group. We find another two candidate members with spectra showing hints of youth but consistent with field gravities. We also find four field brown dwarfs unassociated with the AB Dor Moving Group, three of which have int-g gravity classification. While signatures of youth are present in the spectra of our ≈125 Myr objects, neither their J – K nor W 1 – W 2 colors are significantly redder than field dwarfs with the same spectral types, unlike younger ultracool dwarfs. We also determined PS1 parallaxes for eight of our candidates and one previously identified AB Dor Moving Group candidate. Although radial velocities (and parallaxes, for some) are still needed to fully assess membership, these new objects provide valuable insight into the spectral characteristics and evolution of young brown dwarfs.« less

δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium.

PubMed

Estrada, Juan A; Williams, Arthur G; Sun, Jie; Gonzalez, Leticia; Downey, H Fred; Caffrey, James L; Mallet, Robert T

2016-03-01

Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5-8 daily, 5-10 min cycles of moderate, normobaric hypoxia (FIO2 0.095-0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia.

Accuracy of clinical pallor in the diagnosis of anaemia in children: a meta-analysis

PubMed Central

Chalco, Juan P; Huicho, Luis; Alamo, Carlos; Carreazo, Nilton Y; Bada, Carlos A

2005-01-01

Background Anaemia is highly prevalent in children of developing countries. It is associated with impaired physical growth and mental development. Palmar pallor is recommended at primary level for diagnosing it, on the basis of few studies. The objective of the study was to systematically assess the accuracy of clinical signs in the diagnosis of anaemia in children. Methods A systematic review on the accuracy of clinical signs of anaemia in children. We performed an Internet search in various databases and an additional reference tracking. Studies had to be on performance of clinical signs in the diagnosis of anaemia, using haemoglobin as the gold standard. We calculated pooled diagnostic likelihood ratios (LR's) and odds ratios (DOR's) for each clinical sign at different haemoglobin thresholds. Results Eleven articles met the inclusion criteria. Most studies were performed in Africa, in children underfive. Chi-square test for proportions and Cochran Q for DOR's and for LR's showed heterogeneity. Type of observer and haemoglobin technique influenced the results. Pooling was done using the random effects model. Pooled DOR at haemoglobin <11 g/dL was 4.3 (95% CI 2.6–7.2) for palmar pallor, 3.7 (2.3–5.9) for conjunctival pallor, and 3.4 (1.8–6.3) for nailbed pallor. DOR's and LR's were slightly better for nailbed pallor at all other haemoglobin thresholds. The accuracy did not vary substantially after excluding outliers. Conclusion This meta-analysis did not document a highly accurate clinical sign of anaemia. In view of poor performance of clinical signs, universal iron supplementation may be an adequate control strategy in high prevalence areas. Further well-designed studies are needed in settings other than Africa. They should assess inter-observer variation, performance of combined clinical signs, phenotypic differences, and different degrees of anaemia. PMID:16336667

Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues.

PubMed

Huser, M; Smardova, L; Janku, P; Crha, I; Zakova, J; Stourac, P; Jarkovsky, J; Mayer, J; Ventruba, P

2015-08-01

Aim of this prospective observational study was to analyze fertility status of Hodgkin lymphoma (HL) patients treated with different types of chemotherapy while receiving GnRH analogues to preserve ovarian function. Fertility status was assessed among 108 females in reproductive age treated by curative chemotherapy for freshly diagnosed HL between 2005 and 2010 in university-based tertiary fertility and oncology center. All patients received GnRH analogues during chemotherapy to preserve their ovarian function. Their reproductive functions were assessed by follicle-stimulating hormone (FSH) measurement and pregnancy achievement. Ovarian function was determined separately in three groups with increasing gonadotoxicity of chemotherapy. One year following the treatment, normal ovarian function was found in 89 (82.4%) of patients. Two years after chemotherapy, 98 (90.7%) of patients retained their ovarian function, and 23 (21.3%) achieved clinical pregnancy during the follow-up period. Average FSH after chemotherapy was 11.6 ± 17.9 IU/l 1 year after the treatment resp. 9.0 ± 13.8 at the 2 years interval. There were significantly more patients with chemotherapy induced diminished ovarian reserve (chDOR) among the group receiving escalated BEACOPP chemotherapy in comparison with the other types of treatment (58.1% vs. 87.9% resp. 95.5%). The rate of chDOR is significantly higher after EB poly-chemotherapy and there is no tendency for improvement in time. The 2 + 2 chemotherapy with GnRH-a required for more advanced HL retained ovarian function significantly better after 2 years. Another important advantage of GnRH-a co-treatment is the excellent control of patient's menstrual cycle.

Diagnostic Accuracy of the Veteran Affairs' Traumatic Brain Injury Screen.

PubMed

Louise Bender Pape, Theresa; Smith, Bridget; Babcock-Parziale, Judith; Evans, Charlesnika T; Herrold, Amy A; Phipps Maieritsch, Kelly; High, Walter M

2018-01-31

To comprehensively estimate the diagnostic accuracy and reliability of the Department of Veterans Affairs (VA) Traumatic Brain Injury (TBI) Clinical Reminder Screen (TCRS). Cross-sectional, prospective, observational study using the Standards for Reporting of Diagnostic Accuracy criteria. Three VA Polytrauma Network Sites. Operation Iraqi Freedom, Operation Enduring Freedom veterans (N=433). TCRS, Comprehensive TBI Evaluation, Structured TBI Diagnostic Interview, Symptom Attribution and Classification Algorithm, and Clinician-Administered Posttraumatic Stress Disorder (PTSD) Scale. Forty-five percent of veterans screened positive on the TCRS for TBI. For detecting occurrence of historical TBI, the TCRS had a sensitivity of .56 to .74, a specificity of .63 to .93, a positive predictive value (PPV) of 25% to 45%, a negative predictive value (NPV) of 91% to 94%, and a diagnostic odds ratio (DOR) of 4 to 13. For accuracy of attributing active symptoms to the TBI, the TCRS had a sensitivity of .64 to .87, a specificity of .59 to .89, a PPV of 26% to 32%, an NPV of 92% to 95%, and a DOR of 6 to 9. The sensitivity was higher for veterans with PTSD (.80-.86) relative to veterans without PTSD (.57-.82). The specificity, however, was higher among veterans without PTSD (.75-.81) relative to veterans with PTSD (.36-.49). All indices of diagnostic accuracy changed when participants with questionably valid (QV) test profiles were eliminated from analyses. The utility of the TCRS to screen for mild TBI (mTBI) depends on the stringency of the diagnostic reference standard to which it is being compared, the presence/absence of PTSD, and QV test profiles. Further development, validation, and use of reproducible diagnostic algorithms for symptom attribution after possible mTBI would improve diagnostic accuracy. Published by Elsevier Inc.

Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.

PubMed

Sekulic, Aleksandar; Migden, Michael R; Basset-Seguin, Nicole; Garbe, Claus; Gesierich, Anja; Lao, Christopher D; Miller, Chris; Mortier, Laurent; Murrell, Dedee F; Hamid, Omid; Quevedo, Jorge F; Hou, Jeannie; McKenna, Edward; Dimier, Natalie; Williams, Sarah; Schadendorf, Dirk; Hauschild, Axel

2017-05-16

In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC. One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety. At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib. This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC. This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.

Effectiveness of urine fibronectin as a non-invasive diagnostic biomarker in bladder cancer patients: a systematic review and meta-analysis.

PubMed

Dong, Fan; Shen, Yifan; Xu, Tianyuan; Wang, Xianjin; Gao, Fengbin; Zhong, Shan; Chen, Shanwen; Shen, Zhoujun

2018-03-21

Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection. A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis. Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77-0.83), 0.79 (95%CI = 0.73-0.84), and 15.18 (95%CI = 10.07-22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79-0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82-0.90) and 0.89 (95%CI = 0.86-0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis. Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.

Esophageal Achalasia: Predictive Value of Preoperative Resting Pressure of LES Correlated with Type of Fundoplication.

PubMed

Tancredi, Antonio; Cuttitta, Antonello; Scaramuzzi, Roberto; Scaramuzzi, Gerardo; Taurchini, Marco

2017-02-01

The aim of the present study is to show the predictive value of the preoperative resting pressure of the lower esophageal sphincter (LES) correlated with the type of fundoplication (Nissen or Dor) after Heller myotomy in our series. From January 1998 to June 2010, 88 patients affected by esophageal achalasia underwent surgery at our unit. However, our study focused on a sample of 36 patients, because many data were lost or was never recorded. Among these, 14 patients underwent laparoscopic Heller myotomy plus Nissen fundoplication (group N), whereas 22 patients underwent laparoscopic Heller myotomy plus Dor fundoplication (group D). Clinical evaluation was performed using a modified DeMeester symptom scoring system consisting of the assessment of three symptoms: dysphagia, regurgitation, and heartburn. To each symptom was assigned a score from 0 to 3, depending on its severity, and the reduction in the severity of each symptom after surgery was assessed. The surgical treatment is considered to be effective (p<0.0001). The preoperative resting pressures of LES were compared by Student's t-test, and it was found that patients who reported a greater improvement in the dysphagia symptom had a preoperative average pressure of LES that was significantly higher than that in other patients in both group N (p=0.03) and group D (p=0.01; p=0.003; p=0.001). The Dor treatment was shown to be more effective than the Nissen treatment (p<0.0001). The preoperative resting pressure of LES is a predictive factor of surgical success both before Dor fundoplication and before Nissen fundoplication, but its predictive power is influenced by the chosen type of fundoplication.

Involvement of delta and mu opioid receptors in the acute and sensitized locomotor action of cocaine in mice.

PubMed

Kotlinska, J H; Gibula-Bruzda, E; Witkowska, E; Izdebski, J

2013-10-01

Analogs of deltorphins, such as cyclo(Nδ, Nδ-carbonyl-d-Orn2, Orn4)deltorphin (DEL-6) and deltorphin II N-(ureidoethyl)amide (DK-4) are functional agonists predominantly for the delta opioid receptors (DOR) in the guinea-pig ileum and mouse vas deferens bioassays. The purpose of this study was to examine an influence of these peptides (5, 10 or 20 nmol, i.c.v.) on the acute cocaine-induced (10mg/kg, i.p.) locomotor activity and the expression of sensitization to cocaine locomotor effect. Sensitization to locomotor effect of cocaine was developed by five injections of cocaine at the dose of 10mg/kg, i.p. every 3 days. Our results indicated that DK-4 and DEL-6 differently affected the acute and sensitized cocaine locomotion. Co-administration of DEL-6 with cocaine enhanced acute cocaine locomotion only at the dose of 10 nmol, with minimal effects at the doses 5 and 20 nmol, whereas co-administration of DK-4 with cocaine enhanced acute cocaine-induced locomotion in a dose-dependent manner. Similarly to the acute effects, DEL-6 only at the dose of 10 nmol but DK-4 dose-dependently enhanced the expression of cocaine sensitization. Pre-treatment with DOR antagonist - naltrindole (5 nmol, i.c.v.) and mu opioid receptor (MOR) antagonist, β-funaltrexamine abolished the ability of both peptides to potentiate the effects of cocaine. Our study suggests that MOR and DOR are involved in the interactions between cocaine and both deltorphins analogs. A distinct dose-response effects of these peptides on cocaine locomotion probably arise from differential functional activation (targeting) of the DOR and MOR by both deltorphins analogs. Copyright © 2013 Elsevier Inc. All rights reserved.

The Diagnostic Value of Gastrin-17 Detection in Atrophic Gastritis

PubMed Central

Wang, Xu; Ling, Li; Li, Shanshan; Qin, Guiping; Cui, Wei; Li, Xiang; Ni, Hong

2016-01-01

Abstract A meta-analysis was performed to assess the diagnostic value of gastrin-17 (G-17) for the early detection of chronic atrophic gastritis (CAG). An extensive literature search was performed, with the aim of selecting publications that reported the accuracy of G-17 in predicting CAG, in the following databases: PubMed, Science Direct, Web of Science, Chinese Biological Medicine, Chinese National Knowledge Infrastructure, Wanfang, and VIP. To assess the diagnostic value of G-17, the following statistics were estimated and described: sensitivity, specificity, diagnostic odds ratios (DOR), summary receiver operating characteristic curves, area under the curve (AUC), and 95% confidence intervals (CIs). Thirteen studies that met the inclusion criteria were included in this meta-analysis, comprising 894 patients and 1950 controls. The pooled sensitivity and specificity of these studies were 0.48 (95% CI: 0.45–0.51) and 0.79 (95% CI: 0.77–0.81), respectively. The DOR was 5.93 (95% CI: 2.93–11.99), and the AUC was 0.82. G-17 may have potential diagnostic value because it has good specificity and a moderate DOR and AUC for CAG. However, more studies are needed to improve the sensitivity of this diagnostic tool in the future. PMID:27149493

Intraoperative Assessment of Esophagogastric Junction Distensibility During Laparoscopic Heller Myotomy.

PubMed

DeHaan, Reece K; Frelich, Matthew J; Gould, Jon C

2016-04-01

We sought to characterize the changes in esophagogastric junction (EGJ) distensibility during Heller Myotomy with Dor fundoplication using the EndoFLIP device. Intraoperative distensibility measurements on 14 patients undergoing Heller myotomy with Dor fundoplication were conducted over an 18-month period. Minimum esophageal diameter, cross-sectional areas, and distensibility index were measured at 30 and 40 mL catheter volumes before myotomy, postmyotomy, and following Dor fundoplication. Distensibility index is defined as the narrowest cross-sectional area divided by the corresponding pressure expressed in mm/mm Hg. Heller myotomy was found to lead to significant changes in the distensibility characteristics of the EGJ. Minimum esophageal diameter and EGJ distensibility increased significantly with Heller myotomy.

Evidence and Function Relevance of Native DOR-MOR Heteromers.

PubMed

Cahill, Catherine M; Ong, Edmund

2018-04-10

Opioid receptors are the sites of action for morphine and most other clinically used opioid drugs. Abundant evidence now demonstrates that different opioid receptor types can physically associate to form heteromers. Owing to their constituent monomers' involvement in analgesia, mu/delta opioid receptor (M/DOR) heteromers have been a particular focus of attention. Understandings of the physiological relevance and indisputable proof of M/DOR formation in vivo are still evolving. This aspect of the field has been slow to progress in large part by the limitations of most available experimental models; recently however, promising progress is being made. As a result, the long-repeated promise of opioid receptor heteromers as selective therapeutic targets is now being realized.

Estimating Accurate Relative Spacecraft Angular Position from DSN VLBI Phases Using X-Band Telemetry or DOR Tones

NASA Technical Reports Server (NTRS)

Bagri, Durgadas S.; Majid, Walid

2009-01-01

At present spacecraft angular position with Deep Space Network (DSN) is determined using group delay estimates from very long baseline interferometer (VLBI) phase measurements employing differential one way ranging (DOR) tones. As an alternative to this approach, we propose estimating position of a spacecraft to half a fringe cycle accuracy using time variations between measured and calculated phases as the Earth rotates using DSN VLBI baseline(s). Combining fringe location of the target with the phase allows high accuracy for spacecraft angular position estimate. This can be achieved using telemetry signals of at least 4-8 MSamples/sec data rate or DOR tones.

Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

PubMed Central

Huang, Ya-kai; Yu, Jian-chun; Kang, Wei-ming; Ma, Zhi-qiang; Ye, Xin; Tian, Shu-bo; Yan, Chao

2015-01-01

Background Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection. Methods We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity. Results In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00). Conclusion SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future. PMID:26556485

A Digital Library for Education: The PEN-DOR Project.

ERIC Educational Resources Information Center

Fullerton, Karen; Greenberg, Jane; McClure, Maureen; Rasmussen, Edie; Stewart, Darin

1999-01-01

Describes Pen-DOR (Pennsylvania Education Network Digital Object Repository), a digital library designed to provide K-12 educators with access to multimedia resources and tools to create new lesson plans and modify existing ones via the World Wide Web. Discusses design problems of a distributed, object-oriented database architecture and describes…

Asymmetric synthesis and in vitro and in vivo activity of tetrahydroquinolines featuring a diverse set of polar substitutions at the 6 position as mixed-efficacy μ opioid receptor/δ opioid receptor ligands.

PubMed

Bender, Aaron M; Griggs, Nicholas W; Anand, Jessica P; Traynor, John R; Jutkiewicz, Emily M; Mosberg, Henry I

2015-08-19

We previously reported a small series of mixed-efficacy μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist peptidomimetics featuring a tetrahydroquinoline scaffold and showed the promise of this series as effective analgesics after intraperitoneal administration in mice. We report here an expanded structure-activity relationship study of the pendant region of these compounds and focus in particular on the incorporation of heteroatoms into this side chain. These analogues provide new insight into the binding requirements for this scaffold at MOR, DOR, and the κ opioid receptor (KOR), and several of them (10j, 10k, 10m, and 10n) significantly improve upon the overall MOR agonist/DOR antagonist profile of our previous compounds. In vivo data for 10j, 10k, 10m, and 10n are also reported and show the antinociceptive potency and duration of action of compounds 10j and 10m to be comparable to those of morphine.

14-Alkoxy- and 14-acyloxypyridomorphinans: μ agonist/δ antagonist opioid analgesics with diminished tolerance and dependence side effects.

PubMed

Ananthan, Subramaniam; Saini, Surendra K; Dersch, Christina M; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J; Rothman, Richard B

2012-10-11

In the search for opioid ligands with mixed functional activity, a series of 5'-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h, its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects upon prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine upon repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence, and related side effects.

14-Alkoxy- and 14-Acyloxypyridomorphinans: Mu Agonist/Delta Antagonist Opioid Analgesics with Diminished Tolerance and Dependence Side Effects

PubMed Central

Ananthan, Subramaniam; Saini, Surendra K.; Dersch, Christina M.; Xu, Heng; McGlinchey, Nicholas; Giuvelis, Denise; Bilsky, Edward J.; Rothman, Richard B.

2012-01-01

In the search for opioid ligands with mixed functional activity, a series of 5′-(4-chlorophenyl)-4,5α-epoxypyridomorphinans possessing alkoxy or acyloxy groups at C-14 was synthesized and evaluated. In this series, the affinity and functional activity of the ligands were found to be influenced by the nature of the substituent at C-14 as well as by the substituent at N-17. Whereas the incorporation of a 3-phenylpropoxy group at C-14 on N-methylpyridomorhinan gave a dual MOR agonist/DOR agonist 17h its incorporation on N-cyclopropylmethylpyridomorphinan gave a MOR agonist/DOR antagonist 17d. Interestingly, 17d, in contrast to 17h, did not produce tolerance or dependence effects on prolonged treatment in cells expressing MOR and DOR. Moreover, 17d displayed greatly diminished analgesic tolerance as compared to morphine on repeated administration, thus supporting the hypothesis that ligands with MOR agonist/DOR antagonist functional activity could emerge as novel analgesics devoid of tolerance, dependence and related side effects. PMID:23016952

δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice

PubMed Central

Laurent, Vincent; Bertran-Gonzalez, Jesus; Chieng, Billy C.

2014-01-01

Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of δ-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D1-receptor (D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D1- and D2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-S abolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions. PMID:24453326

Untrained young men have dysfunctional HDL compared with strength-trained men irrespective of body weight status

PubMed Central

Katiraie, Michael; Croymans, Daniel M.; Yang, Otto O.; Kelesidis, Theodoros

2013-01-01

We examined the impact of strength fitness and body weight on the redox properties of high-density lipoprotein (HDL) and associations with indices of vascular and metabolic health. Ninety young men were categorized into three groups: 1) overweight untrained (OU; n = 30; BMI 30.7 ± 2.1 kg/m2); 2) overweight trained [OT; n = 30; BMI 29.0 ± 1.9; ≥4 d/wk resistance training (RT)]; and 3) lean trained (LT; n = 30; BMI 23.7 ± 1.4; ≥4 d/wk RT). Using a novel assay on the basis of the HDL-mediated rate of oxidation of dihydrorhodamine (DOR), we determined the functional (redox) properties of HDL and examined correlations between DOR and indices of vascular and metabolic health in the cohort. DOR was significantly lower in both trained groups compared with the untrained group (LT, 1.04 ± 0.49; OT, 1.39 ± 0.57; OU, 1.80 ± 0.74; LT vs. OU P < 0.00001; OT vs. OU P = 0.02), however, DOR in the OT group was not significantly different from that of the LT group. DOR was negatively associated with HDL-cholesterol (R = −0.64), relative strength (R = −0.42), sex hormone-binding globulin (R = −0.42), and testosterone (R = −0.35) (all P ≤ 0.001); whereas DOR was positively associated with triglycerides (R = 0.39, P = 0.002), oxidized low-density lipoprotein (R = 0.32), body mass index (R = 0.43), total mass (R = 0.35), total fat mass (R = 0.42), waist circumference (R = 0.45), and trunk fat mass (R = 0.42) (all P ≤ 0.001). Chronic RT is associated with improved HDL redox activity. This may contribute to the beneficial effects of RT on reducing cardiovascular disease risk, irrespective of body weight status. PMID:23887902

Characterizing cosmic-ray propagation in massive star-forming regions: The case of 30 Doradus and the large Magellanic cloud

DOE PAGES

Murphy, E. J.; Porter, T. A.; Moskalenko, I. V.; ...

2012-04-24

We investigate the propagation characteristics of cosmic-ray (CR) electrons and nuclei in the 30 Doradus (30 Dor) star-forming region in the Large Magellanic Cloud (LMC) using infrared, radio, and γ-ray data and a phenomenological model based on the radio-far-infrared correlation within galaxies. By employing a correlation analysis, we derive an average propagation length of ~100-140 pc for ~3 GeV CR electrons resident in 30 Dor from consideration of the radio and infrared data. Assuming that the observed γ-ray emission toward 30 Dor is associated with the star-forming region, and applying the same methodology to the infrared and γ-ray data, wemore » estimate a ~20 GeV propagation length of 200-320 pc for the CR nuclei. This is approximately twice as large as for ~3 GeV CR electrons, corresponding to a spatial diffusion coefficient that is ~4 times higher, scaling as (R/GV) δ with δ ≈ 0.7-0.8 depending on the smearing kernel used in the correlation analysis. This value is in agreement with the results found by extending the correlation analysis to include ~70 GeV CR nuclei traced by the 3-10 GeV γ-ray data (δ ≈ 0.66 ± 0.23). Using the mean age of the stellar populations in 30 Dor and the results from our correlation analysis, we estimate a diffusion coefficient D R ≈ (0.9-1.0) × 10 27(R/GV) 0.7 cm 2 s –1. We also compare the values of the CR electron propagation length and surface brightness for 30 Dor and the LMC as a whole with those of entire disk galaxies. We find that the trend of decreasing average CR propagation distance with increasing disk-averaged star formation activity holds for the LMC, and extends down to single star-forming regions, at least for the case of 30 Dor.« less

Pain from the life cycle perspective: Evaluation and Measurement through psychophysical methods of category estimation and magnitude estimation.

PubMed

Sousa, Fátima Aparecida Emm Faleiros; Silva, Talita de Cássia Raminelli da; Siqueira, Hilze Benigno de Oliveira Moura; Saltareli, Simone; Gomez, Rodrigo Ramon Falconi; Hortense, Priscilla

2016-08-18

to describe acute and chronic pain from the perspective of the life cycle. participants: 861 people in pain. The Multidimensional Pain Evaluation Scale (MPES) was used. in the category estimation method the highest descriptors of chronic pain for children/ adolescents were "Annoying" and for adults "Uncomfortable". The highest descriptors of acute pain for children/adolescents was "Complicated"; and for adults was "Unbearable". In magnitude estimation method, the highest descriptors of chronic pain was "Desperate" and for descriptors of acute pain was "Terrible". the MPES is a reliable scale it can be applied during different stages of development. descrever a dor aguda e a crônica na perspectiva do ciclo vital. Métodos: participaram 861 pessoas com dor. Foi utilizada a Escala Multidimensional de Avaliação da Dor (EMADOR). Resultados: no método da estimação de categoria o descritor da dor crônica de maior atribuição para crianças e adolescentes foi "Chata" e para adultos foi "Desconfortável". Os descritores de maior atribuição para dor aguda em crianças e adolescentes foram "Complicada" e em adultos "Insuportável". No método de estimação de magnitude, o descritor de maior atribuição na dor crônica foi "Atormentadora" e na dor aguda foi "Terrível". a EMADOR é uma escala confiável e pode ser utilizada nas diferentes etapas do desenvolvimento humano. la descripción del dolor agudo y crónico desde las perspectiva del ciclo de vida. participaron 861 personas con dolor. Se utilizó la Escala Multidimensional de Evaluación del Dolor (EMEDOR). en el método de estimación de categoría el descriptor de dolor crónico más alto para niños y adolescentes fue de Molesto y para adultos fue Incómodo. Los descriptores mayores de dolor agudo para niños y adolescentes fueron Complejo y para adultos Insoportable. En el método de estimación de magnitud, el mayor descriptor de dolor crónico fueron Atormentador y el mayor de dolor agudo fue Terrible. la EMEDOR es una escala confiable y puede ser utilizada en diferentes etapas de desarrollo.

Design and synthesis of novel δ opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration.

PubMed

Watanabe, Yoshikazu; Hayashida, Kohei; Saito, Daisuke; Takahashi, Toshihiro; Sakai, Junichi; Nakata, Eriko; Kanda, Takashi; Iwai, Takashi; Hirayama, Shigeto; Fujii, Hideaki; Yamakawa, Tomio; Nagase, Hiroshi

2017-08-01

We designed and synthesized novel δ opioid receptor (DOR) agonists 3a-i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore an oxazatricyclodecane skeleton. In vitro assays using the blood-brain barrier (BBB) permeability test kit supported the idea that 3b achieved an excellent BBB permeability by converting an oxygen atom of 2 to a carbon atom (methylene group) in the core skeleton. As a result, 3b showed potent antinociceptive effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deep Space Navigation with Noncoherent Tracking Data

NASA Technical Reports Server (NTRS)

Ellis, J.

1983-01-01

Navigation capabilities of noncoherent tracking data are evaluated for interplanetary cruise phase and planetary (Venus) flyby orbit determination. Results of a formal covariance analysis are presented which show that a combination of one-way Doppler and delta DOR yields orbit accuracies comparable to conventional two-way Doppler tracking. For the interplanetary cruise phase, a tracking cycle consisting of a 3-hour Doppler pass and delta DOR (differential one-way range) from two baselines (one observation per overlap) acquired 3 times a month results in 100-km orbit determination accuracy. For reconstruction of a Venus flyby orbit, 10 days tracking at encounter consisting of continuous one-way Doppler and delta DOR sampled at one observation per overlap is sufficient to satisfy the accuracy requirements.

Size Distribution and Dispersion of Droplets Generated by Impingement of Breaking Waves on Oil Slicks

NASA Astrophysics Data System (ADS)

Li, C.; Miller, J.; Wang, J.; Koley, S. S.; Katz, J.

2017-10-01

This laboratory experimental study investigates the temporal evolution of the size distribution of subsurface oil droplets generated as breaking waves entrain oil slicks. The measurements are performed for varying wave energy, as well as large variations in oil viscosity and oil-water interfacial tension, the latter achieved by premixing the oil with dispersant. In situ measurements using digital inline holography at two magnifications are applied for measuring the droplet sizes and Particle Image Velocimetry (PIV) for determining the temporal evolution of turbulence after wave breaking. All early (2-10 s) size distributions have two distinct size ranges with different slopes. For low dispersant to oil ratios (DOR), the transition between them could be predicted based on a turbulent Weber (We) number in the 2-4 range, suggesting that turbulence plays an important role. For smaller droplets, all the number size distributions have power of about -2.1, and for larger droplets, the power decreases well below -3. The measured steepening of the size distribution over time is predicted by a simple model involving buoyant rise and turbulence dispersion. Conversely, for DOR 1:100 and 1:25 oils, the diameter of slope transition decreases from ˜1 mm to 46 and 14 µm, respectively, much faster than the We-based prediction, and the size distribution steepens with increasing DOR. Furthermore, the concentration of micron-sized droplets of DOR 1:25 oil increases for the first 10 min after entrainment. These phenomena are presumably caused by the observed formation and breakup oil microthreads associated with tip streaming.

Diagnostic Performance of Peripapillary Retinal Nerve Fiber Layer Thickness for Detection of Glaucoma in an Elderly Population: The ALIENOR Study.

PubMed

Schweitzer, Cedric; Korobelnik, Jean-Francois; Le Goff, Melanie; Rahimian, Olivier; Malet, Florence; Rougier, Marie-Benedicte; Delyfer, Marie-Noelle; Dartigues, Jean-Francois; Delcourt, Cecile

2016-11-01

To assess diagnostic accuracy of spectral-domain optical coherence tomography (SD-OCT) to discriminate glaucoma and control subjects in an elderly population. The antioxidants, essential lipids, nutrition and ocular maladies study (ALIENOR: "Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires") is a population-based study. From 2009 to 2010, a total of 624 subjects, aged 74 years or older underwent a complete eye examination, including optic disc color photography and SD-OCT examination of the macula and the optic nerve head. Glaucoma diagnosis was made using retinophotography of the optic nerve head and International Society for Epidemiologic and Geographical Ophthalmology criteria. Average and sectorial peripapillary retinal nerve fiber layer thicknesses (RNFLT) were compared between glaucoma and control subjects using area under the receiver operating characteristic curves (AUC), positive and negative likelihood ratios (LR+/LR-), and diagnostic odds ratios (DOR). A total of 532 subjects had complete data, 492 were classified as controls and 40 were classified as glaucoma. Mean age was 82.1 ± 4.2 years and average RNFLT was significantly different between both groups (controls: 88.7 ± 12.2 μm, glaucoma: 65.4 ± 14.4 μm, P < 0.001). Highest AUC values were observed for average (0.895), temporal-inferior (0.874), and temporal-superior (0.868) RNFLT. Temporal-superior RNFLT had the highest DOR (25.31; LR+, 4.65; LR-, 0.18), followed by average RNFLT (DOR: 24.80; LR+, 6.36; LR-, 0.26). When using the normative database provided by the machine, DOR increased to 31.03 (LR+, 1.75; LR-, 0.06) if at least one parameter was considered abnormal (at P < 0.05). Parameters of SD-OCT RNFL may provide valuable information in a screening strategy to improve glaucoma detection in a general population of elderly people.

Primary afferent neurons express functional delta opioid receptors in inflamed skin.

PubMed

Brederson, Jill-Desiree; Honda, Christopher N

2015-07-21

Peripherally-restricted opiate compounds attenuate hyperalgesia in experimental models of inflammatory pain, but have little discernable effect on nociceptive behavior in normal animals. This suggests that activation of opioid receptors on peripheral sensory axons contributes to decreased afferent activity after injury. Previously, we reported that direct application of morphine to cutaneous receptive fields decreased mechanical and heat-evoked responses in a population of C-fiber nociceptors in inflamed skin. Consistent with reported behavioral studies, direct application of morphine had no effect on fiber activity in control skin. The aim of the present study was to determine whether mechanical responsiveness of nociceptors innervating inflamed skin was attenuated by direct activation of delta opioid receptors (DORs) on peripheral terminals. An ex vivo preparation of rat plantar skin and tibial nerve was used to examine effects of a selective DOR agonist, deltorphin II, on responsiveness of single fibers innervating inflamed skin. Electrical recordings were made eighteen hours after injection of complete Freund's adjuvant into the hindpaw. Deltorphin II produced an inhibition of the mechanical responsiveness of single fibers innervating inflamed skin; an effect blocked by the DOR-selective antagonist, naltrindole. The population of units responsive to deltorphin II was identified as consisting of C fiber mechanical nociceptors. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of Circular Patch Plasty (Dor Procedure) or Linear Repair Techniques in the Treatment of Left Ventricular Aneurysms.

PubMed

Kaya, Ugur; Çolak, Abdurrahim; Becit, Necip; Ceviz, Munacettin; Kocak, Hikmet

2018-01-01

The aim of this study was to evaluate early clinical outcomes and echocardiographic measurements of the left ventricle in patients who underwent left ventricular aneurysm repair using two different techniques associated to myocardial revascularization. Eighty-nine patients (74 males, 15 females; mean age 58±8.4 years; range: 41 to 80 years) underwent post-infarction left ventricular aneurysm repair and myocardial revascularization performed between 1996 and 2016. Ventricular reconstruction was performed using endoventricular circular patch plasty (Dor procedure) (n=48; group A) or linear repair technique (n=41; group B). Multi-vessel disease in 55 (61.7%) and isolated left anterior descending (LAD) disease in 34 (38.2%) patients were identified. Five (5.6%) patients underwent aneurysmectomy alone, while the remaining 84 (94.3%) patients had aneurysmectomy with bypass. The mean number of grafts per patient was 2.1±1.2 with the Dor procedure and 2.9±1.3 with the linear repair technique. In-hospital mortality occurred in 4.1% and 7.3% in group A and group B, respectively (P>0.05). The results of our study demonstrate that post-infarction left ventricular aneurysm repair can be performed with both techniques with acceptable surgical risk and with satisfactory hemodynamic improvement.

Comparing analgesia and μ-opioid receptor internalization produced by intrathecal enkephalin

PubMed Central

Chen, Wenling; Song, Bingbing; Lao, Lijun; Pérez, Orlando A.; Kim, Woojae; Marvizón, Juan Carlos G.

2007-01-01

Summary Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude μ-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or δ-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu-enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was ten times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. PMID:17845806

A Chandra ACIS Study of 30 Doradus. II. X-Ray Point Sources in the Massive Star Cluster R136 and Beyond

NASA Astrophysics Data System (ADS)

Townsley, Leisa K.; Broos, Patrick S.; Feigelson, Eric D.; Garmire, Gordon P.; Getman, Konstantin V.

2006-04-01

We have studied the X-ray point-source population of the 30 Doradus (30 Dor) star-forming complex in the Large Magellanic Cloud using high spatial resolution X-ray images and spatially resolved spectra obtained with the Advanced CCD Imaging Spectrometer (ACIS) on board the Chandra X-Ray Observatory. Here we describe the X-ray sources in a 17'×17' field centered on R136, the massive star cluster at the center of the main 30 Dor nebula. We detect 20 of the 32 Wolf-Rayet stars in the ACIS field. The cluster R136 is resolved at the subarcsecond level into almost 100 X-ray sources, including many typical O3-O5 stars, as well as a few bright X-ray sources previously reported. Over 2 orders of magnitude of scatter in LX is seen among R136 O stars, suggesting that X-ray emission in the most massive stars depends critically on the details of wind properties and the binarity of each system, rather than reflecting the widely reported characteristic value LX/Lbol~=10-7. Such a canonical ratio may exist for single massive stars in R136, but our data are too shallow to confirm this relationship. Through this and future X-ray studies of 30 Dor, the complete life cycle of a massive stellar cluster can be revealed.

PS3-21: Extracting Utilization Data from Clarity into VDW Using Oracle and SAS

PubMed Central

Chimmula, Srivardhan

2013-01-01

Background/Aims The purpose of the presentation is to demonstrate how we use SAS and Oracle to load VDW_Utilization, VDW_DX, and VDW_PX tables from Clarity at the Kaiser Permanente Northern California (KPNC) Division of Research (DOR) site. Methods DOR uses the best of Oracle PL/ SQL and SAS capabilities in building Extract Transform and Load (ETL) processes. These processes extract patient encounter, diagnosis, and procedure data from Teradata-based Clarity. The data is then transformed to fit HMORN’s VDW definitions of the table. This data is then loaded into the Oracle-based VDW table on DOR’s research database and then finally a copy of the table is also created as a SAS dataset. Results DOR builds robust and efficient ETL processes that refresh VDW Utilization table on a monthly basis processing millions of records/observations. The ETL processes have the capability to identify daily changes in Clarity and update the VDW tables on a daily basis. Conclusions KPNC DOR combines the best of both Oracle and SAS worlds to build ETL processes that load the data into VDW Utilization tables efficiently.

Detection of a large sample of γ Doradus stars from Kepler space photometry and high-resolution ground-based spectroscopy

NASA Astrophysics Data System (ADS)

Tkachenko, A.; Aerts, C.; Yakushechkin, A.; Debosscher, J.; Degroote, P.; Bloemen, S.; Pápics, P. I.; de Vries, B. L.; Lombaert, R.; Hrudkova, M.; Frémat, Y.; Raskin, G.; Van Winckel, H.

2013-08-01

Context. The launches of the MOST, CoRoT, and Kepler missions opened up a new era in asteroseismology, the study of stellar interiors via interpretation of pulsation patterns observed at the surfaces of large groups of stars. These space missions deliver a huge amount of high-quality photometric data suitable to study numerous pulsating stars. Aims: Our ultimate goal is a detection and analysis of an extended sample of γ Dor-type pulsating stars with the aim to search for observational evidence of non-uniform period spacings and rotational splittings of gravity modes in main-sequence stars typically twice as massive as the Sun. This kind of diagnostic can be used to deduce the internal rotation law and to estimate the amount of rotational mixing in the near core regions. Methods: We applied an automated supervised photometric classification method to select a sample of 69 Gamma Doradus (γ Dor) candidate stars. We used an advanced method to extract the Kepler light curves from the pixel data information using custom masks. For 36 of the stars, we obtained high-resolution spectroscopy with the HERMES spectrograph installed at the Mercator telescope. The spectroscopic data are analysed to determine the fundamental parameters like Teff, log g, vsini, and [M/H]. Results: We find that all stars for which spectroscopic estimates of Teff and log g are available fall into the region of the HR diagram, where the γ Dor and δ Sct instability strips overlap. The stars cluster in a 700 K window in effective temperature; log g measurements suggest luminosity class IV-V, i.e. sub-giant or main-sequence stars. From the Kepler photometry, we identify 45 γ Dor-type pulsators, 14 γ Dor/δ Sct hybrids, and 10 stars, which are classified as "possibly γ Dor/δ Sct hybrid pulsators". We find a clear correlation between the spectroscopically derived vsini and the frequencies of independent pulsation modes. Conclusions: We have shown that our photometric classification based on the light curve morphology and colour information is very robust. The results of spectroscopic classification perfectly agree with the photometric classification. We show that the detected correlation between vsini and frequencies has nothing to do with rotational modulation of the stars but is related to their stellar pulsations. Our sample and frequency determinations offer a good starting point for seismic modelling of slow to moderately rotating γ Dor stars. Based on data gathered with NASA Discovery mission Kepler and spectra obtained with the HERMES spectrograph, which is installed at the Mercator Telescope, operated on the island of La Palma by the Flemish Community at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, and supported by the Fund for Scientific Research of Flanders (FWO), Belgium, the Research Council of KU Leuven, Belgium, the Fonds National de la Recherche Scientifique (F.R.S.-FNRS), Belgium, the Royal Observatory of Belgium, the Observatoire de Genève, Switzerland, and the Thüringer Landessternwarte Tautenburg, Germany.Tables A.1 and B.1 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/556/A52

Laparoscopic Heller Myotomy and Dor Fundoplication for Esophageal Achalasia: Technique and Perioperative Management.

PubMed

Andolfi, Ciro; Fisichella, P Marco

2016-11-01

Surgical correction of achalasia using laparoscopic Heller myotomy with Dor fundoplication is argued to be the gold standard treatment for patients with achalasia. The goal of this technical report is to illustrate our preferred approach to patients with achalasia and to provide the reader with a detailed description of our operative technique, its rationale, and our pre and postoperative management.

Kinematic structure of the 30 Doradus giant H II region

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Kennicutt, Robert C., Jr.

1994-01-01

We have used the echelle CCD spectrograph on the Cerro Tololo Inter-American Observatory (CTIO) 4 m telescope to map the nebular velocity field in the 30 Doradus giant H II region. The kinematics of 30 Dor are very complex. The outer regions are charaterized by a smooth velocity field, but its turbulent velocity, 30-40 km/s Full Width Half Maximum (FWHM), is considerably higher than those in most smaller H II regions. In the central 9 min core, multiple velocity components are observed at most positions. The velocity field is dominated by a large number of expanding structures, ranging in size from 1 to 100 pc and expansion velocities of 20-200 km/s, and often organized into large hierarchical networks. The integral of these complex expanding structures in 30 Dor produces a surprisingly simple profile with a broad Gaussian core and faint extended wings. Several fast-expanding shells, with diameters of 2-20 pc, expansion velocities of 100-300 km/s, and kinetic energies of 0.5-10 x 10(exp 50) ergs have been identified. The large fast-expanding shells and networks are coincident with extended X-ray sources and are probably associated with supernova remnants embedded in supershells produced by the combined effects of stellar winds and supernovae from OB associations. We have used the intensity-calibrated echelle spectra to determine the basic physical and dynamical properties of the kinematic features in 30 Dor. The expanding shells contain roughly half of the kinetic energy in the 30 Dor complex, and this energy is several times higher than the gravitational binding energy of the region. The energetic requirements of the gas are consistent with the observed stellar content of 30 Dor, if the gas is accelerated by a combination of stellar winds and supernovae. Extrapolating the current energy injection rate in the nebula over the lifetime of the OB complex suggest that 30 Dor and its vicinity will evolve into a supergiant shell as seen in the LMC and other nearby galaxies.

Reported estimates of diagnostic accuracy in ophthalmology conference abstracts were not associated with full-text publication

PubMed Central

Korevaar, Daniël A.; Cohen, Jérémie F.; Spijker, René; Saldanha, Ian J.; Dickersin, Kay; Virgili, Gianni; Hooft, Lotty; Bossuyt, Patrick M.M.

2016-01-01

Objective To assess whether conference abstracts that report higher estimates of diagnostic accuracy are more likely to reach full-text publication in a peer-reviewed journal. Study Design and Setting We identified abstracts describing diagnostic accuracy studies, presented between 2007 and 2010 at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. We extracted reported estimates of sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and diagnostic odds ratio (DOR). Between May and July 2015, we searched MEDLINE and EMBASE to identify corresponding full-text publications; if needed, we contacted abstract authors. Cox regression was performed to estimate associations with full-text publication, where sensitivity, specificity, and AUC were logit transformed, and DOR was log transformed. Results A full-text publication was found for 226/399 (57%) included abstracts. There was no association between reported estimates of sensitivity and full-text publication (hazard ratio [HR] 1.09 [95% confidence interval {CI} 0.98, 1.22]). The same applied to specificity (HR 1.00 [95% CI 0.88, 1.14]), AUC (HR 0.91 [95% CI 0.75, 1.09]), and DOR (HR 1.01 [95% CI 0.94, 1.09]). Conclusion Almost half of the ARVO conference abstracts describing diagnostic accuracy studies did not reach full-text publication. Studies in abstracts that mentioned higher accuracy estimates were not more likely to be reported in a full-text publication. PMID:27312228

A systematic review and meta-analysis of tests to predict wound healing in diabetic foot.

PubMed

Wang, Zhen; Hasan, Rim; Firwana, Belal; Elraiyah, Tarig; Tsapas, Apostolos; Prokop, Larry; Mills, Joseph L; Murad, Mohammad Hassan

2016-02-01

This systematic review summarized the evidence on noninvasive screening tests for the prediction of wound healing and the risk of amputation in diabetic foot ulcers. We searched MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus from database inception to October 2011. We pooled sensitivity, specificity, and diagnostic odds ratio (DOR) and compared test performance. Thirty-seven studies met the inclusion criteria. Eight tests were used to predict wound healing in this setting, including ankle-brachial index (ABI), ankle peak systolic velocity, transcutaneous oxygen measurement (TcPo2), toe-brachial index, toe systolic blood pressure, microvascular oxygen saturation, skin perfusion pressure, and hyperspectral imaging. For the TcPo2 test, the pooled DOR was 15.81 (95% confidence interval [CI], 3.36-74.45) for wound healing and 4.14 (95% CI, 2.98-5.76) for the risk of amputation. ABI was also predictive but to a lesser degree of the risk of amputations (DOR, 2.89; 95% CI, 1.65-5.05) but not of wound healing (DOR, 1.02; 95% CI, 0.40-2.64). It was not feasible to perform meta-analysis comparing the remaining tests. The overall quality of evidence was limited by the risk of bias and imprecision (wide CIs due to small sample size). Several tests may predict wound healing in the setting of diabetic foot ulcer; however, most of the available evidence evaluates only TcPo2 and ABI. The overall quality of the evidence is low, and further research is needed to provide higher quality comparative effectiveness evidence. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

A Spatial Study of X-ray Properties in Superbubble 30 Dor C with XMM-Newton

NASA Astrophysics Data System (ADS)

Babazaki, Yasunori; Mitsuishi, Ikuyuki; SANO, Hidetoshi; Yoshiike, Satoshi; Fukuda, Tatsuya; Maruyama, Shohei; Fujii, Kosuke; Fukui, Yasuo; Tawara, Yuzuru; Matsumoto, Hironori

2015-08-01

Supernova remnants (SNRs) in the Galaxy are believed to be most likely accelerators of cosmic-rays (CRs) in an energy range less than 3×10^15 eV. Thus SNRs emit synchrotron X-rays by high-energy electrons. Sano et al. (2014) investigated spatially-resolved X-ray spectral properties of a shell-type SNR RX1713.77-3946 which shows strong non-thermal X-ray emissions. A large variation in the photon index is found and the photon index tends to be hard with increasing an interstellar gas density, suggesting that CR electrons are efficiently accelerated in denser interstellar gas environments. Few studies have focused on a photon index variation in superbubbles which possess 100-1000 pc diameter shells of swept-up interstellar materials containing hot (~10^6 K) shock-heated gas. The superbubble 30 Dor C in the Large Magellanic Cloud is one of the best targets for examining the photon index variation, because 30 Dor C is by far strong non-thermal X-ray emissions, and thus provides an ideal laboratory for probing non-thermal emission mechanisms in the supperbubble. We investigated X-ray spectral properties of the superbubble with a high spatial resolution of on the order of 10 pc. Consequently, the spectra in the west region of 30 Dor C can be described with a combination of absorbed thermal and non-thermal models while the spectra in the east region can be fitted with an absorbed non-thermal model. The photon index and intensity in 2-10 keV show variations of 2.0-3.5 and (0.6-8.0) × 10^-7 erg/s/cm^2, respectively. The temperature of the thermal component ranges from ~0.1 to ~0.3 keV. We will discuss an interaction between the hot gas and an interstellar gas using mutiwavelength data.

X-rays from superbubbles in the Large Magellanic Cloud

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Mac Low, Mordecai-Marc

1990-01-01

Diffuse X-ray emission not associated with known supernova remnants (SNRs) are found in seven Large Magellanic Cloud H II complexes encompassing 10 OB associations: N44, N51D, N57A, N70, N154, N157 (30 Dor), and N158. Their X-ray luminosities range from 7 x 10 to the 34th ergs/s in N57A to 7 x 10 to the 36th ergs/s in 30 Dor. All, except 30 Dor, have simple ring morphologies, indicating shell structures. Modeling these as superbubbles, it is found that the X-ray luminosities expected from their hot interiors fall an order of magnitude below the observed values. SNRs close to the center of a superbubble add very little emission, but it is calculated that off-center SNRs hitting the ionized shell could explain the observed emission.

Arrestin–dependent but G–protein coupled receptor kinase–independent uncoupling of D2–dopamine receptors

PubMed Central

Celver, Jeremy; Sharma, Meenakshi; Thanawala, Vaidehi; Octeau, J. Christopher; Kovoor, Abraham

2016-01-01

We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (Kir3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-Kir3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor. PMID:23815307

Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors.

PubMed

Celver, Jeremy; Sharma, Meenakshi; Thanawala, Vaidehi; Christopher Octeau, J; Kovoor, Abraham

2013-10-01

We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-K(ir)3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor. © 2013 International Society for Neurochemistry.

Laparoscopic Heller-Dor for primary esophageal achalasia: outcomes in 173 patients.

PubMed

Rosati, Riccardo; Fumagalli Romario, Uberto; Ceolin, Martina; Massaron, Simonetta; Peracchia, Alberto

2013-01-01

Laparoscopic Heller myotomy combined with anterior (Dor) fundoplication is the most widely-used surgical procedure for treating esophageal achalasia in Europe From November 1992 through May 2010 we performed laparoscopic Heller-Dor on 173 patients Conversion to laparotomy was required in three cases (1.7%) at the beginning of the experience (for mucosal) perforation which was the most frequent intraoperative complication, managed laparoscopically with the increasing experience. Five (2.9%) cases had minor postoperative complications. Clinical results were satisfactory in 99.4% of cases. One patient (0.6%) had severe persistent dysphagia. Mean esophageal diameter decreased from 50 mm ± 12 (range 20- 90) to 25 mm ± 7 (range 15-80). Lower esophageal sphincter pressure decreased from 32 mmHg (median, range 10- 93) pre-operatively to 11 mmHg (median, range 5-21) at one year follow up and residual pressure from 12 mmHg (median, range 3-30) to 4 mmHg (median, range 1-8). Impedance and pH monitoring showed normal levels in 39/47 (83%) patients who agreed to testing. The good outcomes of this experience, in part due to careful adherence to technical aspects of the operation, confirm that the laparoscopic Heller-Dor is the gold standard surgical treatment for esophageal achalasia.

Rotation of the asymptotic giant branch star R Doradus

NASA Astrophysics Data System (ADS)

Vlemmings, W. H. T.; Khouri, T.; Beck, E. De; Olofsson, H.; García-Segura, G.; Villaver, E.; Baudry, A.; Humphreys, E. M. L.; Maercker, M.; Ramstedt, S.

2018-05-01

High-resolution observations of the extended atmospheres of asymptotic giant branch (AGB) stars can now directly be compared to the theories that describe stellar mass loss. Using Atacama Large Millimeter/submillimeter Array (ALMA) high angular resolution (30 × 42 mas) observations, we have for the first time resolved stellar rotation of an AGB star, R Dor. We measure an angular rotation velocity of ωR sin i = (3.5 ± 0.3) × 10-9 rad s-1, which indicates a rotational velocity of |υrot sin i| = 1.0 ± 0.1 km s-1 at the stellar surface (R* = 31.2 mas at 214 GHz). The rotation axis projected on the plane of the sky has a position angle Φ = 7 ± 6°. We find that the rotation of R Dor is two orders of magnitude faster than expected for a solitary AGB star that will have lost most of its angular momentum. Its rotational velocity is consistent with angular momentum transfer from a close companion. As a companion has not been directly detected, we suggest R Dor has a low-mass, close-in companion. The rotational velocity approaches the critical velocity, set by the local sound speed in the extended envelope, and is thus expected to affect the mass-loss characteristics of R Dor.

Trapezium Systems and Stellar Jets in 30 Doradus

NASA Astrophysics Data System (ADS)

Walborn, Nolan

1999-07-01

30 Doradus is the nearest and best resolved extragalactic starburst, hence a paradigm for the phenomenon. Recent NICMOS observations of the new stellar generation being triggered by the outflows from R136 establish 30 Dor as a prime region for investigation of massive-star formation as well. Since 1" already subtends 50, 000 AU at 50 kpc, HST makes unique contributions to the study of 30 Dor. A recent groundbased spectral-classification study has provided new insights into the stellar content of 30 Dor, but many of the targets are resolved into multiple systems in the available WFPC2 images. We propose to obtain spatially resolved STIS blue spectroscopy of some of the newly found multiple systems, which is essential to determine accurate stellar tempertures and masses. Several systems each in the new and previous stellar generations are included. The HST spatial resolution also reduces the contamination of t he stellar spectra by the nebula r emission lines, which is a critical advantage. We also propose dithered PC nebular-line images of the young Trapezium systems Knots 1-3, which interact strongly with the surrounding interstellar medium, forming several parsec-scale jets. Finally, we shall do two WFPC2 pointings with continuum filters, to complete the coverage of the field, which currently limits the search for multiple systems and the illuminating comparisons with IR and other data.

Amplitude Variability in gamma Dor and delta Sct Stars Observed by Kepler

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guzik, Joyce Ann; Kosak, Mary Katherine; Bradley, Paul Andrew

2015-08-17

The NASA Kepler spacecraft data revealed a large number of new multimode nonradially pulsating gamma Dor and delta Sct variable stars. The Kepler high-precision long time-series photometry makes it possible to study amplitude variations of the frequencies, and recent literature on amplitude and frequency variations in nonradially pulsating variables is summarized. Several methods are applied to study amplitude variability in about a dozen gamma Doradus or delta Scuti candidate variable stars observed for several quarters as part of the Kepler Guest Observer program. The magnitude and timescale of the amplitude variations are discussed, along with the presence or absence ofmore » correlations between amplitude variations for different frequencies of a given star. Proposed causes of amplitude spectrum variability that will require further investigation are also discussed.« less

Endogenous opioid system: a promising target for future smoking cessation medications.

PubMed

Norman, Haval; D'Souza, Manoranjan S

2017-05-01

Nicotine addiction continues to be a health challenge across the world. Despite several approved medications, smokers continue to relapse. Several human and animal studies have evaluated the role of the endogenous opioid system as a potential target for smoking cessation medications. In this review, studies that have elucidated the role of the mu (MORs), delta (DORs), and kappa (KORs) opioid receptors in nicotine reward, nicotine withdrawal, and reinstatement of nicotine seeking will be discussed. Additionally, the review will discuss discrepancies in the literature and therapeutic potential of the endogenous opioid system, and suggest studies to address gaps in knowledge with respect to the role of the opioid receptors in nicotine dependence. Data available till date suggest that blockade of the MORs and DORs decreased the rewarding effects of nicotine, while activation of the MORs and DORs decreased nicotine withdrawal-induced aversive effects. In contrast, activation of the KORs decreased the rewarding effects of nicotine, while blockade of the KORs decreased nicotine withdrawal-induced aversive effects. Interestingly, blockade of the MORs and KORs attenuated reinstatement of nicotine seeking. In humans, MOR antagonists have shown benefits in select subpopulations of smokers and further investigation is required to realize their full therapeutic potential. Future work must assess the influence of polymorphisms in opioid receptor-linked genes in nicotine dependence, which will help in both identifying individuals vulnerable to nicotine addiction and the development of opioid-based smoking cessation medications. Overall, the endogenous opioid system continues to be a promising target for future smoking cessation medications.

Do Individuals with Fragile X Syndrome Show Developmental Stuttering or Not? Comment on "Speech Fluency in Fragile X Syndrome" by Van Borsel, Dor and Rondal

ERIC Educational Resources Information Center

Howell, Peter

2008-01-01

Van Borsel, Dor, and Rondal (2007) examined the speech of seven boys and two young male adults with fragile X syndrome and considered whether their speech was comparable to that reported in the developmental stuttering literature. They listed five criteria which led them to conclude that the speech patterns of speakers with fragile X syndrome…

The Mars Observer differential one-way range demonstration

NASA Technical Reports Server (NTRS)

Kroger, P. M.; Border, J. S.; Nandi, S.

1994-01-01

Current methods of angular spacecraft positioning using station differenced range data require an additional observation of an extragalactic radio source (quasar) to estimate the timing offset between the reference clocks at the two Deep Space Stations. The quasar observation is also used to reduce the effects of instrumental and media delays on the radio metric observable by forming a difference with the spacecraft observation (delta differential one-way range, delta DOR). An experiment has been completed using data from the Global Positioning System satellites to estimate the station clock offset, eliminating the need for the quasar observation. The requirements for direct measurement of the instrumental delays that must be made in the absence of a quasar observation are assessed. Finally, the results of the 'quasar-free' differential one-way range, or DOR, measurements of the Mars Observer spacecraft are compared with those of simultaneous conventional delta DOR measurements.

Case report of robotic dor fundoplication for scleroderma esophagus with aperistalsis on manometry.

PubMed

Andrade, Alonso; Folstein, Matthew K; Davis, Brian R

2017-01-01

Scleroderma is a systemic disease of collagen deposition resulting in fibrosis of small arteries and arterioles. It commonly affects the skin, lungs, and gastrointestinal tract. The most common site of GI tract involvement is the esophagus. We present the case report of a 44year old female with scleroderma esophagus and severe reflux which was successfully treated with robotic dor fundoplication. Because of the wide variety of symptoms with which this problem can present, a tailored approach taking into consideration the patient's symptomatology and findings during diagnostic work-up was implemented with good results. The patient exhibited complete resolution of symptoms at short term follow up. Robotic dor fundoplication is an effective option for patients with scleroderma esophagus and no evidence of hiatal hernia or esophageal shortening. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Are Immigrants More Physically Active Than Native-Born Australians and Does it Changes Over Time? Evidence From a Nationally Representative Longitudinal Survey.

PubMed

Joshi, Suresh; Jatrana, Santosh; Paradies, Yin

2017-02-01

We investigated the differences and over time changes in recommended physical activity among foreign-born (FB) from English speaking countries (ESC) and non-English speaking countries (NESC) relative to native-born (NB) Australians, and whether the association between nativity and duration of residence (DoR) and physical activity is mediated by English language proficiency, socioeconomic status and social engagement/membership. This study applies multilevel group-meancentered mixed (hybrid) logistic regression models to 12 waves of longitudinal data (12,634 individuals) from the Household, Income and Labor Dynamics in Australia survey with engagement in physical activities for more than 3 times a week as the outcome variable. Immigrants from ESC had higher odds of physical activity, while immigrants from NESC had significantly lower odds of physical activity than NB Australians, after adjusting for covariates. There was no evidence that these differences changed by DoR among immigrants from NESC, whereas ESC immigrants had higher odds of physical activity when their DoR was more than 20 years. We also found a mediating role of English language proficiency on immigrants physical activities. Appropriate health promotion interventions should be implemented to foster physical activities among NESC immigrants, considering English language proficiency as an important factor in designing interventions.

First discovery of a magnetic field in a main-sequence δ Scuti star: the Kepler star HD 188774

NASA Astrophysics Data System (ADS)

Neiner, C.; Lampens, P.

2015-11-01

The Kepler space mission provided a wealth of δ Sct-γ Dor hybrid candidates. While some may be genuine hybrids, others might be misclassified due to the presence of a binary companion or to rotational modulation caused by magnetism and related surface inhomogeneities. In particular, the Kepler δ Sct-γ Dor hybrid candidate HD 188774 shows a few low frequencies in its light and radial velocity curves, whose origin is unclear. In this work, we check for the presence of a magnetic field in HD 188774. We obtained two spectropolarimetric measurements with an Echelle SpectroPolarimetric Device for the Observation of Stars (ESPaDOnS) at Canada-France-Hawaii Telescope. The data were analysed with the least-squares deconvolution (LSD) method. We detected a clear magnetic signature in the Stokes V LSD profiles. The origin of the low frequencies detected in HD 188774 is therefore most probably the rotational modulation of surface spots possibly related to the presence of a magnetic field. Consequently, HD 188774 is not a genuine hybrid δ Sct-γ Dor star, but the first known magnetic main-sequence δ Sct star. This makes it a prime target for future asteroseismic and spot modelling. This result casts new light on the interpretation of the Kepler results for other δ Sct-γ Dor hybrid candidates.

An alternative derivatization reaction to the determination of doramectin in bovine milk using spectrofluorimetry

NASA Astrophysics Data System (ADS)

Maia, Priscila M. S.; de F. Rezende, Flavia B.; Netto, Annibal D. Pereira; de C. Marques, Flávia F.

The doramectin (DOR), which belongs to the avermectins group (AVM), has a high antiparasitic activity and so it has been widely used in food-producing animals. The DOR shows low fluorescence quantum efficiency and as a consequence, chemical derivatization reactions are necessary to produce derivatives with improved luminescent properties before its determination by fluorimetry. As the presence of this compound in food represents a risk to human health, an easy, clean and low cost derivatization reaction, which is alternative to those usually employed and that enables its spectrofluorimetric determination in milk samples, was developed. Ethanolic solutions of DOR, containing sodium hydroxide at a final concentration of 0.25 mol L-1, after 60 min of heating at 50 °C, produced fluorescent signals 1000 times higher than the original ethanolic solution. Using these optimized conditions, a linear response range that extended from 50.00 to 1000 μg L-1, with a value of (R2) equal to 0.9970, was obtained. Average recovery of DOR was 92.5 ± 1.5% (n = 3) in bovine milk fortified samples submitted to a liquid-liquid extraction at low temperature and pre concentration process, indicating the usefulness and effectiveness of the proposed method. The proposed spectrofluorimetric method is an alternative to high-performance liquid chromatography (HPLC) based methods, allowing rapid and simple detection of doramectin in milk samples.

Chemical dispersants: Oil biodegradation friend or foe?

PubMed

Rahsepar, Shokouh; Smit, Martijn P J; Murk, Albertinka J; Rijnaarts, Huub H M; Langenhoff, Alette A M

2016-07-15

Chemical dispersants were used in response to the Deepwater Horizon oil spill in the Gulf of Mexico, both at the sea surface and the wellhead. Their effect on oil biodegradation is unclear, as studies showed both inhibition and enhancement. This study addresses the effect of Corexit on oil biodegradation by alkane and/or aromatic degrading bacterial culture in artificial seawater at different dispersant to oil ratios (DORs). Our results show that dispersant addition did not enhance oil biodegradation. At DOR 1:20, biodegradation was inhibited, especially when only the alkane degrading culture was present. With a combination of cultures, this inhibition was overcome after 10days. This indicates that initial inhibition of oil biodegradation can be overcome when different bacteria are present in the environment. We conclude that the observed inhibition is related to the enhanced dissolution of aromatic compounds into the water, inhibiting the alkane degrading bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic nicotine-induced changes in gene expression of delta and kappa-opioid receptors and their endogenous ligands in the mesocorticolimbic system of the rat.

PubMed

Ugur, Muzeyyen; Kaya, Egemen; Gozen, Oguz; Koylu, Ersin O; Kanit, Lutfiye; Keser, Aysegul; Balkan, Burcu

2017-09-01

Delta and kappa opioid receptors (DOR and KOR, respectively) and their endogenous ligands, proenkephalin (PENK) and prodynorphin (PDYN)-derived opioid peptides are proposed as important mediators of nicotine reward. This study investigated the regulatory effect of chronic nicotine treatment on the gene expression of DOR, KOR, PENK and PDYN in the mesocorticolimbic system. Three groups of rats were injected subcutaneously with nicotine at doses of 0.2, 0.4, or 0.6 mg/kg/day for 6 days. Rats were decapitated 1 hr after the last dose on day six, as this timing coincides with increased dopamine release in the mesocorticolimbic system. mRNA levels in the ventral tegmental area (VTA), lateral hypothalamic area (LHA), amygdala (AMG), dorsal striatum (DST), nucleus accumbens, and medial prefrontal cortex were measured by quantitative real-time PCR. Our results showed that nicotine upregulated DOR mRNA in the VTA at all of the doses employed, in the AMG at the 0.4 and 0.6 mg/kg doses, and in the DST at the 0.4 mg/kg dose. Conversely, PDYN mRNA was reduced in the LHA with 0.6 mg/kg nicotine and in the AMG with 0.4 mg/kg nicotine. KOR mRNA was also decreased in the DST with 0.6 mg/kg nicotine. Nicotine did not regulate PENK mRNA in any brain region studied. © 2017 Wiley Periodicals, Inc.

[Voix d'Or, an audio tool to revive memories].

PubMed

Braunschweig, Lina

2010-01-01

Voix d'Or is an audio tool designed to awaken the affective memory of elderly people and particularly those suffering from Alzheimer's disease. Every month it offers new radio programmes to initiate or facilitate leisure and entertainment activities, memory workshops or provide the basis of quiet moments. The tool has a double objective: to procure well-being, boost the individual's self-esteem and recognise his/her history and to facilitate exchange and communication between the residents and the staff of a care home.

DADLE enhances viability and anti-inflammatory effect of human MSCs subjected to 'serum free' apoptotic condition in part via the DOR/PI3K/AKT pathway.

PubMed

Reddy, L Vinod Kumar; Sen, Dwaipayan

2017-12-15

Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala 2 , D-Leu 5 ]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. Cell viability was measured using MTT and Annexin V/PI assays. Expressions of pro-apoptotic (Bcl2) and anti-apoptotic genes (Bax/Bad), levels of activated p44/42 MAPK, Akt, PI3-kinase-p110γ and cleaved caspase-3 were determined by qPCR and western blot. Levels of secreted cytokines were measured by ELISA. In comparison to the control, DADLE significantly increased cell survivability under serum deprived condition as confirmed by MTT (71% vs 45%) and Annexin V/PI assays (25.9% vs 3.7%). Significant up-regulation of pro-apoptotic Bcl2 (~2.1 folds), down-regulations of anti-apoptotic Bax/Bad (~2.6/2.7 folds) as well as of cleaved caspase-3, increased expression of PI3kinase subunit p110γ and activation of Akt (Ser473) were observed following DADLE treatment in cells under 'serum deprivation' stress. In addition, DADLE treated hMSCs secreted increased levels of anti-inflammatory cytokines (IL10/IL4/TGF-β) under serum deprived condition. LPS stimulated macrophages showed abated release of pro-inflammatory cytokines (IL1/TNFα/IL6) when grown in hMSC conditioned 'serum deprived' media treated with DADLE. Both the cytoprotective and anti-inflammatory effects of DADLE were inhibited by the DOR specific antagonist naltrindole. The DOR signaling pathway improved cell viability and enhanced anti-inflammatory effect of hMSCs subjected to 'serum deprivation' stress that could have potential therapeutic benefits in reparative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Protection of adult rat cardiac myocytes from ischemic cell death: role of caveolar microdomains and delta-opioid receptors.

PubMed

Patel, Hemal H; Head, Brian P; Petersen, Heidi N; Niesman, Ingrid R; Huang, Diane; Gross, Garrett J; Insel, Paul A; Roth, David M

2006-07-01

The role of caveolae, membrane microenvironments enriched in signaling molecules, in myocardial ischemia is poorly defined. In the current study, we used cardiac myocytes prepared from adult rats to test the hypothesis that opioid receptors (OR), which are capable of producing cardiac protection in vivo, promote cardiac protection in cardiac myocytes in a caveolae-dependent manner. We determined protein expression and localization of delta-OR (DOR) using coimmunohistochemistry, caveolar fractionation, and immunoprecipitations. DOR colocalized in fractions with caveolin-3 (Cav-3), a structural component of caveolae in muscle cells, and could be immunoprecipitated by a Cav-3 antibody. Immunohistochemistry confirmed plasma membrane colocalization of DOR with Cav-3. Cardiac myocytes were subjected to simulated ischemia (2 h) or an ischemic preconditioning (IPC) protocol (10 min ischemia, 30 min recovery, 2 h ischemia) in the presence and absence of methyl-beta-cyclodextrin (MbetaCD, 2 mM), which binds cholesterol and disrupts caveolae. We also assessed the cardiac protective effects of SNC-121 (SNC), a selective DOR agonist, on cardiac myocytes with or without MbetaCD and MbetaCD preloaded with cholesterol. Ischemia, simulated by mineral oil layering to inhibit gas exchange, promoted cardiac myocyte cell death (trypan blue staining), a response blunted by SNC (37 +/- 3 vs. 59 +/- 3% dead cells in the presence and absence of 1 muM SNC, respectively, P < 0.01) or by use of the IPC protocol (35 +/- 4 vs. 62 +/- 3% dead cells, P < 0.01). MbetaCD treatment, which disrupted caveolae (as detected by electron microscopy), fully attenuated the protective effects of IPC or SNC, resulting in cell death comparable to that of the ischemic group. By contrast, SNC-induced protection was not abrogated in cells incubated with cholesterol-saturated MbetaCD, which maintained caveolae structure and function. These findings suggest a key role for caveolae, perhaps through enrichment of signaling molecules, in contributing to protection of cardiac myocytes from ischemic damage.

Assessment and management of pain in newborns hospitalized in a Neonatal Intensive Care Unit: a cross-sectional study.

PubMed

Sposito, Natália Pinheiro Braga; Rossato, Lisabelle Mariano; Bueno, Mariana; Kimura, Amélia Fumiko; Costa, Taine; Guedes, Danila Maria Batista

2017-09-12

to determine the frequency of pain, to verify the measures adopted for pain relief during the first seven days of hospitalization in the Neonatal Intensive Care Unit and to identify the type and frequency of invasive procedures to which newborns are submitted. cross-sectional retrospective study. Out of the 188 hospitalizations occurred during the 12-month period, 171 were included in the study. The data were collected from the charts and the presence of pain was analyzed based on the Neonatal Infant Pain Scale and on nursing notes suggestions of pain. For statistical analysis, the Statistical Package for the Social Sciences was used, and the significance level was set at 5%. there was at least one record of pain in 50.3% of the hospitalizations, according to the pain scale adopted or nursing note. The newborns underwent a mean of 6.6 invasive procedures per day. Only 32.5% of the pain records resulted in the adoption of pharmacological or non-pharmacological intervention for pain relief. newborns are frequently exposed to pain and the low frequency of pharmacological or non-pharmacological interventions reinforces the undertreatment of this condition. determinar a frequência de dor e verificar as medidas realizadas para seu alívio durante os sete primeiros dias de internação na Unidade de Terapia Intensiva Neonatal, bem como identificar o tipo e frequência de procedimentos invasivos aos quais os recém-nascidos foram submetidos. estudo retrospectivo transversal. Das 188 internações ocorridas no período estipulado de 12 meses, 171 foram incluídas na pesquisa. Os dados foram coletados a partir dos prontuários e a presença de dor foi analisada tanto com base na escala de dor Neonatal Infant Pain Scale quanto mediante anotação de enfermagem sugestiva de dor. Para análise estatística, utilizou-se o programa Statistical Package for the Social Sciences, adotando-se nível de significância de 5%. em 50,3% das internações houve ao menos um registro de dor, conforme escala de dor adotada ou anotação de enfermagem. Os recém-nascidos foram submetidos à média de 6,6 procedimentos invasivos por dia. Apenas 32,5% dos registros de dor resultaram na adoção de condutas farmacológicas ou não farmacológicas para seu alívio. observa-se que os recém-nascidos são frequentemente expostos à dor e a baixa frequência de intervenções farmacológicas ou não farmacológicas reforça o subtratamento dessa condição. determinar la frecuencia del dolor, comprobar las medidas tomadas para su alivio durante los siete primeros días de internación en una Unidad de Terapia Intensiva Neonatal e identificar el tipo de procedimientos invasivos y la frecuencia a que se sometieron los recién nacidos. estudio retrospectivo transversal. De las 188 internaciones realizadas en el período estipulado de 12 meses, se incluyeron 171 en la investigación. Los datos se recolectaron a partir de los prontuarios; la presencia de dolor se analizó según la Escala de Valorización del Dolor en el Neonato (Neonatal Infant Pain Scale) y las notas de enfermería sobre el dolor. Para el análisis estadístico, se utilizó el programa 'Paquete estadístico para las ciencias sociales' (Statistical Package for the Social Sciences), adoptándose el nivel de significación del 5%. en el 50,3% de las internaciones hubo al menos un registro de dolor, según la escala de dolor adoptada o las notas de la enfermería. Se sometió a los recién nacidos a un promedio de 6,6 procedimientos invasivos por día. Sólo el 32,5% de los registros de dolor resultaron en la adopción de conductas farmacológicas o no farmacológicas para su alivio. se observa que los recién nacidos a menudo están expuestos al dolor, y la frecuencia baja de intervenciones farmacológicas o de las no farmacológicas refuerza el subtratamiento de dicha condición.

Phase 2 prospective analysis of alectinib in ALK-positive, crizotinib-resistant non-small-cell lung cancer

PubMed Central

Shaw, Alice T.; Gandhi, Leena; Gadgeel, Shirish; Riely, Gregory J.; Cetnar, Jeremy; West, Howard; Camidge, D. Ross; Socinski, Mark A.; Chiappori, Alberto; Mekhail, Tarek; Chao, Bo H.; Borghaei, Hossein; Gold, Kathryn A.; Zeaiter, Ali; Bordogna, Walter; Balas, Bogdana; Puig, Oscar; Henschel, Volkmar; Ignatius Ou, Sai-Hong

2016-01-01

Summary Background Alectinib, a highly selective, central nervous system (CNS)-active anaplastic lymphoma kinase (ALK) inhibitor, demonstrated promising clinical activity in crizotinib-naïve and crizotinib-resistant ALK-positive non-small-cell lung cancer (NSCLC). This phase 2 study evaluated the safety and efficacy of alectinib in ALK-positive NSCLC patients who progressed on previous crizotinib. Methods This ongoing North American study (NCT01871805) enrolled patients with stage IIIB/IV ALK-positive NSCLC, who had progressed following crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death or withdrawal. Primary endpoint was overall response rate (ORR) by independent review committee (IRC) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), intracranial ORR and DOR, safety, and patient-reported outcomes. The intent-to-treat population was used for efficacy and safety analyses, with the response evaluable population used for response endpoints. Findings A total of 87 patients were enrolled in the intent-to-treat population. All patients had received prior crizotinib therapy, and 64 patients (74%) had also received prior chemotherapy. Fifty-two patients (60%) had baseline CNS metastases, of whom 18 (35%) had received no prior brain radiation therapy. At the time of primary analysis (median follow-up 4.8 months), ORR by IRC was 48% (95% CI 36–60). Adverse events were predominantly grade 1 or 2, most commonly constipation, fatigue, myalgia and peripheral edema. The most common grade ≥3 AEs were changes in laboratory values, including increased blood creatine phosphokinase (in 8%, n=7), increased alanine aminotransferase (in 6% n=5), and increased aspartate aminotransferase (in 5% n=4). Interpretation Alectinib demonstrated clinical efficacy and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Alectinib was active in the CNS, as demonstrated by durable responses in the majority of crizotinib-resistant patients with CNS disease. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib. PMID:26708155

Opioid Peptidomimetics: Leads for the Design of Bioavailable Mixed Efficacy Mu Opioid Receptor (MOR) Agonist/Delta Opioid Receptor (DOR) Antagonist Ligands

PubMed Central

Mosberg, Henry I.; Yeomans, Larisa; Harland, Aubrie A.; Bender, Aaron M.; Sobczyk-Kojiro, Katarzyna; Anand, Jessica P.; Clark, Mary J.; Jutkiewicz, Emily M.; Traynor, John R.

2013-01-01

We have previously described opioid peptidomimetic, 1, employing a tetrahydroquinoline scaffold and modeled on a series of cyclic tetrapeptide opioid agonists. We have recently described modifications to these peptides that confer a mu opioid receptor (MOR) agonist, delta opioid receptor (DOR) antagonist profile, which has been shown to reduce the development of tolerance to the analgesic actions of MOR agonists. Several such bifunctional ligands have been reported, but none has been demonstrated to cross the blood brain barrier. Here we describe the transfer of structural features that evoked MOR agonist/DOR antagonist behavior in the cyclic peptides to the tetrahydroquinoline scaffold and show that the resulting peptidomimetics maintain the desired pharmacological profile. Further, the 4R diastereomer of 1 was fully efficacious and approximately equipotent to morphine in the mouse warm water tail withdrawal assay following intraperitoneal administration and thus a promising lead for the development of opioid analgesics with reduced tolerance. PMID:23419026

Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.

PubMed

Le Naour, Morgan; Lunzer, Mary M; Powers, Michael D; Kalyuzhny, Alexander E; Benneyworth, Michael A; Thomas, Mark J; Portoghese, Philip S

2014-08-14

It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.

The change of nuclear LC3 distribution in acute myeloid leukemia cells.

PubMed

Guo, Wenjian; Jin, Jingrui; Pan, Jiajia; Yao, Rongxing; Li, Xia; Huang, Xin; Ma, Zhixing; Huang, Sujuan; Yan, Xiao; Jin, Jie; Dong, Aishu

2018-05-09

Making sure the change of nuclear LC3 distribution in the autophagy of acute myeloid leukemia (AML) cell and finding out the regulation mechanism may lead to a breakthrough for killing AML cells. Western blots were performed to assess the expression of autophagy proteins. Changes in the LC3 distribution were monitored by immunofluorescence assays together with western blots, and the expression levels of Sirt1, DOR, Beclin1, HMGB1, and AMPK mRNA were detected via fluorescent quantitative PCR. The effects of Sirt1 and DOR on cell proliferation and survival were analyzed by MTT, flow cytometry, and western blotting assays. We found that treating AML cells with Ara-c or Sorafenib resulted in autophagy enhancement, and when autophagy was enhanced, nuclear LC3 moved into the cytoplasm. Notably, when autophagy was inhibited by blocking the nuclear LC3 shift, the cytotoxicity of drugs was enhanced. Our results also identified Sirt1 and DOR as regulatory molecules for the observed nuclear LC3 shift, and these molecules further affected the expression of Beclin1, HMGB1, and AMPK. Our results suggest the distribution of nuclear LC3 can be a novel way for further studying death of AML cells,and the regulatory molecules may be new targets for treating AML. Copyright © 2018 Elsevier Inc. All rights reserved.

Theoretical study of homonuclear J coupling between quadrupolar spins: single-crystal, DOR, and J-resolved NMR.

PubMed

Perras, Frédéric A; Bryce, David L

2014-05-01

The theory describing homonuclear indirect nuclear spin-spin coupling (J) interactions between pairs of quadrupolar nuclei is outlined and supported by numerical calculations. The expected first-order multiplets for pairs of magnetically equivalent (A2), chemically equivalent (AA'), and non-equivalent (AX) quadrupolar nuclei are given. The various spectral changeovers from one first-order multiplet to another are investigated with numerical simulations using the SIMPSON program and the various thresholds defining each situation are given. The effects of chemical equivalence, as well as quadrupolar coupling, chemical shift differences, and dipolar coupling on double-rotation (DOR) and J-resolved NMR experiments for measuring homonuclear J coupling constants are investigated. The simulated J coupling multiplets under DOR conditions largely resemble the ideal multiplets predicted for single crystals, and a characteristic multiplet is expected for each of the A2, AA', and AX cases. The simulations demonstrate that it should be straightforward to distinguish between magnetic inequivalence and equivalence using J-resolved NMR, as was speculated previously. Additionally, it is shown that the second-order quadrupolar-dipolar cross-term does not affect the splittings in J-resolved experiments. Overall, the homonuclear J-resolved experiment for half-integer quadrupolar nuclei is demonstrated to be robust with respect to the effects of first- and second-order quadrupolar coupling, dipolar coupling, and chemical shift differences. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined time-series resistivity and geochemical tracer techniques to examine submarine groundwater discharge at Dor Beach, Israel

USGS Publications Warehouse

Swarzenski, P.W.; Burnett, W.C.; Greenwood, W.J.; Herut, B.; Peterson, R.; Dimova, N.; Shalem, Y.; Yechieli, Y.; Weinstein, Y.

2006-01-01

A high-resolution, stationary geophysical and geochemical survey was conducted at Dor Beach, Israel, to examine the shallow coastal hydrogeology and its control on the exchange of submarine groundwater with the shallow Mediterranean Sea. Time-series resistivity profiles using a new 56 electrode (112-m long) marine cable produced detailed profiles of the fresh water/salt water interface and the subtle response of this interface to tidal excursions and other forcing factors. Such information, when ground-truthed with representative pore water salinities and formation resistivity values, can provide unique information of the extent and rates of submarine groundwater discharge (SGD). Time-series 222Rn measurements of the adjacent coastal water column complemented these geophysical techniques and were modeled to yield integrated advective flow rates across the sediment/water interface, which at Dor Beach ranged from about 0 to 30 cm day-1 (mean = 7.1 cm d-1), depending on the tidal range. Such results suggest that the underlying hydrogeologic framework at Dor is favorable for substantial SGD. Extrapolating these SGD estimates across a 100-m wide coastal zone implies that the Rn-derived SGD rate would equal ???7.1 m3 d-1 per m of shoreline, and that the source of this discharging groundwater is a complex mixture of fresh groundwater derived from the upland Kurkar deposits, as well as locally recycled seawater. Copyright 2006 by the American Geophysical Union.

Vocational Rehabilitation Outcomes: Relationship between Individualized Plan for Employment Goals and Employment Outcomes

ERIC Educational Resources Information Center

Beveridge, Scott; Fabian, Ellen

2007-01-01

This study examined the relationship between attaining a job congruent with the Individualized Plan for Employment (IPE) vocational rehabilitation goal and vocational rehabilitation outcomes. Study participants were 171 vocational rehabilitation clients served by the Maryland State Department of Education Division of Rehabilitation Services (DORS)…

Identification of risk factors for mucosal injury during laparoscopic Heller myotomy for achalasia.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shusuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-02-01

Mucosal injury during myotomy is the most frequent complication seen with the Heller-Dor procedure for achalasia. The present study aimed to examine risk factors for such mucosal injury during this procedure. This was a retrospective analysis of patients who underwent the laparoscopic Heller-Dor procedure for achalasia at a single facility. Variables for evaluation included patient characteristics, preoperative pathophysiological findings, and surgeon's operative experience. Logistic regression was used to identify risk factors. We also examined surgical outcomes and the degree of patient satisfaction in relation to intraoperative mucosal injury. Four hundred thirty-five patients satisfied study criteria. Intraoperative mucosal injury occurred in 67 patients (15.4%). In univariate analysis, mucosal injury was significantly associated with the patient age ≥60 years, disease history ≥10 years, prior history of cardiac diseases, preoperative esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. In multivariate analysis involving these factors, the following variables were identified as risk factors: age ≥60 years, esophageal transverse diameter ≥80 mm, and surgeon's operative experience with fewer than five cases. The mucosal injury group had significant extension of the operative time and increased blood loss. However, there were no significant differences between the two groups in the incidence of reflux esophagitis or the degree of symptom alleviation postoperatively. The fragile esophagus caused by advanced patient age and/or dilatation were risk factor for mucosal injury during laparoscopic Heller-Dor procedure. And novice surgeon was also identified as an isolated risk factor for mucosal injury.

Periapical and endodontic status scale based on periapical bone lesions and endodontic treatment quality evaluation using cone-beam computed tomography.

PubMed

Venskutonis, Tadas; Plotino, Gianluca; Tocci, Luigi; Gambarini, Gianluca; Maminskas, Julius; Juodzbalys, Gintaras

2015-02-01

The purpose of this study was to present a new periapical and endodontic status scale (PESS) that is based on the complex periapical index (COPI), which was designed for the identification and classification of periapical bone lesions in cases of apical periodontitis, and the endodontically treated tooth index, which was designed for endodontic treatment quality evaluation by means of cone-beam computed tomographic (CBCT) analysis. Periapical and endodontic status parameters were selected from the already known indexes and scientific literature for radiologic evaluation. Radiographic images (CBCT imaging, digital orthopantomography [DOR], and digital periapical radiography) from 55 patients were analyzed. All parameters were evaluated on CBCT, DOR, and digital periapical radiographic images by 2 external observers. The statistical analysis was performed with software SPSS version 19.0 (SPSS Inc, Chicago, IL). Chi-square tests were used to compare frequencies of qualitative variables. The level of significance was set at P ≤ .05. Overall intraobserver and interobserver agreements were very good and good, respectively. CBCT analysis found more lesions and lesions of bigger dimension (P < .001). CBCT imaging was also superior in locating lesions in the apical part on the side compared with DOR and in the diagnosis of cortical bone destruction compared with both methods (P < .001). Through CBCT analysis, more root canals and more canals associated with lesions were found. The most informative and reproducible periapical and endodontic status parameters were selected, and a new PESS was proposed. The classification proposed in the present study seems to be reproducible and objective and adds helpful information with respect to the existing indexes. Future studies need to be conducted to validate PESS. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The Perceived Importance of Role-Specific Competencies for Health Care Leaders Establishes the Need to Expand Role Theory.

PubMed

Babinski, Paul J

2016-01-01

This cross-sectional quantitative study was undertaken to determine the extent to which individuals who have differing health care leadership roles perceived the importance of selected leadership competencies in their specific roles based on their experience. A total of 313 participants responded to the health care questionnaire. Principal component analysis identified factor structure and Cronbach α at .96 supported the reliability of the factor analysis. Multivariate analysis of variance tested the 4 health care leadership roles to determine if an effect was present among the competencies. A subsequent analysis of variance test was conducted on the competencies to confirm an effect was present, and a Games-Howell post hoc test followed. These tests indicated that there was a significant difference in rating the perceived importance of specific leadership competencies by the health care leaders in each competency domain. The participants included in this study consisted of the chief executive officer (CEO), director of nursing (DON), operating room director (ORD), and director of radiology (DOR). Based on the Games-Howell post hoc test, a commonality existed between the leaders. The CEOs and DONs often indicated no significant difference in competency perception to one another in relation to the dependent variables, yet indicated a significant difference in competency perception when compared with the ORDs and DORs. Similarly, the ORD and DOR variables often indicated no significant difference in competency perception to one another in relation to the dependent variables, yet indicated a significant difference in competency perception compared with the CEO and DON variables. This study positively indicated that health care leadership's perception of competencies does differ between the various leadership roles.

ACCURACY OF PLASMA FREE METANEPHRINES IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA AND PARAGANGLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

PubMed

Chen, Yan; Xiao, Huangmeng; Zhou, Xieda; Huang, Xiaoyu; Li, Yanbing; Xiao, Haipeng; Cao, Xiaopei

2017-10-01

Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the overall diagnostic accuracy of this biochemical test for PPGL. We searched the PubMed, the Cochrane Library, Web of Science, Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from January 1, 1995 to December 2, 2016 and selected studies written in English that assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the included studies. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve (AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed by I 2 . To identify the source of heterogeneity, we evaluated the threshold effect and performed a meta-regression. Deeks' funnel plot was selected for investigating any potential publication bias. Although the combination of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94, 95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99), DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94-0.98) values. Threshold effect and meta-regression analyses showed that different cut-offs, blood sampling positions, study types and test methods contributed to heterogeneity. This meta-analysis suggested an effective value for combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires more standardization using tightly regulated studies. AUC = area under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN = normetaneprhine; PPGL = pheochromocytoma and paraganglioma; QUADAS-2 = Quality Assessment of Diagnostic Accuracy Studies 2.

[Clinical experience of combined laparoscopic-endoscopic Heller myotomy and modified Dor fundoplication for cardiochalasia].

PubMed

Qiao, Xiaofang; Li, Jinlong; Xu, Hua; Wan, Xin; Zhu, Jiaming

2017-08-25

To investigate the efficacy of combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication for cardiochalasia patients. Clinical data of 11 cardiochalasia patients who underwent combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication by the same medical team from January 2015 to December 2016 at The Second Hospital of Jilin University were retrospectively analyzed. The procedure was as follows: an incision was made in the anterior wall of esophagus and dissection of esophageal muscular layer was performed, then the bulged esophageal mucosa was covered by the fundus after 180 degrees fold to the right (fundoplication), finally the gastric fundus was joined to the right diaphragmatic foot by 3 to 5 knotted suture. The efficacy was judged by the Eckardt scoring standard: the postoperative Eckardt score ≤3 points indicated effectiveness, otherwise the treatment was invalid. Combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication was completed successfully in all the 11 patients without any subsequent laparotomy and death. The mean operative time was 85 (78 to 137) min, blood loss was 15 (5 to 35) ml, and no upper digestive tract perforation occurred. The mean postoperative hospital stay was 7.0(6 to 9) d. After the operation, the pressure of lower esophageal sphincter decreased significantly compared to that before operation [(5.31±6.23) mmHg vs. (35.72±17.13) mmHg, P<0.05], and the Eckardt score decreased significantly as well (0.53±0.56 vs. 6.17±1.17, P<0.05). During the follow-up of 2 to 23 months, there was no postoperative mortality. One case experienced mild gastroesophageal reflux 6 months after operation, and another patient had recurrent dysphagia 17 months after operation, who both were improved after receiving proton pump inhibitors or gastric dynamic drugs, and balloon dilation. Combined laparoscopic-endoscopic lower esophageal sphincterotomy and modified Dor fundoplication is an effective and safe surgical procedure for cardiochalasia with minimal invasion and fast recovery.

Effects of Intrathecal SNC80, a Delta Receptor Ligand, on Nociceptive Threshold and Dorsal Horn Substance P Release

PubMed Central

Kouchek, Milad; Takasusuki, Toshifumi; Terashima, Tetsuji; Yaksh, Tony L.

2013-01-01

Delta-opioid receptors (DOR) are present in the superficial dorsal horn and are believed to regulate the release of small afferent transmitters as evidenced by the effects of spinally delivered delta-opioid preferring peptides. Here we examined the effects of intrathecal SNC80 [(+)-4-[α(R)-α-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-(methoxybenzyl)-N,N-diethylbenzamide], a selective nonpeptidic DOR agonist, in three preclinical pain models, acute thermal escape, intraplantar carrageenan-tactile allodynia, and intraplantar formalin flinches, and on the evoked release of substance P (SP) from small primary afferents. Rats with chronic intrathecal catheters received intrathecal vehicle or SNC80 (100 or 200 μg). Intrathecal SNC80 did not change acute thermal latencies or carrageenan-induced thermal hyperalgesia. However, SNC80 attenuated carrageenan-induced tactile allodynia and significantly reduced both phase 1 and phase 2 formalin-induced paw flinches, as assessed by an automatic flinch counting device. These effects were abolished by naltrindole (3 mg/kg i.p.), a selective DOR antagonist, but not CTOP (10 µg i.t.), a selective MOR antagonist. Furthermore, intrathecal SNC80 (200 μg) blocked formalin-induced substance P release otherwise evoked in the ispilateral superficial dorsal horn as measured by NK1 receptor internalization. In conclusion, intrathecal SNC80 alleviated pain hypersensitivity after peripheral inflammation in a fashion paralleling its ability to block peptide transmitter release from small peptidergic afferents, which by its pharmacology appears to represent an effect mediated by a spinal DOR. PMID:23978562

Ciguatoxin-like substances in edible fish on the eastern Mediterranean.

PubMed

Bentur, Yedidia; Spanier, Ehud

2007-09-01

The consumption of edible fish (e.g., Siganus spp) was assumed to have caused ciguatera poisoning at an atypical site, the eastern Mediterranean. This pilot study assesses the presence of ciguatoxin-like substances in edible fish on the eastern Mediterranean coast of Israel. Samples of Siganus rivulatus from polluted seawater (Haifa Bay), Siganus rivulatus from relatively clean seawater (Dor), and fish from the freshwater Sea of Galilee not inhabited by toxic algae were analyzed during summertime. Ciguatoxin-like substances were tested by a membrane immunobead assay that yields a color reaction (positive, weakly positive, negative). Significantly more large and small fish from Haifa Bay yielded positive color reactions compared to fish from Dor. Sea of Galilee fish gave no positive color reactions. Our results suggest the presence of ciguatoxin-like substances in edible fish of the eastern Mediterranean. Additional analyses are needed to determine whether these substances are ciguatoxins or related polyethers.

The occurrence of non-pulsating stars in the γ Dor and δ Sct pulsation instability regions: Results from Kepler quarter 14–17 data

DOE PAGES

Guzik, J. A.; Bradley, P. A.; Jackiewicz, J.; ...

2015-04-21

In this study, the high precision long time-series photometry of the NASA Kepler spacecraft provides an excellent means to discover and characterize variability in main-sequence stars, and to make progress in interpreting the pulsations to derive stellar interior structure and test stellar models. For stars of spectral types A–F, the Kepler data revealed a number of surprises, such as more hybrid pulsating Sct and Dor pulsators than expected, pulsators lying outside of the instability regions predicted by theory, and stars that were expected to pulsate, but showed no variability. In our 2013 Astronomical Review article, we discussed the statistics ofmore » variability for 633 faint (Kepler magnitude 14–16) spectral type A–F stars observed by Kepler during Quarters 6–13 (June 2010–June 2012).« less

The occurrence of non-pulsating stars in the γ Dor and δ Sct pulsation instability regions: Results from Kepler quarter 14–17 data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guzik, J. A.; Bradley, P. A.; Jackiewicz, J.

In this study, the high precision long time-series photometry of the NASA Kepler spacecraft provides an excellent means to discover and characterize variability in main-sequence stars, and to make progress in interpreting the pulsations to derive stellar interior structure and test stellar models. For stars of spectral types A–F, the Kepler data revealed a number of surprises, such as more hybrid pulsating Sct and Dor pulsators than expected, pulsators lying outside of the instability regions predicted by theory, and stars that were expected to pulsate, but showed no variability. In our 2013 Astronomical Review article, we discussed the statistics ofmore » variability for 633 faint (Kepler magnitude 14–16) spectral type A–F stars observed by Kepler during Quarters 6–13 (June 2010–June 2012).« less

Parallel Synthesis of Hexahydrodiimidazodiazepines Heterocyclic Peptidomimetics and Their in Vitro and in Vivo Activities at μ (MOR), δ (DOR), and κ (KOR) Opioid Receptors.

PubMed

Eans, Shainnel O; Ganno, Michelle L; Mizrachi, Elisa; Houghten, Richard A; Dooley, Colette T; McLaughlin, Jay P; Nefzi, Adel

2015-06-25

In the development of analgesics with mixed-opioid agonist activity, peripherally selective activity is expected to decrease side effects, minimizing respiratory depression and reinforcing properties generating significantly safer analgesic therapeutics. We synthesized diazaheterocyclics from reduced tripeptides. In vitro screening with radioligand competition binding assays demonstrated variable affinity for μ (MOR), δ (DOR), and κ (KOR) opioid receptors across the series, with the diimidazodiazepine 14 (2065-14) displaying good affinity for DOR and KOR. Central (icv), intraperitoneal (ip), or oral (po) administration of 14 produced dose-dependent, opioid-receptor mediated antinociception in the mouse, as determined from a 55 °C warm-water tail-withdrawal assay. Only trace amounts of compound 14 was found in brain up to 90 min later, suggesting poor BBB penetration and possible peripherally restricted activity. Central administration of 14 did not produce locomotor effects, acute antinociceptive tolerance, or conditioned-place preference or aversion. The data suggest these diazaheterocyclic mixed activity opioid receptor agonists may hold potential as new analgesics with fewer liabilities of use.

A new multiperiodic gamma Doradus variable in Andromedae.

NASA Astrophysics Data System (ADS)

Rodríguez, E.; Amado, P. J.; Costa, V.; Suárez, J. C.; Moya, A.; Poretti, E.; López-González, M. J.; Rolland, A.; López de Coca, P.

gamma Dor-type oscillations have been discovered in the star HD 218427 through simultaneous uvby photometric observations carried out in the year 2003. A few Hbeta -Crawford measurements were also collected for calibration purposes which place this star well-located inside the gamma Dor instability region. Frecuency analysis was carried out for different filters, the combined ``vby'' filter was also used and five frequencies were found as significant with periods ranging between 0.3 and 0.8 days. The recently developed Frequency Ratio Method (FRM, Moya et al. 2005) is used in order to perform a modal identification of the peaks.

Dor procedure for pulmonary atresia with intact ventricular septum in an infant.

PubMed

Kang, Yoonjin; Kwak, Jae Gun; Kim, Eung Rae; Kim, Woong-Han

2018-02-01

Pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation confers a high risk for myocardial infarction and complications of ischaemia, including left ventricle aneurysms. We describe an infant with pulmonary atresia with intact ventricular septum and right ventricle-dependent coronary circulation and a left ventricle apical aneurysm who successfully underwent the Dor procedure and a subsequent Fontan operation. Surgery for postinfarction left ventricle aneurysm can be considered in infants. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Simultaneous inter-arm and inter-leg systolic blood pressure differences to diagnose peripheral artery disease: a diagnostic accuracy study.

PubMed

Herráiz-Adillo, Ángel; Soriano-Cano, Alba; Martínez-Hortelano, José Alberto; Garrido-Miguel, Miriam; Mariana-Herráiz, Julián Ángel; Martínez-Vizcaíno, Vicente; Notario-Pacheco, Blanca

2018-04-01

Inter-arm systolic blood pressure differences (IASBPD) and inter-leg systolic blood pressure differences (ILSBPD) have arisen as potential tools to detect peripheral artery disease (PAD) and individuals at high cardiovascular risk. This study aims to evaluate the diagnostic accuracy of IASBPD and ILSBPD to detect PAD, and whether IASBPD or ILSBPD improves diagnostic accuracy of the oscillometric ankle-brachial index (ABI). In this prospective study, eligible for inclusion were consecutive adults, with at least one of the following cardiovascular risk factors: diabetes, dyslipidemia, hypertension, smoking habit or age ≥65. IASBPD, ILSBPD and ankle-brachial index (ABI) were measured in all participants through four-limb simultaneous oscillometric measurements and compared with Doppler ABI (reference test, positive cut-off: ≤ 0.9). Of 171 subjects included, PAD was confirmed in 23 and excluded in 148. Thirteen and 38 subjects had IASBPD and ILSBPD ≥10 mmHg, respectively. Pearson correlation with Doppler ABI of IASBPD and ILSBPD was 0.073 (P = .343) and -0.628 (P < .001), respectively. Diagnostic accuracy of an ILSBPD ≥10 mmHg to detect PAD was: sensitivity = 69.6% (95%CI = 48.6-90.5), specificity = 85.1% (79.1-91.2), diagnostic odds ratio (dOR) = 13.1 (4.8-35.5) and area under ROC curve (AUC) = 0.765 (0.616-0.915). IASBPD had an AUC = 0.532 (0.394-0.669), and oscillometric ABI had an AUC = 0.977 (0.950-1.000). The addition of ILSBPD to oscillometric ABI reduced dOR from 174.0 (38.3-789.9) to 34.4 (9.5-125.1). Similarly, the addition of IASBPD reduced dOR to 49.3 (14.6-167.0). In a Primary Care population with ≥1 cardiovascular risk factors, ILSBPD showed acceptable diagnostic accuracy for PAD, whilst IASBPD accuracy was negligible. However, the combination of ILSBPD (or IASBPD) with oscillometric ABI did not improve the ability to detect PAD. Thus, oscillometer ABI seems to be preferable to detect PAD and individuals at high cardiovascular risk. ILSBPD could be uniquely recommended for the diagnosis of PAD when blood pressure measurements in upper limbs are not possible.

Long-term results of the Heller-Dor operation with intraoperative manometry for the treatment of esophageal achalasia.

PubMed

Mattioli, Sandro; Ruffato, Alberto; Lugaresi, Marialuisa; Pilotti, Vladimiro; Aramini, Beatrice; D'Ovidio, Frank

2010-11-01

Quality of outcome of the Heller-Dor operation is sometimes different between studies, likely because of technical reasons. We analyze the details of myotomy and fundoplication in relation to the results achieved over a 30-year single center's experience. From 1979-2008, a long esophagogastric myotomy and a partial anterior fundoplication to protect the surface of the myotomy was routinely performed with intraoperative manometry in 202 patients (97 men; median age, 55.5 years; interquartile range, 43.7-71 years) through a laparotomy and in 60 patients (24 men; median age, 46 years; interquartile range, 36.2-63 years) through a laparoscopy. The follow-up consisted of periodical interview, endoscopy, and barium swallow, and a semiquantitative scale was used to grade results. Mortality was 1 of 202 in the laparotomy group and 0 of 60 in the laparoscopy group. Median follow-up was 96 months (interquartile range, 48-190.5 months) in the laparotomy group and 48 months (interquartile range, 27-69.5 months) in the laparoscopy group. At intraoperative manometry, complete abolition of the high-pressure zone was obtained in 100%. The Dor-related high-pressure zone length and mean pressure were 4.5 ± 0.4 cm and 13.3 ± 2.2 mm Hg in the laparotomy group and 4.5 ± 0.5 cm and 13.2 ± 2.2 mm Hg in the laparoscopy group (P = .75). In the laparotomy group poor results (19/201 [9.5%]) were secondary to esophagitis in 15 (7.5%) of 201 patients (in 2 patients after 184 and 252 months, respectively) and to recurrent dysphagia in 4 (2%) of 201 patients, all with end-stage sigmoid achalasia. In the laparoscopy group 2 (3.3%) of 60 had esophagitis. A long esophagogastric myotomy protected by means of Dor fundoplication cures or substantially reduces dysphagia in the great majority of patients affected by esophageal achalasia and effectively controls postoperative esophagitis. Intraoperative manometry is likely the key factor for achieving the reported results. Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Boron environments in Pyrex® glass--a high resolution, Double-Rotation NMR and thermodynamic modelling study.

PubMed

Howes, A P; Vedishcheva, N M; Samoson, A; Hanna, J V; Smith, M E; Holland, D; Dupree, R

2011-07-07

It is shown, using the important technological glass Pyrex® as an example, that 1D and 2D (11)B Double-Rotation (DOR) NMR experiments, in combination with thermodynamic modelling, are able to provide unique structural information about complex glasses. (11)B DOR NMR has been applied to Pyrex® glass in order to remove both dipolar and quadrupolar broadening of the NMR lines, leading to high resolution spectra that allow unambiguous, accurate peak fitting to be carried out, of particular importance in the case of the 3-coordinated [BO(3)] (B3) trigonal planar environments. The data obtained are of sufficient quality that they can be used to test the distributions of borate and borosilicate superstructural units predicted by the thermodynamics-based Model of Associated Solutions. The model predicts the dominant boron-containing chemical groupings in Pyrex® glass to be those associated with B(2)O(3) and sodium tetraborate (with smaller amounts of sodium triborate, sodium diborate, sodium pentaborate, danburite and reedmergnerite). Excellent agreement is found between model and experiment provided the (11)B peaks with isotropic chemical shifts of -1.4 ppm and 0.5 ppm are assigned to B4 species from borosilicate units ([B(OSi)(4)] and [B(OSi)(3)(OB)]) and borate superstructural units (mainly triborate rings with some pentaborate and diborate) respectively. The peaks with isotropic shifts of 14 ppm and 18.1 ppm are then assigned to B3 in borate superstructural units (mainly triborate and pentaborate along with connecting B3) and boroxol rings respectively. The assignments of the DOR NMR peaks, are supported by the presence of cross-peaks in (11)B spin-diffusion DOR NMR spectra which can be used to develop a structural model in which B(2)O(3)-like regions are linked, via borate and borosilicate superstructural units, to the majority silica network. Pyrex® is thus shown to have a heterogeneous structure, with distinct molecular groupings that are far removed from a random distribution of network polyhedra with only short-range order. This journal is © the Owner Societies 2011

Laparoscopic diverticulectomy with the aid of intraoperative gastrointestinal endoscopy to treat epiphrenic diverticulum.

PubMed

Yu, Lei; Wu, Ji-Xiang; Chen, Xiao-Hong; Zhang, Yun-Feng; Ke, Ji

2016-01-01

Most researchers believe that the presence of large epiphrenic diverticulum (ED) with severe symptoms should lead to the consideration of surgical options. The choice of minimally invasive techniques and whether Heller myotomy with antireflux fundoplication should be employed after diverticulectomy became points of debate. The aim of this study was to describe how to perform laparoscopic transhiatal diverticulectomy (LTD) and oesophagomyotomy with the aid of intraoperative gastrointestinal (GI) endoscopy and how to investigate whether the oesophagomyotomy should be performed routinely after LTD. From 2008 to 2013, 11 patients with ED underwent LTD with the aid of intraoperative GI endoscopy at our department. Before surgery, 4 patients successfully underwent oesophageal manometry: Oesophageal dysfunction and an increase of the lower oesophageal sphincter pressure (LESP) were found in 2 patients. There were 2 cases of conversion to an open transthoracic procedure. Six patients underwent LTD, Heller myotomy and Dor fundoplication; and 3 patients underwent only LTD. The dysphagia and regurgitation 11 patients experienced before surgery improved significantly. Motor function studies showed that there was no oesophageal peristalsis in 5 patients during follow-up, while 6 patients showed seemingly normal oesophageal motility. The LESP of 6 patients undergoing LTD, myotomy and Dor fundoplication was 16.7 ± 10.2 mmHg, while the LESPs of 3 patients undergoing only LTD were 26 mmHg, 18 mmHg and 21 mmHg, respectively. In 4 cases experiencing LTD, myotomy and Dor fundoplication, the gastro-oesophageal reflux occurred during the sleep stage. LTD constitutes a safe and valid approach for ED patients with severe symptoms. As not all patients with large ED have oesophageal disorders, according to manometric and endoscopic results, surgeons can categorise and decide whether or not myotomy and antireflux surgery after LTD will be conducted.

Laparoscopic treatment in achalasia of the cardia.

PubMed

Ursut, B; Alecu, L; Tulin, A; Enciu, O

2014-01-01

Achalasia, although a rare disease (an incidence of 1 100 000 individuals each year) is one of the common causes of motor dysphagia and is characterized by loss of peristalsis in the esophageal body and lack of relaxation of the lower esophageal sphincter. The aim of our study was to perform a clinical,therapeutic and evolution evaluation in patients diagnosed with achalasia and operated in our department between 1997 and 2013. We performed a retrospective study using the clinical charts, operatory protocols, imagistic and video database of the 17 patients with achalasia operated in our department. We encountered an equal repartition in women and men and a predominance of urban provenience. Ages were between 24 and 86 years (with an average age of 51). There were two cases of recurrent achalasia at 2, respectively 5 years after the first operation. In all cases, Heller myotomy was used, with the addition of a Dor fundoplication in 12 cases and Toupet fundoplication in five cases, as an antireflux procedure. Mean operation time was 117.6 minutes.There were three iatrogenic perforations of the esophageal mucosa, all of them recognized and treated in the same operative time. No postoperative complications related to the Heller-Dor Heller-Toupet procedure were encountered.The follow-up was between 3 and 72 months. Laparoscopic approach in the treatment of achalasia provides the advantages of minimally invasive surgery, but also and very important, a good visualization of the abdominal esophagus and gastroesophageal junction.Heller esocardiomyotomy is usually associated with anantireflux procedure. A Dor fundoplication is generally used,although the Toupet fundoplication may also be used with the same advantages. It is important to monitor these patients on a yearly basis, knowing the risk of dysplasia carcinoma in achalasia. Celsius.

Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethylarginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve.

PubMed

de la Barca, J M Chao; Boueilh, T; Simard, G; Boucret, L; Ferré-L'Hotellier, V; Tessier, L; Gadras, C; Bouet, P E; Descamps, P; Procaccio, V; Reynier, P; May-Panloup, P

2017-11-01

Does the metabolomic profile of the follicular fluid (FF) of patients with a diminished ovarian reserve (DOR) differ from that of patients with a normal ovarian reserve (NOR)? The metabolomic signature of the FF reveals a significant decrease in polyunsaturated choline plasmalogens and methyl arginine transferase activity in DOR patients compared to NOR patients. The composition of the FF reflects the exchanges between the oocyte and its microenvironment during its acquisition of gametic competence. Studies of the FF have allowed identification of biomarkers and metabolic pathways involved in various pathologies affecting oocyte quality, but no large metabolomic analysis in the context of ovarian ageing and DOR has been undertaken so far. This was an observational study of the FF retrieved from 57 women undergoing in vitro fertilization at the University Hospital of Angers, France, from November 2015 to September 2016. The women were classified in two groups: one including 28 DOR patients, and the other including 29 NOR patients, serving as controls. Patients were enrolled in the morning of oocyte retrieval after ovarian stimulation. Once the oocytes were isolated for fertilization and culture, the FF was pooled and centrifuged for analysis. A targeted quantitative metabolomic analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit. The FF levels of 188 metabolites and several sums and ratios of metabolic significance were assessed by multivariate and univariate analyses. A total of 136 metabolites were accurately quantified and used for calculating 23 sums and ratios. Samples were randomly divided into training and validation sets. The training set, allowed the construction of multivariate statistical models with a projection-supervised method, i.e. orthogonal partial least squares discriminant analysis (OPLS-DA), applied to the full set of metabolites, or the penalized least absolute shrinkage and selection operator with logistic regression (LASSO-LR), applied to the ratios and sums of the metabolites. Both multivariate models showed good predictive performances when applied to the validation set. The final penalized model retained the three most significant variables, i.e. the total dimethylarginine-to-arginine ratio (Total DMA/Arginine), the sum of the polyunsaturated choline plasmalogens (PUFA ae), and the patient's age. The negative coefficients of Total DMA/Arginine and PUFA ae indicated that these FF variables had lower values in DOR patients than in NOR patients. N/A. This study presents two limitations. First, with this targeted metabolomics analysis, we have explored only a limited portion of the FF metabolome. Second, although the signature found was highly significant, the mechanism underlying the dysfunction remains undetermined. The understanding of the mechanisms implied in ovarian ageing is essential for providing an adequate response to affected women desiring pregnancy. Our study proposes an incoming signature that may open new paths towards this goal. This study was supported by the University Hospital of Angers, the University of Angers, and the French national research centers, INSERM and the CNRS. There were no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Chemical characterization and effects on Lepidium sativum of the native and bioremediated components of dry olive mill residue.

PubMed

Aranda, E; García-Romera, I; Ocampo, J A; Carbone, V; Mari, A; Malorni, A; Sannino, F; De Martino, A; Capasso, R

2007-09-01

Dry olive mill residue (DOR) from the olive oil production by two phase centrifugation system was fractionated by a consecutive continuous solid-liquid extraction obtaining the EAF, PF, MF and WF fractions with ethyl acetate, n-propanol, methanol and water, respectively. The chemical, chromatographic and mass spectrometric analyses showed EAF, PF and MF to be mainly composed of simple phenols, phenolic acids, flavonoids and glycosilated phenols (glycosides of phenols, secoiridoids and flavonoids), whereas WF was mainly consisting of polymerin, the metal organic polymeric mixture previously identified in olive oil mill waste waters and composed of carbohydrates, melanin, proteins and metals (K, Na, Ca, Mg and Fe). The identification in DOR of oleoside, 6'-beta-glucopyranosyl-oleoside and 6'-beta-rhamnopyranosyl-oleoside, and of its organic polymeric component, known as polymerin, are reported for the first time in this paper. The inoculation of the previously mentioned fractions with saprobe fungi Coriolopsis rigida, Pycnoporus cynnabarinus or Trametes versicolor indicated these fungi to be able to metabolize both the phenols and glycosilated phenols, but not polymerin. In correspondence, EAF, PF, MF and WF, which proved to be toxic on Lepidium sativum, decreased their toxicity after incubation with the selected fungi, WF showing to be also able to stimulate the growth of the selected seeds. The phytotoxicity appeared mainly correlated to the monomeric phenols and, to a lesser extent, to the glycosilated phenols, whereas polymerin proved to be non toxic. However, the laccase activity was not associated with the decrease of phytotoxicity. The valorization of DOR as a producer of high added value substances of industrial and agricultural interest in native form and after their bioremediation for a final objective of the total DOR recycling is also discussed.

Can crosstalk between DOR and PARP reduce oxidative stress mediated neurodegeneration?

PubMed

Raina, Rutika; Sen, Dwaipayan

2018-01-01

The progressive loss of structure and function of neurons leads to neurodegenerative processes which become the causative reason for various neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD) etc. These diseases are multifactorial in nature but they have been seen to possess similar causative agents to a certain extent. Oxidative Stress (OS) has been identified as a major stressor and a mediator in most of these diseases. OS not only leads to the generation of free radical species but if persistent, can possibly lead to lipid peroxidation, protein damage, DNA damage, and cell death. Anti-oxidants are endogenously present in our body to tackle oxygen metabolites but their levels reduce greatly under continuous OS conditions. In such a case, dietary supplements to replenish the anti-oxidant levels in our body is a good way of treatment but it is very slow and may not be as effective in chronic stress conditions. Thus, there is a need for more effective mechanisms to attenuate OS. Two such mechanisms which can be considered are the activation of Delta opioid receptor (DOR) and Inhibition of Poly (ADP-ribose)-polymerase1 (PARP1), which have been suggested to protect neurons and increase neuronal cell survivability in both in-vitro and in-vivo disease models. Various signaling pathways have been highlighted to probably play a significant role in attenuating OS by the activation of DOR. It would be an interesting topic of investigation to see if one of the probable mechanisms by which DOR attenuates OS could be by modulation of PARP through a cascade of intracellular signaling reactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health-related quality of life after laparoscopic Heller myotomy and Dor fundoplication for achalasia.

PubMed

Asti, Emanuele; Sironi, Andrea; Lovece, Andrea; Bonavina, Giulia; Fanelli, Melania; Bonitta, Gianluca; Bonavina, Luigi

2017-04-01

In addition to symptom scores, a person's perception of health and quality of life assessment is an important indicator of quality of treatment and can provide an efficient index to compare different therapeutic modalities in chronic disease states. Only a few studies have investigated quality of life comprehensively in patients with achalasia, and therefore the controversy regarding the best treatment algorithm continues. The primary study outcome was pre- and postoperative quality of life in patients with achalasia undergoing laparoscopic Heller myotomy and Dor fundoplication. The study is a retrospective, observational cohort. The hospital registry and the updated research database were reviewed to identify all patients who were treated for achalasia between 2010 and 2015. Patients were eligible for the study if they had a minimum 1-year follow-up and had pre-and postoperative Eckardt, Short Form-36, and Gastro-Esophageal Reflux Disease Health-Related Quality of Life scores. Patients with previous operative and/or endoscopic treatments for achalasia were excluded. One-hundred and eighteen patients were identified. The median follow-up was 40 months (interquartile range 27). The proportion of patients with Eckardt stage II-III decreased from 94.9-13% (P < .001). The mean Eckardt score decreased from 6.9 ± 1.9 to 1.7 ± 1.2 (P < .001); the mean Short Form-36 scores significantly increased in all 8 domains; the mean Gastro-Esophageal Reflux Disease Health-Related Quality of Life score decreased from 13.9 ± 5.7 to 5.5 ± 5.4 (P < .001). Finally, 88% (confidence interval 81-93) of patients were satisfied regarding their present condition. Quality of life assessed with generic and disease-specific validated instruments significantly improved after laparoscopic Heller myotomy combined with Dor fundoplication. Copyright © 2016 Elsevier Inc. All rights reserved.

Robotic heller myotomy and Dor fundoplication for achalasia in a woman with morbid obesity.

PubMed

Bedirli, Abdulkadir; Dogan, Ibrahim; Kozan, Ramazan

2012-12-01

Achalasia is a relatively rare condition with a prevalence estimated at less than 0.001 %. Laparoscopic or robotic Heller myotomy is an effective surgical treatment for achalasia. We present the first published case of a morbidly obese achalasia patient treated with robotic Heller myotomy and Dor fundoplication. The operative time was 175 min, with an estimated blood loss of 110 ml. The patient had a normal bowel transit on postoperative day 2, and he was discharged on postoperative day 4 on a liquid diet. A follow-up at 2 months showed significant resolved symptoms of achalasia.

Levels and associations among self-esteem, fertility distress, coping, and reaction to potentially being a genetic carrier in women with diminished ovarian reserve.

PubMed

Cizmeli, Ceylan; Lobel, Marci; Franasiak, Jason; Pastore, Lisa M

2013-06-01

To measure the level of distress and its relationship with other psychologic factors in women with diminished ovarian reserve (DOR) who participated in a fragile X genetics study. Longitudinal data analyzed with structural equation modeling. Four U.S. private and academic fertility centers. Sixty-two infertile patients with DOR. None. Fertility Problem Inventory, Coping Scale for Infertile Couples, Rosenberg Self-Esteem, Health Orientation Scale. Nineteen percent had low fertility distress, 56% had average fertility distress, and 24% had high fertility distress. Thirty-six percent self-reported a "favorable" or "very favorable" emotional response to potentially being a fragile X carrier (termed "emotions"), 53% were "ambivalent," and 11% had an unfavorable reaction. Three months after learning that they were not a carrier, these percentages were 91%, 9%, and 0%, respectively. Emotions at this second time point were significantly more positive than at pretesting. At baseline, higher self-esteem was a significant predictor of reduced fertility distress both directly and indirectly through emotions. Fertility distress was not associated with coping. Self-esteem, fertility distress, pretesting emotions, and coping were unrelated to posttesting emotions. The potential of having an explanation for one's DOR condition may have a beneficial impact on women's psychologic states during the process of genetic testing, and this appeared to be especially true for women with higher self-esteem. Psychologic interventions targeted to women with low self-esteem may reduce distress and improve reactions to genetic testing. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiss, Anika; Ammer, Hermann; Eisinger, Daniela A., E-mail: eisinger@pharmtox.vetmed.uni-muenchen.de

{delta}-Opioid receptor (DOR) agonists possess cytoprotective properties, an effect associated with activation of the 'pro-survival' kinase Akt. Here we delineate the signal transduction pathway by which opioids induce Akt activation in neuroblastoma x glioma (NG108-15) hybrid cells. Exposure of the cells to both [D-Pen{sup 2,5}]enkephalin and etorphine resulted in a time- and dose-dependent increase in Akt activity, as measured by means of an activation-specific antibody recognizing phosphoserine-473. DOR-mediated Akt signaling is blocked by the opioid antagonist naloxone and involves inhibitory G{sub i/o} proteins, because pre-treatment with pertussis toxin, but not over-expression of the G{sub q/11} scavengers EBP50 and GRK2-K220R, preventedmore » this effect. Further studies with Wortmannin and LY294002 revealed that phophoinositol-3-kinase (PI3K) plays a central role in opioid-induced Akt activation. Opioids stimulate Akt activity through transactivation of receptor tyrosine kinases (RTK), because pre-treatment of the cells with inhibitors for neurotrophin receptor tyrosine kinases (AG879) and the insulin-like growth factor receptor IGF-1 (AG1024), but not over-expression of the G{beta}{gamma} scavenger phosducin, abolished this effect. Activated Akt translocates to the nuclear membrane, where it promotes GSK3 phosphorylation and prevents caspase-3 cleavage, two key events mediating inhibition of cell apoptosis and enhancement of cell survival. Taken together, these results demonstrate that in NG108-15 hybrid cells DOR agonists possess cytoprotective properties mediated by activation of the RTK/PI3K/Akt signaling pathway.« less

Multicentre external validation of IOTA prediction models and RMI by operators with varied training

PubMed Central

Sayasneh, A; Wynants, L; Preisler, J; Kaijser, J; Johnson, S; Stalder, C; Husicka, R; Abdallah, Y; Raslan, F; Drought, A; Smith, A A; Ghaem-Maghami, S; Epstein, E; Van Calster, B; Timmerman, D; Bourne, T

2013-01-01

Background: Correct characterisation of ovarian tumours is critical to optimise patient care. The purpose of this study is to evaluate the diagnostic performance of the International Ovarian Tumour Analysis (IOTA) logistic regression model (LR2), ultrasound Simple Rules (SR), the Risk of Malignancy Index (RMI) and subjective assessment (SA) for preoperative characterisation of adnexal masses, when ultrasonography is performed by examiners with different background training and experience. Methods: A 2-year prospective multicentre cross-sectional study. Thirty-five level II ultrasound examiners contributed in three UK hospitals. Transvaginal ultrasonography was performed using a standardised approach. The final outcome was the surgical findings and histological diagnosis. To characterise the adnexal masses, the six-variable prediction model (LR2) with a cutoff of 0.1, the RMI with cutoff of 200, ten SR (five rules for malignancy and five rules for benignity) and SA were applied. The area under the curves (AUCs) for performance of LR2 and RMI were calculated. Diagnostic performance measures for all models assessed were sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and the diagnostic odds ratio (DOR). Results: Nine-hundred and sixty-two women with adnexal masses underwent transvaginal ultrasonography, whereas 255 had surgery. Prevalence of malignancy was 29% (49 primary invasive epithelial ovarian cancers, 18 borderline ovarian tumours, and 7 metastatic tumours). The AUCs for LR2 and RMI for all masses were 0.94 (95% confidence interval (CI): 0.89–0.97) and 0.90 (95% CI: 0.83–0.94), respectively. In premenopausal women, LR2−RMI difference was 0.09 (95% CI: 0.03–0.15) compared with −0.02 (95% CI: −0.08 to 0.04) in postmenopausal women. For all masses, the DORs for LR2, RMI, SR+SA (using SA when SR inapplicable), SR+MA (assuming malignancy when SR inapplicable), and SA were 62 (95% CI: 27–142), 43 (95% CI: 19–97), 109 (95% CI: 44–274), 66 (95% CI: 27–158), and 70 (95% CI: 30–163), respectively. Conclusion: Overall, the test performance of IOTA prediction models and rules as well as the RMI was maintained in examiners with varying levels of training and experience. PMID:23674083

Diagnosis and medical treatment of neuropathic pain in leprosy.

PubMed

Arco, Rogerio Del; Nardi, Susilene Maria Tonelli; Bassi, Thiago Gasperini; Paschoal, Vania Del Arco

2016-08-08

to identify the difficulties in diagnosing and treating neuropathic pain caused by leprosy and to understand the main characteristics of this situation. 85 patients were treated in outpatient units with reference to leprosy and the accompanying pain. We used a questionnaire known as the Douleur Neuropathic 4 test and we conducted detailed neurological exams. As a result, 42 patients were excluded from the study for not having proved their pain. Out of the 37 patients that experienced pain, 22 (59.5%) had neuropathic pain (or a mixture of this pain and their existing pain) and of these 90.8% considered this pain to be moderate or severe. 81.8% of the sample suffered with this pain for more than 6 months. Only 12 (54.5%) of the patients had been diagnosed with neuropathic pain and in almost half of these cases, this pain had not been diagnosed. With reference to medical treatment (n=12) for neuropathic pain, 5 (41.6%) responded that they became better. For the other 7 (58.4%) there were no changes in relation to the pain or in some cases the pain worsened in comparison to their previous state. Statistical analysis comparing improvements in relation to the pain amongst the patients that were treated (n=12) and those that were not, showed significant differences (value p=0.020). we noted difficulties in diagnosing neuropathic pain for leprosy in that almost half of the patients that were studied had not had their pain diagnosed. We attributed this to some factors such as the non-adoption of the appropriate protocols which led to inadequate diagnosis and treatment that overlooked the true picture. identificar as dificuldades em diagnosticar e tratar a dor neuropática causada pela hanseníase, bem como determinar as características principais dessa situação. examinaram-se 85 pacientes tratados no ambulatório de referência para hanseníase e referiam dor. Aplicou-se questionário, o teste Douleur Neuropathic 4, e criterioso exame neurológico pelo qual excluíram-se 42 pacientes por não se comprovar dor. dos 37 pacientes com dor, 22 (59,5%) tinham Douleur Neuropathic ou mista e, desses, 90,8% caracterizavam essa dor como de intensidade moderada ou severa, sendo que 81,8% sofriam por mais de 6 meses. Apenas 12 (54,5%) pacientes haviam sido diagnosticados com Douleur Neuropathic e quase metade dos casos (45,5%) estava sem reconhecimento. Quanto ao tratamento medicamentoso (n=12) para a Douleur Neuropathic, 5 (41,6%) responderam que tiveram melhora, nos outros 7 (58,4%) não houve alteração da dor ou pioraram quando se comparou ao quadro inicial. A análise estatística, comparando a melhora da dor entre os pacientes tratados (n=12) e aqueles não tratados (n=10), foi significante (valor-p=0,020). identificou-se dificuldade em diagnosticar a dor neuropática em hanseníase, haja vista que quase metade dos pacientes estudados estava sem reconhecimento desse quadro. Atribuíram-se, como fatores associados, a não adoção de protocolo apropriado para efetivo diagnóstico e tratamentos inadequados que podem mascarar o quadro. identificar las dificultades de diagnosticar y tratar el dolor neuropático causado por la lepra, así como determinar las características principales de esa situación. se examinaron 85 pacientes tratados en ambulatorio de referencia para lepra y que refirieron dolor. Se aplicó el cuestionario test Douleur Neuropathic 4, y se hizo un minucioso examen neurológico a través del cual se excluyeron 42 pacientes por no haberse comprobado dolor. de los 37 pacientes con dolor, 22 (59,5%) tenían dolor neuropático o mixto y, de esos, 90,8% caracterizaban ese dolor como de intensidad moderada o severa, siendo que 81,8% sufrían de él hace más de 6 meses. Apenas 12 (54,5%) pacientes habían sido diagnosticados con dolor neuropático y casi mitad de los casos (45,5%) estaba sin reconocimiento. En cuanto al tratamiento medicamentoso (n=12) para el dolor neuropático, 5 (41,6%) respondieron que tuvieron mejoría; en los otros 7 (58,4%) no hubo alteración del dolor o empeoraron cuando se comparó con el cuadro inicial. El análisis estadístico, comparando la mejoría del dolor entre los pacientes tratados (n=12) y aquellos no tratados (n=10), fue significativa (valor-p=0,020). se identificó dificultad en diagnosticar el dolor neuropático en la lepra, considerando que casi la mitad de los pacientes estudiados estaban sin reconocimiento de ese cuadro. Se atribuyeron como factores asociados la no adopción de protocolo apropiado para un efectivo diagnóstico y tratamientos inadecuados que pudieron haber enmascarar el cuadro.

Effect of surfactant assisted sonic pretreatment on liquefaction of fruits and vegetable residue: Characterization, acidogenesis, biomethane yield and energy ratio.

PubMed

Shanthi, M; Rajesh Banu, J; Sivashanmugam, P

2018-05-15

The present study explored the disintegration potential of fruits and vegetable residue through sodium dodecyl sulphate (SDS) assisted sonic pretreatment (SSP). In SSP method, initially the biomass barrier (lignin) was removed using SDS at different dosage, subsequently it was sonically disintegrated. The effect of SSP were assessed based on dissolved organic release (DOR) of fruits and vegetable waste and specific energy input. SSP method achieved higher DOR rate and suspended solids reduction (26% and 16%) at optimum SDS dosage of 0.035 g/g SS with least specific energy input of 5400 kJ/kg TS compared to ultrasonic pretreatment (UP) (16% and 10%). The impact of fermentation and biomethane potential assay revealed highest production of volatile fatty acid and methane yield in SSP (1950 mg/L, 0.6 g/g COD) than UP. The energy ratio obtained was 0.9 for SSP, indicating proposed method is energetically efficient. Copyright © 2018 Elsevier Ltd. All rights reserved.

Separating Automatic and Intentional Inhibitory Mechanisms of Attention in Adults with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Roberts, Walter; Fillmore, Mark T.; Milich, Richard

2011-01-01

Researchers in the cognitive sciences recognize a fundamental distinction between automatic and intentional mechanisms of inhibitory control. The use of eye-tracking tasks to assess selective attention has led to a better understanding of this distinction in specific populations such as children with attention-deficit/hyperactivity disorder (ADHD). This study examined automatic and intentional inhibitory control mechanisms in adults with ADHD using a saccadic interference (SI) task and a delayed ocular response (DOR) task. Thirty adults with ADHD were compared to 27 comparison adults on measures of inhibitory control. The DOR task showed that adults with ADHD were less able than comparison adults to inhibit a reflexive saccade towards the sudden appearance of a stimulus in the periphery. However, SI task performance showed that the ADHD group did not differ significantly from the comparison group on a measure of automatic inhibitory control. These findings suggest a dissociation between automatic and intentional inhibitory deficits in adults with ADHD. PMID:21058752

EUS for the staging of gastric cancer: a meta-analysis.

PubMed

Mocellin, Simone; Marchet, Alberto; Nitti, Donato

2011-06-01

The role of EUS in the locoregional staging of gastric carcinoma is undefined. We aimed to comprehensively review and quantitatively summarize the available evidence on the staging performance of EUS. We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for relevant studies published until July 2010. Formal meta-analysis of diagnostic accuracy parameters was performed by using a bivariate random-effects model. Fifty-four studies enrolling 5601 patients with gastric cancer undergoing disease staging with EUS were eligible for the meta-analysis. EUS staging accuracy across eligible studies was measured by computing overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI, 0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI, 0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic performance of EUS for lymph node status is less reliable, with overall sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84 (95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95% CI, 9-16), respectively. Results regarding single T categories (including T1 substages) and Bayesian nomograms to calculate posttest probabilities for any target condition prevalence are also provided. Statistical heterogeneity was generally high; unfortunately, subgroup analysis did not identify a consistent source of the heterogeneity. Our results support the use of EUS for the locoregional staging of gastric cancer, which can affect the therapeutic management of these patients. However, clinicians must be aware of the performance limits of this staging tool. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Antimüllerian hormone as predictor of implantation and clinical pregnancy after assisted conception: a systematic review and meta-analysis.

PubMed

Tal, Reshef; Tal, Oded; Seifer, Benjamin J; Seifer, David B

2015-01-01

To assess whether antimüllerian hormone (AMH) is a predictor of implantation and/or clinical pregnancy in women undergoing assisted reproductive technology. Systematic review and meta-analysis. Not applicable. Women undergoing IVF/intracytoplasmic sperm injection in nondonor cycles. Measurement of serum AMH level. Diagnostic odds ratio (OR) and summary receiver operating characteristic curve (AUC) for AMH as a predictor of implantation and/or clinical pregnancy. A total of 525 observational studies were identified, of which 19 were selected (comprising 5,373 women). Studies reporting clinical pregnancy rates in women with unspecified ovarian reserve (n = 11), diminished ovarian reserve (DOR) (n = 4), and polycystic ovary syndrome (n = 4) were included, together with studies reporting implantation rates (n = 4). The OR for AMH as a predictor of implantation in women with unspecified ovarian reserve (n = 1,591) was 1.83 (95% confidence interval [CI] 1.49-2.25), whereas the AUC was 0.591 (95% CI 0.563-0.618). The OR for AMH as a predictor of clinical pregnancy in these women (n = 4,324) was 2.10 (95% CI 1.82-2.41), whereas the AUC was 0.634 (95% CI 0.618-0.650). The predictive ability of AMH for pregnancy was greatest in women with DOR (n = 615), with OR and AUC of 3.96 (95% CI 2.57-6.10) and 0.696 (95% CI 0.641-0.751), respectively. In contrast, AMH had no significant predictive ability in women with PCOS (n = 414), with OR and AUC of 1.18 (95% CI 0.53-2.62) and 0.600 (95% CI 0.547-0.653), respectively. Antimüllerian hormone has weak association with implantation and clinical pregnancy rates in assisted reproductive technology but may still have some clinical utility in counseling women undergoing fertility treatment regarding pregnancy rates, particularly those with DOR. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Resolution of massive compact clusters in the 30 Doradus periphery with the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Walborn, Nolan R.; Mackenty, John W.; Saha, Abhijit; White, Richard L.; Parker, Joel WM.

1995-01-01

Hubble Space Telescope Wide Field/Planetary Camera UBV images of three massive, compact multiple systems with the SNR 30 Dor B/NGC 2060 and 30 Dor C/NGC 2044 are discussed and illustrated. In two cases, WN+OB objects have been resolved into additional components to those previously known from ground-based observations, substantially reducing the luminosities of the WN stars and rendering them currently unidentified; in the third case, the components of a B+K composite-spectrum object have been clearly identified. The results are of significance for evolutionary interpretations of these massive stars and for determinations of the upper IMF in extragalactic systems.

Internal motions of HII regions and giant HII regions

NASA Technical Reports Server (NTRS)

Chu, You-Hua; Kennicutt, Robert C., Jr.

1994-01-01

We report new echelle observations of the kinematics of 30 HII regions in the Large Magellanic Clouds (LMC), including the 30 Doradus giant HII region. All of the HII regions possess supersonic velocity dispersions, which can be attributed to a combination of turbulent motions and discrete velocity splitting produced by stellar winds and/or embedded supernova remnants (SNRs). The core of 30 Dor is unique, with a complex velocity structure that parallels its chaotic optical morphology. We use our calibrated echelle data to measure the physical properties and energetic requirements of these velocity structures. The most spectacular structures in 30 Dor are several fast expanding shells, which appear to be produced at least partially by SNRs.

First finding of a dual-meaning X wave for phloem and xylem fluid ingestion: characterization of Scaphoideus titanus (Hemiptera: Cicadellidae) EPG waveforms

USDA-ARS?s Scientific Manuscript database

Scaphoideus titanus, an invasive species introduced into Europe from North America, is the vector of the most important phytoplasma disease in European viticulture, flavescence dorée. In this first electropenetrography (EPG) study of S. titanus, its feeding waveforms were characterized and their bio...

Use of a Differential Observing Response to Expand Restricted Stimulus Control

ERIC Educational Resources Information Center

Walpole, Carrie Wallace; Roscoe, Eileen M.; Dube, William V.

2007-01-01

This study extends previous work on the use of differential observing responses (DOR) to remediate atypically restricted stimulus control. A participant with autism had high matching-to-sample accuracy scores with printed words that had no letters in common (e.g., "cat," "lid," "bug") but poor accuracy with words that had two letters in common…

Synthetic Flight Training System Study

DTIC Science & Technology

1983-12-23

Distribution unlimited IC. SUPPLEMENTARY NOTiS - 19. KEY WORDS (Continue on reveree side if necoeeary and Identify by block nunber) Visual Systems Computer ...platforms, instructional features, computer hardware and software, student stations, etc. DOR 1473 EDITON OF INMOV6S ISOSOLETE Unclassified SECURITY... Computational Systems .................................... 4-I I 4.5.3 Visual Processing Systems .......................... 4-13 4.5.4 Instructor Stations

Training model for laparoscopic Heller and Dor fundoplication: a tool for laparoscopic skills training and assessment-construct validity using the GOALS score.

PubMed

Bellorin, Omar; Kundel, Anna; Sharma, Saurabh; Ramirez-Valderrama, Alexander; Lee, Paul

2016-08-01

Laparoscopic training demands practice. The transfer of laparoscopic skills from training models to real surgical procedures has been proven. The global operative assessment of laparoscopic skills (GOALS) score is a 5-item global rating scale developed to evaluate laparoscopic skills by direct observation. This scale has been used to demonstrate construct validity of several laparoscopic training models. Here, we present a low-cost model of laparoscopic Heller-Dor for advanced laparoscopic training. The aim of this study was to determine the capability of a training model for laparoscopic Heller-Dor to discriminate between different levels of laparoscopic expertise. The performance of two groups with different levels of expertise, novices (<30 laparoscopic procedures PGY1-2) and experts (>300 laparoscopic procedures PGY4-5) was assessed. All participants were instructed to perform two tasks (esophageal myotomy and fundoplication). All the performances were recorded in a digital format. A laparoscopic expert who was blinded to subject's identity evaluated the recordings using the GOALS score. Autonomy, one of the five items of GOALS, was removed since the evaluator and the trainee did not have interaction. The time required to finish each task was also recorded. Performance was compared using the Mann-Whitney U test (p < 0.05 was significant). Twenty subjects were evaluated: ten in each group, using the GOALS score. The mean total GOALS score for novices was 7.5 points (SD: 1.64) and 13.9 points (SD: 1.66) for experts (p < 0.05).The expert group was superior in each domain of the GOALS score compared to novices: depth perception (mean: 3.3 vs 2 p < 0.05), bimanual dexterity (mean 3.4 vs 2.1 p < 0.05), efficiency (mean 3.4 vs 1.7 p < 0.05) and tissue handling (mean 3.6 vs 1.7 p < 0.05). With regard to time, experts were superior in task 1 (mean 9.7 vs 14.9 min p < 0.05) and task 2 (mean 24 vs 47.1 min p < 0.05) compared to novices. The laparoscopic Heller-Dor training model has construct validity. The model may be used as a tool for training of the surgical resident.

Weighing the Smallest Stars

NASA Astrophysics Data System (ADS)

2005-01-01

VLT Finds Young, Very Low Mass Objects Are Twice As Heavy As Predicted Summary Thanks to the powerful new high-contrast camera installed at the Very Large Telescope, photos have been obtained of a low-mass companion very close to a star. This has allowed astronomers to measure directly the mass of a young, very low mass object for the first time. The object, more than 100 times fainter than its host star, is still 93 times as massive as Jupiter. And it appears to be almost twice as heavy as theory predicts it to be. This discovery therefore suggests that, due to errors in the models, astronomers may have overestimated the number of young "brown dwarfs" and "free floating" extrasolar planets. PR Photo 03/05: Near-infrared image of AB Doradus A and its companion (NACO SDI/VLT) A winning combination A star can be characterised by many parameters. But one is of uttermost importance: its mass. It is the mass of a star that will decide its fate. It is thus no surprise that astronomers are keen to obtain a precise measure of this parameter. This is however not an easy task, especially for the least massive ones, those at the border between stars and brown dwarf objects. Brown dwarfs, or "failed stars", are objects which are up to 75 times more massive than Jupiter, too small for major nuclear fusion processes to have ignited in its interior. To determine the mass of a star, astronomers generally look at the motion of stars in a binary system. And then apply the same method that allows determining the mass of the Earth, knowing the distance of the Moon and the time it takes for its satellite to complete one full orbit (the so-called "Kepler's Third Law"). In the same way, they have also measured the mass of the Sun by knowing the Earth-Sun distance and the time - one year - it takes our planet to make a tour around the Sun. The problem with low-mass objects is that they are very faint and will often be hidden in the glare of the brighter star they orbit, also when viewed in large telescopes. Astronomers have however found ways to overcome this difficulty. For this, they rely on a combination of a well-considered observational strategy with state-of-the-art instruments. High contrast camera First, astronomers searching for very low mass objects look at young nearby stars because low-mass companion objects will be brightest while they are young, before they contract and cool off. In this particular case, an international team of astronomers [1] led by Laird Close (Steward Observatory, University of Arizona), studied the star AB Doradus A (AB Dor A). This star is located about 48 light-years away and is "only" 50 million years old. Because the position in the sky of AB Dor A "wobbles", due to the gravitational pull of a star-like object, it was believed since the early 1990s that AB Dor A must have a low-mass companion. To photograph this companion and obtain a comprehensive set of data about it, Close and his colleagues used a novel instrument on the European Southern Observatory's Very Large Telescope. This new high-contrast adaptive optics camera, the NACO Simultaneous Differential Imager, or NACO SDI [2], was specifically developed by Laird Close and Rainer Lenzen (Max-Planck-Institute for Astronomy in Heidelberg, Germany) for hunting extrasolar planets. The SDI camera enhances the ability of the VLT and its adaptive optics system to detect faint companions that would normally be lost in the glare of the primary star. A world premiere ESO PR Photo 03/05 ESO PR Photo 03/05 Infrared image of AB Doradus A and its companion [Preview - JPEG: 400 x 406 pix - 99k] [Normal - JPEG: 800 x 812 pix - 235k] Caption: ESO PR Photo 03/05 is an enhanced, false-colour near-infrared image of AB Dor A and C. The faint companion "AB Dor C" - seen as the pink dot at 8 o'clock - is 120 times fainter than its primary star. The tiny separation between A and C, only 0.156 arcsec, is smaller than a one Euro coin seen at 20 km distance. Nevertheless, the new NACO SDI camera was able to distinguish it as a "redder" dot surrounded by the "bluer" light from AB Dor A. The orbit of AB Dor C around AB Dor A is shown as a yellow ellipse. It takes 11.75 years for the 93 Jupiter-mass companion to complete this orbit. Turning this camera towards AB Dor A in February 2004, they were able for the first time to image a companion so faint - 120 times fainter than its star - and so near its star. Says Markus Hartung (ESO), member of the team: "This world premiere was only possible because of the unique capabilities of the NACO SDI instrument on the VLT. In fact, the Hubble Space Telescope tried but failed to detect the companion, as it was too faint and too close to the glare of the primary star." The tiny distance between the star and the faint companion (0.156 arcsec) is the same as the width of a one Euro coin (2.3 cm) when seen 20 km away. The companion, called AB Dor C, was seen at a distance of 2.3 times the mean distance between the Earth and the Sun. It completes a cycle around its host star in 11.75 years on a rather eccentric orbit. Using the companion's exact location, along with the star's known 'wobble', the astronomers could then accurately determine the companion's mass. The object, more than 100 times fainter than its close primary star, has one tenth of the mass of its host star, i.e., it is 93 times more massive than Jupiter. It is thus slightly above the brown dwarf limit. Using NACO on the VLT, the astronomers further observed AB Dor C at near infrared wavelengths to measure its temperature and luminosity. "We were surprised to find that the companion was 400 degrees (Celsius) cooler and 2.5 times fainter than the most recent models predict for an object of this mass," Close said. "Theory predicts that this low-mass, cool object would be about 50 Jupiter masses. But theory is incorrect: this object is indeed between 88 to 98 Jupiter masses." These new findings therefore challenge current ideas about the brown dwarf population and the possible existence of widely publicized "free-floating" extrasolar planets. Indeed, if young objects hitherto identified as brown dwarfs are twice as massive as was thought, many must rather be low-mass stars. And objects recently identified as "free-floating" planets are in turn likely to be low-mass brown dwarfs. For Close and his colleagues, "this discovery will force astronomers to rethink what masses of the smallest objects produced in nature really are."

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain.

PubMed

Miranda, Hugo F; Noriega, Viviana; Zanetta, Pilar; Prieto, Juan Carlos; Prieto-Rayo, Juan Carlos; Aranda, Nicolás; Sierralta, Fernando

2014-07-15

Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain

PubMed Central

2014-01-01

Background Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. Results The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50 was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. Conclusion These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity. PMID:25017386

V850 Cyg: An eclipsing binary with a giant γ Dor pulsator

NASA Astrophysics Data System (ADS)

Çakırlı, Ö.; Ibanoglu, C.; Sipahi, E.; Akan, M. C.

2017-04-01

We present new spectroscopic observations of the double-lined eclipsing binary V850 Cyg. The long-cadence photometric observations obtained by Kepler were analysed and combined with the analysis of radial velocities for deriving the absolute parameters of the components. Masses and radii were determined as Mp=1.601 ± 0.076 M⊙ and Rp=4.239 ± 0.076 R⊙, Ms=0.851 ± 0.053 M⊙ and Rs=5.054 ± 0.087 R⊙ for the components of V850 Cyg. We estimate an interstellar reddening of 0.28 ± 0.12 mag and a distance of 1040 ± 160 pc for the system. The measured rotational velocity of the secondary appears to lower than that of synchronize rotation. However its spectral lines are too weak to be measured the rotational velocity with reasonable accuracy. We have extracted the synthetic light curve from the observations and excluded the data within the eclipses for the frequency analysis. We obtained at least nine frequencies in the γ Dor regime. It seems that the primary component oscillates with a dominant period of about 1.152549 ± 0.000009 days. We also compare pulsational properties of the primary star of V850 Cyg with the γ Dor type pulsating components in other binaries.

Embedding an Identity-Matching Task within a Prompting Hierarchy to Facilitate Acquisition of Conditional Discriminations in Children with Autism

PubMed Central

Fisher, Wayne W; Kodak, Tiffany; Moore, James W

2007-01-01

Least-to-most prompting hierarchies (e.g., progressing from verbal to modeled to physical prompts until the target response occurs) may be ineffective when the prompts do not cue the individual to attend to the relevant stimulus dimensions. In such cases, emission of the target response persistently requires one or more of the higher level prompts, a condition called prompt dependence (Clark & Green, 2004). Reinforcement of differential observing responses (DORs) has sometimes been used to ensure that participants attend to the relevant stimulus dimensions in matching-to-sample (MTS) tasks (e.g., Dube & McIlvane, 1999). For 2 participants with autism, we embedded an identity-matching task within a prompting hierarchy as a DOR to increase the likelihood that the participants attended to and discriminated the relevant features of the comparison stimuli in an MTS task. This procedure was compared with a traditional least-to-most prompting hierarchy and a no-reinforcement control condition in a multielement design. Results for both participants indicated that mastery-level acquisition of spoken-word-to-picture relations occurred only under the identity-matching condition. Findings are discussed relative to the use of DORs to facilitate acquisition of conditional discriminations in persons with autism or other conditions who do not attend to the comparison stimuli. PMID:17970262

Embedding an identity-matching task within a prompting hierarchy to facilitate acquisition of conditional discriminations in children with autism.

PubMed

Fisher, Wayne W; Kodak, Tiffany; Moore, James W

2007-01-01

Least-to-most prompting hierarchies (e.g., progressing from verbal to modeled to physical prompts until the target response occurs) may be ineffective when the prompts do not cue the individual to attend to the relevant stimulus dimensions. In such cases, emission of the target response persistently requires one or more of the higher level prompts, a condition called prompt dependence (Clark & Green, 2004). Reinforcement of differential observing responses (DORs) has sometimes been used to ensure that participants attend to the relevant stimulus dimensions in matching-to-sample (MTS) tasks (e.g., Dube & McIlvane, 1999). For 2 participants with autism, we embedded an identity-matching task within a prompting hierarchy as a DOR to increase the likelihood that the participants attended to and discriminated the relevant features of the comparison stimuli in an MTS task. This procedure was compared with a traditional least-to-most prompting hierarchy and a no-reinforcement control condition in a multielement design. Results for both participants indicated that mastery-level acquisition of spoken-word-to-picture relations occurred only under the identity-matching condition. Findings are discussed relative to the use of DORs to facilitate acquisition of conditional discriminations in persons with autism or other conditions who do not attend to the comparison stimuli.

Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PubMed Central

Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

2015-01-01

Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

Inguinodynia in patients submitted to conventional inguinal hernioplasty.

PubMed

Dias, Bruno Garcia; Santos, Marcelo Protásio Dos; Chaves, Ana Barbara DE Jesus; Willis, Mariana; Gomes, Marcio Couto; Andrade, Fernandes Tavares; Melo, Valdinaldo Aragão DE; Santos, Paulo Vicente Dos

2017-01-01

to evaluate the incidence of chronic pain and its impact on the quality of life of patients submitted to inguinal hernioplasty using the Lichtenstein technique. this was a descriptive, cross-sectional study of patients operated under spinal anesthesia from February 2013 to February 2015 and who had already completed six postoperative months. We questioned patients about the presence of chronic inguinal pain and, if confirmed, invited them to a consultation in which we assessed the pain and its impact on quality of life. out of 158 patients submitted to the procedure, we identified 7.6% as having inguinodynia. Of these, there was an impact on the quality of life in 25%. the incidence of inguinodynia after hernioplasty with repercussion in quality of life was similar to the one of found in the world literature. avaliar a incidência de dor crônica e o seu impacto na qualidade de vida de pacientes submetidos à hernioplastia inguinal pela técnica de Lichtenstein. trata-se de estudo transversal descritivo, de pacientes operados de hérnia inguinal pela técnica de Lichtenstein sob anestesia raquidiana, no período de fevereiro de 2013 a fevereiro de 2015, e que já haviam completado seis meses de pós-operatório. Os pacientes foram questionados sobre a presença de dor inguinal crônica e, caso confirmada, convidados a uma consulta na qual foi feita análise da qualidade da dor e seu impacto na qualidade de vida. do total de 158 pacientes submetidos ao procedimento, 7,6% foram identificados como portadores de inguinodinia. Destes, houve impacto na qualidade de vida em 25%. observou-se incidência de inguinodinia pós-hernioplastia com repercussão na qualidade de vida semelhante à literatura mundial.

Development of a tool to assess adherence to a model of the division of responsibility in feeding young children: using response mapping to capacitate validation measures.

PubMed

Lohse, Barbara; Satter, Ellyn; Arnold, Kristen

2014-04-01

Accurate early assessment and targeted intervention with problematic parent/child feeding dynamics is critical for the prevention and treatment of child obesity. The division of responsibility in feeding (sDOR), articulated by the Satter Feeding Dynamics Model (fdSatter), has been demonstrated clinically as an effective approach to reduce child feeding problems, including those leading to obesity. Lack of a tested instrument to examine adherence to fdSatter stimulated initial construction of the Satter Feeding Dynamics Inventory (fdSI). The aim of this project was to refine the item pool to establish translational validity, making the fdSI suitable for advanced psychometric analysis. Cognitive interviews (n = 80) with caregivers of varied socioeconomic strata informed revisions that demonstrated face and content validity. fdSI responses were mapped to interviews using an iterative, multi-phase thematic approach to provide an instrument ready for construct validation. fdSI development required five interview phases over 32 months: Foundational; Refinement; Transitional; Assurance; and Launching. Each phase was associated with item reduction and revision. Thirteen items were removed from the 38-item Foundational phase and seven were revised in the Refinement phase. Revisions, deletions, and additions prompted by Transitional and Assurance phase interviews resulted in the 15-item Launching phase fdSI. Only one Foundational phase item was carried through all development phases, emphasizing the need to test for item comprehension and interpretation before psychometric analyses. Psychometric studies of item pools without encrypted meanings will facilitate progress toward a tool that accurately detects adherence to sDOR. Ability to measure sDOR will facilitate focus on feeding behaviors associated with reduced risk of childhood obesity.

Levels and associations among self-esteem, fertility distress, coping, and reaction to potentially being a genetic carrier in women with diminished ovarian reserve

PubMed Central

Cizmeli, Ceylan; Lobel, Marci; Franasiak, Jason; Pastore, Lisa M.

2013-01-01

Objective To measure the level of distress and its relationship with other psychologic factors in women with diminished ovarian reserve (DOR) who participated in a fragile X genetics study. Design Longitudinal data analyzed with structural equation modeling. Setting Four U.S. private and academic fertility centers. Patient(s) Sixty-two infertile patients with DOR. Intervention(s) None. Main Outcome Measure(s) Fertility Problem Inventory, Coping Scale for Infertile Couples, Rosenberg Self-Esteem, Health Orientation Scale. Result(s) Nineteen percent had low fertility distress, 56% had average fertility distress, and 24% had high fertility distress. Thirty-six percent self-reported a “favorable” or “very favorable” emotional response to potentially being a fragile X carrier (termed “emotions”), 53% were “ambivalent,” and 11% had an unfavorable reaction. Three months after learning that they were not a carrier, these percentages were 91%, 9%, and 0%, respectively. Emotions at this second time point were significantly more positive than at pretesting. At baseline, higher self-esteem was a significant predictor of reduced fertility distress both directly and indirectly through emotions. Fertility distress was not associated with coping. Self-esteem, fertility distress, pretesting emotions, and coping were unrelated to posttesting emotions. Conclusion(s) The potential of having an explanation for one’s DOR condition may have a beneficial impact on women’s psychologic states during the process of genetic testing, and this appeared to be especially true for women with higher self-esteem. Psychologic interventions targeted to women with low self-esteem may reduce distress and improve reactions to genetic testing. PMID:23498890

Diagnostic accuracy of 22/25-gauge core needle in endoscopic ultrasound-guided sampling: systematic review and meta-analysis.

PubMed

Oh, Hyoung-Chul; Kang, Hyun; Lee, Jae Young; Choi, Geun Joo; Choi, Jung Sik

2016-11-01

To compare the diagnostic accuracy of endoscopic ultrasound-guided core needle aspiration with that of standard fine-needle aspiration by systematic review and meta-analysis. Studies using 22/25-gauge core needles, irrespective of comparison with standard fine needles, were comprehensively reviewed. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic curves for the diagnosis of malignancy were used to estimate the overall diagnostic efficiency. The pooled sensitivity, specificity, and DOR of the core needle for the diagnosis of malignancy were 0.88 (95% confidence interval [CI], 0.84 to 0.90), 0.99 (95% CI, 0.96 to 1), and 167.37 (95% CI, 65.77 to 425.91), respectively. The pooled sensitivity, specificity, and DOR of the standard needle were 0.84 (95% CI, 0.79 to 0.88), 1 (95% CI, 0.97 to 1), and 130.14 (95% CI, 34.00 to 495.35), respectively. The area under the curve of core and standard needle in the diagnosis of malignancy was 0.974 and 0.955, respectively. The core and standard needle were comparable in terms of pancreatic malignancy diagnosis. There was no significant difference in procurement of optimal histologic cores between core and standard needles (risk ratio [RR], 0.545; 95% CI, 0.187 to 1.589). The number of needle passes for diagnosis was significantly lower with the core needle (standardized mean difference, -0.72; 95% CI, -1.02 to -0.41). There were no significant differences in overall complications (RR, 1.26; 95% CI, 0.34 to 4.62) and technical failure (RR, 5.07; 95% CI, 0.68 to 37.64). Core and standard needles were comparable in terms of diagnostic accuracy, technical performance, and safety profile.

DOR agonist (SNC-80) exhibits anti-parkinsonian effect via downregulating UPR/oxidative stress signals and inflammatory response in vivo.

PubMed

Begum M, Erfath Thanjeem; Sen, Dwaipayan

2018-06-21

The pathophysiology of Parkinson's disease exhibit imperative roles in unfolded protein response stress-induced oxidative stress and inflammation in general. Although, delta opioid receptor (DOR), has been found to represent anti-parkinsonian effect at behavioral level, its underlying mechanism remains elusive till date. In the present study the role of DOR agonist, SNC-80 and the consorted molecular mechanisms, which translates to behavioral recuperation, has been delineated. In order to mimic PD, mice were intra-peritoneally injected with MPTP, following exposure to SNC-80 and L-DOPA to elucidate amelioration of the MPTP-induced behavioral impairments. The results obtained suggest that the severity of the compromised motor functions up-regulated the UPR stress sensors: IRE-1α/Bip/CHOP, oxidative stress along with the pro-inflammatory cytokines: IL1β/IFNγ/TNFα and IL-6. These inimical factors combined, aids the persistence of the disease in MPTP intoxicated mice. Supplementation with SNC-80 significantly improved motor functions via down-regulation of the UPR stress sensors and inflammatory cytokines. Additionally, SNC-80 could upregulate Nrf-2 and Heme oxygenase-1 (HO-1) protein expression indicating their involvement in SNC-80's potential anti-oxidant function. There was also a significant reduction in protein carbonyl content indicating the positive role of SNC-80 in dampening MPTP induced oxidative stress. Concomitantly, L-DOPA also demonstrated an enhanced effect towards improvement of motor functions but did not suppress the UPR and inflammatory responses caused due to MPTP intoxication. Hence, these results suggest that SNC-80 could hold a pivotal role in replenishing motor functions essentially via regulating UPR and inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib.

PubMed

Larkins, Erin; Blumenthal, Gideon M; Chen, Huanyu; He, Kun; Agarwal, Rajiv; Gieser, Gerlie; Stephens, Olen; Zahalka, Eias; Ringgold, Kimberly; Helms, Whitney; Shord, Stacy; Yu, Jingyu; Zhao, Hong; Davis, Gina; McKee, Amy E; Keegan, Patricia; Pazdur, Richard

2016-11-01

On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46-74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6. ©2016 AACR. ©2016 American Association for Cancer Research.

Guest-host interactions in sodium zeolite Y: Structural and dynamical [sup 23]Na double-rotation NMR study of H[sub 2]O, PMe[sub 3], Mo(CO)[sub 6], and Mo(CO)[sub 4](PMe[sub 3])[sub 2] adsorption in Na[sub 56]Y

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jelinek, R.; Oezkar, S.; Malek, A.

1993-01-27

[sup 23]Na double-rotation NMR (DOR) provides site-specific structural and dynamical information on guest-host interactions within sodium zeolite Y pores. Quantitative adsorption of H[sub 2]O, PMe[sub 3], and Mo(CO)[sub 6] guests affects both the positions and line shapes of the [sup 23]Na resonances from specific extraframework Na[sup +] sites. The evolution of the [sup 23]Na DOR spectra with the progressive introduction of guest molecules allows one to probe direct solvation' effects involving the Na[sup +] cations in the larger supercages, as well as indirect effects on the Na[sup +] cations in adjacent smaller sodalite cavities. [sup 23]Na DOR experiments conducted atmore » two magnetic field strengths confirm that PMe[sub 3] coadsorption in 8[l brace]Mo(CO)[sub 6][r brace],16[l brace]PMe[sub 3][r brace]-Na[sub 56]Y, and PMe[sub 3] ligand-substitution in 8[l brace]cis-Mo(CO)[sub 4](PMe[sub 3])[sub 2][r brace]-Na[sub 56]Y give rise to progressive deshielding and enhanced quadrupolar interactions of the anchoring Na[sup +] cations in the [alpha]-cages, relative to those of the starting material, 8[l brace]Mo(CO)[sub 6][r brace]-Na[sub 56]Y. Spin-lattice relaxation measurements indicate that adsorption of PMe[sub 3] facilitates an increased motion of the Na[sup +] cations and/or guest species inside the [alpha]-cages. 22 refs., 6 figs., 1 tab.« less

AUDIT and AUDIT-C as screening instruments for alcohol problem use in adolescents.

PubMed

Liskola, Joni; Haravuori, Henna; Lindberg, Nina; Niemelä, Solja; Karlsson, Linnea; Kiviruusu, Olli; Marttunen, Mauri

2018-07-01

The Alcohol Use Disorders Identification Test (AUDIT) is commonly used in adults to screen for harmful alcohol consumption but few studies exist on its use among adolescents. Our aim was to validate the AUDIT and its derivative consumption questionnaire (AUDIT-C) as screening instruments for the detection of problem use of alcohol in adolescents. 621 adolescents (age-range, 12-19 years) were drawn from clinical and population samples who completed the AUDIT questionnaire. Psychiatric diagnoses were assessed using K-SADS-PL. A rating based on the K-SADS-PL was used to assess alcohol use habits, alcohol use disorders, screening and symptom criteria questions. Screening performance of the AUDIT and AUDIT-C sum scores and Receiver Operating Characteristic (ROC) curves were calculated. The diagnostic odds ratios (dOR) were calculated to express the overall discrimination between cut-offs. Comparisons of ROC between the AUDIT and AUDIT-C pairs indicated a slightly better test performance by AUDIT for the whole sample and in a proportion of the subsamples. Optimal cut-off value for the AUDIT was ≥5 (sensitivity 0.931, specificity 0.772, dOR 45.22; 95% CI: 24.72-83.57) for detecting alcohol problem use. The corresponding optimal cut-off value for the AUDIT-C was ≥3 in detecting alcohol problem use (sensitivity 0.952, specificity 0.663, dOR 39.31; 95% CI: 19.46-78.97). Agreement between the AUDIT and AUDIT-C using these cut-off scores was high at 91.9%. Our results for the cut-off scores for the early detection of alcohol problem use in adolescents are ≥5 for AUDIT, and ≥3 for AUDIT-C. Copyright © 2018 Elsevier B.V. All rights reserved.

Using Standardized Interpretation of Chest Radiographs to Identify Adults with Bacterial Pneumonia--Guatemala, 2007-2012.

PubMed

Wortham, Jonathan M; Gray, Jennifer; Verani, Jennifer; Contreras, Carmen Lucia; Bernart, Chris; Moscoso, Fabiola; Moir, Juan Carlos; Reyes Marroquin, Emma Lissette; Castellan, Rigoberto; Arvelo, Wences; Lindblade, Kim; McCracken, John P

2015-01-01

Bacterial pneumonia is a leading cause of illness and death worldwide, but quantifying its burden is difficult due to insensitive diagnostics. Although World Health Organization (WHO) protocol standardizes pediatric chest radiograph (CXR) interpretation for epidemiologic studies of bacterial pneumonia, its validity in adults is unknown. Patients (age ≥ 15 years) admitted with respiratory infections to two Guatemalan hospitals between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal (NP/OP) swabs collected; blood cultures and CXR were also performed at physician clinical discretion. 'Any bacterial infection' was defined as a positive urine pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood culture, or detection of an atypical bacterial pathogen by polymerase chain reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral infection' was defined as detection of viral pathogens by PCR of NP/OP specimens. CXRs were interpreted according to the WHO protocol as having 'endpoint consolidation', 'other infiltrate', or 'normal' findings. We examined associations between bacterial and viral infections and endpoint consolidation. Urine antigen and/or blood culture results were available for 721 patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119 (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3-7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7-4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not significantly associated with 'endpoint consolidation', 'other infiltrate,' or 'normal' findings. 'Endpoint consolidation' was associated with 'any bacterial infection,' specifically pneumococcal infection. Therefore, endpoint consolidation may be a useful surrogate for studies measuring the impact of interventions, such as conjugate vaccines, against bacterial pneumonia.

Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma.

PubMed

Toumishey, Ethan; Prasad, Angeli; Dueck, Greg; Chua, Neil; Finch, Daygen; Johnston, James; van der Jagt, Richard; Stewart, Doug; White, Darrell; Belch, Andrew; Reiman, Tony

2015-03-01

Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma. © 2014 American Cancer Society.

Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis.

PubMed

Henry, Brandon Michael; Roy, Joyeeta; Ramakrishnan, Piravin Kumar; Vikse, Jens; Tomaszewski, Krzysztof A; Walocha, Jerzy A

2016-07-01

Several studies have explored the use of serum procalcitonin (PCT) in differentiating between bacterial and viral etiologies in children with suspected meningitis. We pooled these studies into a meta-analysis to determine the PCT diagnostic accuracy. All major databases were searched through March 2015. No date or language restrictions were applied. Eight studies (n = 616 pediatric patients) were included. Serum PCT assay was found to be very accurate for differentiating the etiology of pediatric meningitis with pooled sensitivity and specificity of 0.96 (95% CI = 0.92-0.98) and 0.89 (95% CI = 0.86-0.92), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) for PCT were 7.5 (95% CI = 5.6-10.1), 0.08(95% CI = 0.04-0.14), 142.3 (95% CI = 59.5-340.4), and 0.97 (SE = 0.01), respectively. In 6 studies, PCT was found to be superior than CRP, whose DOR was only 16.7 (95%CI = 8.8-31.7). Our meta-analysis demonstrates that serum PCT assay is a highly accurate and powerful test for rapidly differentiating between bacterial and viral meningitis in children. © The Author(s) 2015.

Saturation of an intra-gene pool linkage map: toward unified consensus linkage map in common bean

USDA-ARS?s Scientific Manuscript database

Map-based cloning to find genes of interest and marker assisted selection (MAS) requires good genetic maps with high reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers in includin...

Resolving the Shell of the Superbubble 30 Doradus C with Chandra

NASA Astrophysics Data System (ADS)

Lopez, Laura

2017-09-01

We propose to observe the superbubble (SB) 30 Doradus C (30 Dor C) with ACIS-S for 100 ks to resolve and characterize the non-thermal shell, point sources, and the young supernova remnant (SNR) J0536 6913 at sub-arcsecond scales. 30 Dor C has been imaged off axis repeatedly by Chandra due to its proximity to SN 1987A, but the majority of the shell has only been observed <20 ks at off-axis distances of >10 arcminutes. The on-axis spatial resolution, sensitivity, and low background of ACIS-S are necessary to disentangle point sources from diffuse emission, to localize synchrotron filaments associated with accelerated electrons, and to investigate the SNR J0536 6913.

Hypoandrogenism in association with diminished functional ovarian reserve.

PubMed

Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-04-01

Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age <38 years and abnormally low FOR by age-specific FSH and/or anti-Müllerian hormone (AMH), 166 women with DOR, defined as women age >40 years. Forty-nine control patients <38 years demonstrated normal FOR by FSH and/or AMH. In all three patient groups dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), total testosterone (TT) and free testosterone (FT) at the time of initial presentation to our fertility center were assessed. In a small subgroup of women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels. While results support lower androgen levels in women with DOR, and even more so in women with POA/OPOI, presented data should be viewed as preliminary, considering the known variability of androgen levels and the small number of women in whom morning cortisol levels were available. Especially at young ages DFOR appears associated with significant hypoandrogenism (low T) in comparison with young control patients with normal FOR, raising the question whether this hypoandrogenism originates in adrenals or ovaries. POA/OPOI, thus, phenotypically mimics the polycystic ovary syndrome, where similar questions arise, though in regard to hyperandrogenism. This research was supported by the Foundation for Reproductive Medicine, a not-for-profit medical research foundation and intramural funds from the Center for Human Reproduction. N.G. and D.H.B are members of the Board of the Foundation for Reproductive Medicine. N.G., A.W. and D.H.B. received research support, lecture fees and travel support from a variety of pharmaceutical and medical device companies, none in any way related to the issues discussed in this manuscript. N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents, claiming diagnostic and therapeutic benefits from the determination of CGG repeats on the FMR1 gene. N.G. is the owner of the Center for Human Reproduction, where this research was performed.

FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

PubMed

de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

2015-08-15

On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

Laparoscopic calibrated total vs partial fundoplication following Heller myotomy for oesophageal achalasia

PubMed Central

Martino, Natale Di; Brillantino, Antonio; Monaco, Luigi; Marano, Luigi; Schettino, Michele; Porfidia, Raffaele; Izzo, Giuseppe; Cosenza, Angelo

2011-01-01

AIM: To compare the mid-term outcomes of laparoscopic calibrated Nissen-Rossetti fundoplication with Dor fundoplication performed after Heller myotomy for oesophageal achalasia. METHODS: Fifty-six patients (26 men, 30 women; mean age 42.8 ± 14.7 years) presenting for minimally invasive surgery for oesophageal achalasia, were enrolled. All patients underwent laparoscopic Heller myotomy followed by a 180° anterior partial fundoplication in 30 cases (group 1) and calibrated Nissen-Rossetti fundoplication in 26 (group 2). Intraoperative endoscopy and manometry were used to calibrate the myotomy and fundoplication. A 6-mo follow-up period with symptomatic evaluation and barium swallow was undertaken. One and two years after surgery, the patients underwent symptom questionnaires, endoscopy, oesophageal manometry and 24 h oesophago-gastric pH monitoring. RESULTS: At the 2-year follow-up, no significant difference in the median symptom score was observed between the 2 groups (P = 0.66; Mann-Whitney U-test). The median percentage time with oesophageal pH < 4 was significantly higher in the Dor group compared to the Nissen-Rossetti group (2; range 0.8-10 vs 0.35; range 0-2) (P < 0.0001; Mann-Whitney U-test). CONCLUSION: Laparoscopic Dor and calibrated Nissen-Rossetti fundoplication achieved similar results in the resolution of dysphagia. Nissen-Rossetti fundoplication seems to be more effective in suppressing oesophageal acid exposure. PMID:21876635

DISCOVERY OF 14 NEW SLOWLY PULSATING B STARS IN THE OPEN CLUSTER NGC 7654

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Y. P.; Han, Z. W.; Zhang, X. B.

2012-02-10

We carried out time-series BV CCD photometric observations of the open cluster NGC 7654 (Messier 52) to search for variable stars. Eighteen slowly pulsating B (SPB) stars have been detected, among which 14 candidates are newly discovered, three known ones are confirmed, and a previously found {delta} Scuti star is also identified as an SPB candidate. Twelve SPBs are probable cluster members based on membership analysis. This makes NGC 7654 the richest galactic open cluster in terms of SPB star content. It is also a new discovery that NGC 7654 hosts three {gamma} Dor star candidates. We found that allmore » these stars (18 SPB and 3 {gamma} Dor stars) have periods longer than their corresponding fundamental radial mode. With such a big sample of g-mode pulsators in a single cluster, it is clear that multi-mode pulsation is more common in the upper part of the main sequence than in the lower part. All the stars span a narrow strip on the period-luminosity plane, which also includes the {gamma} Dor stars at the low-luminosity extension. This result implies that there may be a single period-luminosity relation applicable to all g-mode main-sequence pulsators. As a by-product, three EA-type eclipsing binaries and an EW-type eclipsing binary are also discovered.« less

The light gene of Drosophila melanogaster encodes a homologue of VPS41, a yeast gene involved in cellular-protein trafficking.

PubMed

Warner, T S; Sinclair, D A; Fitzpatrick, K A; Singh, M; Devlin, R H; Honda, B M

1998-04-01

Mutations in a number of genes affect eye colour in Drosophila melanogaster; some of these "eye-colour" genes have been shown to be involved in various aspects of cellular transport processes. In addition, combinations of viable mutant alleles of some of these genes, such as carnation (car) combined with either light (lt) or deep-orange (dor) mutants, show lethal interactions. Recently, dor was shown to be homologous to the yeast gene PEP3 (VPS18), which is known to be involved in intracellular trafficking. We have undertaken to extend our earlier work on the lt gene, in order to examine in more detail its expression pattern and to characterize its gene product via sequencing of a cloned cDNA. The gene appears to be expressed at relatively high levels in all stages and tissues examined, and shows strong homology to VPS41, a gene involved in cellular-protein trafficking in yeast and higher eukaryotes. Further genetic experiments also point to a role for lt in transport processes: we describe lethal interactions between viable alleles of lt and dor, as well as phenotypic interactions (reductions in eye pigment) between allels of lt and another eye-colour gene, garnet (g), whose gene product has close homology to a subunit of the human adaptor complex, AP-3.

VLBI observations to the APOD satellite

NASA Astrophysics Data System (ADS)

Sun, Jing; Tang, Geshi; Shu, Fengchun; Li, Xie; Liu, Shushi; Cao, Jianfeng; Hellerschmied, Andreas; Böhm, Johannes; McCallum, Lucia; McCallum, Jamie; Lovell, Jim; Haas, Rüdiger; Neidhardt, Alexander; Lu, Weitao; Han, Songtao; Ren, Tianpeng; Chen, Lue; Wang, Mei; Ping, Jinsong

2018-02-01

The APOD (Atmospheric density detection and Precise Orbit Determination) is the first LEO (Low Earth Orbit) satellite in orbit co-located with a dual-frequency GNSS (GPS/BD) receiver, an SLR reflector, and a VLBI X/S dual band beacon. From the overlap statistics between consecutive solution arcs and the independent validation by SLR measurements, the orbit position deviation was below 10 cm before the on-board GNSS receiver got partially operational. In this paper, the focus is on the VLBI observations to the LEO satellite from multiple geodetic VLBI radio telescopes, since this is the first implementation of a dedicated VLBI transmitter in low Earth orbit. The practical problems of tracking a fast moving spacecraft with current VLBI ground infrastructure were solved and strong interferometric fringes were obtained by cross-correlation of APOD carrier and DOR (Differential One-way Ranging) signals. The precision in X-band time delay derived from 0.1 s integration time of the correlator output is on the level of 0.1 ns. The APOD observations demonstrate encouraging prospects of co-location of multiple space geodetic techniques in space, as a first prototype.

Neutral gas and diffuse interstellar bands in the LMC

NASA Technical Reports Server (NTRS)

Danks, Anthony C.; Penprase, Brian

1994-01-01

Tracing the dynamics of the neutral gas and observing diffuse interstellar bands in the LMC (Large Magellanic Cloud) was the focus of this study. The S/N values, a Quartz lamp exposure, a T horium Argon Comparision lamp exposure, and spectral plots for each star observed were taken. The stars observed were selected to sample the 30 Dor vicinty. NaI absorption profiles are included.

The diagnostic performance of CT-derived fractional flow reserve for evaluation of myocardial ischaemia confirmed by invasive fractional flow reserve: a meta-analysis.

PubMed

Li, S; Tang, X; Peng, L; Luo, Y; Dong, R; Liu, J

2015-05-01

To review the literature on the diagnostic accuracy of CT-derived fractional flow reserve (FFRCT) for the evaluation of myocardial ischaemia in patients with suspected or known coronary artery disease, with invasive fractional flow reserve (FFR) as the reference standard. A PubMed, EMBASE, and Cochrane cross-search was performed. The pooled diagnostic accuracy of FFRCT, with FFR as the reference standard, was primarily analysed, and then compared with that of CT angiography (CTA). The thresholds to diagnose ischaemia were FFR ≤0.80 or CTA ≥50% stenosis. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Three multicentre studies (NXT Trial, DISCOVER-FLOW study and DeFACTO study) were included, examining 609 patients and 1050 vessels. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) for FFRCT were 89% (85-93%), 71% (65-75%), 70% (65-75%), 90% (85-93%), 3.31 (1.79-6.14), 0.16 (0.11-0.23), and 21.21 (9.15-49.15) at the patient-level, and 83% (78-63%), 78% (75-81%), 61% (56-65%), 92% (89-90%), 4.02 (1.84-8.80), 0.22 (0.13-0.35), and 19.15 (5.73-63.93) at the vessel-level. At per-patient analysis, FFRCT has similar sensitivity but improved specificity, PPV, NPV, LR+, LR-, and DOR versus those of CTA. At per-vessel analysis, FFRCT had a slightly lower sensitivity, similar NPV, but improved specificity, PPV, LR+, LR-, and DOR compared with those of CTA. The area under the summary receiver operating characteristic curves for FFRCT was 0.8909 at patient-level and 0.8865 at vessel-level, versus 0.7402 for CTA at patient-level. FFRCT, which was associated with improved diagnostic accuracy versus CTA, is a viable alternative to FFR for detecting coronary ischaemic lesions. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

PubMed

Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

2013-08-01

The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation markers.

Surgical management of esophageal achalasia: Evolution of an institutional approach to minimally invasive repair.

PubMed

Petrosyan, Mikael; Khalafallah, Adham M; Guzzetta, Phillip C; Sandler, Anthony D; Darbari, Anil; Kane, Timothy D

2016-10-01

Surgical management of esophageal achalasia (EA) in children has transitioned over the past 2 decades to predominantly involve laparoscopic Heller myotomy (LHM) or minimally invasive surgery (MIS). More recently, peroral endoscopic myotomy (POEM) has been utilized to treat achalasia in children. Since the overall experience with surgical management of EA is contingent upon disease incidence and surgeon experience, the aim of this study is to report a single institutional contemporary experience for outcomes of surgical treatment of EA by LHM and POEM, with regards to other comparable series in children. An IRB approved retrospective review of all patients with EA who underwent treatment by a surgical approach at a tertiary US children's hospital from 2006 to 2015. Data including demographics, operative approach, Eckardt scores pre- and postoperatively, complications, outcomes, and follow-up were analyzed. A total of 33 patients underwent 35 operative procedures to treat achalasia. Of these operations; 25 patients underwent laparoscopic Heller myotomy (LHM) with Dor fundoplication; 4 patients underwent LHM alone; 2 patients underwent LHM with Thal fundoplication; 2 patients underwent primary POEM; 2 patients who had had LHM with Dor fundoplication underwent redo LHM with takedown of Dor fundoplication. Intraoperative complications included 2 mucosal perforations (6%), 1 aspiration, 1 pneumothorax (1 POEM patient). Follow ranged from 8months to 7years (8-84months). There were no deaths and no conversions to open operations. Five patients required intervention after surgical treatment of achalasia for recurrent dysphagia including 3 who underwent between 1 and 3 pneumatic dilations; and 2 who had redo LHM with takedown of Dor fundoplication with all patients achieving complete resolution of symptoms. Esophageal achalasia in children occurs at a much lower incidence than in adults as documented by published series describing the surgical treatment in children. We believe the MIS surgical approach remains the standard of care for this condition in children and describe the surgical outcomes and complications for LHM, as well as, the introduction of the POEM technique in our center for treating achalasia. Our institutional experience described herein represents the largest in the "MIS era" with excellent results. We will refer to alterations in our practice that have included the use of flexible endoscopy in 100% of LHM cases and use of the endoscopic functional lumen imaging probe (EndoFLIP) in both LHM and POEM cases which we believe enables adequate Heller myotomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of auriculotherapy on labour pain: a randomized clinical trial.

PubMed

Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

2016-01-01

Assessing the effects of auriculotherapy in pain control and its outcomes on the duration of labour. This is a randomized, controlled, double-blind trial with preliminary data. Thirty pregnant women with gestational age ≥ 37 weeks, cervical dilatation ≥ 4 cm and two or more contractions in 10 minutes were selected and randomly divided into three groups: auriculotherapy, placebo and control. Auriculotherapy was applied using crystal beads on four strategic points. No statistical significance was found between the groups with regard to pain; however, the women from the auriculotherapy group had lower intensity and less perception of pain at 30, 60 and 120 minutes of treatment. The average duration of labour was shorter in the auriculotherapy group (248.7 versus placebo 414.8 versus control 296.3 minutes); caesarean section rates were higher in the placebo group (50%) and the same in the other groups (10%). Mothers who received auriculotherapy presented a tendency for greater pain control and shorter labour duration; however, caesarean section rates in this group were similar to the control group. This trial precedes a larger study in progress. Registration of Brazilian Clinical Trials: RBR-47hhbj. Avaliar os efeitos da auriculoterapia no controle da dor e seus desfechos na duração do trabalho de parto. Trata-se de um ensaio controlado, randomizado e duplo-cego, com dados preliminares. Foram selecionadas 30 parturientes com idade gestacional ≥ 37 semanas, dilatação cervical ≥ 4 cm e duas ou mais contrações em 10 minutos, divididas aleatoriamente em três grupos: auriculoterapia, placebo ou controle. A auriculoterapia foi aplicada com microesferas de cristais em quatro pontos estratégicos. Não houve significância estatística entre os grupos com relação à dor; no entanto, as mulheres do grupo de auriculoterapia, apresentaram menor intensidade e menor percepção da dor aos 30, 60 e 120 minutos do tratamento. A média de duração do trabalho de parto foi menor no grupo de auriculoterapia (248,7 versus placebo 414,8 versus controle 296,3 minutos); a taxa de cesárea foi maior no grupo placebo (50%) e igual nos outros (10%). As parturientes que receberam auriculoterapia apresentaram tendência a um maior controle da dor e menor duração do trabalho de parto, porém a taxa de cesárea neste grupo foi semelhante à do grupo controle. Este ensaio precede um estudo maior, em andamento. Registro Brasileiro de Ensaio Clínico: RBR-47hhbj.

Diagnostic accuracy of contrast enhanced ultrasound in patients with blunt abdominal trauma presenting to the emergency department: a systematic review and meta-analysis.

PubMed

Zhang, Zhongheng; Hong, Yucai; Liu, Ning; Chen, Yuhao

2017-06-30

We aimed to investigate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in evaluating blunt abdominal trauma for patients presenting to the emergency department. Electronic search of Scopus and Pubmed was performed from inception to September 2016. Human studies investigating the diagnostic accuracy of CEUS in identifying abdominal solid organ injuries were included. Risk of bias was assessed using the QUADAS tool. A total of 10 studies were included in the study and 9 of them were included for meta-analysis. The log(DOR) values ranged from 3.80 (95% CI: 2.81-4.79) to 8.52 (95% CI: 4.58-12.47) in component studies. The combined log(DOR) was 6.56 (95% CI: 5.66-7.45). The Cochran's Q was 11.265 (p = 0.793 with 16 degrees of freedom), and the Higgins' I 2 was 0%. The CEUS had a sensitivity of 0.981 (95% CI: 0.868-0.950) and a false positive rate of 0.018 (95% CI: 0.010-0.032) for identifying parenchymal injuries, with an AUC of 0.984. CEUS performed at emergency department had good diagnostic accuracy in identifying abdominal solid organ injuries. CEUS can be recommended in monitoring solid organ injuries, especially for patients managed with non-operative strategy.

Synthesis and Structure-Activity Relationships of (-)-cis-N-Normetazocine-Based LP1 Derivatives.

PubMed

Pasquinucci, Lorella; Parenti, Carmela; Amata, Emanuele; Georgoussi, Zafiroula; Pallaki, Paschalina; Camarda, Valeria; Calò, Girolamo; Arena, Emanuela; Montenegro, Lucia; Turnaturi, Rita

2018-05-05

(−)- cis - N -Normetazocine represents a rigid scaffold able to mimic the tyramine moiety of endogenous opioid peptides, and the introduction of different N -substituents influences affinity and efficacy of respective ligands at MOR (mu opioid receptor), DOR (delta opioid receptor), and KOR (kappa opioid receptor). We have previously identified LP1, a MOR/DOR multitarget opioid ligand, with an N -phenylpropanamido substituent linked to (−)- cis - N -Normetazocine scaffold. Herein, we report the synthesis, competition binding and calcium mobilization assays of new compounds 10 ⁻ 16 that differ from LP1 by the nature of the N -substituent. In radioligand binding experiments, the compounds 10 ⁻ 13 , featured by an electron-withdrawing or electron-donating group in the para position of phenyl ring, displayed improved affinity for KOR (K i = 0.85⁻4.80 μM) in comparison to LP1 (7.5 μM). On the contrary, their MOR and DOR affinities were worse (K i = 0.18⁻0.28 μM and K i = 0.38⁻1.10 μM, respectively) with respect to LP1 values (K i = 0.049 and 0.033 μM). Analogous trends was recorded for the compounds 14 ⁻ 16 , featured by indoline, tetrahydroquinoline, and diphenylamine functionalities in the N -substituent. In calcium mobilization assays, the compound 10 with a p -fluorophenyl in the N -substituent shared the functional profile of LP1 (pEC 50 MOR = 7.01), although it was less active. Moreover, the p -methyl- ( 11 ) and p -cyano- ( 12 ) substituted compounds resulted in MOR partial agonists and DOR/KOR antagonists. By contrast, the derivatives 13 ⁻ 15 resulted as MOR antagonists, and the derivative 16 as a MOR/KOR antagonist (pK B MOR = 6.12 and pK B KOR = 6.11). Collectively, these data corroborated the critical role of the N -substituent in (−)- cis - N -Normetazocine scaffold. Thus, the new synthesized compounds could represent a template to achieve a specific agonist, antagonist, or mixed agonist/antagonist functional profile.

Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial.

PubMed

Kaufman, Howard L; Russell, Jeffery S; Hamid, Omid; Bhatia, Shailender; Terheyden, Patrick; D'Angelo, Sandra P; Shih, Kent C; Lebbé, Céleste; Milella, Michele; Brownell, Isaac; Lewis, Karl D; Lorch, Jochen H; von Heydebreck, Anja; Hennessy, Meliessa; Nghiem, Paul

2018-01-19

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer associated with poor survival outcomes in patients with distant metastatic disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2, prospective, open-label, single-arm trial in mMCC, avelumab-a human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy and a safety profile that was generally manageable and tolerable. Here, we report the efficacy of avelumab after ≥1 year of follow-up in patients with distant mMCC that had progressed following prior chemotherapy for metastatic disease. Patients received avelumab 10 mg/kg by 1-h intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was best overall response. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Patients (N = 88) were followed for a minimum of 12 months. The confirmed objective response rate was 33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of responses lasted ≥1 year, and 72.4% of responses were ongoing at data cutoff. Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months-not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI, 21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95% CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of response in patients receiving fewer prior lines of systemic therapy, with a lower baseline disease burden, and with PD-L1-positive tumors; however, durable responses occurred irrespective of baseline factors, including tumor Merkel cell polyomavirus status. With longer follow-up, avelumab continues to show durable responses and promising survival outcomes in patients with distant mMCC whose disease had progressed after chemotherapy. Clinicaltrials.gov identifier: NCT02155647.

Metabolic Consequences of Infection of Grapevine (Vitis vinifera L.) cv. “Modra frankinja” with Flavescence Dorée Phytoplasma

PubMed Central

Prezelj, Nina; Covington, Elizabeth; Roitsch, Thomas; Gruden, Kristina; Fragner, Lena; Weckwerth, Wolfram; Chersicola, Marko; Vodopivec, Maja; Dermastia, Marina

2016-01-01

Flavescence dorée, caused by the quarantine phytoplasma FDp, represents the most devastating of the grapevine yellows diseases in Europe. In an integrated study we have explored the FDp–grapevine interaction in infected grapevines of cv. “Modra frankinja” under natural conditions in the vineyard. In FDp-infected leaf vein-enriched tissues, the seasonal transcriptional profiles of 14 genes selected from various metabolic pathways showed an FDp-specific plant response compared to other grapevine yellows and uncovered a new association of the SWEET17a vacuolar transporter of fructose with pathogens. Non-targeted metabolome analysis from leaf vein-enriched tissues identified 22 significantly changed compounds with increased levels during infection. Several metabolites corroborated the gene expression study. Detailed investigation of the dynamics of carbohydrate metabolism revealed significant accumulation of sucrose and starch in the mesophyll of FDp-infected leaves, as well as significant up-regulation of genes involved in their biosynthesis. In addition, infected leaves had high activities of ADP-glucose pyrophosphorylase and, more significantly, sucrose synthase. The data support the conclusion that FDp infection inhibits phloem transport, resulting in accumulation of carbohydrates and secondary metabolites that provoke a source-sink transition and defense response status. PMID:27242887

Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats.

PubMed

de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel

2016-01-01

Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals' nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3-L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals' nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression.

The diagnostic value of polymerase chain reaction for Mycobacterium tuberculosis to distinguish intestinal tuberculosis from crohn's disease: A meta-analysis.

PubMed

Jin, Ting; Fei, Baoying; Zhang, Yu; He, Xujun

2017-01-01

Intestinal tuberculosis (ITB) and Crohn's disease (CD) are important differential diagnoses that can be difficult to distinguish. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis (MTB) is an efficient and promising tool. This meta-analysis was performed to systematically and objectively assess the potential diagnostic accuracy and clinical value of PCR for MTB in distinguishing ITB from CD. We searched PubMed, Embase, Web of Science, Science Direct, and the Cochrane Library for eligible studies, and nine articles with 12 groups of data were identified. The included studies were subjected to quality assessment using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The summary estimates were as follows: sensitivity 0.47 (95% CI: 0.42-0.51); specificity 0.95 (95% CI: 0.93-0.97); the positive likelihood ratio (PLR) 10.68 (95% CI: 6.98-16.35); the negative likelihood ratio (NLR) 0.49 (95% CI: 0.33-0.71); and diagnostic odds ratio (DOR) 21.92 (95% CI: 13.17-36.48). The area under the curve (AUC) was 0.9311, with a Q* value of 0.8664. Heterogeneity was found in the NLR. The heterogeneity of the studies was evaluated by meta-regression analysis and subgroup analysis. The current evidence suggests that PCR for MTB is a promising and highly specific diagnostic method to distinguish ITB from CD. However, physicians should also keep in mind that negative results cannot exclude ITB for its low sensitivity. Additional prospective studies are needed to further evaluate the diagnostic accuracy of PCR.

Diagnostic Value of Endorectal Ultrasound in Preoperative Assessment of Lymph Node Involvement in Colorectal Cancer: a Meta-analysis.

PubMed

Li, Li; Chen, Shi; Wang, Ke; Huang, Jiao; Liu, Li; Wei, Sheng; Gao, Hong-Yu

2015-01-01

Nodal invasion by colorectal cancer is a critical determinant in estimating patient survival and in choosing appropriate preoperative treatment. The present meta-analysis was designed to evaluate the diagnostic value of endorectal ultrasound (EUS) in preoperative assessment of lymph node involvement in colorectal cancer. We systematically searched PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases for relevant studies published on or before December 10th, 2014. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and area under the summary receiver operating characteristics curve (AUC) were assessed to estimate the diagnostic value of EUS. Subgroup analysis and meta-regression were performed to explore heterogeneity across studies. Thirty-three studies covering 3,016 subjects were included. The pooled sensitivity and specificity were 0.69 (95%CI: 0.63-0.75) and 0.77 (95%CI: 0.73-0.82), respectively. The positive and negative likelihood ratios were 3.09 (95%CI: 2.52-3.78) and 0.39 (95%CI: 0.32-0.48), respectively. The DOR was 7.84 (95%CI: 5.56-11.08), and AUC was 0.80 (95%CI: 0.77-0.84). This meta-analysis indicated that EUS has moderate diagnostic value in preoperative assessment of lymph node involvement in colorectal cancer. Further refinements in technology and diagnostic criteria are necessary to improve the diagnostic accuracy of EUS.

Minimally invasive management of achalasia cardia: results from a single center study.

PubMed

Palanivelu, C; Maheshkumar, G S; Jani, Kalpesh; Parthasarthi, R; Sendhilkumar, K; Rangarajan, M

2007-01-01

Since the performance of the first laparoscopic cardiomyotomy for achalasia cardia in 1991, the popularity of the minimally invasive approach for this troublesome disease has been growing. We present our experience of 226 patients who underwent laparoscopic cardiomyotomy and discuss the relevant issues. A retrospective analysis was carried out of 226 patients who have undergone laparoscopic cardiomyotomy since 1993. The preoperative workup, surgical technique, and postoperative management are described. Patients included 146 males and 80 females; average age was 36.4 years (range, 6 to 85). Mean duration of symptoms was 1.4 years. Nearly half of the patients (112) had undergone prior pneumatic dilatation. In 20 patients, myotomy alone was done, 44 patients had a Dor's fundoplication, and 162 had Toupet's fundoplication. The average operating time was 96 minutes. Mean postoperative hospital stay was 2.2 days. Dysphagia was eliminated in 88.9% of the patients with an overall morbidity of 4.4% and nil mortality over a mean follow-up of 4.3 years. Laparoscopic cardiomyotomy with Toupet's fundoplication is a safe and effective treatment of achalasia cardia. Dor's fundoplication is done selectively, especially when suspicion is present of mucosal injury.

Minimally Invasive Management of Achalasia Cardia: Results From a Single Center Study

PubMed Central

Palanivelu, C.; Maheshkumar, G. S.; Parthasarthi, R.; Sendhilkumar, K.; Rangarajan, M.

2007-01-01

Background: Since the performance of the first laparoscopic cardiomyotomy for achalasia cardia in 1991, the popularity of the minimally invasive approach for this troublesome disease has been growing. We present our experience of 226 patients who underwent laparoscopic cardiomyotomy and discuss the relevant issues. Methods: A retrospective analysis was carried out of 226 patients who have undergone laparoscopic cardiomyotomy since 1993. The preoperative workup, surgical technique, and postoperative management are described. Results: Patients included 146 males and 80 females; average age was 36.4 years (range, 6 to 85). Mean duration of symptoms was 1.4 years. Nearly half of the patients (112) had undergone prior pneumatic dilatation. In 20 patients, myotomy alone was done, 44 patients had a Dor's fundoplication, and 162 had Toupet's fundoplication. The average operating time was 96 minutes. Mean postoperative hospital stay was 2.2 days. Dysphagia was eliminated in 88.9% of the patients with an overall morbidity of 4.4% and nil mortality over a mean follow-up of 4.3 years. Conclusion: Laparoscopic cardiomyotomy with Toupet's fundoplication is a safe and effective treatment of achalasia cardia. Dor's fundoplication is done selectively, especially when suspicion is present of mucosal injury. PMID:17931518

Performance of procalcitonin in diagnosing parapneumonic pleural effusions: A clinical study and meta-analysis.

PubMed

He, Chao; Wang, Bo; Li, Danni; Xu, Huan; Shen, Yongchun

2017-08-01

Parapneumonic pleural effusion (PPE) is a common complication of pneumonia. The accurate diagnosis of PPE remains a challenge. Recent studies suggest that procalcitonin (PCT) emerges as a potential biomarker for PPE. Our study aimed to determine the diagnostic value of PCT for PPE by a clinical study and summarize the overall diagnostic performance of PCT through a meta-analysis. Demographic and clinical data of the patients with PPE and controls were collected in our clinical study. The diagnostic performances of serum PCT (s-PCT) were analyzed via receiver operating characteristic (ROC) curve analysis, using area under the curve (AUC) as a measure of accuracy. Literature databases were systematically searched for the studies examining the accuracy of PCT for diagnosing PPE. Data on sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary ROC curves and AUC were used to evaluate overall test performance. In our clinical study, 47 patients with PPE and 101 controls were included. The s-PCT levels were significantly increased in the setting of PPE (5.44 ± 9.82 ng/mL) compared with malignant PE (0.15 ± 0.19 ng/mL), tuberculous PE (0.18 ± 0.16 ng/mL), and transudates (0.09 ± 0.03 ng/mL) (P < .001). Using a cutoff value of 0.195 ng/mL, the sensitivity and specificity of s-PCT in diagnosing PPE were 0.83 and 0.80, respectively, and AUC was 0.89. In addition, 11 studies were included in our meta-analysis. Summary performance estimates for s-PCT in diagnosing PPE were as follows: sensitivity, 0.78 (95% CI: 0.71-0.84); specificity, 0.74 (95% CI: 0.69-0.78); PLR, 3.46 (95% CI: 2.09-5.74); NLR, 0.27 (95% CI: 0.14-0.54); DOR, 12.37 (95% CI: 4.34-41.17); and AUC, 0.84. The corresponding estimates for p-PCT were as follows: sensitivity, 0.62 (95% CI: 0.57-0.67); specificity, 0.71 (95% CI: 0.68-0.75); PLR 2.31 (95% CI: 1.81-2.95); NLR, 0.47 (95% CI: 0.35-0.63); DOR, 5.48 (95% CI: 3.07-9.77); and AUC, 0.80. Both s-PCT and p-PCT might have modest performance in diagnosing PPE. However, more studies on a large scale should be performed to confirm our findings.

Screening tests for aphasia in patients with stroke: a systematic review.

PubMed

El Hachioui, Hanane; Visch-Brink, Evy G; de Lau, Lonneke M L; van de Sandt-Koenderman, Mieke W M E; Nouwens, Femke; Koudstaal, Peter J; Dippel, Diederik W J

2017-02-01

Aphasia has a large impact on the quality of life and adds significantly to the costs of stroke care. Early recognition of aphasia in stroke patients is important for prognostication and well-timed treatment planning. We aimed to identify available screening tests for differentiating between aphasic and non-aphasic stroke patients, and to evaluate test accuracy, reliability, and feasibility. We searched PubMed, EMbase, Web of Science, and PsycINFO for published studies on screening tests aimed at assessing aphasia in stroke patients. The reference lists of the selected articles were scanned, and several experts were contacted to detect additional references. Of each screening test, we estimated the sensitivity, specificity, likelihood ratio of a positive test, likelihood ratio of a negative test, and diagnostic odds ratio (DOR), and rated the degree of bias of the validation method. We included ten studies evaluating eight screening tests. There was a large variation across studies regarding sample size, patient characteristics, and reference tests used for validation. Many papers failed to report on the consecutiveness of patient inclusion, time between aphasia onset and administration of the screening test, and blinding. Of the three studies that were rated as having an intermediate or low risk of bias, the DOR was highest for the Language Screening Test and ScreeLing. Several screening tools for aphasia in stroke are available, but many tests have not been verified properly. Methodologically sound validation studies of aphasia screening tests are needed to determine their usefulness in clinical practice.

Astrophysics. The exceptionally powerful TeV γ-ray emitters in the Large Magellanic Cloud.

PubMed

2015-01-23

The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of 100 billion electron volts for a deep exposure of 210 hours. Three sources of different types were detected: the pulsar wind nebula of the most energetic pulsar known, N 157B; the radio-loud supernova remnant N 132D; and the largest nonthermal x-ray shell, the superbubble 30 Dor C. The unique object SN 1987A is, unexpectedly, not detected, which constrains the theoretical framework of particle acceleration in very young supernova remnants. These detections reveal the most energetic tip of a γ-ray source population in an external galaxy and provide via 30 Dor C the unambiguous detection of γ-ray emission from a superbubble. Copyright © 2015, American Association for the Advancement of Science.

Navigating highly elliptical earth orbiters with simultaneous VLBI from orthogonal baseline pairs

NASA Technical Reports Server (NTRS)

Frauenholz, Raymond B.

1986-01-01

Navigation strategies for determining highly elliptical orbits with VLBI are described. The predicted performance of wideband VLBI and Delta VLBI measurements obtained by orthogonal baseline pairs are compared for a 16-hr equatorial orbit. It is observed that the one-sigma apogee position accuracy improves two orders of magnitude to the meter level when Delta VLBI measurements are added to coherent Doppler and range, and the simpler VLBI strategy provides nearly the same orbit accuracy. The effects of differential measurement noise and acquisition geometry on orbit accuracy are investigated. The data reveal that quasar position uncertainty limits the accuracy of wideband Delta VLBI measurements, and that polar motion and baseline uncertainties and offsets between station clocks affect the wideband VLBI data. It is noted that differential one-way range (DOR) has performance nearly equal to that of the more complex Delta DOR and is recommended for use on spacecraft in high elliptical orbits.

VizieR Online Data Catalog: Massive stars in 30 Dor (Schneider+, 2018)

NASA Astrophysics Data System (ADS)

Schneider, F. R. N.; Sana, H.; Evans, C. J.; Bestenlehner, J. M.; Castro, N.; Fossati, L.; Grafener, G.; Langer, N.; Ramirez-Agudelo, O. H.; Sabin-Sanjulian, C.; Simon-Diaz, S.; Tramper, F.; Crowther, P. A.; de Koter, A.; de Mink, S. E.; Dufton, P. L.; Garcia, M.; Gieles, M.; Henault-Brunet, V.; Herrero, A.; Izzard, R. G.; Kalari, V.; Lennon, D. J.; Apellaniz, J. M.; Markova, N.; Najarro, F.; Podsiadlowski, P.; Puls, J.; Taylor, W. D.; van Loon, J. T.; Vink, J. S.; Norman, C.

2018-02-01

Through the use of the Fibre Large Array Multi Element Spectrograph (FLAMES) on the Very Large Telescope (VLT), the VLT-FLAMES Tarantula Survey (VFTS) has obtained optical spectra of ~800 massive stars in 30 Dor, avoiding the core region of the dense star cluster R136 because of difficulties with crowding. Repeated observations at multiple epochs allow determination of the orbital motion of potentially binary objects. For a sample of 452 apparently single stars, robust stellar parameters-such as effective temperatures, luminosities, surface gravities, and projected rotational velocities-are determined by modeling the observed spectra. Composite spectra of visual multiple systems and spectroscopic binaries are not considered here because their parameters cannot be reliably inferred from the VFTS data. To match the derived atmospheric parameters of the apparently single VFTS stars to stellar evolutionary models, we use the Bayesian code Bonnsai. (2 data files).

Far-infrared line images of dwarf galaxies

NASA Technical Reports Server (NTRS)

Poglitsch, A.; Geis, N.; Herrmann, F.; Madden, S. C.; Stacey, G. J.; Townes, C. H.; Genzel, R.

1993-01-01

Irregular dwarf galaxies are about ten times more widespread in the universe than regular spiral galaxies. They are characterized by a relatively low metallicity, i.e., lower abundance of the heavier elements (metals) with respect to hydrogen than in the solar neighborhood. These heavier elements in the form of molecules, atoms, or ions, which have radiative transitions in the infrared play a decisive role in the energy balance of the ISM and thereby for the formation of stars. Dwarf galaxies are thus model cases for the physical conditions in the early phase of the universe. Large Magellanic Cloud: 30 Doradus. The two nearest dwarf galaxies are the Magellanic clouds at a distance approximately 50 kpc. The LMC contains 30 Dor, a region with young, extremely massive stars which strongly interact with the surrounding ISM on account of their stellar winds and intense UV radiation. 30 Dor is the brightest object in the LMC at almost all wavelengths.

Bradycardia alters Ca2+ dynamics enhancing dispersion of repolarization and arrhythmia risk

PubMed Central

Kim, Jong J.; Němec, Jan; Papp, Rita; Strongin, Robert; Abramson, Jonathan J.

2013-01-01

Bradycardia prolongs action potential (AP) durations (APD adaptation), enhances dispersion of repolarization (DOR), and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Ca2+ transients and APs were measured optically from Langendorff rabbit hearts at high (150 × 150 μm2) or low (1.5 × 1.5 cm2) magnification while pacing at a physiological (120 beats/min) or a slow heart rate (SHR = 50 beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia. As a result, bradycardia (SHR 50 beats/min) increased APDs gradually (time constant τf→s = 48 ± 9.2 s) and caused a secondary Ca2+ release (SCR) from the sarcoplasmic reticulum during AP plateaus, occurring at the base on average of 184.4 ± 9.7 ms after the Ca2+ transient upstroke. In subcellular imaging, SCRs were temporally synchronous and spatially homogeneous within myocytes. In diastole, SHR elicited variable asynchronous sarcoplasmic reticulum Ca2+ release events leading to subcellular Ca2+ waves, detectable only at high magnification. SCR was regionally heterogeneous, correlated with APD prolongation (P < 0.01, n = 5), enhanced DOR (r = 0.9277 ± 0.03, n = 7), and was gradually reversed by pacing at 120 beats/min along with APD shortening (P < 0.05, n = 5). A stabilizer of leaky ryanodine receptors (RyR2), 3-(4-benzylcyclohexyl)-1-(7-methoxy-2,3-dihydrobenzo[f][1,4]thiazepin-4(5H)-yl)propan-1-one (K201; 1 μM), suppressed SCR and reduced APD at the base, thereby reducing DOR (P < 0.02, n = 5). Ventricular ectopy induced by bradycardia (n = 5/15) was suppressed by K201. Western blot analysis revealed spatial differences of voltage-gated L-type Ca2+ channel protein (Cav1.2α), Na+-Ca2+ exchange (NCX1), voltage-gated Na+ channel (Nav1.5), and rabbit ether-a-go-go-related (rERG) protein [but not RyR2 or sarcoplasmic reticulum Ca2+ ATPase 2a] that correlate with the SCR distribution and explain the molecular basis for SCR heterogeneities. In conclusion, acute bradycardia elicits synchronized subcellular SCRs of sufficient magnitude to overcome the source-sink mismatch and to promote afterdepolarizations. PMID:23316064

Diagnostic performance of instantaneous wave-free ratio for the evaluation of coronary stenosis severity confirmed by fractional flow reserve: A PRISMA-compliant meta-analysis of randomized studies.

PubMed

Man, Wanrong; Hu, Jianqiang; Zhao, Zhijing; Zhang, Mingming; Wang, Tingting; Lin, Jie; Duan, Yu; Wang, Ling; Wang, Haichang; Sun, Dongdong; Li, Yan

2016-09-01

The instantaneous wave-free ratio (iFR) is a new vasodilator-free index of coronary stenosis severity. The aim of this meta-analysis is to assess the diagnostic performance of iFR for the evaluation of coronary stenosis severity with fractional flow reserve as standard reference. We searched PubMed, EMBASE, CENTRAL, ProQuest, Web of Science, and International Clinical Trials Registry Platform (ICTRP) for publications concerning the diagnostic value of iFR. We used a random-effects covariate to synthesize the available data of sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR). Overall test performance was summarized by the summary receiver operating characteristic curve (sROC) and the area under the curve (AUC). Eight studies with 1611 subjects were included in the meta-analysis. The pooled sensitivity, specificity, LR+, LR-, and DOR for iFR were respectively 73.3% (70.1-76.2%), 86.4% (84.3-88.3%), 5.71 (4.43-7.37), 0.29 (0.22-0.38), and 20.54 (16.11-26.20). The area under the summary receiver operating characteristic curves for iFR was 0.8786. No publication bias was identified. The available evidence suggests that iFR may be a new, simple, and promising technology for coronary stenosis physiological assessment.

Laparoscopic extended cardiomyotomy in children: an effective procedure for the treatment of esophageal achalasia.

PubMed

Tannuri, Ana Cristina Aoun; Tannuri, Uenis; Velhote, Manoel Carlos Prieto; Romão, Rodrigo Luiz Pinto

2010-07-01

Achalasia of the esophagus is characterized by aperistalsis and incomplete relaxation of the lower esophageal sphincter in response to swallowing. The objective of the present study is to present the experience of a modified Heller myotomy via a laparoscopic approach for the treatment of children who had this condition. A retrospective review of medical records of all patients who underwent this procedure from 2000 to 2009 was performed. The procedure consisted of an extended esophagomyotomy beginning on the lower part of the lower esophageal sphincter and continuing 5 to 6 cm above on the lower third of the esophagus, and then extended 3 to 4 cm below to the stomach, associated with an anterior 180-degree hemi-fundoplication according to Dor's technique. Fifteen patients were included in the study. There were 8 female and 7 male patients. Mean operating time was 190 minutes with no intraoperative complications and 1 conversion to open surgery because of difficulty in dissecting an inflamed distal esophagus. In a mean follow-up period of 32.3 months, 2 patients had recurrence of mild dysphagia that disappeared spontaneously, and 1 required a single botulinum toxin injection with complete resolution of symptoms. We conclude that the laparoscopic extended Heller myotomy with Dor fundoplication is a safe and effective method for the treatment for achalasia in the pediatric population even in advanced cases. Copyright 2010 Elsevier Inc. All rights reserved.

Spatial distribution of nymphs of Scaphoideus titanus (Homoptera: Cicadellidae) in grapes, and evaluation of sequential sampling plans.

PubMed

Lessio, Federico; Alma, Alberto

2006-04-01

The spatial distribution of the nymphs of Scaphoideus titanus Ball (Homoptera Cicadellidae), the vector of grapevine flavescence dorée (Candidatus Phytoplasma vitis, 16Sr-V), was studied by applying Taylor's power law. Studies were conducted from 2002 to 2005, in organic and conventional vineyards of Piedmont, northern Italy. Minimum sample size and fixed precision level stop lines were calculated to develop appropriate sampling plans. Model validation was performed, using independent field data, by means of Resampling Validation of Sample Plans (RVSP) resampling software. The nymphal distribution, analyzed via Taylor's power law, was aggregated, with b = 1.49. A sample of 32 plants was adequate at low pest densities with a precision level of D0 = 0.30; but for a more accurate estimate (D0 = 0.10), the required sample size needs to be 292 plants. Green's fixed precision level stop lines seem to be more suitable for field sampling: RVSP simulations of this sampling plan showed precision levels very close to the desired levels. However, at a prefixed precision level of 0.10, sampling would become too time-consuming, whereas a precision level of 0.25 is easily achievable. How these results could influence the correct application of the compulsory control of S. titanus and Flavescence dorée in Italy is discussed.

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies.

PubMed

Rule, Simon; Dreyling, Martin; Goy, Andre; Hess, Georg; Auer, Rebecca; Kahl, Brad; Cavazos, Nora; Liu, Black; Yang, Shiyi; Clow, Fong; Goldberg, Jenna D; Beaupre, Darrin; Vermeulen, Jessica; Wildgust, Mark; Wang, Michael

2017-11-01

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease. © 2017 John Wiley & Sons Ltd.

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

PubMed Central

Ban, Jong-Wook; Emparanza, José Ignacio; Urreta, Iratxe; Burls, Amanda

2016-01-01

Background Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules’ performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. Methods Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. Results A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2–4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. Conclusion Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved. PMID:26730980

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study.

PubMed

Ban, Jong-Wook; Emparanza, José Ignacio; Urreta, Iratxe; Burls, Amanda

2016-01-01

Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved.

Synovial Fluid α-Defensin as a Biomarker for Peri-Prosthetic Joint Infection: A Systematic Review and Meta-Analysis.

PubMed

Li, Bin; Chen, Fei; Liu, Yi; Xu, Guokang

Total joint arthroplasty (TJA) has been one of the most beneficial interventions for treating patients suffering from joint disorders. However, peri-prosthetic joint infection (PJI) is a serious complication that often accompanies TJA and the diagnosis of PJI is remains difficult. Questions remain regarding whether certain biomarkers can be valuable in the diagnosis of PJI. We conducted our systematic review by searching PubMed, Embase, Web of Science, the Cochrane Library, and Science Direct with the key words "periprosthetic joint infection," "synovial fluid," and "α-defensin." Studies that provided sufficient data to construct 2 × 2 contingency tables were chosen based on inclusion and exclusion criteria. The quality of included studies was assessed according to the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated for the included studies. The summary receiver operating characteristic (SROC) curve and the area under the summary receiver operating characteristic (AUSROC) were used to evaluate the overall diagnostic performance. Eight studies were included in this systematic review. Among them four articles were included in meta-analysis. A total of 421 participants were studied in the meta-analysis. The pooled sensitivity, specificity, and DOR were 0.98 (95% confidence interval [CI]: 0.94-1.00), 0.97 (95% CI: 0.95-0.99), and 1095.49 (95% CI: 283.68.58-4230.45), respectively. The AUSROC was 0.9949 (standard error [SE] 0.0095). Synovial fluid α-defensin is a biomarker of high sensitivity and specificity for the diagnosis of PJI.

Accuracy of Percutaneous Core Biopsy in the Diagnosis of Small Renal Masses (≤ 4.0 cm): A Meta-analysis.

PubMed

He, Qiqi; Wang, Hanzhang; Kenyon, Jonathan; Liu, Guiming; Yang, Li; Tian, Junqiang; Yue, Zhongjin; Wang, Zhiping

2015-01-01

To use meta-analysis to determine the accuracy of percutaneous core needle biopsy in the diagnosis of small renal masses (SMRs ≤ 4.0 cm). Studies were identified by searching PubMed, Embase, and the Cochrane Library database up to March 2013. Two of the authors independently assessed the study quality using QUADAS-2 tool and extracted data that met the inclusion criteria. The sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR) and also summary receiver operating characteristic (SROC) curve were investigated and draw. Deek's funnel plot was used to evaluate the publication bias. A total of 9 studies with 788 patients (803 biopsies) were included. Failed biopsies without repeated or aborted from follow-up/surgery result were excluded (232 patients and 353 biopsies). For all cases, the pooled sensitivity was 94.0% (95% CI: 91.0%, 95.0%), the pooled positive likelihood was 22.57 (95 % CI: 9.20-55.34), the pooled negative likelihood was 0.09 (95 % CI: 0.06-0.13), the pooled DOR was 296.52(95 % CI: 99. 42-884.38). The area under the curve of SROC analysis was 0.959 ± 0.0254. Imaging-guided percutaneous core needle biopsy of small renal masses (SMRs ≤ 4.0 cm) is highly accurate to malignant tumor diagnosis with unknown metastatic status and could be offered to some patients after clinic judgment prior to surgical intervention consideration.

Superposition of tectonic structures leading elongated intramontane basin: the Alhabia basin (Internal Zones, Betic Cordillera)

NASA Astrophysics Data System (ADS)

Martínez-Martos, Manuel; Galindo-Zaldivar, Jesús; Martínez-Moreno, Francisco José; Calvo-Rayo, Raquel; Sanz de Galdeano, Carlos

2017-10-01

The relief of the Betic Cordillera was formed since the late Serravallian inducing the development of intramontane basins. The Alhabia basin, situated in the central part of the Internal Zones, is located at the intersection of the Alpujarran Corridor, the Tabernas basin, both trending E-W, and the NW-SE oriented Gádor-Almería basin. The geometry of the basin has been constrained by new gravity data. The basin is limited to the North by the Sierra de Filabres and Sierra Nevada antiforms that started to develop in Serravallian times under N-S shortening and to the south by Sierra Alhamilla and Sierra de Gádor antiforms. Plate convergence in the region rotated counter-clockwise in Tortonian times favouring the formation of E-W dextral faults. In this setting, NE-SW extension, orthogonal to the shortening direction, was accommodated by normal faults on the SW edge of Sierra Alhamilla. The Alhabia basin shows a cross-shaped depocentre in the zone of synform and fault intersection. This field example serves to constrain recent counter-clockwise stress rotation during the latest stages of Neogene-Quaternary basin evolution in the Betic Cordillera Internal Zones and underlines the importance of studying the basins' deep structure and its relation with the tectonic structures interactions.

[In Process Citation].

PubMed

Fubini, Lidia; Pasqualini, Osvaldo; Gilardi, Luisella; Ferro, Elisa; Marino, Maurizio; Santoro, Silvano; Tosco, Eleonora; Bena, Antonella; Coffano, Maria Elena

2016-05-26

Many authors consider narrative descriptions of injuries gathered by OSH inspectors extremely important in identifying causes, setting priorities and drawing up intervention strategies. Narratives provide additional insight regarding complex behaviour, attitudes and interactions, which help to understand the decision patterns and the context of the injury. Storytelling is an effective way of sharing and remembering information. The main aim was to describe the experience of collecting stories from injury investigation reports, backed up by systematic prevention guidelines, that will improve information sharing by means of a knowledge transfer method based on storytelling. OSH operators from Health Units, who were invited to provide the injury stories, were enrolled through educational workshops aimed at selecting the injuries to relate following the sentinel event approach, using an effective style of writing, identifying the key elements of the story and using witnesses' narratives to study in depth the critical points identified during the investigation. 110 OSH operators voluntarily joined the project between 2012 and first half of 2015. 33 injury stories were collected, discussed and published on Dors' website http://www.dors.it/storiedinfortunio. The results show that prevention and protection measures do indeed benefit from a narrative-based approach, so that health and safety can be viewed in a more comprehensive way by facilitating knowledge improvement and sharing.

A descriptive title

NASA Astrophysics Data System (ADS)

Martin, John C.; Williams, Steven C.; Darnley, Matt; Humphreys, Roberta M.

2017-06-01

In ATEL 10383 we reported the classical Luminous Blue Variable (Humphreys & Davidson, 1994) AF And = J004333.08+411210.3 = Var 19 in M31 (Hubble & Sandage, 1953) has brightened and grown redder over the last 800 days, indicating the start of a possible S Dor outburst.

Standard-b-Value Versus Low-b-Value Diffusion-Weighted Imaging in Hepatic Lesion Discrimination: A Meta-analysis.

PubMed

Xiong, Hui; Zeng, Yuan-Lin

2016-01-01

We sought to determine the comparative diagnostic performance of standard-b-value (500-1000s/mm) versus low-b-value (≤500 s/mm) diffusion-weighted imaging (DWI) in the discrimination of hepatic lesions. A total of 1775 hepatic malignant lesions and 1120 benign hepatic lesions from 21 studies were included. (1) The global sensitivity was 0.86 (95% confidence interval [CI], 0.847-0.879), the specificity was 0.82 (95% CI, 0.797-0.842), the positive likelihood ratio (PLR) was 6.234 (95% CI, 4.260-9.123), the negative likelihood ratio (NLR) was 0.175 (95% CI, 0.135-0.227), and diagnostic odds ratio (DOR) was 42.836 (95% CI, 24.134-76.031). The area under the curve (AUC) and Q* index were 0.93 and 0.87. Publication bias was not present (P > 0.05). (2)The sensitivity of a subgroup meta-analysis of standard-b-value DWI was 0.858 (95% CI, 0.835-0.880), the specificity was 0.836 (95% CI, 0.807-0.863), the PLR was 6.527 (95% CI, 3.857-11.046), the NLR was 0.168 (95% CI, 0.123-0.239), and the DOR was 49.716 (95% CI, 22.897-107.98). The AUC and Q* index were 0.941 and 0.88. (3)The sensitivity of a subgroup meta-analysis of low-b-value DWI was 0.87 (95% CI, 0.84-0.89), the specificity was 0.80 (95% CI, 0.76-0.83), the PLR was 6.22 (95% CI, 3.29-11.76), the NLR was 0.19 (95% CI, 0.12-0.29), and the DOR was 37.14 (95% CI, 14.80-93.18). The AUC and Q* index were 0.922 and 0.86. Hepatic DWI is useful in differentiating between malignant and benign hepatic lesions. Standard-b-value DWI displayed an overall superior diagnostic accuracy over low-b-value DWI. Further trials needed to determine whether increasing b values beyond 1000 s/mm affects the diagnostic accuracy of hepatic lesion discrimination.

Determining an anti-Mullerian hormone cutoff level to predict clinical pregnancy following in vitro fertilization in women with severely diminished ovarian reserve.

PubMed

Merhi, Zaher; Zapantis, Athena; Berger, Dara S; Jindal, Sangita K

2013-10-01

Serum anti-Mullerian hormone (AMH) levels estimate ovarian reserve. The purpose of this study was to identify a minimum serum AMH level that correlates with acceptable clinical pregnancy rate (CPR) in women with severe diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). A historical cohort of severe DOR participants (age ≥35) with day 3 FSH of >10 ng/mL were included (n = 120). Participants were categorized into 3 groups: AMH <0.2 (Group 1, n = 38), AMH = 0.2-0.79 (Group 2, n = 57) and AMH ≥ 0.8 (Group 3, n = 25) ng/mL. The main outcome was CPR. The number of retrieved and mature oocytes, transferred embryos, spontaneous abortion (SAB) and live birth (LB) rates were also evaluated. Among the three groups, there was no difference in day 3 FSH and estradiol, total gonadotropins dose used per cycle, or LB. Participants in Group 1 were two years older than those in Group 2 and had significantly higher BMI than those in Groups 2 and 3. The three groups significantly differed in AFC (Group 1< Group 2< Group 3; p = 0.001) and cycle cancellation rate (Group 1> Group 2> Group 3; p = 0.006), and had a trend toward significance in SAB rate (Group 1> Group 2> Group 3; p = 0.06). Group 3 had significantly more retrieved and mature oocytes than Groups 1 or 2. Group 2 and 3 had significantly higher CPR per cycle start compared to Group 1. Although Group 2 had significantly fewer oocytes retrieved and mature oocytes than Group 3, CPR per cycle start for both groups was not different. ROC curve indicated that the point of maximal inflection between lower and higher CPR represents an AMH value of 0.2 ng/mL. AMH of 0.2 ng/mL appears to be a meaningful threshold for predicting CPR in women with severe DOR at our practice. This information can be crucial during the pre-cycle counseling of these women.

Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis

PubMed Central

Deng, Han; Qi, Xingshun; Guo, Xiaozhong

2015-01-01

Abstract Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis. All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated. Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively. APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis. PMID:26496312

From gas to stars in energetic environments: dense gas clumps in the 30 Doradus region within the Large Magellanic Cloud

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Crystal N.; Meier, David S.; Ott, Jürgen

2014-09-20

We present parsec-scale interferometric maps of HCN(1-0) and HCO{sup +}(1-0) emission from dense gas in the star-forming region 30 Doradus, obtained using the Australia Telescope Compact Array. This extreme star-forming region, located in the Large Magellanic Cloud (LMC), is characterized by a very intense ultraviolet ionizing radiation field and sub-solar metallicity, both of which are expected to impact molecular cloud structure. We detect 13 bright, dense clumps within the 30 Doradus-10 giant molecular cloud. Some of the clumps are aligned along a filamentary structure with a characteristic spacing that is consistent with formation via varicose fluid instability. Our analysis showsmore » that the filament is gravitationally unstable and collapsing to form stars. There is a good correlation between HCO{sup +} emission in the filament and signatures of recent star formation activity including H{sub 2}O masers and young stellar objects (YSOs). YSOs seem to continue along the same direction of the filament toward the massive compact star cluster R136 in the southwest. We present detailed comparisons of clump properties (masses, linewidths, and sizes) in 30Dor-10 to those in other star forming regions of the LMC (N159, N113, N105, and N44). Our analysis shows that the 30Dor-10 clumps have similar masses but wider linewidths and similar HCN/HCO{sup +} (1-0) line ratios as clumps detected in other LMC star-forming regions. Our results suggest that the dense molecular gas clumps in the interior of 30Dor-10 are well shielded against the intense ionizing field that is present in the 30 Doradus region.« less

Laparoscopic surgery for esophageal achalasia: Multiport vs single-incision approach.

PubMed

Fukuda, Shuichi; Nakajima, Kiyokazu; Miyazaki, Yasuhiro; Takahashi, Tsuyoshi; Makino, Tomoki; Kurokawa, Yukinori; Yamasaki, Makoto; Miyata, Hiroshi; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2016-02-01

SILS can potentially improve aesthetic outcomes without adversely affecting treatment outcomes, but these outcomes are uncertain in laparoscopic Heller-Dor surgery. We determined if the degree of patient satisfaction with aesthetic outcomes progressed with the equivalent treatment outcomes after the introduction of a single-incision approach to laparoscopic Heller-Dor surgery. We retrospectively reviewed 20 consecutive esophageal achalasia patients (multiport approach, n = 10; single-incision approach, n = 10) and assessed the treatment outcomes and patient satisfaction with the aesthetic outcomes. In the single-incision approach, thin supportive devices were routinely used to gain exposure to the esophageal hiatus. No statistically significant differences in the operating time (210.2 ± 28.8 vs 223.5 ± 46.3 min; P = 0.4503) or blood loss (14.0 ± 31.7 vs 16.0 ± 17.8 mL; P = 0.8637) were detected between the multiport and single-incision approaches. We experienced no intraoperative complications. Mild dysphagia, which resolved spontaneously, was noted postoperatively in one patient treated with the multiport approach. The reduction rate of the maximum lower esophageal sphincter pressure was 25.1 ± 34.4% for the multiport approach and 21.8 ± 19.2% for the single-incision approach (P = 0.8266). Patient satisfaction with aesthetic outcomes was greater for the single-incision approach than for the multiport approach. When single-incision laparoscopic Heller-Dor surgery was performed adequately and combined with the use of thin supportive devices, patient satisfaction with the aesthetic outcomes was higher and treatment outcomes were equivalent to those of the multiport approach. © 2015 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Opioid receptor and β-arrestin2 densities and distribution change after sexual experience in the ventral tegmental area of male rats.

PubMed

Garduño-Gutiérrez, René; León-Olea, Martha; Rodríguez-Manzo, Gabriela

2018-05-15

Sexual experience modifies brain functioning and copulatory efficiency. Sexual activity, ejaculation in particular, is a rewarding behavior associated with the release of endogenous opioids, which modulate the activity of the mesolimbic dopaminergic system (MLS). In sexually exhausted rats, repeated ejaculation produces μ (MOR) and δ opioid receptor (DOR) internalization in ventral tegmental area (VTA) neurons, as well as long-lasting behavioral changes suggestive of brain plasticity processes. We hypothesized that in sexually naïve rats the endogenous opioids released during sexual experience acquisition, might contribute to brain plasticity processes involved in the generation of the behavioral changes induced by sexual experience. To this aim, using double immunohistochemistry and confocal microscopy, we compared in vivo MOR, DOR and β-arrestin2 densities and activation in the VTA of sexually naïve males, sexually experienced rats not executing sexual activity prior to sacrifice and sexually experienced animals that ejaculated once before sacrifice. Results showed that sexual experience acquisition improved male's copulatory ability and induced persistent changes in the density, cellular distribution and activation of MOR and β-arrestin2 in VTA neurons. DOR density was not modified, but its cellular location changed after sexual experience, revealing that these two opioid receptors were differentially activated during sexual experience acquisition. It is concluded that the endogenous opioids released during sexual activity produce adjustments in VTA neurons of sexually naïve male rats that might contribute to the behavioral plasticity expressed as an improvement in male copulatory parameters, promoted by the acquisition of sexual experience. Copyright © 2018 Elsevier Inc. All rights reserved.

On the G-Protein-Coupled Receptor Heteromers and Their Allosteric Receptor-Receptor Interactions in the Central Nervous System: Focus on Their Role in Pain Modulation

PubMed Central

Borroto-Escuela, Dasiel O.; Romero-Fernandez, Wilber; Rivera, Alicia; Van Craenenbroeck, Kathleen; Tarakanov, Alexander O.; Agnati, Luigi F.; Fuxe, Kjell

2013-01-01

The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer. This heteromer contributes to morphine-induced tolerance and dependence, since it becomes abundant and develops a reduced G-protein-coupling with reduced signaling mainly operating via β-arrestin2 upon chronic morphine treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to the heteromer and the biological actions of morphine. The gender- and ovarian steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR) heterodimers enhances antinociceptive functions and if impaired could contribute to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch. Other mechanism for the antinociceptive actions of acupuncture along meridians may be that it enhances the cross-desensitization of the TRPA1 (chemical nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the nociceptor terminals located along these meridians. Selective ionotropic cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1 heteromeric nociceptor channels by being negative allosteric modulators of these channels leading to antinociception and antihyperalgesia. PMID:23956775

Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters.

PubMed

Maslow, Bat-Sheva L; Davis, Stephanie; Engmann, Lawrence; Nulsen, John C; Benadiva, Claudio A

2016-09-01

This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Müllerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters.

A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL)

PubMed Central

Spurgeon, Stephen E.; Furman, Richard R.; Flinn, Ian W.; Coutre, Steven E.; Brown, Jennifer R.; Benson, Don M.; Byrd, John C.; Peterman, Sissy; Cho, Yoonjin; Yu, Albert; Godfrey, Wayne R.; Wagner-Johnston, Nina D.

2014-01-01

Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase δ (PI3Kδ), was evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 40 patients with relapsed or refractory mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (range, 52-83) and received median of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Common grade ≥3 adverse events (AEs) included (total%/grade ≥3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3Kδ is a viable strategy and worthy of additional study in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528. PMID:24615778

Potential diagnostic value of serum p53 antibody for detecting colorectal cancer: A meta-analysis.

PubMed

Meng, Rongqin; Wang, Yang; He, Liang; He, Yuanqing; Du, Zedong

2018-04-01

Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS). The result of pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were analyzed and compared with overall accuracy measures using diagnostic odds ratios (DORs) and area under the curve (AUC) analysis. Publication bias and heterogeneity were also assessed. A total of 11 trials that enrolled a combined 3,392 participants were included in the meta-analysis. Approximately 72.73% (8/11) of the included studies were of high quality (QUADAS score >7), and all were retrospective case-control studies. The pooled sensitivity was 0.19 [95% confidence interval (CI), 0.18-0.21] and pooled specificity was 0.93 (95% CI, 0.92-0.94). Results also demonstrated a PLR of 4.56 (95% CI, 3.27-6.34), NLR of 0.78 (95% CI, 0.71-0.85) and DOR of 6.70 (95% CI, 4.59-9.76). The symmetrical summary receiver operating characteristic curve was 0.73. Furthermore, no evidence of publication bias or heterogeneity was observed in the meta-analysis. Meta-analysis data indicated that s-p53 antibody possesses potential diagnostic value for CRC. However, discrimination power was somewhat limited due to the low sensitivity.

UPTAKE AND ELIMINATION OF DICHLOROACETIC ACID BY RAINBOW TROUT

EPA Science Inventory

Dichloroacetic acid (DCA) is a by-product of drinking water chlorination and is a hepatocarcinogen in rodents. Preliminary results of a chronic testing effort with Japanese medaka suggest the possibility of similar effects is fish. Adult rainbow trout were cannulated from the dor...

Reusing ethyl acetate and aqueous exhausted fractions of dry olive mill residue by saprobe fungi.

PubMed

Aranda, E; García-Romera, I; Ocampo, J A; Carbone, V; Malorni, A; Sannino, F; De Martino, A; Capasso, R

2007-01-01

Some saprobe fungi (Phlebia radiata, Trametes versicolor, Coriolopsis rigida, Pycnoporus cinnabarinus, Fomes sclerodermus or Pleurotus pulmonarius) were able to bioconvert the ethyl acetate fraction (DEAF) and the corresponding aqueous exhausted fraction (EAF) of dry olive mill residue (DOR), reducing their phytotoxicity on Lepidium sativum seeds. Large amount of hydroxytyrosol together with other eight monomeric phenols were found in the native DEAF fraction, which represents a good source of antioxidants. P. radiata, T. versicolor and F. sclerodermus caused an effective phytotoxicity reduction of EAF in the concentration range of 25-3 gl(-1). In particular, in the range between 12.5 and 3 gl(-1), the EAF samples inoculated with P. radiata and F. sclerodermus surprisingly stimulated the germinability of L. sativum, suggesting their use as a potential biofertilizer. This is the first report which showed the bioconversion of the above fractions in shorter time with respect to the previous findings concerning DOR. The possible implications of laccase in the decrease of DEAF and EAF phytotoxicity was also discussed.

Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses.

PubMed

Di Legge, A; Testa, A C; Ameye, L; Van Calster, B; Lissoni, A A; Leone, F P G; Savelli, L; Franchi, D; Czekierdowski, A; Trio, D; Van Holsbeke, C; Ferrazzi, E; Scambia, G; Timmerman, D; Valentin, L

2012-09-01

To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Postoperative Gastroesophageal Reflux After Laparoscopic Heller-Dor for Achalasia: True Incidence with an Objective Evaluation.

PubMed

Salvador, Renato; Pesenti, Elisa; Gobbi, Laura; Capovilla, Giovanni; Spadotto, Lorenzo; Voltarel, Guerrino; Cavallin, Francesco; Nicoletti, Loredana; Valmasoni, Michele; Ruol, Alberto; Merigliano, Stefano; Costantini, Mario

2017-01-01

The most common complication after laparoscopic Heller-Dor (LHD) is gastroesophageal reflux disease (GERD). The present study aimed (a) to analyze the true incidence of postoperative reflux by objectively assessing a large group of LHD patients and (b) to see whether the presence of typical GERD symptoms correlates with the real incidence of postoperative reflux. After LHD, patients were assessed by means of a symptom score, endoscopy, esophageal manometry, and 24-h pH monitoring. Patients were assigned to three groups: those did not accept to perform 24-h pH monitoring (group NP); those with normal postoperative pH findings (group A); and those with pathological postoperative acid exposure (group B). Four hundred sixty-three of the 806 LHD patients agreed to undergo follow-up 24-h pH monitoring. Normal pH findings were seen in 423 patients (group A, 91.4 %), while 40 (8.6 %) had a pathological acid exposure (group B). The median symptom scores were similar: 3.0 (IQR 0-8) in group A and 6.0 (IQR 0-10) in group B (p = 0.29). At endoscopy, the percentage of esophagitis was also similar (11 % in group A, 19 % in group B; p = 0.28). This study demonstrated that, after LHD was performed by experienced surgeons, the true incidence of postoperative GERD is very low. The incidence of this possible complication should be assessed by pH monitoring because endoscopic findings and symptoms may be misleading.

Exploring Molecular Mechanisms of Ligand Recognition by Opioid Receptors with Metadynamics†

PubMed Central

Provasi, Davide; Bortolato, Andrea; Filizola, Marta

2009-01-01

Opioid receptors are G protein-coupled receptors (GPCRs) of utmost significance in the development of potent analgesic drugs for the treatment of severe pain. An accurate evaluation at the molecular level of the ligand binding pathways into these receptors may play a key role in the design of new molecules with more desirable properties and reduced side effects. The recent characterization of high-resolution X-ray crystal structures of non-rhodopsin GPCRs for diffusible hormones and neurotransmitters presents an unprecedented opportunity to build improved homology models of opioid receptors, and to study in more detail their molecular mechanisms of ligand recognition. In this study, possible entry pathways of the non-selective antagonist naloxone (NLX) from the water environment into the well-accepted alkaloid binding pocket of a delta opioid receptor (DOR) molecular model based on the β2-adrenergic receptor crystal structure are explored using microsecond-scale well-tempered metadynamics simulations. Using as collective variables distances that account for the position of NLX and of the receptor extracellular loop 2 in relation to the DOR binding pocket, we were able to distinguish between the different states visited by the ligand (i.e., docked, undocked, and metastable bound intermediates), and to predict a free energy of binding close to experimental values after correcting for possible drawbacks of the sampling approach. The strategy employed herein holds promise for its application to the docking of diverse ligands to the opioid receptors as well as to other GPCRs. PMID:19785461

Exploring molecular mechanisms of ligand recognition by opioid receptors with metadynamics.

PubMed

Provasi, Davide; Bortolato, Andrea; Filizola, Marta

2009-10-27

Opioid receptors are G protein-coupled receptors (GPCRs) of utmost significance in the development of potent analgesic drugs for the treatment of severe pain. An accurate evaluation at the molecular level of the ligand binding pathways into these receptors may play a key role in the design of new molecules with more desirable properties and reduced side effects. The recent characterization of high-resolution X-ray crystal structures of non-rhodopsin GPCRs for diffusible hormones and neurotransmitters presents an unprecedented opportunity to build improved homology models of opioid receptors, and to study in more detail their molecular mechanisms of ligand recognition. In this study, possible pathways for entry of the nonselective antagonist naloxone (NLX) from the water environment into the well-accepted alkaloid binding pocket of a delta opioid receptor (DOR) molecular model based on the beta2-adrenergic receptor crystal structure are explored using microsecond-scale well-tempered metadynamics simulations. Using as collective variables distances that account for the position of NLX and of the receptor extracellular loop 2 in relation to the DOR binding pocket, we were able to distinguish between the different states visited by the ligand (i.e., docked, undocked, and metastable bound intermediates) and to predict a free energy of binding close to experimental values after correcting for possible drawbacks of the sampling approach. The strategy employed herein holds promise for its application to the docking of diverse ligands to the opioid receptors as well as to other GPCRs.

A meta-analysis on diagnostic value of serum cystatin C and creatinine for the evaluation of glomerular filtration function in renal transplant patients.

PubMed

Pan, Pan; Binjie, Hu; Min, Li; Lipei, Fan; Yanli, Ni; Junwen, Zhou; Xianghua, Shi

2014-12-01

This meta-analysis aimed to perform a systematic review on comparing the diagnostic value of serum cystatin C and creatinine for glomerular filtration rate in renal transplant patients. The data was extracted into 2×2 table after the articles were assessed by the tool of QUADAS and heterogeneity analysis. The SROC curve and meta-analysis were performed by MetaDisc1.4. Meta-analysis showed that the serum cystatin C had no heterogeneity (P=0.418, I2=2.2%, DOR=25.03), while creatinine heterogeneity was high (P=0.109, I2=37.5%, DOR=9.11). The values of SEN, SPE and SAUC were calculated as 0.86, 0.70 and 0.9015 for cystatin C, and 0.78, 0.73 and 0.8285 for creatinine individually. This study utilized GFR detection and subgroups analysis by cutoff. The PLR was 6.13 and the NLR was 0.12 for cystatin C, compared to SCr (3.72, 0.32). There was homogeneity among these studies using PENIA testing for cystatin C (χ2=2.61, P=0.4560, I2=0.0%. There were significant correlations among cystatin C , creatinine and glomerular filtration rate (GFR). Cystatin C had more sensitivity but less specificity than creatinine for evaluation of GFR. Cystatin C had strong ability in diagnosing renal function after renal transplant and ruling out diagnostic efficacy.

Diagnostic value of panoramic radiography in predicting inferior alveolar nerve injury after mandibular third molar extraction: a meta-analysis.

PubMed

Liu, W; Yin, W; Zhang, R; Li, J; Zheng, Y

2015-06-01

The aim of this study was to evaluate the predictive value of panoramic radiography on inferior alveolar nerve (IAN) injury after extraction of the mandibular third molar. Relevant studies up to 1 June 2014 that discussed the association of panoramic radiography signs and post-mandibular third molar extraction IAN injury were systematically retrieved from the databases of PubMed, Embase, Springerlink, Web of Science and Cochrane library. The effect size of pooled sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR) and diagnostic odds ratio (DOR) with their 95% confidence intervals (CI) were statistically analysed with Meta-disc 1.4 software. Nine articles were included in this meta-analysis. The pooled estimates of sensitivity and specificity were 0.56 (95% CI: 0.50-0.61) and 0.86 (95% CI: 0.84-0.87), respectively. The overall PLR was 3.46 (95% CI: 2.02-5.92) and overall NLR was 0.58 (95% CI: 0.45-0.73). The pooled estimate of DOR was 6.49 (95% CI: 2.92-14.44). The area under the summary receiver operating characteristic curve was 0.7143 ± 0.0604. The meta-analysis indicated that interpretation of panoramic radiography based on darkening of the root had a high specificity in predicting IAN injury after mandibular third molar extraction. However, the ability of this panoramic radiography marker to detect true positive IAN injury was not satisfactory. © 2015 Australian Dental Association.

Can CT imaging features of ground-glass opacity predict invasiveness? A meta-analysis.

PubMed

Dai, Jian; Yu, Guoyou; Yu, Jianqiang

2018-04-01

A meta-analysis was conducted to investigate the diagnostic performance of computed tomography (CT) imaging features of ground-glass opacity (GGO) to predict invasiveness. Two reviewers independently searched PubMed, Medline, Web of Science, Cochrane Embase and CNKI for relevant studies. CT imaging signs of bubble lucency, speculation, lobulated margin, and pleural indentation were used as diagnostic references to discriminate pre-invasive and invasive disease. The sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the area under the SROC curve (AUC) were calculated to evaluate diagnostic efficiency. Twelve studies were finally included. Diagnostic performance ranged from 0.41 to 0.52 for sensitivity and 0.56 to 0.63 for specificity. The diagnostic positive and negative likelihood ratios ranged from 1.03 to 2.13 and 0.52 to 1.05, respectively. The DORs of the GGO CT features for discriminating invasive disease ranged from 1.02 to 4.00. The area under the ROC curve was also low, with a range of 0.60 to 0.67 for discriminating pre-invasive and invasive disease. The diagnostic value of a single CT imaging sign of GGO, such as bubble lucency, speculation, lobulated margin, or pleural indentation is limited for discriminating pre-invasive and invasive disease because of low sensitivity, specificity, and AUC. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Diagnostic Performance of Bronchoalveolar Lavage Fluid CD4/CD8 Ratio for Sarcoidosis: A Meta-analysis.

PubMed

Shen, Yongchun; Pang, Caishuang; Wu, Yanqiu; Li, Diandian; Wan, Chun; Liao, Zenglin; Yang, Ting; Chen, Lei; Wen, Fuqiang

2016-06-01

The usefulness of bronchoalveolar lavage fluid (BALF) CD4/CD8 ratio for diagnosing sarcoidosis has been reported in many studies with variable results. Therefore, we performed a meta-analysis to estimate the overall diagnostic accuracy of BALF CD4/CD8 ratio based on the bulk of published evidence. Studies published prior to June 2015 and indexed in PubMed, OVID, Web of Science, Scopus and other databases were evaluated for inclusion. Data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled from included studies. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deeks's funnel plot was used to detect publication bias. Sixteen publications with 1885 subjects met our inclusion criteria and were included in this meta-analysis. Summary estimates of the diagnostic performance of the BALF CD4/CD8 ratio were as follows: sensitivity, 0.70 (95%CI 0.64-0.75); specificity, 0.83 (95%CI 0.78-0.86); PLR, 4.04 (95%CI 3.13-5.20); NLR, 0.36 (95%CI 0.30-0.44); and DOR, 11.17 (95%CI 7.31-17.07). The area under the SROC curve was 0.84 (95%CI 0.81-0.87). There was no evidence of publication bias. Measuring the BALF CD4/CD8 ratio may assist in the diagnosis of sarcoidosis when interpreted in parallel with other diagnostic factors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: a systematic review and a meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Zakavi, Seyed Rasoul; Caldarella, Carmelo; Muoio, Barbara; Bertagna, Francesco; Ceriani, Luca; Giovanella, Luca

2013-12-01

To systematically review and meta-analyse published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in osteomyelitis related to diabetic foot. A comprehensive literature search of studies on (18)F-FDG-PET and PET/CT in patients with diabetic foot was performed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) and area under the summary ROC curve of (18)F-FDG-PET and PET/CT in patients with osteomyelitis related to diabetic foot were calculated. Nine studies comprising 299 patients with diabetic foot were included in the qualitative analysis (systematic review) and discussed. The quantitative analysis (meta-analysis) of four selected studies provided the following results on a per patient-based analysis: sensitivity was 74% [95% confidence interval (95%CI): 60-85%], specificity 91% (95%CI: 85-96%), LR+ 5.56 (95%CI: 2.02-15.27), LR- 0.37 (95%CI: 0.10-1.35), and DOR 16.96 (95%CI: 2.06-139.66). The area under the summary ROC curve was 0.874. In patients with suspected osteomyelitis related to diabetic foot (18)F-FDG-PET and PET/CT demonstrated a high specificity, being potentially useful tools if combined with other imaging methods such as MRI. Nevertheless, the literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diagnostic accuracy of contrast-enhanced ultrasound in assessing the therapeutic response to radio frequency ablation for liver tumors: systematic review and meta-analysis.

PubMed

Xuan, Min; Zhou, Fengsheng; Ding, Yan; Zhu, Qiaoying; Dong, Ji; Zhou, Hao; Cheng, Jun; Jiang, Xiao; Wu, Pengxi

2018-04-01

To review the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) used to detect residual or recurrent liver tumors after radiofrequency ablation (RFA). This technique uses contrast-enhanced computer tomography or/and contrast-enhanced magnetic resonance imaging as the gold standard of investigation. MEDLINE, EMBASE, and COCHRANE were systematically searched for all potentially eligible studies comparing CEUS with the reference standard that follows RFA. Risk of bias and applicability concerns were addressed by adopting the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled point estimates for sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios (DOR) with 95% CI were computed before plotting the sROC (summary receiver operating characteristic) curve. Meta-regression and subgroup analysis were used to identify the source of the heterogeneity that was detected. Publication bias was evaluated using Deeks' funnel plot asymmetry test. Ten eligible studies on 1162 lesions that occurred between 2001 and 2016 were included in the final analysis. The quality of the included studies assessed by the QUADAS-2 tool was considered reasonable. The pooled sensitivity and specificity of CEUS in detecting residual or recurrent liver tumors had the following values: 0.90 (95% CI 0.85-0.94) and 1.00 (95% CI 0.99-1.00), respectively. Overall DOR was 420.10 (95% CI 142.30-1240.20). The sources of heterogeneity could not be precisely identified by meta-regression or subgroup analysis. No evidence of publication bias was found. This study confirmed that CEUS exhibits high sensitivity and specificity in assessing therapeutic responses to RFA for liver tumors.

Diagnostic accuracy of 18F-FDG-PET and PET/CT in the differential diagnosis between malignant and benign pleural lesions: a systematic review and meta-analysis.

PubMed

Treglia, Giorgio; Sadeghi, Ramin; Annunziata, Salvatore; Lococo, Filippo; Cafarotti, Stefano; Bertagna, Francesco; Prior, John O; Ceriani, Luca; Giovanella, Luca

2014-01-01

To systematically review and meta-analyze published data about the diagnostic accuracy of fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the differential diagnosis between malignant and benign pleural lesions. A comprehensive literature search of studies published through June 2013 regarding the diagnostic performance of (18)F-FDG-PET and PET/CT in the differential diagnosis of pleural lesions was carried out. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odds ratio (DOR) of (18)F-FDG-PET or PET/CT in the differential diagnosis of pleural lesions on a per-patient-based analysis were calculated. The area under the summary receiver operating characteristic curve (AUC) was calculated to measure the accuracy of these methods. Subanalyses considering device used (PET or PET/CT) were performed. Sixteen studies including 745 patients were included in the systematic review. The meta-analysis of 11 selected studies provided the following results: sensitivity 95% (95% confidence interval [95%CI]: 92-97%), specificity 82% (95%CI: 76-88%), LR+ 5.3 (95%CI: 2.4-11.8), LR- 0.09 (95%CI: 0.05-0.14), DOR 74 (95%CI: 34-161). The AUC was 0.95. No significant improvement of the diagnostic accuracy considering PET/CT studies only was found. (18)F-FDG-PET and PET/CT demonstrated to be accurate diagnostic imaging methods in the differential diagnosis between malignant and benign pleural lesions; nevertheless, possible sources of false-negative and false-positive results should be kept in mind. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

The Thermal Stabilization of Vaccines Against Agents of Bioterrorism

DTIC Science & Technology

2005-09-01

to determine (1) whether rPA in the formulation buffer in the absence of excipients binds to Alhydrogel®and (2) the binding capacity . The aluminum...botulinum toxin (Allergan), A ricin vaccine (DOR Biopharma ) and a vaccine against Norwalk virus (Ligocyte) were also initiated and are in various

Accurate radio and optical positions for the radio star HD 36705 (AB Doradus)

NASA Technical Reports Server (NTRS)

White, Graeme L.; Jauncey, David L.; Batty, Michael J.; Peters, W. L.; Gulkis, S.

1988-01-01

Arc-second position measurements of the active star HD 36705 (AB Dor) and of the variable radio source found nearby are presented. These measurements show that the radio source is clearly identified with HD 36705 and not with the nearby red-dwarf star Rst 137B.

National Association Links, Alaska Oil and Gas Conservation Commission,

Science.gov Websites

Oil and Gas Conservation Commission Alaska Department of Administration, Alaska Oil and Gas Guidelines Regulatory Regulations Statutes Industry Guidance Bulletins Memorandums of Agreement Links Oil Field Terms (Schlumberger) Spot Price Information (DOE) West Coast Price - NS Oil (DOR) Calendar State

What is the role of fresh groundwater and recirculated seawater in conveying nutrients to the coastal ocean?

USGS Publications Warehouse

Weinstein, Y.; Yechieli, Y.; Shalem, Y.; Burnett, W.C.; Swarzenski, P.W.; Herut, B.

2011-01-01

Submarine groundwater discharge (SGD) is a major process operating at the land-sea interface. Quantifying the SGD nutrient loads and the marine/terrestrial controls of this transport is of high importance, especially in oligotrophic seas such as the eastern Mediterranean. The fluxes of nutrients in groundwater discharging from the seafloor at Dor Bay (southeastern Mediterranean) were studied in detail using seepage meters. Our main finding is that the terrestrial, fresh groundwater is the main conveyor of DIN and silica to the coastal water, with loads of 500 and 560 mol/yr, respectively, per 1 m shoreline. Conversely, recirculated seawater is nutrient-poor, and its role is mainly as a dilution agent. The nutrient loads regenerated in the subterranean estuary (sub-bay sediment) are relatively small, consisting mostly of ammonium (24 mol/yr). On the other hand, the subterranean estuary at Dor Bay sequesters as much as 100 mol N/yr per 1 m shoreline, mainly via denitrification processes. These, and observations from other SGD sites, imply that the subterranean estuary at some coastal systems may function more as a sink for nitrogen than a source. This further questions the extent of nutrient contributions to the coastal water by some subterranean estuaries and warrants systematic evaluation of this process in various hydrological and marine trophic conditions. ?? 2011 American Chemical Society.

Diagnostic Accuracy of Computer Tomography Angiography and Magnetic Resonance Angiography in the Stenosis Detection of Autologuous Hemodialysis Access: A Meta-Analysis

PubMed Central

Liu, Shiyuan

2013-01-01

Purpose To compare the diagnostic performances of computer tomography angiography (CTA) and magnetic resonance angiography (MRA) for detection and assessment of stenosis in patients with autologuous hemodialysis access. Materials and Methods Search of PubMed, MEDLINE, EMBASE and Cochrane Library database from January 1984 to May 2013 for studies comparing CTA or MRA with DSA or surgery for autologuous hemodialysis access. Eligible studies were in English language, aimed to detect more than 50% stenosis or occlusion of autologuous vascular access in hemodialysis patients with CTA and MRA technology and provided sufficient data about diagnosis performance. Methodological quality was assessed by the Quality Assessment of Diagnostic Studies (QUADAS) instrument. Sensitivities (SEN), specificities (SPE), positive likelihood ratio (PLR), negative likelihood values (NLR), diagnostic odds ratio (DOR) and areas under the receiver operator characteristic curve (AUC) were pooled statistically. Potential threshold effect, heterogeneity and publication bias was evaluated. The clinical utility of CTA and MRA in detection of stenosis was also investigated. Result Sixteen eligible studies were included, with a total of 500 patients. Both CTA and MRA were accurate modality (sensitivity, 96.2% and 95.4%, respectively; specificity, 97.1 and 96.1%, respectively; DOR [diagnostic odds ratio], 393.69 and 211.47, respectively) for hemodialysis vascular access. No significant difference was detected between the diagnostic performance of CTA (AUC, 0.988) and MRA (AUC, 0.982). Meta-regression analyses and subgroup analyses revealed no statistical difference. The Deek’s funnel plots suggested a publication bias. Conclusion Diagnostic performance of CTA and MRA for detecting stenosis of hemodialysis vascular access had no statistical difference. Both techniques may function as an alternative or an important complement to conventional digital subtraction angiography (DSA) and may be able to help guide medical management. PMID:24194928

Do individuals with fragile X syndrome show developmental stuttering or not? Comment on "Speech fluency in fragile X syndrome" by van Borsel, Dor and Rondal.

PubMed

Howell, Peter

2008-02-01

Van Borsel, Dor, and Rondal (2007) examined the speech of seven boys and two young male adults with fragile X syndrome and considered whether their speech was comparable to that reported in the developmental stuttering literature. They listed five criteria which led them to conclude that the speech patterns of speakers with fragile X syndrome differed from those observed in developmental stuttering. The differences noted were: 1) distribution of type of dysfluency; 2) the class of word on which dysfluency occurred; 3) whether word length affected dysfluency; 4) number of times words and phrases were repeated; and 5) whether there were influences of material type on fluency (spontaneous speech, repeated material etc.). They concluded that the speech of speakers with fragile X syndrome differed from developmental stuttering. The comparisons that van Borsel et al. (2007) made between participant groups were not for speakers of comparable ages. Comparisons with groups of corresponding ages support the opposite conclusion, namely the young speakers with fragile X syndrome show patterns similar to developmental stuttering.

An astrophysical interpretation of the remarkable g-mode frequency groups of the rapidly rotating γ Dor star, KIC 5608334

NASA Astrophysics Data System (ADS)

Saio, Hideyuki; Bedding, Timothy R.; Kurtz, Donald W.; Murphy, Simon J.; Antoci, Victoria; Shibahashi, Hiromoto; Li, Gang; Takata, Masao

2018-06-01

The Fourier spectrum of the γ-Dor variable KIC 5608334 shows remarkable frequency groups at ˜3, ˜6, ˜9, and 11-12 d-1. We explain the four frequency groups as prograde sectoral g modes in a rapidly rotating star. Frequencies of intermediate-to-high radial order prograde sectoral g modes in a rapidly rotating star are proportional to |m| (i.e. ν ∝ |m|) in the corotating frame as well as in the inertial frame. This property is consistent with the frequency groups of KIC 5608334 as well as the period versus period-spacing relation present within each frequency group, if we assume a rotation frequency of 2.2 d-1, and that each frequency group consists of prograde sectoral g modes of |m| = 1, 2, 3, and 4, respectively. In addition, these modes naturally satisfy near-resonance conditions νi ≈ νj + νk with mi = mj + mk. We even find exact resonance frequency conditions (within the precise measurement uncertainties) in many cases, which correspond to combination frequencies.

LAMP assay and rapid sample preparation method for on-site detection of flavescence dorée phytoplasma in grapevine

PubMed Central

Kogovšek, P; Hodgetts, J; Hall, J; Prezelj, N; Nikolić, P; Mehle, N; Lenarčič, R; Rotter, A; Dickinson, M; Boonham, N; Dermastia, M; Ravnikar, M

2015-01-01

In Europe the most devastating phytoplasma associated with grapevine yellows (GY) diseases is a quarantine pest, flavescence dorée (FDp), from the 16SrV taxonomic group. The on-site detection of FDp with an affordable device would contribute to faster and more efficient decisions on the control measures for FDp. Therefore, a real-time isothermal LAMP assay for detection of FDp was validated according to the EPPO standards and MIQE guidelines. The LAMP assay was shown to be specific and extremely sensitive, because it detected FDp in all leaf samples that were determined to be FDp infected using quantitative real-time PCR. The whole procedure of sample preparation and testing was designed and optimized for on-site detection and can be completed in one hour. The homogenization procedure of the grapevine samples (leaf vein, flower or berry) was optimized to allow direct testing of crude homogenates with the LAMP assay, without the need for DNA extraction, and was shown to be extremely sensitive. PMID:26146413

Diagnostic accuracy of droplet digital PCR for detection of EGFR T790M mutation in circulating tumor DNA

PubMed Central

Tong, Xiang; Wang, Ye; Wang, Chengdi; Jin, Jing; Tian, Panwen; Li, Weimin

2018-01-01

Objectives Although different methods have been established to detect epidermal growth factor receptor (EGFR) T790M mutation in circulating tumor DNA (ctDNA), a wide range of diagnostic accuracy values were reported in previous studies. The aim of this meta-analysis was to provide pooled diagnostic accuracy measures for droplet digital PCR (ddPCR) in the diagnosis of EGFR T790M mutation based on ctDNA. Materials and methods A systematic review and meta-analysis were carried out based on resources from Pubmed, Web of Science, Embase and Cochrane Library up to October 11, 2017. Data were extracted to assess the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio (NLR), diagnostic OR (DOR), and areas under the summary receiver-operating characteristic curve (SROC). Results Eleven of 311 studies identified have met the including criteria. The sensitivity and specificity of ddPCR for the detection of T790M mutation in ctDNA ranged from 0.0% to 100.0% and 63.2% to 100.0%, respectively. For the pooled analysis, ddPCR had a performance of 70.1% (95% CI, 62.7%–76.7%) sensitivity, 86.9 % (95% CI, 80.6%–91.7%) specificity, 3.67 (95% CI, 2.33–5.79) PLR, 0.41 (95% CI, 0.32–0.55) NLR, and 10.83 (95% CI, 5.86–20.03) DOR, with the area under the SROC curve being 0.82. Conclusion The ddPCR harbored a good performance for detection of EGFR T790M mutation in ctDNA. PMID:29844700

[Smoothing Gan Reinforcing Shen Method Adjuvantly Treated Poor Response of Diminished Ovari- an Reserve Patients in in vitro Fertilization and Embryo Transfer: a Clinical Study].

PubMed

Zhang, Zheng; Zhang, Xue-hong; He, Tian-you

2015-10-01

To study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET). Totally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups. The total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05). SGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos.

Planets around Low-mass Stars (PALMS). VI. Discovery of a Remarkably Red Planetary-mass Companion to the AB Dor Moving Group Candidate 2MASS J22362452+4751425*

NASA Astrophysics Data System (ADS)

Bowler, Brendan P.; Liu, Michael C.; Mawet, Dimitri; Ngo, Henry; Malo, Lison; Mace, Gregory N.; McLane, Jacob N.; Lu, Jessica R.; Tristan, Isaiah I.; Hinkley, Sasha; Hillenbrand, Lynne A.; Shkolnik, Evgenya L.; Benneke, Björn; Best, William M. J.

2017-01-01

We report the discovery of an extremely red planetary-mass companion to 2MASS J22362452+4751425, a ≈0.6 M⊙ late-K dwarf likely belonging to the ˜120 Myr AB Doradus moving group. 2M2236+4751 b was identified in multi-epoch NIRC2 adaptive optics imaging at Keck Observatory at a separation of 3\\buildrel{\\prime\\prime}\\over{.} 7, or 230 ± 20 AU in projection at the kinematic distance of 63 ± 5 pc to its host star. Assuming membership in the AB Dor group, as suggested from its kinematics, the inferred mass of 2M2236+4751 b is 11-14 MJup. Follow-up Keck/OSIRIS K-band spectroscopy of the companion reveals strong CO absorption similar to other faint red L dwarfs and lacks signs of methane absorption, despite having an effective temperature of ≈900-1200 K. With a (J-K)MKO color of 2.69 ± 0.12 mag, the near-infrared slope of 2M2236+4751 b is redder than all of the HR 8799 planets and instead resembles the ≈23 Myr isolated planetary-mass object PSO J318.5-22, implying that similarly thick photospheric clouds can persist in the atmospheres of giant planets at ages beyond 100 Myr. In near-infrared color-magnitude diagrams, 2M2236+4751 b is located at the tip of the red L dwarf sequence and appears to define the “elbow” of the AB Dor substellar isochrone separating low-gravity L dwarfs from the cooler young T dwarf track. 2M2236+4751 b is the reddest substellar companion to a star and will be a valuable benchmark to study the shared atmospheric properties of young low-mass brown dwarfs and extrasolar giant planets. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W.M. Keck Foundation.

Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

PubMed

Deng, Han; Qi, Xingshun; Guo, Xiaozhong

2015-10-01

Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.

Variation and inheritance of iron reductase activity in the roots of common bean (Phaseolus vulgaris L.) and association with seed iron accumulation QTL.

PubMed

Blair, Matthew W; Knewtson, Sharon Jb; Astudillo, Carolina; Li, Chee-Ming; Fernandez, Andrea C; Grusak, Michael A

2010-10-05

Iron deficiency anemia is a global problem which often affects women and children of developing countries. Strategy I plants, such as common bean (Phaseolus vulgaris L.) take up iron through a process that involves an iron reduction mechanism in their roots; this reduction is required to convert ferric iron to ferrous iron. Root absorbed iron is critical for the iron nutrition of the plant, and for the delivery of iron to the shoot and ultimately the seeds. The objectives of this study were to determine the variability and inheritance for iron reductase activity in a range of genotypes and in a low × high seed iron cross (DOR364 x G19833), to identify quantitative trait loci (QTL) for this trait, and to assess possible associations with seed iron levels. The experiments were carried out with hydroponically grown plants provided different amounts of iron varying between 0 and 20 μM Fe(III)-EDDHA. The parents, DOR364 and G19833, plus 13 other cultivated or wild beans, were found to differ in iron reductase activity. Based on these initial experiments, two growth conditions (iron limited and iron sufficient) were selected as treatments for evaluating the DOR364 × G19833 recombinant inbred lines. A single major QTL was found for iron reductase activity under iron-limited conditions (1 μM Fe) on linkage group b02 and another major QTL was found under iron sufficient conditions (15 μM Fe) on linkage group b11. Associations between the b11 QTL were found with several QTL for seed iron. Genes conditioning iron reductase activity in iron sufficient bean plants appear to be associated with genes contributing to seed iron accumulation. Markers for bean iron reductase (FRO) homologues were found with in silico mapping based on common bean synteny with soybean and Medicago truncatula on b06 and b07; however, neither locus aligned with the QTL for iron reductase activity. In summary, the QTL for iron reductase activity under iron limited conditions may be useful in environments where beans are grown in alkaline soils, while the QTL for iron reductase under sufficiency conditions may be useful for selecting for enhanced seed nutritional quality.

BONA FIDE, STRONG-VARIABLE GALACTIC LUMINOUS BLUE VARIABLE STARS ARE FAST ROTATORS: DETECTION OF A HIGH ROTATIONAL VELOCITY IN HR CARINAE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groh, J. H.; Damineli, A.; Moises, A. P.

2009-11-01

We report optical observations of the luminous blue variable (LBV) HR Carinae which show that the star has reached a visual minimum phase in 2009. More importantly, we detected absorptions due to Si IV lambdalambda4088-4116. To match their observed line profiles from 2009 May, a high rotational velocity of v{sub rot} approx = 150 +- 20 km s{sup -1} is needed (assuming an inclination angle of 30 deg.), implying that HR Car rotates at approx =0.88 +- 0.2 of its critical velocity for breakup (v{sub crit}). Our results suggest that fast rotation is typical in all strong-variable, bona fide galacticmore » LBVs, which present S-Dor-type variability. Strong-variable LBVs are located in a well-defined region of the HR diagram during visual minimum (the 'LBV minimum instability strip'). We suggest this region corresponds to where v{sub crit} is reached. To the left of this strip, a forbidden zone with v{sub rot}/v{sub crit}>1 is present, explaining why no LBVs are detected in this zone. Since dormant/ex LBVs like P Cygni and HD 168625 have low v{sub rot}, we propose that LBVs can be separated into two groups: fast-rotating, strong-variable stars showing S-Dor cycles (such as AG Car and HR Car) and slow-rotating stars with much less variability (such as P Cygni and HD 168625). We speculate that supernova (SN) progenitors which had S-Dor cycles before exploding (such as in SN 2001ig, SN 2003bg, and SN 2005gj) could have been fast rotators. We suggest that the potential difficulty of fast-rotating Galactic LBVs to lose angular momentum is additional evidence that such stars could explode during the LBV phase.« less

Role of mu, but not delta or kappa, opioid receptors in context-induced reinstatement of oxycodone seeking.

PubMed

Bossert, Jennifer M; Hoots, Jennifer K; Fredriksson, Ida; Adhikary, Sweta; Zhang, Michelle; Venniro, Marco; Shaham, Yavin

2018-05-19

Relapse to nonmedical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta, and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/d in Context A; lever pressing was paired with a discrete cue. Next, we extinguished the lever pressing in the presence of the discrete cue in Context B and then tested the rats for reinstatement of oxycodone seeking in both contexts. We retrained rats to self-administer oxycodone in Context A, re-extinguished their lever pressing in Context B, and retested them for reinstatement in both contexts. Prior to testing, we injected the rats with vehicle or antagonists of MOR (naltrexone; 0.5 or 1.0 mg/kg), DOR (naltrindole; 7.5 or 15 mg/kg), or KOR (LY2456302; 5 or 10 mg/kg). We also tested the effect of naltrexone, naltrindole, and LY2456302 on oxycodone self-administration under fixed-ratio-1 (FR1) and progressive-ratio (PR) reinforcement schedules. We observed context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction. Naltrexone, but not naltrindole or LY2456302, injections decreased this reinstatement. Additionally, naltrexone increased oxycodone self-administration under the FR1 schedule and decreased oxycodone self-administration under the PR schedule; naltrindole and LY2456302 were ineffective. Results demonstrate a critical role of MOR, but not DOR or KOR, in context-induced reinstatement of oxycodone seeking and oxycodone self-administration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Effects of laparoscopic myotomy on the esophageal motility pattern of esophageal achalasia as measured by high-resolution manometry.

PubMed

Salvador, Renato; Savarino, Edoardo; Pesenti, Elisa; Spadotto, Lorenzo; Voltarel, Guerrino; Capovilla, Giovanni; Cavallin, Francesco; Nicoletti, Loredana; Valmasoni, Michele; Ruol, Alberto; Merigliano, Stefano; Costantini, Mario

2017-09-01

Esophageal achalasia can be classified on the grounds of three distinct manometric patterns that correlate well with final outcome after laparoscopic Heller-Dor myotomy (LHM). No analytical data are available, however, on the postoperative picture and its possible correlation with final outcome. The aims of this study were: (a) to investigate whether manometric patterns change after LHM for achalasia; (b) to ascertain whether postoperative patterns and/or changes can predict final outcome; and (c) to test the hypothesis that the three known patterns represent different stages in the evolution of the disease. During the study period, we prospectively enlisted 206 consecutive achalasia patients who were assessed using high-resolution manometry (HRM) before undergoing LHM. Symptoms were scored using a detailed questionnaire. Barium swallow, endoscopy and HRM were performed, before and again 6 months after surgery. Preoperative HRM revealed the three known patterns with statistically different esophageal diameters (pattern I having the largest), and patients with pattern I had the highest symptom scores. The surgical treatment failed in 10 cases (4.9%). The only predictor of final outcome was the preoperative manometric pattern (p = 0.01). All patients with pattern I preoperatively had the same pattern afterward, whereas nearly 50% of patients with pattern III before LHM had patterns I or II after surgery. There were no cases showing the opposite trend. Neither a change of manometric pattern after surgery nor a patient's postoperative pattern was a predictor of final outcome, whereas preoperative pattern confirmed its prognostic significance. The three manometric patterns distinguishable in achalasia may represent different stages in the disease's evolution, pattern III and pattern I coinciding with the early and final stages of the disease, respectively.

Spleen Stiffness Is Superior to Liver Stiffness for Predicting Esophageal Varices in Chronic Liver Disease: A Meta-Analysis.

PubMed

Ma, Xiaowen; Wang, Le; Wu, Hao; Feng, Yuemin; Han, Xibiao; Bu, Haoran; Zhu, Qiang

2016-01-01

Liver stiffness (LS) and spleen stiffness (SS) are two most widely accessible non-invasive parameters for predicting esophageal varices (EV), but the reported accuracy of the two predictors have been inconsistent across studies. This meta-analysis aims to evaluate the diagnostic performance of LS and SS measurement for detecting EV in patients with chronic liver disease (CLD), and compare their accuracy. Pubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models. In detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78-0.87), and the specificity was 0.66 (95% CI: 0.60-0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83-0.92) and 0.78 (95% CI: 0.73-0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77-0.84) and 0.88 (95% CI: 0.85-0.91) respectively, and the results had statistical significance (P<0.01). The diagnostic odds ratio (DOR) of SS (25.73) was significantly higher than that of LS (9.54), with the relative DOR value was 2.48 (95%CI: 1.10-5.60), P<0.05. Under current techniques, SS is significantly superior to LS for identifying the presence of EV in patients with CLD. SS measurement may help to select patients for endoscopic screening.

[Role of plasma procalcitonin in the diagnosis of ventilator-associated pneumonia: systematic review and metaanalysis].

PubMed

Sotillo-Díaz, J C; Bermejo-López, E; García-Olivares, P; Peral-Gutiérrez, J A; Sancho-González, M; Guerrero-Sanz, J E

2014-01-01

To determine the role of plasma procalcitonin (PCT) levels in diagnosing ventilator-associated pneumonia. A systematic review of publications prospectively assessing the diagnostic role of PCT in ventilator-associated pneumonia was carried out. The search was performed using Medline, Embase, the Cochrane Collaboration and MEDION, with reviewing of the references of retrieved articles. We extracted data that allowed the calculation of sensitivity, specificity, likelihood ratios and diagnostic odds ratio. Intervention Metaregression was performed to determine whether exposure to previous antibiotic treatment, the time to occurrence of ventilator-associated pneumonia and the type of patients had an impact upon the diagnostic performance of procalcitonin. Seven studies were considered (373 patients, 434 episodes). We found no publication bias or threshold effect. High plasma PCT levels were associated to an increased risk of suffering ventilator-associated pneumonia (OR: 8.39; 95% CI: 5.4-12.6). The pooled data on sensitivity, specificity, positive and negative likelihood ratio, and diagnostic odds ratio found were 76% (69-82), 79% (74-84), 4.35 (2.48-7.62), 0.26 (0.15-0.46) and 17.9 (10.1-31.7), respectively. Diagnostic yield was modified by prior exposure to antibiotics (rDOR 0.11, 0.02-0.069), but not by the type of critically ill patient or the time to occurrence of ventilator-associated pneumonia. Our results suggest that PCT provides additional information on the risk of VAP. Inclusion of PCT in diagnostic algorithms could improve their effectiveness. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

STEREO observations of HD90386 (RX Sex): a δ-Scuti or a hybrid star?

NASA Astrophysics Data System (ADS)

Ozuyar, D.; Stevens, I. R.; Whittaker, G.; Sangaralingam, V.

2016-04-01

HD90386 is a rarely studied bright A2V type δ Scuti star (V = 6.66 mag). It displays short-term light curve variations which are originated due to either a beating phenomenon or a non-periodic variation. In this paper, we presented high-precision photometric data of HD90386 taken by the STEREO satellite between 2007 and 2011 to shed light on its internal structure and evolution stage. From the frequency analysis of the four-year data, we detected that HD90386 had at least six different frequencies between 1 and 15 c d-1. The most dominant frequencies were found at around 10.25258 c d-1 (A ∼ 1.92 mmag) and 12.40076 c d-1 (A ∼ 0.61 mmag). Based on the ratio between these frequencies, the star was considered as an overtone pulsator. The variation in pulsation period over 35 years was calculated to be dP/Pdt = 5.39(2) x 10-3 yr-1. Other variabilities at around 1.0 c d-1 in the amplitude spectrum of HD90386 were also discussed. In order to explain these variabilities, possible rotational effects and γ Dor type variations were focused. Consequently, depending on the rotation velocity of HD90386, we speculated that these changes might be related to γ Dor type high-order g-modes shifted to the higher frequencies and that HD90386 might be a hybrid star.

Structure and Feedback in 30 Doradus. II. Structure and Chemical Abundances

NASA Astrophysics Data System (ADS)

Pellegrini, E. W.; Baldwin, J. A.; Ferland, G. J.

2011-09-01

We use our new optical-imaging and spectrophotometric survey of key diagnostic emission lines in 30 Doradus, together with CLOUDY photoionization models, to study the physical conditions and ionization mechanisms along over 4000 individual lines of sight at points spread across the face of the extended nebula, out to a projected radius 75 pc from R136 at the center of the ionizing cluster NGC 2070. We focus on the physical conditions, geometry, and importance of radiation pressure on a point-by-point basis, with the aim of setting observational constraints on important feedback processes. We find that the dynamics and large-scale structure of 30 Dor are set by a confined system of X-ray bubbles in rough pressure equilibrium with each other and with the confining molecular gas. Although the warm (10,000 K) gas is photoionized by the massive young stars in NGC 2070, the radiation pressure does not currently play a major role in shaping the overall structure. The completeness of our survey also allows us to create a composite spectrum of 30 Doradus, simulating the observable spectrum of a spatially unresolved, distant giant extragalactic H II region. We find that the highly simplified models used in the "strong line" abundance technique do in fact reproduce our observed line strengths and deduced chemical abundances, in spite of the more than one order of magnitude range in the ionization parameter and density of the actual gas in 30 Dor.

LATE EVALUATION OF DYSPHAGIA AFTER HELLER ESOPHAGEAL MYOTOMY WITH DOR FUNDOPLICATION FOR ACHALASIA.

PubMed

Câmara, Eduardo Rodrigues Zarco; Madureira, Fernando Athayde Veloso; Madureira, Delta; Salomão, Renato Manganelli; Iglesias, Antonio Carlos Ribeiro Garrido

2017-01-01

All available treatments for achalasia are palliative and aimed to eliminate the flow resistance caused by a hypertensive lower esophageal sphincter. To analyze the positive and negative prognostic factors in the improvement of dysphagia and to evaluate quality of life in patients undergoing surgery to treat esophageal achalasia by comparing findings before, immediately after, and in long follow-up. A total of 84 patients who underwent surgery for achalasia between 2001 and 2014 were retrospectively studied. The evaluation protocol with dysphagia scores compared preoperative, immediate (up to three months) postoperative and late (over one year) postoperative scores to estimate quality of life. The surgical procedure was Heller-Dor in 100% of cases, with 84 cases performed laparoscopically. The percent reduction in pre- and immediate postoperative lower esophageal sphincter pressurewas 60.35% in the success group and 32.49% in the failure group. Regarding the late postoperative period, the mean percent decrease was 60.15% in the success group and 31.4% in the failure group. The mean overall drop in dysphagia score between the pre- and immediate postoperative periods was 7.33 points, which represents a decrease of 81.17%. Reduction greater than 60% percent in lower esophageal sphincter pressurebetween the pre- and postoperative periods suggests that this metric is a predictor of good prognosis for surgical response. Surgical treatment was able to have a good affect in quality of life and drastically changed dysphagia over time.

Excellence within the Navy Health Care System.

DTIC Science & Technology

1984-12-01

in the Navy Medical Department. 13y-- Ia Sc ." . ’Eq’ Im T _ _ _ _ _ 2 SECURITY CASFAIN f !iy.i Di~tribut;-/ _.-, Availabilit Codes DcTAvail a"d/or jp...overwillingness to hand out awards as a weakness, that this waters down the meaning of the awards. 52 • . - Whether you agree or not with the past and

Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data.

PubMed

Kaiser, Kathryn A; Affuso, Olivia; Desmond, Renee; Allison, David B

Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs) in obesity randomized controlled trials (RCT) by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively). There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04). As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on treatment.

Diagnostic Value of Methylated Septin9 for Colorectal Cancer Screening: A Meta-Analysis

PubMed Central

Yan, Shirong; Liu, Zijing; Yu, Shuang; Bao, Yixi

2016-01-01

Background Septin9 is a member of GTP-binding protein family, and is used as a predictive diagnostic index. However, it has not been widely adopted due to inconsistent results reported in the literature. The present study was performed to determine the diagnostic accuracy of methylated Septin9 (mSEPT9) for colorectal cancer (CRC) and to evaluate its utility in CRC screening. Material/Methods After reviewing relevant studies, accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratio [PLR/NLR], and diagnostic odds ratio [DOR]) were calculated for mSEPT9 in the diagnosis of CRC. Overall test performance was summarized using summary receiver operating characteristic curve analysis. Potential between-study heterogeneity was explored by use of a meta-regression model. We divided included studies into Epi proColon test and non-Epi proColon test subgroups. We compared the effects of mSEPT9 and fecal occult blood test (FOBT) for CRC screening. Results A total of 9870 subjects in 14 studies were recruited. Pooled sensitivity and specificity, PLR, NLR, DOR, and corresponding 95% confidence intervals (CI) of mSEPT9 for CRC diagnosis were 0.66 (95% CI: 0.64–0.69), 0.91 (95% CI: 0.90–0.91), 5.59 (95% CI: 4.03–7.74), 0.37 (95% CI: 0.29–0.48), and 16.79 (95% CI: 10.54–26.76), respectively. The area under the summary ROC curve (AUC) was 0.8563. The AUCs in the Epi proColon test and non-Epi proColon test for CRC diagnosis were 0.8709 and 0.7968, respectively. In head-to-head comparison, AUC of mSEPT9 and FOBT for CRC diagnosis were 0.7857 and 0.6571, respectively. Conclusions The present study demonstrates that mSEPT9 can be a good diagnostic biomarker complementary to FOBT as a screening tool for CRC. PMID:27665580

Diagnostic Value of Methylated Septin9 for Colorectal Cancer Screening: A Meta-Analysis.

PubMed

Yan, Shirong; Liu, Zijing; Yu, Shuang; Bao, Yixi

2016-09-25

BACKGROUND Septin9 is a member of GTP-binding protein family, and is used as a predictive diagnostic index. However, it has not been widely adopted due to inconsistent results reported in the literature. The present study was performed to determine the diagnostic accuracy of methylated Septin9 (mSEPT9) for colorectal cancer (CRC) and to evaluate its utility in CRC screening. MATERIAL AND METHODS After reviewing relevant studies, accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratio [PLR/NLR], and diagnostic odds ratio [DOR]) were calculated for mSEPT9 in the diagnosis of CRC. Overall test performance was summarized using summary receiver operating characteristic curve analysis. Potential between-study heterogeneity was explored by use of a meta-regression model. We divided included studies into Epi proColon test and non-Epi proColon test subgroups. We compared the effects of mSEPT9 and fecal occult blood test (FOBT) for CRC screening. RESULTS A total of 9870 subjects in 14 studies were recruited. Pooled sensitivity and specificity, PLR, NLR, DOR, and corresponding 95% confidence intervals (CI) of mSEPT9 for CRC diagnosis were 0.66 (95% CI: 0.64-0.69), 0.91 (95% CI: 0.90-0.91), 5.59 (95% CI: 4.03-7.74), 0.37 (95% CI: 0.29-0.48), and 16.79 (95% CI: 10.54-26.76), respectively. The area under the summary ROC curve (AUC) was 0.8563. The AUCs in the Epi proColon test and non-Epi proColon test for CRC diagnosis were 0.8709 and 0.7968, respectively. In head-to-head comparison, AUC of mSEPT9 and FOBT for CRC diagnosis were 0.7857 and 0.6571, respectively. CONCLUSIONS The present study demonstrates that mSEPT9 can be a good diagnostic biomarker complementary to FOBT as a screening tool for CRC.

Diagnostic performance of coronary computed tomography angiography versus exercise electrocardiography for coronary artery disease: a systematic review and meta-analysis.

PubMed

Yin, Xinxin; Wang, Jiali; Zheng, Wen; Ma, Jingjing; Hao, Panpan; Chen, Yuguo

2016-07-01

Both coronary computed tomography angiography (CCTA) and exercise electrocardiography (ExECG) are non-invasive testing methods for the evaluation of coronary artery disease (CAD). However, there was controversy on the diagnostic performance of these methods due to the limited data in each single study. Therefore, we performed a meta-analysis to address these issues. We searched PubMed and Embase databases up to May 22, 2015. Two authors identified eligible studies, extracted data and accessed quality. Pooled estimation of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver-operating characteristic curve (SROC) and the area under curve (AUC) of CCTA and ExECG for the diagnosis of CAD were calculated using Stata, Meta-Disc and Review Manager statistical software. Seven articles were included. Pooled sensitivity of CCTA and ExECG were 0.98 [95% confidence intervals (CIs): 0.95-0.99] and 0.66 (95% CIs: 0.59-0.72); pooled specificity of CCTA and ExECG were 0.84 (95% CIs: 0.81-0.87) and 0.75 (95% CIs: 0.71-0.79); pooled DOR of CCTA and ExECG were 110.24 (95% CIs: 35.07-346.55) and 6.28 (95% CIs: 2.06-19.13); and AUC of CCTA and ExECG were 0.9950±0.0046 and 0.7727±0.0638, respectively. There is no heterogeneity caused by threshold effect in CCTA or ExECG analysis. The Deeks' test showed no potential publication bias (P=0.17). CCTA has better diagnostic performance than ExECG in the evaluation of CAD, which can provide a better solution for the clinical problem of the diagnosis for CAD.

Hubble:WFPC2 and ESO:2.2-m Composite Image of 30 Dor Runaway Star

NASA Image and Video Library

2017-12-08

NASA image release May 11, 2010 Hubble Catches Heavyweight Runaway Star Speeding from 30 Doradus Image: Hubble/WFPC2 and ESO/2.2-m Composite Image of 30 Dor Runaway Star A blue-hot star, 90 times more massive than our Sun, is hurtling across space fast enough to make a round trip from Earth to the Moon in merely two hours. Though the speed is not a record-breaker, it is unique to find a homeless star that has traveled so far from its nest. The only way the star could have been ejected from the star cluster where it was born is through a tussle with a rogue star that entered the binary system where the star lived, which ejected the star through a dynamical game of stellar pinball. This is strong circumstantial evidence for stars as massive as 150 times our Sun's mass living in the cluster. Only a very massive star would have the gravitational energy to eject something weighing 90 solar masses. The runaway star is on the outskirts of the 30 Doradus nebula, a raucous stellar breeding ground in the nearby Large Magellanic Cloud. The finding bolsters evidence that the most massive stars in the local universe reside in 30 Doradus, making it a unique laboratory for studying heavyweight stars. 30 Doradus, also called the Tarantula Nebula, is roughly 170,000 light-years from Earth. To learn more about this image go to: www.nasa.gov/mission_pages/hubble/science/runaway-star.html Credit: NASA, ESA, J. Walsh (ST-ECF), and ESO NASA Goddard Space Flight Center is home to the nation's largest organization of combined scientists, engineers and technologists that build spacecraft, instruments and new technology to study the Earth, the sun, our solar system, and the universe.

Contrast-Enhanced Ultrasonography in Differential Diagnosis of Benign and Malignant Ovarian Tumors

PubMed Central

Qiao, Jing-Jing; Yu, Jing; Yu, Zhe; Li, Na; Song, Chen; Li, Man

2015-01-01

Objective To evaluate the accuracy of contrast-enhanced ultrasonography (CEUS) in differential diagnosis of benign and malignant ovarian tumors. Methods The scientific literature databases PubMed, Cochrane Library and CNKI were comprehensively searched for studies relevant to the use of CEUS technique for differential diagnosis of benign and malignant ovarian cancer. Pooled summary statistics for specificity (Spe), sensitivity (Sen), positive and negative likelihood ratios (LR+/LR−), and diagnostic odds ratio (DOR) and their 95%CIs were calculated. Software for statistical analysis included STATA version 12.0 (Stata Corp, College Station, TX, USA) and Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). Results Following a stringent selection process, seven high quality clinical trials were found suitable for inclusion in the present meta-analysis. The 7 studies contained a combined total of 375 ovarian cancer patients (198 malignant and 177 benign). Statistical analysis revealed that CEUS was associated with the following performance measures in differential diagnosis of ovarian tumors: pooled Sen was 0.96 (95%CI = 0.92∼0.98); the summary Spe was 0.91 (95%CI = 0.86∼0.94); the pooled LR+ was 10.63 (95%CI = 6.59∼17.17); the pooled LR− was 0.04 (95%CI = 0.02∼0.09); and the pooled DOR was 241.04 (95% CI = 92.61∼627.37). The area under the SROC curve was 0.98 (95% CI = 0.20∼1.00). Lastly, publication bias was not detected (t = −0.52, P = 0.626) in the meta-analysis. Conclusions Our results revealed the high clinical value of CEUS in differential diagnosis of benign and malignant ovarian tumors. Further, CEUS may also prove to be useful in differential diagnosis at early stages of this disease. PMID:25764442

The preoperative manometric pattern predicts the outcome of surgical treatment for esophageal achalasia.

PubMed

Salvador, Renato; Costantini, Mario; Zaninotto, Giovanni; Morbin, Tiziana; Rizzetto, Christian; Zanatta, Lisa; Ceolin, Martina; Finotti, Elena; Nicoletti, Loredana; Da Dalt, Gianfranco; Cavallin, Francesco; Ancona, Ermanno

2010-11-01

A new manometric classification of esophageal achalasia has recently been proposed that also suggests a correlation with the final outcome of treatment. The aim of this study was to investigate this hypothesis in a large group of achalasia patients undergoing laparoscopic Heller-Dor myotomy. We evaluated 246 consecutive achalasia patients who underwent surgery as their first treatment from 2001 to 2009. Patients with sigmoid-shaped esophagus were excluded. Symptoms were scored and barium swallow X-ray, endoscopy, and esophageal manometry were performed before and again at 6 months after surgery. Patients were divided into three groups: (I) no distal esophageal pressurization (contraction wave amplitude <30 mmHg); (II) rapidly propagating compartmentalized pressurization (panesophageal pressurization >30 mmHg); and (III) rapidly propagating pressurization attributable to spastic contractions. Treatment failure was defined as a postoperative symptom score greater than the 10th percentile of the preoperative score (i.e., >7). Type III achalasia coincided with a longer overall lower esophageal sphincter (LES) length, a lower symptom score, and a smaller esophageal diameter. Treatment failure rates differed significantly in the three groups: I = 14.6% (14/96), II = 4.7% (6/127), and III = 30.4% (7/23; p = 0.0007). At univariate analysis, the manometric pattern, a low LES resting pressure, and a high chest pain score were the only factors predicting treatment failure. At multivariate analysis, the manometric pattern and a LES resting pressure <30 mmHg predicted a negative outcome. This is the first study by a surgical group to assess the outcome of surgery in 3 manometric achalasia subtypes: patients with panesophageal pressurization have the best outcome after laparoscopic Heller-Dor myotomy.

Performance of pfHRP2 versus pLDH antigen rapid diagnostic tests for the detection of Plasmodium falciparum: a systematic review and meta-analysis.

PubMed

Li, Bo; Sun, Zhiqiang; Li, Xiaohan; Li, Xiaoxi; Wang, Han; Chen, Weijiao; Chen, Peng; Qiao, Mengran; Mao, Yuanli

2017-04-01

There have been many inconsistent reports about the performance of histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens as rapid diagnostic tests (RDTs) for the diagnosis of past Plasmodium falciparum infections. This meta-analysis was performed to determine the performance of pfHRP2 versus pLDH antigen RDTs in the detection of P. falciparum . After a systematic review of related studies, Meta-DiSc 1.4 software was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Forest plots and summary receiver operating characteristic curve (SROC) analysis were used to summarize the overall test performance. Fourteen studies which met the inclusion criteria were included in the meta-analysis. The summary performances for pfHRP2- and pLDH-based tests in the diagnosis of P. falciparum infections were as follows: pooled sensitivity, 96.3% (95.8-96.7%) vs. 82.6% (81.7-83.5%); specificity, 86.1% (85.3-86.8%) vs. 95.9% (95.4-96.3%); diagnostic odds ratio (DOR), 243.31 (97.679-606.08) vs. 230.59 (114.98-462.42); and area under ROCs, 0.9822 versus 0.9849 (all p < 0.001). The two RDTs performed satisfactorily for the diagnosis of P. falciparum , but the pLDH tests had higher specificity, whereas the pfHRP2 tests had better sensitivity. The pfHRP2 tests had slightly greater accuracy compared to the pLDH tests. A combination of both antigens might be a more reliable approach for the diagnosis of malaria.

Young, active radio stars in the AB Doradus moving group

NASA Astrophysics Data System (ADS)

Azulay, R.; Guirado, J. C.; Marcaide, J. M.; Martí-Vidal, I.; Ros, E.; Tognelli, E.; Hormuth, F.; Ortiz, J. L.

2017-06-01

Context. Precise determination of stellar masses is necessary to test the validity of pre-main-sequence (PMS) stellar evolutionary models, whose predictions are in disagreement with measurements for masses below 1.2 M⊙. To improve such a test, and based on our previous studies, we selected the AB Doradus moving group (AB Dor-MG) as the best-suited association on which to apply radio-based high-precision astrometric techniques to study binary systems. Aims: We seek to determine precise estimates of the masses of a set of stars belonging to the AB Dor-MG using radio and infrared observations. Methods: We observed in phase-reference mode with the Very Large Array (VLA) at 5 GHz and with the European VLBI Network (EVN) at 8.4 GHz the stars HD 160934, EK Dra, PW And, and LO Peg. We also observed some of these stars with the near-infrared CCD AstraLux camera at the Calar Alto observatory to complement the radio observations. Results: We determine model-independent dynamical masses of both components of the star HD 160934, A and c, which are 0.70 ± 0.07 M⊙ and 0.45 ± 0.04 M⊙, respectively. We revised the orbital parameters of EK Dra and we determine a sum of the masses of the system of 1.38 ± 0.08 M⊙. We also explored the binarity of the stars LO Peg and PW And. Conclusions: We found observational evidence that PMS evolutionary models underpredict the mass of PMS stars by 10%-40%, as previously reported by other authors. We also inferred that the origin of the radio emission must be similar in all observed stars, that is, extreme magnetic activity of the stellar corona that triggers gyrosynchrotron emission from non-thermal, accelerated electrons.

Heller Myotomy for Achalasia: Quality of Life Comparison of Laparoscopic and Open Approaches

PubMed Central

Katilius, Marius

2001-01-01

Background: Achalasia is a relatively rare disorder with a variety of treatment options. Although laparoscopic Heller myotomy has become the surgical treatment of choice, little data exist on the overall quality of life of patients undergoing this technique versus standard open approaches. Methods: We prospectively evaluated all patients surgically treated for achalasia by a single surgeon. Laparoscopic Heller myotomy consisted of a long (≥ 6 cm) esophageal cardiomyotomy extending at least 2 cm onto the gastric cardia, with a concomitant Dor fundoplication. Patients were evaluated preoperatively and postoperatively for symptoms and quality of life using the SF-36, a standardized, generic quality of life instrument. Results: A total of 23 patients were surgically treated: 15 patients had a planned laparoscopic procedure, with 3 conversions; 8 had planned open procedures. Dysphagia resolved in 20 of 21 patients, with 1 patient in the laparoscopic group requiring reoperation due to an inadequate gastric myotomy. Compared with preoperative scores, a statistically significant improvement occurred in the general health domain of the SF-36 (70 to 82, P = 0.04). Compared with that in patients undergoing open surgery, the laparoscopic group had better scores in the domains of physical functioning and bodily pain. Conclusions: Laparoscopic Heller myotomy has comparable success to open Heller myotomy, and causes less early detriment to quality of life. This should be the primary treatment in all fit surgical patients with achalasia. PMID:11548827

Saccadic Eye Movement Task Identifies Cognitive Deficits in Children with Schizophrenia, but Not in Unaffected Child Relatives

ERIC Educational Resources Information Center

Ross, Randal G.; Heinlein, Shari; Zerbe, Gary O.; Radant, Allen

2005-01-01

Background: The delayed oculomotor response (DOR) task requires response inhibition followed by movement of gaze towards a known spatial location without a current stimulus. Abnormalities in response inhibition and in the spatial accuracy of the eye movement are found in individuals with schizophrenia and in many of their relatives, supporting the…

The VLT-FLAMES Tarantula Survey. XI. A census of the hot luminous stars and their feedback in 30 Doradus

NASA Astrophysics Data System (ADS)

Doran, E. I.; Crowther, P. A.; de Koter, A.; Evans, C. J.; McEvoy, C.; Walborn, N. R.; Bastian, N.; Bestenlehner, J. M.; Gräfener, G.; Herrero, A.; Köhler, K.; Maíz Apellániz, J.; Najarro, F.; Puls, J.; Sana, H.; Schneider, F. R. N.; Taylor, W. D.; van Loon, J. Th.; Vink, J. S.

2013-10-01

Context. The VLT-FLAMES Tarantula Survey has an extensive view of the copious number of massive stars in the 30 Doradus (30 Dor) star forming region of the Large Magellanic Cloud. These stars play a crucial role in our understanding of the stellar feedback in more distant, unresolved star forming regions. Aims: The first comprehensive census of hot luminous stars in 30 Dor is compiled within a 10 arcmin (150 pc) radius of its central cluster, R136. We investigate the stellar content and spectroscopic completeness of the early type stars. Estimates were made for both the integrated ionising luminosity and stellar wind luminosity. These values were used to re-assess the star formation rate (SFR) of the region and determine the ionising photon escape fraction. Methods: Stars were selected photometrically and combined with the latest spectral classifications. Spectral types were estimated for stars lacking spectroscopy and corrections were made for binary systems, where possible. Stellar calibrations were applied to obtain their physical parameters and wind properties. Their integrated properties were then compared to global observations from ultraviolet (UV) to far-infrared (FIR) imaging as well as the population synthesis code, Starburst99. Results: Our census identified 1145 candidate hot luminous stars within 150 pc of R136 of which >700 were considered to be genuine early type stars and contribute to feedback. We assess the survey to be spectroscopically complete to 85% in the outer regions (>5 pc) but only 35% complete in the region of the R136 cluster, giving a total of 500 hot luminous stars in the census which had spectroscopy. Only 31 were found to be Wolf-Rayet (W-R) or Of/WN stars, but their contribution to the integrated ionising luminosity and wind luminosity was ~40% and ~50%, respectively. Similarly, stars with Minit > 100 M⊙ (mostly H-rich WN stars) also showed high contributions to the global feedback, ~25% in both cases. Such massive stars are not accounted for by the current Starburst99 code, which was found to underestimate the integrated ionising luminosity of R136 by a factor ~2 and the wind luminosity by a factor ~9. The census inferred a SFR for 30 Dor of 0.073 ± 0.04 M⊙ yr-1. This was generally higher than that obtained from some popular SFR calibrations but still showed good consistency with the far-UV luminosity tracer as well as the combined Hα and mid-infrared tracer, but only after correcting for Hα extinction. The global ionising output was also found to exceed that measured from the associated gas and dust, suggesting that ~6+55-6 % of the ionising photons escape the region. Conclusions: When studying the most luminous star forming regions, it is essential to include their most massive stars if one is to determine a reliable energy budget. Photon leakage becomes more likely after including their large contributions to the ionising output. If 30 Dor is typical of other massive star forming regions, estimates of the SFR will be underpredicted if this escape fraction is not accounted for. Based on observations collected at the European Southern Observatory under programme ID 182.D-0222.Appendices are available in electronic form at http://www.aanda.orgFull Tables D1 and D2 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/558/A134

FLOWS WITH CROSS SECTIONS

PubMed Central

Verjovsky, Alberto

1970-01-01

Let M be a compact connected C∞-manifold, of dimension n, without boundary. Let ft: M → M be a Cr-flow with cross section. Let Dr(M) be the topological group of diffeomorphisms of M with Cr-topology (1 ≤ r ≤ ∞) and let Dor(M) be its connected component of the identity. Let [unk](M) be the group of I-cobordism classes in Dr(M) generated by orientation-preserving diffeomorphisms. For fεDr(M) denote by [f] its I-cobordism class. Theorem 1 deals with the dependence of M(f) on [f]. Theorem 2: S6 × S1 has at least 28 distinct differentiable structures. Let xoεS1 and let [unk]r be the set of Cr-flows (r ≥ 1) in M × S1 with cross section M × {xo} and inducing in it the identity. Theorem 3: Intuitively to a loop in Dor based at the identity there corresponds a flow in [unk]r, and to homotopic loops correspond isotopic flows. COROLLARY. complete analysis of [unk]r/ [unk] for dim M = 2. Theorems 4 and 5 refer to Anosov flows for dim M > 3. PMID:16591849

Gaia luminosities of pulsating A-F stars in the Kepler field

NASA Astrophysics Data System (ADS)

Balona, L. A.

2018-06-01

All stars in the Kepler field brighter than 12.5 magnitude have been classified according to variability type. A catalogue of δ Scuti and γ Doradus stars is presented. The problem of low frequencies in δ Sct stars, which occurs in over 98 percent of these stars, is discussed. Gaia DR2 parallaxes were used to obtain precise luminosities, enabling the instability strips of the two classes of variable to be precisely defined. Surprisingly, it turns out that the instability region of the γ Dor stars is entirely within the δ Sct instability strip. Thus γDor stars should not be considered a separate class of variable. The observed red and blue edges of the instability strip do not agree with recent model calculations. Stellar pulsation occurs in less than half of the stars in the instability region and arguments are presented to show that this cannot be explained by assuming pulsation at a level too low to be detected. Precise Gaia DR2 luminosities of high-amplitude δ Sct stars (HADS) show that most of these are normal δ Sct stars and not transition objects. It is argued that current ideas on A star envelopes need to be revised.

Pulverized Tejon Lookout Granite: Attempts at Placing Constraints on the Processes

NASA Astrophysics Data System (ADS)

Sisk, M.; Dor, O.; Rockwell, T.; Girty, G.; Ben-Zion, Y.

2007-12-01

We have described and analyzed pulverized Tejon Lookout granite recovered from several transects of the western segment of the Garlock fault on Tejon Ranch in southern California. Observations and data collected at this location are compared to a sampled transect of the San Andreas fault at Tejon Pass previously studied by Wilson et al. (2005), also exposing the Tejon Lookout granite. The purpose of this study is to characterize the physical and chemical properties of the pervasively pulverized leucocratic rocks at multiple locations and to hopefully place constraints on the processes producing them. To accomplish this we performed particle size analysis with the use of both laser particle analyzer and pipette methodology; major and trace chemistry analyses determined by XRF; clay mineralogy determined by XRD; and we evaluated fabric and texture through the study of thin sections. Recovered samples met the field criteria of pulverization developed by Dor et al., 2006 - that is, the individual 1-2 mm-sized crystals can be recognized in the field but the granite (including quartz and feldspar) can be mashed with ones fingers and exhibits the texture of toothpaste. All samples were analyzed on a Horiba LA930 Laser Particle Analyzer in an attempt to reproduce the earlier results of Wilson et al. (2005) with similar methodology. We also utilized the classic pipette methodology to ensure complete discrimination of particle sizes. Our PSD analysis shows that the dominant particle size falls in the 31-125 micron range, much coarser than previously reported by Wilson et al. (2005), with >90% of the total sample falling in the >31 micron size range. We can reproduce the previously documented results by allowing the samples to circulate for long periods of time at slow circulation speeds in the laser particle size analyzer, during which time the coarse fraction settles out, thereby leaving only the fine fraction for detection. However, subsequent increase in the circulation speed leads to a complete recovery of the original PSD. Our XRF and XRD analyses provide evidence of the lack of major weathering products and their inability to skew the PSD results in a significant way. Dor et al. (2007) and Stillings et al. (2007) document evidence that support theoretical predictions and previous inferences of pulverization occurring in the upper few kilometers, especially along faults of the southern San Andreas system. Geophysical observations of Lewis et al. (2005, 2007) provide evidence that low velocity fault- parallel layers, which are likely made of pulverized or highly damaged material, are dominant in the upper few kilometers of the crust. Their asymmetric position with respect to the slipping zone, in agreement with asymmetric patterns of small scale mapped rock damage (Dor et al., 2006), suggest that pulverized rocks are likely the product of a preferred rupture direction during dynamic slip. Our results combined with the above mentioned works imply that pulverized fault zone rocks at multiple locations are much less damaged than suggested in previous studies.

Paleomagnetic Progress in Peri-Gondwanan Terranes of Cape Breton Island, Nova Scotia

NASA Astrophysics Data System (ADS)

Grunow, A. M.; Thompson, M. D.; Barr, S. M.; White, C. E.

2009-05-01

Paleopoles from primary Ediacaran magnetization directions established the Gondwanan origin of northern Appalachian Avalonian terranes, but magnetic overprints in the same rocks also provide useful tectonic information. Thus, in the Southeastern New England Avalon Zone, virtual geomagnetic poles (VGPs) calculated from magnetic B and C components in both 595 Ma Lynn-Mattapan volcanic rocks and 490-488 Ma Nahant Gabbro track mid- and late Paleozoic segments of the North American apparent polar wander path (APWP), suggesting the influence of Acadian and Neo-Acadian accretionary events. We report here on multi- vectorial magnetizations in pilot samples from Cape Breton Island, Nova Scotia where the Bras d'Or and Mira terranes represent both Ganderian and Avalonian elements transferred from Gondwana. Overprint relationships in these terranes may constrain their amalgamation with each other as well their docking with Laurentia. As in southeastern New England, secondary remanences can be identified in Cape Breton Island as consistent magnetization directions in rocks of differing ages. The S- to SSE-trending and gently downward pointing direction reported in 1985 by Johnson and Van der Voo in Middle Cambrian sedimentary rocks of the Bourinot Group (Bras d'Or terrane), for example, is also present in the 563 Ma Main à Dieu Formation and in 620 Ma Chisholm Brook Granite and East Bay Hill rhyolite (Mira terrane). This magnetization represents the C component already found around Boston, MA. The resulting VGPs in both areas occupy positions on the North American APWP consistent with a Neo-Acadian overprint, possibly related to the docking of the Meguma terrane against previously accreted Avalonia. Other overprint directions encountered in this investigation give rise to VGPs that do not coincide with the North American APWP, hence appear to reflect tectonic events independent of Laurentia. One such cluster comprising both Mira and Bras d'Or VGPs includes the paleopole also reported by Johnson and Van der Voo for volcanic rocks in the Bourinot Group. This relationship suggests that the two terranes were neighbors at moderate southerly paleolatitudes by ca. 505 Ma and allows the possibility that Bourinot volcanism played a role in overprinting older rocks including 620 Ma East Bay Hills rhyolite (Mira) and 553 Ma Creignish Hills granite (Bras d'Or). Another intriguing observation from our preliminary data is a low-latitude cluster of VGPs that lies near the Late Ordovician overprint VGPs from Swedish limestones (after rotation into a North American reference frame). Other workers have previously interpreted these Baltic VGPs to reflect the collision between East Avalonia and Baltica during closure of the Tornquist Sea. Peeling away the overprints reveals a possible primary direction in 620 Ma rocks of the Mira terrane. Three pilot samples from two sites show normal and reverse polarity and a positive tilt test. VGPs from these samples resemble the VGP obtained from the 609 Ma Dedham Granite in Boston, Massachusetts.

Diagnostic accuracy of dual-source computed tomography angiography for the detection of coronary in-stent restenosis: A systematic review and meta-analysis.

PubMed

Liu, Wen-Jun; Li, Gui-Zhen; Liu, Hai-Feng; Lei, Jun-Qiang

2018-04-01

We sought to perform a meta-analysis to comprehensively evaluate the diagnostic accuracy of dual-source computed tomography angiography (DSCTA) in detecting coronary in-stent restenosis (CISR) when compared to invasive coronary angiography. The stent-based research studies in which DSCTA was used as diagnostic tool for CISR, as recent as of October 2017, from several reputed scientific libraries (PubMed, Embase, Scopus, The Cochrane Library, and Web of Science) were evaluated. Study inclusion, data extraction, and risk bias assessment were conducted by two researchers independently. Pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under summary receiver operator characteristics (SROC) curve (AUC) were calculated to assess the diagnostic value. In addition, heterogeneity and subgroup analysis were also carried out. A total of 13 studies with a total of 894 patients and 1384 assessable stents were included. The pooled results of DSCTA diagnosing CISR were as follows: SEN 0.92 (95% confidence interval [CI] 0.87-0.96), SPE 0.91 (95% CI 0.87-0.94), PLR 9.83 (95% CI 6.93-13.94), NLR 0.09 (95% CI 0.05-0.15), DOR 114.73 (95% CI 64.12-205.28), and AUC 0.97 (95% CI 0.95-0.98), respectively. The subgroup analysis result suggested that DSTCA performed significantly better in CISR detection when the stent diameter was ≥3 mm compared with the stent diameter <3 mm: (0.98 [0.97-0.99] vs 0.82 [0.79-0.86]) with P < .05. This study revealed that DSCTA has excellent diagnostic performance for detecting CISR and may serve as an alternative for further patient evaluation with CISR, especially for stent diameter ≥3 mm. © 2018 Wiley Periodicals, Inc.

Observer Rated Sleepiness and Real Road Driving: An Explorative Study

PubMed Central

Anund, Anna; Fors, Carina; Hallvig, David; Åkerstedt, Torbjörn; Kecklund, Göran

2013-01-01

The aim of the present study was to explore if observer rated sleepiness (ORS) is a feasible method for quantification of driver sleepiness in field studies. Two measures of ORS were used: (1) one for behavioural signs based on facial expression, body gestures and body movements labelled B-ORS, and (2) one based on driving performance e.g. if swerving and other indicators of impaired driving occurs, labelled D-ORS. A limited number of observers sitting in the back of an experimental vehicle on a motorway about 2 hours repeatedly 3 times per day (before lunch, after lunch, at night) observed 24 participant’s sleepiness level with help of the two observer scales. At the same time the participant reported subjective sleepiness (KSS), EOG was recorded (for calculation of blink duration) and several driving measure were taken and synchronized with the reporting. Based on mixed model Anova and correlation analysis the result showed that observer ratings of sleepiness based on drivers’ impaired performance and behavioural signs are sensitive to extend the general pattern of time awake, circadian phase and time of driving. The detailed analysis of the subjective sleepiness and ORS showed weak correspondence on an individual level. Only 16% of the changes in KSS were predicted by the observer. The correlation between the observer ratings based on performance (D-ORS) and behavioural signs (B-ORS) are high (r = .588), and the B-ORS shows a moderately strong association (r = .360) with blink duration. Both ORS measures show an association (r>0.45) with KSS, whereas the association with driving performance is weak. The results show that the ORS-method detects the expected general variations in sleepy driving in field studies, however, sudden changes in driver sleepiness on a detailed level as 5 minutes is usually not detected; this holds true both when taking into account driving behaviour or driver behavioural signs. PMID:23724094

Diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B: a meta-analysis of diagnostic test.

PubMed

Yin, Zhi; Zou, Jin; Li, Qiongxuan; Chen, Lizhang

2017-04-04

This study is aimed at evaluating the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B through a meta-analysis of diagnostic test. We conducted a comprehensive search in the Pubmed, Embase, Web of Science, and Chinese National Knowledge Infrastructure before October 31, 2016. Stata 14.0 software was used for calculation and statistical analyses. We used the sensitivity, specificity, positive and negative likelihood ratio (PLR, NLR), diagnostic odds ratio (DOR) and 95% confidence intervals (CIs) to evaluate the diagnostic value of FIB-4 for liver fibrosis in patients with hepatitis B. Twenty-six studies were included in the final analyses, with a total of 8274 individuals. The pooled parameters are calculated from all studies: sensitivity of 0.69 (95%CI:0.63-0.75), specificity of 0.81 (95%CI: 0.73-0.87), PLR of 3.63 (95%CI:2.66-4.94), NLR of 0.38 (95%CI:0.32-0.44), DOR of 9.57 (95%CI: 6.67-13.74), and area under the curve (AUC) of 0.80 (95%CI: 0.76-0.83). We also conducted subgroup based on the range of cut-off values. Results from subgroup analysis showed that cut-off was the source of heterogeneity in the present study. The sensitivity and specificity of cut-off>2 were 0.69 and 0.95 with the AUC of 0.90 (95%CI: 0.87-0.92). The overall diagnostic value of FIB-4 is not very high for liver fibrosis in patients with hepatitis B. However, the diagnostic value is affected by the cut-off value. FIB-4 has relatively high diagnostic value for detecting liver fibrosis in patients with hepatitis B when the diagnostic threshold value is more than 2.0.

Thalidomide results in diminished ovarian reserve in reproductive age female IBD patients

PubMed Central

Peng, Xiang; Zhi, Min; Wei, Ming; Li, Ting-Ting; Zhang, Min; Zhang, Yuan-Qi; He, Huan; Su, Mingli; Wang, Wei; Chen, Jun-rong; Tang, Jian; Gao, Xiang; Hu, Pin-Jin; Liang, Xiao-Yan

2017-01-01

Abstract The effectiveness of thalidomide in treating inflammatory bowel disease (IBD) has been widely recognized. Meanwhile, many serious adverse drug reactions have been observed, but no know reports on ovarian reserve function. Female patients, ranging in age between 18 and 40, were referred to our institution to undergo sex hormone detection and ultrasonic scanning for ovarian function assessment, between February 1, 2016 and September 31, 2016. Thirty-three patients treated with thalidomide (group A), 73 patients without thalidomide (group B), and 78 healthy women as control were studied. Menstrual disorder was higher in group A than group B (78.8% vs 57.2%, P < 0.05), and both groups were higher than control group 33.3%, P < 0.05. Anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) in group A were lower than group B, P < 0.05, while estradiol (E2) and follicle-stimulating hormone (FSH) levels were no different between 2 groups. Crohn Disease Endoscopic Index of Severity (CDEIS) and thalidomide were the independent risk factors in diminished ovarian reserve (DOR), and when dose reached 75 mg/day, 5 g total, or when treatment time reached 10 months respectively. These influence may increasing (P < 0.05), but they may recover after stopping (P < 0.05). Thalidomide was an independent risk factor leading to DOR in female IBD patients, the influence may increasing when daily dose and accumulated dose reached 75 mg/day and 5 g total dose, but may be reversed by stopping. PMID:28538364

Laparoscopic Heller Myotomy for Non-Dilated Esophageal Achalasia in Children with Intraoperative Stepped Dilation Under Image Guidance: Attempting Complete Myotomy.

PubMed

Miyano, Go; Miyake, Hiromu; Koyama, Mariko; Morita, Keiichi; Kaneshiro, Masakatsu; Nouso, Hiroshi; Yamoto, Masaya; Fukumoto, Koji; Urushihara, Naoto

2016-05-01

This study presents a modified surgical approach to laparoscopic myotomy for achalasia using stepped dilation with a Rigiflex balloon and contrast medium under image guidance. A 10-year-old boy with persistent dysphagia and vomiting had ingested only liquids for 3 months, losing >10 kg in body weight. Barium swallow and esophageal manometry diagnosed esophageal achalasia with mild esophageal dilatation. After failed pneumatic dilatation, laparoscopic Heller myotomy with Dor fundoplication was performed. Prior to surgery, a Rigiflex balloon dilator was placed within the esophagus near the diaphragmatic hiatus. A four-port technique was used, and mobilization of the esophagus was limited to the anterior aspect. A 5-cm Heller myotomy was performed, extending another 2 cm onto the anterior gastric wall. During myotomy, the Rigiflex balloon was serially dilated from 30 to 50 mL, and filled with contrast medium under fluoroscopic image guidance in order to maintain appropriate tension on the esophagus to facilitate myotomy, and to confirm adequate myotomy with sufficient release of lower esophageal sphincter by resecting residual circular muscle fibers. Residual circular muscle fibers can be simultaneously visualized under both fluoroscopic image guidance and direct observation through the laparoscope, and they were cut precisely until the residual notch fully disappeared. Dor fundoplication was completed. The operative time was 180 minutes, and oral intake was started after esophagography on postoperative day 1. As of the 12-month follow-up, the patient has not shown any symptoms, and his postoperative course appeared satisfactory.

The outcome of laparoscopic Heller myotomy for achalasia is not influenced by the degree of esophageal dilatation.

PubMed

Sweet, Matthew P; Nipomnick, Ian; Gasper, Warren J; Bagatelos, Karen; Ostroff, James W; Fisichella, Piero M; Way, Lawrence W; Patti, Marco G

2008-01-01

In the past, a Heller myotomy was considered to be ineffective in patients with achalasia and a markedly dilated or sigmoid-shaped esophagus. Esophagectomy was the standard treatment. The aims of this study were (a) to evaluate the results of laparoscopic Heller myotomy and Dor fundoplication in patients with achalasia and various degrees of esophageal dilatation; and (b) to assess the role of endoscopic dilatation in patients with postoperative dysphagia. One hundred and thirteen patients with esophageal achalasia were separated into four groups based on the maximal diameter of the esophageal lumen and the shape of the esophagus: group A, diameter<4.0 cm, 46 patients; group B, esophageal diameter 4.0-6.0 cm, 32 patients; group C, diameter>6.0 cm and straight axis, 23 patients; and group D, diameter>6.0 cm and sigmoid-shaped esophagus, 12 patients. All had a laparoscopic Heller myotomy and Dor fundoplication. The median length of follow-up was 45 months (range 7 months to 12.5 years). The postoperative recovery was similar among the four groups. Twenty-three patients (20%) had postoperative dilatations for dysphagia, and five patients (4%) required a second myotomy. Excellent or good results were obtained in 89% of group A and 91% of groups B, C, and D. None required an esophagectomy to maintain clinically adequate swallowing. These data show that (a) a laparoscopic Heller myotomy relieved dysphagia in most patients with achalasia, even when the esophagus was dilated; (b) about 20% of patients required additional treatment; (c) in the end, swallowing was good in 90%.

The Role of Standards in Cloud-Computing Interoperability

DTIC Science & Technology

2012-10-01

services are not shared outside the organization. CloudStack, Eucalyptus, HP, Microsoft, OpenStack , Ubuntu, and VMWare provide tools for building...center requirements • Developing usage models for cloud ven- dors • Independent IT consortium OpenStack http://www.openstack.org • Open-source...software for running private clouds • Currently consists of three core software projects: OpenStack Compute (Nova), OpenStack Object Storage (Swift

Induced Stress, Artificial Environment, Simulated Tactical Operations Center Model

DTIC Science & Technology

1973-06-01

oriented 4 activities or, at best , tre application of dor:trinal i. 14 concepts to command post exercises. Unlike mechanical skills, weapon’s...training model identified as APSTRAT, an acronym indicating aptitude and strategies , be considered as a point of reference. Several instructional...post providing visual and aural sensing tasks and training objective oriented performance tasks. Vintilly, ho concludes that failure should be

"L'Invisible Voyeur du Monde des Voyants": Critiques of French Society in Michel Tournier's "La Goutte d'or" and Guy Hocquenghem's "L'Amour en Relief"

ERIC Educational Resources Information Center

Barclay, Fiona

2006-01-01

Since decolonisation, the increase in immigration from France's former colonies in North Africa has prompted metropolitan writers to reconsider conceptions of French society. In their novels, Tournier and Hocquenghem present contemporary France through the defamiliarising eyes of a North African immigrant, who serves as a device for the critique…

Einstein observations of three classical Cepheids

NASA Technical Reports Server (NTRS)

Bohm-Vitense, E.; Parsons, S. B.

1983-01-01

We have looked for X-ray emission from the classical Cepheids delta Cep, beta Dor, and zeta Gem during phases when the latter two stars show emission in low excitation chromospheric lines. No X-ray flux was detected except possibly from zeta Gem at phase 0.26. Derived upper limits are in line with emission flux or upper limits obtained for other F and G supergiants.

Gene-based SSR markers for common bean (Phaseolus vulgaris L.) derived from root and leaf tissue ESTs: an integration of the BMc series.

PubMed

Blair, Matthew W; Hurtado, Natalia; Chavarro, Carolina M; Muñoz-Torres, Monica C; Giraldo, Martha C; Pedraza, Fabio; Tomkins, Jeff; Wing, Rod

2011-03-22

Sequencing of cDNA libraries for the development of expressed sequence tags (ESTs) as well as for the discovery of simple sequence repeats (SSRs) has been a common method of developing microsatellites or SSR-based markers. In this research, our objective was to further sequence and develop common bean microsatellites from leaf and root cDNA libraries derived from the Andean gene pool accession G19833 and the Mesoamerican gene pool accession DOR364, mapping parents of a commonly used reference map. The root libraries were made from high and low phosphorus treated plants. A total of 3,123 EST sequences from leaf and root cDNA libraries were screened and used for direct simple sequence repeat discovery. From these EST sequences we found 184 microsatellites; the majority containing tri-nucleotide motifs, many of which were GC rich (ACC, AGC and AGG in particular). Di-nucleotide motif microsatellites were about half as common as the tri-nucleotide motif microsatellites but most of these were AGn microsatellites with a moderate number of ATn microsatellites in root ESTs followed by few ACn and no GCn microsatellites. Out of the 184 new SSR loci, 120 new microsatellite markers were developed in the BMc (Bean Microsatellites from cDNAs) series and these were evaluated for their capacity to distinguish bean diversity in a germplasm panel of 18 genotypes. We developed a database with images of the microsatellites and their polymorphism information content (PIC), which averaged 0.310 for polymorphic markers. The present study produced information about microsatellite frequency in root and leaf tissues of two important genotypes for common bean genomics: namely G19833, the Andean genotype selected for whole genome shotgun sequencing from race Peru, and DOR364 a race Mesoamerica subgroup 2 genotype that is a small-red seeded, released variety in Central America. Both race Peru and Mesoamerica subgroup 2 (small red beans) have been understudied in comparison to race Nueva Granada and Mesoamerica subgroup 1 (black beans) both with regards to gene expression and as sources of markers. However, we found few differences between SSR type and frequency between the G19833 leaf and DOR364 root tissue-derived ESTs. Overall, our work adds to the analysis of microsatellite frequency evaluation for common bean and provides a new set of 120 BMc markers which combined with the 248 previously developed BMc markers brings the total in this series to 368 markers. Once we include BMd markers, which are derived from GenBank sequences, the current total of gene-based markers from our laboratory surpasses 500 markers. These markers are basic for studies of the transcriptome of common bean and can form anchor points for genetic mapping studies in the future.

Computer Controlled Microwave Oven System for Rapid Water Content Determination

DTIC Science & Technology

1988-11-01

Codes - .d/or CONTENTS Page PREFACE .................................................................... 1 CONVERSION FACTORS, NON- SI TO SI (METRIC...CONVERSION FACTORS, NON- SI TO SI (METRIC) UNITS OF MEASUREMENT Non- SI units of measurement used in this report can be converted to SI (metric) units as...formula: C = (5/9)(F - 32) . To obtain Kelvin ( K ) readings, use: K = (5/9)(F - 32) + 273.15 3 COMPUTER CONTROLLED MICROWAVE OVEN SYSTEM FOR RAPID WATER

2D and 3D Models of Convective Turbulence and Oscillations in Intermediate-Mass Main-Sequence Stars

NASA Astrophysics Data System (ADS)

Guzik, Joyce Ann; Morgan, Taylor H.; Nelson, Nicholas J.; Lovekin, Catherine; Kitiashvili, Irina N.; Mansour, Nagi N.; Kosovichev, Alexander

2015-08-01

We present multidimensional modeling of convection and oscillations in main-sequence stars somewhat more massive than the sun, using three separate approaches: 1) Applying the spherical 3D MHD ASH (Anelastic Spherical Harmonics) code to simulate the core convection and radiative zone. Our goal is to determine whether core convection can excite low-frequency gravity modes, and thereby explain the presence of low frequencies for some hybrid gamma Dor/delta Sct variables for which the envelope convection zone is too shallow for the convective blocking mechanism to drive g modes; 2) Using the 3D planar ‘StellarBox’ radiation hydrodynamics code to model the envelope convection zone and part of the radiative zone. Our goals are to examine the interaction of stellar pulsations with turbulent convection in the envelope, excitation of acoustic modes, and the role of convective overshooting; 3) Applying the ROTORC 2D stellar evolution and dynamics code to calculate evolution with a variety of initial rotation rates and extents of core convective overshooting. The nonradial adiabatic pulsation frequencies of these nonspherical models will be calculated using the 2D pulsation code NRO of Clement. We will present new insights into gamma Dor and delta Sct pulsations gained by multidimensional modeling compared to 1D model expectations.

Acquisition of Flavescence Dorée Phytoplasma by Scaphoideus titanus Ball from Different Grapevine Varieties.

PubMed

Galetto, Luciana; Miliordos, Dimitrios E; Pegoraro, Mattia; Sacco, Dario; Veratti, Flavio; Marzachì, Cristina; Bosco, Domenico

2016-09-15

Flavescence dorée (FD) is a threat for wine production in the vineyard landscape of Piemonte, Langhe-Roero and Monferrato, Italy. Spread of the disease is dependent on complex interactions between insect, plant and phytoplasma. In the Piemonte region, wine production is based on local cultivars. The role of six local grapevine varieties as a source of inoculum for the vector Scaphoideus titanus was investigated. FD phytoplasma (FDP) load was compared among red and white varieties with different susceptibility to FD. Laboratory-reared healthy S. titanus nymphs were caged for acquisition on infected plants to measure phytoplasma acquisition efficiency following feeding on different cultivars. FDP load for Arneis was significantly lower than for other varieties. Acquisition efficiency depended on grapevine variety and on FDP load in the source plants, and there was a positive interaction for acquisition between variety and phytoplasma load. S. titanus acquired FDP with high efficiency from the most susceptible varieties, suggesting that disease diffusion correlates more with vector acquisition efficiency than with FDP load in source grapevines. In conclusion, although acquisition efficiency depends on grapevine variety and on FDP load in the plant, even varieties supporting low FDP multiplication can be highly susceptible and good sources for vector infection, while poorly susceptible varieties may host high phytoplasma loads.

Learning curve for laparoscopic Heller myotomy and Dor fundoplication for achalasia

PubMed Central

Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Seryung; Akimoto, Shunsuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2017-01-01

Purpose Although laparoscopic Heller myotomy and Dor fundoplication (LHD) is widely performed to address achalasia, little is known about the learning curve for this technique. We assessed the learning curve for performing LHD. Methods Of the 514 cases with LHD performed between August 1994 and March 2016, the surgical outcomes of 463 cases were evaluated after excluding 50 cases with reduced port surgery and one case with the simultaneous performance of laparoscopic distal partial gastrectomy. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value for the number of surgical experiences necessary to become proficient with LHD, which was defined as the completion of the learning curve. Results We defined the completion of the learning curve when the following 3 conditions were satisfied. 1) The operation time was less than 165 minutes. 2) There was no blood loss. 3) There was no intraoperative complication. In order to establish the appropriate number of surgical experiences required to complete the learning curve, the cut-off value was evaluated by using a ROC curve (AUC 0.717, p < 0.001). Finally, we identified the cut-off value as 16 surgical cases (sensitivity 0.706, specificity 0.646). Conclusion Learning curve seems to complete after performing 16 cases. PMID:28686640

Learning curve for laparoscopic Heller myotomy and Dor fundoplication for achalasia.

PubMed

Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Seryung; Akimoto, Shunsuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2017-01-01

Although laparoscopic Heller myotomy and Dor fundoplication (LHD) is widely performed to address achalasia, little is known about the learning curve for this technique. We assessed the learning curve for performing LHD. Of the 514 cases with LHD performed between August 1994 and March 2016, the surgical outcomes of 463 cases were evaluated after excluding 50 cases with reduced port surgery and one case with the simultaneous performance of laparoscopic distal partial gastrectomy. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value for the number of surgical experiences necessary to become proficient with LHD, which was defined as the completion of the learning curve. We defined the completion of the learning curve when the following 3 conditions were satisfied. 1) The operation time was less than 165 minutes. 2) There was no blood loss. 3) There was no intraoperative complication. In order to establish the appropriate number of surgical experiences required to complete the learning curve, the cut-off value was evaluated by using a ROC curve (AUC 0.717, p < 0.001). Finally, we identified the cut-off value as 16 surgical cases (sensitivity 0.706, specificity 0.646). Learning curve seems to complete after performing 16 cases.

Nanoparticules d'or: De l'imagerie par resonance magnetique a la radiosensibilisation

NASA Astrophysics Data System (ADS)

Hebert, Etienne M.

Cette thèse approfondit l'étude de nanoparticules d'or de 5 nm de diamètre recouvertes de diamideéthanethioldiethylènetriaminepentacétate de gadolinium (DTDTPA:Gd), un agent de contraste pour l'imagerie par résonance magnétique (IRM). En guise de ciblage passif, la taille des nanoparticules a été contrôlée afin d'utiliser le réseau de néovaisseaux poreux et perméable des tumeurs. De plus les tumeurs ont un drainage lymphatique déficient qui permet aux nanoparticules de demeurer plus longtemps dans le milieu interstitiel de la tumeur. Les expériences ont été effectuées sur des souris Balb/c femelles portant des tumeurs MC7-L1. La concentration de nanoparticules a pu être mesurée à l'IRM in vivo. La concentration maximale se retrouvait à la fin de l'infusion de 10 min. La concentration s'élevait à 0.3 mM dans la tumeur et de 0.12 mM dans le muscle environnant. Les nanoparticules étaient éliminées avec une demi-vie de 22 min pour les tumeurs et de 20 min pour le muscle environnant. Les nanoparticules ont été fonctionnalisées avec le peptide Tat afin de leur conférer des propriétés de ciblage actif La rétention de ces nanoparticules a ainsi été augmentée de 1600 %, passant d'une demi-vie d'élimination de 22 min à 350 min. La survie des souris a été mesurée à l'aide de courbes Kaplan-Meier et d'un modèle mathématique évalue l'efficacité de traitements. Le modèle nous permet, à l'aide de la vitesse de croissance des tumeurs et de l'efficacité des traitements, de calculer la courbe de survie des spécimens. Un effet antagoniste a été observé au lieu de l'effet synergétique attendu entre une infusion de Au@DTDTPA:Gd et l'irradiation aux rayons X. L'absence d'effet synergétique a été attribuée à l'épaisseur du recouvrement de DTDTPA:Gd qui fait écran aux électrons produits par l'or. De plus, le moyen d'ancrage du recouvrement utilise des thiols qui peuvent s'avérer être des capteurs de radicaux. De plus, contrairement a ce qui était escompté, un effet chimiothérapeutique de ces nanoparticules a été observé in vitro et in vivo. Par contre, le mécanisme précis de cet effet est encore à être expliquer, mais on sait déjà que les nanoparticules d'or affectent les fonctions des macrophages ainsi que l'angiogenèse. MOTS-CLÉS : Radiosensibilisateur, Nanoparticules d'or, Agent de contraste pour l'IRM, Électrons de basses énergies, Kaplan-Meier, Effet chimiothérapeutique.

Short-term surgical outcomes of reduced port surgery for esophageal achalasia.

PubMed

Omura, Nobuo; Yano, Fumiaki; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Ishibashi, Yoshio; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2015-09-01

To clarify the feasibility and utility of reduced port surgery (RPS) for achalasia. Between September 2005 and June 2013, 359 patients with esophageal achalasia, excluding cases of reoperation, underwent laparoscopic Heller myotomy and Dor fundoplication (LHD) according to our clinical pathway. Three-hundred and twenty-seven patients underwent LHD with five incisions (conventional approach), while the other 32 patients underwent RPS, including eight via SILS. The clinical data were collected in a prospective fashion and retrospectively reviewed. We selected 24 patients matched for gender, age and morphologic type with patients in the RPS group from among the 327 patients (C group). The surgical outcomes were compared between the C and RPS groups. There were no significant differences between the two groups in the duration of symptoms, dysphagia score, chest pain score, shape of the distal esophagus and esophageal clearance. The operative time was significantly longer in the RPS group than in the C group (p < 0.001). There were no significant differences between the two groups in the length of postoperative hospital stay or rates of bleeding, mucosal injury of the esophagus and/or stomach and postoperative complications. The symptom scores significantly improved after surgery in both groups (p < 0.001). Furthermore, there were no significant differences between the C group and RPS group in terms of the postoperative symptom scores or satisfaction scores after surgery. The surgical outcomes of RPS for achalasia are comparable to those obtained with the conventional method.

Cool Dwarfs 1o-7

NASA Astrophysics Data System (ADS)

Ambruster, Carol W.

Most of the cool dwarfs in the interesting age range 10^7-10^8 yr are too faint for IUE, yet such stars are critically important from the viewpoint of stellar evolution. Among stars of this age are the Pleiades K dwarfs, some of which appear to be on the main sequence, and some of which are still arriving there. Up until last year, only 2 stars in this age range had been observed by IUE, both recently: HD 36705 (AB Dor) and HD 17433. Three more stars were identified by the present investigators and observed with IUE during the past (11th) year: HD 129333, a single, nearby solar-type GOV star; HD 82558, a rapidly rotating, single, K2V star; and Ross 137B, the M dwarf common proper motion companion to AB Dor. We have since identified 5 more stars between 10^7 and 10^8 years old that are bright enough to be observed by IUE. They are physically associated, but distant, companions to main sequence O and B stars, identified in the survey of Lindroos (1986). Their ages are thus determined by the short main sequence lifetimes of the hot primaries. Rotational velocities are not yet known for our 5 proposed targets; we will be obtaining these and other data in the coming year. We therefore request time for basic IUE observations of these stars, an LWP-lo, LWP-hi and SWP-lo, for each star. This will ensure that crucial basic fluxes are in the IUE archives, should the satellite die in the coming year. Furthermore these data are immediately useful in filling the gap in the exhaustive study by Simon, Herbig and Boesgaard (1985) of the evolution of TR and chromospheric activity with age. More in-depth coverage will be proposed next year.

Sec34 is implicated in traffic from the endoplasmic reticulum to the Golgi and exists in a complex with GTC-90 and ldlBp.

PubMed

Loh, Eva; Hong, Wanjin

2002-06-14

Sec34p/Grd20p has been implicated in endoplasmic reticulum (ER)-to-Golgi transport and/or post-Golgi trafficking events and exists in a protein complex consisting of at least eight subunits in yeast. Although the mammalian counterpart (Sec34) of Sec34p has been molecularly identified, its role and interacting partners remain undefined. In this study, we have prepared antibodies specifically against the recombinant N-terminal fragment of Sec34 that recognize a polypeptide of about 93 kDa and label the Golgi apparatus. In a well-characterized semi-intact cell assay that reconstitutes transport of the envelope glycoprotein (VSVG) of vesicular stomatitis virus from the ER to the Golgi apparatus, anti-Sec34 antibodies inhibited the transport in a dose-dependent manner. The inhibition by anti-Sec34 antibodies could be neutralized by a noninhibitory amount of the antigen. Large-scale immunoprecipitation of rat liver cytosol with immobilized anti-Sec34 antibodies has co-immunoprecipitated GTC-90 and ldlBp, two peripheral Golgi proteins previously shown to exist in separate protein complexes. Two mammalian homologues (Dor1 and Cod1) of the yeast Sec34 complex were similarly recovered in the Sec34 immunoprecipitates. When expressed in transfected cells, epitope-tagged ldlCp and Cod2 were co-immunoprecipitated with anti-Sec34 antibodies with efficiencies comparable to that observed for tagged ldlBp, Dor1, and Cod1. Direct interactions of Sec34 with ldlBp and ldlCp were further demonstrated in vitro. These results suggest that Sec34, GTC-90, and ldlBp/ldlCp are part of the same protein complex(es) that regulates diverse aspects of Golgi function, including transport from the ER to the Golgi apparatus.

Diagnostic accuracy of PCR for detecting ALK gene rearrangement in NSCLC patients: A systematic review and meta-analysis

PubMed Central

Zhang, Xia; Zhou, Jian-Guo; Wu, Hua-Lian; Ma, Hu; Jiang, Zhi-Xia

2017-01-01

Background Anaplastic lymphoma kinase (ALK) gene fusion has been reported in 3∼5% non-small cell lung carcinoma (NSCLC) patients, and polymerase chain reaction (PCR) is commonly used to detecting the gene status, but the diagnostic capacity of it is still controversial. A systematic review and meta-analysis was conducted to clarify the diagnostic accuracy of PCR for detecting ALK gene rearrangement in NSCLC patients. Results 18 articles were enrolled, which included 21 studies, involving 2800 samples from NSCLC patients. The overall pooled parameters were calculated: sensitivity was 92.4% [95% confidence interval (CI): 82.2%–97.0%], specificity was 97.8% [95% CI: 95.1%–99.0%], PLR was 41.51 [95% CI: 18.10–95.22], NLR was 0.08 [95% CI: 0.03–0.19], DOR was 535.72 [95% CI: 128.48–2233.79], AUROC was 0.99 [95% CI: 0.98–1.00]. Materials and Methods Relevant articles were searched from PubMed, EMBASE, Web of Science, Cochrane library, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), China National Knowledge Infrastructure (CNKI), China Wan Fang databases and Chinese biomedical literature database (CBM). Diagnostic capacity of PCR test was assessed by the pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUROC). Conclusions Based on the results from this review, PCR has good diagnostic performance for detecting the ALK gene fusion in NSCLC patients. Moreover, due to the poor methodology quality of the enrolled trials, more well-designed multi-center trials should be performed. PMID:29088875

Specific esophagogram to assess functional outcomes after Heller's myotomy and Dor's fundoplication for esophageal achalasia.

PubMed

Tsoukali, E; Gouvas, N; Tsiaoussis, J; Pechlivanides, G; Zervakis, N; Mantides, A; Xynos, E

2011-09-01

Esophageal emptying assessed at the 'timed barium' esophagogram correlates well with symptomatic outcomes after pneumatic dilation for esophageal achalasia, although 30% of patients with satisfactory outcome exhibit partial improvement in emptying. The aim of the study was to investigate any correlation of esophageal emptying to symptomatic response after laparoscopic Heller's myotomy and Dor's fundoplication. 'Bread and barium' (transit time of a barium opaque bread bolus) and 'timed barium' (height of esophageal barium column 5 minutes after ingestion of 200-250 mL of barium suspension) esophagogram was used to assess esophageal emptying in 73 patients with esophageal achalasia before 1 and 5 years (31 cases) after laparoscopic myotomy and anterior fundoplication. Symptoms assessment was based to a specific score. At 1-year follow-up, excellent and good symptomatic results were obtained in 95% of the cases. Esophageal maximum diameter, esophageal transit time, and esophageal barium column were significantly correlated to each other and to symptom score postoperatively (P < 0.001). Complete and partial (<90% and 50-90% postoperative reduction in barium column, respectively) emptying was seen in 55% and 31% of patients with excellent result. Patients with a pseudodiverticulum postoperatively had a more delayed esophageal emptying than those without. Symptomatic outcome and esophageal emptying did not deteriorate at 5-year follow-up. Esophageal emptying assessed by 'barium and bread' and 'timed barium' esophagogram correlated well with symptomatic outcome after laparoscopic myotomy for esophageal achalasia. Complete symptomatic relief does not necessarily reflect complete esophageal emptying. Outcomes do not deteriorate by time. Because of wide availability, esophagogram can be applied in follow-up of postmyotomy patients in conjunction with symptomatic evaluation. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain

PubMed Central

2014-01-01

Background The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats. Methods The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury. At the end of the sessions, the PAG was analyzed using Western blot assays for opioid receptors. Locomotion was analyzed by the Sciatic functional index (SFI), and muscle force was analyzed by the BIOPAC system. Results An improvement in locomotion was observed in animals treated with NM compared with injured animals. Animals treated with NM showed an increase in maximal tetanic force of the tibialis anterior muscle of 172% (p < 0.001) compared with the CCI group. We also observed a decrease of 53% (p < 0.001) and 23% (p < 0.05) in DOR and KOR levels, respectively, after CCI injury compared to those from naive animals and an increase of 17% (p < 0.05) in KOR expression only after NM treatment compared to naive animals. There were no significant changes in MOR expression in the PAG. Conclusion These data provide evidence that a non-pharmacological NM technique facilitates pain relief by endogenous analgesic modulation. PMID:24884961

Evaluation of the Aspergillus Western Blot IgG Kit for Diagnosis of Chronic Aspergillosis

PubMed Central

Oliva, A.; Flori, P.; Hennequin, C.; Dubus, J.-C.; Reynaud-Gaubert, M.; Charpin, D.; Vergnon, J. M.; Gay, P.; Colly, A.; Piarroux, R.; Pelloux, H.

2014-01-01

Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method. PMID:25392351

Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic aspergillosis.

PubMed

Oliva, A; Flori, P; Hennequin, C; Dubus, J-C; Reynaud-Gaubert, M; Charpin, D; Vergnon, J M; Gay, P; Colly, A; Piarroux, R; Pelloux, H; Ranque, S

2015-01-01

Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A Model-Based Optimization Plan for the Naval Helicopter Training Program

DTIC Science & Technology

2011-06-01

FF (E. Lashua, personal communication, January 18, 2011). Table 1. Training Costs: Introductory Flight Screening (IFS) (From AMS Aviation at...within the program is historically 3.3% due to DORs and academic failures (E. Lashua, personal communication, January 18, 2011). 18 7. Stage...duty station of NAS Corpus Christi, students are eligible to receive 10 days of house hunting leave to find and set up their house prior to checking

Proceedings of the 27th International Group for the Psychology of Mathematics Education Conference Held Jointly with the 25th PME-NA Conference (Honolulu, Hawaii, July 13-18, 2003). Volume 2

ERIC Educational Resources Information Center

Pateman, Neil A., Ed.; Dougherty, Barbara J., Ed.; Zilliox, Joseph T., Ed.

2003-01-01

This volume of the 27th International Group for the Psychology of Mathematics Education Conference presents the following research reports: (1) Text Talk, Body Talk, Table Talk: A Design of Ratio and Proportion as Classroom Parallel Events (Dor Abrahamson); (2) Generalizing the Context and Generalising the Calculation (Janet Ainley); (3) Interview…

Defense Small Business Innovation Research Program (SBIR). Abstracts of Phase I Awards. 1986.

DTIC Science & Technology

1986-01-01

RELATIVE HUMIDITY AT TEMPERATURES FOUND IN ARCTIC ENVIRONMENTS. IT IS BASED ON THE OBSERVATION THAT CERTAIN FLUORESCENT AND PHOSPHORESCENT COMPOUNDS ...FREEDMAN TITLE: III-V COMPOUNDS TRACE ELEMENT PROFILE ANALYSIS USING LASER ASSISTED S PECTROSCOPY T 55 OFFICE: RADC/DOR A NOVEL MICROPROBE ANALYSIS...AND II-VI AND III-V COMPOUNDS . THESE ADVANTAGES MAKE THE LSCE TECHNIQUE PARTICULARY WELL SUITED TO THE DEPOSITION OF QUANTUM WELL AND SUPERLATT ICE

Computational Fluid Dynamic Solutions of Optimized Heat Shields Designed for Earth Entry

DTIC Science & Technology

2010-01-01

domain ρ = Density (kg/m3) σ = Stefan Boltzmann constant τ = Shear stress tensor τT−V = T-V relaxation time τe−V = e-V relaxation time xi φ = Sweep angle...Vehicle DES = Differential evolutionary Scheme DOR = Design Optimization Tools DPLR = Data Parallel Line Relaxation GSLR = Gauss- Seidel Line... Stefan - Boltzmann constant. This model provides accurate heating predictions, especially for the non-ablating heat-shields explored in this work. Various

Study of the aluminium content in AGB winds using ALMA. Indications for the presence of gas-phase (Al2O3)n clusters

NASA Astrophysics Data System (ADS)

Decin, L.; Richards, A. M. S.; Waters, L. B. F. M.; Danilovich, T.; Gobrecht, D.; Khouri, T.; Homan, W.; Bakker, J. M.; Van de Sande, M.; Nuth, J. A.; De Beck, E.

2017-12-01

Context. The condensation of inorganic dust grains in the winds of evolved stars is poorly understood. As of today, it is not yet known which molecular clusters form the first dust grains in oxygen-rich (C/O < 1) asymptotic giant branch (AGB) winds. Aluminium oxides and iron-free silicates are often put forward as promising candidates for the first dust seeds. Aims: We aim to constrain the dust formation histories in the winds of oxygen-rich AGB stars. Methods: We obtained Atacama Large Millimeter/sub-millimeter array (ALMA) observations with a spatial resolution of 120 × 150 mas tracing the dust formation region of the low mass-loss rate AGB star, R Dor, and the high mass-loss rate AGB star, IK Tau. We detected emission line profiles of AlO, AlOH, and AlCl in the ALMA data and used these line profiles to derive a lower limit of atomic aluminium incorporated in molecules. This constrains the aluminium budget that can condense into grains. Results: Radiative transfer models constrain the fractional abundances of AlO, AlOH, and AlCl in IK Tau and R Dor. We show that the gas-phase aluminium chemistry is completely different in both stars with a remarkable difference in the AlO and AlOH abundance stratification. The amount of aluminium locked up in these three molecules is small, ≤1.1 × 10-7 w.r.t. H2, for both stars, i.e. only ≤2% of the total aluminium budget. An important result is that AlO and AlOH, which are the direct precursors of alumina (Al2O3) grains, are detected well beyond the onset of the dust condensation, which proves that the aluminium oxide condensation cycle is not fully efficient. The ALMA observations allow us to quantitatively assess the current generation of theoretical dynamical-chemical models for AGB winds. We discuss how the current proposed scenario of aluminium dust condensation for low mass-loss rate AGB stars within a few stellar radii from the star, in particular for R Dor and W Hya, poses a challenge if one wishes to explain both the dust spectral features in the spectral energy distribution (SED) in interferometric data and in the polarized light signal. In particular, the estimated grain temperature of Al2O3 is too high for the grains to retain their amorphous structure. We advocate that large gas-phase (Al2O3)n clusters (n > 34) can be the potential agents of the broad 11 μm feature in the SED and in the interferometric data and we propose potential formation mechanisms for these large clusters.

Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis.

PubMed

Liu, Lihua; Wang, Shan; Cao, Xiutang; Liu, Jianchao

2014-12-01

Gastric cancer (GC) accounts for one of the highest mortality worldwide and particularly in East Asia. Many studies have reported on the potential value of microRNAs (miRNAs) detection for diagnosing GC, but their results have proven inconclusive. The present meta-analysis was conducted to assess the diagnostic value of circulating miRNAs for GC diagnosis. A literature search was carried out in databases (PubMed, Embase, Web of Science, The Cochrane Library, and CNKI) and other sources using combinations of keywords relating to GC, miRNAs, and diagnosis. The values of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) reported in individual studies were pooled using random-effects models. Potential sources of heterogeneity were assessed with subgroup and meta-regression analyses. The summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) were used to assess the diagnosis accuracy of miRNAs. This meta-analysis included 1,279 patients with GC and 954 healthy controls from 20 publications. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.78 (95 % CI: 0.73-0.81), 0.80 (95 % CI: 0.76-0.84), 4.0 (95 % CI: 3.1-6.0), 0.28 (95 % CI: 0.23-0.34), 14 (95 % CI: 10-21), and 0.86 (95 % CI: 0.83-0.89), respectively. Subgroup analyses showed that early stages (I and II) GC were more easily detected than later stages and that multiple miRNAs assays were more accurate than single miRNA assays. Our meta-analysis suggests that miRNAs have a high diagnostic value for GC, especially in its early stages (I and II). In addition, multiple miRNAs assays have a better diagnosis value than single miRNA assays. In conclusion, circulating miRNAs might be used as noninvasive biomarkers for the confirmation of GC detection in Asian populations.

Diagnostic performance of coronary computed tomography angiography versus exercise electrocardiography for coronary artery disease: a systematic review and meta-analysis

PubMed Central

Yin, Xinxin; Zheng, Wen; Ma, Jingjing; Hao, Panpan

2016-01-01

Background Both coronary computed tomography angiography (CCTA) and exercise electrocardiography (ExECG) are non-invasive testing methods for the evaluation of coronary artery disease (CAD). However, there was controversy on the diagnostic performance of these methods due to the limited data in each single study. Therefore, we performed a meta-analysis to address these issues. Methods We searched PubMed and Embase databases up to May 22, 2015. Two authors identified eligible studies, extracted data and accessed quality. Pooled estimation of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver-operating characteristic curve (SROC) and the area under curve (AUC) of CCTA and ExECG for the diagnosis of CAD were calculated using Stata, Meta-Disc and Review Manager statistical software. Results Seven articles were included. Pooled sensitivity of CCTA and ExECG were 0.98 [95% confidence intervals (CIs): 0.95–0.99] and 0.66 (95% CIs: 0.59–0.72); pooled specificity of CCTA and ExECG were 0.84 (95% CIs: 0.81–0.87) and 0.75 (95% CIs: 0.71–0.79); pooled DOR of CCTA and ExECG were 110.24 (95% CIs: 35.07–346.55) and 6.28 (95% CIs: 2.06–19.13); and AUC of CCTA and ExECG were 0.9950±0.0046 and 0.7727±0.0638, respectively. There is no heterogeneity caused by threshold effect in CCTA or ExECG analysis. The Deeks’ test showed no potential publication bias (P=0.17). Conclusions CCTA has better diagnostic performance than ExECG in the evaluation of CAD, which can provide a better solution for the clinical problem of the diagnosis for CAD. PMID:27499958

Nursing Diagnosis Based on Signs and Symptoms of Patients With Heart Disease.

PubMed

da Costa, Cíntia; da Costa Linch, Graciele Fernanda; Nogueira de Souza, Emiliane

2016-10-01

The aim was to identify the main signs and symptoms of cardiac patients hospitalized in a unit of intensive cardiology care in order to infer the main nursing diagnoses (NDs). We performed a cross-sectional study; the sample consisted of 77 randomly selected records. Those records included only patients hospitalized for cardiovascular causes and with electronic chart available. Signs and symptoms identified at admission were psychic (40.3%), compressive dressing on arterial puncture site (33.8%), chest pain (29.9%), tachycardia (22.1%), and hemodynamic instability (20.8%). According to the data collected, we were able to infer that acute pain, excess of fluid volume, decreased cardiac output, spontaneous ventilation impaired, anxiety and impaired skin integrity are priority for the NDs in the studied population. OBJETIVO: identificar os principais sinais e sintomas de pacientes cardíacos internados em uma unidade de cuidados intensivos de cardiologia, visando inferir os diagnósticos de enfermagem prioritários. MÉTODO: Estudo transversal; a amostra foi composta por 77 registros selecionados aleatoriamente. Incluíram-se apenas pacientes internados por causa cardiovascular e com registro eletrônico disponível. Os sinais e sintomas identificados na admissão foram psíquicos (40,3%), curativo compressivo em sítio de punção arterial (33,8%), dor torácica (29,9%), taquicardia (22,1%) e instabilidade hemodinâmica (20,8%). CONCLUSÕES E IMPLICAÇÕES PARA A PRÁTICA: De acordo com os dados levantados foram inferidos Dor Aguda, Volume de Líquidos Excessivo, Débito Cardíaco Diminuído, Ventilação Espontânea Prejudicada, Ansiedade e Integridade da Pele Prejudicada como diagnósticos de enfermagem prioritários para a população estudada. © 2016 NANDA International, Inc.

Efficacy according to blind independent central review: Post-hoc analyses from the phase III, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC.

PubMed

Wu, Yi-Long; Saijo, Nagahiro; Thongprasert, Sumitra; Yang, J C-H; Han, Baohui; Margono, Benjamin; Chewaskulyong, Busayamas; Sunpaweravong, Patrapim; Ohe, Yuichiro; Ichinose, Yukito; Yang, Jin-Ji; Mok, Tony S K; Young, Helen; Haddad, Vincent; Rukazenkov, Yuri; Fukuoka, Masahiro

2017-02-01

The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC. Eligible patients (aged ≥18 years; histologically/cytologically confirmed Stage IIB/IV adenocarcinoma NSCLC; non- or former light-smokers; treatment-naïve) were randomly assigned 1:1 to gefitinib (250mg/day) or carboplatin (dose calculated to produce an area under the curve of 5 or 6 mg/mL/minute)/paclitaxel (200mg/m 2 ). Primary endpoint: PFS. BICR analyses included PFS, ORR, and duration of response (DoR). Scans from 186 IPASS patients (gefitinib n=88, carboplatin/paclitaxel n=98) with EGFR mutation-positive NSCLC were available for BICR. Consistent with investigator-assessed results, in patients with EGFR mutation-positive NSCLC: PFS (hazard ratio 0.54; 95% confidence interval [CI] 0.38, 0.79; p=0.0012) and ORR (odds ratio 3.00; 95% CI 1.63, 5.54; p=0.0004) were significantly longer with gefitinib versus carboplatin/paclitaxel. The median DoR by BICR was 9.6 months with gefitinib and 5.5 months with carboplatin/paclitaxel. BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 and ARIEL2.

PubMed

Oza, Amit M; Tinker, Anna V; Oaknin, Ana; Shapira-Frommer, Ronnie; McNeish, Iain A; Swisher, Elizabeth M; Ray-Coquard, Isabelle; Bell-McGuinn, Katherine; Coleman, Robert L; O'Malley, David M; Leary, Alexandra; Chen, Lee-May; Provencher, Diane; Ma, Ling; Brenton, James D; Konecny, Gottfried E; Castro, Cesar M; Giordano, Heidi; Maloney, Lara; Goble, Sandra; Lin, Kevin K; Sun, James; Raponi, Mitch; Rolfe, Lindsey; Kristeleit, Rebecca S

2017-11-01

An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600mg BID, irrespective of BRCA1/2 mutation status and prior treatments. In the efficacy population (n=106), ORR was 53.8% (95% confidence interval [CI], 43.8-63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2months (95% CI, 6.6-11.6). In the safety population (n=377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: A meta-analysis.

PubMed

Gupta, Renu; Talwar, Puneet; Talwar, Pumanshi; Khurana, Sarbjeet; Kushwaha, Suman; Jalan, Nupur; Thakur, Rajeev

2018-05-25

Numerous in-house and commercial nucleic acid amplification tests (NAAT) have been evaluated using variable reference standards for diagnosis of TBM but their diagnostic potential is still not very clear. We conducted a meta-analysis to assess the diagnostic accuracy of different NAAT based assays for diagnosing TBM against 43 data sets of confirmed TBM (n = 1066) and 61 data sets of suspected TBM (n = 3721) as two reference standards. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. QUADAS-2 tool was used to perform the Quality assessment for bias and applicability. Publication bias was assessed with Deeks' funnel plot. Studies with confirmed TBM had better summary estimates as compared to studies with clinically suspected TBM irrespective of NAAT and index tests used. Among in-house assays, MPB as the gene target had best summary estimates in both confirmed [sensitivity:90%(83-95), specificity:97-%(87-99), DOR:247 (50-1221), AUC:99%(97-100), PLR:38.8-(6.6-133), NLR:0.11(0.05-0.18), I 2   = 15%] and clinically suspected [sensitivity:69%(47-85), specificity:96%(90-98), DOR:62(16.8-232), AUC:94%(92-97), PLR:16.9(6.5-36.8), NLR:0.33(0.16-0.56), I 2 :15.3%] groups. GeneXpert revealed good diagnostic accuracy only in confirmed TBM group [sensitivity = 57%(38-74), specificity = 98%(89-100), DOR = 62(7-589), AUC = 87%(79-96), PLR = 33.2(3.8-128), NLR = 0.45(0.26-0.68), I 2   = 0%]. This meta-analysis identified potential role of MPB gene among in-house assays and GeneXpert as commercial assay for diagnosing TBM. Copyright © 2018. Published by Elsevier Ltd.

Review: Diagnostic accuracy of PCR-based detection tests for Helicobacter Pylori in stool samples.

PubMed

Khadangi, Fatemeh; Yassi, Maryam; Kerachian, Mohammad Amin

2017-12-01

Although different methods have been established to detect Helicobacter pylori (H. pylori) infection, identifying infected patients is an ongoing challenge. The aim of this meta-analysis was to provide pooled diagnostic accuracy measures for stool PCR test in the diagnosis of H. pylori infection. In this study, a systematic review and meta-analysis were carried out on various sources, including MEDLINE, Web of Sciences, and the Cochrane Library from April 1, 1999, to May 1, 2016. This meta-analysis adheres to the guidelines provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses report (PRISMA Statement). The clinical value of DNA stool PCR test was based on the pooled false positive, false negative, true positive, and true negative of different genes. Twenty-six of 328 studies identified met the eligibility criteria. Stool PCR test had a performance of 71% (95% CI: 68-73) sensitivity, 96% (95% CI: 94-97) specificity, and 65.6 (95% CI: 30.2-142.5) diagnostic odds ratio (DOR) in diagnosis of H. pylori. The DOR of genes which showed the highest performance of stool PCR tests was as follows: 23S rRNA 152.5 (95% CI: 55.5-418.9), 16S rRNA 67.9 (95%CI: 6.4-714.3), and glmM 68.1 (95%CI: 20.1-231.7). The sensitivity and specificity of stool PCR test are relatively in the same spectrum of other diagnostic methods for the detection of H. pylori infection. In descending order of significance, the most diagnostic candidate genes using PCR detection were 23S rRNA, 16S rRNA, and glmM. PCR for 23S rRNA gene which has the highest performance could be applicable to detect H. pylori infection. © 2017 John Wiley & Sons Ltd.

Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis.

PubMed

Blank, Christian U; Larkin, James; Arance, Ana M; Hauschild, Axel; Queirolo, Paola; Del Vecchio, Michele; Ascierto, Paolo A; Krajsova, Ivana; Schachter, Jacob; Neyns, Bart; Garbe, Claus; Chiarion Sileni, Vanna; Mandalà, Mario; Gogas, Helen; Espinosa, Enrique; Hospers, Geke A P; Miller, Wilson H; Robson, Susan; Makrutzki, Martina; Antic, Vladan; Brown, Michael P

2017-07-01

The orally available BRAF kinase inhibitor vemurafenib is an effective and tolerable treatment option for patients with metastatic melanoma harbouring BRAF V600 mutations. We assessed the safety of vemurafenib in a large population of patients with few alternative treatment options; we report updated 2-year safety. This was an open-label, multicentre study of vemurafenib (960 mg bid) in patients with previously treated or untreated BRAF mutation-positive metastatic melanoma (cobas ® 4800 BRAF V600 Mutation Test). The primary end-point was safety; efficacy end-points were secondary. An exploratory analysis was performed to assess safety outcomes in patients with long duration of response (DOR) (≥12 or ≥24 months). After a median follow-up of 32.2 months (95% CI, 31.1-33.2 months), 3079/3219 patients (96%) had discontinued treatment. Adverse events (AEs) were largely consistent with previous reports; the most common all-grade treatment-related AEs were arthralgia (37%), alopecia (25%) and hyperkeratosis (23%); the most common grade 3/4 treatment-related AEs were squamous cell carcinoma of the skin (8%) and keratoacanthoma (8%). In the exploratory analysis, patients with DOR ≥12 months (n = 287) or ≥24 months (n = 133) were more likely to experience grade 3/4 AEs than the overall population. No new specific safety signals were observed with longer vemurafenib exposure. After 2 years' follow-up, safety was maintained in this large group of patients with BRAF V600 mutation-positive metastatic melanoma who are more representative of routine clinical practice than typical clinical trial populations. These data suggest that long-term vemurafenib treatment is effective and tolerable without the development of new safety signals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interior rotation of a sample of γ Doradus stars from ensemble modelling of their gravity-mode period spacings

NASA Astrophysics Data System (ADS)

Van Reeth, T.; Tkachenko, A.; Aerts, C.

2016-10-01

Context. Gamma Doradus stars (hereafter γ Dor stars) are known to exhibit gravity- and/or gravito-intertial modes that probe the inner stellar region near the convective core boundary. The non-equidistant spacing of the pulsation periods is an observational signature of the stellar evolutions and current internal structure and is heavily influenced by rotation. Aims: We aim to constrain the near-core rotation rates for a sample of γ Dor stars for which we have detected period spacing patterns. Methods: We combined the asymptotic period spacing with the traditional approximation of stellar pulsation to fit the observed period spacing patterns using χ2-optimisation. The method was applied to the observed period spacing patterns of a sample of stars and used for ensemble modelling. Results: For the majority of stars with an observed period spacing pattern we successfully determined the rotation rates and the asymptotic period spacing values, although the uncertainty margins on the latter were typically large. This also resulted directly in the identification of the modes that correspond to the detected pulsation frequencies, which for most stars were prograde dipole gravity and gravito-inertial modes. The majority of the observed retrograde modes were found to be Rossby modes. We also discuss the limitations of the method that are due to the neglect of the centrifugal force and the incomplete treatment of the Coriolis force. Conclusions: Despite its current limitations, the proposed method was successful to derive the rotation rates and to identify the modes from the observed period spacing patterns. It forms the first step towards detailed seismic modelling based on observed period spacing patterns of moderately to rapidly rotating γDor stars. Based on data gathered with the NASA Discovery mission Kepler and the HERMES spectrograph, which is installed at the Mercator Telescope, operated on the island of La Palma by the Flemish Community at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, and supported by the Fund for Scientific Research of Flanders (FWO), Belgium, the Research Council of KU Leuven, Belgium, the Fonds National de la Recherche Scientifique (F.R.S.-FNRS), Belgium, the Royal Observatory of Belgium, the Observatoire de Genève, Switzerland, and the Thüringer Landessternwarte Tautenburg, Germany.

[Effects of "menstrual cycle-based acupuncture therapy" on IVF-ET in patients with decline in ovarian reserve].

PubMed

Zhou, Li; Xia, Youbing; Ma, Xiang; Tang, Limei; Lu, Jing; Tang, Qingqing; Wang, Yinping

2016-01-01

To observe the effects of "menstrual cycle-based acupuncture therapy" on ovarian function and pregnancy results of in vitro fertilization-embryo transfer (IVF-ET) in patients with decline in ovarian reserve (DOR). A total of 63 patients of DOR who received treatment of IVF/intracytoplasmic sperm injection (ICSI) were randomly divided into an observation group (30 cases) and a control group (33 cases). The patients in the observation group were treated with "menstrual cycle-based acupuncture therapy". The syndrome differentiation and treatment were given based on different phases of menstruation. Shiqizhui (EX-B 8) and Mingmen (GV 4) were selected during menstrual phase, Shenshu (BL 23), Geshu (BL 17), Sanyinjiao (SP 6) and Taixi (KI 3) were selected after menstruation, Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36) were selected during ovulatory period, Qihai (CV 6), Guanyuan (CV 4), Yanglingquan (GB 34), Taichong (LR 3) were selected before menstruation. The acupuncture was given twice a week until second menstrual cycle of oocyte retrieval. The total times of acupuncture was (15 ± 2). After acupuncture, patients were treated with IVF-ET. The patients in the control group were treated with IVF-ET but no acupuncture. The indices of ovarian reserve function, including basic follicle-stimulating hormone (FSH), estradiol (E2), antral follicle count (AFC), number of retrieved oocytes, number of fertilization and number of high quality embryo, were compared and analyzed before and after acupuncture in the observation group. The differences of outcomes of IVF-ET, including the cycle cancellation rate, implantation rate, the clinical pregnancy rate, were compared between the two groups. Compared before acupuncture, the E2, AFC, number of retrieved oocytes, number of high quality embrgo and number of fertilization were all increased after acupuncture in the observation group (all P< 0. 05). Compared with the control group, levels of the E2, the number of retrieved oocytes, number of fertilization and number of high quality embryo were all increased in the observation group (all P < 0.05). Also, the implantation rate, the clinical pregnancy rate were improved (both P < 0.01) and cycle cancellation rate was reduced (P< 0.01). The "menstrual cycle-based acupuncture therapy" can effectively improve the ovarian reserve function in DOR patients, leading to an improved clinical pregnancy rate of IVF-ET.

Photometric Determination of the Mass Accretion Rates of Pre-main-sequence Stars. V. Recent Star Formation in the 30 Dor Nebula

NASA Astrophysics Data System (ADS)

De Marchi, Guido; Panagia, Nino; Beccari, Giacomo

2017-09-01

We report on the properties of the low-mass stars that recently formed in the central ˜ 2\\buildrel{ \\prime}\\over{.} 7× 2\\buildrel{ \\prime}\\over{.} 7 of 30 Dor, including the R136 cluster. Using the photometric catalog of De Marchi et al., based on observations with the Hubble Space Telescope, and the most recent extinction law for this field, we identify 1035 bona fide pre-main-sequence (PMS) stars showing {{H}}α excess emission at the 4σ level with an {{H}}α equivalent width of 20 Å or more. We find a wide spread in age spanning the range ˜ 0.1{--}50 {Myr}. We also find that the older PMS objects are placed in front of the R136 cluster and are separated from it by a conspicuous amount of absorbing material, indicating that star formation has proceeded from the periphery into the interior of the region. We derive physical parameters for all PMS stars, including masses m, ages t, and mass accretion rates {\\dot{M}}{acc}. To identify reliable correlations between these parameters, which are intertwined, we use a multivariate linear regression fit of the type {log}{\\dot{M}}{acc}=a× {log}t+b× {log}m+c. The values of a and b for 30 Dor are compatible with those found in NGC 346 and NGC 602. We extend the fit to a uniform sample of 1307 PMS stars with 0.5< m/{M}⊙ < 1.5 and t< 16 {Myr} in six star-forming regions in the Large and Small Magellanic Clouds and Milky Way with metallicities in the range of 0.1-1.0 {{Z}}⊙ . We find a=-0.59+/- 0.02 and b=0.78+/- 0.08. The residuals are systematically different between the six regions and reveal a strong correlation with metallicity Z, of the type c=(-3.69+/- 0.02)-(0.30+/- 0.04)× {log}Z/{Z}⊙ . A possible interpretation of this trend is that when the metallicity is higher so is the radiation pressure, and this limits the accretion process, in both its rate and duration. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by AURA, Inc., under NASA contract NAS5-26555.

Trans-American Security: What’s Missing? Strategic Forum, Number 228, September 2007

DTIC Science & Technology

2007-09-01

at abuses of the rights of suspects. The Inter-American Committee against Ter- rorism (Comité Interamericano Contra el Terrorismo [CICTE]) provides a...differences between Argentina and Chile were resolved with the help of Papal mediation. In 1995, the Upper Cenepa war pitted Ecuador against Peru in sudden...dor- Peru (MOMEP).7 MOMEP’s forces were coordinated by a Brazilian general and suc- ceeded first in separating 5,000 intertwined combatant forces

Word Frequency Analysis. MOS: 19F. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

NUMBER(a) Dr. Alexander A. Longo 9. PERFORMING ORGANIZATION NAME AND ADCRESS 10. PROGRAM ELEMENT, PROJECT, TASK AREA 4 WORK UNIT NUMSERS Training ...Developments Institute ATTN: ATTG-DOR Fort Monroe, VA 23651 -- It. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Training Developments Institute IAvJ...JAW 73 1473 EInON OF I NOV 6S IS OBSOLETE SECURITY CLASSIFICATION O F Tl)lS PAGE (ifNe Dote Entered) Contents and General Information 1. The Word

Critical Problems in Very Large Scale Computer Systems

DTIC Science & Technology

1990-09-30

Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Anant Agarwal (617) 253-1448 William J. Dally (617) 253-6043 Srinivas Devadas ...Contrac t No. N00014-87-K-0825. Srinivs Devada (67 5305 F.pproved f r Public rgt (1 236 Ditribution Unlimited (7 5 8 Contents 1 Research Overview 2...d/or Dist Special I 1 Research Overview • The research vehicle for this contract i/the largest possible computerthat ’ can b conceived for the mid to

Evolutionary Processes in Multiple Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eggleton, P P; Kisseleva-Eggleton, L

There are several ways in which triple stars can evolve in somewhat unusual ways. They discuss two situations where Case A Roche-lobe overflow, followed by a merger, can produce anomalous wide binaries such as {gamma} Per; and Kozai cycles in triples with non-parallel orbits, which can produce merged rapidly-rotating stars like AB Dor, and which can also lead to the delayed ejection of one component of a multiple, as may have been observed in T Tau in 1998.

Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated insulin secretion via sympathetic innervation.

PubMed

Tudurí, Eva; Beiroa, Daniel; Stegbauer, Johannes; Fernø, Johan; López, Miguel; Diéguez, Carlos; Nogueiras, Rubén

2016-11-01

Pancreatic insulin-secreting β-cells express opioid receptors, whose activation by opioid peptides modulates hormone secretion. Opioid receptors are also expressed in multiple brain regions including the hypothalamus, where they play a role in feeding behavior and energy homeostasis, but their potential role in central regulation of glucose metabolism is unknown. Here, we investigate whether central opioid receptors participate in the regulation of insulin secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by intracerebroventricular (i.c.v.) injection with specific agonists for the three main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors: activation of KOR and DOR did not alter glucose tolerance, whereas activation of brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin secretion (GSIS), reduced insulin sensitivity, increased the expression of gluconeogenic genes in the liver and, consequently, impaired glucose tolerance. Pharmacological blockade of α2A-adrenergic receptors prevented DAMGO-induced glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit GSIS and to impair glucose tolerance in α2A-adrenoceptor knockout mice, indicating that the effects of central MOR activation on β-cells are mediated via sympathetic innervation. Our results show for the first time a new role of the central opioid system, specifically the MOR, in the regulation of insulin secretion and glucose metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contrasting Susceptibilities to Flavescence Dorée in Vitis vinifera, Rootstocks and Wild Vitis Species

PubMed Central

Eveillard, Sandrine; Jollard, Camille; Labroussaa, Fabien; Khalil, Dima; Perrin, Mireille; Desqué, Delphine; Salar, Pascal; Razan, Frédérique; Hévin, Cyril; Bordenave, Louis; Foissac, Xavier; Masson, Jean E.; Malembic-Maher, Sylvie

2016-01-01

Flavescence dorée (FD) is a quarantine disease of grapevine, involving interactions between the plants, leafhopper vectors, and FD phytoplasma. Characterizing the susceptibility of vine varieties could limit disease propagation. After extensive surveys in vineyards, we showed that Cabernet Sauvignon (CS) is highly susceptible, with a high proportion of symptomatic branches and phytoplasma titers, in contrast to Merlot (M). Localized insect transmissions and grafting showed that phytoplasma circulate in the whole plant in the CS cultivar, but in M they are restricted to the transmission point. Insect-mediated transmission under high confinement mimicking natural conditions confirmed these phenotypes and allowed the classification of 28 Vitis accessions into three distinct categories, according to the percentage of infected plants and their phytoplasma titers. Reduced symptoms, low phytoplasma titers, and low percentages of infected plants were found to be associated in the Vitis vinifera cultivars tested. Interestingly, the low susceptibility of M was observed for one of its parents, i.e., Magdeleine Noire des Charentes. Rootstocks and their Vitis parents, although having high percentages of infected plants and intermediate to high phytoplasma titers, shared a symptomless response. This is troubling, because rootstocks can constitute a silent reservoir of contamination in mother plants or when they grow wild nearby vineyards. Altogether, data suggest distribution of genetic traits within the Vitis genus involved in insect-mediated phytoplasma transmission, multiplication, circulation, and symptom development. PMID:27965681

Hydrogen Sulfide Induced Disruption of Na+ Homeostasis in the Cortex

PubMed Central

Chao, Dongman; He, Xiaozhou; Yang, Yilin; Balboni, Gianfranco; Salvadori, Severo; Kim, Dong H.; Xia, Ying

2012-01-01

Maintenance of ionic balance is essential for neuronal functioning. Hydrogen sulfide (H2S), a known toxic environmental gaseous pollutant, has been recently recognized as a gasotransmitter involved in numerous biological processes and is believed to play an important role in the neural activities under both physiological and pathological conditions. However, it is unclear if it plays any role in maintenance of ionic homeostasis in the brain under physiological/pathophysiological conditions. Here, we report by directly measuring Na+ activity using Na+ selective electrodes in mouse cortical slices that H2S donor sodium hydrosulfide (NaHS) increased Na+ influx in a concentration-dependent manner. This effect could be partially blocked by either Na+ channel blocker or N-methyl-D-aspartate receptor (NMDAR) blocker alone or almost completely abolished by coapplication of both blockers but not by non-NMDAR blocker. These data suggest that increased H2S in pathophysiological conditions, e.g., hypoxia/ischemia, potentially causes a disruption of ionic homeostasis by massive Na+ influx through Na+ channels and NMDARs, thus injuring neural functions. Activation of delta-opioid receptors (DOR), which reduces Na+ currents/influx in normoxia, had no effect on H2S-induced Na+ influx, suggesting that H2S-induced disruption of Na+ homeostasis is resistant to DOR regulation and may play a major role in neuronal injury in pathophysiological conditions, e.g., hypoxia/ischemia. PMID:22474073

Space-Time Point Pattern Analysis of Flavescence Dorée Epidemic in a Grapevine Field: Disease Progression and Recovery

PubMed Central

Maggi, Federico; Bosco, Domenico; Galetto, Luciana; Palmano, Sabrina; Marzachì, Cristina

2017-01-01

Analyses of space-time statistical features of a flavescence dorée (FD) epidemic in Vitis vinifera plants are presented. FD spread was surveyed from 2011 to 2015 in a vineyard of 17,500 m2 surface area in the Piemonte region, Italy; count and position of symptomatic plants were used to test the hypothesis of epidemic Complete Spatial Randomness and isotropicity in the space-time static (year-by-year) point pattern measure. Space-time dynamic (year-to-year) point pattern analyses were applied to newly infected and recovered plants to highlight statistics of FD progression and regression over time. Results highlighted point patterns ranging from disperse (at small scales) to aggregated (at large scales) over the years, suggesting that the FD epidemic is characterized by multiscale properties that may depend on infection incidence, vector population, and flight behavior. Dynamic analyses showed moderate preferential progression and regression along rows. Nearly uniform distributions of direction and negative exponential distributions of distance of newly symptomatic and recovered plants relative to existing symptomatic plants highlighted features of vector mobility similar to Brownian motion. These evidences indicate that space-time epidemics modeling should include environmental setting (e.g., vineyard geometry and topography) to capture anisotropicity as well as statistical features of vector flight behavior, plant recovery and susceptibility, and plant mortality. PMID:28111581

TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters.

PubMed

Xu, Yinfeng; Wan, Wei; Shou, Xin; Huang, Rui; You, Zhiyuan; Shou, Yanhong; Wang, Lingling; Zhou, Tianhua; Liu, Wei

2016-07-02

Cells control their metabolism through modulating the anabolic and catabolic pathways. TP53INP2/DOR (tumor protein p53 inducible nuclear protein 2), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of TP53INP2 in protein synthesis, a major biosynthetic and energy-consuming anabolic process. TP53INP2 localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of TP53INP2 with the ribosomal DNA (rDNA), when exclusion of TP53INP2 from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of TP53INP2 also impaired the association of the POLR1/RNA polymerase I preinitiation complex (PIC) with rDNA. Further, TP53INP2 interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that TP53INP2 promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of TP53INP2 in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.

Mode identification from spectroscopy of gravity-mode pulsators

NASA Astrophysics Data System (ADS)

Pollard, K. R.; Brunsden, E.; Cottrell, P. L.; Davie, M.; Greenwood, A.; Wright, D. J.; De Cat, P.

2014-02-01

The gravity modes present in γ Doradus stars probe the deep stellar interiors and are thus of particular interest in asteroseismology. For the MUSICIAN programme at the University of Canterbury, we obtain extensive high-resolution echelle spectra of γ Dor stars from the Mt John University Observatory in New Zealand. We analyze these to obtain the pulsational frequencies and identify these with the multiple pulsational modes excited in the star. A summary of recent results from our spectroscopic mode-identification programme is given.

Surgical Tooth Implants, Combat and Field.

DTIC Science & Technology

1981-07-15

conventional dental materials,-usually gold. DOR 3 E-oIN OFt NOV 651IS OBSOLETE SECURITY CLASSIFICATION OF THIS PAGE (When Date Entered) SfECUNITY...AND FIELD by Craig R. Hassler, Robert H. Downes, and Larry G. McCoy BACKGROUND In the last several years a new generation of dental implants has evolved...34, Report No. 7, Contract No. DADA17-69-C-9181 (November, 1976). 5. Rasmussen, J. J., Karagianes, M. T., Westerman, R. B., and Marshall, R. D., " Dental

Angiossarcoma mimetizando endoleak tardio pós-reparo endovascular de aneurisma de aorta infrarrenal: relato de caso

PubMed Central

de Almeida, Bruno Lorenção; Caria, Vinicius Pena; Cavalcante, Sthefanie Fauve Andrade; Ventin, Felipe Carvalho; Vieira, Eduardo Augusto Moreira; Darold, Eduardo Mulinari; de Souza, Rodrigo Américo Cunha; Araújo, Edmur Carlos

2017-01-01

Resumo Em todo paciente submetido a reparo endovascular do aneurisma de aorta abdominal (REVA) que se apresente subitamente com quadro de dor abdominal ou sinais de choque, a hipótese de endoleak ou vazamento, com expansão do aneurisma e ruptura deve ser aventada. Apresentamos o caso de um paciente em pós-operatório de REVA que apresentou uma neoplasia de duodeno mimetizando um endoleak. PMID:29930672

Explaining the Progressively Decreasing Scores on Comprehensive Tests of Basic Skills (CTBS) of the School Children of the District of Columbia Public Schools as They Progress from Elementary School into High School.

ERIC Educational Resources Information Center

Bell, Christopher C., Jr.

This report uses motivation theory, social and cognitive development theory, and a construct, Definition of Reality (DOR), to explain why the black students of the District of Columbia Public Schools (DCPS) do less well on the Comprehensive Tests of Basic Skills as they progress from elementary school into high school. The report is divided into 8…

Achalasia and Respiratory Symptoms: Effect of Laparoscopic Heller Myotomy.

PubMed

Andolfi, Ciro; Kavitt, Robert T; Herbella, Fernando A M; Patti, Marco G

2016-09-01

Dysphagia and regurgitation are considered typical symptoms of achalasia. However, there is mounting evidence that some achalasia patients may also experience respiratory symptoms such as cough, wheezing, and hoarseness. The aims of this study were to determine: (1) what percentage of achalasia patients experience respiratory symptoms and (2) the effect of a laparoscopic Heller myotomy and Dor fundoplication on the typical and respiratory symptoms of achalasia. Between May 2008 and December 2015, 165 patients with achalasia were referred for treatment to the Center for Esophageal Diseases of the University of Chicago. Patients had preoperatively a barium swallow, endoscopy, and esophageal manometry. All patients underwent a Heller myotomy and Dor fundoplication. Based on the presence of respiratory symptoms, patients were divided into two groups: group A, 98 patients (59%) without respiratory symptoms and group B, 67 patients (41%) with respiratory symptoms. The preoperative Eckardt score was similar in the two groups (6.5 ± 2.1 versus 6.4 ± 2.0). The mean esophageal diameter was 27.7 ± 10.8 mm in group A and 42.6 ± 20.1 mm in group B (P < .05). The operation consisted of a myotomy that extended for 5 cm on the esophagus and 2.5 cm onto the gastric wall. At a median postoperative follow-up of 17 months, the Eckardt score improved significantly and similarly in the two groups (0.3 ± 0.8 versus 0.3 ± 1.0). Respiratory symptoms improved or resolved in 62 patients (92.5%). The results of this study showed that: (1) respiratory symptoms were present in 41% of patients; (2) patients with respiratory symptoms had a more dilated esophagus; and (3) surgical treatment resolved or improved respiratory symptoms in 92.5% of patients. This study underlines the importance of investigating the presence of respiratory symptoms along with the more common symptoms of achalasia and of early treatment before lung damage occurs.

Data processing of qualitative results from an interlaboratory comparison for the detection of “Flavescence dorée” phytoplasma: How the use of statistics can improve the reliability of the method validation process in plant pathology

PubMed Central

Renaudin, Isabelle; Poliakoff, Françoise

2017-01-01

A working group established in the framework of the EUPHRESCO European collaborative project aimed to compare and validate diagnostic protocols for the detection of “Flavescence dorée” (FD) phytoplasma in grapevines. Seven molecular protocols were compared in an interlaboratory test performance study where each laboratory had to analyze the same panel of samples consisting of DNA extracts prepared by the organizing laboratory. The tested molecular methods consisted of universal and group-specific real-time and end-point nested PCR tests. Different statistical approaches were applied to this collaborative study. Firstly, there was the standard statistical approach consisting in analyzing samples which are known to be positive and samples which are known to be negative and reporting the proportion of false-positive and false-negative results to respectively calculate diagnostic specificity and sensitivity. This approach was supplemented by the calculation of repeatability and reproducibility for qualitative methods based on the notions of accordance and concordance. Other new approaches were also implemented, based, on the one hand, on the probability of detection model, and, on the other hand, on Bayes’ theorem. These various statistical approaches are complementary and give consistent results. Their combination, and in particular, the introduction of new statistical approaches give overall information on the performance and limitations of the different methods, and are particularly useful for selecting the most appropriate detection scheme with regards to the prevalence of the pathogen. Three real-time PCR protocols (methods M4, M5 and M6 respectively developed by Hren (2007), Pelletier (2009) and under patent oligonucleotides) achieved the highest levels of performance for FD phytoplasma detection. This paper also addresses the issue of indeterminate results and the identification of outlier results. The statistical tools presented in this paper and their combination can be applied to many other studies concerning plant pathogens and other disciplines that use qualitative detection methods. PMID:28384335

Data processing of qualitative results from an interlaboratory comparison for the detection of "Flavescence dorée" phytoplasma: How the use of statistics can improve the reliability of the method validation process in plant pathology.

PubMed

Chabirand, Aude; Loiseau, Marianne; Renaudin, Isabelle; Poliakoff, Françoise

2017-01-01

A working group established in the framework of the EUPHRESCO European collaborative project aimed to compare and validate diagnostic protocols for the detection of "Flavescence dorée" (FD) phytoplasma in grapevines. Seven molecular protocols were compared in an interlaboratory test performance study where each laboratory had to analyze the same panel of samples consisting of DNA extracts prepared by the organizing laboratory. The tested molecular methods consisted of universal and group-specific real-time and end-point nested PCR tests. Different statistical approaches were applied to this collaborative study. Firstly, there was the standard statistical approach consisting in analyzing samples which are known to be positive and samples which are known to be negative and reporting the proportion of false-positive and false-negative results to respectively calculate diagnostic specificity and sensitivity. This approach was supplemented by the calculation of repeatability and reproducibility for qualitative methods based on the notions of accordance and concordance. Other new approaches were also implemented, based, on the one hand, on the probability of detection model, and, on the other hand, on Bayes' theorem. These various statistical approaches are complementary and give consistent results. Their combination, and in particular, the introduction of new statistical approaches give overall information on the performance and limitations of the different methods, and are particularly useful for selecting the most appropriate detection scheme with regards to the prevalence of the pathogen. Three real-time PCR protocols (methods M4, M5 and M6 respectively developed by Hren (2007), Pelletier (2009) and under patent oligonucleotides) achieved the highest levels of performance for FD phytoplasma detection. This paper also addresses the issue of indeterminate results and the identification of outlier results. The statistical tools presented in this paper and their combination can be applied to many other studies concerning plant pathogens and other disciplines that use qualitative detection methods.

Gene-Based Single Nucleotide Polymorphism Markers for Genetic and Association Mapping in Common Bean

PubMed Central

2012-01-01

Background In common bean, expressed sequence tags (ESTs) are an underestimated source of gene-based markers such as insertion-deletions (Indels) or single-nucleotide polymorphisms (SNPs). However, due to the nature of these conserved sequences, detection of markers is difficult and portrays low levels of polymorphism. Therefore, development of intron-spanning EST-SNP markers can be a valuable resource for genetic experiments such as genetic mapping and association studies. Results In this study, a total of 313 new gene-based markers were developed at target genes. Intronic variation was deeply explored in order to capture more polymorphism. Introns were putatively identified after comparing the common bean ESTs with the soybean genome, and the primers were designed over intron-flanking regions. The intronic regions were evaluated for parental polymorphisms using the single strand conformational polymorphism (SSCP) technique and Sequenom MassARRAY system. A total of 53 new marker loci were placed on an integrated molecular map in the DOR364 × G19833 recombinant inbred line (RIL) population. The new linkage map was used to build a consensus map, merging the linkage maps of the BAT93 × JALO EEP558 and DOR364 × BAT477 populations. A total of 1,060 markers were mapped, with a total map length of 2,041 cM across 11 linkage groups. As a second application of the generated resource, a diversity panel with 93 genotypes was evaluated with 173 SNP markers using the MassARRAY-platform and KASPar technology. These results were coupled with previous SSR evaluations and drought tolerance assays carried out on the same individuals. This agglomerative dataset was examined, in order to discover marker-trait associations, using general linear model (GLM) and mixed linear model (MLM). Some significant associations with yield components were identified, and were consistent with previous findings. Conclusions In short, this study illustrates the power of intron-based markers for linkage and association mapping in common bean. The utility of these markers is discussed in relation with the usefulness of microsatellites, the molecular markers by excellence in this crop. PMID:22734675

30 Doradus: The Low-Mass Stars

NASA Astrophysics Data System (ADS)

Zinnecker, H.; Brandl, B.; Brandner, W.; Moneti, A.; Hunter, D.

We have obtained HST/NICMOS H-band images of the central 1'x1' field around the R136 starburst cluster in the 30 Doradus HII region, in an attempt to reveal the presence (or absence) of a low-mass stellar population (M < 1 Mo). We will discuss the fascinating prospect of 30 Dor/R136 being a proto-globular cluster and a template starburst unit. At the time of writing, we are still working to determine which method and photometry package is best suited to our 0.15" NICMOS images, which are characterised by extreme crowding in the cluster center and a peculiar and slightly undersampled NICMOS PSF. The main difficulty with the PSF is identifying the many "dots" that appear outside the Airy ring as PSF features and not as faint stars. Prelimininary analysis suggests that the H-band luminosity function rises at least until H = 20 (2 Mo). We have detected numerous stars with 20.0 < H < 22.5 (the latter corresponding to 0.4 Mo) beyond about 7" from the cluster centre, but we have not yet determined the completeness in that magnitude range, and we are not yet in a position to make a statement about the shape of the H-band luminosity function there. We have combined our infrared data with the optical WFPC2 images of Hunter et al. (1995) to produce a VIH 3-colour image of the central 30" x 30" area. The result clearly shows unexpected patches of extinction, with one patch only about 5" from the cluster core.

Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

PubMed

Boucret, L; Bris, C; Seegers, V; Goudenège, D; Desquiret-Dumas, V; Domin-Bernhard, M; Ferré-L'Hotellier, V; Bouet, P E; Descamps, P; Reynier, P; Procaccio, V; May-Panloup, P

2017-10-01

Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being significantly different (respectively 0.321, SD = 0.547 and 1.075, SD = 1.158) (P < 0.0001). Variants with a potential functional consequence were also overrepresented in CCs compared with oocytes (P = 0.0019). N/A. Limitations may be due to the use of immature oocytes discarded during the assisted reproductive technology procedure, the small size of the sample, and the high-throughput sequencing technology that might not have detected heteroplasmy levels lower than 2%. The alteration of mtDNA integrity in oocytes during ovarian ageing is a recurring question to which our pilot study suggests a reassuring answer. This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centers, INSERM and the CNRS. There are nocompeting interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Dispersion of Louisiana crude oil in salt water environment by Corexit 9500A in the presence of natural coastal materials

NASA Astrophysics Data System (ADS)

Tansel, Berrin; Lee, Mengshan; Berbakov, Jillian; Tansel, Derya Z.; Koklonis, Urpiana

2014-04-01

Effectiveness of Corexit 9500A for dispersing Louisiana crude oil was evaluated in salt water solutions containing natural materials in relation to salinity and dispersant-to-oil ratio (DOR). Experimental results showed that both salinity and DOR had significant effects on dispersion of Louisiana crude oil in the presence of different natural materials. The natural materials added to the salt water solutions included sea sand (South Beach, Miami, Florida), red mangrove leaves (Rhizophora mangle), seaweed (Sargassum natans), and sea grass (Halodule wrightii). Dispersant effectiveness (amount of oil dispersed into the water) was reduced significantly with increasing salinity with the minimum effectiveness observed in the salinity range between 30 and 50 ppt in all aqueous samples containing natural materials. When significant amounts of floating oil were present, the partially submerged natural materials enhanced the transfer of oil into the water column, which improved the dispersion effectiveness. However, dispersant effectiveness was significantly reduced when the amount of floating oil was relatively small and could not be released back to the water column. Surface tension may not be an adequate parameter for monitoring the effectiveness of dispersants in salt water environment. When distilled water was used (i.e., zero salinity), surface tension was significantly reduced with increasing dispersant concentration. However, there was no clear trend in the surface tension of the salt water solutions (17-51 ppt) containing crude oil and natural materials with increasing dispersant concentration.

On the chemical homogeneity of the 30 Doradus H II region and a local enrichment by Wolf-Rayet stars

NASA Technical Reports Server (NTRS)

Rosa, Michael; Mathis, John S.

1987-01-01

Emission-line strengths have been obtained at 10 positions in the outer regions of the 30 Dor nebula and analyzed in the standard way. There are two major results: (1) the elemental abundances for nine of the outer regions are remarkably similar to those previously measured in the core. This result implies the spectra of the cores and halos of giant H II regions (subject to the different ionizing radiation fields) are analyzed correctly by the standard methods. Hence measurements of extragalactic H II regions with poor spatial resolution correctly represent the abundances of the whole nebula. The O/H ratio in 30 Dor, by number, is 0.30 solar. The Ne/O, S/O, Ar/O, and Cl/O are close to solar. The gas-phase Fe/O is about 0.2 solar, which probably implies that most of the iron is within solid grains. The He/H is 0.0810 as shown by each of the three strong lines available. One region is cool and rich in helium and all other heavy elements except nitrogen. The spectrum of the region does not resemble that of a supernova remnant in that the forbidden O I and S II lines are not nearly strong enough. The abundances can be explained fairly well as over 10 solar masses of H-poor material ejected during the evolution of a single massive (about 80 solar masses) star during its late O-star and Wolf-Rayet phases.

Mucosal perforation during laparoscopic surgery for achalasia: impact of preoperative pneumatic balloon dilation.

PubMed

Souma, Yoshihito; Nakajima, Kiyokazu; Taniguchi, Eiji; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Miyazaki, Yasuhiro; Makino, Tomoki; Hamada, Tetsuhiro; Yasuda, Jun; Yumiba, Takeyoshi; Ohashi, Shuichi; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-03-01

Controversy remains whether preoperative pneumatic balloon dilation (PBD) influences the surgical outcome of laparoscopic esophagocardiomyotomy in patients with esophageal achalasia. The aim of this study was to evaluate whether preoperative PBD represents a risk factor for surgical complications and affects the symptomatic and/or functional outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD). A retrospective chart review was conducted on a prospectively compiled surgical database of 103 consecutive patients with esophageal achalasia who underwent LHD from November 1994 to September 2014. The following data were compared between the patients with preoperative PBD (PBD group; n = 26) and without PBD (non-PBD group; n = 77): (1) patients' demographics: age, gender, body mass index, duration of symptoms, maximum transverse diameter of esophagus; (2) operative findings: operating time, blood loss, intraoperative complications; (3) postoperative course: complications, clinical symptoms, postoperative treatment; and (4) esophageal functional tests: preoperative and postoperative manometric data and postoperative profile of 24-h esophageal pH monitoring. (1) No significant differences were observed in the patients' demographics. (2) Operative findings were similar between the two groups; however, the incidence of mucosal perforation was significantly higher in the PBD group (n = 8; 30.7 %) compared to the non-PBD group (n = 6; 7.7 %) (p = 0.005). (3) Postoperative complications were not encountered in either group. The differences were not significant for postoperative clinical symptoms, the incidence of gastroesophageal reflux disease, or necessity of postoperative treatments. (4) Lower esophageal sphincter pressure was effectively reduced in both groups, and no differences were observed in manometric data or 24-h pH monitoring profiles between the two groups. Multivariate logistic regression analysis showed that preoperative PBD and the maximum transverse diameter of esophagus were significantly associated with intraoperative mucosal perforation. Although postoperative outcomes were not affected, additional caution is recommended in identifying intraoperative mucosal perforation in patients with preoperative PBD when performing LHD.

Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease.

PubMed

Sokol, Harry; Beaugerie, Laurent; Maynadié, Marc; Laharie, David; Dupas, Jean-Louis; Flourié, Bernard; Lerebours, Eric; Peyrin-Biroulet, Laurent; Allez, Matthieu; Simon, Tabassome; Carrat, Fabrice; Brousse, Nicole

2012-11-01

It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). Patients with IBD have an increased risk of developing PILD. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Search with UVES and X-Shooter for signatures of the low-mass secondary in the post common-envelope binary AA Doradus

NASA Astrophysics Data System (ADS)

Hoyer, D.; Rauch, T.; Werner, K.; Hauschildt, P. H.; Kruk, J. W.

2015-06-01

Context. AA Dor is a close, totally eclipsing, post common-envelope binary with an sdOB-type primary star and an extremely low-mass secondary star, located close to the mass limit of stable central hydrogen burning. Within error limits, it may either be a brown dwarf or a late M-type dwarf. Aims: We aim to extract the secondary's contribution to the phase-dependent composite spectra. The spectrum and identified lines of the secondary decide on its nature. Methods: In January 2014, we measured the phase-dependent spectrum of AA Dor with X-Shooter over one complete orbital period. Since the secondary's rotation is presumable synchronized with the orbital period, its surface strictly divides into a day and night side. Therefore, we may obtain the spectrum of its cool side during its transit and of its hot, irradiated side close to its occultation. We developed the Virtual Observatory (VO) tool TLISA to search for weak lines of a faint companion in a binary system. We successfully applied it to the observations of AA Dor. Results: We identified 53 spectral lines of the secondary in the ultraviolet-blue, visual, and near-infrared X-Shooter spectra that are strongest close to its occultation. We identified 57 (20 additional) lines in available Ultraviolet and Visual Echelle Spectrograph (UVES) spectra from 2001. The lines are mostly from C ii-iii and O ii, typical for a low-mass star that is irradiated and heated by the primary. We verified the orbital period of P = 22 597.033201 ± 0.00007 s and determined the orbital velocity K_sec = 232.9+16.6-6.5 km s-1 of the secondary. The mass of the secondary is M_sec = 0.081+0.018-0.010 M_⊙ and, hence, it is not possible to reliably determine a brown dwarf or an M-type dwarf nature. Conclusions: Although we identified many emission lines of the secondary's irradiated surface, the resolution and signal-to-noise ratio of our UVES and X-Shooter spectra are not good enough to extract a good spectrum of the secondary's nonirradiated hemisphere. Based on observations collected at the European Southern Observatory, Chile, programs 066.D-1800 and 092.C-0692.Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer.Figures 2-5, 9, and Appendices are available in electronic form at http://www.aanda.org

Experimental study of oil plume stability: Parametric dependences and optimization.

PubMed

Li, Haoshuai; Shen, Tiantian; Bao, Mutai

2016-10-15

Oil plume is known to interact with density layer in spilled oil. Previous studies mainly focused on tracking oil plumes and predicting their impact on marine environment. Here, simulated experiments are presented that investigated the conditions inducing the formation of oil plume, focusing especially on the effects of oil/water volume ratio, oil/dispersant volume rate, ambient stratification and optimal conditions of oil plume on determining whether a plume will trap or escape. Scenario simulations showed that OWR influences the residence time most, dispersants dosage comes second and salinity least. The optimum residence time starts from 2387s, occurred at approximately condition (OWR, 0.1, DOR, 25.53% and salinity, 32.38). No change in the relative distribution under the more scale tank was observed, indicating these provide the time evolution of the oil plumes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system.

PubMed

Springer, Sandra A; Brown, Shan-Estelle; Di Paola, Angela; Altice, Frederick L

2015-12-01

The acceptability of and retention on extended-release naltrexone (XR-NTX), an FDA-approved medication for the treatment of alcohol and opioid use disorders, among persons living with HIV disease (PLH) under criminal justice setting (CJS) supervision has not been evaluated to date. Two double-blind placebo-controlled randomized trials of XR-NTX for inmates with HIV disease transitioning to the community with (1) alcohol use disorders (AUDs) or (2) opioid use disorders, are underway. Reasons for not accepting XR-NTX and an evaluation of differences in demographic features between those who were retained on study drug and those who did not return for their second injection post-release are discussed. 70% of eligible persons consented to participate; almost 90% received their first injection; and almost 60% returned for their first injection after release. Variables found to be associated (p<0.10) with returning for the second injection included: not meeting criteria for hazardous drinking (p=0.035; OR 0.424 (CI 0.191-0.941)); being prescribed antiretroviral therapy (p=0.068; OR 2.170 (CI 0.943-4.992)); expressing experiencing serious depression 30 days prior to incarceration (p=0.068; OR 1.889 (CI 0.955-3.737)); not having a positive cocaine urine screen on the day of release (DOR) (p=0.011; OR 0.258 (CI 0.091-0.729)); and not meeting criteria for an AUD plus any substance use disorder (p=0.068; OR 0.521 (CI 0.259-1.048)). Only positive cocaine urine test on DOR was statistically significant after multivariate regression analyses (p=0.005; OR 0.207 (CI 0.068-0.623)). CJS based XR-NTX programs are highly acceptable among PLH, however retention on XR-NTX after release is negatively impacted by relapse to cocaine use. Published by Elsevier Ireland Ltd.

Pneumonia Severity Assessment Tools for Predicting Mortality in Patients with Healthcare-Associated Pneumonia: A Systematic Review and Meta-Analysis.

PubMed

Noguchi, Shingo; Yatera, Kazuhiro; Kawanami, Toshinori; Fujino, Yoshihisa; Moro, Hiroshi; Aoki, Nobumasa; Komiya, Kosaku; Kadota, Jun-Ichi; Shime, Nobuaki; Tsukada, Hiroki; Kohno, Shigeru; Mukae, Hiroshi

2017-01-01

In contrast to community-acquired pneumonia (CAP), no specific severity assessment tools have been developed for healthcare-associated pneumonia (HCAP) in clinical practice. In this review, we assessed the clinical significance of severity assessment tools for HCAP. We identified related articles from the PubMed database. The eligibility criteria were original research articles evaluating severity scoring tools and reporting the outcomes of mortality in patients with HCAP. Eight articles were included in the meta-analysis. The PORT score and CURB-65 were evaluated in 7 and 8 studies, respectively. Using cutoff values of ≥IV and V for the PORT score, the diagnostic odds ratios (DORs) were 5.28 (2.49-11.17) and 3.76 (2.88-4.92), respectively, and the areas under the curve (AUCs) were 0.68 (0.64-0.72) and 0.71 (0.67-0.75), respectively. Conversely, the AUCs for ≥IV and V were 0.71 (0.67-0.76) and 0.74 (0.70-0.78), respectively, when applied only to nonimmunocompromised patients. In contrast, when using cutoff values of ≥2 and ≥3 for CURB-65, the DORs were 3.35 (2.26-4.97) and 2.65 (2.05-3.43), respectively, and the AUCs were 0.65 (0.61-0.69) and 0.66 (0.62-0.70), respectively. Conversely, the AUCs for ≥2 and ≥3 were 0.65 (0.61-0.69) and 0.68 (0.64-0.72), respectively, when applied only to nonimmunocompromised patients. The PORT score and CURB-65 do not have substantial power compared with the tools for CAP patients, although the PORT score is more useful than CURB-65 for predicting mortality in HCAP patients. According to our results, however, these tools, especially the PORT score, can be more useful when limited to nonimmunocompromised patients. © 2017 S. Karger AG, Basel.

Biostratigraphic data for the Cretaceous marine sediments in the USGS-St. George no. 1 core (DOR-211), Dorchester County, South Carolina

USGS Publications Warehouse

Self-Trail, Jean M.; Gohn, Gregory S.

1997-01-01

The USGS-St. George corehole was drilled for the U.S. Geological Survey (USGS) by a commercial drilling company during 1982. The corehole is located within the Coastal Plain Province in northern Dorchester County, South Carolina, about three miles southeast of the town of St. George near the village of Byrd (fig. 1). Coordinates for the corehole are 33o09'25'N latitude and 80o31'18'W longitude; ground elevation at the site is +78 feet (Reid and others, 1986). The St. George corehole is designated as USGS drill hole DOR-211. The St. George corehole was drilled to a total depth of 2,067 ft. The hole was cored continuously with generally good recovery from 300 ft to its total depth. Spot cores were taken at selected intervals between the top of the hole and a depth of 300 ft (50-55 ft, 100-110 ft, 150-165 ft, 200-205 ft, and 250-255 ft); however, recovery was poor in most of these intervals. The St. George core currently is stored at the USGS National Center, Reston, VA (March, 1997). The St. George corehole bottomed in basalt of probable early Mesozoic age beneath an Upper Cretaceous and Cenozoic sedi-mentary section. Reid and others (1986) placed the top of basalt saprolite at 1,962 ft in the hole. Our examination of the geophysical logs and original core descriptions suggests that the top of the saprolite is higher in the hole, at about 1,939 ft. The Cretaceous-Tertiary boundary was placed at or near 550 ft in the core by Reid and others (1986) and by Habib and Miller (1989). In this report, we provide paleontologic data for marine sediments in the upper part of the Upper Cretaceous section in the St. George core. Biostratigraphic and paleoenvironmental data and interpretations based on the study of calcareous nannofossils and ostracodes from the Cretaceous section are discussed.

Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

PubMed

Ou, Sai-Hong Ignatius; Ahn, Jin Seok; De Petris, Luigi; Govindan, Ramaswamy; Yang, James Chih-Hsin; Hughes, Brett; Lena, Hervé; Moro-Sibilot, Denis; Bearz, Alessandra; Ramirez, Santiago Viteri; Mekhail, Tarek; Spira, Alexander; Bordogna, Walter; Balas, Bogdana; Morcos, Peter N; Monnet, Annabelle; Zeaiter, Ali; Kim, Dong-Wan

2016-03-01

Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50% (95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases. © 2015 by American Society of Clinical Oncology.

National Program for Inspection of Non-Federal Dams. Muddy cove Pond Dam (MA 00793) Taunton River Basin, Dighton, Massachusetts. Phase I Inspection Report.

DTIC Science & Technology

1979-11-01

Oinerra bra msoe Frew T..Tretion................. at. C*rpw ftA Tel Jh 5*1tut __ _ 3 ea at. a the atypon sto TV. T’. CA tya. rs (if mw) e.g...X APPENDIX D)-7 civ .~ CUiMfl co1mI dor FW05 JSO30621 PAGE POJECT M z൒ DATE CHECKED~ ± GLMI--t ATE OSAIL fMD = dopvfCHCDBY1F -A4 *y ourvsrawm_,F -W

Word Frequency Analysis. MOS: 55B. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

AO-AX17 176 ARMY TRAINING DEVELOPMENT$ INS? FORT MONROE VA F/G 5/9WORD FREQUENCY ANALYSIS. NMIS 55. SKILL LEVELS I 2.(U~) MAY SI A A LONSO...UNCLASSIFIED MOS-558 NLSill AD A1171 7 6 HEADQUARTERS DATA CONTROL NNE UNITED STATES ARMY TRAINING AND DOCTRINE COMMAND FORT MONROE, VIRGINIA 23651 . 1w 0 a~t L...O.OANIZATION HA.ME AND ADDRESS 0. PROGRAM ELEMENT. P’IUJECT. TASKAREA At WO K UNIT HM;lEHS Training Developments Institute R ATTN: ATTG-DOR Fort Monroe. VA 71651

Dakar Senegal Limited Surface Observations Climatic Summary (LISOCS). Parts A, C-F.

DTIC Science & Technology

1985-09-01

REING S O NOWO IS N-OUS TOR A D OR RAIN & R A D/OR HAIL 08 WITH FOG AND OR SLOWI G AND OR WITH EST NO OFLO T 5ST-AD TO O DRIZZLE DRIZZ SLEET E . HAZE 0...7.259 7. OURS TOTAL OBS .44 3419 35? 347 371 2 67 371 b3 S 6 3589 333 529 42 USAF ETAC ’om’ 0-69-5 (OL A)oCT 7 o¢1" .. CL ] IA I C L2 N T MEANS AND

Tardigrades from Taiwan, with the description of a new species of Doryphoribius (Tardigrada, Hypsibiidae).

PubMed

Li, Xiaochen; Li, Hongqun

2008-05-01

A total of eleven species of tardigrades from Taiwan are reported in this article. They belong to two classes, three orders, four families, and ten genera. Ten species are new records for Taiwan and one is new to science. Doryphoribius taiwanus sp. nov. is similar to Dor. mariae , but differs from it by larger body size, by conspicuous tubercles on the lateral side and dorsal sides of the body, by lacking gibbosities and undulations, by a narrower buccal tube, and by longer claws.

Use of Electronic Tag Data and Associated Analytical Tools to Identify and Predict Habitat Utilization of Marine Mammals

DTIC Science & Technology

2010-09-30

the fractal landscape method to determine regions of area restricted search (ARS) (Jonsen et al. 2003; Jonsen et al. 2006; Tremblay et al. 2007 ). Next...Information for Society (Vol. 2), Venice, Italy, 21-25 September 2009, Hall, J., Harrison, D.E. & Stammer , D., Eds., ESA Publication WPP-306. O’Dor...D.E. & Stammer , D., Eds., ESA Publication WPP-306. Žydelis, R., Lewison, R.L., Shaffer, S. A., Moore, J.E., Boustany, A.M., Roberts, J.J., Sims

Comparison of the accuracy of Hybrid Capture II and polymerase chain reaction in detecting clinically important cervical dysplasia: a systematic review and meta-analysis

PubMed Central

Luu, Hung N; Dahlstrom, Kristina R; Mullen, Patricia Dolan; VonVille, Helena M; Scheurer, Michael E

2013-01-01

The effectiveness of screening programs for cervical cancer has benefited from the inclusion of Human papillomavirus (HPV) DNA assays; which assay to choose, however, is not clear based on previous reviews. Our review addressed test accuracy of Hybrid Capture II (HCII) and polymerase chain reaction (PCR) assays based on studies with stronger designs and with more clinically relevant outcomes. We searched OvidMedline, PubMed, and the Cochrane Library for English language studies comparing both tests, published 1985–2012, with cervical dysplasia defined by the Bethesda classification. Meta-analysis provided pooled sensitivity, specificity, and 95% confidence intervals (CIs); meta-regression identified sources of heterogeneity. From 29 reports, we found that the pooled sensitivity and specificity to detect high-grade squamous intraepithelial lesion (HSIL) was higher for HCII than PCR (0.89 [CI: 0.89–0.90] and 0.85 [CI: 0.84–0.86] vs. 0.73 [CI: 0.73–0.74] and 0.62 [CI: 0.62–0.64]). Both assays had higher accuracy to detect cervical dysplasia in Europe than in Asia-Pacific or North America (diagnostic odd ratio – dOR = 4.08 [CI: 1.39–11.91] and 4.56 [CI: 1.86–11.17] for HCII vs. 2.66 [CI: 1.16–6.53] and 3.78 [CI: 1.50–9.51] for PCR) and accuracy to detect HSIL than atypical squamous cells of undetermined significance (ASCUS)/ low-grade squamous intraepithelial lesion (LSIL) (HCII-dOR = 9.04 [CI: 4.12–19.86] and PCR-dOR = 5.60 [CI: 2.87–10.94]). For HCII, using histology as a gold standard results in higher accuracy than using cytology (dOR = 2.87 [CI: 1.31–6.29]). Based on higher test accuracy, our results support the use of HCII in cervical cancer screening programs. The role of HPV type distribution should be explored to determine the worldwide comparability of HPV test accuracy. PMID:23930214

Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis.

PubMed

Jia, Hui-Miao; Huang, Li-Feng; Zheng, Yue; Li, Wen-Xiong

2017-03-25

Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G 1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies. Literature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses. A total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79-0.87, heterogeneity I 2  = 68.8%) and 0.55 (95% CI 0.52-0.57, I 2  = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87-2.99, I 2  = 82.6%), 0.30 (95% CI 0.21-0.41, I 2  = 43.4%), and 9.92 (95% CI 6.09-16.18, I 2  = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity. On the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI. PROSPERO registration number: CRD42016051186 . Registered on 10 November 2016.

Distinct Mu, Delta, and Kappa Opioid Receptor Mechanisms Underlie Low Sociability and Depressive-Like Behaviors During Heroin Abstinence

PubMed Central

Lutz, Pierre-Eric; Ayranci, Gulebru; Chu-Sin-Chung, Paul; Matifas, Audrey; Koebel, Pascale; Filliol, Dominique; Befort, Katia; Ouagazzal, Abdel-Mouttalib; Kieffer, Brigitte L

2014-01-01

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood. Here we establish a mouse model of protracted abstinence to heroin, a major abused opiate, where both emotional and working memory deficits unfold. We show that delta and kappa opioid receptor (DOR and KOR, respectively) knockout mice develop either stronger or reduced emotional disruption during heroin abstinence, establishing DOR and KOR activities as protective and vulnerability factors, respectively, that regulate the severity of abstinence. Further, we found that chronic treatment with the antidepressant drug fluoxetine prevents emergence of low sociability, with no impact on the working memory deficit, implicating serotonergic mechanisms predominantly in emotional aspects of abstinence symptoms. Finally, targeting the main serotonergic brain structure, we show that gene knockout of mu opioid receptors (MORs) in the dorsal raphe nucleus (DRN) before heroin exposure abolishes the development of social withdrawal. This is the first result demonstrating that intermittent chronic MOR activation at the level of DRN represents an essential mechanism contributing to low sociability during protracted heroin abstinence. Altogether, our findings reveal crucial and distinct roles for all three opioid receptors in the development of emotional alterations that follow a history of heroin exposure and open the way towards understanding opioid system-mediated serotonin homeostasis in heroin abuse. PMID:24874714

Theory and evidence of global Rossby waves in upper main-sequence stars: r-mode oscillations in many Kepler stars

NASA Astrophysics Data System (ADS)

Saio, Hideyuki; Kurtz, Donald W.; Murphy, Simon J.; Antoci, Victoria L.; Lee, Umin

2018-02-01

Asteroseismic inference from pressure modes (p modes) and buoyancy, or gravity, modes (g modes) is ubiquitous for stars across the Hertzsprung-Russell diagram. Until now, however, discussion of r modes (global Rossby waves) has been rare. Here we derive the expected frequency ranges of r modes in the observational frame by considering the visibility of these modes. We find that the frequencies of r modes of azimuthal order m appear as groups at slightly lower frequency than m times the rotation frequency. Comparing the visibility curves for r modes with Fourier amplitude spectra of Kepler light curves of upper main-sequence B, A, and F stars, we find that r modes are present in many γ Dor stars (as first discovered by Van Reeth et al.), spotted stars, and so-called heartbeat stars, which are highly eccentric binary stars. We also find a signature of r modes in a frequently bursting Be star observed by Kepler. In the amplitude spectra of moderately to rapidly rotating γ Dor stars, r-mode frequency groups appear at lower frequency than prograde g-mode frequency groups, while in the amplitude spectra of spotted early A to B stars, groups of symmetric (with respect to the equator) r-mode frequencies appear just below the frequency of a structured peak that we suggest represents an approximate stellar rotation rate. In many heartbeat stars, a group of frequencies can be fitted with symmetric m = 1 r modes, which can be used to obtain rotation frequencies of these stars.

Aquatic toxicity of four veterinary drugs commonly applied in fish farming and animal husbandry.

PubMed

Kołodziejska, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Steudte, Stephanie; Kumirska, Jolanta; Stepnowski, Piotr; Stolte, Stefan

2013-08-01

Doramectin (DOR), metronidazole (MET), florfenicol (FLO), and oxytetracycline (OXT) are among the most widely used veterinary drugs in animal husbandry or in aquaculture. Contamination of the environment by these pharmaceuticals has given cause for concern in recent years. Even though their toxicity has been thoroughly analyzed, knowledge of their ecotoxicity is still limited. We investigated their aquatic toxicity using tests with marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustaceans (Daphnia magna). All the ecotoxicological tests were supported by chemical analyses to confirm the exposure concentrations of the pharmaceuticals used in the toxicity experiments, since deviations from the nominal concentration can result in underestimation of biological effects. It was found that OXT and FLO have a stronger adverse effect on duckweed (EC50=3.26 and 2.96mgL(-1) respectively) and green algae (EC50=40.4 and 18.0mgL(-1)) than on bacteria (EC50=108 and 29.4mgL(-1)) and crustaceans (EC50=114 and 337mgL(-1)), whereas MET did not exhibit any adverse effect in the tested concentration range. For DOR a very low EC50 of 6.37×10(-5)mgL(-1) towards D. magna was determined, which is five orders of magnitude lower than values known for the toxic reference compound K2Cr2O7. Our data show the strong influence of certain veterinary drugs on aquatic organisms and contribute to a sound assessment of the environmental hazards posed by commonly used pharmaceuticals. Copyright © 2013. Published by Elsevier Ltd.

[Surgical treatment of achalasia - endoscopic or laparoscopic? : Proposal for a tailored approach].

PubMed

Rahden, B H A von; Filser, J; Al-Nasser, M; Germer, C-T

2017-03-01

Primary idiopathic achalasia is the most common form of the rare esophageal motility disorders. A curative therapy which restores the normal motility does not exist; however, the therapeutic principle of cardiomyotomy according to Ernst Heller leads to excellent symptom control in the majority of cases. The established standard approach is Heller myotomy through the laparoscopic route (LHM), combined with Dor anterior fundoplication for reflux prophylaxis/therapy. At least four meta-analyses of randomized controlled trials (RCTs) have demonstrated superiority of LHM over pneumatic dilation (PD); therefore, LHM should be used as first line therapy (without prior PD) in all operable patients. Peroral endoscopic myotomy (POEM) is a new alternative approach, which enables Heller myotomy to be performed though the endoscopic submucosal route. The POEM procedure has a low complication rate and also leads to good control of dysphagia but reflux rates can possibly be slightly higher (20-30%). Long-term results of POEM are still scarce and the results of the prospective randomized multicenter trial POEM vs. LHM are not yet available; however, POEM seems to be the preferred treatment option for certain indications. Within the framework of the tailored approach for achalasia management of POEM vs. LHM established in Würzburg, we recommend long-segment POEM for patients with type III achalasia (spasmodic) and other hypercontractile motility disorders and potentially type II achalasia (panesophageal compression) with chest pain as the lead symptom, whereas LHM can also be selected for type I. For sigmoid achalasia, especially with siphon-like transformation of the esophagogastric junction, simultaneous hiatal hernia and epiphrenic diverticula, LHM is still the preferred approach. The choice of the procedure for revisional surgery in case of recurrent dysphagia depends on the suspected mechanism (morphological vs. functional/neuromotor).

The VLT-FLAMES Tarantula Survey. XII. Rotational velocities of the single O-type stars

NASA Astrophysics Data System (ADS)

Ramírez-Agudelo, O. H.; Simón-Díaz, S.; Sana, H.; de Koter, A.; Sabín-Sanjulían, C.; de Mink, S. E.; Dufton, P. L.; Gräfener, G.; Evans, C. J.; Herrero, A.; Langer, N.; Lennon, D. J.; Maíz Apellániz, J.; Markova, N.; Najarro, F.; Puls, J.; Taylor, W. D.; Vink, J. S.

2013-12-01

Context. The 30 Doradus (30 Dor) region of the Large Magellanic Cloud, also known as the Tarantula nebula, is the nearest starburst region. It contains the richest population of massive stars in the Local Group, and it is thus the best possible laboratory to investigate open questions on the formation and evolution of massive stars. Aims: Using ground-based multi-object optical spectroscopy obtained in the framework of the VLT-FLAMES Tarantula Survey (VFTS), we aim to establish the (projected) rotational velocity distribution for a sample of 216 presumably single O-type stars in 30 Dor. The sample is large enough to obtain statistically significant information and to search for variations among subpopulations - in terms of spectral type, luminosity class, and spatial location - in the field of view. Methods: We measured projected rotational velocities, νesini, by means of a Fourier transform method and a profile fitting method applied to a set of isolated spectral lines. We also used an iterative deconvolution procedure to infer the probability density, P(νe), of the equatorial rotational velocity, νe. Results: The distribution of νesini shows a two-component structure: a peak around 80 kms-1 and a high-velocity tail extending up to ~600 kms-1. This structure is also present in the inferred distribution P(νe) with around 80% of the sample having 0 < νe ≤ 300 kms-1 and the other 20% distributed in the high-velocity region. The presence of the low-velocity peak is consistent with what has been found in other studies for late O- and early B-type stars. Conclusions: Most of the stars in our sample rotate with a rate less than 20% of their break-up velocity. For the bulk of the sample, mass loss in a stellar wind and/or envelope expansion is not efficient enough to significantly spin down these stars within the first few Myr of evolution. If massive-star formation results in stars rotating at birth with a large portion of their break-up velocities, an alternative braking mechanism, possibly magnetic fields, is thus required to explain the present-day rotational properties of the O-type stars in 30 Dor. The presence of a sizeable population of fast rotators is compatible with recent population synthesis computations that investigate the influence of binary evolution on the rotation rate of massive stars. Even though we have excluded stars that show significant radial velocity variations, our sample may have remained contaminated by post-interaction binary products. That the high-velocity tail may be populated primarily (and perhaps exclusively) by post-binary interaction products has important implications for the evolutionary origin of systems that produce gamma-ray bursts. Based on observations collected at the European Southern Observatory under program ID 182.D-0222.Full Tables 3 and 4 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/560/A29

Diagnostic Accuracy of Imaging Modalities and Injection Techniques for the Diagnosis of Femoroacetabular Impingement/Labral Tear: A Systematic Review With Meta-analysis.

PubMed

Reiman, Michael P; Thorborg, Kristian; Goode, Adam P; Cook, Chad E; Weir, Adam; Hölmich, Per

2017-09-01

Diagnosing femoroacetabular impingement/acetabular labral tear (FAI/ALT) and subsequently making a decision regarding surgery are based primarily on diagnostic imaging and intra-articular hip joint injection techniques of unknown accuracy. Summarize and evaluate the diagnostic accuracy and clinical utility of various imaging modalities and injection techniques relevant to hip FAI/ALT. Systematic review with meta-analysis. A computer-assisted literature search was conducted of MEDLINE, CINAHL, and EMBASE databases using keywords related to diagnostic accuracy of hip joint pathologic changes. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used for the search and reporting phases of the study. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies (QUADAS) tool. Random effects models were used to summarize sensitivities (SN), specificities (SP), likelihood ratios (+LR and -LR), diagnostic odds ratios (DOR), and respective confidence intervals (CI). The search strategy and assessment for risk of bias revealed 25 articles scoring above 10/14 on the items of the QUADAS. Four studies investigated FAI, and the data were not pooled. Twenty articles on ALT qualified for meta-analysis. Pretest probability of ALT in the studies in this review was 81% (72%-88%), while the pretest probability of FAI diagnosis was 74% (95% CI, 51%-91%). The meta-analysis showed that computed tomography arthrography (CTA) demonstrated the strongest overall diagnostic accuracy: pooled SN 0.91 (95% CI, 0.83-0.96); SP 0.89 (95% CI, 0.74-0.97); +LR 6.28 (95% CI, 2.78-14.21); -LR 0.11 (95% CI, 0.06-0.21); and DOR 64.38 (95% CI, 19.17-216.21). High pretest probability of disease was demonstrated. Positive imaging findings increased the probability that a labral tear existed by a minimal to small degree with the use of magnetic resonance imaging/magnetic resonance angiogram (MRI/MRA) and ultrasound (US) and by a moderate degree for CTA. Negative imaging findings decreased the probability that a labral tear existed by a minimal degree with the use of MRI and US, a small to moderate degree with MRA, and a moderate degree with CTA. Although findings of the included studies suggested potentially favorable use of these modalities for the diagnosis of ALT and FAI, our results suggest that these findings have limited generalizability and clinical utility given very high pretest prevalence, large confidence intervals, and selection criteria of the studies. Registration: PROSPERO Registration #CRD42015027745.

Far Ultraviolet Spectroscopic Explorer Spectroscopy of the Nova-Like Cataclysmic Variable BB Doradus

DTIC Science & Technology

2008-06-27

which we have best-fit models in the parameter space, we use the infrared magnitudes J, H, and K from the Two Micron All Sky Survey ( 2MASS ) to assess the...in a high state with a visual red magnitude R ¼ 14:60 and a blue magnitude B ¼ 13:90 (whereas B 16:5 in the low state). The 2MASS IR apparent...therefore certainly larger than 300 pc, and most likely in the range of 500 pc. Since BB Dor was observed in a high state (with 2MASS ), it is likely

ALMA Long Baseline Observations of the Dynamical Atmospheres of AGB Stars

NASA Astrophysics Data System (ADS)

Vlemmings, Wouter

2018-04-01

I will present the current status of ALMA long baseline observations of W Hya, R Leo, R Dor and Mira. We have recently obtained band 4, 6 and 7 observations of the line and continuum emission tracing the temperature and dynamics in their extended atmosphere. Our preliminary analysis confirms our previous detection of a hotspot on W Hya, and reveals unexpected lines in most of the sources, as well as possible fast rotation in the atmopshere of one of the stars. The observations show the unique power of ALMA in observing the extended stellar atmospheres.

Navigation of the Galileo mission

NASA Technical Reports Server (NTRS)

Miller, L. J.; Miller, J. K.; Kirhofer, W. E.

1983-01-01

An overview of the navigation of the Galileo mission is given. Predicted navigation performance for the various mission phases is discussed with particular emphasis given to the tour phase. Orbit determination strategies and resulting accuracies are discussed for various data types. In particular, the results of combining a new Very Long Baseline Interferometry (VLBI) data type called Differential One-Way Range (DOR) with conventional radio and optical data types are presented. Maneuver strategy results include the effects of maneuver placement and various targeting methods on propellant consumption and delivery accuracy. Emphasis is placed on new results obtained using asymptote and split targeting.

T-ReX Spies the Stars of 30 Doradus

NASA Astrophysics Data System (ADS)

Broos, Patrick; Townsley, Leisa K.; Pollock, Andrew; Crowther, Paul

2017-08-01

30 Doradus (the Tarantula Nebula) is the Local Group's most massive young star-forming complex. At its heart is R136, the most massive resolved stellar cluster; R136 contains, in turn, the most massive stars known. The Chandra X-ray Observatory has recently observed 30 Dor for the 2-megasecond X-ray Visionary Project ``The Tarantula -- Revealed by X-rays'' (T-ReX). This deep observation exploits Chandra's fine spatial resolution to study the full complement of massive stars and the brightest pre-main sequence stars that trace 25 Myrs of star formation in this incomparable nearby starburst. Here we give preliminary results from the ongoing analyses of the data, focusing on the massive stars. While many remain undetected even in this deep ACIS-I observation, a few show dramatic X-ray lightcurves and/or high luminosities befitting this amazing starburst cluster.

Comparative analysis of diagnostic performance, feasibility and cost of different test-methods for thyroid nodules with indeterminate cytology

PubMed Central

Sciacchitano, Salvatore; Lavra, Luca; Ulivieri, Alessandra; Magi, Fiorenza; De Francesco, Gian Paolo; Bellotti, Carlo; Salehi, Leila B.; Trovato, Maria; Drago, Carlo; Bartolazzi, Armando

2017-01-01

Since it is impossible to recognize malignancy at fine needle aspiration (FNA) cytology in indeterminate thyroid nodules, surgery is recommended for all of them. However, cancer rate at final histology is <30%. Many different test-methods have been proposed to increase diagnostic accuracy in such lesions, including Galectin-3-ICC (GAL-3-ICC), BRAF mutation analysis (BRAF), Gene Expression Classifier (GEC) alone and GEC+BRAF, mutation/fusion (M/F) panel, alone, M/F panel+miRNA GEC, and M/F panel by next generation sequencing (NGS), FDG-PET/CT, MIBI-Scan and TSHR mRNA blood assay. We performed systematic reviews and meta-analyses to compare their features, feasibility, diagnostic performance and cost. GEC, GEC+BRAF, M/F panel+miRNA GEC and M/F panel by NGS were the best in ruling-out malignancy (sensitivity = 90%, 89%, 89% and 90% respectively). BRAF and M/F panel alone and by NGS were the best in ruling-in malignancy (specificity = 100%, 93% and 93%). The M/F by NGS showed the highest accuracy (92%) and BRAF the highest diagnostic odds ratio (DOR) (247). GAL-3-ICC performed well as rule-out (sensitivity = 83%) and rule-in test (specificity = 85%), with good accuracy (84%) and high DOR (27) and is one of the cheapest (113 USD) and easiest one to be performed in different clinical settings. In conclusion, the more accurate molecular-based test-methods are still expensive and restricted to few, highly specialized and centralized laboratories. GAL-3-ICC, although limited by some false negatives, represents the most suitable screening test-method to be applied on a large-scale basis in the diagnostic algorithm of indeterminate thyroid lesions. PMID:28472764

Ligand- and cell-dependent determinants of internalization and cAMP modulation by delta opioid receptor (DOR) agonists

PubMed Central

Charfi, Iness; Nagi, Karim; Mnie-Filali, Ouissame; Thibault, Dominic; Balboni, Gianfranco; Schiller, Peter W.; Trudeau, Louis-Eric

2014-01-01

Signaling bias refers to G protein-coupled receptor ligand ability to preferentially activate one type of signal over another. Bias to evoke signaling as opposed to sequestration has been proposed as a predictor of opioid ligand potential for generating tolerance. Here we measured whether delta opioid receptor agonists preferentially inhibited cyclase activity over internalization in HEK cells. Efficacy (τ) and affinity (KA) values were estimated from functional data and bias was calculated from efficiency coefficients (log τ/KA). This approach better represented the data as compared to alternative methods that estimate bias exclusively from τ values. Log (τ/KA) coefficients indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for UFP-512: 132). Molecular determinants of internalization were different in HEK293 cells and neurons with βarrs contributing to internalization in both cell types, while PKC and GRK2 activities were only involved in neurons. Rank orders of ligand ability to engage different internalization mechanisms in neurons were compared to rank order of Emax values for cyclase assays in HEK cells. Comparison revealed a significant reversal in rank order for cyclase Emax values and βarr-dependent internalization in neurons, indicating that these responses were ligand-specific. Despite this evidence, and because kinases involved in internalization were not the same across cellular backgrounds, it is not possible to assert if the magnitude and nature of bias revealed by rank orders of maximal responses is the same as the one measured in HEK cells. PMID:24022593

On the crystal structure of the vaterite polymorph of CaCO3: a calcium-43 solid-state NMR and computational assessment.

PubMed

Burgess, Kevin M N; Bryce, David L

2015-02-01

The vaterite polymorph of CaCO3 has puzzled crystallographers for decades in part due to difficulties in obtaining single crystals. The multiple proposed structures for the vaterite polymorph of CaCO3 are assessed using a combined (43)Ca solid-state nuclear magnetic resonance (SSNMR) spectroscopic and computational approach. A combination of improved experimental and computational methods, along with a calibrated chemical shift scale and (43)Ca nuclear quadrupole moment, allow for improved insights relative to our earlier work (Bryce et al., J. Am. Chem. Soc. 2008, 130, 9282). Here, we synthesize a (43)Ca isotopically-enriched sample of vaterite and perform high-resolution quadrupolar SSNMR experiments including magic-angle spinning (MAS), double-rotation (DOR), and multiple-quantum (MQ) MAS experiments at magnetic field strengths of 9.4 and 21.1T. We identify one crystallographically unique Ca(2+) site in vaterite with a slight distribution in both chemical shifts and quadrupolar parameters. Both the experimental (43)Ca electric field gradient tensor and the isotropic chemical shift for vaterite are compared to those calculated with the gauge-including projector-augmented-wave (GIPAW) DFT method in an attempt to identify the model that best represents the crystal structure of vaterite. Simulations of (43)Ca DOR and MAS NMR spectra based on the NMR parameters computed for a total of 18 structural models for vaterite allow us to distinguish between these models. Among these 18, the P3221 and C2 structures provide simulated spectra and diffractograms in best agreement with all experimental data. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of the Young-Laplace law and finite element based calculation of ventricular wall stress: implications for postinfarct and surgical ventricular remodeling.

PubMed

Zhang, Zhihong; Tendulkar, Amod; Sun, Kay; Saloner, David A; Wallace, Arthur W; Ge, Liang; Guccione, Julius M; Ratcliffe, Mark B

2011-01-01

Both the Young-Laplace law and finite element (FE) based methods have been used to calculate left ventricular wall stress. We tested the hypothesis that the Young-Laplace law is able to reproduce results obtained with the FE method. Magnetic resonance imaging scans with noninvasive tags were used to calculate three-dimensional myocardial strain in 5 sheep 16 weeks after anteroapical myocardial infarction, and in 1 of those sheep 6 weeks after a Dor procedure. Animal-specific FE models were created from the remaining 5 animals using magnetic resonance images obtained at early diastolic filling. The FE-based stress in the fiber, cross-fiber, and circumferential directions was calculated and compared to stress calculated with the assumption that wall thickness is very much less than the radius of curvature (Young-Laplace law), and without that assumption (modified Laplace). First, circumferential stress calculated with the modified Laplace law is closer to results obtained with the FE method than stress calculated with the Young-Laplace law. However, there are pronounced regional differences, with the largest difference between modified Laplace and FE occurring in the inner and outer layers of the infarct borderzone. Also, stress calculated with the modified Laplace is very different than stress in the fiber and cross-fiber direction calculated with FE. As a consequence, the modified Laplace law is inaccurate when used to calculate the effect of the Dor procedure on regional ventricular stress. The FE method is necessary to determine stress in the left ventricle with postinfarct and surgical ventricular remodeling. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

AB Dor Moving Group Stars Resolved with the CHARA Array

NASA Astrophysics Data System (ADS)

Schaefer, G. H.; White, R. J.; Baines, E. K.; Boyajian, T. S.; ten Brummelaar, T. A.; Farrington, C. D.; Sturmann, J.; Sturmann, L.; Turner, N. H.

2018-05-01

We present interferometric measurements obtained with the CHARA Array of 13 adolescent-age stars in nearby moving groups. The motivation was to spatially resolve the largest stars and to search for binary companions. Nine stars have diameters smaller than the resolution limit and no evidence for companions within 0.5–50 mas and ΔH < 2.0 mag. The diameters of three stars were spatially resolved: GJ 159 (0.582 ± 0.016 mas) and GJ 393 (0.564 ± 0.021 mas) in the AB Dor moving group, and former member HD 89744 (0.556 ± 0.032 mas). Combining the angular diameters with their distances and bolometric fluxes, we measured radii and effective temperatures. The temperatures of GJ 159 (6286 ± 123 K) and GJ 393 (3515 ± 68 K) are consistent with spectroscopic measurements. Comparisons with evolutionary models show that HD 89744 has evolved off the main sequence. GJ 159 and GJ 393 lie within 1.5σ of the zero-age main sequence, complicating their age estimates because it is unclear whether the stars are contracting or expanding. GJ 159 has a mass of 1.2 ± 0.1 {M}ȯ with an age spanning 0.021–3.0 Gyr. Its debris disk and lithium abundance favor a young age. GJ 393 has a mass of 0.42 ± 0.03 {M}ȯ and a lower limit on its age 0.06 Gyr. This overlaps with the age of the moving group; however, an older age would be more consistent with its slow rotation, low activity, and luminosity, suggesting that GJ 393 is a kinematic interloper.

IgD multiple myeloma a descriptive report of 17 cases: survival and response to therapy

PubMed Central

2012-01-01

Background Immunoglobulin D multiple myeloma (MM) is rare and has a poorer prognosis than other MM isotypes. Design and methods Seventeen patients (pts) diagnosed from 1993 to 2009 with IgD MM were selected from six institutions of Multiple Myeloma Latium-Region GIMEMA Working Group. Results Median age was 55 years, 14 patients had bone lesions, eight had renal impairment with estimated glomerular filtration rate (eGFR) < 50 ml/min, one serum calcium ≥ 12 mg/dl, 11 had lambda light chains, five stage III of ISS, six with chromosomal abnormalities. Six pts received conventional chemotherapy (CT): five melphalan + steroids based regimens. Eleven underwent high-doses of chemotherapy with autologous stem cell transplantation (HDT/ASCT), five single and six tandem ASCT: six received bortezomib and/or thalidomide as induction therapy and five VAD. Thalidomide maintenance was used in two pts: one in HDT/ASCT and one in CT group; bortezomib was used in one patient after HDT/ASCT. At a median follow up of 38 (range 19-60) and 50 months (range 17-148) for pts treated with CT and HDT/ASCT, respectively, the overall response rate (ORR) was 83% and 90%. In the group of patients treated with CT, median overall survival (OS) was 34 months (95% CI 15- 54 months), median progression free survival (PFS) was 18 months (95% CI 3-33 months) and median duration of response (DOR) was 7 months (95% CI 5-9 months). Median OS, PFS and DOR were not reached at the time of this analysis in the HDT/ASCT group of patients. Death was observed in 27.3% of pts treated with HDT/ASCT and in 66.7% undergone CT. Conclusions Despite the retrospective analysis and the small number of pts our study showed that the use of HDT/ASCT seems to improve also the prognosis of IgD MM patients. Treatment options including new drugs, before and after stem cell transplantation, may further improve the outcomes of these patients. PMID:22381082

Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean

PubMed Central

Galeano, Carlos H.; Fernandez, Andrea C.; Franco-Herrera, Natalia; Cichy, Karen A.; McClean, Phillip E.; Vanderleyden, Jos; Blair, Matthew W.

2011-01-01

Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning. PMID:22174773

U-isotopes and (226)Ra as tracers of hydrogeochemical processes in carbonated karst aquifers from arid areas.

PubMed

Guerrero, José Luis; Vallejos, Ángela; Cerón, Juan Carlos; Sánchez-Martos, Francisco; Pulido-Bosch, Antonio; Bolívar, Juan Pedro

2016-07-01

Sierra de Gádor is a karst macrosystem with a highly complex geometry, located in southeastern Spain. In this arid environment, the main economic activities, agriculture and tourism, are supported by water resources from the Sierra de Gádor aquifer system. The aim of this work was to study the levels and behaviour of some of the most significant natural radionuclides in order to improve the knowledge of the hydrogeochemical processes involved in this groundwater system. For this study, 28 groundwater and 7 surface water samples were collected, and the activity concentrations of the natural U-isotopes ((238)U, (235)U and (234)U) and (226)Ra by alpha spectrometry were determined. The activity concentration of (238)U presented a large variation from around 1.1 to 65 mBq L(-1). Elevated groundwater U concentrations were the result of oxidising conditions that likely promoted U dissolution. The PHREEQC modelling code showed that dissolved U mainly existed as uranyl carbonate complexes. The (234)U/(238)U activity ratios were higher than unity for all samples (1.1-3.8). Additionally, these ratios were in greater disequilibrium in groundwater than surface water samples, the likely result of greater water-rock contact time. (226)Ra presented a wide range of activity concentrations, (0.8 up to about 4 × 10(2) mBq L(-1)); greatest concentrations were detected in the thermal area of Alhama. Most of the samples showed (226)Ra/(234)U activity ratios lower than unity (median = 0.3), likely the result of the greater mobility of U than Ra in the aquifer system. The natural U-isotopes concentrations were strongly correlated with dissolution of sulphate evaporites (mainly gypsum). (226)Ra had a more complex behaviour, showing a strong correlation with water salinity, which was particularly evident in locations where thermal anomalies were detected. The most saline samples showed the lowest (234)U/(238)U activity ratios, probably due to fast uniform bulk mineral dissolution, which would minimize the impact of solubility-controlled fractionation processes. Furthermore, the high bulk dissolution rates promoted greater groundwater (226)Ra/(234)U ratios because the Ra has a comparatively much greater mobility than U in saline conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

VizieR Online Data Catalog: VLT-FLAMES Tarantula Survey: B supergiants (McEvoy+, 2015)

NASA Astrophysics Data System (ADS)

McEvoy, C. M.; Dufton, P. L.; Evans, C. J.; Kalari, V. M.; Markova, N.; Simon-Diaz, S.; Vink, J. S.; Walborn, N. R.; Crowther, P. A.; de Koter, A.; de Mink, S. E.; Dunstall, P. R.; Henault-Brunet, V.; Herrero, A.; Langer, N.; Lennon, D. J.; Maiz Apellaniz, J.; Najarro, F.; Puls, J.; Sana, H.; Schneider, F. R. N.; Taylor, W. D.

2015-06-01

The majority of the VFTS data were obtained using the Medusa mode of FLAMES, which uses fibres to feed the light from up to 130 targets simultaneously to the Giraffe spectrograph. Nine Medusa configurations (Fields A to I) were observed in the 30 Dor region, with the targets sampling its different clusters and the local field population. The analysis presented here employs the FLAMES-Medusa observations obtained with two of the standard Giraffe settings (LR02 and LR03), giving coverage of the λλ3960-5050Å region at a resolving power of ~7000. (5 data files).

La Vie Politique sous la Restauration a Travers ’Le Rouge et le Noir’ de Stendahl (The Political Life during the Restauration as Depicted in Le Rouge et le Noir by Stendahl)

DTIC Science & Technology

1989-01-01

de la classe dirigeante est le clerg6. M. le vicaire de Frilair est le bras droit de l ’&veque dle Besangon et...sympathique effort de recherche ;la documentation contribue bien A 6clairer lanalyse. INTERPRETATION: L 𔄀tude des aspects de la vie politique sous la...References Ouvrages consultes AXccesion For NTIS CRA&I DTIC TA9 El Unanno ’-,’ 1 : By 442.-. - L -- A, _ojes Aof -d/or * A- Dans l’L*tude des

The VLT-FLAMES Tarantula Survey

NASA Astrophysics Data System (ADS)

Vink, Jorick S.; Evans, C. J.; Bestenlehner, J.; McEvoy, C.; Ramírez-Agudelo, O.; Sana, H.; Schneider, F.; VFTS Collaboration

2017-11-01

We present a number of notable results from the VLT-FLAMES Tarantula Survey (VFTS), an ESO Large Program during which we obtained multi-epoch medium-resolution optical spectroscopy of a very large sample of over 800 massive stars in the 30 Doradus region of the Large Magellanic Cloud (LMC). This unprecedented data-set has enabled us to address some key questions regarding atmospheres and winds, as well as the evolution of (very) massive stars. Here we focus on O-type runaways, the width of the main sequence, and the mass-loss rates for (very) massive stars. We also provide indications for the presence of a top-heavy initial mass function (IMF) in 30 Dor.

Radiometric Spacecraft Tracking for Deep Space Navigation

NASA Technical Reports Server (NTRS)

Lanyi, Gabor E.; Border, James S.; Shin, Dong K.

2008-01-01

Interplanetary spacecraft navigation relies on three types of terrestrial tracking observables.1) Ranging measures the distance between the observing site and the probe. 2) The line-of-sight velocity of the probe is inferred from Doppler-shift by measuring the frequency shift of the received signal with respect to the unshifted frequency. 3) Differential angular coordinates of the probe with respect to natural radio sources are nominally obtained via a differential delay technique of (Delta) DOR (Delta Differential One-way Ranging). The accuracy of spacecraft coordinate determination depends on the measurement uncertainties associated with each of these three techniques. We evaluate the corresponding sources of error and present a detailed error budget.

Galileo Jupiter approach orbit determination

NASA Technical Reports Server (NTRS)

Miller, J. K.; Nicholson, F. T.

1984-01-01

Orbit determination characteristics of the Jupiter approach phase of the Galileo mission are described. Predicted orbit determination performance is given for the various mission events that occur during Jupiter approach. These mission events include delivery of an atmospheric entry probe, acquisition of probe science data by the Galileo orbiter for relay to earth, delivery of an orbiter to a close encounter of the Galilean satellite Io, and insertion of the orbiter into orbit about Jupiter. The orbit determination strategy and resulting accuracies are discussed for the data types which include Doppler, range, optical imaging of Io, and a new Very Long Baseline Interferometry (VLBI) data type called Differential One-Way Range (DOR).

Culinary nationalism.

PubMed

Ferguson, Priscilla Parkhurst

2010-01-01

Culinary consciousness raisers, cooking texts often serve as vehicles of national identification. From Pampille (Marthe Allard Daudet) and her cookbook, Les Bons Plats de France, in 1913 to the international culinary competitions of today such as the Bocuse d'or, culinary distinction promotes national interests. In contrast to the strident nationalism of the early twentieth century, culinary nationalism today operates in an increasingly globalized world. National culinary distinction defines the nation and sells its products in a highly competitive international arena. A recent culinary text, the South Korean film Le Grand Chef [Sik Gaek ] (2007), illustrates the phenomenon, subsuming national culinary promotion in a mega culinary competition, all in the service of Korean culinary achievement.

Chemical Laser Systems: An Engineering Approach. Volume I. Chemical Laser Analysis Program

DTIC Science & Technology

1979-01-31

C* *CPCALC S040 CO CNO C V ALUES ASTORED IN RNITS Of NLUE-DOR JITKROLEoKJ AND TAPULATED *CPCALC OSSO CO BY TEMPERATURE (ROW) FROM 0 K TO 3000 K IM...KMOLEi P PRESSURE EPA) P DENSITY fKG/M31 REI REYNOLDS NUMBER T : TEMPERATURE CKI W i MASS FLOW RATE (KG/S] X a MOLAR FLOW RATE (KNOLE/S) REPEAYEO...200000E#67 PA REI * 21363AE*04 I ZISE0K10 JSSE0RI a .288884E- 1 KS/N3 Pie :174617f#01@ KG/N3 POINT 2 ’PRIMARY NOZZLE EXIT - CONDITIONS IASED ON THE

Efficacy of bacterial cellulose membrane for the treatment of lower limbs chronic varicose ulcers: a randomized and controlled trial.

PubMed

Cavalcanti, Luciana Marins; Pinto, Flávia Cristina Morone; Oliveira, Glícia Maria DE; Lima, Salvador Vilar Correia; Aguiar, José Lamartine DE Andrade; Lins, Esdras Marques

2017-01-01

to evaluate the efficacy of Bacterial Cellulose (BC) membrane dressings in the treatment of lower limb venous ulcers. we carried out a prospective, randomized, controlled study of 25 patients with chronic venous ulcer disease in the lower limbs from the Angiology and Vascular Surgery Service of the Federal University of Pernambuco Hospital and from the Salgado Polyclinic of the County Health Department, Caruaru, Pernambuco. We randomly assigned patients to two groups: control group, receiving dressings with triglyceride oil (11 patients) and experimental group, treated with BC membrane (14 patients). We followed the patients for a period of 120 days. There was a reduction in the wound area in both groups. There were no infections or reactions to the product in any of the groups. Patients in the BC group showed decreased pain and earlier discontinuation of analgesic use. BC membrane can be used as a dressing for the treatment of varicose ulcers of the lower limbs. avaliar a eficácia de curativos com membrana de Celulose Bacteriana (CB) no tratamento de úlceras venosas de membros inferiores. estudo prospectivo, randomizado e controlado de 25 pacientes com úlceras decorrentes de doença venosa crônica nos membros inferiores provenientes do Serviço de Angiologia e Cirurgia Vascular do Hospital de Clínicas da Universidade Federal de Pernambuco e da Policlínica do Salgado da Secretaria Municipal de Saúde, Caruaru, Pernambuco. Os pacientes foram distribuídos aleatoriamente em dois grupos: grupo controle, que recebeu curativos com óleo de triglicerídeos (11 pacientes) e grupo experimental, tratado com membrana de CB (14 pacientes). Os pacientes foram acompanhados por um período de 120 dias. houve uma redução na área de ferida em ambos os grupos. Não houve infecção ou reações ao produto em nenhum dos grupos. Pacientes do grupo CB mostraram diminuição da dor e interrupção mais precoce do uso de analgésicos. a membrana de CB pode ser usada como curativo para o tratamento de úlceras varicosas dos membros inferiores.

On the Nature of the Prototype Luminous Blue Variable Ag Carinae. I. Fundamental Parameters During Visual Minimum Phases and Changes in the Bolometric Luminosity During the S-Dor Cycle

NASA Astrophysics Data System (ADS)

Groh, J. H.; Hillier, D. J.; Damineli, A.; Whitelock, P. A.; Marang, F.; Rossi, C.

2009-06-01

We present a detailed spectroscopic analysis of the luminous blue variable (LBV) AG Carinae (AG Car) during the last two visual minimum phases of its S-Dor cycle (1985-1990 and 2000-2003). The analysis reveals an overabundance of He, N, and Na, and a depletion of H, C, and O, on the surface of the AG Car, indicating the presence of a CNO-processed material. Furthermore, the ratio N/O is higher on the stellar surface than in the nebula. We found that the minimum phases of AG Car are not equal to each other, since we derived a noticeable difference between the maximum effective temperature achieved during 1985-1990 (22, 800 K) and 2000-2001 (17,000 K). Significant differences between the wind parameters in these two epochs were also noticed. While the wind terminal velocity was 300 km s-1 in 1985-1990, it was as low as 105 km s-1 in 2001. The mass-loss rate, however, was lower from 1985-1990 (1.5 × 10-5 M sun yr-1) than from 2000-2001 (3.7 × 10-5 M sun yr-1). We found that the wind of AG Car is significantly clumped (f sime 0.10-0.25) and that clumps must be formed deep in the wind. We derived a bolometric luminosity of 1.5 × 106 L sun during both minimum phases which, contrary to the common assumption, decreases to 1.0 × 106 L sun as the star moves toward the maximum flux in the V band. Assuming that the decrease in the bolometric luminosity of AG Car is due to the energy used to expand the outer layers of the star, we found that the expanding layers contain roughly 0.6-2 M sun. Such an amount of mass is an order of magnitude lower than the nebular mass around AG Car, but is comparable to the nebular mass found around lower-luminosity LBVs and to that of the Little Homunculus of Eta Car. If such a large amount of mass is indeed involved in the S Dor-type variability, we speculate that such instability could be a failed Giant Eruption, with several solar masses never becoming unbound from the star. Based on observations made with the 1.6 m telescope at the Observatório Pico dos Dias (OPD/LNA, Brazil), with the 1.52 m telescope and 8 m Very Large Telescope at the European Southern Observatory (ESO, Chile), with the International Ultraviolet Explorer (IUE) satellite, at the South African Astronomical Observatory (SAAO), and with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer (FUSE), which is operated for NASA by the Johns Hopkins University under NASA contract NAS5-32985.

The effects of acupressure on labor pains during child birth: randomized clinical trial.

PubMed

Mafetoni, Reginaldo Roque; Shimo, Antonieta Keiko Kakuda

2016-08-08

to analyze the effects of acupressure on the sanyinjiao point for pregnant women in labor at public maternity wards. single-blind controlled clinical trial, randomly done employing a pragmatic profile. We selected 156 pregnant women in their ≥ 37 week/s, who had cervical dilations of ≥ 4 cm and with two or more contractions in 10 minutes. The pregnant women were randomly divided into three groups at a university hospital in the suburbs of Sao Paulo, Brazil, in order to receive either acupressure treatment, a placebo or participate as part of a control group. The acupressure was applied on the sanyinjiao point during the contractions for 20 minutes. Then the intensity of the pain was evaluated using the Visual Analogue Scale (VAS). The averages for the pain measured using the VAS were not different for the three groups that were a part of the study (p-value=0.0929), however they were less in the acupressure groups immediately after receiving the treatment (p-value=<0.0001). This was also the case where the treatment lasted for 1 hour (p-value=0.0001). This was the case in comparison with placebo and control groups. the use of acupressure on the sanyinjiao point is a useful way to alleviate pain in a non-invasive manner. It can improve the quality of care given to pregnant women in labor. Register: RBR-9mhs8r. analisar os efeitos da acupressão no ponto sanyinjiao sobre a dor na fase ativa do trabalho de parto, em gestantes atendidas em maternidade pública. trata-se de um ensaio clínico controlado e randomizado, simples-cego e de caráter pragmático. Foram selecionadas 156 mulheres com idade gestacional ≥ 37 semanas, dilatação cervical ≥ 4 cm e com duas ou mais contrações em 10 minutos. As gestantes foram divididas aleatoriamente em três grupos em um hospital universitário do interior do estado de São Paulo, Brasil, para receber acupressão, placebo ou participar como controle. A acupressão foi aplicada no ponto sanyinjiao durante as contrações, por 20 minutos, e a intensidade da dor avaliada por meio de uma Escala Analógica Visual (EAV). as médias de dor pela EAV não foram diferentes nos três grupos na admissão (p-valor=0,0929), porém foram menores no grupo de acupressão imediatamente após (p-valor=<0,0001) e com 1 h do tratamento (p-valor=0,0001) ao se comparar com placebo e controle. a acupressão no ponto sanyinjiao se mostrou uma medida útil no alívio da dor, não invasiva e um meio de melhorar a qualidade dos cuidados a parturiente. Registro: RBR-9mhs8r. analizar los efectos de la acupresión, en el punto sanyinjiao, sobre el dolor en la fase activa del trabajo de parto, en embarazadas atendidas en maternidad pública. ensayo clínico controlado y aleatorio, simple ciego y de carácter pragmático. Fueron seleccionadas 156 mujeres con edad gestacional ≥ 37 semanas, dilatación cervical ≥ 4 cm y con dos o más contracciones en 10 minutos. Las embarazadas fueron divididas aleatoriamente en tres grupos en un hospital universitario del interior del estado de Sao Paulo, Brasil, para recibir acupresión, placebo o participar como control. La acupresión fue aplicada en el punto sanyinjiao durante las contracciones, por 20 minutos; la intensidad del dolor fue evaluada por medio de una Escala Analógica Visual (EAV). los promedios del dolor por la EAV no fueron diferentes en los tres grupos en la admisión (valor p=0,0929), sin embargo fueron menores en el grupo de acupresión inmediatamente después (valor p=<0,0001) y también después de 1 hora del tratamiento (valor p=0,0001) al compararse con el placebo y control. la acupresión en el punto sanyinjiao se mostró una medida útil en el alivio del dolor, no invasiva y un medio de mejorar la calidad de los cuidados la parturienta. Registro: RBR-9mhs8r.

Peripheral Receptor Mechanisms Underlying Orofacial Muscle Pain and Hyperalgesia

NASA Astrophysics Data System (ADS)

Saloman, Jami L.

Musculoskeletal pain conditions, particularly those associated with temporomandibular joint and muscle disorders (TMD) are severely debilitating and affect approximately 12% of the population. Identifying peripheral nociceptive mechanisms underlying mechanical hyperalgesia, a prominent feature of persistent muscle pain, could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. This study provides evidence of functional interactions between ligand-gated channels, P2X3 and TRPV1/TRPA1, in trigeminal sensory neurons, and proposes that these interactions underlie the development of mechanical hyperalgesia. In the masseter muscle, direct P2X3 activation, via the selective agonist αβmeATP, induced a dose- and time-dependent hyperalgesia. Importantly, the αβmeATP-induced hyperalgesia was prevented by pretreatment of the muscle with a TRPV1 antagonist, AMG9810, or the TRPA1 antagonist, AP18. P2X3 was co-expressed with both TRPV1 and TRPA1 in masseter muscle afferents confirming the possibility for intracellular interactions. Moreover, in a subpopulation of P2X3 /TRPV1 positive neurons, capsaicin-induced Ca2+ transients were significantly potentiated following P2X3 activation. Inhibition of Ca2+-dependent kinases, PKC and CaMKII, prevented P2X3-mechanical hyperalgesia whereas blockade of Ca2+-independent PKA did not. Finally, activation of P2X3 induced phosphorylation of serine, but not threonine, residues in TRPV1 in trigeminal sensory neurons. Significant phosphorylation was observed at 15 minutes, the time point at which behavioral hyperalgesia was prominent. Similar data were obtained regarding another nonselective cation channel, the NMDA receptor (NMDAR). Our data propose P2X3 and NMDARs interact with TRPV1 in a facilitatory manner, which could contribute to the peripheral sensitization underlying masseter hyperalgesia. This study offers novel mechanisms by which individual pro-nociceptive ligand gated ion channels form functional complexes in nociceptors. It is also important to further elucidate peripheral anti-nociceptive mechanisms to improve clinical utilization of currently available analgesics and uncover additional therapeutic targets. A side project examined the mechanisms underlying sex differences in the anti-hyperalgesic effects of delta opioid receptors (DORs). This study provides evidence of a sex difference in the potency at DORs that is mediated by differences in the expression of ATP-sensitive potassium channels. Collectively, understanding detailed molecular events that underlie the development of pathological pain conditions could benefit future pharmacotherapies.

Revisiting the white blood cell count: immature granulocytes count as a diagnostic marker to discriminate between SIRS and sepsis--a prospective, observational study.

PubMed

Nierhaus, Axel; Klatte, Stefanie; Linssen, Jo; Eismann, Nina M; Wichmann, Dominic; Hedke, Jörg; Braune, Stephan A; Kluge, Stefan

2013-02-12

Sepsis is a serious disease condition and a major cause of intensive care unit (ICU) admission. Its diagnosis in critically ill patients is complicated. To diagnose an infection rapidly, and to accurately differentiate systemic inflammatory response syndrome (SIRS) from sepsis, is challenging yet early diagnosis is vital for early induction of an appropriate therapy. The aim of this study was to evaluate whether the immature granulocyte (IG) count is a useful early diagnostic marker of sepsis compared to other markers. Therefore, a total of 70 consecutive surgical intensive care patients were assessed. IGs were measured from whole blood samples using an automated analyzer. C-reactive protein (CRP), lipopolysaccharide binding protein (LBP) and interleukin-6 (IL-6) concentrations were also determined. The observation period was a maximum of 21 days and ended with the patients' discharge from ICU or death. Receiver operating characteristic (ROC) analyses were conducted and area under the curve (AUC) was calculated to determine sensitivities and specificities for the parameters. We found that the IG count significantly discriminates between infected and non-infected patients (P < 0.0001) with a sensitivity of 89.2% and a specificity of 76.4%, particularly within the first 48 hours after SIRS onset. Regarding the discriminative power for infection, the IG count was more indicative than other clinical parameters such as CRP, LBP and IL-6, which had a sensitivity of less than 68%. Additionally, the highest diagnostic odds ratio (DOR) with 26.7 was calculated for the IG count within the first 48 hours. During the course of the disease ROC curve analyses showed a superior positive predictive value of the IG count compared to the other measured parameters during the first five days following the fulfillment of SIRS criteria. However, the number of IGs was not correlated with ICU mortality. The total number of IG in peripheral blood from ICU patients is a good marker to discriminate infected and non-infected patients very early during SIRS. However, the IG count is not suitable as a prognostic marker for mortality. Routine and serial measurement of IGs may provide new possibilities for rapid screening of SIRS patients on ICU with suspected infections.

[Doctor and poet as rivals. Sigmund Freud, Alfred von Berger and the narrative of female homosexuality].

PubMed

Goldmann, Stefan

2011-01-01

Starting from a passage in the Dora case history where Freud suggests some differences between a literary and a clinical narrative of female homosexuality, this paper presents examples which he might have had in mind. Besides Balzac's "La fille aux yeux d'or" (1834/35) it is in particular Alfred v. Berger's novella "Die Italienerin [The Italian woman]" (1904) which may have served as a model and counterpoint to the literary strategies used in Freud's case history. Freud had a relationship of long standing with Berger. This newly discovered source may provide a clue for the date at which Freud finalized the Dora manscript which he had held back for years.

An X-ray image of the violent interstellar medium in 30 Doradus

NASA Technical Reports Server (NTRS)

Wang, Q.; Helfand, D. J.

1991-01-01

A detailed analysis of the X-ray emission from the largest H II region complex in the Local Group, 30 Dor, is presented. Applying a new maximum entropy deconvolution algorithm to the Einstein Observatory data, reveals striking correlations among the X-ray, radio, and optical morphologies of the region, with X-ray-emitting bubbles filling cavities surrounded by H-alpha shells and coextensive diffuse X-ray and radio continuum emission from throughout the region. The total X-ray luminosity in the 0.16-3.5 keV band from an area within 160 pc of the central cluster R136 is about 2 x 10 to the 37th ergs/sec.

Bursting star formation and the overabundance of Wolf-Rayet stars

NASA Technical Reports Server (NTRS)

Bodigfee, G.; Deloore, C.

1985-01-01

The ratio of the number of WR-stars to their OB progenitors appears to be significantly higher in some extragalactic systems than in our Galaxy. This overabundance of Wolf-Rayet-stars can be explained as a consequence of a recent burst of star formation. It is suggested that this burst is the manifestation of a long period nonlinear oscillation in the star formation process, produced by positive feedback effects between young stars and the interstellar medium. Star burst galaxies with large numbers of WR-stars must generate gamma - fluxes but due to the distance, all of them are beyond the reach of present-day ray detectors, except probably 30 Dor.

Comfort studies of rail passengers

PubMed Central

Nicol, J. F.; Doré, C.; Weiner, J. S.; Lee, D. E.; Prestidge, S. P.; Andrews, M. J.

1973-01-01

Nicol, J. F., Doré, C., Weiner, J. S., Lee, D. E., Prestidge, S. P., and Andrews, M. J. (1973).British Journal of Industrial Medicine,30, 325-334. Comfort studies of rail passengers. A short series of trials is described in which a specimen car of the new High Density Rolling Stock was laden with passengers at different densities and under different environmental constraints, designed to simulate `shut-down' conditions. The results suggest that the limit for comfort, 21·8°C corrected effective temperature (CET), proposed by Bell and Watts (1971) is reasonable but that temperatures some 3 or 4°C higher can be tolerated without undue discomfort. The physiological limit for safety recommended by Bell and Watts is a CET of 30·6°C. This will be reached in less than 20 minutes if there is a power failure in warm conditions in crowded trains. An undesirable, possibly dangerous, level of discomfort will be experienced by passengers in ventilated but crowded trains after 30 minutes. In any case it is recommended that the globe temperature in a carriage should not exceed 30°C. Images PMID:4753715

MiniCORVET is a Vps8-containing early endosomal tether in Drosophila.

PubMed

Lőrincz, Péter; Lakatos, Zsolt; Varga, Ágnes; Maruzs, Tamás; Simon-Vecsei, Zsófia; Darula, Zsuzsanna; Benkő, Péter; Csordás, Gábor; Lippai, Mónika; Andó, István; Hegedűs, Krisztina; Medzihradszky, Katalin F; Takáts, Szabolcs; Juhász, Gábor

2016-06-02

Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Vps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila.