Group cognitive remediation therapy for chronic schizophrenia: A randomized controlled trial.

PubMed

Tan, Shuping; Zou, Yizhuang; Wykes, Til; Reeder, Clare; Zhu, Xiaolin; Yang, Fude; Zhao, Yanli; Tan, Yunlong; Fan, Fengmei; Zhou, Dongfeng

2016-07-28

Individual-level cognitive remediation therapy (CRT) has been shown to be effective for cognitive improvement and social function amelioration. Here, we aimed to test the efficacy of group-based CRT in Chinese subjects with schizophrenia. One-hundred and four inpatients were randomly assigned to either 40 sessions of small-group CRT therapy or therapeutic contact-matched Musical and Dancing Therapy (MDT). Cognitive and social functioning, as well as clinical symptoms, were evaluated over the course of treatment. Specifically, cognitive function was evaluated using a battery of cognitive measurements, clinical symptoms were evaluated using the Positive and Negative Syndrome Scale, and social function was evaluated using the Nurse's Observation Scale for Inpatient Evaluation-30. All patients were evaluated pre- and post-treatment. Forty-four individuals in the CRT group and 46 in the MDT group completed all of the planned treatments and analyses. Cognitive functions, especially cognitive flexibility and memory, showed significant improvement in the CRT group over the course of the study. The MDT group also showed improvement in several cognitive flexibility assessments, but the degree of improvement was significantly greater in the CRT group. Several social-function factors exhibited a significant improvement in the CRT group, but not in the MDT group. Cognitive function improvement correlated positively with social function without predicting social function change. We conclude that group-based CRT is an effective and promising therapy. Copyright © 2016. Published by Elsevier Ireland Ltd.

A systematic review of maggot debridement therapy for chronically infected wounds and ulcers.

PubMed

Sun, Xinjuan; Jiang, Kechun; Chen, Jingan; Wu, Liang; Lu, Hui; Wang, Aiping; Wang, Jianming

2014-08-01

This study aimed to systematically evaluate maggot debridement therapy (MDT) in the treatment of chronically infected wounds and ulcers. We performed a meta-analysis referring to the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We searched for published articles in the following databases: PubMed, Web of Science, Embase, Wanfang (Chinese), and the China National Knowledge Infrastructure (CNKI). The latest search was updated on March 14, 2014. For dichotomous outcomes, the effects of MDT were expressed as the relative risk (RR) and 95% confidence interval (CI). For continuous outcomes with different measurement scales, we calculated the standardized mean difference (SMD). The pooled effects were estimated using a fixed effect model or random effect model based on the heterogeneity test. Subgroup analyses were performed according to the types of wounds or ulcers. MDT had a significantly increased positive effect on wound healing compared with conventional therapies, with a pooled RR of 1.80 (95% CI 1.24-2.60). The subgroup analysis revealed that the combined RRs were 1.79 (95% CI 0.95-3.38) for patients with diabetic foot ulcers (DFU) and 1.70 (95% CI 1.28-2.27) for patients with other types of ulcers. The time to healing of the ulcers was significantly shorter among patients treated with MDT, with a pooled SMD of -0.95 (95% CI -1.24, -0.65). For patients with DFU, the SMD was -0.79 (95% CI -1.18, -0.41), and for patients with other types of ulcers, the SMD was -1.16 (95% CI -1.63, -0.69). MDT not only shortened the healing time but also improved the healing rate of chronic ulcers. Therefore, MDT may be a feasible alternative in the treatment of chronic ulcers. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Maggot debridement therapy promotes diabetic foot wound healing by up-regulating endothelial cell activity.

PubMed

Sun, Xinjuan; Chen, Jin'an; Zhang, Jie; Wang, Wei; Sun, Jinshan; Wang, Aiping

2016-03-01

To determine the role of maggot debridement therapy (MDT) on diabetic foot wound healing, we compared growth related factors in wounds before and after treatment. Furthermore, we utilized human umbilical vein endothelial cells (HUVECs) to explore responses to maggot excretions/secretions on markers of angiogenesis and proliferation. The results showed that there was neo-granulation and angiogenesis in diabetic foot wounds after MDT. Moreover, significant elevation in CD34 and CD68 levels was also observed in treated wounds. In vitro, ES increased HUVEC proliferation, improved tube formation, and increased expression of vascular endothelial growth factor receptor 2 in a dose dependent manner. These results demonstrate that MDT and maggot ES can promote diabetic foot wound healing by up-regulating endothelial cell activity. Copyright © 2016. Published by Elsevier Inc.

Assessing the treatment effects in apraxia of speech: introduction and evaluation of the Modified Diadochokinesis Test.

PubMed

Hurkmans, Joost; Jonkers, Roel; Boonstra, Anne M; Stewart, Roy E; Reinders-Messelink, Heleen A

2012-01-01

The number of reliable and valid instruments to measure the effects of therapy in apraxia of speech (AoS) is limited. To evaluate the newly developed Modified Diadochokinesis Test (MDT), which is a task to assess the effects of rate and rhythm therapies for AoS in a multiple baseline across behaviours design. The consistency, accuracy and fluency of speech of 24 adults with AoS and 12 unaffected speakers matched for age, gender and educational level were assessed using the MDT. The reliability and validity of the instrument were considered and outcomes compared with those obtained with existing tests. The results revealed that MDT had a strong internal consistency. Scores were influenced by syllable structure complexity, while distinctive features of articulation had no measurable effect. The test-retest and intra- and inter-rater reliabilities were shown to be adequate, and the discriminant validity was good. For convergent validity different outcomes were found: apart from one correlation, the scores on tests assessing functional communication and AoS correlated significantly with the MDT outcome measures. The spontaneous speech phonology measure of the Aachen Aphasia Test (AAT) correlated significantly with the MDT outcome measures, but no correlations were found for the repetition subtest and the spontaneous speech articulation/prosody measure of the AAT. The study shows that the MDT has adequate psychometric properties, implying that it can be used to measure changes in speech motor control during treatment for apraxia of speech. The results demonstrate the validity and utility of the instrument as a supplement to speech tasks in assessing speech improvement aimed at the level of planning and programming of speech. © 2012 Royal College of Speech and Language Therapists.

Transforaminal epidural steroid injections followed by mechanical diagnosis and therapy to prevent surgery for lumbar disc herniation.

PubMed

van Helvoirt, Hans; Apeldoorn, Adri T; Ostelo, Raymond W; Knol, Dirk L; Arts, Mark P; Kamper, Steven J; van Tulder, Maurits W

2014-07-01

Prospective cohort study. To report the clinical course of patients with MRI-confirmed lumbar disc herniation-related radicular noncentralizing pain who received transforaminal epidural steroid injections (TESIs) and mechanical diagnosis and therapy (MDT). Noncentralizing symptoms in patients with lumbar disc herniation are associated with poor outcome. Commonly used treatments for these patients include TESIs and MDT. No study has evaluated the outcome of combining both strategies. Consecutive candidates for herniated lumbar disc surgery with noncentralizing chronic pain were eligible. Patients received TESIs followed by MDT. The primary outcomes were pain severity in the leg, disability (Roland-Morris Disability Questionnaire for Sciatica), and global perceived effect (GPE). Outcomes were measured at baseline, discharge, and 12 months. Linear mixed-models and McNemar's tests were used to analyze outcome data. Sixty-nine patients receive TESIs. After TESIs, symptoms were resolved completely in 11 patients (16%). In these patients, symptom resolution was maintained at 12 months. A second subgroup of 32 patients (46%) reported significantly less pain after TESIs and showed centralization with MDT reassessment (significant reductions in leg pain and disability [P < 0.001]) and a satisfaction rate of 90% at 12 months. A third subgroup of 11 patients (16%) reported significantly less pain after TESIs but still showed noncentralization with MDT reassessment (significant reductions in leg pain and disability [P < 0.05] and a satisfaction rate of 50% at 12 months). A fourth subgroup of 15 patients (22%) did not respond on TESIs and received an operative intervention. The results indicate that a course of TESIs followed by MDT may be able to avoid surgery in a substantial proportion of candidates for herniated lumbar disc surgery. Wiley Periodicals, Inc.

The use of Mechanical Diagnosis and Therapy (MDT) in patients with lower urinary tract symptoms (LUTS): case series.

PubMed

Wu, Di; Rosedale, Richard

2018-02-26

Lower urinary tract symptoms (LUTS) are highly prevalent among men over the age of 40. Even though associations between lumbar spine conditions and LUTS have been documented in the literature, no studies have detailed a specific lumbar assessment and classification process, and the related treatment effects in patients with LUTS. In this case series, we present three male patients with LUTS as primary complaints, who were evaluated and treated with Mechanical Diagnosis and Therapy (MDT) for the lumbar spine. The duration of their symptoms was between 4 months and 7 years. Urogenital pathologies were ruled out for all patients. The Chronic Prostatitis Symptom Index was used as a functional outcome measure. All patients were classified as having lumbar derangements. Treatment of derangements with directional preference exercises resulted in the improvement of their LUTS, with clinically significant improvements (56.0%-77.4%) in functional outcome measures over an average of six sessions. Preliminary indications suggest that these LUTS cases may possibly have had a lumbar spine origin and "mechanical" nature. Therefore, they may be within the scope of MDT assessments and interventions. With careful monitoring of symptoms, MDT may serve as a screening tool and conservative treatment option.

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 2, February/March 1998

DTIC Science & Technology

1998-03-01

comment: Leprosy is a chronic disease, caused by Mycobacterium leprae , that affects the skin and peripheral nerves of human hosts. Individuals with...untreated infections shed M. leprae in high concentrations in their nasal secretions; however, transmission from infected to uninfected persons generally...Individuals infected with M. leprae quickly become noninfectious after initiating multiple drug therapy (MDT). Thus, aggressive case finding linked to MDT

Maggot Debridement Therapy of Infected Ulcers: Patient and Wound Factors Influencing Outcome – A Study on 101 Patients with 117 Wounds

PubMed Central

Steenvoorde, Pascal; Jacobi, Cathrien E; Van Doorn, Louk; Oskam, Jacques

2007-01-01

INTRODUCTION It has been known for centuries that maggots are potent debriding agents capable of removing necrotic tissue and slough. In January 2004, the US Food and Drug Administration decided to regulate maggot debridement therapy (MDT). As it is still not clear which wounds are likely or unlikely to benefit from MDT, we performed a prospective study to gain more insight in patient and wound characteristics influencing outcome. PATIENTS AND METHODS In the period between August 2002 and December 2005, patients with infected wounds with signs of gangrenous or necrotic tissue who seemed suited for MDT were enrolled in the present study. In total, 101 patients with 117 ulcers were treated. Most wounds were worst-case scenarios, in which maggot therapy was a treatment of last resort. RESULTS In total, 72 patients (71%) were classified as ASA III or IV. In total, 78 of 116 wounds (67%) had a successful outcome. These wounds healed completely (n = 60), healed almost completely (n = 12) or were clean at least (n = 6) at last follow-up. These results seem to be in line with those in the literature. All wounds with a traumatic origin (n = 24) healed completely. All wounds with septic arthritis (n = 13), however, failed to heal and led in half of these cases to a major amputation. According to a multivariate analysis, chronic limb ischaemia (odds ratio [OR], 7.5), the depth of the wound (OR, 14.0), and older age (≥ 60 years; OR, 7.3) negatively influenced outcome. Outcome was not influenced by gender, obesity, diabetes mellitus, smoking, ASAclassification, location of the wound, wound size or wound duration. CONCLUSIONS Some patient characteristics (i.e. gender, obesity, smoking behaviour, presence of diabetes mellitus and ASA-classification at presentation) and some wound characteristics (i.e. location of the wound, wound duration and size) do not seem to contra-indicate eligibility for MDT. However, older patients and patients with chronic limb ischaemia or deep wounds are less likely to benefit from MDT. Septic arthritis does not seem to be a good indication for MDT. PMID:18201474

Low back pain: an assessment using positional MRI and MDT.

PubMed

Hedberg, Karen; Alexander, Lyndsay A; Cooper, Kay; Hancock, Elizabeth; Ross, Jenny; Smith, Francis W

2013-04-01

Current guidelines advise against the use of routine imaging for low back pain. Positional MRI can provide enhanced assessment of the lumbar spine in functionally loaded positions which are often relevant to the presenting clinical symptoms. The purpose of this case report is to highlight the use of positional MRI in the assessment and classification of a subject with low back pain. A low back pain subject underwent a Mechanical Diagnosis and Therapy (MDT) assessment and positional MRI scan of the lumbar spine. The MDT assessment classified the subject as "other" since the subjective history indicated a possible posterior derangement whilst the objective assessment indicated a possible anterior derangement. Positional MRI scanning in flexed, upright and extended sitting postures confirmed the MDT assessment findings to reveal a dynamic spinal stenosis which reduced in flexion and increased in extension. Copyright © 2012 Elsevier Ltd. All rights reserved.

Transforaminal epidural steroid injections influence Mechanical Diagnosis and Therapy (MDT) pain response classification in candidates for lumbar herniated disc surgery.

PubMed

van Helvoirt, Hans; Apeldoorn, Adri T; Knol, Dirk L; Arts, Mark P; Kamper, Steven J; van Tulder, Maurits W; Ostelo, Raymond W

2016-04-27

Prospective cohort study. Although lumbar radiculopathy is regarded as a specific diagnosis, the most effective treatment strategy is unclear. Commonly used treatments include transforaminal epidural steroid injections (TESIs) and Mechanical Diagnosis & Therapy (MDT), but no studies have investigated the effectiveness of this combination. MDT differentiates pain centralization (C) from non-centralization (NC), which indicates good vs. poor prognostic validity respectively. The main aims were 1) to determine changes in Mechanical Diagnosis and Therapy (MDT) pain response classifications after transforaminal epidural steroid injections (TESIs) in candidates for lumbar herniated disc surgery and 2) to evaluate differences in short and long term outcomes for patients with different pain response classifications. Candidates for lumbar herniated disc surgery were assessed with a MDT protocol and their pain response classified as centralizing or peripheralizing. For this study,only patients were eligible who showed a peripheralizing pain response at intake. All patients then received TESIs and were reassessed and classified using the MDT protocol, into groups according to pain response (resolved, centralizing, peripheralizing with less pain and peripheralising with severe pain). After receiving targeted treatment based on pain response after TESIs, ranging from advice, MDT or surgery, follow-up assessments were completed at discharge and at 12 months. The primary outcomes were disability (Roland-Morris Disability Questionnaire [RMDQ] for Sciatica), pain severity in leg (visual analogue scale [VAS], 0-100) and global perceived effect (GPE). Linear mixed-models were used to determine between-groups differences in outcome. A total of 77 patients with lumbar disc herniation and peripheralizing symptoms were included. Patients received an average of 2 (SD 0.7) TESIs. After TESIs, 17 patients (22%) were classified as peripheralizing with continuing severe pain.These patients underwent surgery and were not further evaluated. Eleven (14%) patients were classified as resolved, 37 (48%) as centralizing with significant less pain, and 12 (16%) as peripheralizing with significant less pain. None of these patients underwent surgery. Resolved and centralizer subgroups had better outcomes in terms of VAS and RMDQ than the non-operated peripheralizers at discharge and at 12 months. The succes rates (GPE) for the resolved, centralizing, and peripheralizing with less pain patients were 100%, 100% and 33% respectively at short term, and 100%, 92% and 50% respectively at long term. After TESIs, a peripheralizing pain pattern changed to resolved or centralizing in 62% of the patients. For the non-operated patients, those with a centralising pattern after TESIs reported better pain and disability outcomes than those with peripheralizing pattern at short and long term.

International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes

PubMed Central

Manickam, Ponnaiah; Mehendale, Sanjay M.; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D.

2016-01-01

Background & objectives: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Methods: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. Results: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. Interpretation & conclusions: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696] PMID:28256460

International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes.

PubMed

Manickam, Ponnaiah; Mehendale, Sanjay M; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D

2016-10-01

Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

[Leprosy reactions in discharged patients following cure by multidrug therapy].

PubMed

Souza, Linton Wallis Figueiredo

2010-01-01

Reactional states are the main cause of nerve lesions and incapacities provoked by leprosy. Retrospective study aimed at verifying the frequency of leprosy reactions in discharged patients following cure by multidrug therapy (MDT). Among patients who presented reactions during treatment, 35.5% continued after MDT; of those that did not present during treatment, only 12.7% presented after discharge; 63.4% multibacillary patients presented during and 31.7% after; 27.7% paucibacillary patients presented during and 8.3% after. A direct proportional relation exists between the presence of reactions during and after treatment. Multibacillary clinical forms present a greater frequency of reactions during and after cure.

Rapid resolution of chronic shoulder pain classified as derangement using the McKenzie method: a case series

PubMed Central

Aytona, Maria Corazon; Dudley, Karlene

2013-01-01

The McKenzie method, also known as Mechanical Diagnosis and Therapy (MDT), is primarily recognized as an evaluation and treatment method for the spine. However, McKenzie suggested that this method could also be applied to the extremities. Derangement is an MDT classification defined as an anatomical disturbance in the normal resting position of the joint, and McKenzie proposed that repeated movements could be applied to reduce internal joint displacement and rapidly reduce derangement symptoms. However, the current literature on MDT application to shoulder disorders is limited. Here, we present a case series involving four patients with chronic shoulder pain from a duration of 2–18 months classified as derangement and treated using MDT principles. Each patient underwent mechanical assessment and was treated with repeated movements based on their directional preference. All patients demonstrated rapid and clinically significant improvement in baseline measures and the disabilities of the arm, shoulder, and hand (QuickDASH) scores from an average of 38% at initial evaluation to 5% at discharge within 3–5 visits. Our findings suggest that MDT may be an effective treatment approach for shoulder pain. PMID:24421633

The role and structure of the multidisciplinary team in the management of advanced Parkinson’s disease with a focus on the use of levodopa–carbidopa intestinal gel

PubMed Central

Pedersen, Stephen W; Suedmeyer, Martin; Liu, Louis W C; Domagk, Dirk; Forbes, Alison; Bergmann, Lars; Onuk, Koray; Yegin, Ashley; van Laar, Teus

2017-01-01

A multidisciplinary team (MDT) approach is increasingly recommended in Parkinson’s disease (PD) treatment guidelines, but no standard of care exists for such an approach, and the guidelines do not provide clarification on how it should be implemented. This paper reviews evidence of MDT interventions in people with PD and provides expert clinical perspectives for an MDT approach, with a focus on advanced PD and levodopa–carbidopa intestinal gel (carbidopa–levodopa enteral suspension in the USA). The key recommendations are to enable the best possible treatment of people with PD locally by facilitating a close structured collaboration of different health care professionals working in a fixed network structure; to refer people with PD to established MDT centers in a timely manner; to establish regular meetings for the MDT enabling interdisciplinary exchange and learning; to optimize individual treatment and carefully evaluate available treatment options; to ensure treatment decisions are agreed jointly between people with PD, their caregivers, family, and health care professional; and to include specialists outside of neurology from adjuvant medical departments as necessary when implementing advanced therapies. PMID:28115853

SU-F-J-175: Evaluation of Metal Artifact Reduction Algorithms in Computed Tomography and Their Application to Radiation Therapy Treatment Planning

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

Norris, H; Rangaraj, D; Kim, S

Purpose: High-Z (metal) implants in CT scans cause significant streak-like artifacts in the reconstructed dataset. This results in both inaccurate CT Hounsfield units for the tissue as well as obscuration of the target and organs at risk (OARs) for radiation therapy planning. Herein we analyze two metal artifact reduction algorithms: GE’s Smart MAR and a Metal Deletion Technique (MDT) for geometric and Hounsfield Unit (HU) accuracy. Methods: A CT-to-electron density phantom, with multiple inserts of various densities and a custom Cerrobend insert (Zeff=76.8), is utilized in this continuing study. The phantom is scanned without metal (baseline) and again with themore » metal insert. Using one set of projection data, reconstructed CT volumes are created with filtered-back-projection (FBP) and the MAR and the MDT algorithms. Regions-of-Interest (ROIs) are evaluated for each insert for HU accuracy; the metal insert’s Full-Width-Half-Maximum (FWHM) is used to evaluate the geometric accuracy. Streak severity is quantified with an HU error metric over the phantom volume. Results: The original FBP reconstruction has a Root-Mean-Square-Error (RMSE) of 57.55 HU (STD=29.19, range=−145.8 to +79.2) compared to baseline. The MAR reconstruction has a RMSE of 20.98 HU (STD=13.92, range=−18.3 to +61.7). The MDT reconstruction has a RMSE of 10.05 HU (STD=10.5, range=−14.8 to +18.6). FWHM for baseline=162.05; FBP=161.84 (−0.13%); MAR=162.36 (+0.19%); MDT=162.99 (+0.58%). Streak severity metric for FBP=19.73 (22.659% bad pixels); MAR=8.743 (9.538% bad); MDT=4.899 (5.303% bad). Conclusion: Image quality, in terms of HU accuracy, in the presence of high-Z metal objects in CT scans is improved by metal artifact reduction reconstruction algorithms. The MDT algorithm had the highest HU value accuracy (RMSE=10.05 HU) and best streak severity metric, but scored the worst in terms of geometric accuracy. Qualitatively, the MAR and MDT algorithms increased detectability of inserts, although there is a loss of in-plane resolution near the metallic insert.« less

Twenty five years follow up of MB leprosy patients retreated with a modified MDT regimen after a full course of dapsone mono-therapy.

PubMed

Jing, Zhichun; Zhang, Renbao; Zhou, Doahai; Chen, Jiakeun

2009-06-01

The relentless emergence of dapsone resistance amongst M. leprae threatened leprosy control programmes, and increased the relapse rate of patients cured with dapsone monotherapy. The study aimed to analyse the effect on the relapse rate of dapsone-cured multibacillary (MB) leprosy patients, of re-treatment, using a multidrug therapy (MDT) regimen which differed from the WHO recommended regimen. 794 MB leprosy patients who had been released from treatment after dapsone monotherapy were selected, amongst them 657 were re-treated for 1 year using the modified multidrug therapy regimen (mMDT) including rifampicin, clofazimine and dapsone, and 137 patients were observed as control cases. The regimen was well tolerated with good compliance: 620 patients completed re-treatment with mild side effects and a low incidence of leprosy reactions. There was a statistically significant difference between the relapse rates of re-treated and control groups (chi squaredf = 57.44, P < 0.001). Furthermore, the relapses in the re-treated group were significantly more likely to be later than those in the control group (t = 25.62, P < 0.001). Re-treatment with this modified regimen is acceptable and can reduce the risk of early relapse in dapsone-cured patients. The problem of persisters causing late relapse is likely to remain.

Growth and Survival of Bagged Lucilia sericata Maggots in Wounds of Patients Undergoing Maggot Debridement Therapy.

PubMed

Cičková, Helena; Cambal, Marek; Kozánek, Milan; Takáč, Peter

2013-01-01

Maggot debridement therapy (MDT) is an established method of debridement of nonhealing wounds. Despite intense clinical research about its efficacy and effects of substances produced by the larvae, growth and development of maggots in the wounds remain largely unexplored. In the present study, the bags with larvae (n = 52), which had been used to debride traumatic, ischemic, diabetic and venous ulcers, were collected and examined. Survival, length, width and larval instar of the maggots within each bag were recorded and analyzed with respect to the wound type and duration of the treatment. Survival of maggots after a 48-h cycle of MDT ranged between 63.6 and 82.7%. Maggots in venous ulcers had on average 9-19% higher mortality than maggots within traumatic, ischemic, and diabetic ulcers. Length of larvae after 48 h cycle of MDT reached on average 7.09-9.68 mm, and average width varied between 1.77 and 2.26 mm. Larvae in venous ulcers were significantly smaller after 48 h, but not after 72 h treatment compared to the other wound types. Further studies should be aimed to identify other patient-associated factors which might influence growth and survival of the larvae during maggot debridement therapy.

Inter-examiner classification reliability of Mechanical Diagnosis and Therapy for extremity problems - Systematic review.

PubMed

Takasaki, Hiroshi; Okuyama, Kousuke; Rosedale, Richard

2017-02-01

Mechanical Diagnosis and Therapy (MDT) is used in the treatment of extremity problems. Classifying clinical problems is one method of providing effective treatment to a target population. Classification reliability is a key factor to determine the precise clinical problem and to direct an appropriate intervention. To explore inter-examiner reliability of the MDT classification for extremity problems in three reliability designs: 1) vignette reliability using surveys with patient vignettes, 2) concurrent reliability, where multiple assessors decide a classification by observing someone's assessment, 3) successive reliability, where multiple assessors independently assess the same patient at different times. Systematic review with data synthesis in a quantitative format. Agreement of MDT subgroups was examined using the Kappa value, with the operational definition of acceptable reliability set at ≥ 0.6. The level of evidence was determined considering the methodological quality of the studies. Six studies were included and all studies met the criteria for high quality. Kappa values for the vignette reliability design (five studies) were ≥ 0.7. There was data from two cohorts in one study for the concurrent reliability design and the Kappa values ranged from 0.45 to 1.0. Kappa values for the successive reliability design (data from three cohorts in one study) were < 0.6. The current review found strong evidence of acceptable inter-examiner reliability of MDT classification for extremity problems in the vignette reliability design, limited evidence of acceptable reliability in the concurrent reliability design and unacceptable reliability in the successive reliability design. Copyright © 2017 Elsevier Ltd. All rights reserved.

WHO Multidrug Therapy for Leprosy: Epidemiology of Default in Treatment in Agra District, Uttar Pradesh, India

PubMed Central

Kumar, Anil; Girdhar, Anita; Chakma, Joy Kumar; Girdhar, Bhuwneswar Kumar

2015-01-01

Aim. To study the magnitude of default, time of default, its causes, and final clinical outcome. Methods. Data collected in active surveys in Agra is analyzed. Patients were given treatment after medical confirmation and were followed up. The treatment default and other clinical outcomes were recorded. Results. Patients who defaulted have comparable demographic characteristics. However, among defaulters more women (62.7% in PB, 42.6% in MB) were seen than those in treatment completers (PB 52.7% and MB 35.9%). Nerve involvement was high in treatment completers: 45.7% in PB and 91.3% in MB leprosy. Overall default rate was lower (14.8%) in ROM than (28.8%) in standard MDT for PB leprosy (χ 1 2 = 11.6, P = 0.001) and also for MB leprosy: 9.1% in ROM compared to 34.5% in MDT (χ 1 2 = 6.0, P = 0.015). Default rate was not different (28.8% versus 34.5%, P > 0.05) in both types of leprosy given MDT. Most patients defaulted at early stage of treatment and mainly due to manageable side effects. Conclusion. The default in standard MDT both for PB and MB leprosy was observed to be significantly higher than in ROM treatment. Most defaults occurred at early stage of treatment and major contribution of default is due to side effects like drowsiness, weakness, vomiting, diarrhea, and so forth, related to poor general health. Although about half of the defaulters were observed to be cured 2.2% in PB-MDT and 10.9% of MB-MDT developed disability. This is an issue due to default. Attempts are needed to increase treatment compliance. The use of specially designed disease related health education along with easily administered drug regimens may help to reduce default. PMID:25705679

A Review and Empirical Comparison of Two Treatments for Adolescent Males with Conduct and Personality Disorder: Mode Deactivation Therapy and Cognitive Behavior Therapy

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Siv, Alexander M.

2005-01-01

This research study compared the efficacy of two treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

Empirical Comparison of Three Treatments for Adolescent Males with Physical and Sexual Aggression: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.; Jennings, Jerry L.; Murphy, Christopher J.; Hunter, Linda A.; Siv, Alexander M.

2005-01-01

This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

A Review and Empirical Comparison of Three Treatments for Adolescent Males with Conduct and Personality Disorder: Mode Deactivation Therapy, Cognitive Behavior Therapy and Social Skills Training

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.

2006-01-01

This research study compared the efficacy of three treatment methodologies for adolescent males in residential treatment with conduct disorders and/or personality dysfunctions and documented problems with physical and sexual aggression. The results showed that Mode Deactivation Therapy, an advanced form of cognitive behavioral therapy based on…

Defibrillator patients should not be denied a peaceful death.

PubMed

Westerdahl, Annika Kinch; Sutton, Richard; Frykman, Viveka

2015-03-01

Implantable defibrillators (ICDs) prevent sudden cardiac death. With declining health, ICD therapy may prolong death and expose the patient to unnecessary pain and anxiety. Few studies have addressed end of life care in ICD patients. The objective of this study was to investigate end of life in ICD patients, with respect to location of death; duration between do-not-resuscitate (DNR)-orders and deactivation of ICD therapy or DNR and time of death. A descriptive analysis of 65 deceased ICD patients, all whom had a written DNR-order before death, is presented. The majority (86%) was treated in hospitals, mainly (63%) university hospitals, and many (33%) in cardiology wards. Despite DNR-order, ICD shock therapy was active in 51% of all patients. In those with therapy deactivated at death, therapy deactivation was carried out two days or more after DNR-order in more than a third (38%). The time from DNR decision to death in patients with therapy active had a median of four days (IQR 1-38). During the last 24h of life, 24% of the patients experienced shock treatment. The majority of ICD patients with a DNR-order were treated in university hospitals. More than half still had shock treatment active at time of death with a median of four days or more between DNR decision and death. Patients with therapy deactivated, two days or more elapsed in more than a third from DNR decision to deactivation of therapy, exposing patients to a high risk of painful shocks before death. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

EVALUATION AND TREATMENT OF A PATIENT DIAGNOSED WITH ADHESIVE CAPSULITIS CLASSIFIED AS A DERANGEMENT USING THE MCKENZIE METHOD: A CASE REPORT.

PubMed

Bowser, Ashley; Swanson, Brian T

2016-08-01

The McKenzie Method of mechanical diagnosis and therapy (MDT) is supported in the literature as a valid and reliable approach to the management of spine injuries. It can also be applied to the peripheral joints, but has not been explored through research to the same extent. This method sub-classifies an injury based on tissue response to mechanical loading and repeated motion testing, with directional preferences identified in the exam used to guide treatment. The purpose of this case report is to demonstrate the assessment, intervention, and clinical outcomes of a subject classified as having a shoulder derangement syndrome using MDT methodology. The subject was a 52-year-old female with a four-week history of insidious onset left shoulder pain, referred to physical therapy with a medical diagnosis of adhesive capsulitis. She presented with pain (4-7/10 on the visual analog scale [VAS]) and decreased shoulder range of motion that limited her activities of daily living and work capabilities (Upper Extremity Functional Index (UEFI) score: 55/80). Active and passive ranges of motion (A/PROM) were limited in all planes. Repeated motion testing was performed, with an immediate reduction in pain and increased shoulder motion in all planes following repeated shoulder extension. As a result, her MDT classification was determined to be derangement syndrome. Treatment involved specific exercises, primarily repeated motions, identified as symptom alleviating during the evaluation process. The subject demonstrated significant improvements in the UEFI (66/80), VAS (0-2/10), and ROM within six visits over eight weeks. At the conclusion of treatment, A/PROM was observed to be equal to the R shoulder without pain. This subject demonstrated improved symptoms and functional abilities following evaluation and treatment using MDT methodology. While a cause-effect relationship cannot be determined with a single case, MDT methodology may be a useful approach to the examination, and potentially management, of patients with shoulder pain. This method offers a patient specific approach to treating the shoulder, particularly when the pathoanatomic structure affected is unclear. 4.

Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae.

PubMed

Benjak, Andrej; Avanzi, Charlotte; Singh, Pushpendra; Loiseau, Chloé; Girma, Selfu; Busso, Philippe; Fontes, Amanda N Brum; Miyamoto, Yuji; Namisato, Masako; Bobosha, Kidist; Salgado, Claudio G; da Silva, Moisés B; Bouth, Raquel C; Frade, Marco A C; Filho, Fred Bernardes; Barreto, Josafá G; Nery, José A C; Bührer-Sékula, Samira; Lupien, Andréanne; Al-Samie, Abdul R; Al-Qubati, Yasin; Alkubati, Abdul S; Bretzel, Gisela; Vera-Cabrera, Lucio; Sakho, Fatoumata; Johnson, Christian R; Kodio, Mamoudou; Fomba, Abdoulaye; Sow, Samba O; Gado, Moussa; Konaté, Ousmane; Stefani, Mariane M A; Penna, Gerson O; Suffys, Philip N; Sarno, Euzenir Nunes; Moraes, Milton O; Rosa, Patricia S; Baptista, Ida M F Dias; Spencer, John S; Aseffa, Abraham; Matsuoka, Masanori; Kai, Masanori; Cole, Stewart T

2018-01-24

Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.

Australian contemporary management of synchronous metastatic colorectal cancer.

PubMed

Malouf, Phillip; Gibbs, Peter; Shapiro, Jeremy; Sockler, Jim; Bell, Stephen

2018-01-01

This article outlines the current Australian multidisciplinary treatment of synchronous metastatic colorectal adenocarcinoma and assesses the factors that influence patient outcome. This is a retrospective analysis of the prospective 'Treatment of Recurrent and Advanced Colorectal Cancer' registry, describing the patient treatment pathway and documenting the extent of disease, resection of the colorectal primary and metastases, chemotherapy and biological therapy use. Cox regression models for progression-free and overall survival were constructed with a comprehensive set of clinical variables. Analysis was intentionn-ton-treat, quantifying the effect of treatment intent decided at the multidisciplinary team meeting (MDT). One thousand one hundred and nine patients presented with synchronous metastatic disease between July 2009 and November 2015. Median follow-up was 15.8 months; 4.4% (group 1) had already curative resections of primary and metastases prior to MDT, 22.2% (group 2) were considered curative but were referred to MDT for opinion and/or medical oncology treatment prior to resection and 70.2% were considered palliative at MDT (group 3). Overall, 83% received chemotherapy, 55% had their primary resected and 23% had their metastases resected; 13% of resections were synchronous, 20% were staged with primary resected first and 62% had only the colorectal primary managed surgically. Performance status, metastasis resection (R0 versus R1 versus R2 versus no resection), resection of the colorectal primary and treatment intent determined at MDT were the most significant factors for progression-free and overall survival. This is the largest Australian series of synchronous metastatic colorectal adenocarcinoma and offers insight into the nature and utility of contemporary practice. © 2016 Royal Australasian College of Surgeons.

[Pay more attention to the standardized oncologic assessment of gastric cancer prior to starting therapy].

PubMed

Ji, Jiafu; Shan, Fei

2015-02-01

With the development of specialized gastric cancer oncology, multidisciplinary treatment(MDT) model has been widely accepted and implemented. Reasonable combination of comprehensive therapy and individualized treatment can really benefit patients, but its premise is comprehensive and detailed assessment of the tumor. We must pay more attention to the standardized oncologic assessment of gastric cancer prior to starting therapy, including staging, resectability assessment, and the pathological and molecular features.

What Do Clinicians Consider when Assessing Chronic Low Back Pain? A Content Analysis of Multidisciplinary Pain Centre Team Assessments of Functioning, Disability, and Health.

PubMed

Bagraith, Karl S; Strong, Jenny; Meredith, Pamela J; McPhail, Steven M

2018-05-22

Beyond expert suggestions as to the appropriate subject matter for chronic pain assessments, little is known about the actual content of multidisciplinary pain centre (MPC) clinical assessments. The International Classification of Functioning, Disability and Health Low Back Pain Core Set (ICF LBP-CS) provides a universal language to support the consistent description of LBP-related assessments across disciplines within multidisciplinary teams (MDT). This study sought to map the content of MPC clinical assessments to the ICF to: 1) identify and compare the content of clinical MDT assessments using a cross-disciplinary framework and, 2) examine the content validity of the LBP-CS. A qualitative examination of MPC team clinical assessments of CLBP was undertaken. MDT (pain medicine, psychiatry, nursing, physiotherapy, occupational therapy, and psychology) assessments were audio-recorded and transcribed. Concepts were extracted from transcripts using a meaning condensation procedure and then linked to the ICF. Across seven MDT assessments, comprised of 42 discipline-specific assessments and 241,209 transcribed words, 8596 concepts were extracted. Contextual factors (i.e., the person and environment), except for physiotherapy, accounted for almost half of each discipline's assessments (range: 49% - 58%) Concepts spanned 113 second-level ICF categories, including 73/78 LBP-CS categories. Overall, the findings revealed novel insights into the content of MPC clinical assessments that can be used to improve healthcare delivery. ICF-based assessment profiles demonstrated unique contributions from each discipline to CLBP assessment. Finally, users of the LBP-CS can be confident that the tool exhibits sound content validity from the perceptive of MDT assessments of functioning, disability, and health.

Assessing the Treatment Effects in Apraxia of Speech: Introduction and Evaluation of the Modified Diadochokinesis Test

ERIC Educational Resources Information Center

Hurkmans, Joost; Jonkers, Roel; Boonstra, Anne M.; Stewart, Roy E.; Reinders-Messelink, Heleen A.

2012-01-01

Background: The number of reliable and valid instruments to measure the effects of therapy in apraxia of speech (AoS) is limited. Aims: To evaluate the newly developed Modified Diadochokinesis Test (MDT), which is a task to assess the effects of rate and rhythm therapies for AoS in a multiple baseline across behaviours design. Methods: The…

Magnetic field-assisted gene delivery: achievements and therapeutic potential.

PubMed

Schwerdt, Jose I; Goya, Gerardo F; Calatayud, M Pilar; Hereñú, Claudia B; Reggiani, Paula C; Goya, Rodolfo G

2012-04-01

The discovery in the early 2000's that magnetic nanoparticles (MNPs) complexed to nonviral or viral vectors can, in the presence of an external magnetic field, greatly enhance gene transfer into cells has raised much interest. This technique, called magnetofection, was initially developed mainly to improve gene transfer in cell cultures, a simpler and more easily controllable scenario than in vivo models. These studies provided evidence for some unique capabilities of magnetofection. Progressively, the interest in magnetofection expanded to its application in animal models and led to the association of this technique with another technology, magnetic drug targeting (MDT). This combination offers the possibility to develop more efficient and less invasive gene therapy strategies for a number of major pathologies like cancer, neurodegeneration and myocardial infarction. The goal of MDT is to concentrate MNPs functionalized with therapeutic drugs, in target areas of the body by means of properly focused external magnetic fields. The availability of stable, nontoxic MNP-gene vector complexes now offers the opportunity to develop magnetic gene targeting (MGT), a variant of MDT in which the gene coding for a therapeutic molecule, rather than the molecule itself, is delivered to a therapeutic target area in the body. This article will first outline the principle of magnetofection, subsequently describing the properties of the magnetic fields and MNPs used in this technique. Next, it will review the results achieved by magnetofection in cell cultures. Last, the potential of MGT for implementing minimally invasive gene therapy will be discussed.

Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model.

PubMed

Wilsey, Jared T; Block, Julie H

2018-01-01

Previous research suggests that the α 2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action. The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model. The depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone) polymer film containing 3% (w/w) clonidine HCl (MDT3). Fifty-two young adult mix Landrace pigs (9-11 kg) were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8). Group 2 received three placebo strips (PBO, n=8), placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8), Group 4 received two MDT3 and one PBO (n=8), and Group 5 received three MDT3 (n=8). Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8) or clonidine solution (Group 7, 225 µg/day, n=4). The surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg), but not clonidine (up to 225 µg), completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7. These data suggest that a sustained-release clonidine depot may be a viable nonopioid, nonamide anesthetic therapy for the treatment of acute postsurgical nociceptive sensitization.

Characterization and regulation of the resistance-nodulation-cell division-type multidrug efflux pumps MdtABC and MdtUVW from the fire blight pathogen Erwinia amylovora.

PubMed

Pletzer, Daniel; Weingart, Helge

2014-07-11

The Gram-negative bacterium Erwinia amylovora is the causal agent of the devastating disease fire blight in rosaceous plants such as apple, pear, quince, raspberry, and cotoneaster. In order to survive and multiply in a host, microbes must be able to circumvent the toxic effects of antimicrobial plant compounds, such as flavonoids and tannins. E. amylovora uses multidrug efflux transporters that recognize and actively export toxic compounds out of the cells. Here, two heterotrimeric resistance-nodulation-cell division (RND)-type multidrug efflux pumps, MdtABC and MdtUVW, from E. amylovora were identified. These RND systems are unusual in that they contain two different RND proteins forming a functional pump. To find the substrate specificities of the two efflux systems, we overexpressed the transporters in a hypersensitive mutant lacking the major RND pump AcrB. Both transporters mediated resistance to several flavonoids, fusidic acid and novobiocin. Additionally, MdtABC mediated resistance towards josamycin, bile salts and silver nitrate, and MdtUVW towards clotrimazole. The ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock was reduced. Quantitative RT-PCR analyses revealed that the expression of the transporter genes was induced during infection of apple rootstock. The polyphenolic plant compound tannin, as well as the heavy metal salt tungstate was found to induce the expression of mdtABC. Finally, the expression of the mdtABC genes was shown to be regulated by BaeR, the response regulator of the two-component system BaeSR, a cell envelope stress response system that controls the adaptive responses to changes in the environment. The expression of MdtABC and MdtUVW is induced during growth of E. amylovora in planta. We identified the plant polyphenol tannin as inducer of mdtABC expression. The reduced ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock suggests that the efflux pumps are involved in resistance to plant antimicrobials, maybe including flavonoids, which were identified as substrates of both pumps. Furthermore, we found that the mdtABC operon belongs to the regulon of the two-component regulator BaeR suggesting a role of this RND transporter in the cell envelope stress response of E. amylovora.

Characterization and regulation of the Resistance-Nodulation-Cell Division-type multidrug efflux pumps MdtABC and MdtUVW from the fire blight pathogen Erwinia amylovora

PubMed Central

2014-01-01

Background The Gram-negative bacterium Erwinia amylovora is the causal agent of the devastating disease fire blight in rosaceous plants such as apple, pear, quince, raspberry, and cotoneaster. In order to survive and multiply in a host, microbes must be able to circumvent the toxic effects of antimicrobial plant compounds, such as flavonoids and tannins. E. amylovora uses multidrug efflux transporters that recognize and actively export toxic compounds out of the cells. Here, two heterotrimeric resistance-nodulation-cell division (RND)-type multidrug efflux pumps, MdtABC and MdtUVW, from E. amylovora were identified. These RND systems are unusual in that they contain two different RND proteins forming a functional pump. Results To find the substrate specificities of the two efflux systems, we overexpressed the transporters in a hypersensitive mutant lacking the major RND pump AcrB. Both transporters mediated resistance to several flavonoids, fusidic acid and novobiocin. Additionally, MdtABC mediated resistance towards josamycin, bile salts and silver nitrate, and MdtUVW towards clotrimazole. The ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock was reduced. Quantitative RT-PCR analyses revealed that the expression of the transporter genes was induced during infection of apple rootstock. The polyphenolic plant compound tannin, as well as the heavy metal salt tungstate was found to induce the expression of mdtABC. Finally, the expression of the mdtABC genes was shown to be regulated by BaeR, the response regulator of the two-component system BaeSR, a cell envelope stress response system that controls the adaptive responses to changes in the environment. Conclusions The expression of MdtABC and MdtUVW is induced during growth of E. amylovora in planta. We identified the plant polyphenol tannin as inducer of mdtABC expression. The reduced ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock suggests that the efflux pumps are involved in resistance to plant antimicrobials, maybe including flavonoids, which were identified as substrates of both pumps. Furthermore, we found that the mdtABC operon belongs to the regulon of the two-component regulator BaeR suggesting a role of this RND transporter in the cell envelope stress response of E. amylovora. PMID:25012600

The cancer multi-disciplinary team from the co-ordinators’ perspective: results from a national survey in the UK

PubMed Central

2012-01-01

Background The MDT-Coordinators’ role is relatively new, and as such it is evolving. What is apparent is that the coordinator’s work is pivotal to the effectiveness and efficiency of an MDT. This study aimed to assess the views and needs of MDT-coordinators. Methods Views of MDT-coordinators were evaluated through an online survey that covered their current practice and role, MDT chairing, opinions on how to improve MDT meetings, and coordinators’ educational/training needs. Results 265 coordinators responded to the survey. More than one third of the respondents felt that the job plan does not reflect their actual duties. It was reported that medical members of the MDT always contribute to case discussions. 66.9% of the respondents reported that the MDTs are chaired by Surgeons. The majority reported having training on data management and IT skills but more than 50% reported that they felt further training is needed in areas of Oncology, Anatomy and physiology, audit and research, peer-review, and leadership skills. Conclusions MDT-Coordinators’ role is central to the care of cancer patients. The study reveals areas of training requirements that remain unmet. Improving the resources and training available to MDT-coordinators can give them an opportunity to develop the required additional skills and contribute to improved MDT performance and ultimately cancer care. Finally, this study looks forward to the impact of the recent launch of a new e-learning training programme for MDT coordinators and discusses implications for future research. PMID:23237502

Multidisciplinary care model for HIV improves treatment outcome: a single-centre experience from the Middle East.

PubMed

Elgalib, Ali; Al-Sawafi, Halima; Kamble, Bina; Al-Harthy, Saud; Al-Sariri, Qamra

2018-05-24

Multidisciplinary team (MDT) care models have been shown to improve clinical outcomes among HIV patients. We aim to assess the impact of adopting MDT approach in a tertiary HIV clinic in Muscat, Sultanate of Oman. We introduced MDT approach in our HIV centre in January 2016 where existing team members (counsellors, nurses, social workers, pharmacists and doctors) worked together, through care pathways, to support patients as they go through the HIV care continuum from diagnosis to viral suppression. Notes were reviewed for demographics and clinical data. The primary outcome was HIV viral load (VL) suppression (<20, < 200 and < 1000 copies/ml) in measurements by December 2015 and June 2017. In December 2015, 253 patients were in care; 98.4% (249/253) were on antiretroviral therapy (ART). Median age was 41 years and 70% were males. Median baseline CD4 was 204. In June 2017, 294 were in care with similar patient characteristics to those in care in 2015. The majority, 95.9% (282/294), were on ART; 8 of whom started ART within 3 months, hence excluded from the VL analysis. Overall, VL < 200 and < 1000 rates increased from 71.9% and 78.7% in 2015 to 90.5% and 95.6% in 2017, with relative risk (RR) (95% CI) of 1.26 (1.15-1.37) and 1.21 (1.13-1.30), respectively; p value < 0.0001 for both. In a sub-analysis of 214 patients who were in care in 2015 and remained in care in 2017, VL < 200 and < 1000 rates increased from 78.5% and 85% in 2015 to 90.2% and 94.4% in 2016, with RR (95% CI) of 1.15 (1.06 to 1.25) and 1.11 (1.04-1.18), respectively; p values of 0.0010 for both. MDT approach has significantly improved treatment outcome for existing patients and those who have attended our services since the introduction of the MDT model.

What is a virtual multidisciplinary team (vMDT)?

PubMed Central

Munro, A J; Swartzman, S

2013-01-01

Background: Multidisciplinary team meetings (MDTs), also known as tumour boards or multidisciplinary case conferences, are an integral component of contemporary cancer care. There are logistical problems with setting up and maintaining participation in these meetings. An ill-defined concept, the virtual MDT (vMDT), has arisen in response to these difficulties. We have, in order to provide clarity and to generate discussion, attempted to define the concept of the vMDT, outline its advantages and disadvantages, and consider some of the practical aspects involved in setting up a virtual MDT. Methods: This is an unstructured review of published evidence and personal experience relating to virtual teams in general, and to MDTs in particular. Results: We have devised a simple taxonomy for MDTs, discussed some of the practicalities involved in setting up a vMDT, and described some of the potential advantages and disadvantages associated with vMDTs. Conclusion: The vMDT may be useful for discussions concerning rare or unusual tumours, or for helping guide the assessment and management of patients with uncommon complications related to treatment. However, the vMDT is a niche concept and is currently unlikely to replace the more traditional face-to-face MDT in the management of common tumours at specific sites. PMID:23756866

Secondary multidrug efflux pump mutants alter Escherichia coli biofilm growth in the presence of cationic antimicrobial compounds.

PubMed

Bay, Denice C; Stremick, Carol A; Slipski, Carmine J; Turner, Raymond J

2017-04-01

Escherichia coli possesses many secondary active multidrug resistance transporters (MDTs) that confer overlapping substrate resistance to a broad range of antimicrobials via proton and/or sodium motive force. It is uncertain whether redundant MDTs uniquely alter cell survival when cultures grow planktonically or as biofilms. In this study, the planktonic and biofilm growth and antimicrobial resistance of 13 E. coli K-12 single MDT gene deletion strains in minimal and rich media were determined. Antimicrobial tolerance to tetracycline, tobramycin and benzalkonium were also compared for each ΔMDT strain. Four E. coli MDT families were represented in this study: resistance nodulation and cell division members acrA, acrB, acrD, acrE, acrF and tolC; multidrug and toxin extruder mdtK; major facilitator superfamily emrA and emrB; and small multidrug resistance members emrE, sugE, mdtI and mdtJ. Deletions of multipartite efflux system genes acrB, acrE and tolC resulted in significant reductions in both planktonic and biofilm growth phenotypes and enhanced antimicrobial susceptibilities. The loss of remaining MDT genes produced similar or enhanced (acrD, acrE, emrA, emrB, mdtK, emrE and mdtJ) biofilm growth and antimicrobial resistance. ΔMDT strains with enhanced antimicrobial tolerance also enhanced biofilm biomass. These findings suggest that many redundant MDTs regulate biofilm formation and drug tolerance. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Improving patient survival with the colorectal cancer multi-disciplinary team.

PubMed

MacDermid, E; Hooton, G; MacDonald, M; McKay, G; Grose, D; Mohammed, N; Porteous, C

2009-03-01

There is little information on the impact of the colorectal multi-disciplinary team (MDT) in the United Kingdom. Our single operator presented his patients before and after the inception of an MDT meeting in June 2002. The aim of this study was to assess the effect of this on his patients' survival, and trends in the use of adjuvant chemotherapy. Data were collected on all patients (n = 310) undergoing colectomy for colorectal cancer by one surgeon. Excluding patients with Dukes A stage, the pre-MDT cohort from January 1997 to May 2002 was 176 and the post-MDT cohort from June 2002 to December 2005 was 134. Three-year survival rates were calculated using Kaplan-Meier life table analysis. Prognostic factors were analysed using Cox-proportional hazard regression, and chemotherapy data analysed using the chi-squared test. Independent prognostic indicators of chemotherapy prescription were examined using binary logistic testing. MDT status was shown to be an independent predictor of survival on hazard regression analysis (P = 0.044). A significantly greater number of patients were prescribed adjuvant chemotherapy in the post-MDT cohort (P = 0.0002). MDT status was shown to be a significant prognostic indicator of chemotherapy prescription (P < 0.0001). Three-year survival for Dukes C patients was 58% in the pre-MDT group, and 66% in the post-MDT group (P = 0.023). There was a significant increase in patients undergoing adjuvant postoperative chemotherapy after the inception of the MDT. This was associated with a significant survival benefit in patients with Dukes C disease. The data suggest that the MDT process has resulted in an increase in the prescription of adjuvant chemotherapy, with 3-year survival being greater after its inception.

Health plan joins with physical therapy facility to manage back and neck pain.

PubMed

Tomlinson, Charles M; Gray, Chad; Kane, Tom

2008-06-01

Twenty-five billion dollars is spent each year on the medical care of back pain, and $50 billion is lost in productivity. Primary care physicians might have difficulty providing thorough counseling and treatment to their patients about the condition. In 2006, Capital Health Plan (CHP) partnered with Orthopedic and Sports Physical Therapy, which employed the mechanical diagnosis and therapy (MDT) technique. After undergoing this technique, members experienced a 79% improvement in pain scores and a 54% improvement in function scores, compared to when they started treatment.

The MDT Innovation: Machine-Scoring of Fill-in-the-Blank Tests.

ERIC Educational Resources Information Center

Anderson, Paul S.

The Multi-Digit Technologies (MDT) testing technique is discussed as the first major advance in computer assisted testing in several decades. The MDT testing method uses fill-in-the-blank or completion-type questions, with an alphabetized long list of possible responses. An MDT answer sheet is used to record the code number of the answer. For…

The antiviral effects of RSV fusion inhibitor, MDT-637, on clinical isolates, vs its achievable concentrations in the human respiratory tract and comparison to ribavirin.

PubMed

Kim, Young-In; Pareek, Rajat; Murphy, Ryan; Harrison, Lisa; Farrell, Eric; Cook, Robert; DeVincenzo, John

2017-11-01

Respiratory syncytial virus (RSV) viral load and disease severity associate, and the timing of viral load and disease run in parallel. An antiviral must be broadly effective against the natural spectrum of RSV genotypes and must attain concentrations capable of inhibiting viral replication within the human respiratory tract. We evaluated a novel RSV fusion inhibitor, MDT-637, and compared it with ribavirin for therapeutic effect in vitro to identify relative therapeutic doses achievable in humans. MDT-637 and ribavirin were co-incubated with RSV in HEp-2 cells. Quantitative PCR assessed viral concentrations; 50% inhibitory concentrations (IC 50 ) were compared to achievable human MDT-637 and ribavirin peak and trough concentrations. The IC 50 for MDT-637 and ribavirin (against RSV-A Long) was 1.42 and 16 973 ng/mL, respectively. The ratio of achievable peak respiratory secretion concentration to IC 50 was 6041-fold for MDT-637 and 25-fold for aerosolized ribavirin. The ratio of trough concentration to IC 50 was 1481-fold for MDT-637 and 3.29-fold for aerosolized ribavirin. Maximal peak and trough levels of oral or intravenous ribavirin were significantly lower than their IC 50 s. We also measured MDT-637 IC 50 s in 3 lab strains and 4 clinical strains. The IC 50 s ranged from 0.36 to 3.4 ng/mL. Achievable human MDT-637 concentrations in respiratory secretions exceed the IC 50 s by factors from hundreds to thousands of times greater than does ribavirin. Furthermore, MDT-637 has broad in vitro antiviral activity on clinical strains of different RSV genotypes and clades. Together, these data imply that MDT-637 may produce a superior clinical effect compared to ribavirin on natural RSV infections. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

A prospective analysis of implementation of multi-disciplinary team decisions in breast cancer.

PubMed

English, Rachel; Metcalfe, Chris; Day, James; Rayter, Zenon; Blazeby, Jane M

2012-09-01

Multi-disciplinary teams (MDTs) management of patients with cancer is mandatory in the United Kingdom, and auditing team decision-making by examining rates of decision implementation and reasons for nonimplementation may inform this practice. Consecutive breast cancer MDT decisions, subsequent decision implementation, and reasons for nonimplementation were prospectively recorded. Factors associated with nonimplementation of the MDT decision were analyzed with logistic regression. Of 289 consecutive MDT decisions involving 210 women, 20 (6.9%, 95% CIs 4.3%-10.5%) were not implemented. Most changed MDT decisions did so because of patient preferences (n = 13, 65%), with the discovery of new clinical information (n = 3) and individual doctor's views (n = 4) also leading to decision nonimplementation. MDT decisions were significantly less likely to be adhered to in patients with confirmed malignant disease compared to those with benign or 'unknown' disease categories (p < 0.001) and MDT decisions in older patients were significantly more likely not to be implemented than in younger patients (p = 0.002). Auditing nonimplementation of MDT recommendations and examining reasons for changed decisions is a useful process to monitor team performance and to identify factors that need more attention during the MDT meeting to ensure that the process makes optimal patient centered decisions. © 2012 Wiley Periodicals, Inc.

Progression of leprosy disability after discharge: is multidrug therapy enough?

PubMed Central

Sales, Anna Maria; Campos, Dayse Pereira; Hacker, Mariana Andrea; da Costa Nery, José Augusto; Düppre, Nádia Cristina; Rangel, Emanuel; Sarno, Euzenir Nunes; Penna, Maria Lucia Fernandes

2013-01-01

Objective To evaluate the risk factors related to worsening of physical disabilities after treatment discharge among patients with leprosy administered 12 consecutive monthly doses of multidrug therapy (MDT/WHO). Methods Cohort study was carried out at the Leprosy Laboratory in Rio de Janeiro, Brazil. We evaluated patients with multibacillary leprosy treated (MDT/WHO) between 1997 and 2007. The Cox proportional hazards model was used to estimate the relationship between the onset of physical disabilities after release from treatment and epidemiological and clinical characteristics. Results The total observation time period for the 368 patients was 1 570 person-years (PY), averaging 4.3 years per patient. The overall incidence rate of worsening of disability was 6.5/100 PY. Among those who began treatment with no disability, the incidence rate of physical disability was 4.5/100 PY. Among those who started treatment with Grade 1 or 2 disabilities, the incidence rate of deterioration was 10.5/100 PY. The survival analysis evidenced that when disability grade was 1, the risk was 1.61 (95% CI: 1.02–2.56), when disability was 2, the risk was 2.37 (95% CI 1.35–4.16), and when the number of skin lesions was 15 or more, an HR = 1.97 (95% CI: 1.07–3.63). Patients with neuritis showed a 65% increased risk of worsening of disability (HR = 1.65 [95% CI: 1.08–2.52]). Conclusion Impairment at diagnosis was the main risk factor for neurological worsening after treatment/MDT. Early diagnosis and prompt treatment of reactional episodes remain the main means of preventing physical disabilities. PMID:23937704

The value of multidisciplinary team meetings within an early pregnancy assessment unit.

PubMed

Bharathan, Rasiah; Farag, Mena; Hayes, Kevin

2016-08-01

This is the first study to ascertain the value of multidisciplinary team (MDT) meetings within an early pregnancy assessment unit (EPAU). Our national telephone survey identified that in the United Kingdom, overall 37% of EPAU utilise regular MDT meetings. Secondary and tertiary hospitals are just as likely to hold regular MDT meetings. The participants in our interview study expressed the principal benefits of regular MDT meetings as communication, education and effective stress management. The perceived additional benefits included improved care quality, better patient experience and enhanced team cohesion. During the meetings, at least, one representative from every tier of staffing was present. The caseload of the MDT meeting comprised ectopic pregnancies and pregnancies of unknown location. We propose a number of research studies, which would build on this study. Such efforts will help enhance the effectiveness of the MDT-based EPAU service.

An evaluation of treatment decisions at a colorectal cancer multi-disciplinary team.

PubMed

Wood, J J; Metcalfe, C; Paes, A; Sylvester, P; Durdey, P; Thomas, M G; Blazeby, J M

2008-10-01

It is mandatory for treatment decisions for patients with colorectal cancer to be made within the context of a multi-disciplinary team (MDT) meeting. It is currently uncertain, however, how to best evaluate the quality of MDT decision-making. This study examined MDT decision-making by studying whether MDT treatment decisions were implemented and investigated the reasons why some decisions changed after the meeting. Consecutive MDT treatment decisions were prospectively recorded. Implementation of decisions was studied by examining hospital records. Reasons for changes in MDT decisions were identified. In all, 201 consecutive treatment decisions were analysed, concerning 157 patients. Twenty decisions (10.0%, 95% confidence interval 6.3-15.2%) were not implemented. Looking at the reasons for nonimplementation, nine (40%) related to co-morbidity, seven (35%) to patient choice, two changed in light of new clinical information, one doctor changed a decision and for one changed decision, no reason was apparent. When decisions changed, the final treatment was always more conservative than was originally planned and decisions were more likely to change for colon rather than rectal cancer (P = 0.024). The vast majority of colorectal MDT decisions were implemented and when decisions changed, it mostly related to patient factors that had not been taken into account. Analysis of the implementation of team decisions is an informative process to monitor the quality of MDT decision-making.

Multidrug resistance protein MdtM adds to the repertoire of antiporters involved in alkaline pH homeostasis in Escherichia coli

PubMed Central

2013-01-01

Background In neutralophilic bacteria, monovalent metal cation/H+ antiporters play a key role in pH homeostasis. In Escherichia coli, only four antiporters (NhaA, NhaB, MdfA and ChaA) are identified to function in maintenance of a stable cytoplasmic pH under conditions of alkaline stress. We hypothesised that the multidrug resistance protein MdtM, a recently characterised homologue of MdfA and a member of the major facilitator superfamily, also functions in alkaline pH homeostasis. Results Assays that compared the growth of an E. coli ΔmdtM deletion mutant transformed with a plasmid encoding wild-type MdtM or the dysfunctional MdtM D22A mutant at different external alkaline pH values (ranging from pH 8.5 to 10) revealed a potential contribution by MdtM to alkaline pH tolerance, but only when millimolar concentrations of sodium or potassium was present in the growth medium. Fluorescence-based activity assays using inverted vesicles generated from transformants of antiporter-deficient (ΔnhaA, ΔnhaB, ΔchaA) E. coli TO114 cells defined MdtM as a low-affinity antiporter that catalysed electrogenic exchange of Na+, K+, Rb+ or Li+ for H+. The K+/H+ antiport reaction had a pH optimum at 9.0, whereas the Na+/H+ exchange activity was optimum at pH 9.25. Measurement of internal cellular pH confirmed MdtM as contributing to maintenance of a stable cytoplasmic pH, acid relative to the external pH, under conditions of alkaline stress. Conclusions Taken together, the results support a role for MdtM in alkaline pH tolerance. MdtM can therefore be added to the currently limited list of antiporters known to function in pH homeostasis in the model organism E. coli. PMID:23701827

Multidrug resistance protein MdtM adds to the repertoire of antiporters involved in alkaline pH homeostasis in Escherichia coli.

PubMed

Holdsworth, Scarlett R; Law, Christopher J

2013-05-23

In neutralophilic bacteria, monovalent metal cation/H+ antiporters play a key role in pH homeostasis. In Escherichia coli, only four antiporters (NhaA, NhaB, MdfA and ChaA) are identified to function in maintenance of a stable cytoplasmic pH under conditions of alkaline stress. We hypothesised that the multidrug resistance protein MdtM, a recently characterised homologue of MdfA and a member of the major facilitator superfamily, also functions in alkaline pH homeostasis. Assays that compared the growth of an E. coli ΔmdtM deletion mutant transformed with a plasmid encoding wild-type MdtM or the dysfunctional MdtM D22A mutant at different external alkaline pH values (ranging from pH 8.5 to 10) revealed a potential contribution by MdtM to alkaline pH tolerance, but only when millimolar concentrations of sodium or potassium was present in the growth medium. Fluorescence-based activity assays using inverted vesicles generated from transformants of antiporter-deficient (ΔnhaA, ΔnhaB, ΔchaA) E. coli TO114 cells defined MdtM as a low-affinity antiporter that catalysed electrogenic exchange of Na+, K+, Rb+ or Li+ for H+. The K+/H+ antiport reaction had a pH optimum at 9.0, whereas the Na+/H+ exchange activity was optimum at pH 9.25. Measurement of internal cellular pH confirmed MdtM as contributing to maintenance of a stable cytoplasmic pH, acid relative to the external pH, under conditions of alkaline stress. Taken together, the results support a role for MdtM in alkaline pH tolerance. MdtM can therefore be added to the currently limited list of antiporters known to function in pH homeostasis in the model organism E. coli.

Challenges beyond elimination in leprosy.

PubMed

Naaz, Farah; Mohanty, Partha Sarathi; Bansal, Avi Kumar; Kumar, Dilip; Gupta, Umesh Datta

2017-01-01

Every year >200,000 new leprosy cases are registered globally. This number has been fairly stable over the past 8 years. The World Health Organization has set a target to interrupt the transmission of leprosy globally by 2020. It is important, in terms of global action and research activities, to consider the eventuality of multidrug therapy (MDT) resistance developing. It is necessary to measure disease burden comprehensively, and contact-centered preventive interventions should be part of a global elimination strategy. Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. MDT has proven to be a powerful tool in the control of leprosy, especially when patients report early and start prompt treatment. Adherence to and its successful completion is equally important. This paper has reviewed the current state of leprosy worldwide and discussed the challenges and also emphasizes the challenge beyond the elimination in leprosy.

Availability and feasibility of structured, routine collection of comorbidity data in a colorectal cancer multi-disciplinary team (MDT) setting.

PubMed

Abukar, A A; Ramsanahie, A; Martin-Lumbard, K; Herrington, E R; Winslow, V; Wong, S; Ahmed, S; Thaha, M A

2018-05-03

Availability of comorbidity assessment at multi-disciplinary team (MDT) discussions is cornerstone in making the MDT process more robust and decisive in optimising treatment and improving quality of survivorship. Comorbidity assessments using tools, such as the ACE-27 questionnaire would aid in optimising the decision-making process at MDTs so that treatment decisions can be made without delay. This study determined the availability of comorbidity data in a CRC MDT and the feasibility of routine comorbidity data collection using the validated ACE-27 questionnaire. Secondary aims determined the optimal time and method of collecting comorbidity data. A retrospective mapping exercise (phase I; 6-months) examined the availability of comorbidity data within the MDT. Phase II prospectively collected comorbidity data using ACE-27 for a 3-month period following a short pilot. In phase I, 73/135 (54%) patients had comorbidity data readily available informing the MDT discussion; 62 patients lacked this information. After a review of the patient records, it was clear that 41 of these 62 also had comorbidities and 21 out of the 135 had ≥ 2 major system disorders. Common referral sources to the MDT were surgical outpatient clinics (42%) and the endoscopy unit (13%). The average lead-time from referral to MDT discussion was 14 days. In phase II, an ACE-27 questionnaire was prospectively administered in 50 patients, mean age 54 years (range 20-84). Male: female ratio 26:24. Average time to administer ACE-27 was 4.8 min (range 1-15). The phase I study confirmed the widely acknowledged view of poor comorbidity data availability within a CRC MDT. Phase II demonstrated the feasibility of routinely collecting comorbidity data using ACE-27.

Quenching-induced deactivation of photosensitizer by nanoencapsulation to improve phototherapy of cancer.

PubMed

Zeisser-Labouèbe, Magali; Mattiuzzo, Marc; Lange, Norbert; Gurny, Robert; Delie, Florence

2009-09-01

Photodynamic therapy has emerged as a promising alternative to current cancer treatment. However, conventional photosensitizers have several limitations due to their unsuitable pharmaceutical formulations and lack of selectivity. Our strategy was to exploit the advantages of nanoparticles and the quenching-induced deactivation of the model photosensitizer hypericin to produce "activatable" drug delivery systems. Efficient fluorescence and activity quenching were achieved by increasing the drug-loading rate of nanoparticles. In vitro assays confirmed the reversibility of hypericin deactivation, as the hypericin fluorescence and photodynamic activity were recovered upon cell internalization.

Design of Drug Delivery Methods for the Brain and Central Nervous System

NASA Astrophysics Data System (ADS)

Lueshen, Eric

Due to the impermeability of the blood-brain barrier (BBB) to macromolecules delivered systemically, drug delivery to the brain and central nervous system (CNS) is quite difficult and has become an area of intense research. Techniques such as convection-enhanced intraparenchymal delivery and intrathecal magnetic drug targeting offer a means of circumventing the blood-brain barrier for targeted delivery of therapeutics. This dissertation focuses on three aspects of drug delivery: pharmacokinetics, convection-enhanced delivery, and intrathecal magnetic drug targeting. Classical pharmacokinetics mainly uses black-box curve fitting techniques without biochemical or biological basis. This dissertation advances the state-of-the-art of pharmacokinetics and pharmacodynamics by incorporating first principles and biochemical/biotransport mechanisms in the prediction of drug fate in vivo. A whole body physiologically-based pharmacokinetics (PBPK) modeling framework is engineered which creates multiscale mathematical models for entire organisms composed of organs, tissues, and a detailed vasculature network to predict drug bioaccumulation and to rigorously determine kinetic parameters. These models can be specialized to account for species, weight, gender, age, and pathology. Systematic individual therapy design using the proposed mechanistic PBPK modeling framework is also a possibility. Biochemical, anatomical, and physiological scaling laws are also developed to accurately project drug kinetics in humans from small animal experiments. Our promising results demonstrate that the whole-body mechanistic PBPK modeling approach not only elucidates drug mechanisms from a biochemical standpoint, but offers better scaling precision. Better models can substantially accelerate the introduction of drug leads to clinical trials and eventually to the market by offering more understanding of the drug mechanisms, aiding in therapy design, and serving as an accurate dosing tool. Convection-enhanced drug delivery (CED) is a technique used to bypass the BBB via direct intracranial injection using a catheter driven by a positive pressure gradient from an infusion pump. Although CED boasts the advantage of achieving larger drug distribution volumes compared to diffusion driven methods, difficulty in predicting drug spread and preventing backflow along the catheter shaft commonly occur. In this dissertation, a method for predicting drug distributions in the brain using diffusion tensor imaging (DTI) data is employed to show how small variations in catheter placement can lead to drastically different volumes of drug distribution in vivo. The impact that microfluid flow has on deformable brain phantom gel is studied in order to elucidate the causes of backflow, and the results are used to develop backflow-free catheters with safe volumetric flow rates up to 10 ?l/min. Through implementation of our backflow-free catheter designs, physicians will be able to target specific regions of the brain with improved accuracy, increased drug concentration, and larger drug distribution geometries. Intrathecal (IT) drug delivery involves direct drug infusion into the spinal canal and has become standard practice for treating many CNS diseases. Although IT drug delivery boasts the advantage of reduced systemic toxicity compared to oral and intravenous techniques, current IT delivery protocols lack a means of sufficient drug targeting at specific locations of interest within the CNS. In this dissertation, the method of intrathecal magnetic drug targeting (IT-MDT) is developed to overcome the limited targeting capabilities of standard IT drug delivery protocols. The basic idea behind IT-MDT is to guide intrathecally-injected, drug-functionalized magnetic nanoparticles (MNPs) using an external magnetic field to diseased regions within the spinal canal. Cerebrospinal fluid (CSF) transport phenomena are studied, and in vitro human spine surrogates are built. Experiments are run on the in vitro human spine model to determine the feasibility of IT-MDT and to develop novel treatment therapies. Computer simulations are performed to optimize magnetic field placement and/or implant design for generating high gradient magnetic fields, as well as to study how these fields aid in therapeutic nanoparticle localization. Large collection efficiencies of MNPs were achieved during in vitro IT-MDT and implant-assisted IT-MDT experiments with concentration levels nearly nine times that of the control when no magnetic field was present. Testing different magnetizable implants showed that implant design is a key factor in achieving the largest MNP collection efficiency within the targeting region. Knowledge gained from the in vitro IT-MDT experiments and simulations will be used in the future to develop IT-MDT methods in animals and humans.

Mdt1 Facilitates Efficient Repair of Blocked DNA Double-Strand Breaks and Recombinational Maintenance of Telomeres▿

PubMed Central

Pike, Brietta L.; Heierhorst, Jörg

2007-01-01

DNA recombination plays critical roles in DNA repair and alternative telomere maintenance. Here we show that absence of the SQ/TQ cluster domain-containing protein Mdt1 (Ybl051c) renders Saccharomyces cerevisiae particularly hypersensitive to bleomycin, a drug that causes 3′-phospho-glycolate-blocked DNA double-strand breaks (DSBs). mdt1Δ also hypersensitizes partially recombination-defective cells to camptothecin-induced 3′-phospho-tyrosyl protein-blocked DSBs. Remarkably, whereas mdt1Δ cells are unable to restore broken chromosomes after bleomycin treatment, they efficiently repair “clean” endonuclease-generated DSBs. Epistasis analyses indicate that MDT1 acts in the repair of bleomycin-induced DSBs by regulating the efficiency of the homologous recombination pathway as well as telomere-related functions of the KU complex. Moreover, mdt1Δ leads to severe synthetic growth defects with a deletion of the recombination facilitator and telomere-positioning factor gene CTF18 already in the absence of exogenous DNA damage. Importantly, mdt1Δ causes a dramatic shift from the usually prevalent type II to the less-efficient type I pathway of recombinational telomere maintenance in the absence of telomerase in liquid senescence assays. As telomeres resemble protein-blocked DSBs, the results indicate that Mdt1 acts in a novel blocked-end-specific recombination pathway that is required for the efficiency of both drug-induced DSB repair and telomerase-independent telomere maintenance. PMID:17636027

The Experiences of Specialist Nurses Working Within the Uro-oncology Multidisciplinary Team in the United Kingdom

PubMed Central

Punshon, Geoffrey; Endacott, Ruth; Aslett, Phillippa; Brocksom, Jane; Fleure, Louisa; Howdle, Felicity; Masterton, Morven; O’Connor, Anita; Swift, Adrian; Trevatt, Paul; Leary, Alison

2017-01-01

Purpose: United Kingdom prostate cancer nursing care is provided by a variety of urology and uro-oncology nurses. The experience of working in multidisciplinary teams (MDT) was investigated in a national study. Design: The study consisted of a national survey with descriptive statistics and thematic analysis. Methods: A secondary analysis of a data subset from a UK whole population survey was undertaken (n = 285) of the specialist nursing workforce and the services they provide. Data were collected on the experience of working in the MDT. Results: Forty-five percent of the respondents felt that they worked in a functional MDT, 12% felt that they worked in a dysfunctional MDT, and 3.5% found the MDT meeting intimidating. Furthermore, 34% of the nurses felt that they could constructively challenge all members of the MDT in meetings. Themes emerging from open-ended questions were lack of interest in nonmedical concerns by other team members, ability to constructively challenge decisions or views within the meeting, and little opportunity for patients’ wishes to be expressed. Conclusions: Despite expertise and experience, nurses had a variable, often negative, experience of the MDT. It is necessary to ensure that all participants can contribute and are heard and valued. More emphasis should be given to patients’ nonmedical needs. PMID:28594672

The Experiences of Specialist Nurses Working Within the Uro-oncology Multidisciplinary Team in the United Kingdom.

PubMed

Punshon, Geoffrey; Endacott, Ruth; Aslett, Phillippa; Brocksom, Jane; Fleure, Louisa; Howdle, Felicity; Masterton, Morven; O'Connor, Anita; Swift, Adrian; Trevatt, Paul; Leary, Alison

United Kingdom prostate cancer nursing care is provided by a variety of urology and uro-oncology nurses. The experience of working in multidisciplinary teams (MDT) was investigated in a national study. The study consisted of a national survey with descriptive statistics and thematic analysis. A secondary analysis of a data subset from a UK whole population survey was undertaken (n = 285) of the specialist nursing workforce and the services they provide. Data were collected on the experience of working in the MDT. Forty-five percent of the respondents felt that they worked in a functional MDT, 12% felt that they worked in a dysfunctional MDT, and 3.5% found the MDT meeting intimidating. Furthermore, 34% of the nurses felt that they could constructively challenge all members of the MDT in meetings. Themes emerging from open-ended questions were lack of interest in nonmedical concerns by other team members, ability to constructively challenge decisions or views within the meeting, and little opportunity for patients' wishes to be expressed. Despite expertise and experience, nurses had a variable, often negative, experience of the MDT. It is necessary to ensure that all participants can contribute and are heard and valued. More emphasis should be given to patients' nonmedical needs.

The impact of multidisciplinary team meetings on patient assessment, management and outcomes in oncology settings: A systematic review of the literature.

PubMed

Pillay, Brindha; Wootten, Addie C; Crowe, Helen; Corcoran, Niall; Tran, Ben; Bowden, Patrick; Crowe, Jane; Costello, Anthony J

2016-01-01

Conducting regular multidisciplinary team (MDT) meetings requires significant investment of time and finances. It is thus important to assess the empirical benefits of such practice. A systematic review was conducted to evaluate the literature regarding the impact of MDT meetings on patient assessment, management and outcomes in oncology settings. Relevant studies were identified by searching OVID MEDLINE, PsycINFO, and EMBASE databases from 1995 to April 2015, using the keywords: multidisciplinary team meeting* OR multidisciplinary discussion* OR multidisciplinary conference* OR case review meeting* OR multidisciplinary care forum* OR multidisciplinary tumour board* OR case conference* OR case discussion* AND oncology OR cancer. Studies were included if they assessed measurable outcomes, and used a comparison group and/or a pre- and post-test design. Twenty-seven articles met inclusion criteria. There was limited evidence for improved survival outcomes of patients discussed at MDT meetings. Between 4% and 45% of patients discussed at MDT meetings experienced changes in diagnostic reports following the meeting. Patients discussed at MDT meetings were more likely to receive more accurate and complete pre-operative staging, and neo-adjuvant/adjuvant treatment. Quality of studies was affected by selection bias and the use of historical cohorts impacted study quality. MDT meetings impact upon patient assessment and management practices. However, there was little evidence indicating that MDT meetings resulted in improvements in clinical outcomes. Future research should assess the impact of MDT meetings on patient satisfaction and quality of life, as well as, rates of cross-referral between disciplines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clostridium difficile multidisciplinary team root cause analysis: impact on clinical care and circumvention of financial penalties posed by clinical commissioning groups, but at what cost?

PubMed

Saeed, Kordo; Petridou, Christina; Gray, Hazel; Dryden, Matthew; Davis-Blues, Karen; Lucero, Sheryl; Parker, Natalie; Keyser, Taryn; Matthews, Tanya; Cortes, Nick; Kidd, Stephen; Thomas, Claire; Peacock, Heather; Hornzee, Joanna; Wake, Bruce

2018-03-01

In Hampshire Hospitals NHS Foundation Trust, in addition to an on-the-spot investigation into hospital-onset Clostridium difficile infection (CDI) by the infection prevention team, a multidisciplinary team root cause analysis (MDT-RCA) forum has been developed. The MDT-RCA aims to deliver a more thorough investigation into individual cases and the recommendation of cases to the clinical commissioning groups (CCG) appeals panel against potential financial penalties (£10,000 per breached case). We mainly aimed to investigate the financial impact of MDT-RCAs to the Trust. Over two years, 84 cases of hospital-onset CDI cases were reviewed by the MDT-RCA forum. Among this cohort, no additional learning outcomes were identified by the MDT-RCAs over those that were found by on-the-spot investigations. In total, 543 staff members attended the MDT-RCAs at a potential cost to the Trust of £23,795.74-£51,670.10. The Trust appealed against financial penalties for 27 cases and 14 were successful, i.e. £140,000 would have been avoided had targets been breached by 14 cases. However, targets were only breached by two cases, meaning only £20,000 in fines was avoided. Deducting this from the total costs of the MDT-RCA meant the Trust lost £3,795.74-£31,670.10. Over the two years reviewed, the MDT-RCA proved to be costly to the Trust, with no additional learning or quality improvement measures identified.

Technology and medication errors: impact in nursing homes.

PubMed

Baril, Chantal; Gascon, Viviane; St-Pierre, Liette; Lagacé, Denis

2014-01-01

The purpose of this paper is to study a medication distribution technology's (MDT) impact on medication errors reported in public nursing homes in Québec Province. The work was carried out in six nursing homes (800 patients). Medication error data were collected from nursing staff through a voluntary reporting process before and after MDT was implemented. The errors were analysed using: totals errors; medication error type; severity and patient consequences. A statistical analysis verified whether there was a significant difference between the variables before and after introducing MDT. The results show that the MDT detected medication errors. The authors' analysis also indicates that errors are detected more rapidly resulting in less severe consequences for patients. MDT is a step towards safer and more efficient medication processes. Our findings should convince healthcare administrators to implement technology such as electronic prescriber or bar code medication administration systems to improve medication processes and to provide better healthcare to patients. Few studies have been carried out in long-term healthcare facilities such as nursing homes. The authors' study extends what is known about MDT's impact on medication errors in nursing homes.

Analysis of decision making at a multidisciplinary head and neck tumor board incorporating evidence-based National Cancer Comprehensive Network (NCCN) guidelines.

PubMed

Shah, Bhartesh A; Qureshi, Muhammad M; Jalisi, Scharukh; Grillone, Gregory; Salama, Andrew; Cooley, Timothy; Zaner, Ken; Sakai, Osamu; Truong, Minh Tam

2016-01-01

To evaluate incorporation of National Cancer Comprehensive Network (NCCN) guidelines in decision making at a head and neck cancer (HNC) multidisciplinary tumor board (MDT) at an urban academic medical center. A retrospective study of 176 HNC patients was performed. The extent to which MDT decisions and subsequent patient care incorporate NCCN guidelines was evaluated. A total of 173 (98.3%) HNC patients received MDT recommendations according to NCCN guidelines. Of the 159 patients treated, 153 (96.2%) received treatment according to NCCN guidelines. The MDT recommended the highest available evidence-based NCCN category guideline in 78.0%. Subsequent treatment using the same or higher category MDT recommendation occurred in 87.0% of patients. Evaluation of patients at an MDT using NCCN guidelines incorporates the highest level of evidence in approximately 80% of patients and translates well into subsequent care. Incorporation of the highest available NCCN guideline may be improved, although management should be individualized. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Construction and test of new precision drift-tube chambers for the ATLAS muon spectrometer

NASA Astrophysics Data System (ADS)

Kroha, H.; Kortner, O.; Schmidt-Sommerfeld, K.; Takasugi, E.

2017-02-01

ATLAS muon detector upgrades aim for increased acceptance for muon triggering and precision tracking and for improved rate capability of the muon chambers in the high-background regions of the detector with increasing LHC luminosity. The small-diameter Muon Drift Tube (sMDT) chambers have been developed for these purposes. With half of the drift-tube diameter of the MDT chambers and otherwise unchanged operating parameters, sMDT chambers share the advantages of the MDTs, but have an order of magnitude higher rate capability and can be installed in detector regions where MDT chambers do not fit in. The chamber assembly methods have been optimized for mass production, minimizing construction time and personnel. Sense wire positioning accuracies of 5 μm have been achieved in serial production for large-size chambers comprising several hundred drift tubes. The construction of new sMDT chambers for installation in the 2016/17 winter shutdown of the LHC and the design of sMDT chambers in combination with new RPC trigger chambers for replacement of the inner layer of the barrel muon spectrometer are in progress.

Quality improvement in multidisciplinary cancer teams: an investigation of teamwork and clinical decision-making and cross-validation of assessments.

PubMed

Lamb, B W; Sevdalis, N; Mostafid, H; Vincent, C; Green, J S A

2011-12-01

Teamworking and clinical decision-making are important in multidisciplinary cancer teams (MDTs). Our objective is to assess the quality of information presentation and MDT members' contribution to decision-making via expert observation and self-report, aiming to cross-validate the two methods and assess the insight of MDT members into their own team performance. Behaviors were scored using (i) a validated observational tool employing Likert scales with objective anchors, and (ii) a 29-question online self-report tool. Data were collected from observation of 164 cases in five MDTs, and 47 surveys from MDT members (response rate 70%). Presentation of information (case history, radiological, pathological, comorbidities, psychosocial, and patients' views) and quality of contribution to decision-making of MDT members (surgeons, oncologists, radiologists, pathologists, nurses, and MDT coordinators) were analyzed via descriptive statistics and the Jonckheere-Terpstra test. Correlation between observational and self-report assessments was assessed with Spearman's correlations. Quality of information presentation: Case histories and radiology information rated highest; patients' views and comorbidities/psychosocial issues rated lowest (observed: Z = 14.80, P ≤ 0.001; self-report: Z = 3.70, P < 0.001). Contribution to decision-making: Surgeons and oncologists rated highest, nurses and MDT coordinators rated lowest, and others in between (observed: Z = 20.00, P ≤ 0.001; self-report: Z = 8.10, P < 0.001). Correlations between observational and self-report assessments: Median Spearman's rho = 0.74 (range = 0.66-0.91; P < 0.05). The quality of teamworking and clinical decision-making in MDTs can reliably be assessed using observational and self-report metrics. MDT members have good insight into their own team performance. Such robust assessment methods could provide the basis of a toolkit for MDT team evaluation and improvement.

Quality assessment of decision-making in colorectal cancer multidisciplinary meetings.

PubMed

Seretis, Charalampos; Mankotia, Rajnish; Goonetilleke, Kolitha; Rawstorne, Edward

2014-01-01

The quality of decision-making in the colorectal multidisciplinary team (MDT) meetings can significantly affect the quality of care delivered to patients with colorectal cancer. We performed a prospective study to assess the quality of the MDT meetings in a specialized colorectal unit using an externally observational validated tool. An externally validated observational tool, the Colorectal Multidisciplinary Team Metric for Observation of Decision-Making (cMDT-MODe), was used to assess the quality of clinical decision-making in 64 cases. Although case history information presented by the responsible surgeon was rated high (4.4/5), the quality of radiological and histopathological information regarding each patient's case which was available at the time was less adequate, scoring 3.9/5 and 3.8/5, respectively. Moreover, the precise knowledge of patients' personal views and circumstances was a field requiring further improvement. In a general overview however, the quality and extent of the available information enabled the MDT to provide a clear recommendation regarding the patients' treatment plans in 87.5% of the cases. The cMDT-MODe tool can be used to prospectively audit the quality of clinical decision-making in the colorectal MDT meetings and highlight the fields of potential improvement.

Multidisciplinary team management in thoracic oncology: more than just a concept?

PubMed

Powell, Helen A; Baldwin, David R

2014-06-01

Multidisciplinary team (MDT) management in thoracic oncology has been introduced over the past two decades with the aim of improving outcomes for patients. While MDT management has become the standard of care in some countries, not all healthcare systems have adopted this practice. In this article we review the history and implementation of MDT care in thoracic oncology and explore the evidence for, and challenges associated with, this system of working. There are many advantages of an MDT both to the patient, the clinicians and the wider population, but it is difficult to demonstrate a beneficial effect on outcomes such as treatment rates or survival given the substantial number of coexistent changes in the management of thoracic malignancies over the same time period. There are also some disadvantages associated with MDT working, particularly the costs of setting up the service and the time commitment from each of the healthcare professionals involved. Barriers to effective MDT working include poor attendance by some specialists, inadequate preparation and poor quality information about the patient. Variation in quality of MDTs has been reported so it is important that practice is monitored and areas for improvement identified. ©ERS 2014.

Practice Patterns Regarding Multidisciplinary Cancer Management and Suggestions for Further Refinement: Results from a National Survey in Korea.

PubMed

Lee, Yun-Gyoo; Oh, Sukjoong; Kimm, Heejin; Koo, Dong-Hoe; Kim, Do Yeun; Kim, Bong-Seog; Lee, Seung-Sei

2017-10-01

This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were "very satisfied" and "satisfied," respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.

Testing--1,2,...523,...641,...999--Testing: The MDT Multi-Digit Technique Applied to Science Education.

ERIC Educational Resources Information Center

Anderson, Paul S.; Schoner, James S.

The MDT multi-digit technique, a development in testing technology, is described; and its application to science classrooms is discussed. Some actual materials for use in a cell biology class are included. The primary characteristic of an MDT multi-digit test is a long list of possible responses, with each term marked with a three-digit number…

Experimental and theoretical studies of implant assisted magnetic drug targeting

NASA Astrophysics Data System (ADS)

Aviles, Misael O.

One way to achieve drug targeting in the body is to incorporate magnetic nanoparticles into drug carriers and then retain them at the site using an externally applied magnetic field. This process is referred to as magnetic drug targeting (MDT). However, the main limitation of MDT is that an externally applied magnetic field alone may not be able to retain a sufficient number of magnetic drug carrier particles (MDCPs) to justify its use. Such a limitation might not exist when high gradient magnetic separation (HGMS) principles are applied to assist MDT by means of ferromagnetic implants. It was hypothesized that an Implant Assisted -- MDT (IA-MDT) system would increase the retention of the MDCPs at a target site where an implant had been previously located, since the magnetic forces are produced internally. With this in mind, the overall objective of this work was to demonstrate the feasibility of an IA-MDT system through mathematical modeling and in vitro experimentation. The mathematical models were developed and used to demonstrate the behavior and limitations of IA-MDT, and the in vitro experiments were designed and used to validate the models and to further elucidate the important parameters that affect the performance of the system. IA-MDT was studied with three plausible implants, ferromagnetic stents, seed particles, and wires. All implants were studied theoretically and experimentally using flow through systems with polymer particles containing magnetite nanoparticles as MDCPs. In the stent studies, a wire coil or mesh was simply placed in a flow field and the capture of the MDCPs was studied. In the other cases, a porous polymer matrix was used as a surrogate capillary tissue scaffold to study the capture of the MDCPs using wires or particle seeds as the implant, with the seeds either fixed within the polymer matrix or captured prior to capturing the MDCPs. An in vitro heart tissue perfusion model was also used to study the use of stents. In general, all the results demonstrated that IA-MDT is indeed feasible and that careful modification of the MDCP properties and implant properties are fundamental to the success of this technology.

Multidisciplinary team working across different tumour types: analysis of a national survey.

PubMed

Lamb, B W; Sevdalis, N; Taylor, C; Vincent, C; Green, J S A

2012-05-01

Using data from a national survey, this study aimed to address whether the current model for multidisciplinary team (MDT) working is appropriate for all tumour types. Responses to the 2009 National Cancer Action Team national survey were analysed by tumour type. Differences indicate lack of consensus between MDT members in different tumour types. One thousand one hundred and forty-one respondents from breast, gynaecological, colorectal, upper gastrointestinal, urological, head and neck, haematological and lung MDTs were included. One hundred and sixteen of 136 statements demonstrated consensus between respondents in different tumour types. There were no differences regarding the infrastructure for meetings and team governance. Significant consensus was seen for team characteristics, and respondents disagreed regarding certain aspects of meeting organisations and logistics, and patient-centred decision making. Haematology MDT members were outliers in relation to the clinical decision-making process, and lung MDT members disagreed with other tumour types regarding treating patients with advanced disease. This analysis reveals strong consensus between MDT members from different tumour types, while also identifying areas that require a more tailored approach, such as the clinical decision-making process, and preparation for and the organisation of MDT meetings. Policymakers should remain sensitive to the needs of health care teams working in individual tumour types.

Impact of the lung oncology multidisciplinary team meetings on the management of patients with cancer.

PubMed

Ung, Kim Ann; Campbell, Belinda A; Duplan, Danny; Ball, David; David, Steven

2016-06-01

Multidisciplinary team (MDT) meetings are increasingly regarded as a component of multidisciplinary cancer care. We aimed to prospectively measure the impact of MDT meetings on clinicians' management plans for lung oncology patients, and the implementation rate of the meeting recommendations. Consecutive patient cases presented at the weekly lung oncology MDT meetings were prospectively enrolled. Investigators compared the clinicians' management plans pre-meeting with the consensus plans post-meeting. The meeting was considered to have an impact on management plans if ≥1 of the following changes were detected: tumor stage, histology, treatment intent or treatment modality, or if additional investigations were recommended. Investigators reviewed hospital patient records at 4 months to determine if the meeting recommendations were implemented. Reasons for non-implementation were also recorded. Of the 55 eligible cases, the MDT meeting changed management plans in 58% (CI 45-71%; P < 0.005). These changes included: additional investigations (59%), or changes in treatment modality (19%), treatment intent (9%), histology (6%) or tumor stage (6%). The meeting recommendations were implemented in 72% of cases. Reasons for non-implementation included deteriorating patient performance status, clinician's preference, the influence of new clinical information obtained after the meeting or patient decision. MDT meetings significantly impact on the management plans for lung oncology patients. The majority of MDT recommendations (72%) were implemented into patient care. These findings provide further evidence to support the role of MDT meetings as an essential part of the decision-making process for the optimal multidisciplinary management of patients with cancer. © 2014 Wiley Publishing Asia Pty Ltd.

A national survey of pain clinics within the United Kingdom and Ireland focusing on the multidisciplinary team and the incorporation of the extended nursing role.

PubMed

Kailainathan, Pungavi; Humble, Stephen; Dawson, Helen; Cameron, Fiona; Gokani, Shyam; Lidder, Gursimren

2018-02-01

Inconsistencies in the availability and quality of pain service provision have been noted nationally, as have lengthy waiting times for appointments and lack of awareness of the Pain Clinic role. The 2013 NHS England report stated that specialist pain services must offer multispecialty and multidisciplinary pain clinics. This national survey of multidisciplinary pain service provision in the United Kingdom and Ireland provides a snapshot of pain service provision in order to review and highlight what variations exist in multidisciplinary team (MDT) provision and working patterns. A common perception among clinicians is that financial pressures have led to alternate ways of staff utilisation with variable degrees of success. The survey included 143 pain clinics, focusing principally on MDT working patterns, MDT composition and adoption of the extended role. The results identified that the majority of Pain Clinics utilise the MDT approach. However, provision of critical components such as regular MDT meetings is highly variable as is the composition of the MDT itself and also working patterns of the individual clinicians. The survey reports the successful use of the extended roles for specialist nurses in follow up clinics. In contrast, the survey highlights that a large proportion of clinicians surveyed have reservations about both the effectiveness and the safety of utilising specialist nurses in the extended role to see new referrals of complex pain patients to pain clinics. This survey underlines the essential requirement for incorporation of greater MDT working locally and nationally and allocation of appropriate resources to facilitate this.

Ethical challenges of deactivation of cardiac devices in advanced heart failure.

PubMed

Chamsi-Pasha, Hassan; Chamsi-Pasha, Mohammed A; Albar, Mohammed Ali

2014-06-01

More than 23 million adults worldwide have heart failure (HF). Although survival after heart failure diagnosis has improved over time, mortality from heart failure remains high. At the end of life, the chronic HF patient often becomes increasingly symptomatic, and may have other life-limiting comorbidities as well. Multiple trials have shown a clear mortality benefit with the use of implantable cardioverter defibrillators (ICDs) in patients with cardiomyopathy and ventricular arrhythmia. However, patients who have an ICD may be denied the chance of a sudden cardiac death, and instead are committed to a slower terminal decline, with frequent DC shocks that can be painful and decrease the quality of life, greatly contributing to their distress and that of their families during this period. While patients with ICDs are routinely counseled with regard to the benefits of ICDs, they have a poor understanding of the options for device deactivation and related ethical and legal implications. Deactivating an ICD or not performing a generator change is both legal and ethical, and is supported by guidelines from both sides of the Atlantic. Patient autonomy is paramount, and no patient is committed to any therapy that they no longer wish to receive. Left ventricular assist devices (LVADs) were initially used as bridge in patients awaiting heart transplantation, but they are currently implanted as destination therapy (DT) in patients with end-stage heart failure who have failed to respond to optimal medical therapy and who are ineligible for cardiac transplantation. The decision-making process for initiation and deactivation of LVAD is becoming more and more ethically and clinically challenging, particularly for elderly patients.

Determinants of treatment plan implementation in multidisciplinary team meetings for patients with chronic diseases: a mixed-methods study

PubMed Central

Raine, Rosalind; Xanthopoulou, Penny; Wallace, Isla; Nic a’ Bháird, Caoimhe; Lanceley, Anne; Clarke, Alex; Livingston, Gill; Prentice, Archie; Ardron, Dave; Harris, Miriam; King, Michael; Michie, Susan; Blazeby, Jane M; Austin-Parsons, Natalie; Gibbs, Simon; Barber, Julie

2014-01-01

Objective Multidisciplinary team (MDT) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service (NHS). However, evidence for their effectiveness is mixed. Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans. This is a proxy measure of effectiveness, because it lies on the pathway to improvements in health, and reflects team decision making which has taken account of clinical and non-clinical information. Additionally, this measure can be compared across MDTs for different conditions. Methods We undertook a prospective mixed-methods study of 12 MDTs in London and North Thames. Data were collected by observation of 370 MDT meetings, interviews with 53 MDT members, and from 2654 patient medical records. We examined the influence of patient-related factors (disease, age, sex, deprivation, whether their preferences and other clinical/health behaviours were mentioned) and MDT features (as measured using the ‘Team Climate Inventory’ and skill mix) on the implementation of MDT treatment plans. Results The adjusted odds (or likelihood) of implementation was reduced by 25% for each additional professional group represented at the MDT meeting. Implementation was more likely in MDTs with clear goals and processes and a good ‘Team Climate’ (adjusted OR 1.96; 95% CI 1.15 to 3.31 for a unit increase in Team Climate Inventory (TCI) score). Implementation varied by disease category, with the lowest adjusted odds of implementation in mental health teams. Implementation was also lower for patients living in more deprived areas (adjusted odds of implementation for patients in the most compared with least deprived areas was 0.60, 95% CI 0.39 to 0.91). Conclusions Greater multidisciplinarity is not necessarily associated with more effective decision making. Explicit goals and procedures are also crucial. Decision implementation should be routinely monitored to ensure the equitable provision of care. PMID:24915539

Efficiency analysis of diffusion on T-fractals in the sense of random walks.

PubMed

Peng, Junhao; Xu, Guoai

2014-04-07

Efficiently controlling the diffusion process is crucial in the study of diffusion problem in complex systems. In the sense of random walks with a single trap, mean trapping time (MTT) and mean diffusing time (MDT) are good measures of trapping efficiency and diffusion efficiency, respectively. They both vary with the location of the node. In this paper, we analyze the effects of node's location on trapping efficiency and diffusion efficiency of T-fractals measured by MTT and MDT. First, we provide methods to calculate the MTT for any target node and the MDT for any source node of T-fractals. The methods can also be used to calculate the mean first-passage time between any pair of nodes. Then, using the MTT and the MDT as the measure of trapping efficiency and diffusion efficiency, respectively, we compare the trapping efficiency and diffusion efficiency among all nodes of T-fractal and find the best (or worst) trapping sites and the best (or worst) diffusing sites. Our results show that the hub node of T-fractal is the best trapping site, but it is also the worst diffusing site; and that the three boundary nodes are the worst trapping sites, but they are also the best diffusing sites. Comparing the maximum of MTT and MDT with their minimums, we find that the maximum of MTT is almost 6 times of the minimum of MTT and the maximum of MDT is almost equal to the minimum for MDT. Thus, the location of target node has large effect on the trapping efficiency, but the location of source node almost has no effect on diffusion efficiency. We also simulate random walks on T-fractals, whose results are consistent with the derived results.

[Multidisciplinary team meetings settings on the management of women at high risk of inherited breast cancer. A French study].

PubMed

Gillmann, Fanchon; Cordier, Christophe; Taris, Nicolas; Mathelin, Carole; Maugard, Christine M

2016-06-01

In France, 126 centers for cancer genetics coordinate genetic testing and high-risk cancer surveillance for individuals and their families with hereditary cancer syndromes. Since 2012, the French National Cancer Institute (INCa) supports 17 projects to promote and manage the monitoring of individuals genetically predisposed to cancer. They were assigned 4 missions by INCa including expertise for difficult cases. We initiated a national survey to assess how the oncogenetic clinics responded to the 4th mission for women at high risk of developing breast cancers. We sent the survey to all the French oncogeneticists. We aimed at evaluating the modalities and the extent of implementation of the Multidisciplinary team (MDT) meetings regarding the management of women who have genetically higher risks to develop breast cancer. Fourteen people from 12 administrative regions, who represent 10 of the 17 projects, answered the form. Eleven participants reported the submission of medical cases in Oncogenetics MDT meetings (79 %), 5 in senology MDT meetings (36 %), 5 in MDT meetings dedicated to patients at high risk for breast cancer (36 %) and 2 in network meetings (14 %). Some structures discuss medical cases through different MDT meetings. Although MDT meetings are valuable practices to optimize treatment or management options for patients, its settings might be subject to difficulties to federate the appropriate-number of participants as well as cost-effectiveness issues. This survey thus suggests the need of a standardized process of MDT meetings while taking account specificities of oncogenetics. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Invasive placental disease: the impact of a multi-disciplinary team approach to management.

PubMed

Smulian, John C; Pascual, Ana-Liza; Hesham, Helai; Qureshey, Emma; Bijoy Thomas, M; Depuy, Amy M; Flicker, Amanda B; Scorza, William E

2017-06-01

To determine the impact of a structured multi-disciplinary management strategy on clinical outcomes in women with invasive placental disease (IPD). This was a retrospective cohort study of consecutive women having peripartum hysterectomies with IPD over seven years. For the most recent three years, a structured multidisciplinary team (MDT) reviewed each suspected case, created a management plan, and implemented that plan. Outcomes were compared between cases delivered prior to and after the MDT process was started. There were 47 pregnancies with IPD, of which 31 (66.0%) were suspected antenatally and 40 (85.1%) had a prior uterine surgery. An MDT approach was performed in 19 (40.4%) cases. In the MDT group, there were longer operative times (260 min versus 181 min, p = 0.0001), less blood loss (1200 mL versus 2500 mL, p = 0.009), less administration of blood products (47.4% versus 85.7%, p = 0.005), and higher intraoperative lowest mean arterial pressures (MAPs) (57 mmHg versus 48 mmHg, p = 0.002, when compared to the No-MDT (n = 28) approach. No differences were found for other outcomes. Clinically meaningful improvements of less blood loss, fewer transfusions, and higher intraoperative MAPs suggest that MDT cases were more stable intraoperatively, which over a larger number of patients, should translate into improved outcomes.

Global mean dynamic topography based on GOCE data and Wiener filters

NASA Astrophysics Data System (ADS)

Gilardoni, Maddalena; Reguzzoni, Mirko; Albertella, Alberta

2015-04-01

A mean dynamic ocean topography (MDT) has been computed by using a GOCE-only gravity model and a given mean sea surface (MSS) obtained from satellite altimetry. Since the used gravity model, i.e. the fifth release of the time-wise solution covering the full mission lifetime, is truncated at a maximum harmonic degree of 280, the obtained MDT has to be consistently filtered. This has been done globally by using the spherical harmonic representation and following a Wiener minimization principle. This global filtering approach is convenient from the computational point of view but requires to have MDT values all over the Earth surface and therefore to fill the continents with fictitious data. The main improvements with respect to the already presented results are in the MDT filling procedure (to guarantee that the global signal has the same covariance of the one over the oceans), in the error modelling of the input MSS and in the error estimation of the filtered MDT and of the corresponding geostrophic velocities. The impact of GOCE data in the ocean circulation global modelling has been assessed by comparing the pattern of the obtained geostrophic currents with those computed by using EGM2008. Comparisons with independent circulation data based on drifters and other MDT models have been also performed with the aim of evaluating the accuracy of the obtained results.

Microhole Drilling Tractor Technology Development

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

Western Well Tool

2007-07-09

In an effort to increase the U.S. energy reserves and lower costs for finding and retrieving oil, the USDOE created a solicitation to encourage industry to focus on means to operate in small diameter well-Microhole. Partially in response to this solicitation and because Western Well Tool's (WWT) corporate objective to develop small diameter coiled tubing drilling tractor, WWT responded to and was awarded a contract to design, prototype, shop test, and field demonstrate a Microhole Drilling Tractor (MDT). The benefit to the oil industry and the US consumer from the project is that with the MDT's ability to facilitate Coiledmore » Tubing drilled wells to be 1000-3000 feet longer horizontally, US brown fields can be more efficiently exploited resulting in fewer wells, less environmental impact, greater and faster oil recovery, and lower drilling costs. Shortly after award of the contract, WWT was approached by a major oil company that strongly indicated that the specified size of a tractor of 3.0 inches diameter was inappropriate and that immediate applications for a 3.38-inch diameter tractor would substantially increase the usefulness of the tool to the oil industry. Based on this along with an understanding with the oil company to use the tractor in multiple field applications, WWT applied for and was granted a no-cost change-of-scope contract amendment to design, manufacture, assemble, shop test and field demonstrate a prototype a 3.38 inch diameter MDT. Utilizing existing WWT tractor technology and conforming to an industry developed specification for the tool, the Microhole Drilling Tractor was designed. Specific features of the MDT that increase it usefulness are: (1) Operation on differential pressure of the drilling fluid, (2) On-Off Capability, (3) Patented unique gripping elements (4) High strength and flexibility, (5) Compatibility to existing Coiled Tubing drilling equipment and operations. The ability to power the MDT with drilling fluid results in a highly efficient tool that both delivers high level of force for the pressure available and inherently increases downhole reliability because parts are less subject to contamination. The On-Off feature is essential to drilling to allow the Driller to turn off the tractor and pull back while circulating in cleanout runs that keep the hole clean of drilling debris. The gripping elements have wide contact surfaces to the formation to allow high loads without damage to the formation. As part of the development materials evaluations were conducted to verify compatibility with anticipated drilling and well bore fluids. Experiments demonstrated that the materials of the tractor are essentially undamaged by exposure to typical drilling fluids used for horizontal coiled tubing drilling. The design for the MDT was completed, qualified vendors identified, parts procured, received, inspected, and a prototype was assembled. As part of the assembly process, WWT prepared Manufacturing instructions (MI) that detail the assembly process and identify quality assurance inspection points. Subsequent to assembly, functional tests were performed. Functional tests consisted of placing the MDT on jack stands, connecting a high pressure source to the tractor, and verifying On-Off functions, walking motion, and operation over a range of pressures. Next, the Shop Demonstration Test was performed. An existing WWT test fixture was modified to accommodate operation of the 3.38 inch diameter MDT. The fixture simulated the tension applied to a tractor while walking (pulling) inside 4.0 inch diameter pipe. The MDT demonstrated: (1) On-off function, (2) Pulling forces proportional to available differential pressure up to 4000 lbs, (3) Walking speeds to 1100 ft/hour. A field Demonstration of the MDT was arranged with a major oil company operating in Alaska. A demonstration well with a Measured Depth of approximately 15,000 ft was selected; however because of problems with the well drilling was stopped before the planned MDT usage. Alternatively, functional and operational tests were run with the MDT inside 4.5 inch tubing at depths of 800-950 ft. The MDT successfully demonstrated On-Off capability, pulled with up to 1465 lbs force, and verified its capability to transmit torque though it from the Orienter. Forces generated by the tractor were limited due to insufficient differential pressure because of the unloaded downhole motor, which is not typical during drilling conditions. Additionally, the Coefficient of Friction between the MDT grippers and the tubing was much less than the anticipated COF of the sandstone formation. Despite these minor limitations, to summarize the MDT operated as expected. Minor modifications to the MDT are being incorporated to improve gripping capability of the tractor. Additional demonstration wells are being arranged to expand on the project's goals of delivering a fully operational utilitarian tool for use throughout the US to improve reserves.« less

Lumbar lateral shift in a patient with interspinous device implantation: a case report.

PubMed

Peterson, Seth; Hodges, Cheri

2016-09-01

Lumbar lateral shift (LLS) is a common clinical observation but has rarely been described in a patient with a history of lumbar surgery. The purpose of the current case report was to describe the use of the McKenzie Method of Mechanical Diagnosis and Therapy (MDT) in the multi-modal treatment of a patient with an LLS and a history of multiple surgical procedures in the lumbar spine, including interspinous process device (IPD) implantation. A 72-year-old female with chronic low back pain (LBP) and a surgical history in the lumbar spine was referred to physical therapy for radiating leg pain and presented with a right LLS. Her chief complaints included sitting for long periods, vacuuming and ascending stairs into her home. The patient was treated during eight visits over 30 days. Treatment interventions included manual shift correction, self-correction and management, joint mobilisation below the level of IPD implantation ,neurophysiology education, and development of a home exercise programme. At discharge, her leg pain was resolved and all goals had been met. The patient reported maintenance of gains at 6-month follow-up. Utilisation of the MDT approach, including LLS correction, produced positive outcomes in a complex patient with previous IPD implantation. Future research should investigate treatment and outcomes after invasive spinal procedures in similar patient populations to better inform clinical management. 4.

Deactivation of cisplatin-resistant human lung/ovary cancer cells with pyropheophorbide-α methyl ester-photodynamic therapy.

PubMed

Qian, Guanhua; Wang, Li; Zheng, Xueling; Yu, Tinghe

2017-12-02

The aim of this study was to determine whether photodynamic therapy (PDT) alone or combined with cisplatin (DDP), can deactivate cisplatin-resistant cancer cells. Human cancer cell lines A549 and SKOV3, and chemoresistant sublines A549/DDP and SKOV3/DDP, were subjected to PDT, DDP, or PDT combined with DDP. Cell viability and apoptosis were analyzed, and then intracellular reactive oxygen species (ROS) and proteins related to apoptosis were determined. PDT caused cell death, and PDT combined with DDP led to the highest percentage of dead cells in 4 cell lines; similar results were detected in ROS; a quantification evaluation manifested that the combined effect was addition. DDP increased the percentage of apoptotic cells, and the ROS level in A549 and SKOV3 cells, which was not observed in A549/DDP and SKOV3/DDP cells. Western blot revealed an increase of caspase 3 and Bax, and a decrease of Bcl-2, demonstrating the occurrence of apoptosis. The data suggest that PDT can efficiently deactivate resistant cells and enhance the action of DDP against resistant cancer cells.

Social marketing to eliminate leprosy in Sri Lanka.

PubMed

Williams, P G; Dewapura, D; Gunawardene, P; Settinayake, S

1998-01-01

Leprosy is a chronic infectious disease which, if untreated, can lead to permanent and progressive nerve damage and thus to deformities of the limbs, eyes, and face. People with leprosy have long been ostracized by society. The clinical signs of leprosy include insensitive skin lesions and thickened peripheral nerves. Untreated infectious leprosy cases are the main source of infection, transmitting the disease through nasal secretions. People with low cell-mediated immunity are at risk of developing clinically active leprosy irrespective of gender, age, or social class. The World Health Organization (WHO) has, since 1982, recommended multiple drug therapy (MDT) against leprosy, an approach capable of curing the disease within 1 year and interrupting its transmission. According to WHO, leprosy is currently a public health problem in 55 countries and more than 20% of the estimated 1.15 million cases of leprosy worldwide remain undetected. Although Sri Lanka was the first country in South Asia to provide MDT to all registered leprosy patients, first making it available in 1984, the disease continues to be transmitted due to the large number of undetected cases in the country. An ongoing social marketing program was therefore launched in 1990 by the local health ministry and the Novartis Foundation for Sustainable Development to eliminate leprosy from Sri Lanka. The program encourages people with suspicious skin lesions to seek diagnosis and care, teaches health care providers to recognize leprosy and refer cases for treatment, and helps the general public to understand that leprosy is just a normal disease. The socially marketed product is MDT, provided free-of-charge by the Novartis Foundation to all leprosy patients.

Time until diagnosis of clinical events with different remote monitoring systems in Implantable Cardioverter-Defibrillator patients.

PubMed

Söth-Hansen, Malene; Witt, Christoffer Tobias; Rasmussen, Mathis; Kristensen, Jens; Gerdes, Christian; Nielsen, Jens Cosedis

2018-05-24

Remote monitoring (RM) is an established technology integrated into routine follow-up of patients with implantable cardioverter-defibrillator (ICD). Current RM systems differ according to transmission frequency and alert definition. We aimed to compare time difference between detection and acknowledgement of clinically relevant events between four RM systems. We analyzed time delay between detection of ventricular arrhythmic and technical events by the ICD and acknowledgement by hospital staff in 1.802 consecutive patients followed with RM during September 2014 - August 2016. Devices from Biotronik (BIO, n=374), Boston Scientific (BSC, n=196), Medtronic (MDT, n=468) and St Jude Medical (SJM, n=764) were included. We identified all events from RM webpages and their acknowledgement with RM or at in-clinic follow-up. Events occurring during weekends were excluded. We included 3.472 events. Proportion of events acknowledged within 24 hours was 72%, 23%, 18% and 65% with BIO, BSC, MDT and SJM, respectively, with median times of 13, 222, 163 and 18 hours from detection to acknowledgement (p<0.001 for both comparisons between manufacturers). Including only events transmitted as alerts by RM, 72%, 68%, 61% and 65% for BIO, BSC, MDT and SJM, respectively were acknowledged within 24 hours. Variation in time to acknowledgement of ventricular tachyarrhythmia episodes not treated with shock therapy was the primary cause for the difference between manufacturers. Significant and clinically relevant differences in time delay from event detection to acknowledgement exist between RM systems. Varying definitions of which events RM transmits as alerts are important for the differences observed. Copyright © 2018. Published by Elsevier Inc.

Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases

PubMed Central

Bührer-Sékula, Samira; Benjak, Andrej; Loiseau, Chloé; Singh, Pushpendra; Pontes, Maria A. A.; Gonçalves, Heitor S.; Hungria, Emerith M.; Busso, Philippe; Piton, Jérémie; Silveira, Maria I. S.; Cruz, Rossilene; Schetinni, Antônio; Costa, Maurício B.; Virmond, Marcos C. L.; Diorio, Suzana M.; Dias-Baptista, Ida M. F.; Rosa, Patricia S.; Matsuoka, Masanori; Penna, Maria L. F.; Cole, Stewart T.; Penna, Gerson O.

2017-01-01

Background Since leprosy is both treated and controlled by multidrug therapy (MDT) it is important to monitor recurrent cases for drug resistance and to distinguish between relapse and reinfection as a means of assessing therapeutic efficacy. All three objectives can be reached with single nucleotide resolution using next generation sequencing and bioinformatics analysis of Mycobacterium leprae DNA present in human skin. Methodology DNA was isolated by means of optimized extraction and enrichment methods from samples from three recurrent cases in leprosy patients participating in an open-label, randomized, controlled clinical trial of uniform MDT in Brazil (U-MDT/CT-BR). Genome-wide sequencing of M. leprae was performed and the resultant sequence assemblies analyzed in silico. Principal findings In all three cases, no mutations responsible for resistance to rifampicin, dapsone and ofloxacin were found, thus eliminating drug resistance as a possible cause of disease recurrence. However, sequence differences were detected between the strains from the first and second disease episodes in all three patients. In one case, clear evidence was obtained for reinfection with an unrelated strain whereas in the other two cases, relapse appeared more probable. Conclusions/Significance This is the first report of using M. leprae whole genome sequencing to reveal that treated and cured leprosy patients who remain in endemic areas can be reinfected by another strain. Next generation sequencing can be applied reliably to M. leprae DNA extracted from biopsies to discriminate between cases of relapse and reinfection, thereby providing a powerful tool for evaluating different outcomes of therapeutic regimens and for following disease transmission. PMID:28617800

Drug resistance patterns in Mycobacterium leprae isolates from relapsed leprosy patients attending The Leprosy Mission (TLM) Hospitals in India.

PubMed

Lavania, Mallika; Jadhav, Rupendra S; Chaitanya, Vedithi Sundeep; Turankar, Ravindra; Selvasekhar, Abraham; Das, Loretta; Darlong, Famkima; Hambroom, Ujjwal K; Kumar, Sandip; Sengupta, Utpal

2014-09-01

Implementation of multidrug therapy (MDT) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. After many years of use of MDT, it is expected that drug resistance in Mycobacterium leprae may emerge. This is a major concern, especially during the stage of elimination. In the present study, slit-skin smears were collected from 140 leprosy relapse cases from different Leprosy Mission hospitals across India. DNA extracted from 111 (79%) of these samples was analysed for the genes associated with drug resistance in M. leprae. More than 90% of the patients relapsed as multibacillary (MB) cases. In our study, four (3.6%) of the DNA samples analysed showed mutations associated with rifampicin resistance. We also observed that mutations associated with resistance to dapsone and ofloxacin were observed in 9 (8.1%) of the DNA samples each; two samples had both dapsone and ofloxacin resistance. Further surveillance and appropriate interventions are needed to ensure the continued success of chemotherapy for leprosy.

A Process of Multidisciplinary Team Communication to Individualize Stroke Rehabilitation of an 84-Year-Old Stroke Patient.

PubMed

Hiragami, Fukumi; Hiragami, Shogo; Suzuki, Yasuo

Previously, we have used a multidisciplinary team (MDT) approach to individualize rehabilitation of very old stroke patients as a means to establish intervention points for addressing impaired activities of daily living (ADL). However, this previous study was limited because of a lack in describing the communication process over time. This case study characterized the MDT communication process in the rehabilitation of an 84-year-old patient over the course of 15 weeks. The MDT consisted of 3 nurses, 1 doctor, 6 therapists, and the patient/families. Meetings (15 minutes each) were held at 4, 6, 8, and 15 weeks following the patient's admission. To individualize the rehabilitation, the communication process involved gaining knowledge about ADL impairments, sharing assessments, providing treatment options, and reflecting on desired treatment outcomes-a process termed KATR. The knowledge, assessment, treatment, and reflection (KATR) process established intervention points focusing on specific ADL impairments. The team members focused the interventions on the impaired ADL identified in the KATR process, and individualized rehabilitation was generated from the MDT information-sharing knowledge. In the initial meeting (Week 4), intervention points derived from the KATR process focused on rehabilitation of self-care impairments. These impairments improved by Week 15. By the last meeting, the MDT intervention points focused on mobility impairments. Having an organized communication process (i.e., KATR) facilitates individualization of rehabilitation without lengthy and frequent MDT meetings and enhances the quality of rehabilitation after a stroke.

Results from an exploratory study to identify the factors that contribute to success for UK medical device small- and medium-sized enterprises.

PubMed

Hourd, P C; Williams, D J

2008-07-01

This paper reports the results from an exploratory study that sets out to identify and compare the strategic approaches and patterns of business practice employed by 14 UK small- and medium-sized enterprises to achieve success in the medical device sector of the health-care industry. An interview-based survey was used to construct individual case studies of the medical device technology (MDT) companies. A cross-case analysis was performed to search for patterns and themes that cut across these individual cases. Exploratory results revealed the heterogeneity of MDT companies and the distinctive features of the MDT innovation process that emphasize the importance of a strategic approach for achieving milestones in the product development and exploitation process and for creating value for the company and its stakeholders. Recognizing the heterogeneity of MDT companies, these exploratory findings call for further investigation to understand better the influence of components of the MDT innovation process on the commercialization life cycle and value trajectory. This is required to assist start-up or spin-out MDT companies in the UK and worldwide to navigate the critical transitions that determine access to financial and consumer markets and enhance the potential to build a successful business. This will be important not only for bioscience-based companies but also for engineering-based companies aiming to convert their activities into medical devices and the health- and social-care market.

A Permutation-Randomization Approach to Test the Spatial Distribution of Plant Diseases.

PubMed

Lione, G; Gonthier, P

2016-01-01

The analysis of the spatial distribution of plant diseases requires the availability of trustworthy geostatistical methods. The mean distance tests (MDT) are here proposed as a series of permutation and randomization tests to assess the spatial distribution of plant diseases when the variable of phytopathological interest is categorical. A user-friendly software to perform the tests is provided. Estimates of power and type I error, obtained with Monte Carlo simulations, showed the reliability of the MDT (power > 0.80; type I error < 0.05). A biological validation on the spatial distribution of spores of two fungal pathogens causing root rot on conifers was successfully performed by verifying the consistency between the MDT responses and previously published data. An application of the MDT was carried out to analyze the relation between the plantation density and the distribution of the infection of Gnomoniopsis castanea, an emerging fungal pathogen causing nut rot on sweet chestnut. Trees carrying nuts infected by the pathogen were randomly distributed in areas with different plantation densities, suggesting that the distribution of G. castanea was not related to the plantation density. The MDT could be used to analyze the spatial distribution of plant diseases both in agricultural and natural ecosystems.

Semi-automatic volume measurement for orbital fat and total extraocular muscles based on Cube FSE-flex sequence in patients with thyroid-associated ophthalmopathy.

PubMed

Tang, X; Liu, H; Chen, L; Wang, Q; Luo, B; Xiang, N; He, Y; Zhu, W; Zhang, J

2018-05-24

To investigate the accuracy of two semi-automatic segmentation measurements based on magnetic resonance imaging (MRI) three-dimensional (3D) Cube fast spin echo (FSE)-flex sequence in phantoms, and to evaluate the feasibility of determining the volumetric alterations of orbital fat (OF) and total extraocular muscles (TEM) in patients with thyroid-associated ophthalmopathy (TAO) by semi-automatic segmentation. Forty-four fatty (n=22) and lean (n=22) phantoms were scanned by using Cube FSE-flex sequence with a 3 T MRI system. Their volumes were measured by manual segmentation (MS) and two semi-automatic segmentation algorithms (regional growing [RG], multi-dimensional threshold [MDT]). Pearson correlation and Bland-Altman analysis were used to evaluate the measuring accuracy of MS, RG, and MDT in phantoms as compared with the true volume. Then, OF and TEM volumes of 15 TAO patients and 15 normal controls were measured using MDT. Paired-sample t-tests were used to compare the volumes and volume ratios of different orbital tissues between TAO patients and controls. Each segmentation (MS RG, MDT) has a significant correlation (p<0.01) with true volume. There was a minimal bias for MS, and a stronger agreement between MDT and the true volume than RG and the true volume both in fatty and lean phantoms. The reproducibility of Cube FSE-flex determined MDT was adequate. The volumetric ratios of OF/globe (p<0.01), TEM/globe (p<0.01), whole orbit/globe (p<0.01) and bone orbit/globe (p<0.01) were significantly greater in TAO patients than those in healthy controls. MRI Cube FSE-flex determined MDT is a relatively accurate semi-automatic segmentation that can be used to evaluate OF and TEM volumes in clinic. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Rigorous covariance propagation of geoid errors to geodetic MDT estimates

NASA Astrophysics Data System (ADS)

Pail, R.; Albertella, A.; Fecher, T.; Savcenko, R.

2012-04-01

The mean dynamic topography (MDT) is defined as the difference between the mean sea surface (MSS) derived from satellite altimetry, averaged over several years, and the static geoid. Assuming geostrophic conditions, from the MDT the ocean surface velocities as important component of global ocean circulation can be derived from it. Due to the availability of GOCE gravity field models, for the very first time MDT can now be derived solely from satellite observations (altimetry and gravity) down to spatial length-scales of 100 km and even below. Global gravity field models, parameterized in terms of spherical harmonic coefficients, are complemented by the full variance-covariance matrix (VCM). Therefore, for the geoid component a realistic statistical error estimate is available, while the error description of the altimetric component is still an open issue and is, if at all, attacked empirically. In this study we make the attempt to perform, based on the full gravity VCM, rigorous error propagation to derived geostrophic surface velocities, thus also considering all correlations. For the definition of the static geoid we use the third release of the time-wise GOCE model, as well as the satellite-only combination model GOCO03S. In detail, we will investigate the velocity errors resulting from the geoid component in dependence of the harmonic degree, and the impact of using/no using covariances on the MDT errors and its correlations. When deriving an MDT, it is spectrally filtered to a certain maximum degree, which is usually driven by the signal content of the geoid model, by applying isotropic or non-isotropic filters. Since this filtering is acting also on the geoid component, the consistent integration of this filter process into the covariance propagation shall be performed, and its impact shall be quantified. The study will be performed for MDT estimates in specific test areas of particular oceanographic interest.

Ground penetrating radar (GPR) analysis : Phase I.

DOT National Transportation Integrated Search

2009-11-01

"The objective of this work is to evaluate the feasibility of expanding the MDT's Ground Penetrating : Radar (GPR) program to a broader range of pavement evaluation activities. Currently, MDT uses GPR in : conjunction with its Falling Weight Deflecto...

Assessing the effectiveness of Montana's vehicle occupant protection program.

DOT National Transportation Integrated Search

2015-02-01

The purpose of this project was to quantitatively evaluate the relationships between MDT's occupant protection program : activities and seat restraint usage throughout Montana, in an effort to clarify how MDT's occupant protection programs may : affe...

2016 availability and disparity study : final report.

DOT National Transportation Integrated Search

2016-07-01

The study examined whether there was a level playing field for minority- and women-owned firms in the Montana transportation : contracting marketplace and for MDT contracting. This information helps MDT set an overall goal for Disadvantage Business :...

Ride specification review for the Montana Department of Transportation

DOT National Transportation Integrated Search

2006-08-01

This report covers the activities that were performed to enhance the current Montana Department of Transportation (MDT)ride specification for flexible pavements. The project team reviewed the MDT ride specification for flexible pavements and compared...

Optimized exploration resource evaluation using the MDT tool

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

Zainun, K.; Trice, M.L.

1995-10-01

This paper discusses exploration cost reduction and improved resource delineation benefits that were realized by use of the MDT (Modular Formation Dynamic Tester) tool to evaluate exploration prospects in the Malay Basin of the South China Sea. Frequently, open hole logs do not clearly define fluid content due to low salinity of the connate water and the effect of shale laminae or bioturbation in the silty, shaley sandstones. Therefore, extensive pressure measurements and fluid sampling are required to define fluid type and contacts. This paper briefly describes the features of the MDT tool which were utilized to reduce rig timemore » usage while providing more representative fluid samples and illustrates usage of these features with field examples. The tool has been used on several exploration wells and a comparison of MDT pressures and samples to results obtained with earlier vintage tools and production tests is also discussed.« less

New high-precision drift-tube detectors for the ATLAS muon spectrometer

NASA Astrophysics Data System (ADS)

Kroha, H.; Fakhrutdinov, R.; Kozhin, A.

2017-06-01

Small-diameter muon drift tube (sMDT) detectors have been developed for upgrades of the ATLAS muon spectrometer. With a tube diameter of 15 mm, they provide an about an order of magnitude higher rate capability than the present ATLAS muon tracking detectors, the MDT chambers with 30 mm tube diameter. The drift-tube design and the construction methods have been optimised for mass production and allow for complex shapes required for maximising the acceptance. A record sense wire positioning accuracy of 5 μm has been achieved with the new design. In the serial production, the wire positioning accuracy is routinely better than 10 μm. 14 new sMDT chambers are already operational in ATLAS, further 16 are under construction for installation in the 2019-2020 LHC shutdown. For the upgrade of the barrel muon spectrometer for High-Luminosity LHC, 96 sMDT chambers will be contructed between 2020 and 2024.

Mindful decision making and inhibitory control training as complementary means to decrease snack consumption.

PubMed

Forman, Evan M; Shaw, Jena A; Goldstein, Stephanie P; Butryn, Meghan L; Martin, Lindsay M; Meiran, Nachshon; Crosby, Ross D; Manasse, Stephanie M

2016-08-01

Obesity is largely attributable to excess caloric intake, in particular from "junk" foods, including salty snack foods. Evidence suggests that neurobiological preferences to consume highly hedonic foods translate (via implicit processes) into poor eating choices, unless overturned by inhibitory mechanisms or interrupted by explicit processes. The primary aim of the current study was to test the independent and combinatory effects of a computerized inhibitory control training (ICT) and a mindful decision-making training (MDT) designed to facilitate de-automatization. We randomized 119 habitual salty snack food eaters to one of four short, training conditions: MDT, ICT, both MDT and ICT, or neither (i.e., psychoeducation). For 7 days prior to the intervention and 7 days following the intervention, participants reported on their salty snack food consumption 2 times per day, on 3 portions of their days, using a smartphone-based ecological momentary assessment system. Susceptibility to emotional eating cues was measured at baseline. Results indicated that the effect of MDT was consistent across levels of trait emotional eating, whereas the benefit of ICT was apparent only at lower levels of emotional eating. No synergistic effect of MDT and ICT was detected. These results provide qualified support for the efficacy of both types of training for decreasing hedonically-motivated eating. Moderation effects suggest that those who eat snack foods for reasons unconnected to affective experiences (i.e., lower in emotional eating) may derive benefit from a combination of ICT and MDT. Future research should investigate the additive benefit of de-automization training to standard weight loss interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Value of Supraregional Multidisciplinary Review for the Contemporary Management of Testicular Tumors.

PubMed

Purshouse, Karin; Watson, Robert A; Church, David N; Richardson, Charlotte; Crane, Gemma; Traill, Zoe; Sullivan, Mark; Roberts, Ian; Browning, Lisa; Turner, Gareth; Parameshwaran, Vishnu; Johnson, Joseph; Chitnis, Meenali; Protheroe, Andrew; Verrill, Clare

2017-02-01

Testicular cancers are an uncommon and highly curable group of tumors that are typically managed by specialist multidisciplinary teams (MDTs). Although recent guidelines have emphasized the importance of tumor prognostic factors in predicting recurrence and personalizing therapy in early-stage disease, the role of central pathology review in determining these factors is unclear. We compared the referral histopathology reports with those obtained after expert central review for all cases reviewed by the UK Thames Valley Cancer Network testicular tumor MDT from August 2004 to September 2012. For cases in which the findings differed, we recorded the effect of the alteration on the estimates of patient prognosis and predicted clinical management using international (European Society of Medical Oncology [ESMO]) and local guidelines. The histopathology reports were altered after central review in 129 of 465 cases (27.7%) referred to the testicular tumor MDT during the study period. These resulted in changes in the estimation of prognosis for 42 patients (9.0% total), with a predicted affect on management according to the ESMO guidelines in 30 cases (6.5%). These proportions were broadly similar for both seminoma and nonseminoma, although the reasons for the discrepancies differed between the 2 (principally errors in categorization of rete testis invasion in seminoma and of lymphovascular invasion in nonseminoma). Changes to the tumor type were uncommon (2 cases). Central MDT review results in frequent, clinically relevant alterations to testicular tumor histopathology reports for testicular tumors. The results of our study demonstrate the importance of specialist MDTs to inform patient-centered care and ensure best practice in the management of these uncommon cancers. Copyright © 2016 Elsevier Inc. All rights reserved.

A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects E scherichia coli from bile salt stress

PubMed Central

Paul, Stephanie; Alegre, Kamela O; Holdsworth, Scarlett R; Rice, Matthew; Brown, James A; McVeigh, Paul; Kelly, Sharon M; Law, Christopher J

2014-01-01

Resistance to high concentrations of bile salts in the human intestinal tract is vital for the survival of enteric bacteria such as E scherichia coli. Although the tripartite AcrAB–TolC efflux system plays a significant role in this resistance, it is purported that other efflux pumps must also be involved. We provide evidence from a comprehensive suite of experiments performed at two different pH values (7.2 and 6.0) that reflect pH conditions that E . coli may encounter in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitator superfamily, functions in bile salt resistance in E . coli by catalysing secondary active transport of bile salts out of the cell cytoplasm. Furthermore, assays performed on a chromosomal ΔacrB mutant transformed with multicopy plasmid encoding MdtM suggested a functional synergism between the single-component MdtM transporter and the tripartite AcrAB–TolC system that results in a multiplicative effect on resistance. Substrate binding experiments performed on purified MdtM demonstrated that the transporter binds to cholate and deoxycholate with micromolar affinity, and transport assays performed on inverted vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H+ antiport. PMID:24684269

Integration of leprosy in general health system vis-à-vis leprosy endemicity, health situation and socioeconomic development: observations from Chhattisgarh & Kerala.

PubMed

Pandey, Aparna; Rathod, Harish

2010-06-01

This study looked at the integration of leprosy services in the GHS in context of health and socioeconomic situations using predefined indicators. It also looked at clients' perception of MDT services. The Indian states of Chhattisgarh and Kerala, which are at two extremes in leprosy endemicity, health situation and socioeconomic development, have been compared using predefined integration indicators related to the training of health workers, availability of MDT services, maintenance of MDT stock and involvement of Sub-centres in leprosy care. Data was collected by surveys of health facilities, sub-centres and communities in the two states, during 2006-2007. Information was collected by interviewing health personnel and clients, checking of records and on the spot observations using specifically designed formats. Results showed that integration is more inclusive in Chhattisgarh and has reached up to Sub-centre level. Both the community and health systems are sensitive and responsive to leprosy as it is perceived to be a major public health threat. But in Kerala, despite integration, it continues as a vertical programme with dependence on specialists and districts hospitals for diagnosis and treatment. MDT stock management is even poorer. Clients' perception towards MDT services are similar in both states.

Purification of a Multidrug Resistance Transporter for Crystallization Studies

PubMed Central

Alegre, Kamela O.; Law, Christopher J.

2015-01-01

Crystallization of integral membrane proteins is a challenging field and much effort has been invested in optimizing the overexpression and purification steps needed to obtain milligram amounts of pure, stable, monodisperse protein sample for crystallography studies. Our current work involves the structural and functional characterization of the Escherichia coli multidrug resistance transporter MdtM, a member of the major facilitator superfamily (MFS). Here we present a protocol for isolation of MdtM to increase yields of recombinant protein to the milligram quantities necessary for pursuit of structural studies using X-ray crystallography. Purification of MdtM was enhanced by introduction of an elongated His-tag, followed by identification and subsequent removal of chaperonin contamination. For crystallization trials of MdtM, detergent screening using size exclusion chromatography determined that decylmaltoside (DM) was the shortest-chain detergent that maintained the protein in a stable, monodispersed state. Crystallization trials of MdtM performed using the hanging-drop diffusion method with commercially available crystallization screens yielded 3D protein crystals under several different conditions. We contend that the purification protocol described here may be employed for production of high-quality protein of other multidrug efflux members of the MFS, a ubiquitous, physiologically and clinically important class of membrane transporters. PMID:27025617

Air quality analysis of MDT transportation improvements, cost-effectiveness analysis of the MACI Program.

DOT National Transportation Integrated Search

2004-03-01

"Under TEA-21, part of Montana's CMAQ apportionment is dedicated to Missoula and at the direction of the : Montana Transportation Commission, the Montana Department of Transportation (MDT) directs the remainder of : the CMAQ apportionment to areas in...

Air quality analysis of MDT transportation improvements : cost-effectiveness analysis of the MACI program.

DOT National Transportation Integrated Search

2004-03-01

Under TEA-21, part of Montana's CMAQ apportionment is dedicated to Missoula and at the direction of the : Montana Transportation Commission, the Montana Department of Transportation (MDT) directs the remainder of : the CMAQ apportionment to areas in ...

Optimal Geoid Modelling to determine the Mean Ocean Circulation - Project Overview and early Results

NASA Astrophysics Data System (ADS)

Fecher, Thomas; Knudsen, Per; Bettadpur, Srinivas; Gruber, Thomas; Maximenko, Nikolai; Pie, Nadege; Siegismund, Frank; Stammer, Detlef

2017-04-01

The ESA project GOCE-OGMOC (Optimal Geoid Modelling based on GOCE and GRACE third-party mission data and merging with altimetric sea surface data to optimally determine Ocean Circulation) examines the influence of the satellite missions GRACE and in particular GOCE in ocean modelling applications. The project goal is an improved processing of satellite and ground data for the preparation and combination of gravity and altimetry data on the way to an optimal MDT solution. Explicitly, the two main objectives are (i) to enhance the GRACE error modelling and optimally combine GOCE and GRACE [and optionally terrestrial/altimetric data] and (ii) to integrate the optimal Earth gravity field model with MSS and drifter information to derive a state-of-the art MDT including an error assessment. The main work packages referring to (i) are the characterization of geoid model errors, the identification of GRACE error sources, the revision of GRACE error models, the optimization of weighting schemes for the participating data sets and finally the estimation of an optimally combined gravity field model. In this context, also the leakage of terrestrial data into coastal regions shall be investigated, as leakage is not only a problem for the gravity field model itself, but is also mirrored in a derived MDT solution. Related to (ii) the tasks are the revision of MSS error covariances, the assessment of the mean circulation using drifter data sets and the computation of an optimal geodetic MDT as well as a so called state-of-the-art MDT, which combines the geodetic MDT with drifter mean circulation data. This paper presents an overview over the project results with focus on the geodetic results part.

Development and testing of the cancer multidisciplinary team meeting observational tool (MDT-MOT)

PubMed Central

Harris, Jenny; Taylor, Cath; Sevdalis, Nick; Jalil, Rozh; Green, James S.A.

2016-01-01

Abstract Objective To develop a tool for independent observational assessment of cancer multidisciplinary team meetings (MDMs), and test criterion validity, inter-rater reliability/agreement and describe performance. Design Clinicians and experts in teamwork used a mixed-methods approach to develop and refine the tool. Study 1 observers rated pre-determined optimal/sub-optimal MDM film excerpts and Study 2 observers independently rated video-recordings of 10 MDMs. Setting Study 2 included 10 cancer MDMs in England. Participants Testing was undertaken by 13 health service staff and a clinical and non-clinical observer. Intervention None. Main Outcome Measures Tool development, validity, reliability/agreement and variability in MDT performance. Results Study 1: Observers were able to discriminate between optimal and sub-optimal MDM performance (P ≤ 0.05). Study 2: Inter-rater reliability was good for 3/10 domains. Percentage of absolute agreement was high (≥80%) for 4/10 domains and percentage agreement within 1 point was high for 9/10 domains. Four MDTs performed well (scored 3+ in at least 8/10 domains), 5 MDTs performed well in 6–7 domains and 1 MDT performed well in only 4 domains. Leadership and chairing of the meeting, the organization and administration of the meeting, and clinical decision-making processes all varied significantly between MDMs (P ≤ 0.01). Conclusions MDT-MOT demonstrated good criterion validity. Agreement between clinical and non-clinical observers (within one point on the scale) was high but this was inconsistent with reliability coefficients and warrants further investigation. If further validated MDT-MOT might provide a useful mechanism for the routine assessment of MDMs by the local workforce to drive improvements in MDT performance. PMID:27084499

Development and testing of the cancer multidisciplinary team meeting observational tool (MDT-MOT).

PubMed

Harris, Jenny; Taylor, Cath; Sevdalis, Nick; Jalil, Rozh; Green, James S A

2016-06-01

To develop a tool for independent observational assessment of cancer multidisciplinary team meetings (MDMs), and test criterion validity, inter-rater reliability/agreement and describe performance. Clinicians and experts in teamwork used a mixed-methods approach to develop and refine the tool. Study 1 observers rated pre-determined optimal/sub-optimal MDM film excerpts and Study 2 observers independently rated video-recordings of 10 MDMs. Study 2 included 10 cancer MDMs in England. Testing was undertaken by 13 health service staff and a clinical and non-clinical observer. None. Tool development, validity, reliability/agreement and variability in MDT performance. Study 1: Observers were able to discriminate between optimal and sub-optimal MDM performance (P ≤ 0.05). Study 2: Inter-rater reliability was good for 3/10 domains. Percentage of absolute agreement was high (≥80%) for 4/10 domains and percentage agreement within 1 point was high for 9/10 domains. Four MDTs performed well (scored 3+ in at least 8/10 domains), 5 MDTs performed well in 6-7 domains and 1 MDT performed well in only 4 domains. Leadership and chairing of the meeting, the organization and administration of the meeting, and clinical decision-making processes all varied significantly between MDMs (P ≤ 0.01). MDT-MOT demonstrated good criterion validity. Agreement between clinical and non-clinical observers (within one point on the scale) was high but this was inconsistent with reliability coefficients and warrants further investigation. If further validated MDT-MOT might provide a useful mechanism for the routine assessment of MDMs by the local workforce to drive improvements in MDT performance. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Exploration of the psychophysics of a motion displacement hyperacuity stimulus.

PubMed

Verdon-Roe, Gay Mary; Westcott, Mark C; Viswanathan, Ananth C; Fitzke, Frederick W; Garway-Heath, David F

2006-11-01

To explore the summation properties of a motion-displacement hyperacuity stimulus with respect to stimulus area and luminance, with the goal of applying the results to the development of a motion-displacement test (MDT) for the detection of early glaucoma. A computer-generated line stimulus was presented with displacements randomized between 0 and 40 minutes of arc (min arc). Displacement thresholds (50% seen) were compared for stimuli of equal area but different edge length (orthogonal to the direction of motion) at four retinal locations. Also, MDT thresholds were recorded at five values of Michelson contrast (25%-84%) for each of five line lengths (11-128 min arc) at a single nasal location (-27,3). Frequency-of-seeing (FOS) curves were generated and displacement thresholds and interquartile ranges (IQR, 25%-75% seen) determined by probit analysis. Equivalent displacement thresholds were found for stimuli of equal area but half the edge length. Elevations of thresholds and IQR were demonstrated as line length and contrast were reduced. Equivalent displacement thresholds were also found for stimuli of equivalent energy (stimulus area x [stimulus luminance - background luminance]), in accordance with Ricco's law. There was a linear relationship (slope -0.5) between log MDT threshold and log stimulus energy. Stimulus area, rather than edge length, determined displacement thresholds within the experimental conditions tested. MDT thresholds are linearly related to the square root of the total energy of the stimulus. A new law, the threshold energy-displacement (TED) law, is proposed to apply to MDT summation properties, giving the relationship T = K logE where, T is the MDT threshold, Kis the constant, and E is the stimulus energy.

Are multidisciplinary teams in secondary care cost-effective? A systematic review of the literature

PubMed Central

2013-01-01

Objective To investigate the cost effectiveness of management of patients within the context of a multidisciplinary team (MDT) meeting in cancer and non-cancer teams in secondary care. Design Systematic review. Data sources EMBASE, MEDLINE, NHS EED, CINAHL, EconLit, Cochrane Library, and NHS HMIC. Eligibility criteria for selecting studies Randomised controlled trials (RCTs), cohort, case–control, before and after and cross-sectional study designs including an economic evaluation of management decisions made in any disease in secondary care within the context of an MDT meeting. Data extraction Two independent reviewers extracted data and assessed methodological quality using the Consensus on Health Economic Criteria (CHEC-list). MDTs were defined by evidence of two characteristics: decision making requiring a minimum of two disciplines; and regular meetings to discuss diagnosis, treatment and/or patient management, occurring at a physical location or by teleconferencing. Studies that reported on the costs of administering, preparing for, and attending MDT meetings and/or the subsequent direct medical costs of care, non-medical costs, or indirect costs, and any health outcomes that were relevant to the disease being investigated were included and classified as cancer or non-cancer MDTs. Results Fifteen studies (11 RCTs in non-cancer care, 2 cohort studies in cancer and non-cancer care, and 2 before and after studies in cancer and non cancer care) were identified, all with a high risk of bias. Twelve papers reported the frequency of meetings which varied from daily to three monthly and all reported the number of disciplines included (mean 5, range 2 to 9). The results from all studies showed mixed effects; a high degree of heterogeneity prevented a meta-analysis of findings; and none of the studies reported how the potential savings of MDT working may offset the costs of administering, preparing for, and attending MDT meetings. Conclusions Current evidence is insufficient to determine whether MDT working is cost-effective or not in secondary care. Further studies aimed at understanding the key aspects of MDT working that lead to cost-effective cancer and non-cancer care are required. PMID:23557141

Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.

PubMed

Fang, Dongdong; Hu, Shen; Liu, Younan; Quan, Vu-Hung; Seuntjens, Jan; Tran, Simon D

2015-11-03

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named "Bone Marrow (BM) Soup", was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and "deactivated BM Soup" were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the 'deactivated BM Soup' was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.

Microgrid Design Toolkit (MDT) User Guide Software v1.2.

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

Eddy, John P.

2017-08-01

The Microgrid Design Toolkit (MDT) supports decision analysis for new ("greenfield") microgrid designs as well as microgrids with existing infrastructure. The current version of MDT includes two main capabilities. The first capability, the Microgrid Sizing Capability (MSC), is used to determine the size and composition of a new, grid connected microgrid in the early stages of the design process. MSC is focused on developing a microgrid that is economically viable when connected to the grid. The second capability is focused on designing a microgrid for operation in islanded mode. This second capability relies on two models: the Technology Management Optimizationmore » (TMO) model and Performance Reliability Model (PRM).« less

Mycobacterial r32-kDa antigen-specific T-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients.

PubMed

Neela, Venkata Sanjeev Kumar; Devalraju, Kamakshi Prudhula; Pydi, Satya Sudheer; Sunder, Sharada Ramaseri; Adiraju, Kameswara Rao; Singh, Surya Satyanarayana; Anandaraj, M P J S; Valluri, Vijaya Lakshmi

2016-09-01

Immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro T-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. The main goal of this study was to evaluate the use of Mycobacterium bovis recombinant 32-kDa protein (r32-kDa) antigen-stimulated T-cell assay as a surrogate marker for treatment outcome and monitor vitamin D receptor (VDR)-mediated anti-microbial responses during multidrug therapy (MDT) in leprosy. Newly diagnosed tuberculoid and lepromatous leprosy patients were enrolled and followed up during their course of MDT at 6 and 12 months. IFN-γ, IL-10, IL-17 and IL-23 levels in culture supernatants and expression of VDR, TLR2, LL37 and DEFB in r32-kDa-stimulated PBMCs were measured. Controls comprised household contacts (HHCs) and healthy endemic subjects (HCs). Significant differences were observed in the levels of IFN-γ, IL-17, IL-23, VDR and anti-microbial peptides LL37 and DEFB after treatment and when compared with that of HHCs and HCs, respectively. These findings suggest that responses to r32-kDa antigen reflect an improved immunological and anti-microbial response in leprosy patients during therapy, thereby indicating its potential use as an immune correlate in the treatment of leprosy patients. © The Japanese Society for Immunology. 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Leprosy reactions in postelimination stage: the Bangladesh experience.

PubMed

Mowla, M R; Ara, S; Mizanur Rahman, A F M; Tripura, S P; Paul, S

2017-04-01

Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. To describe the pattern and prevalence of leprosy reactions in the postelimination stage. A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services. © 2016 European Academy of Dermatology and Venereology.

Comparing Multiple Discrepancies Theory to Affective Models of Subjective Wellbeing

ERIC Educational Resources Information Center

Blore, Jed D.; Stokes, Mark A.; Mellor, David; Firth, Lucy; Cummins, Robert A.

2011-01-01

The Subjective Wellbeing (SWB) literature is replete with competing theories detailing the mechanisms underlying the construction and maintenance of SWB. The current study aimed to compare and contrast two of these approaches: multiple discrepancies theory (MDT) and an affective-cognitive theory of SWB. MDT posits SWB to be the result of perceived…

Correlates of Parental Differential Treatment: Parental and Contextual Factors during Middle Childhood

ERIC Educational Resources Information Center

Atzaba-Poria, Naama; Pike, Alison

2008-01-01

The current study examined whether parental and contextual risk factors contribute to mothers' and fathers' differential treatment (MDT/FDT) when accounting for sibling dyad characteristics. Also explored was whether family type (single mothers vs. 2 parents) moderated the links between the parental and contextual correlates and MDT. One hundred…

PERSPECTIVES ON MULTIDISCIPLINARY TEAM PROCESSES AMONG HEALTHCARE EXECUTIVES: PROCESSES THAT FACILITATE TEAM EFFECTIVENESS.

PubMed

Landry, Amy; Erwin, Cathleen

2015-01-01

Multidisciplinary teams (MDTs) are used in healthcare organizations to address both clinical and managerial functions. Despite their prevalence, little is known about how team processes work to facilitate effectiveness among MDT leadership teams. This study explores perceptions of MDT participation experienced by organizational leaders in healthcare organizations in the United States. A survey of American College of Healthcare Executives members was conducted to assess involvement and perceptions of MDTs among health care management professionals. Descriptive statistics, independent T-Tests and Chi-square analyses were used to examine participation in MDTs, perception of MDT processes, and the association of participation and perceived processes with employee and organizational characteristics. The survey yielded a sample comprised of 492 healthcare executive or executive-track employees. An overwhelming majority indicated participation in MDTs. The study identified team processes that could use improvement including communication, cooperation, and conflict resolution. The study provides evidence that can help guide the development of training programs that focus on providing managerial leaders with strategies aimed at improving communication, coordination, and conflict resolution that will improve the effectiveness of MDT functioning in healthcare organizations.

Nonlinear diffusion filtering of the GOCE-based satellite-only MDT

NASA Astrophysics Data System (ADS)

Čunderlík, Róbert; Mikula, Karol

2015-04-01

A combination of the GRACE/GOCE-based geoid models and mean sea surface models provided by satellite altimetry allows modelling of the satellite-only mean dynamic topography (MDT). Such MDT models are significantly affected by a stripping noise due to omission errors of the spherical harmonics approach. Appropriate filtering of this kind of noise is crucial in obtaining reliable results. In our study we use the nonlinear diffusion filtering based on a numerical solution to the nonlinear diffusion equation on closed surfaces (e.g. on a sphere, ellipsoid or the discretized Earth's surface), namely the regularized surface Perona-Malik model. A key idea is that the diffusivity coefficient depends on an edge detector. It allows effectively reduce the noise while preserve important gradients in filtered data. Numerical experiments present nonlinear filtering of the satellite-only MDT obtained as a combination of the DTU13 mean sea surface model and GO_CONS_GCF_2_DIR_R5 geopotential model. They emphasize an adaptive smoothing effect as a principal advantage of the nonlinear diffusion filtering. Consequently, the derived velocities of the ocean geostrophic surface currents contain stronger signal.

A combined mean dynamic topography model - DTU17cMDT

NASA Astrophysics Data System (ADS)

Knudsen, P.; Andersen, O. B.; Nielsen, K.; Maximenko, N. A.

2017-12-01

Within the ESA supported Optimal Geoid for Modelling Ocean Circulation (OGMOC) project a new geoid model have been derived. It is based on the GOCO05C setup though the newer DTU15GRA altimetric surface gravity has been used in the combination. Subsequently the model has been augmented using the EIGEN-6C4 coefficients to d/o 2160. Compared to the DTU13MSS, the DTU15MSS has been derived by including re-tracked CRYOSAT-2 altimetry also, hence, increasing its resolution. Also, some issues in the Polar regions have been solved. The new DTU17MDT has been derived using this new geoid model and the DTU15MSS mean sea surface. Compared to other geoid models the new OGMOC geoid model has been optimized to avoid striations and orange skin like features. The filtering was re-evaluated by adjusting the quasi-gaussian filter width to optimize the fit to drifter velocities. The results show that the new MDT improves the resolution of the details of the ocean circulation. Subsequently, the drifter velocities were integrated to enhance the resolution of the MDT. As a contribution to the ESA supported GOCE++ project DYCOT a special concern was devoted to the coastal areas to optimize the extrapolation towards the coast and to integrate mean sea levels at tide gauges into that process. The presentation will focus on the coastal zone when assessing the methodology, the data and the final model DTU17cMDT.

Should centralized histopathological review in penile cancer be the global standard?

PubMed

Tang, Vincent; Clarke, Laurence; Gall, Zara; Shanks, Jonathan H; Nonaka, Daisuke; Parr, Nigel J; Elliott, P Anthony; Clarke, Noel W; Ramani, Vijay; Lau, Maurice W; Sangar, Vijay K

2014-09-01

To assess the role of centralized pathological review in penile cancer management. Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra-network multidisciplinary team (Sn-MDT) between 1 January 2008 and 30 March 2011. Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn-MDT pathologists. The biopsy specimens' histological type, grade and stage reported by the Sn-MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology. Any changes in histological diagnosis were sub-divided into critical changes (i.e. those that could alter management) and non-critical changes (i.e. those that would not affect management). A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North-West England. After review by the Sn-MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management. When comparing the biopsy histology reported by the Sn-MDT with the final histology from the definitive surgical specimens, a good correlation was generally found. In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn-MDT. Many of these changes altered patient management. The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer. In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the 'gold standard'. © 2013 The Authors. BJU International © 2013 BJU International.

Using computerised decision support to improve compliance of cancer multidisciplinary meetings with evidence-based guidance

PubMed Central

Patkar, Vivek; Acosta, Dionisio; Davidson, Tim; Jones, Alison; Fox, John

2012-01-01

Objectives The cancer multidisciplinary team (MDT) meeting (MDM) is regarded as the best platform to reduce unwarranted variation in cancer care through evidence-compliant management. However, MDMs are often overburdened with many different agendas and hence struggle to achieve their full potential. The authors developed an interactive clinical decision support system called MATE (Multidisciplinary meeting Assistant and Treatment sElector) to facilitate explicit evidence-based decision making in the breast MDMs. Design Audit study and a questionnaire survey. Setting Breast multidisciplinary unit in a large secondary care teaching hospital. Participants All members of the breast MDT at the Royal Free Hospital, London, were consulted during the process of MATE development and implementation. The emphasis was on acknowledging the clinical needs and practical constraints of the MDT and fitting the system around the team's workflow rather than the other way around. Delegates, who attended MATE workshop at the England Cancer Networks' Development Programme conference in March 2010, participated in the questionnaire survey. Outcome measures The measures included evidence-compliant care, measured by adherence to clinical practice guidelines, and promoting research, measured by the patient identification rate for ongoing clinical trials. Results MATE identified 61% more patients who were potentially eligible for recruitment into clinical trials than the MDT, and MATE recommendations demonstrated better concordance with clinical practice guideline than MDT recommendations (97% of MATE vs 93.2% of MDT; N=984). MATE is in routine use in breast MDMs at the Royal Free Hospital, London, and wider evaluations are being considered. Conclusions Sophisticated decision support systems can enhance the conduct of MDMs in a way that is acceptable to and valued by the clinical team. Further rigorous evaluations are required to examine cost-effectiveness and measure the impact on patient outcomes. The decision support technology used in MATE is generic and if found useful can be applied across medicine. PMID:22734113

The Impact of a Hepatobiliary Multidisciplinary Team Assessment in Patients with Colorectal Cancer Liver Metastases: A Population-Based Study.

PubMed

Engstrand, Jennie; Kartalis, Nikolaos; Strömberg, Cecilia; Broberg, Mats; Stillström, Anna; Lekberg, Tobias; Jonas, Eduard; Freedman, Jacob; Nilsson, Henrik

2017-09-01

Assessing patients with colorectal cancer liver metastases (CRCLM) by a liver multidisciplinary team (MDT) results in higher resection rates and improved survival. The aim of this study was to evaluate the potentially improved resection rate in a defined cohort if all patients with CRCLM were evaluated by a liver MDT. A retrospective analysis of patients diagnosed with colorectal cancer during 2008 in the greater Stockholm region was conducted. All patients with liver metastases (LM), detected during 5-year follow-up, were re-evaluated at a fictive liver MDT in which previous imaging studies, tumor characteristics, medical history, and patients' own treatment preferences were presented. Treatment decisions for each patient were compared to the original management. Odds ratios (ORs) and 95% confidence intervals were estimated for factors associated with referral to the liver MDT. Of 272 patients diagnosed with LM, 102 patients were discussed at an original liver MDT and 69 patients were eventually resected. At the fictive liver MDT, a further 22 patients were considered as resectable/potentially resectable, none previously assessed by a hepatobiliary surgeon. Factors influencing referral to liver MDT were age (OR 3.12, 1.72-5.65), American Society of Anaesthesiologists (ASA) score (OR 0.34, 0.18-0.63; ASA 2 vs. ASA 3), and number of LM (OR 0.10, 0.04-0.22; 1-5 LM vs. >10 LM), while gender ( p  = .194) and treatment at a teaching hospital ( p  = .838) were not. A meaningful number of patients with liver metastases are not managed according to best available evidence and the potential for higher resection rates is substantial. Patients with liver metastatic colorectal cancer who are assessed at a hepatobiliary multidisciplinary meeting achieve higher resection rates and improved survival. Unfortunately, patients who may benefit from resection are not always properly referred. In this study, the potential improved resection rate was assessed by re-evaluating all patients with liver metastases from a population-based cohort, including patients with extrahepatic metastases and accounting for comorbidity and patients' own preferences towards treatment. An additional 12.9% of the patients were found to be potentially resectable. The results highlight the importance of all patients being evaluated in the setting of a hepatobiliary multidisciplinary meeting. © AlphaMed Press 2017.

Two-year experience of multi-disciplinary team (MDT) outcomes for brain metastases in a tertiary neuro-oncology centre.

PubMed

Loh, Daniel; Hogg, Florence; Edwards, Penelope; MacColl, Jillian; Brogna, Christian; Bhangoo, Ranjeev; Ashkan, Keyoumars; Vergani, Francesco

2017-08-24

Brain metastases (BMs) are the most common intracranial tumour in adults and form a significant proportion of the neuro-oncology workload. Their management has progressed significantly in the last few decades but a gold-standard evidence-based management strategy has not been defined to date and several guidelines based on available evidence exist to support clinical decision-making. This paper evaluates the decision-making process of the neuro-oncology multi-disciplinary team (MDT) in a tertiary neuro-oncology centre over a two-year period. A retrospective review of all patients with BM discussed in the MDT was conducted. Data on patient demographics, tumour characteristics and MDT decision were collected from the MDT database, clinical notes and imaging studies. Patients were stratified into the three recursive partitioning analysis (RPA) classes and according to the graded prognostic assessment (GPA) score. MDT decisions were analysed by RPA class and for GPA score as well as single versus multiple BM. There were 362 patients with BM, representing 22% of the total cases discussed at the MDT. Decision-making was largely consistent with available guidelines. A concrete treatment decision was reached in 77.5% of patients and 32.2% of these received neurosurgical input. More patients with solitary BM underwent surgery compared to multiple BM (p = 0.001), and more patients in RPA classes I and II had surgical resection compared to class III (p = 0.005 and 0.001, respectively). Surgical patients also had higher GPA scores compared to palliative patients (p = 0.005). A greater absolute number and proportion of patients in RPA class II vs. class I underwent neurosurgical intervention. These patients were stratified into class II because of their age but would otherwise have been placed into class I. Survival data were available for 195 patients (53.8%) at 1 year post MDT discussion. A pattern of declining survival was observed along RPA classes which was statistically significant (p = 0.0025). Median survival was 4.7 (0-41), 3.7 (0-23), and 2.5 (range 0-24) months for RPA class I, II and III respectively. A similar pattern that did not reach statistical significance was found between GPA scores (p = 0.101). Median survival was 3 (0-13), 4.6 (range 0-41), and 4.6 (0-35) months for GPA scores 0-1.0, 1.5-2.5 and 3-4.0, respectively. Patient selection was generally in accordance to RPA class and GPA scoring, with the exception of surgery offered to elderly patients: this can be explained by the increasing number of otherwise fit patients as population ages.

Transcranial light-emitting diode therapy for neuropsychological improvement after traumatic brain injury: a new perspective for diffuse axonal lesion management

PubMed Central

dos Santos, João Gustavo Rocha Peixoto; Paiva, Wellingson Silva; Teixeira, Manoel Jacobsen

2018-01-01

The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging. Different brain networks work together to form an important part of the cognition process, and they can be affected by TBI. The default mode network (DMN) plays an important central role in normal brain activities, presenting greater relative deactivation during more cognitively demanding tasks. After deactivation, it allows a distinct network to activate. This network (the central executive network) acts mainly during tasks involving executive functions. The salience network is another network necessary for normal executive function, and its activation leads to deactivation of the DMN. The use of red or near-infrared (NIR) light to stimulate or regenerate tissue is known as photobiomodulation. It was discovered that NIR (wavelength 800–900 nm) and red (wavelength 600 nm) light-emitting diodes (LEDs) are able to penetrate through scalp and skull and have the potential to improve the subnormal, cellular activity of compromised brain tissue. Based on this, different experimental and clinical studies were done to test LED therapy for TBI, and promising results were found. It leads us to consider developing different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. PMID:29731669

Transcranial light-emitting diode therapy for neuropsychological improvement after traumatic brain injury: a new perspective for diffuse axonal lesion management.

PubMed

Dos Santos, João Gustavo Rocha Peixoto; Paiva, Wellingson Silva; Teixeira, Manoel Jacobsen

2018-01-01

The cost of traumatic brain injury (TBI) for public health policies is undeniable today. Even patients who suffer from mild TBI may persist with cognitive symptoms weeks after the accident. Most of them show no lesion in computed tomography or conventional magnetic resonance imaging, but microstructural white matter abnormalities (diffuse axonal lesion) can be found in diffusion tensor imaging. Different brain networks work together to form an important part of the cognition process, and they can be affected by TBI. The default mode network (DMN) plays an important central role in normal brain activities, presenting greater relative deactivation during more cognitively demanding tasks. After deactivation, it allows a distinct network to activate. This network (the central executive network) acts mainly during tasks involving executive functions. The salience network is another network necessary for normal executive function, and its activation leads to deactivation of the DMN. The use of red or near-infrared (NIR) light to stimulate or regenerate tissue is known as photobiomodulation. It was discovered that NIR (wavelength 800-900 nm) and red (wavelength 600 nm) light-emitting diodes (LEDs) are able to penetrate through scalp and skull and have the potential to improve the subnormal, cellular activity of compromised brain tissue. Based on this, different experimental and clinical studies were done to test LED therapy for TBI, and promising results were found. It leads us to consider developing different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients.

Analysis of implantable defibrillator longevity under clinical circumstances: implications for device selection.

PubMed

Knops, Paul; Theuns, Dominic A M J; Res, Jan C J; Jordaens, Luc

2009-10-01

Information about implantable cardioverter-defibrillator (ICD) longevity is mostly calculated from measurements under ideal laboratory conditions. However, little information about longevity under clinical circumstances is available. This survey gives an overview on ICD service times and generator replacements in a cohort of consecutive ICD patients. Indications for replacement were classified as a normal end-of-service (EOS), premature EOS, system malfunction, infection and device advisory, or recall actions. From the premature and normal EOS group, longevity from single-chamber (SC), dual-chamber (DC), and cardiac resynchronization therapy defibrillator (CRT-D), rate-responsive (RR) settings, high output (HO) stimulation, and indication for ICD therapy was compared. Differences between brands were compared as well. In a total of 854 patients, 203 ICD replacements (165 patients) were recorded. Premature and normal EOS replacements consisted of 32 SC, 98 DC and 24 CRT-D systems. Longevity was significantly longer in SC systems compared to DC and CRT-D systems (54 +/- 19 vs. 40 +/- 17 and 42 +/- 15 months; P = 0.008). Longevity between non-RR (n = 143) and RR (n = 11) settings was not significantly different (43 +/- 18 vs. 45 +/- 13 months) as it also was not for HO versus non-HO stimulation (43 +/- 19 vs. 46 +/- 17 months). Longevity of ICDs was not significantly different between primary and secondary prevention (42 +/- 19 vs. 44 +/- 18 months). The average longevity on account of a device-based EOS message was 43 +/- 18 months. Average longevity for Biotronik (BIO, n = 72) was 33 +/- 10 months, for ELA Medical (ELA, n = 12) 44 +/- 17 months, for Guidant (GDT, n = 36) 49 +/- 12 months, for Medtronic (MDT, n = 29) 62 +/- 22 months, and for St. Jude Medical (SJM, n = 5) 31 +/- 9 months (P < 0.001). SC ICD generators had a longer service time compared to DC and CRT-D systems. No influence of indication for ICD therapy and HO stimulation on generator longevity was observed in this study. MDT ICDs had the longest service time.

Multi-disciplinary team for early gastric cancer diagnosis improves the detection rate of early gastric cancer.

PubMed

Di, Lianjun; Wu, Huichao; Zhu, Rong; Li, Youfeng; Wu, Xinglong; Xie, Rui; Li, Hongping; Wang, Haibo; Zhang, Hua; Xiao, Hong; Chen, Hui; Zhen, Hong; Zhao, Kui; Yang, Xuefeng; Xie, Ming; Tuo, Bigung

2017-12-06

Gastric cancer is a frequent malignant tumor worldwide and its early detection is crucial for curing the disease and enhancing patients' survival rate. This study aimed to assess whether the multi-disciplinary team (MDT) can improve the detection rate of early gastric cancer (EGC). The detection rate of EGC at the Digestive Endoscopy Center, Affiliated Hospital, Zunyi Medical College, China between September 2013 and September 2015 was analyzed. MDT for the diagnosis of EGC in the hospital was established in September 2014. The study was divided into 2 time periods: September 1, 2013 to August 31, 2014 (period 1) and September 1, 2014 to September 1, 2015 (period 2). A total of 60,800 patients' gastroscopies were performed during the two years. 61 of these patients (0.1%) were diagnosed as EGC, accounting for 16.44% (61/371) of total patients with gastric cancer. The EGC detection rate before MDT (period 1) was 0.05% (16/29403), accounting for 9.09% (16/176) of total patients with gastric cancer during this period. In comparison, the EGC detection rate during MDT (period 2) was 0.15% (45/31397), accounting for 23% (45/195) of total patients with gastric cancer during this period (P < 0.05). Univariate and multivariate logistic analyses showed that intensive gastroscopy for high risk patients of gastric cancer enhanced the detection rate of EGC in cooperation with Department of Pathology (OR = 10.1, 95% CI 2.39-43.3, P < 0.05). MDT could improve the endoscopic detection rate of EGC.

Remote magnetic targeting of iron oxide nanoparticles for cardiovascular diagnosis and therapeutic drug delivery: where are we now?

PubMed Central

Bietenbeck, Michael; Florian, Anca; Faber, Cornelius; Sechtem, Udo; Yilmaz, Ali

2016-01-01

Magnetic resonance imaging (MRI) allows for an accurate assessment of both functional and structural cardiac parameters, and thereby appropriate diagnosis and validation of cardiovascular diseases. The diagnostic yield of cardiovascular MRI examinations is often increased by the use of contrast agents that are almost exclusively based on gadolinium compounds. Another clinically approved contrast medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These particles may expand the field of contrast-enhanced cardiovascular MRI as recently shown in clinical studies focusing on acute myocardial infarction (AMI) and atherosclerosis. Furthermore, IONs open up new research opportunities such as remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling of bioactive molecules and magnetic nanoparticles to form an injectable complex. This complex, in turn, can be attracted to and retained at a desired target inside the body with the help of applied magnetic fields. In comparison to common systemic drug applications, MDT techniques promise both higher concentrations at the target site and lower concentrations elsewhere in the body. Moreover, concurrent or subsequent MRI can be used for noninvasive monitoring of drug distribution and successful delivery to the desired organ in vivo. This review does not only illustrate the basic conceptual and biophysical principles of IONs, but also focuses on new research activities and achievements in the cardiovascular field, mainly in the management of AMI. Based on the presentation of successful MDT applications in preclinical models of AMI, novel approaches and the translational potential of MDT are discussed. PMID:27486321

Optic nerve involvement in a borderline lepromatous leprosy patient on multidrug therapy.

PubMed

Prabha, Neel; Mahajan, Vikram K; Sharma, Surinder K; Sharma, Vikas; Chauhan, Pushpinder S; Mehta, Karaninder S; Abhinav, C; Khatri, Gaytri; Chander, Bal; Tuli, Rajiv

2013-12-01

Amidst the plethora of ocular complications of leprosy, involvement of the posterior segment or optic nerve is extremely rare. The mechanism of optic neuritis in leprosy is poorly understood. A 47 year-old man presented with a single lesion suggestive of mid-borderline (BB) leprosy over left periorbital region; the histology showed borderline lepromatous (BL) leprosy with a BI of 3+. After initial improvement with WHO MDT-MB and prednisolone (40 mg/d) he developed sudden and painless diminished vision in the left eye, about 3 weeks later. His visual acuity was 6/9 in the left and 6/6 in the right eye, and there was left optic disc edema, hyperemia and blurred disc margins. Treatment with prednisolone (60 mg/d) along with WHO MDT-MB continued. A month later he returned with painless diminished vision in the other eye as well. Visual acuity was 6/6 in the right and 6/12 in the left eye, and there was right optic disc edema and left optic disc atrophy. CT of the head and MRI of the brain were normal. Inflammatory edema of the orbital connective tissue or other surrounding structures, or direct infiltration of vasa nervosa with resultant vascular occlusion leading to optic nerve ischemia, seems the most plausible explanation of optic nerve involvement in this case.

Effects of multidisciplinary teams and an integrated follow-up electronic system on clinical pharmacist interventions in a cancer hospital.

PubMed

Aziz, Muhammad Tahir; Rehman, Tofeeq Ur; Qureshi, Sadia; Andleeb, Sidrah

2017-12-01

Background The aim of drug therapy is to attain distinct therapeutic effects that not only improve patient's quality of life but also reduce the inherent risks associated with the therapeutic use of drugs. Pharmacists play a key role in reducing these risks by developing appropriate interventions. Whether to accept or reject the intervention made by the pharmacist is a relevant consultant's decision. Objective To evaluate the impact of electronic prompts and follow-up of rejected pharmacy interventions by clinical pharmacists in an in-patient setting. Setting Shaukat Khanum Cancer Hospital & Research Center, Lahore, Pakistan. Method The study was conducted in two phases. Data for 3 months were collected for each phase of the study. Systematic and quantifiable consensus validity was developed for rejected interventions in phase 1, based on patient outcome analyses. Severity rating was assigned to assess the significance of interventions. Electronic prompts for follow-on interventions in phase 2 were then developed and implemented, including daily review via a multidisciplinary team (MDT) approach. Main outcome measure Validity of rejected interventions, acceptance of follow-on interventions before and after re-engineering the pharmacy processes, rejection rate and severity rating of follow-on interventions. Result Of a total of 2649 and 3064 interventions that were implemented during phase 1 and phase 2, 238 (9%) and 307 (10%) were rejected, respectively. Additionally, 133 (56%) were inappropriate rejections during phase 1. The estimated reliability between pharmacists regarding rejected interventions was 0.74 (95% CI of 0.69, 0.79, p 0.000). Prospective data were analysed after implementing electronic alerts and an MDT approach. The acceptance rate of follow-on interventions in phase 2 was 60% (184). Conclusion Electronic prompts for follow-on interventions together with an MDT approach enhance the optimization of pharmacotherapy, increase drug rationality and improve patient care.

The Effect of Traditional Cupping on Pain and Mechanical Thresholds in Patients with Chronic Nonspecific Neck Pain: A Randomised Controlled Pilot Study

PubMed Central

Lauche, Romy; Cramer, Holger; Hohmann, Claudia; Choi, Kyung-Eun; Rampp, Thomas; Saha, Felix Joyonto; Musial, Frauke; Langhorst, Jost; Dobos, Gustav

2012-01-01

Introduction. Cupping has been used since antiquity in the treatment of pain conditions. In this pilot study, we investigated the effect of traditional cupping therapy on chronic nonspecific neck pain (CNP) and mechanical sensory thresholds. Methods. Fifty CNP patients were randomly assigned to treatment (TG, n = 25) or waiting list control group (WL, n = 25). TG received a single cupping treatment. Pain at rest (PR), pain related to movement (PM), quality of life (SF-36), Neck Disability Index (NDI), mechanical detection (MDT), vibration detection (MDT), and pressure pain thresholds (PPT) were measured before and three days after a single cupping treatment. Patients also kept a pain and medication diary (PaDi, MeDi) during the study. Results. Baseline characteristics were similar in the two groups. After cupping TG reported significantly less pain (PR: −17.9 mm VAS, 95%CI −29.2 to −6.6; PM: −19.7, 95%CI −32.2 to −7.2; PaDi: −1.5 points on NRS, 95%CI −2.5 to −0.4; all P < 0.05) and higher quality of life than WL (SF-36, Physical Functioning: 7.5, 95%CI 1.4 to 13.5; Bodily Pain: 14.9, 95%CI 4.4 to 25.4; Physical Component Score: 5.0, 95%CI 1.4 to 8.5; all P < 0.05). No significant effect was found for NDI, MDT, or VDT, but TG showed significantly higher PPT at pain-areas than WL (in lg(kPa); pain-maximum: 0.088, 95%CI 0.029 to 0.148, pain-adjacent: 0.118, 95%CI 0.038 to 0.199; both P < 0.01). Conclusion. A single application of traditional cupping might be an effective treatment for improving pain, quality of life, and hyperalgesia in CNP. PMID:22203873

Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

PubMed

Shamsi, Milad; Sedaghatkish, Amir; Dejam, Morteza; Saghafian, Mohsen; Mohammadi, Mehdi; Sanati-Nezhad, Amir

2018-11-01

Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors. We also validated in silico results against experimental results related to tumor interstitial hypertension, conventional IP chemoperfusion, and magnetically actuated movement of MNPs in excised tissue.

Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands

PubMed Central

Fang, Dongdong; Hu, Shen; Liu, Younan; Quan, Vu-Hung; Seuntjens, Jan; Tran, Simon D.

2015-01-01

In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named “Bone Marrow (BM) Soup”, was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and “deactivated BM Soup” were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the ‘deactivated BM Soup’ was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies. PMID:26526154

The nature and treatment of stuttering as revealed by fMRI A within- and between-group comparison.

PubMed

Neumann, Katrin; Euler, Harald A; von Gudenberg, Alexander Wolff; Giraud, Anne-Lise; Lanfermann, Heinrich; Gall, Volker; Preibisch, Christine

2003-01-01

This article reviews some of our recent functional magnetic resonance imaging (fMRI) studies of stuttering. Using event-related fMRI experiments, we investigated brain activation during speech production. Results of three studies comparing persons who stutter (PWS) and persons who do not stutter (PWNS) are outlined. Their findings point to a region in the right frontal operculum (RFO) that was consistently implicated in stuttering. During overt reading and before fluency shaping therapy, PWS showed higher and more distributed neuronal activation than PWNS. Immediately after therapy differential activations were even more distributed and left sided. They extended to frontal, temporal, and parietal regions, anterior cingulate, insula, and putamen. These over-activations were slightly reduced and again more right sided two years after therapy. Left frontal deactivations remained stable over two years of observation, and therefore possibly indicate a dysfunction. After therapy, we noted higher activations in persons who stutter moderately than in those who stutter severely. These activations might reflect patterns of compensation. We discuss why these findings suggest that fluency-inducing techniques might synchronize a disturbed signal transmission between auditory, speech motor planning, and motor areas. The reader will learn about and be able to: (1) identify regions of brain activations and deactivations specific for PWS; (2) describe brain activation changes induced by fluency shaping therapy; and (3) discuss the correlation between stuttering severity and brain activation.

The value of physical performance measurements alongside assessment of sarcopenia in predicting receipt and completion of planned treatment in non-small cell lung cancer: an observational exploratory study.

PubMed

Collins, Jemima T; Noble, Simon; Chester, John; Davies, Helen E; Evans, William D; Farewell, Daniel; Lester, Jason F; Parry, Diane; Pettit, Rebecca; Byrne, Anthony

2018-01-01

The presence of muscle mass depletion is associated with poor outcomes and survival in cancer. Alongside muscle mass, assessment of muscle strength or physical performance is essential for the diagnosis of sarcopenia. Non-small cell lung cancer (NSCLC) is a prevalent form of cancer with high mortality, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) is commonly used to assess patients' suitability for treatment. However, a significant proportion of patients with good PS are unable to complete multidisciplinary team (MDT)-planned treatment. Little is known about the ability of objective measurements of physical performance in predicting patients' ability to complete MDT-planned treatment and outcomes in NSCLC. We sought to establish whether physical performance, utilising the short physical performance battery (SPPB), alongside muscle mass measurements, was able to predict receipt and completion of MDT-planned treatment, with a focus on chemotherapy in NSCLC. Participants with NSCLC treated through a single lung cancer MDT and ECOG PS 0-2 were recruited and the following assessed: body composition [bioelectrical impedance (BIA) and whole body dual-energy X-ray absorptiometry (DXA) in a subset], physical performance (SPPB), PS and nutritional status. We recorded receipt and completion of chemotherapy, as well as any adverse effects, hospitalisations, and treatment delays. We included a total of 62 participants with NSCLC, and in 26 of these, the MDT-planned treatment was chemotherapy. Participants with earlier stage disease and weight loss of <10% were more likely to complete MDT-planned treatment (p < 0.001 and p < 0.05). Patients with a higher total SPPB score were more likely to complete more cycles of chemotherapy as well as the full course. Quicker gait speeds and sit-to-stand times were associated with completion of three or more cycles of chemotherapy (all p < 0.05). For every unit increase in SPPB score, there was a 28.2% decrease in adverse events, hospitalisations and delays of chemotherapy (incidence rate ratio 0.718, p = 0.001), whilst ECOG PS showed no correlation with these outcomes. Assessing physical performance by SPPB is quick and simple to do in clinical settings and may give better indication of likely chemotherapy treatment course completion than muscle mass alone and ECOG PS. In turn, this may identify specific targets for early functional intervention and impact on MDT decision-making and prudent use of resources.

Battery longevity from cardiac resynchronization therapy defibrillators: differences between manufacturers and discrepancies with published product performance reports.

PubMed

Alam, Mian Bilal; Munir, Muhammad Bilal; Rattan, Rohit; Adelstein, Evan; Jain, Sandeep; Saba, Samir

2017-03-01

Cardiac resynchronization therapy (CRT) is an important treatment for heart failure that requires constant ventricular pacing, placing a high energy burden on CRT defibrillators (CRT-D). Longer battery life reduces the need for device changes and associated complications, thereby affecting patient outcomes and cost of care. We therefore investigated the time to battery depletion of CRT-D from different manufacturers and compared these results with manufacturers' published product performance reports (PPRs). All CRT-D recipients at our institution between January 2008 and December 2010 were included in this study cohort. The patients were followed up to the endpoint of battery depletion and were otherwise censored at the time of death, last follow-up, or device removal for any reason other than battery depletion. A total of 621 patients [173 Boston Scientific (BSC), 391 Medtronic (MDT), and 57 St. Jude Medical (SJM)] were followed up for a median of 3.7 (IQR 1.6-5.0) years, during which time 253 (41%) devices were replaced for battery depletion. Compared with MDT devices, battery depletion was 85 and 54% less likely to happen with BSC and SJM devices, respectively (P < 0.001 for pairwise comparisons). Product performance reports from all manufacturers significantly overestimated battery longevity by more than 20% 6 years after device implantation. Large differences in CRT-D battery longevity exist between manufacturers. Industry-published PPRs significantly overestimate device longevity. These data have important implications to patients, healthcare professionals, hospitals, and third-party payers. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Improving the quality of vascular surgical discharge planning in a hub centre

PubMed Central

Wariyapola, C; Littlehales, E; Abayasekara, K; Fall, D; Parker, V; Hatton, G

2016-01-01

Introduction Discharge planning improves patient outcomes, reduces hospital stay and readmission rates, and should involve a multidisciplinary team (MDT) approach. The efficacy of MDT meetings in discharge planning was examined, as well as reasons for delayed discharge among vascular surgical inpatients. Methods Dedicated weekly MDT meetings were held on the vascular ward in Royal Derby Hospital for three months. Each patient was presented to the discharge planning meeting and an expected date of discharge was decided prospectively. Patients who were discharged after this date were considered ‘delayed’ and reasons for delay were explored at the next meeting. Results Overall, 193 patients were included in the study. Of these, 42 patients (22%) had a delayed discharge while 29 (15%) had an early discharge. The main reasons for delay were awaiting beds (30%), social (14%) and medical (45%). In 64%, the cause for delay was avoidable. Two-thirds (67%) of all delays were >24 hours. This totalled 115 bed days, of which 67 could have been avoided. However, 32 bed days were saved by early discharge. This equates to a net loss of 35 bed days, at a net cost of £2,936 per month or £35,235 per year. The MDT meetings also improved the quality of discharge planning; the variability between expected and actual discharge dates decreased after the first month. Conclusions Discharge planning meetings help prepare for patient discharge and are most effective with multidisciplinary input. The majority of delayed discharges from hospital are preventable. The main causes are awaiting transfers, social services input and medical reasons (eg falls). There is an obvious financial incentive to improve discharge planning. The efficiency of the MDT at discharge planning improves with time and this should therefore be continued for best results. PMID:26924480

Improving the quality of vascular surgical discharge planning in a hub centre.

PubMed

Wariyapola, C; Littlehales, E; Abayasekara, K; Fall, D; Parker, V; Hatton, G

2016-04-01

Introduction Discharge planning improves patient outcomes, reduces hospital stay and readmission rates, and should involve a multidisciplinary team (MDT) approach. The efficacy of MDT meetings in discharge planning was examined, as well as reasons for delayed discharge among vascular surgical inpatients. Methods Dedicated weekly MDT meetings were held on the vascular ward in Royal Derby Hospital for three months. Each patient was presented to the discharge planning meeting and an expected date of discharge was decided prospectively. Patients who were discharged after this date were considered 'delayed' and reasons for delay were explored at the next meeting. Results Overall, 193 patients were included in the study. Of these, 42 patients (22%) had a delayed discharge while 29 (15%) had an early discharge. The main reasons for delay were awaiting beds (30%), social (14%) and medical (45%). In 64%, the cause for delay was avoidable. Two-thirds (67%) of all delays were >24 hours. This totalled 115 bed days, of which 67 could have been avoided. However, 32 bed days were saved by early discharge. This equates to a net loss of 35 bed days, at a net cost of £2,936 per month or £35,235 per year. The MDT meetings also improved the quality of discharge planning; the variability between expected and actual discharge dates decreased after the first month. Conclusions Discharge planning meetings help prepare for patient discharge and are most effective with multidisciplinary input. The majority of delayed discharges from hospital are preventable. The main causes are awaiting transfers, social services input and medical reasons (eg falls). There is an obvious financial incentive to improve discharge planning. The efficiency of the MDT at discharge planning improves with time and this should therefore be continued for best results.

Development and field testing of a mobile chlorine dioxide generation system for the decontamination of buildings contaminated with Bacillus anthracis.

PubMed

Wood, Joseph P; Blair Martin, G

2009-05-30

The numerous buildings that became contaminated with Bacillus anthracis (the bacterium causing the disease anthrax) in 2001, and more recent B. anthracis - related events, point to the need to have effective decontamination technologies for buildings contaminated with biological threat agents. The U.S. Government developed a portable chlorine dioxide (ClO(2)) generation system to decontaminate buildings contaminated with B. anthracis spores, and this so-called mobile decontamination trailer (MDT) prototype was tested through a series of three field trials. The first test of the MDT was conducted at Fort McClellan in Anniston, AL. during October 2004. Four test attempts occurred over two weekends; however, a number of system problems resulted in termination of the activity prior to any ClO(2) introduction into the test building. After making several design enhancements and equipment changes, the MDT was subjected to a second test. During this test, extensive leak checks were made using argon and nitrogen in lieu of chlorine gas; each subsystem was checked for functionality, and the MDT was operated for 24h. This second test demonstrated the MDT flow and control systems functioned satisfactorily, and thus it was decided to proceed to a third, more challenging field trial. In the last field test, ClO(2) was generated and routed directly to the scrubber in a 12-h continuous run. Measurement of ClO(2) levels at the generator outlet showed that the desired production rate was not achieved. Additionally, only one of the two scrubbers performed adequately with regard to maintaining ClO(2) emissions below the limit. Numerous lessons were learned in the field trials of this ClO(2) decontamination technology.

Implementation of a lung cancer multidisciplinary team standardised template for reporting to general practitioners: a mixed-method study

PubMed Central

Collett, Gemma K; Brown, Clare M; Shaw, Tim J; White, Kahren M; Beale, Philip J; Anderiesz, Cleola; Barnes, David J

2017-01-01

Objectives Few interventions have been designed that provide standardised information to primary care clinicians about the diagnostic and treatment recommendations resulting from cancer multidisciplinary team (MDT) (tumour board) meetings. This study aimed to develop, implement and evaluate a standardised template for lung cancer MDTs to provide clinical information and treatment recommendations to general practitioners (GPs). Specific objectives were to (1) evaluate template feasibility (acceptability, appropriateness and timeliness) with GPs and (2) document processes of preimplementation, implementation and evaluation within the MDT setting. Design A mixed-method study design using structured interviews with GPs and qualitative documentation of project logs about implementation processes. Setting Two hospitals in Central Sydney, New South Wales, Australia. Participants: 61 GPs evaluated the template. Two lung cancer MDTs, consisting of 33 clinicians, and eight researchers participated in template development and implementation strategy. Results The MDT-reporting template appears to be a feasible way of providing clinical information to GPs following patient presentation at a lung cancer MDT meeting. Ninety-five per cent of GPs strongly agreed or agreed that the standardised template provided useful and relevant information, that it was received in a timely manner (90%) and that the information was easy to interpret and communicate to the patient (84%). Implementation process data show that the investment made in the preimplementation stage to integrate the template into standard work practices was a critical factor in successful implementation. Conclusions This study demonstrates that it is feasible to provide lung cancer MDT treatment recommendations to GPs through implementation of a standardised template. A simple intervention, such as a standardised template, can help to address quality gaps and ensure that timely information is communicated between tertiary and primary care healthcare providers. PMID:29288182

Prisoners' views about the drugs problem in prisons, and the new Prison Service drug strategy.

PubMed

Gore, S M; Bird, A G; Cassidy, J

1999-09-01

Three hundred and seventy-five out of 575 prisoners (222/299 drug users and 153/267 non-users) who responded to a self-completion health care questionnaire at two prisons in 1997 commented on drugs in prisons. One hundred and forty-eight out of 176 responses expressed negative opinions about mandatory drugs testing (MDT), and 107 said that MDT promoted switching to or increased use of heroin/hard drugs'. Sixty-two prisoners suggested that more help/counselling was needed for drug users, 52 segregation of drug users/drug-free wings, and 50 more security on visits/in corridors after medication. The new Prison Service drug strategy has revised random MDT. It targets those who supply drugs, and supports those who want to stop using drugs, and accords with prisoners' views about the heroin problem in prisons.

Hypothalamus and amygdala response to acupuncture stimuli in Carpal Tunnel Syndrome.

PubMed

Napadow, V; Kettner, N; Liu, J; Li, M; Kwong, K K; Vangel, M; Makris, N; Audette, J; Hui, K K S

2007-08-01

Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects. We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI-4 in Carpal Tunnel Syndrome (CTS) patients and healthy controls (HC). CTS patients were retested after 5 weeks of acupuncture therapy. Thus, we investigated both the short-term brain response to acupuncture stimulation, as well as the influence of longer-term acupuncture therapy effects on this short-term response. CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC, controlling for the non-specific effects of sham acupuncture. A similar difference was found between CTS patients at baseline and after acupuncture therapy. For baseline CTS patients responding to verum acupuncture, functional connectivity was found between the hypothalamus and amygdala--the less deactivation in the amygdala, the greater the activation in the hypothalamus, and vice versa. Furthermore, hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients (inter-digit separation distance). This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC, through a coordinated limbic network including the hypothalamus and amygdala.

Radiologist participation in multi-disciplinary teams in breast cancer improves reflective practice, decision making and isolation.

PubMed

Alcantara, S B; Reed, W; Willis, K; Lee, W; Brennan, P; Lewis, S

2014-09-01

This study aims to explore Australian radiologists' experiences of participating in breast cancer multi-disciplinary team (MDT) meetings to identify enablers and barriers to participation as well their perception of confidence and patient care. Qualitative methods incorporating observation and interviews were used. Twenty-one breast cancer MDT meetings were observed across Sydney to study the dynamics of the meetings, the level of participation by radiologists and their most important interactions. Qualitative semi-structured interviews were conducted with 10 radiologists participating in these meetings regarding participation, educational opportunities and improvements to work practices. Radiologists' participation in breast cancer MDT meetings is influenced by the type of meeting they attend with higher levels of participation and a more dominant 'valued' role being evident in pre-interventional meetings. The key themes to emerge from the data include the importance of 'sharing experiences', the 'radiologist-pathologist relationship' and the value of 'continuing participation'. Radiologists believed their confidence in their clinical decision making increased when there was immediate feedback from pathologists. This study highlights the benefits of radiologists regularly participating in breast cancer MDT meetings in terms of continuing professional education resulting from collegial experiential learning. Radiologists' perceived patient care and workplace isolation were improved by sharing experiences with other cancer care colleagues. © 2013 John Wiley & Sons Ltd.

Mathematical decision theory applied to land capability: a case study in the community of madrid.

PubMed

Antón, J M; Saa-Requejo, A; Grau, J B; Gallardo, J; Díaz, M C; Andina, Diego; Sanchez, M E; Tarquis, A M

2014-03-01

In land evaluation science, a standard data set is obtained for each land unit to determine the land capability class for various uses, such as different farming systems, forestry, or the conservation or suitability of a specific crop. In this study, we used mathematical decision theory (MDT) methods to address this task. Mathematical decision theory has been used in areas such as management, finance, industrial design, rural development, the environment, and projects for future welfare to study quality and aptness problems using several criteria. We also review MDT applications in soil science and discuss the suitability of MDT methods for dealing simultaneously with a number of problems. The aim of the work was to show how MDT can be used to obtain a valid land quality index and to compare this with a traditional land capability method. Therefore, an additive classification method was applied to obtain a land quality index for 122 land units that were compiled for a case study of the Community of Madrid, Spain, and the results were compared with a previously assigned land capability class using traditional methods based on the minimum requirements for land attributes. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

Capture Efficiency of Biocompatible Magnetic Nanoparticles in Arterial Flow: A Computer Simulation for Magnetic Drug Targeting.

PubMed

Lunnoo, Thodsaphon; Puangmali, Theerapong

2015-12-01

The primary limitation of magnetic drug targeting (MDT) relates to the strength of an external magnetic field which decreases with increasing distance. Small nanoparticles (NPs) displaying superparamagnetic behaviour are also required in order to reduce embolization in the blood vessel. The small NPs, however, make it difficult to vector NPs and keep them in the desired location. The aims of this work were to investigate parameters influencing the capture efficiency of the drug carriers in mimicked arterial flow. In this work, we computationally modelled and evaluated capture efficiency in MDT with COMSOL Multiphysics 4.4. The studied parameters were (i) magnetic nanoparticle size, (ii) three classes of magnetic cores (Fe3O4, Fe2O3, and Fe), and (iii) the thickness of biocompatible coating materials (Au, SiO2, and PEG). It was found that the capture efficiency of small particles decreased with decreasing size and was less than 5 % for magnetic particles in the superparamagnetic regime. The thickness of non-magnetic coating materials did not significantly influence the capture efficiency of MDT. It was difficult to capture small drug carriers (D<200 nm) in the arterial flow. We suggest that the MDT with high-capture efficiency can be obtained in small vessels and low-blood velocities such as micro-capillary vessels.

Synoptic backgrounds of the widest wildfire in Mazandaran Province of Iran during December 11-13, 2010

NASA Astrophysics Data System (ADS)

Ghavidel, Yousef; Farajzadeh, Manuchehr; Khaleghi Babaei, Meysam

2016-12-01

In this paper, atmospheric origins of the widest wildfire in Mazandaran province on 11-13th of December, 2010 have been investigated. Data sets of this research include maximum daily temperature (MDT), minimum relative humidity (MRH) of terrestrial stations, dynamic and thermodynamic features of the atmosphere, Gridded data sets of Self-Calibrated Palmer drought severity index (SCPDSI) and global drought dataset standardized precipitation-evapotranspiration index (SPEI) and data related to the time and the extent of the wildfire. The ``environmental to circulation'' approach to synoptic classification has been used to investigate relationships between local-scale surface environment (wildfire) and the synoptic-scale atmospheric circulation conditions. Results of study show that during the 3-day wide wildfire, the average of MDT and the MRH was significantly different from the long-term average. During the aforementioned wildfire, the average of MDT in Mazandaran province was 26 °C and the average of MRH was reported 35 %. The long-term average of MDT and the MRH in Mazandaran province during 3 days of wildfire was 12.3 °C and 68 %, respectively. Therefore, the MDT has a positive abnormality of 13.7 °C and the MRH has a negative abnormality of 33 %. In addition, monthly SCPDSI and SPEI indicated severe drought conditions at December 2010 in Mazandaran. Analysis of SLP maps shows that during the 3-day fire, a pressure center of 1110 hPa on Persian Gulf and a very low-pressure center on Turkey and Asia Minor were created. Normally, this event has caused the pressure gradient and warm and dry air advection from Arabian Peninsula to higher longitudes, particularly Mazandaran province. Consequently, the MDT increased and the wildfire of Mazandaran forest took place in an area of 220 ha. Zonal wind maps signify the weakness of Zonal wind and meridional wind maps show the southern direction of meridional wind flow during the wide wildfire. Moreover, Omega maps prove that during the aforementioned wildfire, the Omega flow has been positive and the warm air flow has subsidence. This made the infusion of warm air and increased the MDT substantially and consequently the wildfire occurrence was facilitated. Temperature advection maps showed that in the level of 1000 hPa, the warm air blowing source is originated from Arabian Peninsula, in the level of 850 hPa from the Arabian Peninsula and Iraq and in the level of 700 and 500 hPa from Ethiopia, Arabian Peninsula and Iraq. The Hybrid-Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model outputs confirm the synoptic mechanisms for the discussed wildfire.

Rapid detection of pandemic influenza in the presence of seasonal influenza

PubMed Central

2010-01-01

Background Key to the control of pandemic influenza are surveillance systems that raise alarms rapidly and sensitively. In addition, they must minimise false alarms during a normal influenza season. We develop a method that uses historical syndromic influenza data from the existing surveillance system 'SERVIS' (Scottish Enhanced Respiratory Virus Infection Surveillance) for influenza-like illness (ILI) in Scotland. Methods We develop an algorithm based on the weekly case ratio (WCR) of reported ILI cases to generate an alarm for pandemic influenza. From the seasonal influenza data from 13 Scottish health boards, we estimate the joint probability distribution of the country-level WCR and the number of health boards showing synchronous increases in reported influenza cases over the previous week. Pandemic cases are sampled with various case reporting rates from simulated pandemic influenza infections and overlaid with seasonal SERVIS data from 2001 to 2007. Using this combined time series we test our method for speed of detection, sensitivity and specificity. Also, the 2008-09 SERVIS ILI cases are used for testing detection performances of the three methods with a real pandemic data. Results We compare our method, based on our simulation study, to the moving-average Cumulative Sums (Mov-Avg Cusum) and ILI rate threshold methods and find it to be more sensitive and rapid. For 1% case reporting and detection specificity of 95%, our method is 100% sensitive and has median detection time (MDT) of 4 weeks while the Mov-Avg Cusum and ILI rate threshold methods are, respectively, 97% and 100% sensitive with MDT of 5 weeks. At 99% specificity, our method remains 100% sensitive with MDT of 5 weeks. Although the threshold method maintains its sensitivity of 100% with MDT of 5 weeks, sensitivity of Mov-Avg Cusum declines to 92% with increased MDT of 6 weeks. For a two-fold decrease in the case reporting rate (0.5%) and 99% specificity, the WCR and threshold methods, respectively, have MDT of 5 and 6 weeks with both having sensitivity close to 100% while the Mov-Avg Cusum method can only manage sensitivity of 77% with MDT of 6 weeks. However, the WCR and Mov-Avg Cusum methods outperform the ILI threshold method by 1 week in retrospective detection of the 2009 pandemic in Scotland. Conclusions While computationally and statistically simple to implement, the WCR algorithm is capable of raising alarms, rapidly and sensitively, for influenza pandemics against a background of seasonal influenza. Although the algorithm was developed using the SERVIS data, it has the capacity to be used at other geographic scales and for different disease systems where buying some early extra time is critical. PMID:21106071

Magnetic field-enhanced cellular uptake of doxorubicin loaded magnetic nanoparticles for tumor treatment

NASA Astrophysics Data System (ADS)

Venugopal, Indu; Pernal, Sebastian; Duproz, Alexandra; Bentley, Jeromy; Engelhard, Herbert; Linninger, Andreas

2016-09-01

Cancer remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. In recent years, several varieties of nanoparticles (NPs) have been synthesized with the intent of being utilized as tumor drug delivery vehicles. We have produced superparamagnetic, gold-coated magnetite (Fe3O4@Au) NPs and loaded them with the chemotherapeutic drug doxorubicin (DOX) for magnetic drug targeting (MDT) of tumors. The synthetic strategy uses the food thickening agent gellan gum (Phytagel) as a negatively charged shell around the Fe3O4@Au NP onto which the positively charged DOX molecules are loaded via electrostatic attraction. The resulting DOX-loaded magnetic nanoparticles (DOX-MNPs) were characterized using transmission electron microscopy, energy dispersive x-ray spectroscopy, superconducting quantum interference device magnetometry, surface area electron diffraction, zeta potential measurements, fourier transform infrared spectroscopy as well as UV/Vis and fluorescence spectroscopy. Cytotoxicity of the DOX-MNPs was demonstrated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on C6 glioma cells. Cellular uptake of DOX-MNPs was enhanced with magnetic fields, which was quantitatively determined using flow cytometry. This improved uptake also led to greater tumor cell death, which was measured using MTT assay. These MDT results are promising for a new therapy for cancer.

Psychological benefits of virtual reality for patients in rehabilitation therapy.

PubMed

Chen, Chih-Hung; Jeng, Ming-Chang; Fung, Chin-Ping; Doong, Ji-Liang; Chuang, Tien-Yow

2009-05-01

Whether virtual rehabilitation is beneficial has not been determined. To investigate the psychological benefits of virtual reality in rehabilitation. An experimental group underwent therapy with a virtual-reality-based exercise bike, and a control group underwent the therapy without virtual-reality equipment. Hospital laboratory. 30 patients suffering from spinal-cord injury. A designed rehabilitation therapy. Endurance, Borg's rating-of-perceived-exertion scale, the Activation-Deactivation Adjective Check List (AD-ACL), and the Simulator Sickness Questionnaire. The differences between the experimental and control groups were significant for AD-ACL calmness and tension. A virtual-reality-based rehabilitation program can ease patients' tension and induce calm.

Lung cancer treatment rates and the role of the lung cancer nurse specialist: a qualitative study

PubMed Central

Redman, Judy; McDonnell, Ann; Borthwick, Diana; White, John

2015-01-01

Objectives This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. Setting 4 Hospital NHS Foundation Trusts in England. Design A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. Participants Four LCNSs, comprised the ‘cases’. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took part in a group interview and 60 lung cancer multidisciplinary team (MDT) members and co-ordinators were observed in the MDT meeting. Results The LCNS is crucial within the MDT and can act as a catalyst to patient access to treatment. The study identified the clinical activity (assessment, managing symptoms, psychological support and information provision) and role characteristics that can facilitate treatment access. These characteristics are the LCNS's presence across the patient pathway, acting as the ‘hub’ of the MDT, maintaining a holistic patient focus and working to an advanced level of practice. The findings indicate how factors may have a cumulative impact on treatment access. Conclusions If UK patient with lung cancer survival rates are to improve in line with comparable countries, we need to employ every advantage. This study demonstrates how the LCNS role may open doors to positive patient outcomes, including treatment. Further research is required to explore patients’ experiences, decision-making and attitudes to treatment. PMID:26685023

Use of surface drifters to increase resolution and accuracy of oceanic geostrophic circulation mapped from satellite only (altimetry and gravimetry)

NASA Astrophysics Data System (ADS)

Mulet, Sandrine; Rio, Marie-Hélène; Etienne, Hélène

2017-04-01

Strong improvements have been made in our knowledge of the surface ocean geostrophic circulation thanks to satellite observations. For instance, the use of the latest GOCE (Gravity field and steady-state Ocean Circulation Explorer) geoid model with altimetry data gives good estimate of the mean oceanic circulation at spatial scales down to 125 km. However, surface drifters are essential to resolve smaller scales, it is thus mandatory to carefully process drifter data and then to combine these different data sources. In this framework, the global 1/4° CNES-CLS13 Mean Dynamic Topography (MDT) and associated mean geostrophic currents have been computed (Rio et al, 2014). First a satellite only MDT was computed from altimetric and gravimetric data. Then, an important work was to pre-process drifter data to extract only the geostrophic component in order to be consistent with physical content of satellite only MDT. This step include estimate and remove of Ekman current and wind slippage. Finally drifters and satellite only MDT were combined. Similar approaches are used regionally to go further toward higher resolution, for instance in the Agulhas current or along the Brazilian coast. Also, a case study in the Gulf of Mexico intends to use drifters in the same way to improve weekly geostrophic current estimate.

A new approach to managing patients with problematic metal hip implants: the use of an Internet-enhanced multidisciplinary team meeting: AAOS exhibit selection.

PubMed

Berber, Reshid; Pappas, Yannis; Khoo, Michael; Miles, Jonathan; Carrington, Richard; Skinner, John; Hart, Alister

2015-02-18

Over one million patients worldwide are estimated to have a metal-on-metal hip arthroplasty. To improve the management of these patients and reduce surgeon uncertainty regarding decision-making, we designed an Internet-enhanced multidisciplinary team (iMDT) working approach. From August 2012 to April 2014, the iMDT discussed 215 patients with 266 metal-on-metal hip arthroplasties. Of these, 236 primary arthroplasties (132 hip resurfacing and 104 total hip) were analyzed. The remaining thirty cases involved problematic revised hips and were therefore excluded. The possible recommendations of the iMDT were monitoring, further investigation, or surgery. The concordance between the recommendation and the actual management was used to assess the usefulness of this approach in reducing uncertainty in surgeon-level decision-making. The median Oxford Hip Score was 35 (range, 4 to 48), and median cobalt and chromium levels in whole blood were 3.54 ppb (range, 0.18 to 161.46 ppb) and 3.17 ppb (range, 0.20 to 100.67 ppb), respectively. Magnetic resonance imaging revealed abductor muscle atrophy in ninety-two (39%) of the hips and a pseudotumor in eighty (34%). The iMDT recommended monitoring of 146 (61.9%) of the hips, further investigation of thirty (12.7%), and surgery in sixty (25.4%). The actual outcome was concordant with the recommendation in 211 (91.7%) of the hips. Our iMDT approach to the metal-on-metal hip burden combines the tacit knowledge of an expert panel, regulatory guidance, and up-to-date evidence to improve decision-making among surgeons. The high level of concordance between the recommendation and the actual outcome, combined with the feasibility of the methods used, suggest that this method effectively reduces uncertainty among surgeons and may lead to improved patient outcomes. Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.

Reducing health inequalities in people with learning disabilities: a multi-disciplinary team approach to care under general anaesthesia.

PubMed

Clough, S; Shehabi, Z; Morgan, C

2016-05-27

Background There remains significant inequality in health and healthcare in people with learning disabilities (LD). A lack of coordination and the episodic nature of care provision are contributory factors. Recognising the need to improve outcomes for this group, we evaluate a multi-disciplinary team (MDT) approach to care whereby additional medical procedures are carried out under the same episode of general anaesthesia (GA) as dental treatment for people with severe LD. This is the first published evaluation of its kind in the UK.Aim To evaluate the need and outcomes of an MDT approach to care among people with severe LD receiving dental treatment under GA.Method One hundred patients with severe LD and behaviour that challenges attended Barts Health Dental Hospital for dental assessment and subsequent treatment under GA. Details of failed or forthcoming medical interventions were determined. Where appropriate, care was coordinated with the relevant medical team.Findings Twenty-one percent (n = 21/100) had recent medical interventions attempted that had been abandoned, and 7.0% (n = 7/100) had future investigations or treatment planned under GA with medical specialties. An MDT approach was indicated in 28.0% (n = 28/100). For such complex cases, a successful MDT outcome was achieved in 89.3% (n = 25/28). This included ophthalmological/orthoptic, ENT and gastroenterological interventions in addition to medical imaging.Conclusion An MDT approach to care for people with LD offers improved patient-centred outcomes in addition to financial and resource efficiency. It requires a high level of cooperation between specialties, with consideration of the practicalities of a shared surgical space and equipment needs. Re-shaping of services and contractual flexibility are essential to support the future implementation of MDTs and to ensure long-term sustainability. Adoption of a holistic culture in the care of this vulnerable patient group is encouraged.

Cancer multidisciplinary team meetings in practice: Results from a multi-institutional quantitative survey and implications for policy change.

PubMed

Rankin, Nicole M; Lai, Michelle; Miller, Danielle; Beale, Philip; Spigelman, Allan; Prest, Gabrielle; Turley, Kim; Simes, John

2018-02-01

Multidisciplinary care is advocated as best practice in cancer care. Relatively little is documented about multidisciplinary team (MDT) meeting functioning, decision making and the use of evidence to support decision making in Australia. This descriptive study aimed to examine team functioning, the role of team meetings and evidence use in MDTs whose institutions are members of Sydney Catalyst Translational Cancer Research Centre. We designed a structured 40-item survey instrument about topics that included meeting purpose, organization, resources and documentation; caseload estimates; use of evidence and quality assurance; patient involvement and supportive care needs; and open-ended items about the MDTs strengths and weaknesses. Participants were invited to participate via email and the survey was administered online. Data were analyzed using descriptive and comparative statistics. Thirty-seven MDTs from seven hospitals participated (100% response) and represented common (70%) and rare tumor groups (30%). MDT meeting purpose was reported as treatment (100%) or diagnostic decision making (88%), or for education purposes (70%). Most MDTs based treatment decisions on group consensus (92%), adherence to clinical practice guidelines (57%) or other evidence-based medicine sources (33%). The majority of MDTs discussed only a proportion of new patients at each meeting emphasizing the importance of educational aspects for other cases. Barriers exist in the availability of data to enable audit and reflection on evidence-based practice. MDT strengths included collaboration and quality discussion about patients. MDT meetings focus on treatment decision making, with group consensus playing a significant role in translating research evidence from guidelines into clinical decision making. With a varying proportion of patients discussed in each MDT meeting, a wider audit of multidisciplinary care would enable more accurate assessments of whether treatment recommendations are in accordance with best-practice evidence. © 2017 John Wiley & Sons Australia, Ltd.

14821AT LANCE, Missile Number 2419, Round Number 349APT, 12 May 1980.

DTIC Science & Technology

1980-05-01

WSTRUCTIONUREPOT DCUMNTAIONPAG EPORE COMPLEMON PORN REPORT NUMBER 2GOTACCESSION NO S. RECIPIENT’S CATALOG NUMBER TDR 1148 __7 0_____T___ ~. *.~----...,S. TYPE OF...Data at 0815 MDT ---------- 4 4. White Sands Desert Site (WSD) Significant Level Data at 0815 MDT ------------------------------------ 5 5. WSD Upper...humidity, dew point (0 C), density (gm/n,3), Wind direction and speed, and cloud cover were made at the LC-39 Met Site at T-0 minutes. (2) Monitor of

Microgrid Design Toolkit (MDT) Technical Documentation and Component Summaries

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

Arguello, Bryan; Gearhart, Jared Lee; Jones, Katherine A.

2015-09-01

The Microgrid Design Toolkit (MDT) is a decision support software tool for microgrid designers to use during the microgrid design process. The models that support the two main capabilities in MDT are described. The first capability, the Microgrid Sizing Capability (MSC), is used to determine the size and composition of a new microgrid in the early stages of the design process. MSC is a mixed-integer linear program that is focused on developing a microgrid that is economically viable when connected to the grid. The second capability is focused on refining a microgrid design for operation in islanded mode. This secondmore » capability relies on two models: the Technology Management Optimization (TMO) model and Performance Reliability Model (PRM). TMO uses a genetic algorithm to create and refine a collection of candidate microgrid designs. It uses PRM, a simulation based reliability model, to assess the performance of these designs. TMO produces a collection of microgrid designs that perform well with respect to one or more performance metrics.« less

[Multidisciplinary team building in enhanced recovery after surgery].

PubMed

Jia, W D

2018-01-01

There has been 10 years to explore the road in line with China's actual enhanced recovery after surgery(ERAS) since Academician Li Jieshou introduced the view of ERAS into China. ERAS has been widely carried out in the field of surgery, and gradually formed with Chinese characteristics of ERAS clinical pathway.The clinical implementation of ERAS relies on the effective integration of a series of perioperative methods, and any single technique or method can't completely reduce the perioperative physiological and psychological traumatic stress of the patient, so as to achieve the patient's rapid rehabilitation patient-centered multidisciplinary team(MDT)collaboration is an inevitable trend in ERAS development. On the basis of drawing lessons from foreign experience, the establishment of ERAS-MDT model in line with China's national conditions is a new subject that needs to be studied at present. The construction of ERAS-MDT might promote the development of new ERAS services, new technologies, and ultimately promote the improvement of surgical treatment, and bring the greatest clinical benefit to the society and patients.

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

Multiplex PCR technique could be an alternative approach for early detection of leprosy among close contacts--a pilot study from India.

PubMed

Banerjee, Surajita; Sarkar, Kamalesh; Gupta, Soma; Mahapatra, Prasanta Sinha; Gupta, Siddhartha; Guha, Samudra; Bandhopadhayay, Debasis; Ghosal, Chaitry; Paine, Suman Kalyan; Dutta, Rathindra Nath; Biswas, Nibir; Bhattacharya, Basudev

2010-08-24

Implementation of Multi drug Therapy (MDT) regimen has resulted in the decline of the total number of leprosy cases in the world. Though the prevalence rate has been declining, the incidence rate remains more or less constant and high in South East Asian countries particularly in India, Nepal, Bangladesh, Pakistan and Srilanka. Leprosy, particularly that of multibacillary type spreads silently before it is clinically detected. An early detection and treatment would help to prevent transmission in the community. Multiplex PCR (M-PCR) technique appears to be promising towards early detection among contacts of leprosy cases. A total of 234 paucibacillary (PB) and 205 multibacillary (MB) leprosy cases were studied in a community of an endemic area of Bankura district of West Bengal (Eastern India). They were assessed by smear examination for acid-fast bacilli (AFB) and M-PCR technique. These patients were treated with Multidrug Therapy (MDT) as prescribed by WHO following detection. A total of 110 MB and 72 PB contacts were studied by performing M-PCR in their nasal swab samples. 83.4% of MB patients were observed to be positive by smear examination for AFB and 89.2% by M-PCR. While 22.2% of PB patients were found to be positive by smear examination for AFB, 80.3% of these patients were positive by M-PCR. Among leprosy contacts (using M-PCR), 10.9% were found to be positive among MB contacts and 1.3% among PB contacts. Interestingly, two contacts of M-PCR positive MB cases developed leprosy during the period of two years follow up. The M-PCR technique appears to be an efficient tool for early detection of leprosy cases in community based contact tracing amongst close associates of PB and MB cases. Early contact tracing using a molecular biology tool can be of great help in curbing the incidence of leprosy further.

An Independent Evaluation of Mode Deactivation Therapy for Juvenile Offenders

ERIC Educational Resources Information Center

Thoder, Vincent J.; Cautilli, Joseph D.

2011-01-01

Juveniles who commit crimes are likely to exhibit conduct problems in their youth. Persistent and long-term antisocial behavior can be seen in very young children. To treat these children, programs must be designed to meet the needs of them on an individualized basis. Residential treatment, typically, is the answer, but research has shown its…

Insights into the deactivation of 5-bromouracil after ultraviolet excitation

NASA Astrophysics Data System (ADS)

Peccati, Francesca; Mai, Sebastian; González, Leticia

2017-03-01

5-Bromouracil is a nucleobase analogue that can replace thymine in DNA strands and acts as a strong radiosensitizer, with potential applications in molecular biology and cancer therapy. Here, the deactivation of 5-bromouracil after ultraviolet irradiation is investigated in the singlet and triplet manifold by accurate quantum chemistry calculations and non-adiabatic dynamics simulations. It is found that, after irradiation to the bright ππ* state, three main relaxation pathways are, in principle, possible: relaxation back to the ground state, intersystem crossing (ISC) and C-Br photodissociation. Based on accurate MS-CASPT2 optimizations, we propose that ground-state relaxation should be the predominant deactivation pathway in the gas phase. We then employ different electronic structure methods to assess their suitability to carry out excited-state dynamics simulations. MRCIS (multi-reference configuration interaction including single excitations) was used in surface hopping simulations to compute the ultrafast ISC dynamics, which mostly involves the 1nOπ* and 3ππ* states. This article is part of the themed issue 'Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces'.

Insights into the deactivation of 5-bromouracil after ultraviolet excitation

PubMed Central

2017-01-01

5-Bromouracil is a nucleobase analogue that can replace thymine in DNA strands and acts as a strong radiosensitizer, with potential applications in molecular biology and cancer therapy. Here, the deactivation of 5-bromouracil after ultraviolet irradiation is investigated in the singlet and triplet manifold by accurate quantum chemistry calculations and non-adiabatic dynamics simulations. It is found that, after irradiation to the bright ππ* state, three main relaxation pathways are, in principle, possible: relaxation back to the ground state, intersystem crossing (ISC) and C–Br photodissociation. Based on accurate MS-CASPT2 optimizations, we propose that ground-state relaxation should be the predominant deactivation pathway in the gas phase. We then employ different electronic structure methods to assess their suitability to carry out excited-state dynamics simulations. MRCIS (multi-reference configuration interaction including single excitations) was used in surface hopping simulations to compute the ultrafast ISC dynamics, which mostly involves the 1nOπ* and 3ππ* states. This article is part of the themed issue ‘Theoretical and computational studies of non-equilibrium and non-statistical dynamics in the gas phase, in the condensed phase and at interfaces’. PMID:28320905

Design of an eMonitor system to transport electronic patient care report (ePCR) information in unstable MobileIP wireless environment.

PubMed

Giovanni, Mazza G; Shenvi, Rohit; Battles, Marcie; Orthner, Helmuth F

2008-11-06

The eMonitor is a component of the ePatient system; a prototype system used by emergency medical services (EMS) personnel in the field to record and transmits electronic patient care report (ePCR) information interactively. The eMonitor component allows each Mobile Data Terminal (MDT) on an unreliable Cisco MobileIP wireless network to securely send and received XML messages used to update patient information to and from the MDT before, during and after the transport of a patient.

Formalising multidisciplinary peer review: developing a haematological malignancy-specific electronic proforma and standard operating procedure to facilitate procedural efficiency and evidence-based clinical practice.

PubMed

Trotman, Judith; Trinh, Jimmy; Kwan, Yiu Lam; Estell, Jane A; Fletcher, Julie; Archer, Kate; Lee, Kenneth; Foo, Kerwin; Curnow, Jennifer; Bianchi, Alessandra; Wignall, Lynda; Verner, Emma; Gasiorowski, Robin; Siedlecka, Elizabeth; Cunningham, Ilona

2017-05-01

Multidisciplinary team (MDT) meetings aimed at facilitating peer review have become standard practice in oncology. However, there is scant literature on the optimal structure and conduct of such meetings. To develop a process for formal peer review of patients with haematological malignancies and to audit any resulting changes made to the management recommendations of the treating physician. A standard operating procedure (SOP) for MDT meetings was developed essentially to integrate clinical peer review with weekly pathology and radiology meetings. The centrepiece is the electronic submission of a patient-specific proforma (Microsoft InfoPath) prior to the meeting. It serves as the template for presentation, discussion and recording of recommendations and conclusions. The final verified document is stored in the electronic patient record, and a copy is sent to the general practitioner. The proposed management plans were compared to the consensus recommendations of the meeting for the first 4 years since inception. Both SOP and proforma underwent continual improvements. These provided the framework for the conduct of a robust weekly MDT meeting for peer review of the management of patients with haematological malignancies. On 20% of occasions, patient management plans were altered to optimise patient care as a direct consequence on peer review at the MDT. Our streamlined process, in its ultimate format, has provided a mature and efficient forum for formal peer review in a genuine multidisciplinary environment. Both initial data and informal feedback support its ongoing activity as an integral component of delivering quality patient care. © 2016 Royal Australasian College of Physicians.

Psycho acoustical Measures in Individuals with Congenital Visual Impairment.

PubMed

Kumar, Kaushlendra; Thomas, Teenu; Bhat, Jayashree S; Ranjan, Rajesh

2017-12-01

In congenital visual impaired individuals one modality is impaired (visual modality) this impairment is compensated by other sensory modalities. There is evidence that visual impaired performed better in different auditory task like localization, auditory memory, verbal memory, auditory attention, and other behavioural tasks when compare to normal sighted individuals. The current study was aimed to compare the temporal resolution, frequency resolution and speech perception in noise ability in individuals with congenital visual impaired and normal sighted. Temporal resolution, frequency resolution, and speech perception in noise were measured using MDT, GDT, DDT, SRDT, and SNR50 respectively. Twelve congenital visual impaired participants with age range of 18 to 40 years were taken and equal in number with normal sighted participants. All the participants had normal hearing sensitivity with normal middle ear functioning. Individual with visual impairment showed superior threshold in MDT, SRDT and SNR50 as compared to normal sighted individuals. This may be due to complexity of the tasks; MDT, SRDT and SNR50 are complex tasks than GDT and DDT. Visual impairment showed superior performance in auditory processing and speech perception with complex auditory perceptual tasks.

Correlates of violence in Guinea's Maison Centrale Prison: a statistical approach to documenting human rights abuses.

PubMed

Osborn, Ronald E

2010-12-15

Les Mêmes Droits Pour Tous (MDT) is a human rights NGO in Guinea, West Africa that focuses on the rights of prisoners in Maison Centrale, the country's largest prison located in the capital city of Conakry. In 2007, MDT completed a survey of the prison population to assess basic legal and human rights conditions. This article uses statistical tools to explore MDT's survey results in greater depth, shedding light on human rights violations in Guinea. It contributes to human rights literature that argues for greater use of econometric tools in rights reporting, and demonstrates how human rights practitioners and academics can work together to construct an etiology of violence and torture by state actors, as physical violence is perhaps the most extreme violation of the individual's right to health. Copyright © 2010 Osborn. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

The McDermitt Caldera, NV-OR, USA: Geologic mapping, volcanology, mineralization, and high precision 40Ar/39Ar dating of early Yellowstone hotspot magmatism

NASA Astrophysics Data System (ADS)

Henry, C. D.; Castor, S. B.; Starkel, W. A.; Ellis, B. S.; Wolff, J. A.; Heizler, M. T.; McIntosh, W. C.

2012-12-01

The irregularly keyhole-shaped, 40x30 to 22 km, McDermitt caldera formed at 16.35±0.03 Ma (n=4; Fish Canyon sanidine = 28.201 Ma) during eruption of a zoned, aphyric, mildly peralkaline rhyolite to abundantly anorthoclase-phyric, metaluminous dacite (McDermitt Tuff, MDT). Intracaldera MDT is locally strongly rheomorphic and, where MDT and caldera floor are well-exposed along the western margin, contains abundant megabreccia but is a maximum of ~450 m thick. If this thickness is representative of the caldera, intracaldera MDT has a volume of ~400 km3. Outflow MDT is currently known up to 13 km south of the caldera but only 3 km north of the caldera. Maximum outflow thickness is ~100 m, and outflow volume is probably no more than about 10% that of intracaldera MDT. The thickness and volume relations indicate collapse began very early during eruption, and most tuff ponded within the caldera. Outflow is strongly rheomorphic where draped over paleotopography. Late, undated icelandite lavas and domes are probably residual magma from the caldera chamber. Resurgence is expressed as both a broad, symmetrical dome in the north part and a fault-bound uplift in the south part of the caldera. Mineralization associated with the caldera includes Zr-rich U deposits that are indistinguishable in age with the McDermitt Tuff, Hg, Au, Ga, and Li-rich intracaldera tuffaceous sediments. Although formed during probable regional extension, the caldera is flat-lying and cut only at its west and east margins by much younger, high-angle normal faults. The caldera formed in an area of highly diverse Cenozoic volcanic rocks. The oldest are 39 and 46 Ma metaluminous dacite lavas along the northwest margin. Coarsely plagioclase-phyric to aphyric Steens Basalt lavas crop out around the west, northwest, and northeast margin. An anorthoclase-phyric, low-Si rhyolite lava (16.69±0.02 Ma) that is interbedded with probable Steens lavas northeast of the caldera and a biotite rhyolite lava dome (16.62±0.02 Ma) in the west floor of the caldera are the oldest middle Miocene silicic rocks near the caldera. Other pre-caldera rocks are a mix of variably peralkaline, distal ignimbrites; biotite rhyolite domes and lavas; and variably peralkaline rhyolite lavas that were emplaced between about 16.50 and 16.36 Ma. Silicic volcanism around the McDermitt caldera is some of the oldest of the Yellowstone hotspot track, but two known calderas in NW Nevada and unidentified sources of distal ignimbrites near McDermitt are older than the McDermitt caldera. Initial hotspot silicic volcanism occurred over a large area across NW Nevada, SE Oregon, and SW Idaho.

The occurrence of reactions and impairments in leprosy: experience in the leprosy control program of three provinces in northeastern Thailand, 1987-1995 [correction of 1978-1995]. I. Overview of the study.

PubMed

Schreuder, P A

1998-06-01

This paper is the first in a series of three reports on the occurrence of reactions and impairments in leprosy in Thailand. This first paper gives a general overview about the methodology of the study, some epidemiological observations, delay in detection, multidrug therapy (MDT) completion rates and relapses. The other two papers report on: II. Reactions and III. Neural and Other Impairments. This study was carried out from 1987 until 1995 in three neighboring provinces in northeastern Thailand. A population-based, prospective cohort study. All 640 newly diagnosed leprosy patients in the three provinces, registered between October 1987 and September 1990, were included [420 paucibacillary (PB) and 220 multibacillary (MB)]. This group was followed up (actively and passively) until the end of 1995. Patients were found by active and passive case finding. All new, untreated leprosy patients from the area were enrolled and started on the World Health Organization (WHO) MDT (WHO/MDT) regimen. A vertical control service was run by specialized leprosy workers. During treatment the patients received their monthly doses at home. During surveillance the patients were followed up once a year by a special team. Patients were questioned about delay in detection. Treatment completion rates were calculated. The occurrence of reactions and neural and other impairments at the beginning of, during and after treatment was ascertained. After treatment, the occurrence of late reactions and relapses was recorded. A higher frequency of leprosy was found among the male patients, especially in the MB group. However, in the PB group a higher female/male ratio was found in the age group 55 years and older. There was an increase in the detection rate from the youngest age group to the age group 55 years and older, which showed the highest detection rate. Treatment completion rates were high, 95% in both in the PB and MB treatment groups. About 50% of the new cases reported a delay between onset and registration of 1 year or more. By 1995, 93% of the original patient group was still available for follow up. By the end of 1995, 8 PB and 2 MB relapses were recorded.

Evaluating the impact of an integrated multidisciplinary head & neck competency-based anatomy & radiology teaching approach in radiation oncology: a prospective cohort study

PubMed Central

2014-01-01

Background Modern radiation oncology demands a thorough understanding of gross and cross-sectional anatomy for diagnostic and therapeutic applications. Complex anatomic sites present challenges for learners and are not well-addressed in traditional postgraduate curricula. A multidisciplinary team (MDT) based head-and-neck gross and radiologic anatomy program for radiation oncology trainees was developed, piloted, and empirically assessed for efficacy and learning outcomes. Methods Four site-specific MDT head-and-neck seminars were implemented, each involving a MDT delivering didactic and case-based instruction, supplemented by cadaveric presentations. There was no dedicated contouring instruction. Pre- and post-testing were performed to assess knowledge, and ability to apply knowledge to the clinical setting as defined by accuracy of contouring. Paired analyses of knowledge pretests and posttests were performed by Wilcoxon matched-pair signed-rank test. Results Fifteen post-graduate trainees participated. A statistically significant (p < 0.001) mean absolute improvement of 4.6 points (17.03%) was observed between knowledge pretest and posttest scores. Contouring accuracy was analyzed quantitatively by comparing spatial overlap of participants’ pretest and posttest contours with a gold standard through the dice similarity coefficient. A statistically significant improvement in contouring accuracy was observed for 3 out of 20 anatomical structures. Qualitative and quantitative feedback revealed that participants were more confident at contouring and were enthusiastic towards the seminars. Conclusions MDT seminars were associated with improved knowledge scores and resident satisfaction; however, increased gross and cross-sectional anatomic knowledge did not translate into improvements in contouring accuracy. Further research should evaluate the impact of hands-on contouring sessions in addition to dedicated instructional sessions to develop competencies. PMID:24969509

Availability analysis of the traveling-wave maser amplifiers in the deep space network. Part 1: The 70-meter antennas

NASA Technical Reports Server (NTRS)

Issa, T. N.

1992-01-01

The results of the reliability and availability analyses of the individual S- and X-band traveling-wave maser (TWM) assemblies and their operational configurations in the 70-meter antennas of NASA's Deep Space Network (DSN) are described. For the period 1990 through 1991, the TWM availability parameters for the Telemetry Data System are: mean time between failures (MTBF), 930 hr; mean time to restore services (MTTRS), 1.4 hr; and the average availability, 99.85 percent. In previously published articles, the performance analysis of the TWM assemblies was confined to the determination of the parameters specified above. However, as the mean down time (MDT) for the repair of TWM's increases, the levels of the TWM operational availabilities and MTTRS are adversely affected. A more comprehensive TWM availability analysis is presented to permit evaluation of both MTBF and MDT effects. Performance analysis of the TWM assemblies, based on their station monthly failure reports, indicates that the TWM's required MTBF and MDT levels of 3000 hr and 36 to 48 hr, respectively, have been achieved by the TWM's only at the Canberra Deep Space Station (DSS 43). The Markov Process technique is employed to develop suitable availability measures for the S- and X-band TWM configurations when each is operated in a two-assembly standby mode. The derived stochastic expressions allow for the evaluation of those configurations' simultaneous availability for the Antenna Microwave Subsystem. The application of these expressions to demonstrate the impact of various levels of TWM maintainability (or MDT) on their configurations' operational availabilities is presented for each of the 70-m antenna stations.

Understanding the dynamics of superparamagnetic particles under the influence of high field gradient arrays

NASA Astrophysics Data System (ADS)

Barnsley, Lester C.; Carugo, Dario; Aron, Miles; Stride, Eleanor

2017-03-01

The aim of this study was to characterize the behaviour of superparamagnetic particles in magnetic drug targeting (MDT) schemes. A 3-dimensional mathematical model was developed, based on the analytical derivation of the trajectory of a magnetized particle suspended inside a fluid channel carrying laminar flow and in the vicinity of an external source of magnetic force. Semi-analytical expressions to quantify the proportion of captured particles, and their relative accumulation (concentration) as a function of distance along the wall of the channel were also derived. These were expressed in terms of a non-dimensional ratio of the relevant physical and physiological parameters corresponding to a given MDT protocol. The ability of the analytical model to assess magnetic targeting schemes was tested against numerical simulations of particle trajectories. The semi-analytical expressions were found to provide good first-order approximations for the performance of MDT systems in which the magnetic force is relatively constant over a large spatial range. The numerical model was then used to test the suitability of a range of different designs of permanent magnet assemblies for MDT. The results indicated that magnetic arrays that emit a strong magnetic force that varies rapidly over a confined spatial range are the most suitable for concentrating magnetic particles in a localized region. By comparison, commonly used magnet geometries such as button magnets and linear Halbach arrays result in distributions of accumulated particles that are less efficient for delivery. The trajectories predicted by the numerical model were verified experimentally by acoustically focusing magnetic microbeads flowing in a glass capillary channel, and optically tracking their path past a high field gradient Halbach array.

Evaluating the impact of an integrated multidisciplinary head & neck competency-based anatomy & radiology teaching approach in radiation oncology: a prospective cohort study.

PubMed

D'Souza, Leah; Jaswal, Jasbir; Chan, Francis; Johnson, Marjorie; Tay, Keng Yeow; Fung, Kevin; Palma, David

2014-06-26

Modern radiation oncology demands a thorough understanding of gross and cross-sectional anatomy for diagnostic and therapeutic applications. Complex anatomic sites present challenges for learners and are not well-addressed in traditional postgraduate curricula. A multidisciplinary team (MDT) based head-and-neck gross and radiologic anatomy program for radiation oncology trainees was developed, piloted, and empirically assessed for efficacy and learning outcomes. Four site-specific MDT head-and-neck seminars were implemented, each involving a MDT delivering didactic and case-based instruction, supplemented by cadaveric presentations. There was no dedicated contouring instruction. Pre- and post-testing were performed to assess knowledge, and ability to apply knowledge to the clinical setting as defined by accuracy of contouring. Paired analyses of knowledge pretests and posttests were performed by Wilcoxon matched-pair signed-rank test. Fifteen post-graduate trainees participated. A statistically significant (p < 0.001) mean absolute improvement of 4.6 points (17.03%) was observed between knowledge pretest and posttest scores. Contouring accuracy was analyzed quantitatively by comparing spatial overlap of participants' pretest and posttest contours with a gold standard through the dice similarity coefficient. A statistically significant improvement in contouring accuracy was observed for 3 out of 20 anatomical structures. Qualitative and quantitative feedback revealed that participants were more confident at contouring and were enthusiastic towards the seminars. MDT seminars were associated with improved knowledge scores and resident satisfaction; however, increased gross and cross-sectional anatomic knowledge did not translate into improvements in contouring accuracy. Further research should evaluate the impact of hands-on contouring sessions in addition to dedicated instructional sessions to develop competencies.

Principles of Carbon Catabolite Repression in the Rice Blast Fungus: Tps1, Nmr1-3, and a MATE–Family Pump Regulate Glucose Metabolism during Infection

PubMed Central

Hartline, David; Quispe, Cristian F.; Madayiputhiya, Nandakumar; Wilson, Richard A.

2012-01-01

Understanding the genetic pathways that regulate how pathogenic fungi respond to their environment is paramount to developing effective mitigation strategies against disease. Carbon catabolite repression (CCR) is a global regulatory mechanism found in a wide range of microbial organisms that ensures the preferential utilization of glucose over less favourable carbon sources, but little is known about the components of CCR in filamentous fungi. Here we report three new mediators of CCR in the devastating rice blast fungus Magnaporthe oryzae: the sugar sensor Tps1, the Nmr1-3 inhibitor proteins, and the multidrug and toxin extrusion (MATE)–family pump, Mdt1. Using simple plate tests coupled with transcriptional analysis, we show that Tps1, in response to glucose-6-phosphate sensing, triggers CCR via the inactivation of Nmr1-3. In addition, by dissecting the CCR pathway using Agrobacterium tumefaciens-mediated mutagenesis, we also show that Mdt1 is an additional and previously unknown regulator of glucose metabolism. Mdt1 regulates glucose assimilation downstream of Tps1 and is necessary for nutrient utilization, sporulation, and pathogenicity. This is the first functional characterization of a MATE–family protein in filamentous fungi and the first description of a MATE protein in genetic regulation or plant pathogenicity. Perturbing CCR in Δtps1 and MDT1 disruption strains thus results in physiological defects that impact pathogenesis, possibly through the early expression of cell wall–degrading enzymes. Taken together, the importance of discovering three new regulators of carbon metabolism lies in understanding how M. oryzae and other pathogenic fungi respond to nutrient availability and control development during infection. PMID:22570632

The impact of a dedicated multidisciplinary team on the management of early rectal cancer.

PubMed

Vaughan-Shaw, P G; Wheeler, J M D; Borley, N R

2015-08-01

Local excision of early rectal cancer (ERCa) offers comparable survival and reduced operative morbidity compared with radical surgery, yet it risks an adverse oncological outcome if performed in the wrong setting. This retrospective review considers the impact of the introduction of a specialist early rectal cancer multidisciplinary team (ERCa MDT) on the investigation and management of ERCa. A retrospective comparative cohort study was undertaken. Patients with a final diagnosis of pT1 rectal cancer at our unit were identified for two 12-month periods before and after the introduction of the specialist ERCa MDT. Data on investigations and therapeutic interventions were compared. Nineteen patients from 2006 and 24 from 2011 were included. In 2006, 12 patients underwent MRI and four transrectal ultrasound (TRUS) examination, while in 2011, 18 and 20, respectively, received MRI and TRUS. In 2006 four patients underwent incidental ERCa polypectomy, with all having a positive resection margin leading to anterior resection. In 2011 only one case with a positive margin following extended endoscopic mucosal resection was identified. Definitive local excision without subsequent resection occurred in two patients in 2006 and in 16 in 2011. The study demonstrates an improvement in preoperative ERCa staging, a reduction in margin positivity and an increase in the use of local excision following the implementation of a specialist ERCa MDT. The increased detection of rectal neoplasms through screening and surveillance programmes requires further investigation and management. A specialist ERCa MDT will improve management and should be available to all practitioners involved with patients with ERCa. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Establishing a Multidisciplinary Head and Neck Clinical Pathway: An Implementation Evaluation and Audit of Dysphagia-Related Services and Outcomes.

PubMed

Messing, Barbara Pisano; Ward, Elizabeth C; Lazarus, Cathy; Ryniak, Keri; Kim, Melissa; Silinonte, Jessica; Gold, Dorothy; Thompson, Carol B; Pitman, Karen T; Blanco, Ray; Sobel, Ryan; Harrer, Karen; Ulmer, Karen; Neuner, Geoffrey; Patel, Kruti; Tang, Mei; Lee, Gregory

2018-06-19

Head and neck cancer (HNC) guidelines recommend regular multidisciplinary team (MDT) monitoring and early intervention to optimize dysphagia outcomes; however, many factors affect the ability to achieve these goals. The aims of this study were to explore the barriers/facilitators to establishing and sustaining a MDT HNC care pathway and to examine the dysphagia-related speech-language pathology (SLP) and dietetic components of the pathway. Using the Consolidated Framework for Implementation Research (CFIR), a mixed methods study design was used to evaluate an established MDT HNC pathway. Ten MDT members provided perceptions of facilitators/barriers to implementing and sustaining the pathway. Patients attending the SLP and dietetic components of the pathway who commenced treatment between 2013 and 2014 (n = 63) were audited for attendance, outcome data collected per visit, and swallowing outcomes to 24-month post-treatment. Dysphagia outcomes were compared to a published cohort who had received intensive prophylactic dysphagia management. Multiple CFIR constructs were identified as critical to implementing and sustaining the pathway. Complexity was a barrier. Patient attendance was excellent during treatment, with low rates of non-compliance (< 15%) to 24 months. Collection of clinician/patient outcome tools was good during treatment, but lower post-treatment. Dysphagia outcomes were good and comparable to prior published data. The pathway provided patients with access to regular supportive care and provided staff opportunities to provide early and ongoing dysphagia monitoring and management. However, implementing and sustaining a HNC pathway is complex, requiring significant staff resources, financial investment, and perseverance. Regular audits are necessary to monitor the quality of the pathway.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PubMed

Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

2015-09-01

Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO).

PubMed

Popescu, R A; Schäfer, R; Califano, R; Eckert, R; Coleman, R; Douillard, J-Y; Cervantes, A; Casali, P G; Sessa, C; Van Cutsem, E; de Vries, E; Pavlidis, N; Fumasoli, K; Wörmann, B; Samonigg, H; Cascinu, S; Cruz Hernández, J J; Howard, A J; Ciardiello, F; Stahel, R A; Piccart, M

2014-01-01

The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire 'cancer journey'. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care.

Molecular detection of multidrug-resistant Mycobacterium leprae from Indian leprosy patients.

PubMed

Lavania, Mallika; Singh, Itu; Turankar, Ravindra P; Ahuja, Madhvi; Pathak, Vinay; Sengupta, Utpal; Das, Loretta; Kumar, Archana; Darlong, Joydeepa; Nathan, Rajeev; Maseey, Asha

2018-03-01

The emergence of multidrug-resistant (MDR) organisms for any infectious disease is a public health concern. Global efforts to control leprosy by intensive chemotherapy have led to a significant decrease in the number of registered patients. Currently recommended control measures for treating leprosy with multidrug therapy (MDT) were designed to prevent the spread of dapsone-resistant Mycobacterium leprae strains. Here we report the identification of MDR M. leprae from relapse leprosy patients from endemic regions in India. Resistance profiles to rifampicin, dapsone and ofloxacin of the isolated strains were confirmed by identification of mutations in genes previously shown to be associated with resistance to each drug. Between 2009-2016, slit-skin smear samples were collected from 239 relapse and 11 new leprosy cases from hospitals of The Leprosy Mission across India. DNA was extracted from the samples and was analysed by PCR targeting the rpoB, folP and gyrA genes associated with resistance to rifampicin, dapsone and ofloxacin, respectively, in M. leprae. M. leprae Thai-53 (wild-type) and Zensho-4 (MDR) were used as reference strains. Fifteen strains showed representative mutations in at least two resistance genes. Two strains showed mutations in all three genes responsible for drug resistance. Seven, seven and one strain, respectively, showed mutations in genes responsible for rifampicin and dapsone resistance, for dapsone and ofloxacin resistance and for rifampicin and ofloxacin resistance. This study showed the emergence of MDR M. leprae in MDT-treated leprosy patients from endemic regions of India. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

Preoperative neo-adjuvant therapy for curable rectal cancer--reaching a consensus 2008.

PubMed

Scott, N A; Susnerwala, S; Gollins, S; Myint, A Sun; Levine, E

2009-03-01

Our aim was to determine the range of neo-adjuvant therapy the multidisciplinary team (MDT) currently offers patients with curable (M(0)) rectal cancer. A senior oncologist from each of the four oncology centres in north Wales and the north-west of England (approximate target population 8 million - Glan Clwyd, Clatterbridge, Christie and Preston) reviewed his/her understanding of the current evidence of neo-adjuvant therapy in rectal cancer. Then a representative from each centre was asked to identify which of three neo-adjuvant options (no neo-adjuvant therapy, short-course radiotherapy 25 Gy over five fractions and long-course chemoradiotherapy) he/she would use for a rectal cancer in the upper, middle or lower third of the rectum staged by magnetic resonance imaging as being T(2)-T(4) and/or N(0)-N(2). In all cases of locally advanced rectal cancer (T(3a) N(1)-T(4)), oncologists from the four oncology centres recommended long-course chemoradiotherapy before rectal resection. This consensus was maintained for cases of lower third T(3a) N(0) cancers. Thereafter, the majority of patients with rectal cancer are offered adjuvant short-course radiotherapy. Neo-adjuvant therapy is less likely to be offered if the tumour is early (T(2), N(0)) and/or situated in the upper third of the rectum.

Determining Coastal Mean Dynamic Topography by Geodetic Methods

NASA Astrophysics Data System (ADS)

Huang, Jianliang

2017-11-01

In geodesy, coastal mean dynamic topography (MDT) was traditionally determined by spirit leveling technique. Advances in navigation satellite positioning (e.g., GPS) and geoid determination enable space-based leveling with an accuracy of about 3 cm at tide gauges. Recent CryoSat-2, a satellite altimetry mission with synthetic aperture radar (SAR) and SAR interferometric measurements, extends the space-based leveling to the coastal ocean with the same accuracy. However, barriers remain in applying the two space-based geodetic methods for MDT determination over the coastal ocean because current geoid modeling focuses primarily on land as a substitute to spirit leveling to realize the vertical datum.

Construction of a smart medication dispenser with high degree of scalability and remote manageability.

PubMed

Pak, JuGeon; Park, KeeHyun

2012-01-01

We propose a smart medication dispenser having a high degree of scalability and remote manageability. We construct the dispenser to have extensible hardware architecture for achieving scalability, and we install an agent program in it for achieving remote manageability. The dispenser operates as follows: when the real-time clock reaches the predetermined medication time and the user presses the dispense button at that time, the predetermined medication is dispensed from the medication dispensing tray (MDT). In the proposed dispenser, the medication for each patient is stored in an MDT. One smart medication dispenser contains mainly one MDT; however, the dispenser can be extended to include more MDTs in order to support multiple users using one dispenser. For remote management, the proposed dispenser transmits the medication status and the system configurations to the monitoring server. In the case of a specific event such as a shortage of medication, memory overload, software error, or non-adherence, the event is transmitted immediately. All these operations are performed automatically without the intervention of patients, through the agent program installed in the dispenser. Results of implementation and verification show that the proposed dispenser operates normally and performs the management operations from the medication monitoring server suitably.

Visualization of superparamagnetic nanoparticles in vascular tissue using XμCT and histology.

PubMed

Tietze, Rainer; Rahn, Helene; Lyer, Stefan; Schreiber, Eveline; Mann, Jenny; Odenbach, Stefan; Alexiou, Christoph

2011-02-01

In order to increase the dose of antineoplastic agents in the tumor area, the concept of magnetic drug targeting (MDT) has been developed. Magnetic nanoparticles consisting of iron oxide and a biocompatible cover layer suspended in an aqueous solution (ferrofluid) serve as carriers for chemotherapeutics being enriched by an external magnetic field after intra-arterial application in desired body compartments (i.e., tumor). We established an ex vivo model to simulate in vivo conditions in a circulating system consisting of magnetic iron oxide nanoparticles passing an intact bovine artery and being focused by an external magnetic field to study their distribution in the vessel. Micro-computed X-ray tomography (XμCT) and histology can elucidate the arrangement of these particles after application. XμCT-analysis has been performed on arterial sections after MDT in order to determine the distribution of the nanoparticles. These measurements have been carried out with a cone X-ray source and corresponding histological sections were stained with Prussian blue. It could be shown that combining XμCT and histology offers the opportunity for a better understanding of the mechanisms of nanoparticle deposition in the vascular system after MDT.

Building the multidisciplinary team for management of patients with hepatocellular carcinoma.

PubMed

Naugler, Willscott E; Alsina, Angel E; Frenette, Catherine T; Rossaro, Lorenzo; Sellers, Marty T

2015-05-01

Optimal care of the patient with hepatocellular carcinoma (HCC) necessitates the involvement of multiple providers. Because the patient with HCC often carries 2 conditions with competing mortality risks (cancer and underlying cirrhosis), no single provider is equipped to deal with all of these patients' needs adequately. Multidisciplinary teams (MDTs) have evolved to facilitate care coordination, reassessments of clinical course, and nimble changes in treatment plans required for this complex group of patients. Providers or sites that elect to manage patients with HCC thus are increasingly aware of the need to build their own MDT or communicate with an established one. The availability of new communication technologies, such as teleconferencing or teleconsultation, offers the possibility of MDT expansion into underserved or rural areas, as well as areas such as correctional facilities. Although the availability of resources for HCC patient care varies from site to site, construction of an MDT is possible in a wide spectrum of clinical practices, and this article suggests a blueprint for assembly of such collaboration. Research strategies are needed to explain how MDTs improve clinical outcomes so that MDTs themselves can be improved. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

3-D trajectory model for MDT using micro-spheres implanted within large blood vessels

NASA Astrophysics Data System (ADS)

Choomphon-anomakhun, Natthaphon; Natenapit, Mayuree

2016-09-01

Implant assisted magnetic drug targeting (IA-MDT) using ferromagnetic spherical targets implanted within large blood vessels and subjected to a uniform externally applied magnetic field (H0) has been investigated and reported for the first time. The capture areas (As) of magnetic drug carrier particles (MDCPs) were determined from the analysis of particle trajectories simulated from equations of motion. Then, the effects of various parameters, such as types of ferromagnetic materials in the targets and MDCPs, blood flow rates, mass fraction of the ferromagnetic material in the MDCPs, average radii of MDCPs (Rp) and the strength of H0 on the As were obtained. Furthermore, the effects of saturation magnetization of the ferromagnetic materials in the MDCPs and within the targets on the As were analyzed. After this, the suitable strengths of H0 and Rp for IA-MDT designs were reported. Dimensionless As, ranging from 2 to 7, was obtained with Rp ranging from 500 to 2500 nm, μ0H0 less than 0.8 T and a blood flow rate of 0.1 m s-1. The target-MDCP materials considered are iron-iron, iron-magnetite and SS409-magnetite, respectively.

Analyzing the Effects of Climate Factors on Soybean Protein, Oil Contents, and Composition by Extensive and High-Density Sampling in China.

PubMed

Song, Wenwen; Yang, Ruping; Wu, Tingting; Wu, Cunxiang; Sun, Shi; Zhang, Shouwei; Jiang, Bingjun; Tian, Shiyan; Liu, Xiaobing; Han, Tianfu

2016-05-25

From 2010 to 2013, 763 soybean samples were collected from an extensive area of China. The correlations between seed compositions and climate data were analyzed. The contents of crude protein and water-soluble protein, total amount of protein plus oil, and most of the amino acids were positively correlated with an accumulated temperature ≥15 °C (AT15) and the mean daily temperature (MDT) but were negatively correlated with hours of sunshine (HS) and diurnal temperature range (DTR). The correlations of crude oil and most fatty acids with climate factors were opposite to those of crude protein. Crude oil content had a quadratic regression relationship with MDT, and a positive correlation between oil content and MDT was found when the daily temperature was <19.7 °C. A path analysis indicated that DTR was the main factor that directly affected soybean protein and oil contents. The study illustrated the effects of climate factors on soybean protein and oil contents and proposed agronomic practices for improving soybean quality in different regions of China. The results provide a foundation for the regionalization of high-quality soybean production in China and similar regions in the world.

X-ray Absorption Spectroscopy Systematics at the Tungsten L-Edge

PubMed Central

2015-01-01

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, was interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W0(PMe3)6], [WIICl2(PMePh2)4], [WIIICl2(dppe)2][PF6] (dppe = 1,2-bis(diphenylphosphino)ethane), [WIVCl4(PMePh2)2], [WV(NPh)Cl3(PMe3)2], and [WVICl6], correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio of the L3,2-edges and the L1 rising-edge energy with metal Zeff, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [WIV(mdt)2(CO)2] and [WIV(mdt)2(CN)2]2– (mdt2– = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively WIV species even though the mdt ligands exist at different redox levels in the two compounds. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: (1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Zeff in the species of interest. (2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS. (3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal–ligand distances, exaggerate the difference between formal oxidation state and metal Zeff or, as in the case of [WIV(mdt)2(CO)2], exert the subtle effect of modulating the redox level of other ligands in the coordination sphere. PMID:25068843

X-ray absorption spectroscopy systematics at the tungsten L-edge.

PubMed

Jayarathne, Upul; Chandrasekaran, Perumalreddy; Greene, Angelique F; Mague, Joel T; DeBeer, Serena; Lancaster, Kyle M; Sproules, Stephen; Donahue, James P

2014-08-18

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, was interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W(0)(PMe3)6], [W(II)Cl2(PMePh2)4], [W(III)Cl2(dppe)2][PF6] (dppe = 1,2-bis(diphenylphosphino)ethane), [W(IV)Cl4(PMePh2)2], [W(V)(NPh)Cl3(PMe3)2], and [W(VI)Cl6], correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio of the L3,2-edges and the L1 rising-edge energy with metal Zeff, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W(IV)(mdt)2(CO)2] and [W(IV)(mdt)2(CN)2](2-) (mdt(2-) = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W(IV) species even though the mdt ligands exist at different redox levels in the two compounds. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: (1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Zeff in the species of interest. (2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS. (3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Zeff or, as in the case of [W(IV)(mdt)2(CO)2], exert the subtle effect of modulating the redox level of other ligands in the coordination sphere.

Task deactivation reductions and atrophy within parietal default mode regions are overlapping but only weakly correlated in mild cognitive impairment

PubMed Central

Threlkeld, Zachary D.; Jicha, Greg A.; Smith, Charles D.; Gold, Brian T.

2012-01-01

Reduced task deactivation within regions of the default mode network (DMN) has been frequently reported in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). As task deactivations reductions become increasingly used in the study of early AD states, it is important to understand their relationship to atrophy. To address this issue, the present study compared task deactivation reductions during a lexical decision task and atrophy in aMCI, using a series of parallel voxel-wise and region-wise analyses of fMRI and structural data. Our results identified multiple regions within parietal cortex as convergence areas of task deactivation and atrophy in aMCI. Relationships between parietal regions showing overlapping task deactivation reductions and atrophy in aMCI were then explored. Regression analyses demonstrated minimal correlation between task deactivation reductions and either local or global atrophy in aMCI. In addition, a logistic regression model which combined task deactivation reductions and atrophy in parietal DMN regions showed higher classificatory accuracy of aMCI than separate task deactivation or atrophy models. Results suggest that task deactivation reductions and atrophy in parietal regions provide complementary rather than redundant information in aMCI. Future longitudinal studies will be required to assess the utility of combining task deactivation reductions and atrophy in the detection of early AD. PMID:21860094

Stress and Pore Pressure Measurement in IODP Riser Drilling: An Example from Expedition 319, Kumano Basin offshore SW Honshu, Japan

NASA Astrophysics Data System (ADS)

Saffer, D. M.; McNeill, L. C.; Byrne, T. B.; Araki, E.; Flemings, P. B.; Conin, M.; Eguchi, N. O.; Takahashi, K.; Toczko, S.; Boutt, D. F.; Doan, M.; Kano, Y.; Ito, T.; Lin, W.

2009-12-01

In summer 2009, Integrated Ocean Drilling Program (IODP) Expedition 319 drilled a 1600 m deep riser borehole (Site C0009) in the Kumano Basin offshore SW Japan, to investigate the properties, structure and state of stress in the hanging wall above the subduction plate boundary. The first riser-based scientific drilling in IODP history allowed us to make several new scientific measurements including in situ stress magnitude, pore pressure and permeability using the Modular Formation Dynamics Tester (MDT) wireline tool, and measurement of minimum stress magnitude from Leak-off Tests (LOT). In addition, continuous monitoring of mud weight, mud gas, annular pressure, and mud losses provided data to constrain formation pore fluid pressure and stress. At Site C0009, we conducted 2 LOTs below a casing shoe at 708.6 m depth and 11 successful MDT measurements, including 9 single probe tests to measure pore pressure and fluid mobility and 2 dual packer tests: 1 to measure permeability by a drawdown test, and 1 to measure in situ stress. Measured pore pressures are approximately hydrostatic to 1463.7 m depth. We observed only minor gas shows when drilling ahead (as in-place methane was liberated from the rock at the bit) but little or no gas during pipe connections. This indicates that the borehole mud pressure exceeded the formation pore pressure, and is consistent with the MDT measurements. Permeabilities range from ~10-16 m2 - 10-14 m2, and the observed variation is consistent with lithologic changes defined in gamma ray logs. The MDT measurement at 874.3 mbsf and the LOT at 708.6 m yield values for the least principal stress of 34.8 MPa and 30.2 MPa, respectively. Both are less than the vertical stress (Sv) computed from density logs. Partial mud circulation losses occurred when the borehole mud pressure exceeded the leak-off stress measured at the base of the casing shoe; this provides an additional indirect constraint on Shmin magnitude. Mud pressure slightly in excess of the leak-off stress may have also generated poorly-developed drilling-induced tensile fractures (DITF) observed in resistivity image logs between ~750 - 1000 m. From the presence of DITF, Shmin measurements, and assuming a rock tensile strength of 1 MPa, we determine that SHmax is 35.1 MPa for the MDT stress measurement, and 30.2 MPa for the LOT. Using the MDT measurement of Shmin, the resulting principal stress magnitudes define a strike-slip faulting regime with effective stresses of Shmax’ = 14 MPa, Sv' = 7.3 MPa, and Shmin’ = 6.4 MPa. In contrast, using the LOT measurement of Shmin, the stress magnitudes indicate a normal faulting regime in which Sv’ = 6.2 MPa, Shmax’ = 2.8 MPa, and Shmin’ = 2.6 MPa.

Specialization in the default mode: Task-induced brain deactivations dissociate between visual working memory and attention.

PubMed

Mayer, Jutta S; Roebroeck, Alard; Maurer, Konrad; Linden, David E J

2010-01-01

The idea of an organized mode of brain function that is present as default state and suspended during goal-directed behaviors has recently gained much interest in the study of human brain function. The default mode hypothesis is based on the repeated observation that certain brain areas show task-induced deactivations across a wide range of cognitive tasks. In this event-related functional resonance imaging study we tested the default mode hypothesis by comparing common and selective patterns of BOLD deactivation in response to the demands on visual attention and working memory (WM) that were independently modulated within one task. The results revealed task-induced deactivations within regions of the default mode network (DMN) with a segregation of areas that were additively deactivated by an increase in the demands on both attention and WM, and areas that were selectively deactivated by either high attentional demand or WM load. Attention-selective deactivations appeared in the left ventrolateral and medial prefrontal cortex and the left lateral temporal cortex. Conversely, WM-selective deactivations were found predominantly in the right hemisphere including the medial-parietal, the lateral temporo-parietal, and the medial prefrontal cortex. Moreover, during WM encoding deactivated regions showed task-specific functional connectivity. These findings demonstrate that task-induced deactivations within parts of the DMN depend on the specific characteristics of the attention and WM components of the task. The DMN can thus be subdivided into a set of brain regions that deactivate indiscriminately in response to cognitive demand ("the core DMN") and a part whose deactivation depends on the specific task. 2009 Wiley-Liss, Inc.

INACTIVATION OF E. COLI PYRUVATE FORMATE-LYASE: ROLE OF AdhE AND SMALL MOLECULES

PubMed Central

Nnyepi, Mbako R.; Peng, Yi; Broderick, Joan B.

2007-01-01

E. coli AdhE has been reported to harbor three distinct enzymatic activities: alcohol dehydrogenase, acetaldehyde-CoA dehydrogenase, and pyruvate formate-lyase (PFL) deactivase. Herein we report on the cloning, expression, and purification of E. coli AdhE, and the re-investigation of its purported enzymatic activities. While both the alcohol dehydrogenase and acetaldehyde-CoA dehydrogenase activities were readily detectible, we were unable to obtain any evidence for catalytic deactivation of PFL by AdhE, regardless of whether the reported cofactors for deactivation (Fe(II), NAD, and CoA) were present. Our results demonstrate that AdhE is not a PFL deactivating enzyme. We have also examined the potential for deactivation of active PFL by small-molecule thiols. Both β-mercaptoethanol and dithiothreitol deactivate PFL efficiently, with the former providing quite rapid deactivation. PFL deactivated by these thiols can be reactivated, suggesting that this deactivation is non-destructive transfer of an H atom equivalent to quench the glycyl radical. PMID:17280641

49 CFR 192.727 - Abandonment or deactivation of facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Abandonment or deactivation of facilities. 192.727... Abandonment or deactivation of facilities. (a) Each operator shall conduct abandonment or deactivation of... pipeline facility or each abandoned onshore pipeline facility that crosses over, under or through a...

Clofazimine Modulates the Expression of Lipid Metabolism Proteins in Mycobacterium leprae-Infected Macrophages

PubMed Central

Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

2012-01-01

Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine. PMID:23236531

Cost-Effectiveness of a Chemoprophylactic Intervention with Single Dose Rifampicin in Contacts of New Leprosy Patients

PubMed Central

Idema, Willemijn J.; Majer, Istvan M.; Pahan, David; Oskam, Linda; Polinder, Suzanne; Richardus, Jan Hendrik

2010-01-01

Background With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR) for contacts as chemoprophylactic intervention in the control of leprosy. Methods We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER) between the standard multidrug therapy (MDT) program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case. Findings Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214), slightly less cost-effective in next door neighbours (ICER $497) and least cost-effective among household contacts (ICER $856). Conclusion Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world. PMID:21072235

Clofazimine modulates the expression of lipid metabolism proteins in Mycobacterium leprae-infected macrophages.

PubMed

Degang, Yang; Akama, Takeshi; Hara, Takeshi; Tanigawa, Kazunari; Ishido, Yuko; Gidoh, Masaichi; Makino, Masahiko; Ishii, Norihisa; Suzuki, Koichi

2012-01-01

Mycobacterium leprae (M. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. The lipids provide essential nutrition for the mycobacteria, and M. leprae infection modulates expression of important host proteins related to lipid metabolism. Thus, M. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (ADRP) and decreases hormone-sensitive lipase (HSL), facilitating the accumulation and maintenance of lipid-rich environments suitable for the intracellular survival of M. leprae. HSL levels are not detectable in skin smear specimens taken from leprosy patients, but re-appear shortly after multidrug therapy (MDT). This study examined the effect of MDT components on host lipid metabolism in vitro, and the outcome of rifampicin, dapsone and clofazimine treatment on ADRP and HSL expression in THP-1 cells. Clofazimine attenuated the mRNA and protein levels of ADRP in M. leprae-infected cells, while those of HSL were increased. Rifampicin and dapsone did not show any significant effects on ADRP and HSL expression levels. A transient increase of interferon (IFN)-β and IFN-γ mRNA was also observed in cells infected with M. leprae and treated with clofazimine. Lipid droplets accumulated by M. leprae-infection were significantly decreased 48 h after clofazimine treatment. Such effects were not evident in cells without M. leprae infection. In clinical samples, ADRP expression was decreased and HSL expression was increased after treatment. These results suggest that clofazimine modulates lipid metabolism in M. leprae-infected macrophages by modulating the expression of ADRP and HSL. It also induces IFN production in M. leprae-infected cells. The resultant decrease in lipid accumulation, increase in lipolysis, and activation of innate immunity may be some of the key actions of clofazimine.

Contrast-Enhanced Ultrasound Guided Biopsy of Undetermined Abdominal Lesions: A Multidisciplinary Decision-Making Approach.

PubMed

Mao, Feng; Dong, Yi; Ji, Zhengbiao; Cao, Jiaying; Wang, Wen-Ping

2017-01-01

Aim. To investigate the value of contrast-enhanced ultrasound (CEUS) guided biopsy of undetermined abdominal lesions in multidisciplinary treatment (MDT) decision-making approach. Methods. Between Jan 2012 and Dec 2015, 60 consecutive patients (male, 37; female, 23; mean age, 51.3 years ± 14.6) who presented with undetermined abdominal lesions were included. CEUS and core needle percutaneous biopsy was performed under real-time CEUS guidance in all lesions. Data were recorded and compared with conventional ultrasound (US) guidance group ( n = 75). All CEUS findings and clinical data were evaluated in MDT. Results. CEUS enabled the delimitation of more (88.3% versus 41.3%) and larger (14.1 ± 10.7 mm versus 32.3 ± 18.5 mm) nonenhanced necrotic areas. More inner (20.0% versus 6.7%) and surrounding (18.3% versus 2.7%) major vessels were visualized and avoided during biopsies. CEUS-guided biopsy increased the diagnostic accuracy from 93.3% to 98.3%, with correct diagnosis in 57 of 60 lesions (95.0%). The therapeutic plan was influenced by CEUS guided biopsies findings in the majority of patients (98.3%). Conclusion. The combination of CEUS guided biopsy and MDT decision-making approach is useful in the diagnostic work-up and therapeutic management.

Young drivers' engagement with social interactive technology on their smartphone: Critical beliefs to target in public education messages.

PubMed

Gauld, Cassandra S; Lewis, Ioni M; White, Katherine M; Watson, Barry

2016-11-01

The current study forms part of a larger study based on the Step Approach to Message Design and Testing (SatMDT), a new and innovative framework designed to guide the development and evaluation of health communication messages, including road safety messages. This four step framework is based on several theories, including the Theory of Planned Behaviour. The current study followed steps one and two of the SatMDT framework and utilised a quantitative survey to validate salient beliefs (behavioural, normative, and control) about initiating, monitoring/reading, and responding to social interactive technology on smartphones by N=114 (88F, 26M) young drivers aged 17-25 years. These beliefs had been elicited in a prior in-depth qualitative study. A subsequent critical beliefs analysis identified seven beliefs as potential targets for public education messages, including, 'slow-moving traffic' (control belief - facilitator) for both monitoring/reading and responding behaviours; 'feeling at ease that you had received an expected communication' (behavioural belief -advantage) for monitoring/reading behaviour; and 'friends/peers more likely to approve' (normative belief) for responding behaviour. Potential message content targeting these seven critical beliefs is discussed in accordance with the SatMDT. Copyright © 2016 Elsevier Ltd. All rights reserved.

[¹⁸F]Altanserin and small animal PET: impact of multidrug efflux transporters on ligand brain uptake and subsequent quantification of 5-HT₂A receptor densities in the rat brain.

PubMed

Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Celik, A Avdo; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas

2014-01-01

The selective 5-hydroxytryptamine type 2a receptor (5-HT(2A)R) radiotracer [(18)F]altanserin is a promising ligand for in vivo brain imaging in rodents. However, [(18)F]altanserin is a substrate of P-glycoprotein (P-gp) in rats. Its applicability might therefore be constrained by both a differential expression of P-gp under pathological conditions, e.g. epilepsy, and its relatively low cerebral uptake. The aim of the present study was therefore twofold: (i) to investigate whether inhibition of multidrug transporters (MDT) is suitable to enhance the cerebral uptake of [(18)F]altanserin in vivo and (ii) to test different pharmacokinetic, particularly reference tissue-based models for exact quantification of 5-HT(2A)R densities in the rat brain. Eighteen Sprague-Dawley rats, either treated with the MDT inhibitor cyclosporine A (CsA, 50 mg/kg, n=8) or vehicle (n=10) underwent 180-min PET scans with arterial blood sampling. Kinetic analyses of tissue time-activity curves (TACs) were performed to validate invasive and non-invasive pharmacokinetic models. CsA application lead to a two- to threefold increase of [(18)F]altanserin uptake in different brain regions and showed a trend toward higher binding potentials (BP(ND)) of the radioligand. MDT inhibition led to an increased cerebral uptake of [(18)F]altanserin but did not improve the reliability of BP(ND) as a non-invasive estimate of 5-HT(2A)R. This finding is most probable caused by the heterogeneous distribution of P-gp in the rat brain and its incomplete blockade in the reference region (cerebellum). Differential MDT expressions in experimental animal models or pathological conditions are therefore likely to influence the applicability of imaging protocols and have to be carefully evaluated. © 2013.

Formation pressure testing at the Mount Elbert Gas Hydrate Stratigraphic Test Well, Alaska North Slope: Operational summary, history matching, and interpretations

USGS Publications Warehouse

Anderson, B.; Hancock, S.; Wilson, S.; Enger, C.; Collett, T.; Boswell, R.; Hunter, R.

2011-01-01

In February 2007, the U.S. Department of Energy, BP Exploration (Alaska), and the U.S. Geological Survey, collected open-hole pressure-response data, as well as gas and water sample collection, in a gas hydrate reservoir (the BPXA-DOE-USGS Mount Elbert Gas Hydrate Stratigraphic Test Well) using Schlumberger's Modular Dynamics Formation Tester (MDT) wireline tool. Four such MDT tests, ranging from six to twelve hours duration, and including a series of flow, sampling, and shut-in periods of various durations, were conducted. Locations for the testing were selected based on NMR and other log data to assure sufficient isolation from reservoir boundaries and zones of excess free water. Test stages in which pressure was reduced sufficiently to mobilize free water in the formation (yet not cause gas hydrate dissociation) produced readily interpretable pressure build-up profiles. Build-ups following larger drawdowns consistently showed gas-hydrate dissociation and gas release (as confirmed by optical fluid analyzer data), as well as progressive dampening of reservoir pressure build-up during sequential tests at a given MDT test station.History matches of one multi-stage, 12-h test (the C2 test) were accomplished using five different reservoir simulators: CMG-STARS, HydrateResSim, MH21-HYDRES, STOMP-HYD, and TOUGH. +. HYDRATE. Simulations utilized detailed information collected across the reservoir either obtained or determined from geophysical well logs, including thickness (11.3. m, 37 ft.), porosity (35%), hydrate saturation (65%), both mobile and immobile water saturations, intrinsic permeability (1000 mD), pore water salinity (5 ppt), and formation temperature (3.3-3.9 ??C). This paper will present the approach and preliminary results of the history-matching efforts, including estimates of initial formation permeability and analyses of the various unique features exhibited by the MDT results. ?? 2010 Elsevier Ltd.

Multispectral decomposition for the removal of out-of-band effects of visible/infrared imaging radiometer suite visible and near-infrared bands.

PubMed

Gao, Bo-Cai; Chen, Wei

2012-06-20

The visible/infrared imaging radiometer suite (VIIRS) is now onboard the first satellite platform managed by the Joint Polar Satellite System of the National Oceanic and Atmospheric Administration and NASA. It collects scientific data from an altitude of approximately 830 km in 22 narrow bands located in the 0.4-12.5 μm range. The seven visible and near-infrared (VisNIR) bands in the wavelength interval between 0.4-0.9 μm are known to suffer from the out-of-band (OOB) responses--a small amount of radiances far away from the center of a given band that can pass through the filter and reach detectors in the focal plane. A proper treatment of the OOB effects is necessary in order to obtain calibrated at-sensor radiance data [referred to as the Sensor Data Records (SDRs)] from measurements with these bands and subsequently to derive higher-level data products [referred to as the Environmental Data Records (EDRs)]. We have recently developed a new technique, called multispectral decomposition transform (MDT), which can be used to correct/remove the OOB effects of VIIRS VisNIR bands and to recover the true narrow band radiances from the measured radiances containing OOB effects. An MDT matrix is derived from the laboratory-measured filter transmittance functions. The recovery of the narrow band signals is performed through a matrix multiplication--the production between the MDT matrix and a multispectral vector. Hyperspectral imaging data measured from high altitude aircraft and satellite platforms, the complete VIIRS filter functions, and the truncated VIIRS filter functions to narrower spectral intervals, are used to simulate the VIIRS data with and without OOB effects. Our experimental results using the proposed MDT method have demonstrated that the average errors after decomposition are reduced by more than one order of magnitude.

Changes in Cytokines, Sensory Tests, and Self-reported Pain Levels After Manual Treatment of Low Back Pain.

PubMed

Degenhardt, Brian F; Johnson, Jane C; Fossum, Christian; Andicochea, Chad T; Stuart, Melissa K

2017-07-01

Unbalanced 3-factor design with repeated measures on 1 factor. To determine the effect of manual treatment (MT) on cytokine and pain sensations in those with and without low back pain (LBP). Evidence suggests that MT reduces LBP but by unknown mechanisms. Certain cytokines have been elevated in patients with LBP and may be affected by MT. Participants aged 20-60 years with chronic LBP or without LBP were recruited and randomly assigned to MT, sham ultrasound treatment, or no treatment groups. Venous blood samples were collected and pain levels assessed at baseline, 1 hour later, and 24 hours later. Blood was analyzed for interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and C-reactive protein. Pain levels were measured by pressure pain threshold (PPT), mechanical detection threshold (MDT), dynamic mechanical allodynia, and self-report. Forty (30 women, age 36±11 y) participants completed the study, 33 with LBP (13 MT, 13 sham ultrasound treatment, and 7 no treatment) and 7 without LBP. Participants with or without LBP could not be differentiated on the basis of serum cytokine levels, PPT, or MDT (P≥0.08). There were no significant differences between the groups at 1 hour or 24 hours on serum cytokines, PPT, or MDT (P≥0.07). There was a significant decrease from baseline in IL-6 for the no treatment (LBP) group (P=0.04), in C-reactive protein for the sham ultrasound treatment group (P=0.03), in MDT for all 3 LBP groups (P≤0.02), and in self-reported pain for the MT and sham ultrasound treatment groups (P=0.03 and 0.01). Self-reported pain was reduced with MT and sham ultrasound treatment 24 hours after treatment, but inflammatory markers within venous circulation and quantitative sensory tests were unable to differentiate between study groups. Therefore, we were unable to characterize mechanisms underlying chronic LBP.

Assessing performance of gravity models in the Arctic and the implications for polar oceanography

NASA Astrophysics Data System (ADS)

Thomas, S. F.; McAdoo, D. C.; Farrell, S. L.; Brozena, J. M.; Childers, V. A.; Ziebart, M. K.; Shepherd, A.

2014-12-01

The circulation of the Arctic Ocean is of great interest to both the oceanographic and cryospheric communities. Understanding both the steady state and variations of this circulation is essential to building our knowledge of Arctic climate. With the advent of high inclination altimeter missions such as CryoSat and ICESat, it is now feasible to produce Mean Dynamic Topography (MDT) products for the region, which allow a comprehensive investigation of geostrophic currents. However, the accuracy of these products is largely limited by our knowledge of the marine geoid in the Arctic. There are a number of publicly available gravity models commonly used to derive the geoid. These use different combinations of available data (satellite gravimetry, altimetry, laser ranging, and in-situ) and are calculated using different mathematical techniques. However, the effect of these differences on the real world performance of these models when used for oceanographic studies in the Arctic is not well known. Given the unique problems for gravimetry in the region (especially data gaps) and their potential impact on MDT products, it is especially important that the relative performance of these models be assessed We consider the needs of the "end user" satellite oceanographer in the Arctic with respect to gravimetry, and the relationship between the precision of gravity data and the accuracy of a final MDT/current velocity product. Using high-precision aerogravity data collected over 3 years of campaigns by NASA's Operation IceBridge we inter-compare 10 of the leading gravity models and assess their performance in the Arctic. We also use historical data from campaigns flown by the US Naval Research Laboratory (NRL) to demonstrate the impact of gravity errors on MDT products. We describe how gravity models for the region might be improved in the future, in an effort to maximize the level at which Arctic currents may be resolved.

Geographic and socioeconomic factors in patients with malignant pleural mesothelioma in New South Wales and their impact upon clinical outcomes.

PubMed

Linton, Anthony; Soeberg, Matthew; Broome, Richard; Kao, Steven; van Zandwijk, Nico

2017-07-01

Whilst the impact of clinicopathological factors on the prognosis of malignant pleural mesothelioma (MPM) is well understood, socioeconomic and geographic factors have received less attention. We analysed the relationship between geographic and socioeconomic factors upon survival and treatment provision in a large series of patients with MPM. We assessed MPM patients awarded compensation between 2002 and 2009 with additional MPM incidence data from the New South Wales (NSW) Cancer Registry. The impact of geographic remoteness, distance from oncological multidisciplinary team (MDT) and Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) upon survival, clinical features and treatment received was analysed. We identified 910 patients (67% residing in major cities; 92% <50 km from MDT). Median overall survival was 10.0 months. On multivariate analysis, age >70 (hazard ratio (HR) = 1.39), male gender (HR =1.36), non-epithelioid histological subtype (HR = 2.18) and IRSAD status by decreasing quintile (HR = 1.06) were independent prognostic factors. There was no significant advantage for patients residing in major cities (10.6 months vs 8.8 months; P = 0.162) or within 50 km of MDT (10.3 months vs 7.8 months; P = 0.539). Patient's geographic location and distance to MDT did not impact chemotherapy, adjuvant radiotherapy or extrapleural pneumonectomy provision. Socioeconomically disadvantaged patients were significantly less likely to receive chemotherapy (37.4% vs 54.8%; P = 0.001). This study provides evidence for differences in the treatment and survival according to socioeconomic status for compensated MPM patients in NSW. Further research is warranted to seek additional explanations for the differences noted by comparing the treatments and outcomes of compensated and non-compensated MPM patients in NSW. © 2017 Asian Pacific Society of Respirology.

Determination of Mean Dynamic Topography (MDT) to Bridge Geoid and Mean Sea Surface Height (SSH) with a New Elliptic Equation

NASA Astrophysics Data System (ADS)

Chu, P. C.

2016-12-01

Mean dynamic topography (MDT, η) bridges the geoid and the mean sea surface (from satellite altimetry) and constrains large scale surface geostrophic circulations. It can be estimated from either satellite or underwater ocean temperature (T) and salinity (S) data. Satellite altimeter measures sea surface height (SSH) with high precision and unique resolution above a reference ellipsoid (not geoid). Two Gravity Recovery and Climate Experiment (GRACE) satellites launched in 2002, provide data to compute the marine geoid [called the GRACE Gravity Model (GGM)] (see website: http://www.csr.utexas.edu/grace/). The MDT is the difference of altimetry-derived mean SSH and the mean marine geoid (using GGM or pre-GRACE gravity model such as EGM96). A major difficulty arises that the spatial variations in mean SSH and marine geoid are approximately two orders of magnitude larger than the spatial variations in η.The second approach (using T, Sdata) is based on geostrophic balance, which is at the minimum energy state in the linear Boussinesq primitive equations with conservation of potential vorticity. In this paper, a new elliptic equation, -[∂x(gh/f2)∂xη+∂y(gh/f2)∂yη]+η = (g/f2)(∂C/∂x-∂B/∂y)is derived to determine MDT with H the water depth, g the gravitational acceleration, and coefficients (B, C) depend on 3D mean temperature (T) and salinity (S) data. Numerical approach transforms the elliptic equation into a set of well-posed linear algebraic equations of η at grid points. The solution for the North Atlantic Ocean (100oW-6oW, 7oN-72oN) on 1oX1ogrids with the coefficients (B, C) calculated from the three-dimensional (T, S) data of the NOAA National Centers for Environmental Information (NCEI) World Ocean Atlas 2013 version 2 (http://www.nodc.noaa.gov/OC5/woa13/woa13data.html) and H from the NOAA ETOPO5 (https://www.ngdc.noaa.gov/mgg/fliers/93mgg01.html), compares well with the difference (also considered as the MDT) between the time-averaged SSH and the geoid from the NASA/JPL (http://gracetellus.jpl.nasa.gov/data/dot/). Further application of this elliptic equation method on the high-precision altimetry measurements of SSH such as the Surface Water and Ocean Topography (SWOT) is also presented.

PUREX/UO{sub 3} deactivation project management plan

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

Washenfelder, D.J.

1993-12-01

From 1955 through 1990, the Plutonium-Uranium Extraction Plant (PUREX) provided the United States Department of Energy Hanford Site with nuclear fuel reprocessing capability. It operated in sequence with the Uranium Trioxide (UO{sub 3}) Plant, which converted the PUREX liquid uranium nitrate product to solid UO{sub 3} powder. Final UO{sub 3} Plant operation ended in 1993. In December 1992, planning was initiated for the deactivation of PUREX and UO{sub 3} Plant. The objective of deactivation planning was to identify the activities needed to establish a passively safe, environmentally secure configuration at both plants, and ensure that the configuration could be retainedmore » during the post-deactivation period. The PUREX/UO{sub 3} Deactivation Project management plan represents completion of the planning efforts. It presents the deactivation approach to be used for the two plants, and the supporting technical, cost, and schedule baselines. Deactivation activities concentrate on removal, reduction, and stabilization of the radioactive and chemical materials remaining at the plants, and the shutdown of the utilities and effluents. When deactivation is completed, the two plants will be left unoccupied and locked, pending eventual decontamination and decommissioning. Deactivation is expected to cost $233.8 million, require 5 years to complete, and yield $36 million in annual surveillance and maintenance cost savings.« less

Analysis and evaluation of the moral distress theory.

PubMed

Wilson, Melissa A

2018-04-01

Moral distress is a pervasive problem in nursing resulting in a detriment to patient care, providers, and organizations. Over a decade ago, the moral distress theory (MDT) was proposed and utilized in multiple research studies. This middle range theory explains and predicts the distress that occurs in a nurse because of moral conflict. The research findings born from this theory have been substantial. Since inception of this theory, moral distress has been extensively examined which has further elaborated its understanding. This paper provides an analysis and evaluation of the MDT according to applicable guidelines. Current understanding of the phenomenon indicates that a new theory may be warranted to better predict, treat, and manage moral distress. © 2017 Wiley Periodicals, Inc.

Comparison of Methodologies of Activation Barrier Measurements for Reactions with Deactivation

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

Xie, Zhenhua; Yan, Binhang; Zhang, Li

In this work, methodologies of activation barrier measurements for reactions with deactivation were theoretically analyzed. Reforming of ethane with CO 2 was introduced as an example for reactions with deactivation to experimentally evaluate these methodologies. Both the theoretical and experimental results showed that due to catalyst deactivation, the conventional method would inevitably lead to a much lower activation barrier, compared to the intrinsic value, even though heat and mass transport limitations were excluded. In this work, an optimal method was identified in order to provide a reliable and efficient activation barrier measurement for reactions with deactivation.

Comparison of Methodologies of Activation Barrier Measurements for Reactions with Deactivation

DOE PAGES

Xie, Zhenhua; Yan, Binhang; Zhang, Li; ...

2017-01-25

In this work, methodologies of activation barrier measurements for reactions with deactivation were theoretically analyzed. Reforming of ethane with CO 2 was introduced as an example for reactions with deactivation to experimentally evaluate these methodologies. Both the theoretical and experimental results showed that due to catalyst deactivation, the conventional method would inevitably lead to a much lower activation barrier, compared to the intrinsic value, even though heat and mass transport limitations were excluded. In this work, an optimal method was identified in order to provide a reliable and efficient activation barrier measurement for reactions with deactivation.

Intra-dialytic exercise training: a pragmatic approach.

PubMed

Greenwood, Sharlene A; Naish, Patrick; Clark, Rachel; O'Connor, Ellen; Pursey, Victoria A; Macdougall, Iain C; Mercer, Thomas H; Koufaki, Pelagia

2014-09-01

This continuing education paper outlines the skills and knowledge required to plan, implement and evaluate a pragmatic approach to intra-dialytic exercise training. The aim of this continuing education article is to enable the nephrology multi-disciplinary team (MDT) to plan, implement and evaluate the provision of intra-dialytic exercise training for patients receiving haemodialysis therapy. After reading this article the reader should be able to: Appreciate the level of evidence base for the clinical effectiveness of renal exercise rehabilitation and locate credible sources of research and educational information Understand and consider the need for appropriate evaluation and assessment outcomes as part of a renal rehabilitation plan Understand the components of exercise programming and prescription as part of an integrated renal rehabilitation plan Develop a sustainable longer term exercise and physical activity plan. © 2014 The Authors Journal of Renal Care published by John Wiley & Sons Ltd on behalf of European Dialysis & Transplant Nurses Association/European Renal Care Association.

Electroconvulsive therapy for depression in a patient with an Inspire hypoglossal nerve stimulator device for obstructive sleep apnea: A case report.

PubMed

Mingo, Katie; Kominsky, Alan

2018-04-19

METHODS: This is a case report of a patient who underwent placement and initiation of a hypoglossal nerve stimulator device in the context of receiving electroconvulsive therapy for bipolar depression between February and September 2016. To our knowledge, this has not yet been reported in the literature. Outcome measurements included successful device activation and successful device use throughout electroconvulsive therapy. The patient underwent successful device implantation, activation, and use without disruption throughout electroconvulsive therapy sessions. No special device deactivation was required during electroconvulsive therapy sessions. Obstructive sleep apnea is a common disorder that causes significant reduction in quality of life and is an independent risk factor for multiple comorbidities. Electroconvulsive therapy is an established treatment for medication-refractory depression with minimal risk in most patient populations. This is the first report in the literature of a patient undergoing ECT for bipolar depression with recent activation of Inspire hypoglossal nerve stimulator who had no disruption in the function of his implanted device. Copyright © 2018. Published by Elsevier Inc.

Random mandatory drugs testing of prisoners: a biassed means of gathering information.

PubMed

Gore, S M; Bird, A G; Strang, J S

1999-01-01

Our objective was to develop and test a methodology for inferring the percentage of prisoners currently using opiates from the percentage of prisoners testing positive for opiates in random mandatory drugs testing (rMDT). The study used results from Willing Anonymous Salivary HIV (WASH) studies (1994-6) in six adult Scottish prisons, and surveys (1994-5 and 1997) in 14 prisons in England and Wales. For Scottish prisons, the percentage of prisoners currently using opiates was determined by assuming, with varying empirical support, that: current users of opiates in prison were 1.5 times as many as current inside-injectors; and current inside-injectors were 0.75 times as many as ever injectors in prison. We also assumed that current inside-users' frequency of use of opiates (by any route) was equal to the frequency of inside-injecting by current inside-injectors in Aberdeen and Lowmoss Prisons in 1996, namely six times in 4 weeks. We assumed that some scheduling of heroin-use prior to weekends takes place, so that only 50% of current inside-users of opiates would test positive for opiates in rMDT: these assumptions allow us to arrive at WASH-based expectations for the total percentage of prisoners testing positive for opiates in rMDT. For England and Wales, a multiplier of 118/68 was applied which was derived from prisoners' interviews, to convert the results from ever inside-injectors, as determined by WASH studies, to the percentage of current inside users of opiates. We made the same assumptions on frequency of inside-use of opiates as in dealing with the Scottish results. We expected 202.7 opiate positive results in April to September 1997 in rMDTs at six adult prisons in Scotland, 226 were observed. We expected 227.0 at a set of 13 adult prisons and one other in England and Wales; 211 were observed. Further testing of the methodology for prisons in England and Wales will be possible when 1997 WASH data are released. So far, the methodology has performed well. From it, we infer that 24% of inmates at the six adult prisons in Scotland were current inside-users of opiates, compared to 11% at the 14 adult prisons where survey data were available in England and Wales. The corresponding April to September 1997 percentage of opiate positives in rMDT were: 13% (results from the six Scottish prisons) and 5.4% (results from 14 prisons in England and Wales), a two-fold under-estimate of % current users of opiates in prison (24% and 11%). Planning of drug rehabilitation places for prisoners should thus be based on twice the percentage of prisoners testing opiate positive in rMDT. This correction factor of two should be kept under review.

Automated Activation and Deactivation of a System Under Test

NASA Technical Reports Server (NTRS)

Poff, Mark A.

2006-01-01

The MPLM Automated Activation/Deactivation application (MPLM means Multi-Purpose Logistic Module) was created with a three-fold purpose in mind: 1. To reduce the possibility of human error in issuing commands to, or interpreting telemetry from, the MPLM power, computer, and environmental control systems; 2. To reduce the amount of test time required for the repetitive activation/deactivation processes; and 3. To reduce the number of on-console personnel required for activation/ deactivation. All of these have been demonstrated with the release of the software. While some degree of automated end-item commanding had previously been performed for space-station hardware in the test environment, none approached the functionality and flexibility of this application. For MPLM activation, it provides mouse-click selection of the hardware complement to be activated, activates the desired hardware and verifies proper feedbacks, and alerts the user when telemetry indicates an error condition or manual intervention is required. For MPLM deactivation, the product senses which end items are active and deactivates them in the proper sequence. For historical purposes, an on-line log is maintained of commands issued and telemetry points monitored. The benefits of the MPLM Automated Activation/ Deactivation application were demonstrated with its first use in December 2002, when it flawlessly performed MPLM activation in 8 minutes (versus as much as 2.4 hours for previous manual activations), and performed MPLM deactivation in 3 minutes (versus 66 minutes for previous manual deactivations). The number of test team members required has dropped from eight to four, and in actuality the software can be operated by a sole (knowledgeable) system engineer.

Serum resistance to singlet oxygen in patients with diabetes mellitus in comparison to healthy donors.

PubMed

Lhommeau, Isabelle; Douillard, Samuel; Bigot, Edith; Benoit, Isabelle; Krempf, Michel; Patrice, Thierry

2011-09-01

Diabetes mellitus causes endothelial injury through oxidative stress involving reactive oxygen species and peroxides as well as inflammation, both of which consume antioxidant defenses. Singlet oxygen ((1)O(2)) is produced by leukocytes during inflammatory and biochemical reactions and deactivated by producing reactive oxygen species and peroxides. To determine whether serum was capable of deactivating (1)O(2), we triggered a photo reaction in sera from 53 healthy donors and 52 diabetic patients. Immediately after light delivery, dichlorofluorescein was added and then its fluorescence was recorded. The mean capacity of (1)O(2) or secondary oxidant deactivation was reduced in patients with diabetes mellitus. Hemolysis reduced deactivation of (1)O(2)-induced secondary oxidants in both healthy and diabetic patients. Body mass index, age, platelet counts, and blood cell numbers exerted a nonlinear influence. High levels of glycated hemoglobin were associated with an increased deactivation of oxidative species, whereas high-density lipoprotein cholesterol, total cholesterol, and the total cholesterol to high-density lipoprotein cholesterol ratio decreased the serum deactivation capacity. Oral antidiabetics bore no influence on deactivation, which was restored by insulin in women. Deactivation capacity was lower in women, who had half the complications found in men, suggesting that, with more severe diabetes mellitus, protection was maintained against complications. Resistance to (1)O(2) should be considered during the monitoring of diabetes mellitus. Copyright © 2011 Elsevier Inc. All rights reserved.

Highway project cost estimating and management.

DOT National Transportation Integrated Search

2009-02-01

"This report provides detailed information about the project objectives, deliverables, and findings. The project team : thoroughly reviewed the Montana Department of Transportation (MDT) structure, operations, and current procedures as : related to M...

Research peer exchange.

DOT National Transportation Integrated Search

2005-10-01

The Montana Department of Transportation hosted a research management peer exchange October 3-7, 2005. The : objectives of the peer exchange were to: identify strengths, challenges, and opportunities for the information services : component of MDT...

Elder Abuse FAQS

MedlinePlus

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Deactivation of cellulases by phenols

USDA-ARS?s Scientific Manuscript database

Pretreatment of lignocellulosic materials may result in the release of inhibitors and deactivators of cellulose enzyme hydrolysis. We report the identification of phenols with major inhibition and/or deactivation effect on enzymes used for conversion of cellulose to ethanol. The inhibition effects w...

Therapy-induced brain reorganization patterns in aphasia.

PubMed

Abel, Stefanie; Weiller, Cornelius; Huber, Walter; Willmes, Klaus; Specht, Karsten

2015-04-01

Both hemispheres are engaged in recovery from word production deficits in aphasia. Lexical therapy has been shown to induce brain reorganization even in patients with chronic aphasia. However, the interplay of factors influencing reorganization patterns still remains unresolved. We were especially interested in the relation between lesion site, therapy-induced recovery, and beneficial reorganization patterns. Thus, we applied intensive lexical therapy, which was evaluated with functional magnetic resonance imaging, to 14 chronic patients with aphasic word retrieval deficits. In a group study, we aimed to illuminate brain reorganization of the naming network in comparison with healthy controls. Moreover, we intended to analyse the data with joint independent component analysis to relate lesion sites to therapy-induced brain reorganization, and to correlate resulting components with therapy gain. As a result, we found peri-lesional and contralateral activations basically overlapping with premorbid naming networks observed in healthy subjects. Reduced activation patterns for patients compared to controls before training comprised damaged left hemisphere language areas, right precentral and superior temporal gyrus, as well as left caudate and anterior cingulate cortex. There were decreasing activations of bilateral visuo-cognitive, articulatory, attention, and language areas due to therapy, with stronger decreases for patients in right middle temporal gyrus/superior temporal sulcus, bilateral precuneus as well as left anterior cingulate cortex and caudate. The joint independent component analysis revealed three components indexing lesion subtypes that were associated with patient-specific recovery patterns. Activation decreases (i) of an extended frontal lesion disconnecting language pathways occurred in left inferior frontal gyrus; (ii) of a small frontal lesion were found in bilateral inferior frontal gyrus; and (iii) of a large temporo-parietal lesion occurred in bilateral inferior frontal gyrus and contralateral superior temporal gyrus. All components revealed increases in prefrontal areas. One component was negatively correlated with therapy gain. Therapy was associated exclusively with activation decreases, which could mainly be attributed to higher processing efficiency within the naming network. In our joint independent component analysis, all three lesion patterns disclosed involved deactivation of left inferior frontal gyrus. Moreover, we found evidence for increased demands on control processes. As expected, we saw partly differential reorganization profiles depending on lesion patterns. There was no compensatory deactivation for the large left inferior frontal lesion, with its less advantageous outcome probably being related to its disconnection from crucial language processing pathways. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The interplay between biological and physical scenarios of bacterial death induced by non-thermal plasma.

PubMed

Lunov, Oleg; Zablotskii, Vitalii; Churpita, Olexander; Jäger, Ales; Polívka, Leoš; Syková, Eva; Dejneka, Alexandr; Kubinová, Šárka

2016-03-01

Direct interactions of plasma matter with living cells and tissues can dramatically affect their functionality, initiating many important effects from cancer elimination to bacteria deactivation. However, the physical mechanisms and biochemical pathways underlying the effects of non-thermal plasma on bacteria and cell fate have still not been fully explored. Here, we report on the molecular mechanisms of non-thermal plasma-induced bacteria inactivation in both Gram-positive and Gram-negative strains. We demonstrate that depending on the exposure time plasma induces either direct physical destruction of bacteria or triggers programmed cell death (PCD) that exhibits characteristic features of apoptosis. The interplay between physical disruption and PCD is on the one hand driven by physical plasma parameters, and on the other hand by biological and physical properties of bacteria. The explored possibilities of the tuneable bacteria deactivation provide a basis for the development of advanced plasma-based therapies. To a great extent, our study opens new possibilities for controlled non-thermal plasma interactions with living systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deactivation of implantable cardioverter defibrillators in terminal illness and end of life care.

PubMed

Kirkpatrick, James N; Gottlieb, Maia; Sehgal, Priya; Patel, Rutuke; Verdino, Ralph J

2012-01-01

Cardiology professional societies have recommended that patients with cardiovascular implantable electronic devices complete advance directives (ADs). However, physicians rarely discuss end of life handling of implantable cardioverter defibrillators (ICDs), and standard AD forms do not address the presence of ICDs. We conducted a telephone survey of 278 patients with an ICD from a large, academic hospital. The average period since implantation was 5.15 years. More than 1/3 (38%) had been shocked, with a mean of 4.69 shocks. More than 1/2 had executed an AD, but only 3 had included a plan for their ICD. Most subjects (86%) had never considered what to do with their ICD if they had a serious illness and were unlikely to survive. When asked about ICD deactivation in an end of life situation, 42% said it would depend, 28% favored deactivation, and 11% would not deactivate. One quarter (26%) thought ICD deactivation was a form of assisted suicide, 22% thought a do not resuscitate order did not mean that the ICD should be deactivated, and 46% responded that the ICD should not be automatically deactivated in hospice. The answers did not correlate with any demographic factors. Almost all (95%) agreed that patients should have the opportunity to execute an AD that directs handing of an ICD. When asked who should be responsible for discussing this device for an AD, 31% said electrophysiologists, 45% said general cardiologists, and 14% said primary care physicians. In conclusion, the results of the present study highlight the lack of consensus among patients with an ICD on the issue of deactivation at the end of a patient's life. These findings suggest cardiologists should discuss end of life care and device deactivation with their patients with an ICD. Copyright © 2012 Elsevier Inc. All rights reserved.

Montana Highway Reconfiguration Study

DOT National Transportation Integrated Search

2005-02-01

"The 2001 Montana State legislature and Governors Office directed the Department (MDT) to conduct a study : examining the economic impact of reconfiguring the States major two-lane highways. To achieve this overall goal, : the Governor created ...

Structure of the Deactive State of Mammalian Respiratory Complex I.

PubMed

Blaza, James N; Vinothkumar, Kutti R; Hirst, Judy

2018-02-06

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, active complex I gradually enters a pronounced resting or deactive state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly active preparation of Bos taurus complex I into the biochemically defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state and offers new insights into its physiological and cellular roles. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Focal Dystonia in Hemiplegic Upper Limb: Favorable Effect of Cervical Microsurgical DREZotomy Involving the Ventral Horn - A Report of 3 Patients.

PubMed

Sindou, Marc; Georgoulis, George

2016-01-01

Focal dystonia in hemiplegic upper limbs is poorly responsive to medications or classical neurosurgical treatments. Only repeated botulinum toxin injections show efficacy, but in most severe cases effects are transient. Cervical DREZ lesioning, which has proven efficacious in hyperspasticity when done deeply (3-5 mm) in the dorsal horn, may have favorable effects on the dystonic component when performed down to, and including, the base of the ventral horn (5-6 mm in depth). Three patients underwent deep cervical microsurgical DREZotomy (MDT) for focal dystonia in the upper limb. Hypertonia was reduced, and sustained dystonic postures were suppressed. Residual motor function (hidden behind hypertonia) came to the surface. Cervical MDT may be a useful armamentarium for treating refractory focal dystonia in the upper limb. © 2016 S. Karger AG, Basel.

Successful management of a complicated clinical crisis: A patient with left-sided endocarditis and secondary hemophagocytic lymphohistiocytosis: a rare case report and literature review.

PubMed

Xu, Peipei; Zeng, Hui; Zhou, Min; Ouyang, Jian; Chen, Bing; Zhang, Qiguo

2017-12-01

Hemophagocytic lymphohistiocytosis (HLH) secondary to methicillin-resistant Staphylococcus epidermidis (MRSE)-related left-sided infectious endocarditis had never been reported before. In the last decade, daptomycin, a novel lipopeptide antibiotic, showed its excellent role in anti-Gram-positive bacteria, including soft tissue infection, bloodstream and deep tissueinfection. An Asian women under sever condition due to the cooccurrence of HLH and MRSE-related endocarditis while also be allergic to vancomycin. The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. IE was made on March 27according to the modified Duke criteria. HLH was diagnosed too. The patient was cured by high-dose daptomycin monotheraphy, HLH-2004 protocol and cardiothoracic surgery to remove the valve at last, and was obviously benefit from the endeavor of a multidisciplinary team (MDT) strategy. The patient was healthy andstable when we published this case. This case proves high-dose daptomycin monotheraphy could be used as an effective alternative regimen for vancomycin in treating MRSE-related left-sided endocarditis and highlight the importance of early diagnosis and appropriate management for HLH. Furthermore, our work suggests an MDT model as a practical strategy in managing similar clinical situation. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Comparison of elastic properties of nickel-titanium orthodontic archwires.

PubMed

Sarul, Michał; Kowala, Beata; Antoszewska, Joanna

2013-01-01

Cognizance of the mechanical properties of nickel-titanium archwires is necessary for the management of orthodontic therapy with fixed appliances. Acting on the periodontium with forces that are too heavy may lead to such complications as: pain, tooth root resorption and destruction of the alveolar bone and may also lead to retardation in tooth movement. The aim of the study was to assess the activation and deactivation forces of nickel-titanium archwires: Titanol Superelastic, Copper NiTi 35oC and NeoSentalloy. The examined material was 90 samples of Titanol Superelastic, Copper NiTi 35oC and NeoSentalloy with diameters of 0.016 and 0.016 x 0.022. All tests were carried out on the Zwick mechanical tests machine at a temperature of 30o C. In the group of archwires with diameters 0.016, the levels of deactivation forces were, respectively, from highest to lowest: Titanol Supertelastic, NeoSentalloy, Copper NiTi 35oC. In the group of rectangular archwires 0.016 x 0.022, the highest deactivation forces were released in Titanol Superelastic. With the high levels of deflection, 0.016 x 0.022 NeoSentalloy archwires released statistically significantly higher levels of force than 0.016 x 0.022 Copper NiTi 35o C, but this force diminished rapidly with lower deflection and below 3 mm of deflection, the highest forces were released by Copper NiTi 35o C. Testing the mechanical properties of the nickel-titanium wires of various diameters, it was found that round section wires release forces which fall within the range of optimal forces.

49 CFR 195.59 - Abandonment or deactivation of facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Abandonment or deactivation of facilities. 195.59... Abandonment or deactivation of facilities. For each abandoned offshore pipeline facility or each abandoned onshore pipeline facility that crosses over, under or through a commercially navigable waterway, the last...

Plasma flux-dependent lipid A deactivation

NASA Astrophysics Data System (ADS)

Chang, Hung-Wen; Hsu, Cheng-Che; Ahmed, Musahid; Liu, Suet Yi; Fang, Yigang; Seog, Joonil; Oehrlein, Gottlieb S.; Graves, David B.

2014-06-01

This paper reports the influence of gas plasma flux on endotoxin lipid A film deactivation. To study the effect of the flux magnitude of reactive species, a modified low-pressure inductively coupled plasma (ICP) with O radical flux ˜1016 cm-2 s-1 was used. After ICP exposures, it was observed that while the Fourier transform infrared absorbance of fatty chains responsible for the toxicity drops by 80% through the film, no obvious film endotoxin deactivation is seen. This is in contrast to that previously observed under low flux exposure conducted in a vacuum beam system: near-surface only loss of fatty chains led to significant film deactivation. Secondary ion mass spectrometry characterization of changes at the film surface did not appear to correlate with the degree of deactivation. Lipid A films need to be nearly completely removed in order to detect significant deactivation under high flux conditions. Additional high reactive species flux experiments were conducted using an atmospheric pressure helium plasma jet and a UV/ozone device. Exposure of lipid A films to reactive species with these devices showed similar deactivation behaviour. The causes for the difference between low and high flux exposures may be due to the nature of near-surface structural modifications as a function of the rate of film removal.

Evaluating Montana's ITEEM : successes and lessons for Eco-logical

DOT National Transportation Integrated Search

2011-01-01

Up until the late 1990s, the Montana Department of Transportation (MDT) performed environmental mitigation for transportation projects on an individual-project basis. Similar experiences at State Departments of Transportation (DOTs) nationwide have s...

Highway construction on-the-job training program review.

DOT National Transportation Integrated Search

2007-05-01

"This study provides information about the experiences of trainees, contractors, Montana Department of : Transportation (MDT) field staff, and other state DOT staff in their states On-the-Job Training (OJT) Program. : Obtaining this information is...

Rockfall Hazard Process Assessment : [Project Summary

DOT National Transportation Integrated Search

2017-10-01

The Montana Department of Transportation (MDT) implemented its Rockfall Hazard Rating System (RHRS) between 2003 and 2005, obtaining information on the state's rock slopes and their associated hazards. The RHRS data facilitated decision-making in an ...

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

Tomasi, D.; Fowler, J.; Tomasi, D.

Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task. For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [{sup 11}C]cocaine used as DAT radiotracer)more » and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus. These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.« less

Selective inhibition of deactivated mitochondrial complex I by biguanides.

PubMed

Matsuzaki, Satoshi; Humphries, Kenneth M

2015-03-24

Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate-limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates but is rapidly and fully reversed to the active state in the presence of NADH. The objective of this study was to determine the relative sensitivity of active/de-active complex I to biguanide-mediated inhibition and resulting superoxide radical (O₂(•⁻)) production. Using isolated rat heart mitochondria, we show that deactivation of complex I sensitizes it to metformin and phenformin (4- and 3-fold, respectively), but not to other known complex I inhibitors, such as rotenone. Mitochondrial O₂(•⁻) production by deactivated complex I was measured fluorescently by NADH-dependent 2-hydroxyethidium formation at alkaline pH to impede reactivation. Superoxide production was 260.4% higher than in active complex I at pH 9.4. However, phenformin treatment of de-active complex I decreased O₂(•⁻) production by 14.9%, while rotenone increased production by 42.9%. Mitochondria isolated from rat hearts subjected to cardiac ischemia, a condition known to induce complex I deactivation, were sensitized to phenformin-mediated complex I inhibition. This supports the idea that the effects of biguanides are likely to be influenced by the complex I state in vivo. These results demonstrate that the complex I active and de-active states are a determinant in biguanide-mediated inhibition.

Long-term Survival and Virulence of Mycobacterium leprae in Amoebal Cysts

PubMed Central

Wheat, William H.; Casali, Amy L.; Thomas, Vincent; Spencer, John S.; Lahiri, Ramanuj; Williams, Diana L.; McDonnell, Gerald E.; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J.; Jackson, Mary

2014-01-01

Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs due to MDT. PMID:25521850

Long-term survival and virulence of Mycobacterium leprae in amoebal cysts.

PubMed

Wheat, William H; Casali, Amy L; Thomas, Vincent; Spencer, John S; Lahiri, Ramanuj; Williams, Diana L; McDonnell, Gerald E; Gonzalez-Juarrero, Mercedes; Brennan, Patrick J; Jackson, Mary

2014-12-01

Leprosy is a curable neglected disease of humans caused by Mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. Despite the global success of multi-drug therapy (MDT), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of possible non-human sources of the bacteria. In this study we show that common free-living amoebae (FLA) can phagocytose M. leprae, and allow the bacillus to remain viable for up to 8 months within amoebic cysts. Viable bacilli were extracted from separate encysted cocultures comprising three common Acanthamoeba spp.: A. lenticulata, A. castellanii, and A. polyphaga and two strains of Hartmannella vermiformis. Trophozoites of these common FLA take up M. leprae by phagocytosis. M. leprae from infected trophozoites induced to encyst for long-term storage of the bacilli emerged viable by assessment of membrane integrity. The majority (80%) of mice that were injected with bacilli extracted from 35 day cocultures of encysted/excysted A. castellanii and A. polyphaga showed lesion development that was similar to mice challenged with fresh M. leprae from passage mice albeit at a slower initial rate. Mice challenged with coculture-extracted bacilli showed evidence of acid-fast bacteria and positive PCR signal for M. leprae. These data support the conclusion that M. leprae can remain viable long-term in environmentally ubiquitous FLA and retain virulence as assessed in the nu/nu mouse model. Additionally, this work supports the idea that M. leprae might be sustained in the environment between hosts in FLA and such residence in FLA may provide a macrophage-like niche contributing to the higher-than-expected rate of leprosy transmission despite a significant decrease in human reservoirs due to MDT.

77 FR 41895 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-17

... bushing with a new bushing and deactivation pin, and installing a new or serviceable stowage bracket for... installation of a new bracket for stowing the deactivation pin. We are issuing this AD to prevent failure of... installing a new or serviceable stowage bracket for the deactivation pins on all airplanes powered by Pratt...

Attention-Induced Deactivations in Very Low Frequency EEG Oscillations: Differential Localisation According to ADHD Symptom Status

PubMed Central

Broyd, Samantha J.; Helps, Suzannah K.; Sonuga-Barke, Edmund J. S.

2011-01-01

Background The default-mode network (DMN) is characterised by coherent very low frequency (VLF) brain oscillations. The cognitive significance of this VLF profile remains unclear, partly because of the temporally constrained nature of the blood oxygen-level dependent (BOLD) signal. Previously we have identified a VLF EEG network of scalp locations that shares many features of the DMN. Here we explore the intracranial sources of VLF EEG and examine their overlap with the DMN in adults with high and low ADHD ratings. Methodology/Principal Findings DC-EEG was recorded using an equidistant 66 channel electrode montage in 25 adult participants with high- and 25 participants with low-ratings of ADHD symptoms during a rest condition and an attention demanding Eriksen task. VLF EEG power was calculated in the VLF band (0.02 to 0.2 Hz) for the rest and task condition and compared for high and low ADHD participants. sLORETA was used to identify brain sources associated with the attention-induced deactivation of VLF EEG power, and to examine these sources in relation to ADHD symptoms. There was significant deactivation of VLF EEG power between the rest and task condition for the whole sample. Using s-LORETA the sources of this deactivation were localised to medial prefrontal regions, posterior cingulate cortex/precuneus and temporal regions. However, deactivation sources were different for high and low ADHD groups: In the low ADHD group attention-induced VLF EEG deactivation was most significant in medial prefrontal regions while for the high ADHD group this deactivation was predominantly localised to the temporal lobes. Conclusions/Significance Attention-induced VLF EEG deactivations have intracranial sources that appear to overlap with those of the DMN. Furthermore, these seem to be related to ADHD symptom status, with high ADHD adults failing to significantly deactivate medial prefrontal regions while at the same time showing significant attenuation of VLF EEG power in temporal lobes. PMID:21408092

Role of N-terminal domain and accessory subunits in controlling deactivation-inactivation coupling of Kv4.2 channels.

PubMed

Barghaan, Jan; Tozakidou, Magdalini; Ehmke, Heimo; Bähring, Robert

2008-02-15

We examined the relationship between deactivation and inactivation in Kv4.2 channels. In particular, we were interested in the role of a Kv4.2 N-terminal domain and accessory subunits in controlling macroscopic gating kinetics and asked if the effects of N-terminal deletion and accessory subunit coexpression conform to a kinetic coupling of deactivation and inactivation. We expressed Kv4.2 wild-type channels and N-terminal deletion mutants in the absence and presence of Kv channel interacting proteins (KChIPs) and dipeptidyl aminopeptidase-like proteins (DPPs) in human embryonic kidney 293 cells. Kv4.2-mediated A-type currents at positive and deactivation tail currents at negative membrane potentials were recorded under whole-cell voltage-clamp and analyzed by multi-exponential fitting. The observed changes in Kv4.2 macroscopic inactivation kinetics caused by N-terminal deletion, accessory subunit coexpression, or a combination of the two maneuvers were compared with respective changes in deactivation kinetics. Extensive correlation analyses indicated that modulatory effects on deactivation closely parallel respective effects on inactivation, including both onset and recovery kinetics. Searching for the structural determinants, which control deactivation and inactivation, we found that in a Kv4.2 Delta 2-10 N-terminal deletion mutant both the initial rapid phase of macroscopic inactivation and tail current deactivation were slowed. On the other hand, the intermediate and slow phase of A-type current decay, recovery from inactivation, and tail current decay kinetics were accelerated in Kv4.2 Delta 2-10 by KChIP2 and DPPX. Thus, a Kv4.2 N-terminal domain, which may control both inactivation and deactivation, is not necessary for active modulation of current kinetics by accessory subunits. Our results further suggest distinct mechanisms for Kv4.2 gating modulation by KChIPs and DPPs.

Livability for Montana transportation.

DOT National Transportation Integrated Search

2012-03-01

The concept of livability is not new to Montana or the Montana Department of Transportation (MDT). Helping build great places in great environments has long been embedded in the departments mission, and even the state constitution. In light of the...

Speed limits set lower than engineering recommendations.

DOT National Transportation Integrated Search

2016-08-01

The purpose of this project is to provide the Montana Department of Transportation (MDT) with a better understanding of the : operational and safety impacts of setting posted speed limits below engineering recommended values. This practice has been :...

FFY 2007 annual report for the Montana Department of Transportation Research Programs

DOT National Transportation Integrated Search

2008-01-01

The Montana Department of Transportation (MDT) conducts research to discover, develop, or extend knowledge needed to operate, maintain, and improve the statewide multimodal transportation system. Specific goals include: evaluation and advancement of ...

Rockfall Hazard Process Assessment : Implementation Report

DOT National Transportation Integrated Search

2017-10-01

The Montana Department of Transportation (MDT) commissioned a new research program to improve assessment and management of its rock slope assets. The Department implemented a Rockfall Hazard Rating System (RHRS) program in 2005 and wished to add valu...

Mean Dynamic Topography of the Arctic Ocean

NASA Technical Reports Server (NTRS)

Farrell, Sinead Louise; Mcadoo, David C.; Laxon, Seymour W.; Zwally, H. Jay; Yi, Donghui; Ridout, Andy; Giles, Katherine

2012-01-01

ICESat and Envisat altimetry data provide measurements of the instantaneous sea surface height (SSH) across the Arctic Ocean, using lead and open water elevation within the sea ice pack. First, these data were used to derive two independent mean sea surface (MSS) models by stacking and averaging along-track SSH profiles gathered between 2003 and 2009. The ICESat and Envisat MSS data were combined to construct the high-resolution ICEn MSS. Second, we estimate the 5.5-year mean dynamic topography (MDT) of the Arctic Ocean by differencing the ICEn MSS with the new GOCO02S geoid model, derived from GRACE and GOCE gravity. Using these satellite-only data we map the major features of Arctic Ocean dynamical height that are consistent with in situ observations, including the topographical highs and lows of the Beaufort and Greenland Gyres, respectively. Smaller-scale MDT structures remain largely unresolved due to uncertainties in the geoid at short wavelengths.

Lustre Distributed Name Space (DNE) Evaluation at the Oak Ridge Leadership Computing Facility (OLCF)

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

Simmons, James S.; Leverman, Dustin B.; Hanley, Jesse A.

This document describes the Lustre Distributed Name Space (DNE) evaluation carried at the Oak Ridge Leadership Computing Facility (OLCF) between 2014 and 2015. DNE is a development project funded by the OpenSFS, to improve Lustre metadata performance and scalability. The development effort has been split into two parts, the first part (DNE P1) providing support for remote directories over remote Lustre Metadata Server (MDS) nodes and Metadata Target (MDT) devices, while the second phase (DNE P2) addressed split directories over multiple remote MDS nodes and MDT devices. The OLCF have been actively evaluating the performance, reliability, and the functionality ofmore » both DNE phases. For these tests, internal OLCF testbed were used. Results are promising and OLCF is planning on a full DNE deployment by mid-2016 timeframe on production systems.« less

The Black Hills-Rapid City flood of June 9-10, 1972: A description of the storm and flood

USGS Publications Warehouse

Schwarz, Francis K.; Hughes, L.A.; Hansen, E.M.; Petersen, M.S.; Kelly, Donovan B.

1975-01-01

Almost all the flood peaks occurred between 2230 MDT on June 9 and 0100 MDT on June 10, 1972, in a flood belt about 40 miles long and 20 miles wide along the eastern slopes of the Black Hills. This belt extended from Sturgis, S. Dak., on the north to Hermosa, S. Dak., on the south, with Rapid City near the center. To document the flood, peak discharge determinations were made at 49 sites. Records show that about 13,000 acre-feet of water flowed through Rapid City during the 2 days of flooding. At one point during the night of June 9, the floodwaters rose about 3.5 feet in 15 minutes. Coming off the slopes of the Black Hills, the flood peak traveled the 22 miles between Deer Creek and Rapid City in about 3.5 hours.

Immuno-Oncology-The Translational Runway for Gene Therapy: Gene Therapeutics to Address Multiple Immune Targets.

PubMed

Weß, Ludger; Schnieders, Frank

2017-12-01

Cancer therapy is once again experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing only single targets or pathways. Even the combination of several neo-antigens in cancer vaccines is not sufficient for successful, lasting tumor eradication. The focus has therefore shifted to the immune system's role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells. Immune processes, however, require novel concepts beyond the traditional "single-target-single drug" paradigm and need parallel targeting of diverse cells and mechanisms. This review gives a perspective on the role of gene therapy technologies in the evolving immuno-oncology space and identifies gene therapy as a major driver in the development and regulation of effective cancer immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the most prominent technology enabling effective immuno-oncology strategies.

Attention, Emotion, and Deactivation of Default Activity in Inferior Medial Prefrontal Cortex

ERIC Educational Resources Information Center

Geday, Jacob; Gjedde, Albert

2009-01-01

Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water…

Rank-dependent deactivation in network evolution.

PubMed

Xu, Xin-Jian; Zhou, Ming-Chen

2009-12-01

A rank-dependent deactivation mechanism is introduced to network evolution. The growth dynamics of the network is based on a finite memory of individuals, which is implemented by deactivating one site at each time step. The model shows striking features of a wide range of real-world networks: power-law degree distribution, high clustering coefficient, and disassortative degree correlation.

Numbness in clinical and experimental pain--a cross-sectional study exploring the mechanisms of reduced tactile function.

PubMed

Geber, Christian; Magerl, Walter; Fondel, Ricarda; Fechir, Marcel; Rolke, Roman; Vogt, Thomas; Treede, Rolf-Detlef; Birklein, Frank

2008-09-30

Pain patients often report distinct numbness of the painful skin although no structural peripheral or central nerve lesion is obvious. In this cross-sectional study we assessed the reduction of tactile function and studied underlying mechanisms in patients with chronic pain and in healthy participants exposed to phasic and tonic experimental nociceptive stimulation. Mechanical detection (MDT) and pain thresholds (MPT) were assessed in the painful area and the non-painful contralateral side in 10 patients with unilateral musculoskeletal pain. Additionally, 10 healthy participants were exposed to nociceptive stimulation applied to the volar forearms (capsaicin; electrical stimulation, twice each). Areas of tactile hypaesthesia and mechanical hyperalgesia were assessed. MDT and MPT were quantified adjacent to the stimulation site. Tactile hypaesthesia in pain patients and in experimental pain (MDT-z-scores: -0.66+/-0.30 and -0.42+/-0.15, respectively, both p<0.01) was paralleled by mechanical hyperalgesia (MPT-z-scores: +0.51+/-0.27, p<0.05; and +0.48+/-0.10, p<0.001). However, hypaesthesia and hyperalgesia were not correlated. Although 9 patients reported numbness, only 3 of them were able to delineate circumscript areas of tactile hypaesthesia. In experimental pain, the area of tactile hypaesthesia could be mapped in 31/40 experiments (78%). Irrespective of the mode of nociceptive stimulation (phasic vs. tonic) tactile hypaesthesia and hyperalgesia developed with a similar time course and disappeared within approximately 1 day. Hypaesthesia (numbness) often encountered in clinical pain can be reproduced by experimental nociceptive stimulation. The time course of effects suggests a mechanism involving central plasticity.

Physical and functional outcomes following multidisciplinary residential rehabilitation for prearthritic hip pain among young active UK military personnel

PubMed Central

Coppack, Russell J; Bilzon, James L; Wills, Andrew K; McCurdie, Ian M; Partridge, Laura K; Nicol, Alastair M; Bennett, Alexander N

2016-01-01

Background There are no studies describing the clinical outcomes of a residential, multidisciplinary team (MDT) rehabilitation intervention for patients with prearthritic hip pain. The aim of this cohort study was to describe the functional and physical outcomes of multidisciplinary residential rehabilitation for UK military personnel with prearthritic hip pain. Methods Participants (N=40) with a mean age of 33 years referred to a specialist residential rehabilitation centre completed a comprehensive multidisciplinary residential intervention. The main outcome measures were mean pain, physical function (modified shuttle test (MST) and Y-balance test), hip range of motion (HROM) and a patient-reported outcome measure (The Copenhagen Hip and Groin Outcome Score, HAGOS). All scores for symptomatic hips were taken at baseline and post-treatment. Results There were improvements in the Y-balance test and HROM following rehabilitation. There were significant improvements in mean difference (T1-to-T2) for Y-balance scores (15.8 cm, 95% CI 10.7 to 20.9, p<0.001), HROM (6.5° increase in hip flexion, 95% CI 4.6 to 9.4, p<0.001) and hip internal rotation (4.6°, 95% CI 2.7 to 6.6, p<0.001). Scores for HAGOS, pain, MST and functional activity assessment showed no improvement. Conclusions Among UK military personnel with prearthritic hip pain, MDT residential rehabilitation resulted in improvements in a functional Y-balance test, hip flexion and internal rotation. The study suggests short-term benefits across some outcomes for the current UK military approach to MDT residential rehabilitation. PMID:27900174

Physical and functional outcomes following multidisciplinary residential rehabilitation for prearthritic hip pain among young active UK military personnel.

PubMed

Coppack, Russell J; Bilzon, James L; Wills, Andrew K; McCurdie, Ian M; Partridge, Laura K; Nicol, Alastair M; Bennett, Alexander N

2016-01-01

There are no studies describing the clinical outcomes of a residential, multidisciplinary team (MDT) rehabilitation intervention for patients with prearthritic hip pain. The aim of this cohort study was to describe the functional and physical outcomes of multidisciplinary residential rehabilitation for UK military personnel with prearthritic hip pain. Participants (N=40) with a mean age of 33 years referred to a specialist residential rehabilitation centre completed a comprehensive multidisciplinary residential intervention. The main outcome measures were mean pain, physical function (modified shuttle test (MST) and Y-balance test), hip range of motion (HROM) and a patient-reported outcome measure (The Copenhagen Hip and Groin Outcome Score, HAGOS). All scores for symptomatic hips were taken at baseline and post-treatment. There were improvements in the Y-balance test and HROM following rehabilitation. There were significant improvements in mean difference (T1-to-T2) for Y-balance scores (15.8 cm, 95% CI 10.7 to 20.9, p<0.001), HROM (6.5° increase in hip flexion, 95% CI 4.6 to 9.4, p<0.001) and hip internal rotation (4.6°, 95% CI 2.7 to 6.6, p<0.001). Scores for HAGOS, pain, MST and functional activity assessment showed no improvement. Among UK military personnel with prearthritic hip pain, MDT residential rehabilitation resulted in improvements in a functional Y-balance test, hip flexion and internal rotation. The study suggests short-term benefits across some outcomes for the current UK military approach to MDT residential rehabilitation.

Patients' perception of implantable cardioverter defibrillator deactivation at the end of life.

PubMed

Hill, Loreena; McIlfatrick, Sonja; Taylor, Brian; Dixon, Lana; Harbinson, Mark; Fitzsimons, Donna

2015-04-01

Individualised care at the end of life requires professional understanding of the patient's perception of implantable cardioverter defibrillator deactivation. The aim was to evaluate the evidence on patients' perception of implantable cardioverter defibrillator deactivation at end of life. Systematic narrative review of empirical studies was published during 2008-2014. Data were collected from six databases, citations from relevant articles and expert recommendations. In all, 18 studies included with collective population of n = 5810. Concept mapping highlighted three themes: (1) Diverse preferences regarding discussion and deactivation. Deactivation was rarely discussed pre-implantation, with some studies demonstrating patients' reluctance to discuss implantable cardioverter defibrillator deactivation at any stage. Two studies found the majority of patients valued such discussions. Diversity was reflected in patients' willingness to deactivate, ranging from 12% (n = 9) in Irish cohort to 79% (n = 195) in Dutch study. (2) Ethical and legal considerations were predominant in Canadian and American literature as patients wanted to contribute but felt the decision should be a doctor's responsibility. Advance directives were uncommon in Europe, and where they existed the implantable cardioverter defibrillator was not mentioned. (3) 'Living in the now' was evident as despite deteriorating symptoms many patients maintained a positive outlook and anticipated surviving more than 10 years. Several studies asserted living longer was more important than quality of life. Patients regard the implantable cardioverter defibrillator as a complex and solely beneficial device, with little insight regarding its potential impact on a peaceful death. This review confirms the need for professionals to discuss with patients and families implantable cardioverter defibrillator functionality and deactivation at appropriate opportunities. © The Author(s) 2014.

Ridership impacts of South Florida's EASY smart card.

DOT National Transportation Integrated Search

2013-07-01

Smart card-based Automated Fare Collection Systems (AFCS) are being increasingly deployed in transit systems across the US. Miami-Dade Transit (MDT) has recently deployed such a system branded as the EASY Card. The South Florida Regional Transportati...

Testing and evaluation of recovered traction sanding material.

DOT National Transportation Integrated Search

2013-04-01

The Montana Department of Transportation (MDT) is searching for a solution to the accumulation of traction sand that is applied to Montana highways every winter. An analysis of reuse and recycle options for salvaged traction sand was conducted using ...

Rockfall Hazard Process Assessment : Final Project Report

DOT National Transportation Integrated Search

2017-10-01

After a decade of using the Rockfall Hazard Rating System (RHRS), the Montana Department of Transportation (MDT) sought a reassessment of their rockfall hazard evaluation process. Their prior system was a slightly modified version of the RHRS and was...

Traveler safety policy paper : TranPlan 21, amended in 2007

DOT National Transportation Integrated Search

2007-01-01

This policy paper describes the current initiatives and potential policy goals and actions that the Montana Department of Transportation (MDT) could implement to improve public safety on the State's public roadways. these goals and actions were adopt...

Evaluation of the Lewis and Clark travel and tourism information kiosk

DOT National Transportation Integrated Search

2003-12-08

Interactive touch screen kiosks can be a useful access point for people seeking tourism information. The Montana Department of Transportation (MDT) has successfully installed a network of traveler information kiosks under the Greater Yellowstone Regi...

Ridership impacts of South Florida's EASY smart card : [summary].

DOT National Transportation Integrated Search

2013-07-01

Transit agencies across the U.S. increasingly are replacing electronic fare reading systems with Advanced Fare Collection (AFC) or smart card systems. In 2009, Miami-Dade Transit (MDT) was the first Florida transit agency to deploy AFC, branded...

A comparison of multidisciplinary team residential rehabilitation with conventional outpatient care for the treatment of non-arthritic intra-articular hip pain in UK Military personnel - a protocol for a randomised controlled trial.

PubMed

Coppack, Russell J; Bilzon, James L; Wills, Andrew K; McCurdie, Ian M; Partridge, Laura; Nicol, Alastair M; Bennett, Alexander N

2016-11-08

Non-arthritic hip disorders are defined as abnormalities of the articulating surfaces of the acetabulum and femur before the onset of osteoarthritis, including intra-articular structures such as the acetabular labrum and chondral surfaces. Abnormal femoroacetabular morphology is commonly seen in young men who constitute much of the UK military population. Residential multidisciplinary team (MDT) rehabilitation for patients with musculoskeletal injuries has a long tradition in the UK military, however, there are no studies presenting empirical data on the efficacy of a residential MDT approach compared with individualised conventional outpatient treatment. With no available data, the sustainability of this care pathway has been questioned. The purpose of this randomised controlled trial is to compare the effects of a residential multidisciplinary intervention, to usual outpatient care, on the clinical outcomes of young active adults undergoing treatment for non-arthritic intra-articular hip pain. The trial will be conducted at the Defence Medical Rehabilitation Centre, Headley Court, UK. One hundred military male participants with clinical indicators of non-arthritic intra-articular hip pain will be randomly allocated to either: (1) 7-day residential multidisciplinary team intervention, n = 50; (2) 6-week physiotherapist-led outpatient intervention (conventional care), n = 50. Measurements will be taken at baseline, post-treatment (1-week MDT group; 6-weeks physiotherapy group), and 12-weeks. The primary outcome measures are the function in daily living sub-scale of the Copenhagen Hip and Groin Outcome Score (HAGOS), the physical function subscale of the Non-arthritic Hip Score (NAHS), and VAS pain scale. Secondary outcomes include objective measures of physical capacity and general health. An intention-to-treat analysis will be performed using linear and mixed models. This study will be the first to assess the efficacy of intensive MDT rehabilitation, versus conventional outpatient care, for the management of non-arthritic hip pain. The results from this study will add to the evidence-base and inform clinical practice for the management of intra-articular non-arthritic hip pain and femoroacetabular impingement in young active adults. ISRCTN Reference: ISRCTN 59255714 dated 11-Nov-2015.

The role of boundary spanners in delivering collaborative care: a process evaluation.

PubMed

Hunt, Carianne M; Spence, Michael; McBride, Anne

2016-07-29

On average, people with schizophrenia and psychosis die 13-30 years sooner than the general population (World Psychiatry 10 (1):52-77, 2011). Mental and physical health care is often provided by different organisations, different practitioners and in different settings which makes collaborative care difficult. Research is needed to understand and map the impact of new collaborative ways of working at the primary/secondary care interface (PloS One 7 (5); e36468). The evaluation presented in this paper was designed to explore the potential of a Community and Physical Health Co-ordinator role (CPHC) (CPHCs were previously Care Co-ordinators within the Community Mental Health Team, Community in the title CPHC refers to Community Mental Health) and Multi-Disciplinary Team (MDT) meetings across primary and community care, with the aim of improving collaboration of mental and physical health care for service users with Severe Mental Illness (SMI). Data collection took place across five general practices (GPs) and a Community Mental Health Team (CMHT) in the Northwest of England, as part of a process evaluation. Semi-structured interviews were conducted with a purposive sample of GP staff (n= 18) and CMHT staff (n=4), a focus group with CMHT staff (n=8) and a survey completed by 13 CMHT staff, alongside cardiovascular risk data and MDT actions. Framework analysis was used to manage and interpret data. The results from the evaluation demonstrate that a CPHC role and MDT meetings are effective mechanisms for improving the collaboration and co-ordination of physical health care for SMI service users. The findings highlight the importance of embedding and supporting the CPHC role, with an emphasis on protected time and continuing professional roles and integrating multiple perspectives through MDT meetings. Considering the importance of physical health care for SMI service users and the complex environment, these are important findings for practitioners, researchers and policy makers in the field of primary care and mental health. There is an increasing focus on integration and collaborative working to ensure the delivery of quality care across the whole patient pathway, with a growing need for professionals to work together across service and professional boundaries. The introduction of a two pronged approach to collaboration has shown some important improvements in the management of physical health care for service users with SMI.

Common and unique responses to dopamine agonist therapy and deep brain stimulation in Parkinson's disease: an H(2)(15)O PET study.

PubMed

Bradberry, Trent J; Metman, Leonard Verhagen; Contreras-Vidal, José L; van den Munckhof, Pepijn; Hosey, Lara A; Thompson, Jennifer L W; Schulz, Geralyn M; Lenz, Fredrick; Pahwa, Rajesh; Lyons, Kelly E; Braun, Allen R

2012-10-01

Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements. The purpose of this study was to identify common and unique brain network features of these standard treatments. We analyzed images produced by H(2)(15)O positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on. Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions. Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model. Published by Elsevier Inc.

Activated Carbon-Based System for the Disposal of Psychoactive Medications

PubMed Central

Song, Yang; Manian, Mahima; Fowler, William; Korey, Andrew; Kumar Banga, Ajay

2016-01-01

The misuse and improper disposal of psychoactive medications is a major safety and environmental concern. Hence, the proper disposal of these medications is critically important. A drug deactivation system which contains activated carbon offers a unique disposal method. In the present study, deactivation efficiency of this system was tested by using three model psychoactive drugs. HPLC validation was performed for each drug to ensure that the analytical method employed was suitable for its intended use. The method was found to be specific, accurate and precise for analyzing the drugs. The extent and rate of deactivation of the drugs was determined at several time points. After 28 days in the presence of activated carbon, the extent of leaching out of the drugs was evaluated. Deactivation started immediately after addition of the medications into the disposal pouches. Within 8 h, around 47%, 70% and 97% of diazepam, lorazepam and buprenorphine were adsorbed by the activated carbon, respectively. By the end of 28 days, over 99% of all drugs were deactivated. The desorption/leaching study showed that less than 1% of the active ingredients leached out from the activated carbon. Thus, this deactivation system can be successfully used for the disposal of psychoactive medications. PMID:27827989

Functional Consequences of Complementarity-determining Region Deactivation in a Multifunctional Anti-nucleic Acid Antibody*

PubMed Central

Lee, Jiyeon; Kim, Hye-Jin; Roh, Jooho; Seo, Youngsil; Kim, Minjae; Jun, Hye-Ryeong; Pham, Chuong D.; Kwon, Myung-Hee

2013-01-01

Many murine monoclonal anti-DNA antibodies (Abs) derived from mice models for systemic lupus erythematosus have additional cell-penetration and/or nucleic acid-hydrolysis properties. Here, we examined the influence of deactivating each complementarity-determining region (CDR) within a multifunctional anti-nucleic acid antibody (Ab) that possesses these activities, the catalytic 3D8 single chain variable fragment (scFv). CDR-deactivated 3D8 scFv variants were generated by replacing all of the amino acids within each CDR with Gly/Ser residues. The structure of 3D8 scFv accommodated single complete CDR deactivations. Different functional activities of 3D8 scFv were affected differently depending on which CDR was deactivated. The only exception was CDR1, located within the light chain (LCDR1); deactivation of LCDR1 abolished all of the functional activities of 3D8 scFv. A hybrid Ab, HW6/3D8L1, in which the LCDR1 from an unrelated Ab (HW6) was replaced with the LCDR1 from 3D8, acquired all activities associated with the 3D8 scFv. These results suggest that the activity of a multifunctional 3D8 scFv Ab can be modulated by single complete CDR deactivation and that the LCDR1 plays a crucial role in maintaining Ab properties. This study presents a new approach for determining the role of individual CDRs in multifunctional Abs with important implications for the future of Ab engineering. PMID:24155236

Characterization of Deactivated Bio-oil Hydrotreating Catalysts

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

Wang, Huamin; Wang, Yong

Deactivation of bio-oil hydrotreating catalysts remains a significant challenge because of the poor quality of pyrolysis bio-oil input for hydrotreating and understanding their deactivation mode is critical to developing improved catalysts and processes. In this research, we developed an understanding of the deactivation of two-step bio-oil hydrotreating catalysts (sulfided Ru/C and sulfided CoMo/C) through detailed characterization of the catalysts using various complimentary analytical techniques. Severe fouling of both catalysts by carbonaceous species was the major form of deactivation, which is consistent with the significant loss of surface area and pore volume of both deactivated catalysts and the significant increase ofmore » the bulk density. Further analysis of the carbonaceous species by thermogravimetric analysis and x-ray photoelectron spectroscopy indicated that the carbonaceous species was formed by condensation reaction of active species such as sugars and sugar derivatives (aldehydes and ketones) in bio-oil feedstock during bio-oil hydrotreating under the conditions and catalysts used. Microscopy results did not show metal sintering of the Ru/C catalyst. However, X-ray diffraction indicated a probable transformation of the highly-active CoMoS phase in the sulfided CoMo/C catalyst to Co8S9 and MoS2 phase with low activity. Loss of the active site by transport of inorganic elements from the bio-oil and the reactor construction material onto the catalyst surface also might be a cause of deactivation as indicated by elemental analysis of spent catalysts.« less

Understanding the mechanism of DNA deactivation in ion therapy of cancer cells: hydrogen peroxide action*

NASA Astrophysics Data System (ADS)

Piatnytskyi, Dmytro V.; Zdorevskyi, Oleksiy O.; Perepelytsya, Sergiy M.; Volkov, Sergey N.

2015-11-01

Changes in the medium of biological cells under ion beam irradiation has been considered as a possible cause of cell function disruption in the living body. The interaction of hydrogen peroxide, a long-lived molecular product of water radiolysis, with active sites of DNA macromolecule was studied, and the formation of stable DNA-peroxide complexes was considered. The phosphate groups of the macromolecule backbone were picked out among the atomic groups of DNA double helix as a probable target for interaction with hydrogen peroxide molecules. Complexes consisting of combinations including: the DNA phosphate group, H2O2 and H2O molecules, and Na+ counterion, were considered. The counterions have been taken into consideration insofar as under the natural conditions they neutralise DNA sugar-phosphate backbone. The energy of the complexes have been determined by considering the electrostatic and the Van der Waals interactions within the framework of atom-atom potential functions. As a result, the stability of various configurations of molecular complexes was estimated. It was shown that DNA phosphate groups and counterions can form stable complexes with hydrogen peroxide molecules, which are as stable as the complexes with water molecules. It has been demonstrated that the formation of stable complexes of H2O2-Na+-PO4- may be detected experimentally by observing specific vibrations in the low-frequency Raman spectra. The interaction of H2O2 molecule with phosphate group of the double helix backbone can disrupt DNA biological function and induce the deactivation of the cell genetic apparatus. Thus, the production of hydrogen peroxide molecules in the nucleus of living cells can be considered as an additional mechanism by which high-energy ion beams destroy tumour cells during ion beam therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey Solov'yov, Nigel Mason, Gustavo García, Eugene Surdutovich.

Steep cut slope composting : field trials and evaluation : project summary report.

DOT National Transportation Integrated Search

2011-04-01

This project is a continuation of earlier work performed by Montana State University (Jennings et al. 2007) evaluating compost application on, and incorporation into, soils on steep cut slopes for the Montana Department of Transportation (MDT). The e...

Montana Highway Safety Improvement Program : an RSPCB Peer Excahnge

DOT National Transportation Integrated Search

2011-05-01

This report provides a summary of a peer-to-peer (P2P) videoconference sponsored by the Montana Department of Transportation (MDT) and the Federal Highway Administration (FHWA) Office of Safety. The videoconference format provided a low-cost opportun...

Montana rest area usage : data acquisition and usage estimation.

DOT National Transportation Integrated Search

2011-02-01

The Montana Department of Transportation (MDT) has initiated research to refine the figures employed in the : estimation of Montana rest area use. This work seeks to obtain Montana-specific data related to rest area usage, : including water flow, eff...

Evaluation of the Montana Department of Transportation's research project solicitation, prioritization, and selection process

DOT National Transportation Integrated Search

2008-05-01

The Montana Department of Transportation (MDT) contracted the Bureau of Business and Economic Research at the University of Montana Missoula to conduct research to determine how other states solicit, prioritize, and select research problem statem...

Determining the current rates of motor fuel tax evasion for the State of Montana.

DOT National Transportation Integrated Search

2006-11-01

"The report uses data collected through interviews with neighboring states and provincial tax administrators as well as : audit, enforcement and collections data provided by the Montana Department of Transportation (MDT) to determine : the extent and...

Strategic Enterprise Architecture Design and Implementation Plan for the Montana Department of Transportation

DOT National Transportation Integrated Search

2016-08-01

The purpose of this research report is to develop a Strategic Enterprise Architecture (EA) Design and Implementation Plan for the Montana Department of Transportation (MDT). Information management systems are vital to maintaining the States transp...

Speed limits set lower than engineering recommendations : project summary report.

DOT National Transportation Integrated Search

2016-08-01

The Montana Department of Transportation (MDT) generally ensures that posted speed limits are set in accordance with engineering recommendations, which means that speed limits are typically set such that they are about equal to the observed 85th-perc...

Ground penetrating radar (GPR) analysis : Phase II field evaluation.

DOT National Transportation Integrated Search

2011-10-01

"The objective of this work was to evaluate the feasibility and value of expanding the MDT's Ground : Penetrating Radar (GPR) program to pavement design and rehabilitation, and to network level : evaluation. Phase I of this project concluded that in ...

A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel.

PubMed

Tang, Cheng; Zhou, Xi; Nguyen, Phuong Tran; Zhang, Yunxiao; Hu, Zhaotun; Zhang, Changxin; Yarov-Yarovoy, Vladimir; DeCaen, Paul G; Liang, Songping; Liu, Zhonghua

2017-07-01

Voltage-gated sodium channels (Na V s) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial Na V s have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial Na V s. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic Na V s Ns V Ba (nonselective voltage-gated Bacillus alcalophilus ) and NaChBac (bacterial sodium channel from Bacillus halodurans ) (IC 50 = 112 nM and 30 nM, respectively). JZTx-27 was more efficacious at weaker depolarizing voltages and significantly slowed the activation but accelerated the deactivation of Ns V Ba, whereas the local anesthetic drug lidocaine was shown to antagonize Ns V Ba without affecting channel gating. Mutation analysis confirmed that JZTx-27 bound to S3-4 linker of Ns V Ba, with F98 being the critical residue in determining toxin affinity. All electrophysiological data and in silico analysis suggested that JZTx-27 trapped VSM of Ns V Ba in one of the deactivated states. In mammalian Na V s, JZTx-27 preferably inhibited the inactivation of Na V 1.5 by targeting the fourth transmembrane domain. To our knowledge, this is the first report of peptide antagonist for prokaryotic Na V s. More important, we proposed that JZTx-27 stabilized the Ns V Ba VSM in the deactivated state and may be used as a probe to determine the structure of the deactivated VSM of Na V s.-Tang, C., Zhou, X., Nguyen, P. T., Zhang, Y., Hu, Z., Zhang, C., Yarov-Yarovoy, V., DeCaen, P. G., Liang, S., Liu, Z. A novel tarantula toxin stabilizes the deactivated voltage sensor of bacterial sodium channel. © FASEB.

Boron deactivation in heavily boron-doped Czochralski silicon during rapid thermal anneal: Atomic level understanding

NASA Astrophysics Data System (ADS)

Gao, Chao; Lu, Yunhao; Dong, Peng; Yi, Jun; Ma, Xiangyang; Yang, Deren

2014-01-01

The changes in hole concentration of heavily boron (B)-doped Czochralski silicon subjected to high temperature rapid thermal anneal (RTA) and following conventional furnace anneal (CFA) have been investigated. It is found that decrease in hole concentration, namely, B deactivation, is observed starting from 1050 °C and increases with RTA temperature. The following CFA at 300-500 °C leads to further B deactivation, while that at 600-800 °C results in B reactivation. It is supposed that the interaction between B atoms and silicon interstitials (I) thus forming BI pairs leads to the B deactivation during the high temperature RTA, and, moreover, the formation of extended B2I complexes results in further B deactivation in the following CFA at 300-500 °C. On the contrary, the dissociation of BI pairs during the following CFA at 600-800 °C enables the B reactivation. Importantly, the first-principles calculation results can soundly account for the above-mentioned supposition.

A rational approach to the management of chronic migraine.

PubMed

Evans, Randolph W

2013-01-01

About 2% of the adult population has chronic migraine with only 20% diagnosed with this disorder. Those with medication overuse may improve with withdrawal of overuse medications. The intravenous dihydroergotamine regimen usually produces short-term benefit for those with medically refractory chronic migraine. OnabotulinumtoxinA and topiramate have shown efficacy in large placebo-controlled randomized trials. Sodium valproate, gabapentin, tizanidine, amitriptyline, fluoxetine, zonisamide, and possibly memantine may be alternative or possibly combined treatment options but with lesser levels of evidence supporting their use. Preliminary evidence suggests that nerve blocks might be beneficial. Acupuncture, biofeedback, relaxation therapy, and cognitive behavioral therapy might be of benefit. Surgical treatments including bariatric and deactivation of trigger points are of growing interest but not appropriate for most sufferers. Occipital nerve stimulation is a promising treatment with ongoing studies defining its use. © 2013 American Headache Society.

Development of high-performance concrete mixtures for durable bridge decks in Montana using locally available materials.

DOT National Transportation Integrated Search

2005-03-01

"The Montana Department of Transportation (MDT) is performing research to develop a cost-effective, indigenous highperformance : concrete (HPC) for use in bridge deck applications. The investigation was divided into two tasks: 1) : identification of ...

75 FR 56627 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

..., IYR, MDT, MGM, NLY, NVDA, NWSA, ORCL, PFE, QCOM, QQQQ, SBUX, SH, SLV, SMH, SSO, SYMC, TBT, TSM, TXN... order routing behavior that selects CBSX as the first destination. The changes will take effect on...

Top-down deactivation of interference from irrelevant spatial or verbal stimulus features.

PubMed

Frings, Christian; Wühr, Peter

2014-11-01

The selective-attention model of Houghton and Tipper (1994) assumes top-down deactivation of (conflicting) distractor representations as a mechanism of visual attention. Deactivation should produce an inverted-U-shaped activation function for distractor representations. In a recent study, Frings, Wentura, and Wühr (2012) tested this prediction in a variant of the flanker task in which a cue sometimes required participants to respond to the distractors rather than to the target. When reaction times and error rates were plotted as a function of the target-cue stimulus onset asynchrony, a quadratic trend emerged, consistent with the notion of distractor deactivation. However, in the flanker task, an alternative explanation for the quadratic trend in terms of attentional zooming is possible. The present experiments tested the deactivation account against the attentional-zooming account with the Stroop and the Simon task, in which attentional zooming should have minimal effects on distractor processing, because the target and distractor are presented at the same spatial location. Both experiments replicated the quadratic trend in the performance functions for responses to incongruent distractors, and additionally showed linear trends in the performance functions for responses to congruent distractors. These results provide additional support for the notion of top-down deactivation of distractor representations as a mechanism of visual selective attention.

Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus.

PubMed

Lomber, Stephen G; Payne, Bertram R; Hilgetag, Claus C; Rushmore, JarrettR

2002-02-01

A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent area 7 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither area 7 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits.

FROM CONCEPT TO REALITY, IN-SITU DECOMMISSIONING OF THE P AND R REACTORS AT THE SAVANNAH RIVER SITE

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

Musall, J.; Blankenship, J.; Griffin, W.

2012-01-09

SRS recently completed an approximately three year effort to decommission two SRS reactors: P-Reactor (Building 105-P) and R-Reactor (Building 105-R). Completed in December 2011, the concurrent decommissionings marked the completion of two relatively complex and difficult facility disposition projects at the SRS. Buildings 105-P and 105-R began operating as production reactors in the early 1950s with the mission of producing weapons material (e.g., tritium and plutonium-239). The 'P' Reactor and was shutdown in 1991 while the 'R' Reactor and was shutdown in 1964. In the intervening period between shutdown and deactivation & decommissioning (D&D), Buildings 105-P and 105-R saw limitedmore » use (e.g., storage of excess heavy water and depleted uranium oxide). For Building 105-P, deactivation was initiated in April 2007 and was essentially complete by June 2010. For Building 105-R, deactivation was initiated in August 2008 and was essentially complete by September 2010. For both buildings, the primary objective of deactivation was to remove/mitigate hazards associated with the remaining hazardous materials, and thus prepare the buildings for in-situ decommissioning. Deactivation removed the following hazardous materials to the extent practical: combustibles/flammables, residual heavy water, acids, friable asbestos (as needed to protect workers performing deactivation and decommissioning), miscellaneous chemicals, lead/brass components, Freon(reg sign), oils, mercury/PCB containing components, mold and some radiologically-contaminated equipment. In addition to the removal of hazardous materials, deactivation included the removal of hazardous energy, exterior metallic components (representing an immediate fall hazard), and historical artifacts along with the evaporation of water from the two Disassembly Basins. Finally, so as to facilitate occupancy during the subsequent in-situ decommissioning, deactivation implemented repairs to the buildings and provided temporary power.« less

Vaginal Construction and Treatment Providers' Experiences: A Qualitative Analysis.

PubMed

Roen, Katrina; Creighton, Sarah M; Hegarty, Peter; Liao, Lih-Mei

2018-06-01

To investigate specialist clinicians' experiences of treating vaginal agenesis. Semi-structured interviews. Twelve hospitals in Britain and Sweden. Thirty-two health professionals connected to multidisciplinary teams (MDTs) including medical specialists and psychologists. Theoretical thematic analysis of recorded verbatim data. The gynecologist and psychologist interviewees share certain observations including the importance of psychological readiness for and appropriate timing of treatment. Three overlapping themes are identified in our theoretical analysis of the MDT clinicians' talk: (1) the stigma of vaginal agenesis and the pressure to be "normal" can lead patients to minimize the time, effort, physical discomfort, and emotional cost inherent in treatment. (2) Under pressure, treatment might be presented to patients with insufficient attention to the potential psychological effect of the language used. Furthermore, the opportunity to question what is "normal" in sex is generally not taken up. It can be challenging to help the women to transcend their medicalized experiences to come to experiencing their bodies as sexual and enjoyable. (3) The reality of treatment demands, which are not always adequately processed before treatment, can lead to discontinuation and even disengagement with services. The MDT clinicians in this study emphasized the importance of psychological input in vaginal construction. However, such input should proactively question social norms about how women's genitalia should appear and function. Furthermore, rather than steering patients (back) to treatment, the entire MDT could more explicitly question social norms and help the women to do the same. By shifting the definition of success from anatomy to personal agency, the clinical focus is transformed from treatment to women. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Comparison between geodetic and oceanographic approaches to estimate mean dynamic topography for vertical datum unification: evaluation at Australian tide gauges

NASA Astrophysics Data System (ADS)

Filmer, M. S.; Hughes, C. W.; Woodworth, P. L.; Featherstone, W. E.; Bingham, R. J.

2018-04-01

The direct method of vertical datum unification requires estimates of the ocean's mean dynamic topography (MDT) at tide gauges, which can be sourced from either geodetic or oceanographic approaches. To assess the suitability of different types of MDT for this purpose, we evaluate 13 physics-based numerical ocean models and six MDTs computed from observed geodetic and/or ocean data at 32 tide gauges around the Australian coast. We focus on the viability of numerical ocean models for vertical datum unification, classifying the 13 ocean models used as either independent (do not contain assimilated geodetic data) or non-independent (do contain assimilated geodetic data). We find that the independent and non-independent ocean models deliver similar results. Maximum differences among ocean models and geodetic MDTs reach >150 mm at several Australian tide gauges and are considered anomalous at the 99% confidence level. These differences appear to be of geodetic origin, but without additional independent information, or formal error estimates for each model, some of these errors remain inseparable. Our results imply that some ocean models have standard deviations of differences with other MDTs (using geodetic and/or ocean observations) at Australian tide gauges, and with levelling between some Australian tide gauges, of ˜ ± 50 mm . This indicates that they should be considered as an alternative to geodetic MDTs for the direct unification of vertical datums. They can also be used as diagnostics for errors in geodetic MDT in coastal zones, but the inseparability problem remains, where the error cannot be discriminated between the geoid model or altimeter-derived mean sea surface.

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: an international case–cohort study

PubMed Central

Maher, Toby M.; Kolb, Martin; Poletti, Venerino; Nusser, Richard; Richeldi, Luca; Vancheri, Carlo; Wilsher, Margaret L.; Antoniou, Katerina M.; Behr, Jüergen; Bendstrup, Elisabeth; Brown, Kevin; Calandriello, Lucio; Corte, Tamera J.; Crestani, Bruno; Flaherty, Kevin; Glaspole, Ian; Grutters, Jan; Inoue, Yoshikazu; Kokosi, Maria; Kondoh, Yasuhiro; Kouranos, Vasileios; Kreuter, Michael; Johannson, Kerri; Judge, Eoin; Ley, Brett; Margaritopoulos, George; Martinez, Fernando J.; Molina-Molina, Maria; Morais, António; Nunes, Hilario; Raghu, Ganesh; Ryerson, Christopher J.; Selman, Moises; Spagnolo, Paolo; Taniguchi, Hiroyuki; Tomassetti, Sara; Valeyre, Dominique; Wijsenbeek, Marlies; Wuyts, Wim; Hansell, David; Wells, Athol

2017-01-01

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw=0.65, IQR 0.53–0.72, p<0.0001) than academic physicians (κw=0.56, IQR 0.45–0.65, p<0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κw=0.54, IQR 0.45–0.64, p<0.0001). The prognostic accuracy of academic physicians with >20 years of experience (C-index=0.72, IQR 0.0–0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70–0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72–0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts. PMID:28860269

Introduction of a new ward round approach in a cardiothoracic critical care unit.

PubMed

Shaughnessy, Liz; Jackson, Jo

2015-07-01

Francis (2013) described inconsistent ward rounds and failures to conduct ward rounds properly as contributing factors to the poor care seen at the Mid Staffordshire Foundation Trust. He suggested that the absence of a nurse at the bedside had clear consequences for communication, ward round efficiency and patient safety. He recommended that nurses should be actively involved in ward rounds and linked this to high quality patient care. To share an experience of introducing a ward round checklist, a bedside nurse verbal summary and the development of standard operating procedure for Ward Rounds in cardiothoracic critical care unit to improve patient safety and care. Semi structured interviews of six registered nurses. A questionnaire to 69 registered nurses. An electronic questionnaire sent to 23 members of the MDT. An observational audit of seven ward rounds reviewing 69 patients. 97% of nurses agreed that verbal summarizing had improved clarity and 90% felt that it had improved patient care. 87% of the MDT respondents stated that they had noticed an improvement in the attendance of the bedside nurse at the ward round review. The ward round checklist reduced omissions. Communication with patients during ward rounds was an area which needed to be improved. The introduction of a new ward round approach and audit of its practice has enabled an improvement in the quality of patient care by: Giving more opportunity for the nurse to participate and feel part of the ward round. Reduction of omissions through the use of a ward round checklist. Improved clarity among the MDT by the use of bedside nurse verbal summarizing of the plan of care. Nurses' full participation in ward rounds is essential to ensure effective communication and enhance patient safety. © 2015 British Association of Critical Care Nurses.

Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging

PubMed Central

2013-01-01

Abstract High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient’s quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist’s role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients’ life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer. PMID:23876415

Development and validation of a new screening questionnaire for dysphagia in early stages of Parkinson's disease.

PubMed

Simons, Janine A; Fietzek, Urban M; Waldmann, Annika; Warnecke, Tobias; Schuster, Tibor; Ceballos-Baumann, Andrés O

2014-09-01

Dysphagia in patients with Parkinson's disease (PD) significantly reduces quality of life and predicted lifetime. Current screening procedures are insufficiently evaluated. We aimed to develop and validate a patient-reported outcome questionnaire for early diagnosis of dysphagia in patients with PD. The two-phased project comprised the questionnaire, diagnostic scales construction (N = 105), and a validation study (N = 82). Data for the project were gathered from PD patients at a German Movement Disorder Center. For validation purposes, a clinical evaluation focusing on swallowing tests, tests of sensory reflexes, and fiberoptic endoscopic evaluation of swallowing (FEES) was performed that yielded a criteria sum score against which the results of the questionnaire were compared. Specificity and sensitivity were evaluated for the detection of noticeable dysphagia and for the risk of aspiration. The Munich Dysphagia Test - Parkinson's disease (MDT-PD) consists of 26 items that show high internal consistency (α = 0.91). For the validation study, 82 patients, aged 70.9 ± 8.7 (mean ± SD), with a median Hoehn & Yahr stage of 3, were assessed. 73% of patients had dysphagia with noticeable oropharyngeal symptoms (44%) or with penetration/aspiration (29%). The criteria sum score correlated positively with the screening result (r = 0.70, p < 0.001). The MDT-PD sum score classified not noticeable dysphagia vs. risk of aspiration (noticeable dysphagia) with a sensitivity of 90% (82%) and a specificity of 86% (71%), and yielded similar results in cross-validation, respectively. MDT-PD is a valid screening tool for early diagnosis of swallowing problems and aspiration risk, as well as initial graduation of dysphagia severity in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rectal cancer staging: focus on the prognostic significance of the findings described by high-resolution magnetic resonance imaging.

PubMed

Dieguez, Adriana

2013-07-22

High-resolution (HR) magnetic resonance imaging (MRI) has become an indispensable tool for multidisciplinary teams (MDTs) addressing rectal cancer. It provides anatomic information for surgical planning and allows patients to be stratified into different groups according to the risk of local and distant recurrence. One of the objectives of the MDT is the preoperative identification of high-risk patients who will benefit from neoadjuvant treatment. For this reason, the correct evaluation of the circumferential resection margin (CRM), the depth of tumor spread beyond the muscularis propria, extramural vascular invasion and nodal status is of the utmost importance. Low rectal tumors represent a special challenge for the MDT, because decisions seek a balance between oncologic safety, in the pursuit of free resection margins, and the patient's quality of life, in order to preserve sphincter function. At present, the exchange of information between the different specialties involved in dealing with patients with rectal cancer can rank the contribution of colleagues, auditing their work and incorporating knowledge that will lead to a better understanding of the pathology. Thus, beyond the anatomic description of the images, the radiologist's role in the MDT makes it necessary to know the prognostic value of the findings that we describe, in terms of recurrence and survival, because these findings affect decision making and, therefore, the patients' life. In this review, the usefulness of HR MRI in the initial staging of rectal cancer and in the evaluation of neoadjuvant treatment, with a focus on the prognostic value of the findings, is described as well as the contribution of HR MRI in assessing patients with suspected or confirmed recurrence of rectal cancer.

A multidisciplinary audit of clinical coding accuracy in otolaryngology: financial, managerial and clinical governance considerations under payment-by-results.

PubMed

Nouraei, S A R; O'Hanlon, S; Butler, C R; Hadovsky, A; Donald, E; Benjamin, E; Sandhu, G S

2009-02-01

To audit the accuracy of otolaryngology clinical coding and identify ways of improving it. Prospective multidisciplinary audit, using the 'national standard clinical coding audit' methodology supplemented by 'double-reading and arbitration'. Teaching-hospital otolaryngology and clinical coding departments. Otolaryngology inpatient and day-surgery cases. Concordance between initial coding performed by a coder (first cycle) and final coding by a clinician-coder multidisciplinary team (MDT; second cycle) for primary and secondary diagnoses and procedures, and Health Resource Groupings (HRG) assignment. 1250 randomly-selected cases were studied. Coding errors occurred in 24.1% of cases (301/1250). The clinician-coder MDT reassigned 48 primary diagnoses and 186 primary procedures and identified a further 209 initially-missed secondary diagnoses and procedures. In 203 cases, patient's initial HRG changed. Incorrect coding caused an average revenue loss of 174.90 pounds per patient (14.7%) of which 60% of the total income variance was due to miscoding of a eight highly-complex head and neck cancer cases. The 'HRG drift' created the appearance of disproportionate resource utilisation when treating 'simple' cases. At our institution the total cost of maintaining a clinician-coder MDT was 4.8 times lower than the income regained through the double-reading process. This large audit of otolaryngology practice identifies a large degree of error in coding on discharge. This leads to significant loss of departmental revenue, and given that the same data is used for benchmarking and for making decisions about resource allocation, it distorts the picture of clinical practice. These can be rectified through implementing a cost-effective clinician-coder double-reading multidisciplinary team as part of a data-assurance clinical governance framework which we recommend should be established in hospitals.

Radiotherapy access in Belgium: How far are we from evidence-based utilisation?

PubMed

Lievens, Y; De Schutter, H; Stellamans, K; Rosskamp, M; Van Eycken, L

2017-10-01

Underutilisation of radiotherapy has been observed worldwide. To evaluate the current situation in Belgium, optimal utilisation proportions (OUPs) adopted from the European SocieTy for Radiotherapy and Oncology - Health Economics in Radiation Oncology (ESTRO-HERO) project were compared to actual utilisation proportions (AUPs) and with radiotherapy advised during the multidisciplinary cancer team (MDT) meetings. In addition, the impact of independent variables was analysed. AUPs and advised radiotherapy were calculated overall and by cancer type for 110,810 unique cancer diagnoses in 2009-2010. Radiotherapy utilisation was derived from reimbursement data and distinguished between palliative and curative intent external beam radiotherapy (EBRT) and/or brachytherapy (BT). Sensitivity analyses regarding the influence of the follow-up period, the survival length and patient's age were performed. Advised radiotherapy was calculated based on broad treatment categories as reported at MDT meetings. The overall AUP of 37% (39% including BT) was lower than the OUP of 53%, but in line with advised radiotherapy (35%). Large variations by tumour type were observed: in some tumours (e.g. lung and prostate cancer) AUP was considerably lower than OUP, whereas in others there was reasonable concordance (e.g. breast and rectal cancer). Overall, 84% of treatments started within 9 months following diagnosis. Survival time influenced AUP in a cancer type-dependent way. Elderly patients received less radiotherapy. Although the actually delivered radiotherapy in Belgium aligns well to MDT advices, it is lower than the evidence-based optimum. Further analysis of potential barriers is needed for radiotherapy forecasting and planning, and in order to promote adequate access to radiotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.

PubMed

Grants, Jennifer M; Ying, Lisa T L; Yoda, Akinori; You, Charlotte C; Okano, Hideyuki; Sawa, Hitoshi; Taubert, Stefan

2016-02-01

Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. Copyright © 2016 by the Genetics Society of America.

Role of cellulose ether polymers on ibuprofen release from matrix tablets.

PubMed

Vueba, M L; Batista de Carvalho, L A E; Veiga, F; Sousa, J J; Pina, Maria Eugénia

2005-08-01

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

Annual and semiannual variations of the geomagnetic field at equatorial locations

USGS Publications Warehouse

Campbell, W.H.

1981-01-01

For a year of quiet solar-activity level, geomagnetic records from American hemisphere observatories located between about 0?? and 30?? north geomagnetic latitude were used to compare the annual and semiannual variations of the geomagnetic field associated with three separate contributions: (a) the quiet-day midnight level, MDT; (b) the solar-quiet daily variation, Sq; (c) the quiet-time lunar semidiurnal tidal variation, L(12). Four Fourier spectral constituents (24, 12, 8, 6 h periods) of Sq were individually treated. All three orthogonal elements (H, D and Z) were included in the study. The MDT changes show a dominant semiannual variation having a range of about 7 gammas in H and a dominant annual variation in Z having a range of over 8 gammas. These changes seem to be a seasonal response to the nightside distortions by magnetospheric currents. There is a slow decrease in MDT amplitudes with increasing latitude. The Sq changes follow the patterns expected from an equatorial ionospheric dynamo electrojet current system. The dominant seasonal variations occur in H having a range of over 21 gammas for the 24 h period and over 12 gammas for the 12 h period spectral components. The higher-order components are relatively smaller in size. The Sq(H) amplitudes decrease rapidly with increasing latitude. Magnetospheric contributions to the equatorial Sq must be less than a few per cent of the observed magnitude. The L(12) variation shows the ionospheric electrojet features by the dominance of H and the rapid decrease in amplitude with latitude away from the equator. However, the seasonal variation range of over 7 gammas has a maximum in early February and minimum in late June that is not presently explainable by the known ionospheric conductivity and tidal behavior. ?? 1981.

In situ stress and pore pressure in the Kumano Forearc Basin, offshore SW Honshu from downhole measurements during riser drilling

NASA Astrophysics Data System (ADS)

Saffer, D. M.; Flemings, P. B.; Boutt, D.; Doan, M.-L.; Ito, T.; McNeill, L.; Byrne, T.; Conin, M.; Lin, W.; Kano, Y.; Araki, E.; Eguchi, N.; Toczko, S.

2013-05-01

situ stress and pore pressure are key parameters governing rock deformation, yet direct measurements of these quantities are rare. During Integrated Ocean Drilling Program (IODP) Expedition #319, we drilled through a forearc basin at the Nankai subduction zone and into the underlying accretionary prism. We used the Modular Formation Dynamics Tester tool (MDT) for the first time in IODP to measure in situ minimum stress, pore pressure, and permeability at 11 depths between 729.9 and 1533.9 mbsf. Leak-off testing at 708.6 mbsf conducted as part of drilling operations provided a second measurement of minimum stress. The MDT campaign included nine single-probe (SP) tests to measure permeability and in situ pore pressure and two dual-packer (DP) tests to measure minimum principal stress. Permeabilities defined from the SP tests range from 6.53 × 10-17 to 4.23 × 10-14 m2. Pore fluid pressures are near hydrostatic throughout the section despite rapid sedimentation. This is consistent with the measured hydraulic diffusivity of the sediments and suggests that the forearc basin should not trap overpressures within the upper plate of the subduction zone. Minimum principal stresses are consistently lower than the vertical stress. We estimate the maximum horizontal stress from wellbore failures at the leak-off test and shallow MDT DP test depths. The results indicate a normal or strike-slip stress regime, consistent with the observation of abundant active normal faults in the seaward-most part of the basin, and a general decrease in fault activity in the vicinity of Site C0009.

Deactivating stimulation sites based on low-rate thresholds improves spectral ripple and speech reception thresholds in cochlear implant users.

PubMed

Zhou, Ning

2017-03-01

The study examined whether the benefit of deactivating stimulation sites estimated to have broad neural excitation was attributed to improved spectral resolution in cochlear implant users. The subjects' spatial neural excitation pattern was estimated by measuring low-rate detection thresholds across the array [see Zhou (2016). PLoS One 11, e0165476]. Spectral resolution, as assessed by spectral-ripple discrimination thresholds, significantly improved after deactivation of five high-threshold sites. The magnitude of improvement in spectral-ripple discrimination thresholds predicted the magnitude of improvement in speech reception thresholds after deactivation. Results suggested that a smaller number of relatively independent channels provide a better outcome than using all channels that might interact.

Deactivation of Zeolite Catalyst H-ZSM-5 during Conversion of Methanol to Gasoline: Operando Time- and Space-Resolved X-ray Diffraction.

PubMed

Rojo-Gama, Daniel; Mentel, Lukasz; Kalantzopoulos, Georgios N; Pappas, Dimitrios K; Dovgaliuk, Iurii; Olsbye, Unni; Lillerud, Karl Petter; Beato, Pablo; Lundegaard, Lars F; Wragg, David S; Svelle, Stian

2018-03-15

The deactivation of zeolite catalyst H-ZSM-5 by coking during the conversion of methanol to hydrocarbons was monitored by high-energy space- and time-resolved operando X-ray diffraction (XRD) . Space resolution was achieved by continuous scanning along the axial length of a capillary fixed bed reactor with a time resolution of 10 s per scan. Using real structural parameters obtained from XRD, we can track the development of coke at different points in the reactor and link this to a kinetic model to correlate catalyst deactivation with structural changes occurring in the material. The "burning cigar" model of catalyst bed deactivation is directly observed in real time.

Sourcing made easy.

PubMed

2005-09-01

MDT Sourcing is a free online service for buyers seeking the range of services used in the design, manufacture and marketing of finished medical devices. Take up of the service has been good since its launch earlier this year. Some of the latest requests for quotations are outlined here.

Research management peer exchange hosted by the Montana Department of Transportation, May 4-8, 1997.

DOT National Transportation Integrated Search

1997-05-01

The objectives of the peer exchange process were to: : learn how the Montana Department of Transportation manages and conducts research; : share information among members of the exchange team and customers of MDT Research : involved in the pe...

Montana Department of Transportation Research Peer Exchange : Implementation, Performance Measures, and the Value of Research

DOT National Transportation Integrated Search

2018-01-01

The Montana Department of Transportation (MDT) Research Program hosted a peer exchange in Helena, Montana, from September 12-14, 2017. The objective for the peer exchange was to explore best practices on implementation, performance measures, and the ...

78 FR 42551 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-16

....m., MDT, and it will be followed by the meeting of the Board of Directors which will commence..., 2013 1. Governance and Performance Review 8:30 a.m. Committee 2. Board of Directors \\*\\ Please note... business 10. Consider and act on adjournment of meeting [[Page 42552

The Step approach to Message Design and Testing (SatMDT): A conceptual framework to guide the development and evaluation of persuasive health messages.

PubMed

Lewis, Ioni; Watson, Barry; White, Katherine M

2016-12-01

This paper provides an important and timely overview of a conceptual framework designed to assist with the development of message content, as well as the evaluation, of persuasive health messages. While an earlier version of this framework was presented in a prior publication by the authors in 2009, important refinements to the framework have seen it evolve in recent years, warranting the need for an updated review. This paper outlines the Step approach to Message Design and Testing (or SatMDT) in accordance with the theoretical evidence which underpins, as well as empirical evidence which demonstrates the relevance and feasibility of, each of the framework's steps. The development and testing of the framework have thus far been based exclusively within the road safety advertising context; however, the view expressed herein is that the framework may have broader appeal and application to the health persuasion context. Copyright © 2015 Elsevier Ltd. All rights reserved.

Numerical simulation of magnetic nanoparticles targeting in a bifurcation vessel

NASA Astrophysics Data System (ADS)

Larimi, M. M.; Ramiar, A.; Ranjbar, A. A.

2014-08-01

Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of super paramagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. The present paper is devoted to study on MDT (Magnetic Drug Targeting) technique by particle tracking in the presence of magnetic field in a bifurcation vessel. The blood flow in bifurcation is considered incompressible, unsteady and Newtonian. The flow analysis applies the time dependent, two dimensional, incompressible Navier-Stokes equations for Newtonian fluids. The Lagrangian particle tracking is performed to estimate particle behavior under influence of imposed magnetic field gradients along the bifurcation. According to the results, the magnetic field increased the volume fraction of particle in target region, but in vessels with high Reynolds number, the efficiency of MDT technique is very low. Also the results showed that in the bifurcation vessels with lower angles, wall shear stress is higher and consequently the risk of the vessel wall rupture increases.

TELEMAM: a cluster randomised trial to assess the use of telemedicine in multi-disciplinary breast cancer decision making.

PubMed

Kunkler, I H; Prescott, R J; Lee, R J; Brebner, J A; Cairns, J A; Fielding, R G; Bowman, A; Neades, G; Walls, A D F; Chetty, U; Dixon, J M; Smith, M E; Gardner, T W; Macnab, M; Swann, S; Maclean, J R

2007-11-01

The TELEMAM trial aimed to assess the clinical effectiveness and costs of telemedicine in conducting breast cancer multi-disciplinary meetings (MDTs). Over 12 months 473 MDT patient discussions in two district general hospitals (DGHs) were cluster randomised (2:1) to the intervention of telemedicine linkage to breast specialists in a cancer centre or to the control group of 'in-person' meetings. Primary endpoints were clinical effectiveness and costs. Economic analysis was based on a cost-minimisation approach. Levels of agreement of MDT members on a scale from 1 to 5 were high and similar in both the telemedicine and standard meetings for decision sharing (4.04 versus 4.17), consensus (4.06 versus 4.20) and confidence in the decision (4.16 versus 4.07). The threshold at which the telemedicine meetings became cheaper than standard MDTs was approximately 40 meetings per year. Telemedicine delivered breast cancer multi-disciplinary meetings have similar clinical effectiveness to standard 'in-person' meetings.

Photosensitized enzyme deactivation and protein oxidation by axial-substituted phosphorus(V) tetraphenylporphyrins.

PubMed

Ouyang, Dongyan; Hirakawa, Kazutaka

2017-10-01

The activity for photodynamic therapy of water-soluble cationic porphyrins, tetraphenylporphyrin P(V) complexes, was investigated. Bis(cyclohexylmethoxy)P(V)tetraphenylporphyrin (DCHMP(V)TPP), dichloroP(V)tetraphenylporphyrin (Cl 2 P(V)TPP), and dimethoxyP(V)tetraphenylporphyrin (DMP(V)TPP) could cause the photosensitized deactivation of tyrosinase. The tryptophan residue of human serum albumin (HSA) and several kinds of amino acids could be damaged by these P(V)porphyrins under visible light irradiation. The photosensitized damage of these biomolecules was inhibited by sodium azide, a singlet oxygen ( 1 O 2 ) quencher, and enhanced in deuterium oxide, suggesting the contribution of 1 O 2 . However, an excess amount of sodium azide did not completely inhibit the photosensitized damage. In addition, the redox potential measurements demonstrated the possibility of electron transfer from tryptophan and tyrosine to photoexcited P(V)porphyrins. These results suggest that electron transfer-mediated oxidation of amino acids contributes to the photosensitized protein and amino acid damage by these P(V)porphyrins. Specifically, Cl 2 P(V)TPP showed the highest photodamaging activity in the P(V)porphyrins used in this study. Oxidized products of amino acids by photoexcited P(V)porphyrins were analyzed with a liquid chromatography-mass spectrometer. Because of the hypoxic condition of a tumor, photodynamic therapy through a 1 O 2 -mediated mechanism should be restricted, and the electron transfer-mediated mechanism may improve the photodynamic effect. In the cases of these P(V)porphyrins, redox potential is the most important factor for photosensitized protein and amino acid oxidation through photoinduced electron transfer. Copyright © 2017 Elsevier B.V. All rights reserved.

Work plan for the Isotopes Facilities Deactivation Project at Oak Ridge National Laboratory, Oak Ridge, Tennessee

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

NONE

1995-08-01

The purpose of the Isotopes Facilities Deactivation Project (IFDP) is to place former isotopes production facilities at the Oak Ridge National Laboratory in a safe, stable, and environmentally sound condition; suitable for an extended period of minimum surveillance and maintenance (S and M) and as quickly and economical as possible. Implementation and completion of the deactivation project will further reduce the risks to the environment and to public safety and health. Furthermore, completion of the project will result in significant S and M cost savings in future years. The IFDP work plan defines the project schedule, the cost estimate, andmore » the technical approach for the project. A companion document, the EFDP management plan, has been prepared to document the project objectives, define organizational relationships and responsibilities, and outline the management control systems to be employed in the management of the project. The project has adopted the strategy of deactivating the simple facilities first, to reduce the scope of the project and to gain experience before addressing more difficult facilities. A decision support system is being developed to identify the activities that best promote the project mission and result in the largest cost savings. This work plan will be reviewed and revised annually. Deactivation of EFDP Facilities was initiated in FY 1994 and will be completed in FY 2000. The schedule for deactivation of facilities is shown. The total cost of the project is estimated to be $51M. The costs are summarized. Upon completion of deactivation, annual S and M costs of these facilities will be reduced from the current level of $5M per year to less than $1M per year.« less

Mechanistic Insight into Human ether-à-go-go-related Gene (hERG) K+ Channel Deactivation Gating from the Solution Structure of the EAG Domain

PubMed Central

Muskett, Frederick W.; Thouta, Samrat; Thomson, Steven J.; Bowen, Alexander; Stansfeld, Phillip J.; Mitcheson, John S.

2011-01-01

Human ether-à-go-go-related gene (hERG) K+ channels have a critical role in cardiac repolarization. hERG channels close (deactivate) very slowly, and this is vital for regulating the time course and amplitude of repolarizing current during the cardiac action potential. Accelerated deactivation is one mechanism by which inherited mutations cause long QT syndrome and potentially lethal arrhythmias. hERG deactivation is highly dependent upon an intact EAG domain (the first 135 amino acids of the N terminus). Importantly, deletion of residues 2–26 accelerates deactivation to a similar extent as removing the entire EAG domain. These and other experiments suggest the first 26 residues (NT1–26) contain structural elements required to slow deactivation by stabilizing the open conformation of the pore. Residues 26–135 form a Per-Arnt-Sim domain, but a structure for NT1–26 has not been forthcoming, and little is known about its site of interaction on the channel. In this study, we present an NMR structure for the entire EAG domain, which reveals that NT1–26 is structurally independent from the Per-Arnt-Sim domain and contains a stable amphipathic helix with one face being positively charged. Mutagenesis and electrophysiological studies indicate that neutralizing basic residues and breaking the amphipathic helix dramatically accelerate deactivation. Furthermore, scanning mutagenesis and molecular modeling studies of the cyclic nucleotide binding domain suggest that negatively charged patches on its cytoplasmic surface form an interface with the NT1–26 domain. We propose a model in which NT1–26 obstructs gating motions of the cyclic nucleotide binding domain to allosterically stabilize the open conformation of the pore. PMID:21135103

Selective Inhibition of Deactivated Mitochondrial Complex I by Biguanides †

PubMed Central

Matsuzaki, Satoshi; Humphries, Kenneth M.

2015-01-01

Biguanides are widely used antihyperglycemic agents for diabetes mellitus and prediabetes treatment. Complex I is the rate limiting step of the mitochondrial electron transport chain (ETC), a major source of mitochondrial free radical production, and a known target of biguanides. Complex I has two reversible conformational states, active and de-active. The deactivated state is promoted in the absence of substrates, but is rapidly and fully reversed to the active state in the presence of NADH. The objective of this study was to determine the relative sensitivity of active/de-active complex I to biguanide-mediated inhibition and resulting superoxide radical (O2•−) production. Using isolated rat heart mitochondria, we show that deactivation of complex I sensitizes it to metformin and phenformin (4- and 3-fold, respectively), but not to other known complex I inhibitors, such as rotenone. Mitochondrial O2•− production by deactivated complex I was measured fluorescently by the NADH-dependent 2-hydroxyethidium formation at alkaline pH to impede reactivation. Superoxide production was 260.4% higher than in active complex I at pH 9.4. However, phenformin treatment of de-active complex I decreased O2•− production by 14.9% while rotenone increased production by 42.9%. Mitochondria isolated from rat hearts subjected to cardiac ischemia, a condition known to induce complex I deactivation, were sensitized to phenformin:mediated complex I inhibition. This supports that the effects of biguanides are likely to be influenced by the complex I state in vivo. These results demonstrate that the complex I active/de-active states are a determinant in biguanide-mediated inhibition. PMID:25719498

Spread of activation and deactivation in the brain: does age matter?

PubMed Central

Gordon, Brian A.; Tse, Chun-Yu; Gratton, Gabriele; Fabiani, Monica

2014-01-01

Cross-sectional aging functional MRI results are sometimes difficult to interpret, as standard measures of activation and deactivation may confound variations in signal amplitude and spread, which however, may be differentially affected by age-related changes in various anatomical and physiological factors. To disentangle these two types of measures, here we propose a novel method to obtain independent estimates of the peak amplitude and spread of the BOLD signal in areas activated (task-positive) and deactivated (task-negative) by a Sternberg task, in 14 younger and 28 older adults. The peak measures indicated that, compared to younger adults, older adults had increased activation of the task-positive network, but similar levels of deactivation in the task-negative network. Measures of signal spread revealed that older adults had an increased spread of activation in task-positive areas, but a starkly reduced spread of deactivation in task-negative areas. These effects were consistent across regions within each network. Further, there was greater variability in the anatomical localization of peak points in older adults, leading to reduced cross-subject overlap. These results reveal factors that may confound the interpretation of studies of aging. Additionally, spread measures may be linked to local connectivity phenomena and could be particularly useful to analyze age-related deactivation patterns, complementing the results obtained with standard peak and region of interest analyses. PMID:25360115

The N–Terminal Tail of hERG Contains an Amphipathic α–Helix That Regulates Channel Deactivation

PubMed Central

Mobli, Mehdi; Ke, Ying; Kuchel, Philip W.; King, Glenn F.; Stock, Daniela; Vandenberg, Jamie I.

2011-01-01

The cytoplasmic N–terminal domain of the human ether–a–go–go related gene (hERG) K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s) by which the N–terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N–terminal 135 residues of hERG contains a previously described Per–Arnt–Sim (PAS) domain (residues 26–135) as well as an amphipathic α–helix (residues 13–23) and an initial unstructured segment (residues 2–9). Deletion of residues 2–25, only the unstructured segment (residues 2–9) or replacement of the α–helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α–helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N–terminal α–helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel. PMID:21249148

Age and Alzheimer's pathology disrupt default mode network functioning via alterations in white matter microstructure but not hyperintensities.

PubMed

Brown, Christopher A; Jiang, Yang; Smith, Charles D; Gold, Brian T

2018-04-19

The default mode network (DMN) comprises defined brain regions contributing to internally-directed thought processes. Reductions in task-induced deactivation in the DMN have been associated with increasing age and poorer executive task performance, but factors underlying these functional changes remain unclear. We investigated contributions of white matter (WM) microstructure, WM hyperintensities (WMH) and Alzheimer's pathology to age-related alterations in DMN function. Thirty-five cognitively normal older adults and 29 younger adults underwent working memory task fMRI and diffusion tensor imaging. In the older adults, we measured cerebrospinal fluid tau and Aβ 42 (markers of AD pathology), and WMH on FLAIR imaging (marker of cerebrovascular disease). We identified a set of regions showing DMN deactivation and a set of inter-connecting WM tracts (DMN-WM) common to both age groups. There were negative associations between DMN deactivation and task performance in older adults, consistent with previous studies. Decreased DMN deactivation was associated with AD pathology and WM microstructure but not with WMH volume. Mediation analyses showed that WM microstructure mediated declines in DMN deactivation associated with both aging and AD pathology. Together these results suggest that AD pathology may exert a "second-hit" on WM microstructure, over-and-above the effects of age, both contributing to diminished DMN deactivation in older adults. Copyright © 2018 Elsevier Ltd. All rights reserved.

Boron deactivation in heavily boron-doped Czochralski silicon during rapid thermal anneal: Atomic level understanding

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

Gao, Chao; Dong, Peng; Yi, Jun

The changes in hole concentration of heavily boron (B)-doped Czochralski silicon subjected to high temperature rapid thermal anneal (RTA) and following conventional furnace anneal (CFA) have been investigated. It is found that decrease in hole concentration, namely, B deactivation, is observed starting from 1050 °C and increases with RTA temperature. The following CFA at 300–500 °C leads to further B deactivation, while that at 600–800 °C results in B reactivation. It is supposed that the interaction between B atoms and silicon interstitials (I) thus forming BI pairs leads to the B deactivation during the high temperature RTA, and, moreover, the formation of extendedmore » B{sub 2}I complexes results in further B deactivation in the following CFA at 300–500 °C. On the contrary, the dissociation of BI pairs during the following CFA at 600–800 °C enables the B reactivation. Importantly, the first-principles calculation results can soundly account for the above-mentioned supposition.« less

Asymmetry between Activation and Deactivation during a Transcriptional Pulse.

PubMed

Dunham, Lee S S; Momiji, Hiroshi; Harper, Claire V; Downton, Polly J; Hey, Kirsty; McNamara, Anne; Featherstone, Karen; Spiller, David G; Rand, David A; Finkenstädt, Bärbel; White, Michael R H; Davis, Julian R E

2017-12-27

Transcription in eukaryotic cells occurs in gene-specific bursts or pulses of activity. Recent studies identified a spectrum of transcriptionally active "on-states," interspersed with periods of inactivity, but these "off-states" and the process of transcriptional deactivation are poorly understood. To examine what occurs during deactivation, we investigate the dynamics of switching between variable rates. We measured live single-cell expression of luciferase reporters from human growth hormone or human prolactin promoters in a pituitary cell line. Subsequently, we applied a statistical variable-rate model of transcription, validated by single-molecule FISH, to estimate switching between transcriptional rates. Under the assumption that transcription can switch to any rate at any time, we found that transcriptional activation occurs predominantly as a single switch, whereas deactivation occurs with graded, stepwise decreases in transcription rate. Experimentally altering cAMP signalling with forskolin or chromatin remodelling with histone deacetylase inhibitor modifies the duration of defined transcriptional states. Our findings reveal transcriptional activation and deactivation as mechanistically independent, asymmetrical processes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Tyrosine Residues from the S4-S5 Linker of Kv11.1 Channels Are Critical for Slow Deactivation.

PubMed

Ng, Chai-Ann; Gravel, Andrée E; Perry, Matthew D; Arnold, Alexandre A; Marcotte, Isabelle; Vandenberg, Jamie I

2016-08-12

Slow deactivation of Kv11.1 channels is critical for its function in the heart. The S4-S5 linker, which joins the voltage sensor and pore domains, plays a critical role in this slow deactivation gating. Here, we use NMR spectroscopy to identify the membrane-bound surface of the S4S5 linker, and we show that two highly conserved tyrosine residues within the KCNH subfamily of channels are membrane-associated. Site-directed mutagenesis and electrophysiological analysis indicates that Tyr-542 interacts with both the pore domain and voltage sensor residues to stabilize activated conformations of the channel, whereas Tyr-545 contributes to the slow kinetics of deactivation by primarily stabilizing the transition state between the activated and closed states. Thus, the two tyrosine residues in the Kv11.1 S4S5 linker play critical but distinct roles in the slow deactivation phenotype, which is a hallmark of Kv11.1 channels. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Montachusett Area Regional Transit Authority (MART) automatic vehicle location and mobile data terminal (AVL/MDT) pilot program report

DOT National Transportation Integrated Search

2003-02-14

The Montachusett Area Regional Transit Authority (MART) MART was established in 1978 to provide public transportation to the 18 Massachusetts communities. MART fixed-route service operates with 26 buses. Its paratransit services are more extensive, a...

Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

PubMed Central

Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

2010-01-01

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

Deactivation of 6-Aminocoumarin Intramolecular Charge Transfer Excited State through Hydrogen Bonding

PubMed Central

Krystkowiak, Ewa; Dobek, Krzysztof; Maciejewski, Andrzej

2014-01-01

This paper presents results of the spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in various aprotic hydrogen-bond forming solvents. It was established that solvent polarity as well as hydrogen-bonding ability influence solute properties. The hydrogen-bonding interactions between S1-electronic excited solute and solvent molecules were found to facilitate the nonradiative deactivation processes. The energy-gap dependence on radiationless deactivation in aprotic solvents was found to be similar to that in protic solvents. PMID:25244014

Frequency-dependent actions of benzodiazepines on GABAA receptors in cultured murine cerebellar granule cells.

PubMed Central

Mellor, J R; Randall, A D

1997-01-01

1. Miniature IPSCs recorded from cultured murine cerebellar granule cells increased in half-width and amplitude following application of the benzodiazepine (BDZ) Flunitrazepam (Flu, 1 microM). The increase in the half-width was much greater than that in the amplitude. 2. Five-millisecond applications of 1 mM GABA to nucleated outside-out patches elicited rapidly rising biexponentially decaying responses that resembled IPSCs. Flu had no effect on the amplitude of such responses, but consistently slowed their deactivation by approximately 50%. This effect was reversed by Flu washout or application of the BDZ antagonist Ro15-1788. The partial inverse agonist. Ro15-4513 speeded deactivation and depressed peak current amplitude by 23 +/- 12%. 3. The EC50 for GABA was between 45 and 50 microM. At submaximally effective agonist concentrations, Flu increased response amplitude and slowed response deactivation. Both effects were present in all cells taken from young cultures (4-7 days in vitro) but the latter was absent in 55% of the neurones obtained from older cultures (14-27 days in vitro). 4. With 120 ms applications of 20 microM GABA, responses activated monoexponentially (time constant, 39.8 +/- 2.8 ms) and deactivated biexponentially (time constants, 40.4 +/- 2.1 and 251 +/- 15 ms). Application of Flu slowed both activation and deactivation. The latter effect arose from an increased contribution of the slower component of decay. 5. Desensitization of responses to 1 mM GABA was biexponential, with time constants of 47 +/- 11 and 479 +/- 49 ms. Flu speeded desensitization by decreasing both fast and slow time constants. GABAA receptor desensitization consistently slowed subsequent deactivation. No significant relationship between the level of desensitization and the amount of slowing of deactivation produced by Flu was found. 6. Responses to paired 5 ms applications of 1 mM GABA indicated that the slowing of deactivation and the speeding of desensitization produced by Flu combine to generate a marked frequency dependence in the actions of this BDZ. Thus when compared with control responses, GABA-induced charge transfer was only enhanced by Flu during the first of two successive agonist applications. PMID:9306278

Photodynamic action of LED-activated pyropheophorbide-α methyl ester in cisplatin-resistant human ovarian carcinoma cells

NASA Astrophysics Data System (ADS)

Tan, Y.; Xu, C. S.; Xia, X. S.; Yu, H. P.; Bai, D. Q.; He, Y.; Leung, A. W. N.

2009-04-01

Cisplatin-resistance is a major obstacle for the successful therapy to ovarian cancer, and exploring novel approach to deactivate cisplatin-resistant ovarian cells will improve the clinical outcomes. Our present study showed that there was no dark cytotoxicity of MPPa in the COC1/DDP cells at the dose of 0.25 - 4 μM, and LED-activated MPPa resulted in drug dose- and light-dependent cytotoxicity. Apoptotic rate 6 h after LED-activated MPPa (2 μM) increased to 16.71% under the light energy of 1 J/cm2. Confocal laser scanning microscopy showed that MPPa mainly localized in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria in the COC1/DDP cells. Mitochondrial membrane potential (ΔΨm) was collapsed when COC1/DDP cells were exposed to 2 μM MPPa for 20 h and then 1 J/cm2 irradiation of LED source. These data demonstrated that LED-activated MPPa significantly deactivated cisplatin-resistant ovarian cell line COC1/DDP cells and enhanced apoptosis and decreased ΔΨm, which suggests LED is an efficient light source for PDT and LED-activated MPPa can be developed as new modality for treating cisplatin-resistant ovarian.

Mentored Discussions of Teaching: An Introductory Teaching Development Program for Future STEM Faculty

ERIC Educational Resources Information Center

Baiduc, Rachael R.; Linsenmeier, Robert A.; Ruggeri, Nancy

2016-01-01

Today's science, technology, engineering, and mathematics (STEM) graduate students and postdoctoral fellows are tomorrow's new faculty members; but these junior academicians often receive limited pedagogical training. We describe four iterations of an entry-level program with a low time commitment, Mentored Discussions of Teaching (MDT). The…

Obesity drug therapy.

PubMed

Baretić, M

2013-09-01

Obesity is a chronic disease, and it requires chronic therapy. Hypertension, dyslipidemia, diabetes and cardiovascular diseases are leading causes of mortality in the modern world. All of them are strongly linked to obesity. While treating obesity, those conditions are also managed. Obese patients should always be treated through lifestyle interventions, though the results of such interventions are modest. Pharmacotherapy is a second step in the treatment of obesity, approved only when weight loss targets were not reached through lifestyle intervention. During the history of antiobesity drugs, many of them were withdrawn because of their side effects. Various guidelines recommend prescribing drug therapy for obesity through consideration of the potential benefits and limitations. Orlistat deactivates intestinal lipase and inhibits intestinal fat lipolysis. It is actually the only drug on the European market approved for the treatment of obesity. Orlistat therapy reduces weight to a modest extent, but it reduces the incidence of diabetes beyond the result achieved with lifestyle changes. Recently, some effective antiobesity drugs like sibutramine and rimonabant have been removed from the market due to their side effects. The new combination of topimarate and fentermine is approved in the US but not in Europe. The cost effectiveness of long-term pharmacotherapy of obesity is still an unresolved question.

Evaluating the Impact of a Canadian National Anatomy and Radiology Contouring Boot Camp for Radiation Oncology Residents

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

Jaswal, Jasbir; D'Souza, Leah; Johnson, Marjorie

Background: Radiation therapy treatment planning has advanced over the past 2 decades, with increased emphasis on 3-dimensional imaging for target and organ-at-risk (OAR) delineation. Recent studies suggest a need for improved resident instruction in this area. We developed and evaluated an intensive national educational course (“boot camp”) designed to provide dedicated instruction in site-specific anatomy, radiology, and contouring using a multidisciplinary (MDT) approach. Methods: The anatomy and radiology contouring (ARC) boot camp was modeled after prior single-institution pilot studies and a needs-assessment survey. The boot camp incorporated joint lectures from radiation oncologists, anatomists, radiologists, and surgeons, with hands-on contouring instructionmore » and small group interactive seminars using cadaveric prosections and correlative axial radiographs. Outcomes were evaluated using pretesting and posttesting, including anatomy/radiology multiple-choice questions (MCQ), timed contouring sessions (evaluated relative to a gold standard using Dice similarity metrics), and qualitative questions on satisfaction and perceived effectiveness. Analyses of pretest versus posttest scores were performed using nonparametric paired testing. Results: Twenty-nine radiation oncology residents from 10 Canadian universities participated. As part of their current training, 29%, 75%, and 21% receive anatomy, radiology, and contouring instruction, respectively. On posttest scores, the MCQ knowledge scores improved significantly (pretest mean 60% vs posttest mean 80%, P<.001). Across all contoured structures, there was a 0.20 median improvement in students' average Dice score (P<.001). For individual structures, significant Dice improvements occurred in 10 structures. Residents self-reported an improved ability to contour OARs and interpret radiographs in all anatomic sites, 92% of students found the MDT format effective for their learning, and 93% found the boot camp more effective than educational sessions at their own institutions. All of the residents (100%) would recommend this course to others. Conclusions: The ARC boot camp is an effective intervention for improving radiation oncology residents' knowledge and understanding of anatomy and radiology in addition to enhancing their confidence and accuracy in contouring.« less

The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain--a randomised controlled pilot study.

PubMed

Lauche, Romy; Cramer, Holger; Choi, Kyung-Eun; Rampp, Thomas; Saha, Felix Joyonto; Dobos, Gustav J; Musial, Frauke

2011-08-15

In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100-mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF-36). In addition, the mechanical-detection thresholds (MDT), vibration-detection thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain-related and control areas. Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001). There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006) and vitality (Δ10.2, p = 0.006). Group differences in PPT were significant at pain-related and control areas (all p < 0.05), but were not significant for MDT or VDT. A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing. The trial was registered at clinicaltrials.gov (NCT01289964).

The influence of a series of five dry cupping treatments on pain and mechanical thresholds in patients with chronic non-specific neck pain - a randomised controlled pilot study

PubMed Central

2011-01-01

Background In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. Methods Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100-mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF-36). In addition, the mechanical-detection thresholds (MDT), vibration-detection thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain-related and control areas. Results Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001). There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006) and vitality (Δ10.2, p = 0.006). Group differences in PPT were significant at pain-related and control areas (all p < 0.05), but were not significant for MDT or VDT. Conclusions A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing. Trial registration The trial was registered at clinicaltrials.gov (NCT01289964). PMID:21843336

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

PubMed

Vieira, Ana Paula; Trindade, Maria Angela Bianconcini; de Paula, Flávio Jota; Sakai-Valente, Neusa Yurico; Duarte, Alberto José da Silva; Lemos, Francine Brambate Carvalhinho; Benard, Gil

2017-04-24

Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Evaluating the impact of a Canadian national anatomy and radiology contouring boot camp for radiation oncology residents.

PubMed

Jaswal, Jasbir; D'Souza, Leah; Johnson, Marjorie; Tay, KengYeow; Fung, Kevin; Nichols, Anthony; Landis, Mark; Leung, Eric; Kassam, Zahra; Willmore, Katherine; D'Souza, David; Sexton, Tracy; Palma, David A

2015-03-15

Radiation therapy treatment planning has advanced over the past 2 decades, with increased emphasis on 3-dimensional imaging for target and organ-at-risk (OAR) delineation. Recent studies suggest a need for improved resident instruction in this area. We developed and evaluated an intensive national educational course ("boot camp") designed to provide dedicated instruction in site-specific anatomy, radiology, and contouring using a multidisciplinary (MDT) approach. The anatomy and radiology contouring (ARC) boot camp was modeled after prior single-institution pilot studies and a needs-assessment survey. The boot camp incorporated joint lectures from radiation oncologists, anatomists, radiologists, and surgeons, with hands-on contouring instruction and small group interactive seminars using cadaveric prosections and correlative axial radiographs. Outcomes were evaluated using pretesting and posttesting, including anatomy/radiology multiple-choice questions (MCQ), timed contouring sessions (evaluated relative to a gold standard using Dice similarity metrics), and qualitative questions on satisfaction and perceived effectiveness. Analyses of pretest versus posttest scores were performed using nonparametric paired testing. Twenty-nine radiation oncology residents from 10 Canadian universities participated. As part of their current training, 29%, 75%, and 21% receive anatomy, radiology, and contouring instruction, respectively. On posttest scores, the MCQ knowledge scores improved significantly (pretest mean 60% vs posttest mean 80%, P<.001). Across all contoured structures, there was a 0.20 median improvement in students' average Dice score (P<.001). For individual structures, significant Dice improvements occurred in 10 structures. Residents self-reported an improved ability to contour OARs and interpret radiographs in all anatomic sites, 92% of students found the MDT format effective for their learning, and 93% found the boot camp more effective than educational sessions at their own institutions. All of the residents (100%) would recommend this course to others. The ARC boot camp is an effective intervention for improving radiation oncology residents' knowledge and understanding of anatomy and radiology in addition to enhancing their confidence and accuracy in contouring. Copyright © 2015 Elsevier Inc. All rights reserved.

Insight into the role of the promoters Pt, Ru and B in inhibiting the deactivation of Co catalysts in Fischer-Tropsch synthesis

NASA Astrophysics Data System (ADS)

Zhang, Riguang; Liu, Hongxia; Li, Qiaohong; Wang, Baojun; Ling, Lixia; Li, Debao

2018-09-01

In order to probe into the roles of the promoters Pt, Ru and B in inhibiting the deactivation of Co catalysts in FTS reactions, the adsorption ability of neighboring surface C and subsurface C atom around the promoters (Pt, Ru and B), and the mechanisms of surface C diffusion, accumulation, hydrogenation and penetration are examined by density functional theory calculations over the promoters Pt, Ru and B-modified Co catalysts, as well as the pure Co catalysts. Our results clearly show that compared to Co catalysts, both PtCo and RuCo bimetallic catalysts promote surface C hydrogenation, and inhibit surface C diffusion, accumulation and penetration, and therefore the ability of resistance toward deactivation and the stability of Co-based catalysts are enhanced; the promoter B cannot effectively improve the ability of resistance toward deactivation. Thus, the sequence for resistance toward deactivation of Co-based catalyst is BCo < Co < PtCo < RuCo. Moreover, the activation free energy of surface C accumulation to C2 species increases with the increasing of surface C adsorption free energy, namely, the adsorption characteristic of surface C species well represent the surface carbon deposition. Our results not only give an explanation for reported experiment that the Pt, Ru and B-modified Co catalysts exhibit ability of resistance toward deactivation in FTS at a molecular level, but also provide a clue for the design of efficient Co-based catalysts in FTS reactions.

Computer animated relaxation therapy in children between 7 and 13 years with tension-type headache: a pilot study.

PubMed

Tornoe, Birte; Skov, Liselotte

2012-03-01

This pilot study evaluated the effect of computer animated relaxation therapy in children between 7 and 13 years with tension-type headache and the children's experiences with the therapy. The therapy consisted of an uncontrolled nine-session course in modified progressive relaxation therapy assisted by computer animated surface EMG provided from the trapezius muscles and with the physiotherapist as a participant observer. Outcome measures were (a) headache frequency and intensity, (b) pericranial tenderness, (c) tension patterns, and (d) evaluations assessed at baseline and at 3 months follow up. Nine children, mean age 10.9 (SD 1.7) years, diagnosed with frequent episodic or chronic tension-type headache completed the course. The results showed a mean improvement of 45% for headache frequency at 3 months follow up versus baseline and a significant reduction in headache frequency for all participants and in Total Tenderness Score for children with frequent episodic tension-type headache. The children expressed a growing understanding of body reactions and an acquired ability to deactivate and regulate these reactions. Computer animated SEMG seems an applicable learning strategy for young headache sufferers. This study suggests that children below the age of 13 need both the dialog and guidance from a participant observer in order to achieve body awareness.

Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

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

Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina

Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

Patterns of Default Mode Network Deactivation in Obsessive Compulsive Disorder

PubMed Central

Gonçalves, Óscar F.; Soares, José Miguel; Carvalho, Sandra; Leite, Jorge; Ganho-Ávila, Ana; Fernandes-Gonçalves, Ana; Pocinho, Fernando; Carracedo, Angel; Sampaio, Adriana

2017-01-01

The objective of the present study was to research the patterns of Default Mode Network (DMN) deactivation in Obsessive Compulsive Disorder (OCD) in the transition between a resting and a non-rest emotional condition. Twenty-seven participants, 15 diagnosed with OCD and 12 healthy controls (HC), underwent a functional neuroimaging paradigm in which DMN brain activation in a resting condition was contrasted with activity during a non-rest condition consisting in the presentation of emotionally pleasant and unpleasant images. Results showed that HC, when compared with OCD, had a significant deactivation in two anterior nodes of the DMN (medial frontal and superior frontal) in the non-rest pleasant stimuli condition. Additional analysis for the whole brain, contrasting the resting condition with all the non-rest conditions grouped together, showed that, compared with OCD, HC had a significantly deactivation of a widespread brain network (superior frontal, insula, middle and superior temporal, putamen, lingual, cuneus, and cerebellum). Concluding, the present study found that OCD patients had difficulties with the deactivation of DMN even when the non-rest condition includes the presentation of emotional provoking stimuli, particularly evident for images with pleasant content. PMID:28287615

Deactivation of Legionella Pneumophila in municipal wastewater by ozone generated in arrays of microchannel plasmas

NASA Astrophysics Data System (ADS)

Dong, Shengkun; Li, Jun; Kim, Min-Hwan; Cho, Jinhoon; Park, Sung-Jin; Nguyen, Thanh H.; Eden, J. Gary

2018-06-01

A greater than four log10 reduction in the concentration of Legionella pneumophila in municipal wastewater has been achieved in 1 min with ozone produced by a microchannel plasma reactor. Requiring less than 22 W of electrical power, and ambient air as the feedstock gas, the microplasma ozone generator is robust and a promising alternative to conventional corona and dielectric barrier discharge (DBD) technologies. Contrary to previous studies, the Ct model for pathogen deactivation (i.e. rate proportional to the product of the available disinfectant concentration and the exposure duration) is found to be valid for L. pneumophila. Accordingly, wastewater-specific Ct equations have been developed to predict the deactivation of L. pneumophila in the secondary wastewater environment. Inactivation of this pathogen was found to be dependent on temperature only in the absence of wastewater organic matter (WOM). In the presence of WOM, pathogen deactivation is controlled by the disinfection contact time, initial ozone concentration (varied between 15 and 281 µg l‑1), and initial WOM loading. The data reported here will assist in the implementation of plasma ozone generators for L. pneumophila deactivation in cooling towers, point-of-use systems, and wastewater reclamation facilities.

Catalytic cracking of model compounds of bio-oil over HZSM-5 and the catalyst deactivation.

PubMed

Chen, Guanyi; Zhang, Ruixue; Ma, Wenchao; Liu, Bin; Li, Xiangping; Yan, Beibei; Cheng, Zhanjun; Wang, Tiejun

2018-08-01

The catalytic cracking upgrading reactions over HZSM-5 of different model compounds of bio-oil have been studied with a self-designed fluid catalytic cracking (FCC) equipment. Typical bio-oil model compounds, such as acetic acid, guaiacol, n-heptane, acetol and ethyl acetate, were chosen to study the products distribution, reaction pathway and deactivation of catalysts. The results showed: C 6 -C 8 aromatic hydrocarbons, C 2 -C 4 olefins, C 1 -C 5 alkanes, CO and CO 2 were the main products, and the selectivity of olefins was: ethylene>propylene>butylene. Catalyst characterization methods, such as FI-IR, TG-TPO and Raman, were used to study the deactivation mechanism of catalysts. According to the catalyst characterization results, a catalyst deactivation mechanism was proposed as follows: Firstly, the precursor which consisted of a large number of long chain saturated aliphatic hydrocarbons and a small amount CC of aromatics formed on the catalyst surface. Then the active sites of catalysts had been covered, the coke type changed from thermal coke to catalytic coke and gradually blocked the channels of the molecular sieve, which accelerated the deactivation of catalyst. Copyright © 2018 Elsevier B.V. All rights reserved.

Deactivation of Multilayered MFI Nanosheet Zeolite during Upgrading of Biomass Pyrolysis Vapors

DOE PAGES

Xu, Mengze; Mukarakate, Calvin; Iisa, Kristiina; ...

2017-05-02

Here, the catalytic fast pyrolysis (CFP) of biomass is a promising technology for producing renewable transportation fuels and chemicals. MFI-type catalysts have shown promise for CFP because they produce gasoline range hydrocarbons from oxygenated pyrolysis compounds; however, rapid catalyst deactivation due to coking is one of the major technical barriers inhibiting the commercialization of this technology. Coke deposited on the surface of the catalysts blocks access to active sites in the micropores leading to rapid catalyst deactivation. Our strategy is to minimize rapid catalyst deactivation by adding mesoporosity through forming MFI nanosheet materials. The synthesized MFI nanosheet catalysts were fullymore » characterized and evaluated for cellulose pyrolysis vapor upgrading to produce olefins and aromatic hydrocarbons. The data obtained from pyrolysis-GCMS (py-GCMS), showed that fresh MFI nanosheets produced similar aromatic hydrocarbon and olefin yields compared to conventional HZSM-5. However, MFI nanosheets demonstrated a longer lifetime than HZSM-5 even though coke contents were also higher than for HZSM-5 because the mesopores enabled better accessibility to active acid sites. This conclusion was supported by results from post-reaction analysis of various spent catalysts collected at different points during the deactivation experiments.« less

Graphene quantum dot synthesis using nanosecond laser pulses and its comparison to Methylene Blue

NASA Astrophysics Data System (ADS)

Kholikov, Khomidkhodza; Thomas, Zachary; Seyitliyev, Dovletgeldi; Smith, Skylar

A biocompatible photodynamic therapy agent that generates a high amount of singlet oxygen with high water dispersibility and excellent photostability is desirable. In this work, a graphene based biomaterial which is a promising alternative to a standard photosensitizers was produced. Methylene blue was used as a reference photosensitizer. Bacteria deactivation by methylene blue was shown to be inhibited inside human blood due to protein binding. Graphene quantum dots (GQD) were synthesized by irradiating benzene and nickel oxide mixture using nanosecond laser pulses. High resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) were used for characterization of GQDs. Initial results show graphene quantum dots whose size less than 5 nm were successfully obtained. UV-VIS spectra shows absorption peak around 310 nm. The results of these studies can potentially be used to develop therapies for the eradication of pathogens in open wounds, burns, or skin cancers. New therapies for these conditions are particularly needed when antibiotic-resistant infections are present. NIH KBRIN.

CRISPR-Cas9: a new and promising player in gene therapy.

PubMed

Xiao-Jie, Lu; Hui-Ying, Xue; Zun-Ping, Ke; Jin-Lian, Chen; Li-Juan, Ji

2015-05-01

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a cost-effective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9-mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Two Small Molecules Restore Stability to a Subpopulation of the Cystic Fibrosis Transmembrane Conductance Regulator with the Predominant Disease-causing Mutation.

PubMed

Meng, Xin; Wang, Yiting; Wang, Xiaomeng; Wrennall, Joe A; Rimington, Tracy L; Li, Hongyu; Cai, Zhiwei; Ford, Robert C; Sheppard, David N

2017-03-03

Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl - channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopic CFTR Cl - currents. At 37 °C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wild-type CFTR, the full-length F508del-CFTR was about 10 °C less thermostable. Lumacaftor partially stabilized purified full-length F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl - channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl - currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl - channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Examination of safety improvement by failure record analysis that uses reliability engineering].

PubMed

Kato, Kyoichi; Sato, Hisaya; Abe, Yoshihisa; Ishimori, Yoshiyuki; Hirano, Hiroshi; Higashimura, Kyoji; Amauchi, Hiroshi; Yanakita, Takashi; Kikuchi, Kei; Nakazawa, Yasuo

2010-08-20

How the maintenance checks of the medical treatment system, including start of work check and the ending check, was effective for preventive maintenance and the safety improvement was verified. In this research, date on the failure of devices in multiple facilities was collected, and the data of the trouble repair record was analyzed by the technique of reliability engineering. An analysis of data on the system (8 general systems, 6 Angio systems, 11 CT systems, 8 MRI systems, 8 RI systems, and the radiation therapy system 9) used in eight hospitals was performed. The data collection period assumed nine months from April to December 2008. Seven items were analyzed. (1) Mean time between failures (MTBF) (2) Mean time to repair (MTTR) (3) Mean down time (MDT) (4) Number found by check in morning (5) Failure generation time according to modality. The classification of the breakdowns per device, the incidence, and the tendency could be understood by introducing reliability engineering. Analysis, evaluation, and feedback on the failure generation history are useful to keep downtime to a minimum and to ensure safety.

Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior.

PubMed

Miller, Oliver H; Bruns, Andreas; Ben Ammar, Imen; Mueggler, Thomas; Hall, Benjamin J

2017-08-22

The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT)→mPFC circuit that controls depression-like behavior. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Leprosy and human rights: trends in Japan and in the world].

PubMed

Yokota, Yozo

2014-12-01

Leprosy, or Hansen's disease, has long been regarded as an incurable and dreadful contagious disease. The patients have been forcefully hospitalized and deprived of many basic human rights. Their family members have often been discriminated against due to stigma associated with this disease. Soon after the Second World War, a specific remedy called "multi-drug therapy" (MDT) was discovered and leprosy became a relatively easily curable disease. Despite this medical development, it took time to change the policy and legislation of forceful hospitalization of leprosy patients. The stigma surrounding leprosy and consequent discrimination have continued. In Japan, it was only in 1996 that the legislation requiring forceful hospitalization of leprosy patients was repealed. The Government decided to provide remedies to the former patients who had suffered from this policy. At the United Nations, the General Assembly adopted a resolution to eradicate discrimination against persons affected by leprosy and their family members. It is hoped that discrimination associated with Hansen's disease will soon be overcome by the efforts of all concerned, particularly doctors and nurses who are specialists of this disease.

Progression of leprosy neuropathy: a case series study

PubMed Central

Vital, Robson T; Illarramendi, Ximena; Nascimento, Osvaldo; Hacker, Mariana A; Sarno, Euzenir N; Jardim, Marcia R

2012-01-01

A need still exists to determine the clinical and neurophysiological characteristics of leprosy neuropathy at distinct times of the disease by different methods that measure the various nerve fiber functions. A prospective clinical study was performed with 10 paucibacillary (PB) and 12 multibacillary (MB) patients evaluated at diagnosis and one year after cessation of multidrug therapy (MDT). Peripheral nerve function was assessed clinically and by means of the sympathetic skin response, skin vasomotor reflex, and nerve conduction study (NCS). At diagnosis, 73% of the total 22 patients had nerve function impairment (NFI). Autonomic function (χ2= 5.5, P= 0.019) and NCS (χ2= 7.765, P= 0.01) were significantly more altered in MB than PB patients. At final evaluation, NFI of the MB patients had worsened, especially among the six who had leprosy reaction. As the NFI of PB patients showed improvement, a significant difference between the two groups (χ2= 12.320, P= 0.001) was observed. A high prevalence of neuropathy was observed in newly diagnosed patients. Associating different tests with a thorough clinical neurological evaluation increases detection rates. PMID:22741099

75 FR 17987 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-08

... time on an intraday basis at its discretion if it determined that volatility warranted deactivation. Members would be notified of intraday OPP deactivation due to volatility and any subsequent intraday...

N Reactor Deactivation Program Plan. Revision 4

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

Walsh, J.L.

1993-12-01

This N Reactor Deactivation Program Plan is structured to provide the basic methodology required to place N Reactor and supporting facilities {center_dot} in a radiologically and environmentally safe condition such that they can be decommissioned at a later date. Deactivation will be in accordance with facility transfer criteria specified in Department of Energy (DOE) and Westinghouse Hanford Company (WHC) guidance. Transition activities primarily involve shutdown and isolation of operational systems and buildings, radiological/hazardous waste cleanup, N Fuel Basin stabilization and environmental stabilization of the facilities. The N Reactor Deactivation Program covers the period FY 1992 through FY 1997. The directivemore » to cease N Reactor preservation and prepare for decommissioning was issued by DOE to WHC on September 20, 1991. The work year and budget data supporting the Work Breakdown Structure in this document are found in the Activity Data Sheets (ADS) and the Environmental Restoration Program Baseline, that are prepared annually.« less

Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

DOE PAGES

Cheng, Shouyun; Wei, Lin; Zhao, Xianhui; ...

2016-12-07

The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction,more » and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.« less

Application, Deactivation, and Regeneration of Heterogeneous Catalysts in Bio-Oil Upgrading

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

Cheng, Shouyun; Wei, Lin; Zhao, Xianhui

The massive consumption of fossil fuels and associated environmental issues are leading to an increased interest in alternative resources such as biofuels. The renewable biofuels can be upgraded from bio-oils that are derived from biomass pyrolysis. Catalytic cracking and hydrodeoxygenation (HDO) are two of the most promising bio-oil upgrading processes for biofuel production. Heterogeneous catalysts are essential for upgrading bio-oil into hydrocarbon biofuel. Although advances have been achieved, the deactivation and regeneration of catalysts still remains a challenge. This review focuses on the current progress and challenges of heterogeneous catalyst application, deactivation, and regeneration. The technologies of catalysts deactivation, reduction,more » and regeneration for improving catalyst activity and stability are discussed. Some suggestions for future research including catalyst mechanism, catalyst development, process integration, and biomass modification for the production of hydrocarbon biofuels are provided.« less

Deactivation of TEM-1 β-Lactamase Investigated by Isothermal Batch and Non-Isothermal Continuous Enzyme Membrane Reactor Methods

PubMed Central

Rogers, Thomas A.

2011-01-01

The thermal deactivation of TEM-1 β-lactamase was examined using two experimental techniques: a series of isothermal batch assays and a single, continuous, non-isothermal assay in an enzyme membrane reactor (EMR). The isothermal batch-mode technique was coupled with the three-state “Equilibrium Model” of enzyme deactivation, while the results of the EMR experiment were fitted to a four-state “molten globule model”. The two methods both led to the conclusions that the thermal deactivation of TEM-1 β-lactamase does not follow the Lumry-Eyring model and that the Teq of the enzyme (the point at which active and inactive states are present in equal amounts due to thermodynamic equilibrium) is at least 10 °C from the Tm (melting temperature), contrary to the idea that the true temperature optimum of a biocatalyst is necessarily close to the melting temperature. PMID:22039393

The ethics of deactivating a pacemaker in a pacing-dependent patient: reflections on a case study.

PubMed

Malpas, Phillipa J; Cooper, Lisa

2012-11-01

The decision to deactivate a pacemaker in a pacing-dependent patient is troubling for some health professionals who may regard such interventions as hastening death and therefore ethically impermissible. This may be especially concerning in situations where a patient is unable to clearly state what their preferences may be and the decision--were it to be made--will almost certainly result in the patient's immediate death. In this discussion, we reflect on some of the ethical aspects that arise when JP, a 75-year-old woman who is pacing dependent, suffers a significant brain injury, and the family request that her pacemaker be deactivated. Taking into account the clinical reality of her situation, the united wishes and loving concern of her husband and family, and their substituted judgment regarding her likely preferences, we claim that the decision to deactivate her pacemaker was ethically sound.

Highly controlled nest homeostasis of honey bees helps deactivate phenolics in nectar

NASA Astrophysics Data System (ADS)

Liu, Fanglin; He, Jianzhong; Fu, Wenjun

2005-06-01

Honey bees have a highly developed nest homeostasis, for example, maintaining low CO2 levels and stable nest temperatures at 35°C.We investigate the role of nest homeostasis in deactivating phenolic compounds present in the nectar of Aloe littoralis. We show that the phenolic content in nectar was reduced (from 0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it was reduced still more (from 0.65% to 0.37%) if nectar was mixed with hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a nest. HGP had little effect on samples outside a nest, indicating that nest conditions are necessary for HGP to deactivate phenolics in nectar. Consequently, the highly controlled nest homeostasis of honey bees facilitates direct deactivation of phenolics in nectar, and plays a role in the action of HGP as well.

Ligand functionalization as a deactivation pathway in a fac-Ir(ppy)3-mediated radical addition.

PubMed

Devery Iii, James J; Douglas, James J; Nguyen, John D; Cole, Kevin P; Flowers Ii, Robert A; Stephenson, Corey R J

2015-01-01

Knowledge of the kinetic behavior of catalysts under synthetically relevant conditions is vital for the efficient use of compounds that mediate important transformations regardless of their composition or driving force. In particular, these data are of great importance to add perspective to the growing number of applications of photoactive transition metal complexes. Here we present kinetic, synthetic, and spectroscopic evidence of the mechanistic behavior of fac -Ir(ppy) 3 in a visible light-mediated radical addition to 3-methylindole, demonstrating the instability of fac -Ir(ppy) 3 under these conditions. During the reaction, rapid in situ functionalization of the photocatalyst occurs, eventually leading to deactivation. These findings demonstrate a conceivable deactivation process for catalytic single electron reactions in the presence of radicophilic ligands. Attempts to inhibit photocatalyst deactivation through structural modification provide further insight into catalyst selection for a given system of interest.

On the CCN (de)activation nonlinearities

NASA Astrophysics Data System (ADS)

Arabas, Sylwester; Shima, Shin-ichiro

2017-09-01

We take into consideration the evolution of particle size in a monodisperse aerosol population during activation and deactivation of cloud condensation nuclei (CCN). Our analysis reveals that the system undergoes a saddle-node bifurcation and a cusp catastrophe. The control parameters chosen for the analysis are the relative humidity and the particle concentration. An analytical estimate of the activation timescale is derived through estimation of the time spent in the saddle-node bifurcation bottleneck. Numerical integration of the system coupled with a simple air-parcel cloud model portrays two types of activation/deactivation hystereses: one associated with the kinetic limitations on droplet growth when the system is far from equilibrium, and one occurring close to equilibrium and associated with the cusp catastrophe. We discuss the presented analyses in context of the development of particle-based models of aerosol-cloud interactions in which activation and deactivation impose stringent time-resolution constraints on numerical integration.

Scoring and Classifying Examinees Using Measurement Decision Theory

ERIC Educational Resources Information Center

Rudner, Lawrence M.

2009-01-01

This paper describes and evaluates the use of measurement decision theory (MDT) to classify examinees based on their item response patterns. The model has a simple framework that starts with the conditional probabilities of examinees in each category or mastery state responding correctly to each item. The presented evaluation investigates: (1) the…

The Incidence of Training-Related Job Placement of Draper Vocational Trainees: A Preliminary Report.

ERIC Educational Resources Information Center

Gwozdecki, Joseph; And Others

A preliminary survey of trainees' pre- and postrelease interactions with the State Employment Service (ES) was conducted by the Experimental Manpower Laboratory for Corrections (EMLC) as part of an overall evaluation of Manpower Development and Training (MDT) program effectiveness at Draper Correctional Center, Elmore, Alabama. Measures of the…

NORAD & U.S. Northern Command

Science.gov Websites

NORAD and USNORTHCOM Change of Command is tomorrow at 9 a.m. MDT. Watch it o... Twitter Logo N&NC Academic Engagement Opportunities N&NC Volunteer Student Internship Program Arctic Edge 2018 Sgt - Because N&NC are joint commands the commander can be from any US military branch. @USArmy@usairforce

Role of the cell envelope stress regulators BaeR and CpxR in control of RND-type multidrug efflux pumps and transcriptional cross talk with exopolysaccharide synthesis in Erwinia amylovora.

PubMed

Pletzer, Daniel; Stahl, Antje; Oja, Anna Elisabeth; Weingart, Helge

2015-08-01

The purpose of this study was to identify the role of the cell envelope stress-sensing systems BaeSR and CpxARP in regulation of multidrug efflux and exopolysaccharide synthesis in Erwinia amylovora. We have previously reported that BaeR activates transcription of the RND-type efflux pumps AcrD and MdtABC. In this study, we found that a cpxR-deficient mutant was highly susceptible to β-lactams, aminoglycosides and lincomycin, whereas a baeR mutant showed no change in antimicrobial sensitivity. However, overexpression of BaeR in a mutant lacking the major RND pump AcrB increased resistance of E. amylovora to several compounds that are not substrates of AcrD or MdtABC. Furthermore, we observed that overexpression of BaeR significantly increased amylovoran production. Moreover, the expression of RND-type efflux pumps was changed in regulatory mutants of exopolysaccharide production. Our data suggest that BaeSR and CpxARP regulate additional mechanisms, beside efflux, which are responsible for antimicrobial resistance of E. amylovora.

The Dynamics of Agglomerated Ferrofluid in Steady and Pulsatile Flows

NASA Astrophysics Data System (ADS)

Williams, Alicia; Stewart, Kelley; Vlachos, Pavlos

2007-11-01

Magnetic Drug Targeting (MDT) is a promising technique to deliver medication via functionalized magnetic particles to target sites in the treatment of diseases. In this work, the physics of steady and pulsatile flows laden with superparamagnetic nanoparticles in a square channel under the influence of a magnetic field induced by a 0.6 Tesla permanent magnet is studied. Herein, the dynamics of ferrofluid shedding from an initially accumulated mass in water are examined through shadowgraph imaging using two orthogonal cameras. Fundamental differences in the ferrofluid behavior occur between the steady and pulsatile flow cases, as expected. For steady flows, vortex ring shedding is visualized from the mass, and periodic shedding occurs only for moderate mass sizes where the shear forces in the flow interact with the magnetic forces. At Reynolds numbers below 500 with pulsatile flow, suction and roll up of the ferrofluid is seen during the low and moderate periods of flow, followed by the ejection of ferrofluid during high flow. These shadowgraphs illustrate the beauty and richness of ferrofluid dynamics, an understanding of which is instrumental to furthering MDT as an effective drug delivery device.

Case report of a pituitary thyrotropin-secreting macroadenoma with Hashimoto thyroiditis and infertility.

PubMed

Li, Jiaqi; Li, Jianwei; Jiang, Shu; Yu, Ruichao; Yu, Yerong

2018-01-01

Thyrotropin-secreting adenoma (TSHoma) is rare, diagnosis and treatment are often delayed if the condition coexists with Hashimoto thyroiditis. The enlarged pituitary adenoma may eventually induce panhypopituitarism, infertility, or the compression of optic nerves and optic chiasma. This patient was a 36-year-old man who had been referred to the pituitary disease multidisciplinary team (MDT) of the West China Hospital, due to infertility. Examinations revealed pituitary thyrotropin-secreting macroadenoma. We conducted trans-sphenoidal surgery. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were used for reproductive reconstruction after surgery. This patient successfully fathered a child. To date, the multidisciplinary team treatment of TSHoma was rare, TSHomas are often misdiagnosed as macroadenomas, because the clinical features are varied and it often takes a long time to be diagnosed. So the purpose of this case report is to attract attention to the manifestation of increased thyroid stimulating hormone (TSH) concentration and discuss MDT treatment for TSH-secreting adenoma. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

PubMed Central

Babot, Marion; Labarbuta, Paola; Birch, Amanda; Kee, Sara; Fuszard, Matthew; Botting, Catherine H.; Wittig, Ilka; Heide, Heinrich; Galkin, Alexander

2014-01-01

An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III2 + IV (S1) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover. PMID:24560811

Oral Bacterial Deactivation Using a Low-Temperature Atmospheric Argon Plasma Brush

PubMed Central

Yang, Bo; Chen, Jierong; Yu, Qingsong; Li, Hao; Lin, Mengshi; Mustapha, Azlin; Hong, Liang; Wang, Yong

2010-01-01

Summary Objectives To study the plasma treatment effects on deactivation effectiveness of oral bacteria. Methods A low temperature atmospheric argon plasma brush were used to study the oral bacterial deactivation effects in terms of plasma conditions, plasma exposure time, and bacterial supporting media. Oral bacteria of Streptococcus mutans and Lactobacillus acidophilus with an initial bacterial population density between 1.0 × 108 and 5.0 × 108 cfu/ml were seeded on various media and their survivability with plasma exposure was examined. Scanning electron microscopy was used to examine the morphological changes of the plasma treated bacteria. Optical absorption was used to determine the leakage of intracellular proteins and DNAs of the plasma treated bacteria. Results The experimental data indicated that the argon atmospheric plasma brush was very effective in deactivating oral bacteria. The plasma exposure time for a 99.9999% cell reduction was less than 15 seconds for S. mutans and within 5 minutes for L. acidophilus. It was found that the plasma deactivation efficiency was also dependent on the bacterial supporting media. With plasma exposure, significant damages to bacterial cell structures were observed with both bacterium species. Leakage of intracellular proteins and DNAs after plasma exposure was observed through monitoring the absorbance peaks at wavelengths of 280nm and 260nm, respectively. Conclusion The experimental results from this study indicated that low temperature atmospheric plasma treatment was very effective in deactivation of oral bacteria and could be a promising technique in various dental clinical applications such as bacterial disinfection and caries early prevention, etc. PMID:20951184

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

PubMed

Celone, Kim A; Calhoun, Vince D; Dickerson, Bradford C; Atri, Alireza; Chua, Elizabeth F; Miller, Saul L; DePeau, Kristina; Rentz, Doreen M; Selkoe, Dennis J; Blacker, Deborah; Albert, Marilyn S; Sperling, Reisa A

2006-10-04

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Developing an energy efficient steam reforming process to produce hydrogen from sulfur-containing fuels

NASA Astrophysics Data System (ADS)

Simson, Amanda

Hydrogen powered fuel cells have the potential to produce electricity with higher efficiency and lower emissions than conventional combustion technology. In order to realize the benefits of a hydrogen fuel cell an efficient method to produce hydrogen is needed. Currently, over 90% of hydrogen is produced from the steam reforming of natural gas. However, for many applications including fuel cell vehicles, the use of a liquid fuel rather than natural gas is desirable. This work investigates the feasibility of producing hydrogen efficiently by steam reforming E85 (85% ethanol/15% gasoline), a commercially available sulfur-containing transportation fuel. A Rh-Pt/SiO2-ZrO2 catalyst has demonstrated good activity for the E85 steam reforming reaction. An industrial steam reforming process is often run less efficiently, with more water and at higher temperatures, in order to prevent catalyst deactivation. Therefore, it is desirable to develop a process that can operate without catalyst deactivation at more energy efficient conditions. In this study, the steam reforming of a sulfur-containing fuel (E85) was studied at near stoichiometric steam/carbon ratios and at 650C, conditions at which catalyst deactivation is normally measured. At these conditions the catalyst was found to be stable steam reforming a sulfur-free E85. However, the addition of low concentrations of sulfur significantly deactivated the catalyst. The presence of sulfur in the fuel caused catalyst deactivation by promoting ethylene which generates surface carbon species (coke) that mask catalytic sites. The amount of coke increased during time on stream and became increasingly graphitic. However, the deactivation due to both sulfur adsorption and coke formation was reversible with air treatment at 650°C. However, regenerations were found to reduce the catalyst life. Air regenerations produce exotherms on the catalyst surface that cause structural changes to the catalyst. During regenerations the accessibility of the precious metal particles is reduced which causes the catalyst to deactivate more rapidly during subsequent steam reforming cycles. Changes to the carrier morphology also occur at these conditions. Regenerating the catalyst before significant deactivation is measured can improve the stability of the catalyst. Thus a process with preemptive controlled air regenerations is proposed in order to run a steam reforming process with sulfur containing fuels.

Analysis of time taken to discuss new patients with head and neck cancer in multidisciplinary team meetings.

PubMed

Mullan, B J; Brown, J S; Lowe, D; Rogers, S N; Shaw, R J

2014-02-01

Multidisciplinary team (MDT) meetings have an important role in the management of head and neck cancer. Increasing incidence of the disease and a drive towards centralised meetings on large numbers of patients mean that effective discussions are pertinent. We aimed to evaluate new cases within a single high volume head and neck cancer MDT and to explore the relation between the time taken to discuss each case, the number of discussants, and type of case. A total of 105 patients with a new diagnosis of head and neck malignancy or complex benign tumour were discussed at 10 head and neck cancer MDT meetings. A single observer timed each discussion using a stopwatch, and recorded the number of discussants and the diagnosis and characteristics of each patient. Timings ranged from 15 to 480 s (8 min) with a mean of 119 s (2 min), and the duration of discussion correlated closely with the number of discussants (rs=0.63, p<0.001). The longest discussions concerned patients with advanced T stage (p=0.006) and advanced N stage (p=0.009) disease, the elderly (p=0.02) and male patients (p=0.05). Tumour site and histological findings were not significant factors in the duration of discussion. Most discussions on patients with early stage tumours were short (T1: 58% less than 60s, mean 90) and fewer people contributed. Many patients, particularly those with early stage disease, require little discussion, and their treatment might reasonably be planned according to an agreed protocol, which would leave more time and resources for those that require greater multidisciplinary input. Further studies may highlight extended discussions on patients with head and neck cancer, which may prompt a review of protocols and current evidence. Copyright © 2013 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members

PubMed Central

2010-01-01

Background The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. Methods The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Results Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Conclusions Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further. PMID:20587062

Patients' Non-Medical Characteristics Contribute to Collective Medical Decision-Making at Multidisciplinary Oncological Team Meetings.

PubMed

Restivo, Léa; Apostolidis, Thémis; Bouhnik, Anne-Déborah; Garciaz, Sylvain; Aurran, Thérèse; Julian-Reynier, Claire

2016-01-01

The contribution of patients' non-medical characteristics to individual physicians' decision-making has attracted considerable attention, but little information is available on this topic in the context of collective decision-making. Medical decision-making at cancer centres is currently carried out using a collective approach, at MultiDisciplinary Team (MDT) meetings. The aim of this study was to determine how patients' non-medical characteristics are presented at MDT meetings and how this information may affect the team's final medical decisions. Observations were conducted at a French Cancer Centre during MDT meetings at which non-standard cases involving some uncertainty were discussed from March to May 2014. Physicians' verbal statements and predefined contextual parameters were collected with a non-participant observational approach. Non numerical data collected in the form of open notes were then coded for quantitative analysis. Univariate and multivariate statistical analyses were performed. In the final sample of patients' records included and discussed (N = 290), non-medical characteristics were mentioned in 32.8% (n = 95) of the cases. These characteristics corresponded to demographics in 22.8% (n = 66) of the cases, psychological data in 11.7% (n = 34), and relational data in 6.2% (n = 18). The patient's age and his/her "likeability" were the most frequently mentioned characteristics. In 17.9% of the cases discussed, the final decision was deferred: this outcome was positively associated with the patients' non-medical characteristics and with uncertainty about the outcome of the therapeutic options available. The design of the study made it difficult to draw definite cause-and-effect conclusions. The Social Representations approach suggests that patients' non-medical characteristics constitute a kind of tacit professional knowledge that may be frequently mobilised in physicians' everyday professional practice. The links observed between patients' attributes and the medical decisions made at these meetings show that these attributes should be taken into account in order to understand how medical decisions are reached in difficult situations of this kind.

A pre-post test evaluation of the impact of the PELICAN MDT-TME Development Programme on the working lives of colorectal cancer team members.

PubMed

Taylor, Cath; Sippitt, Joanna M; Collins, Gary; McManus, Chris; Richardson, Alison; Dawson, Jeremy; Richards, Michael; Ramirez, Amanda J

2010-06-29

The PELICAN Multidisciplinary Team Total Mesorectal Excision (MDT-TME) Development Programme aimed to improve clinical outcomes for rectal cancer by educating colorectal cancer teams in precision surgery and related aspects of multidisciplinary care. The Programme reached almost all colorectal cancer teams across England. We took the opportunity to assess the impact of participating in this novel team-based Development Programme on the working lives of colorectal cancer team members. The impact of participating in the programme on team members' self-reported job stress, job satisfaction and team performance was assessed in a pre-post course study. 333/568 (59%) team members, from the 75 multidisciplinary teams who attended the final year of the Programme, completed questionnaires pre-course, and 6-8 weeks post-course. Across all team members, the main sources of job satisfaction related to working in multidisciplinary teams; whilst feeling overloaded was the main source of job stress. Surgeons and clinical nurse specialists reported higher levels of job satisfaction than team members who do not provide direct patient care, whilst MDT coordinators reported the lowest levels of job satisfaction and job stress. Both job stress and satisfaction decreased after participating in the Programme for all team members. There was a small improvement in team performance. Participation in the Development Programme had a mixed impact on the working lives of team members in the immediate aftermath of attending. The decrease in team members' job stress may reflect the improved knowledge and skills conferred by the Programme. The decrease in job satisfaction may be the consequence of being unable to apply these skills immediately in clinical practice because of a lack of required infrastructure and/or equipment. In addition, whilst the Programme raised awareness of the challenges of teamworking, a greater focus on tackling these issues may have improved working lives further.

Hurricane Odile

NASA Image and Video Library

2017-12-08

At about 10:45 p.m. Mountain Daylight Time (MDT) on September 14, 2014, Hurricane Odile made landfall as a Category 3 storm near Cabo San Lucas, Mexico. According to the U.S. National Hurricane Center, Odile arrived with wind speeds of 110 knots (204 kilometers or 127 miles per hour). The storm tied Olivia (1967) as the strongest hurricane to make landfall in the state of Baja California Sur in the satellite era. The Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA’s Terra satellite acquired this natural-color view of the storm at about noon MDT on September 14, when it was still southeast of the Baja California peninsula. Unisys Weather reported that the Category 4 storm had maximum sustained wind speeds of 115 knots (213 kilometers per hour) at the time. Odile had weakened to a Category 2 hurricane by 6 a.m. MDT on September 15. The storm was expected to continue weakening as it moved up the peninsula and over the area’s rough terrain, according to weather blogger Jeff Masters. Meteorologists noted that while damaging winds posed the biggest threat in the short term, inland areas of the U.S. Southwest could face heavy rainfall by September 16. The rain expected from Odile came one week after the U.S. Southwest experienced flash floods from the remnants of Hurricane Norbert. According to weather and climate blogger Eric Holthaus, those floods did little to relieve the area’s ongoing drought. NASA image by Jeff Schmaltz, LANCE/EOSDIS Rapid Response. Caption by Kathryn Hansen. Instrument(s): Terra - MODIS Read more: earthobservatory.nasa.gov/IOTD/view.php?id=84378&eocn... NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Developmental changes in autonomic responses are associated with future reward/punishment expectations: A study of sympathetic skin responses in the Markov decision task.

PubMed

Hosaka, Hiromi; Aoyagi, Kakuro; Kaga, Yoshimi; Kanemura, Hideaki; Sugita, Kanji; Aihara, Masao

2017-08-01

Autonomic nervous system activity is recognized as a major component of emotional responses. Future reward/punishment expectations depend upon the process of decision making in the frontal lobe, which is considered to play an important role in executive function. The aim of this study was to investigate the relationship between autonomic responses and decision making during reinforcement tasks using sympathetic skin responses (SSR). Nine adult and 9 juvenile (mean age, 10.2years) volunteers were enrolled in this study. SSRs were measured during the Markov decision task (MDT), which is a reinforcement task. In this task, subjects must endure a small immediate loss to ultimately get a large reward. The subjects had to undergo three sets of tests and their scores in these tests were assessed and evaluated. All adults showed gradually increasing scores for the MDT from the first to third set. As the trial progressed from the first to second set in adults, SSR appearance ratios remarkably increased for both punishment and reward expectations. In comparison with adults, children showed decreasing scores from the first to second set. There were no significant inter-target differences in the SSR appearance ratio in the first and second set in children. In the third set, the SSR appearance ratio for reward expectations was higher than that in the neutral condition. In reinforcement tasks, such as MDT, autonomic responses play an important role in decision making. We assume that SSRs are elicited during efficient decision making tasks associated with future reward/punishment expectations, which demonstrates the importance of autonomic function. In contrast, in children around the age of 10years, the autonomic system does not react as an organized response specific to reward/punishment expectations. This suggests the immaturity of the future reward/punishment expectations process in children. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

76 FR 23351 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... Exchange would also be able to temporarily deactivate OPP from time to time on an intraday basis at its... intraday OPP deactivation due to volatility and any subsequent intraday reactivation by the Exchange...

Systems and methods for deactivating a matrix converter

DOEpatents

Ransom, Ray M.

2013-04-02

Systems and methods are provided for deactivating a matrix conversion module. An electrical system comprises an alternating current (AC) interface, a matrix conversion module coupled to the AC interface, an inductive element coupled between the AC interface and the matrix conversion module, and a control module. The control module is coupled to the matrix conversion module, and in response to a shutdown condition, the control module is configured to operate the matrix conversion module to deactivate the first conversion module when a magnitude of a current through the inductive element is less than a threshold value.

Nanotube-assisted protein deactivation

NASA Astrophysics Data System (ADS)

Joshi, Amit; Punyani, Supriya; Bale, Shyam Sundhar; Yang, Hoichang; Borca-Tasciuc, Theodorian; Kane, Ravi S.

2008-01-01

Conjugating proteins onto carbon nanotubes has numerous applications in biosensing, imaging and cellular delivery. However, remotely controlling the activity of proteins in these conjugates has never been demonstrated. Here we show that upon near-infrared irradiation, carbon nanotubes mediate the selective deactivation of proteins in situ by photochemical effects. We designed nanotube-peptide conjugates to selectively destroy the anthrax toxin, and also optically transparent coatings that can self-clean following either visible or near-infrared irradiation. Nanotube-assisted protein deactivation may be broadly applicable to the selective destruction of pathogens and cells, and will have applications ranging from antifouling coatings to functional proteomics.

Regional brain activation/deactivation during word generation in schizophrenia: fMRI study.

PubMed

John, John P; Halahalli, Harsha N; Vasudev, Mandapati K; Jayakumar, Peruvumba N; Jain, Sanjeev

2011-03-01

Examination of the brain regions that show aberrant activations and/or deactivations during semantic word generation could pave the way for a better understanding of the neurobiology of cognitive dysfunction in schizophrenia. To examine the pattern of functional magnetic resonance imaging blood oxygen level dependent activations and deactivations during semantic word generation in schizophrenia. Functional magnetic resonance imaging was performed on 24 participants with schizophrenia and 24 matched healthy controls during an overt, paced, 'semantic category word generation' condition and a baseline 'word repetition' condition that modelled all the lead-in/associated processes involved in the performance of the generation task. The brain regions activated during word generation in healthy individuals were replicated with minimal redundancies in participants with schizophrenia. The individuals with schizophrenia showed additional activations of temporo-parieto-occipital cortical regions as well as subcortical regions, despite significantly poorer behavioural performance than the healthy participants. Importantly, the extensive deactivations in other brain regions during word generation in healthy individuals could not be replicated in those with schizophrenia. More widespread activations and deficient deactivations in the poorly performing participants with schizophrenia may reflect an inability to inhibit competing cognitive processes, which in turn could constitute the core information-processing deficit underlying impaired word generation in schizophrenia.

Multiple Interactions between Cytoplasmic Domains Regulate Slow Deactivation of Kv11.1 Channels*

PubMed Central

Ng, Chai Ann; Phan, Kevin; Hill, Adam P.; Vandenberg, Jamie I.; Perry, Matthew D.

2014-01-01

The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg56 of the PAS domain and Asp803 of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels. PMID:25074935

Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

PubMed Central

Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

2013-01-01

The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

Brain activation and deactivation during location and color working memory tasks in 11-13-year-old children.

PubMed

Vuontela, Virve; Steenari, Maija-Riikka; Aronen, Eeva T; Korvenoja, Antti; Aronen, Hannu J; Carlson, Synnöve

2009-02-01

Using functional magnetic resonance imaging (fMRI) and n-back tasks we investigated whether, in 11-13-year-old children, spatial (location) and nonspatial (color) information is differentially processed during visual attention (0-back) and working memory (WM) (2-back) tasks and whether such cognitive task performance, compared to a resting state, results in regional deactivation. The location 0-back task, compared to the color 0-back task, activated segregated areas in the frontal, parietal and occipital cortices whereas no differentially activated voxels were obtained when location and color 2-back tasks were directly contrasted. Several midline cortical areas were less active during 0- and 2-back task performance than resting state. The task-induced deactivation increased with task difficulty as demonstrated by larger deactivation during 2-back than 0-back tasks. The results suggest that, in 11-13-year-old children, the visual attentional network is differently recruited by spatial and nonspatial information processing, but the functional organization of cortical activation in WM in this age group is not based on the type of information processed. Furthermore, 11-13-year-old children exhibited a similar pattern of cortical deactivation that has been reported in adults during cognitive task performance compared to a resting state.

Distinctive Spectral Features of Exciton and Excimer States in the Ultrafast Electronic Deactivation of the Adenine Dinucleotide

NASA Astrophysics Data System (ADS)

Stuhldreier, Mayra C.; Röttger, Katharina; Temps, Friedrich

We report the observation by transient absorption spectroscopy of distinctive spectro-temporal signatures of delocalized exciton versus relaxed, weakly bound excimer states in the ultrafast electronic deactivation after UV photoexcitation of the adenine dinucleotide.

Sources of deactivation during glycerol conversion on Ni/γ-Al 2 O 3

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

Chimentão, R. J.; Miranda, B. C.; Szanyi, J.

Hydrogenolysis of glycerol was studied using a diluted aqueous solution of glycerol in gas phase and atmospheric pressure on Ni/γ-Al2O3 catalyst. The catalytic transformation of glycerol generates products derived from dehydration, dehydrogenation, hydrogenolysis and condensation reactions. Deep hydrogenolysis route to produce CH4 prevails in the first few hours of reaction. As the reaction time progress, dehydration-dehydrogenation products start to appear. Here, a description of the deactivation sources and its effects on the catalytic performance of Ni catalyst was proposed. The catalyst was characterized before and after the catalytic reaction by high-resolution transmission electron microscopy (HRTEM) and by employing Fourier transformedmore » infrared spectroscopy (FTIR) of adsorbed CO. A source of deactivation was due to carbonaceous deposition. FTIR at low CO dosing pressure reveal bands assignments species essentially due to linear and bridge carbonyls, whereas high pressure CO dosing produces a complex spectra due to polycarbonyls. X-ray absorption near edge structure (XANES) analysis was employed to reveal the initial degree of reduction of the fresh catalyst. The oxidation of metallic Ni in the course of reaction may also be considered as a source of deactivation. Ni oxide species promote dehydration routes. Alumina support facilitates nickel species to be more active toward interacting with glycerol. Dehydration, which takes place on the acid sites, is the mainly route related to the generation of carbon deposition and to the observed catalyst deactivation. Another source of deactivation was due to carbiding of Ni to form Ni3C. The regeneration of used Ni catalyst was achieved by oxidation-reduction steps at 723 K.« less

Implantable cardioverter defibrillator knowledge and end-of-life device deactivation: A cross-sectional survey.

PubMed

McEvedy, Samantha M; Cameron, Jan; Lugg, Eugene; Miller, Jennifer; Haedtke, Chris; Hammash, Muna; Biddle, Martha J; Lee, Kyoung Suk; Mariani, Justin A; Ski, Chantal F; Thompson, David R; Chung, Misook Lee; Moser, Debra K

2018-01-01

End-of-life implantable cardioverter defibrillator deactivation discussions should commence before device implantation and be ongoing, yet many implantable cardioverter defibrillators remain active in patients' last days. To examine associations among implantable cardioverter defibrillator knowledge, patient characteristics and attitudes to implantable cardioverter defibrillator deactivation. Cross-sectional survey using the Experiences, Attitudes and Knowledge of End-of-Life Issues in Implantable Cardioverter Defibrillator Patients Questionnaire. Participants were classified as insufficient or sufficient implantable cardioverter defibrillator knowledge and the two groups were compared. Implantable cardioverter defibrillator recipients ( n = 270, mean age 61 ± 14 years; 73% male) were recruited from cardiology and implantable cardioverter defibrillator clinics attached to two tertiary hospitals in Melbourne, Australia, and two in Kentucky, the United States. Participants with insufficient implantable cardioverter defibrillator knowledge ( n = 77, 29%) were significantly older (mean age 66 vs 60 years, p = 0.001), less likely to be Caucasian (77% vs 87%, p  = 0.047), less likely to have received implantable cardioverter defibrillator shocks (26% vs 40%, p = 0.031), and more likely to have indications of mild cognitive impairment (Montreal Cognitive Assessment score <24: 44% vs 16%, p < 0.001). Insufficient implantable cardioverter defibrillator knowledge was associated with attitudes suggesting unwillingness to discuss implantable cardioverter defibrillator deactivation, even during the last days towards end of life ( p < 0.05). Implantable cardioverter defibrillator recipients, especially those who are older or have mild cognitive impairment, often have limited knowledge about implantable cardioverter defibrillator deactivation. This study identified several potential teachable moments throughout the patients' treatment trajectory. An interdisciplinary approach is required to ensure that discussions about implantable cardioverter defibrillator deactivation issues are initiated at appropriate time points, with family members ideally also included.

Negative BOLD in sensory cortices during verbal memory: a component in generating internal representations?

PubMed

Azulay, Haim; Striem, Ella; Amedi, Amir

2009-05-01

People tend to close their eyes when trying to retrieve an event or a visual image from memory. However the brain mechanisms behind this phenomenon remain poorly understood. Recently, we showed that during visual mental imagery, auditory areas show a much more robust deactivation than during visual perception. Here we ask whether this is a special case of a more general phenomenon involving retrieval of intrinsic, internally stored information, which would result in crossmodal deactivations in other sensory cortices which are irrelevant to the task at hand. To test this hypothesis, a group of 9 sighted individuals were scanned while performing a memory retrieval task for highly abstract words (i.e., with low imaginability scores). We also scanned a group of 10 congenitally blind, which by definition do not have any visual imagery per se. In sighted subjects, both auditory and visual areas were robustly deactivated during memory retrieval, whereas in the blind the auditory cortex was deactivated while visual areas, shown previously to be relevant for this task, presented a positive BOLD signal. These results suggest that deactivation may be most prominent in task-irrelevant sensory cortices whenever there is a need for retrieval or manipulation of internally stored representations. Thus, there is a task-dependent balance of activation and deactivation that might allow maximization of resources and filtering out of non relevant information to enable allocation of attention to the required task. Furthermore, these results suggest that the balance between positive and negative BOLD might be crucial to our understanding of a large variety of intrinsic and extrinsic tasks including high-level cognitive functions, sensory processing and multisensory integration.

Establishment of Interdisciplinary Child Protection Teams in Turkey 2002-2006: Identifying the Strongest Link Can Make a Difference!

ERIC Educational Resources Information Center

Agirtan, Canan A.; Akar, Taner; Akbas, Seher; Akdur, Recep; Aydin, Cahide; Aytar, Gulsen; Ayyildiz, Suat; Baskan, Sevgi; Belgemen, Tugba; Bezirci, Ozdecan; Beyazova, Ufuk; Beyaztas, Fatma Yucel; Buken, Bora; Buken, Erhan; Camurdan, Aysu D.; Can, Demet; Canbaz, Sevgi; Canturk, Gurol; Ceyhan, Meltem; Coskun, Abdulhakim; Celik, Ahmet; Cetin, Fusun C.; Coskun, Ayse Gul; Dagcinar, Adnan; Dallar, Yildiz; Demirel, Birol; Demirogullari, Billur; Derman, Orhan; Dilli, Dilek; Ersahin, Yusuf; Esiyok, Burcu; Evinc, Gulin; Gencer, Ozlem; Gokler, Bahar; Hanci, Hamit; Iseri, Elvan; Isir, Aysun Baransel; Isiten, Nukhet; Kale, Gulsev; Karadag, Ferda; Kanbur, Nuray; Kilic, Birim; Kultur, Ebru; Kurtay, Derya; Kuruoglu, Asli; Miral, Suha; Odabasi, Aysun B.; Oral, Resmiye; Orhon, Filiz Simsek; Ozbesler, Cengiz; Ozdemir, Dilsad Foto; Ozkok, M. Selim; Ozmert, Elif; Oztop, Didem B.; Ozyurek, Hamit; Pasli, Figen; Peksen, Yildiz; Polat, Onur; Sahin, Figen; Sahin, Ahmet Rifat; Salacin, Serpil; Suskan, Emine; Tander, Burak; Tekin, Deniz; Teksam, Ozlem; Tiras, Ulku; Tomak, Yilmaz; Tumer, Ali Riza; Turla, Ahmet; Ulukol, Betul; Uslu, Runa; Tas, Fatma V.; Vatandas, Nilgun; Velipasaoglu, Sevtap; Yagmur, Fatih; Yagmurlu, Aydin; Yalcin, Songul; Yavuz, Sukruye; Yurdakok, Kadriye

2009-01-01

Objectives: The University of Iowa Child Protection Program collaborated with Turkish professionals to develop a training program on child abuse and neglect during 2002-2006 with the goals of increasing professional awareness and number of multidisciplinary teams (MDT), regional collaborations, and assessed cases. This paper summarizes the 5-year…

How Does the Supply Requisitioning Process Affect Average Customer Wait Time Onboard U.S. Navy Destroyers?

DTIC Science & Technology

2013-06-01

17  D.  NAVAL TACTICAL COMMAND SUPPORT SYSTEM .........................17  1.  Operational Maintenance Management System–Next Generation...Management .......................................................................................21  4.  Method ...Business Administration MDT Mean Down Time MTBM Mean Time Between Maintenance NAVSUP Naval Supply Systems Command NC Not Carried NIS Not in Stock

Booster Test for Space Launch System Rocket

NASA Image and Video Library

2016-06-26

The test area where the second and final qualification motor (QM-2) test for the Space Launch System’s booster is seen Sunday, June 26, 2016, at Orbital ATK Propulsion Systems test facilities in Promontory, Utah. The test is scheduled for Tuesday, June 28 at 10:05 a.m. EDT (8:05 a.m. MDT). Photo Credit: (NASA/Bill Ingalls)

Prostanoid Production by Lipopolysaccharide-Stimulated Kupffer Cells

DTIC Science & Technology

1985-05-01

RONALD D. NELSONJt RUDOLPH J. ROETHEL, B.S.,t AND MITCHELL P. FINK, M.D.t *lrored Fores~ Radiwhwlogy Research Instt ute, . ineNcerIi’nv Bethesda. Var viand ...Multip~ le system 19. Knook, D. L., and Sleyster. E. Ch. Preparation and organ failure. Suv.k. C/in North-I ier. 63: 315, 1993. characterization of

78 FR 32001 - Public Notice for a Change in Use of Aeronautical Property and Long-Term Lease Approval at...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-28

... International Airport approved Airport Layout Plan (ALP). There is to be no sale or transfer of property rights... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Public Notice for a Change in Use of Aeronautical Property and Long-Term Lease Approval at Harrisburg International Airport (MDT), Middletown, PA...

GUIDE FOR COURSE OF STUDY FOR WAITER, WAITRESS, INFORMAL, WAITER, WAITRESS, COUNTER ATTENDANT, FOOD SERVICE WORKER.

ERIC Educational Resources Information Center

MCDONOUGH, FRANCES S.

MATERIAL IN THIS GUIDE IS FOR TEACHER USE IN TRAINING PROGRAMS FOR FOOD SERVICE WORKERS. IT WAS ORGANIZED AND WRITTEN BY A CURRICULUM DEVELOPMENT SPECIALIST FOR MANPOWER DEVELOPMENT TRAINING (MDT) ASSISTED BY INSTRUCTORS IN THE FIELD. THE GENERAL OBJECTIVE IS TO DEVELOP ABILITIES, UNDERSTANDINGS, ATTITUDES, AND INTERESTS NEEDED FOR ENTRY LEVEL…

Fuel Efficiency Mapping of a 2014 6-Cylinder GM EcoTec 4.3L Engine with Cylinder Deactivation (SAE 2016-01-0662)

EPA Science Inventory

This paper describes the method and test results of the engine dyno portion of the benchmarking test results including engine fuel consumption maps showing the effects of cylinder deactivation engine technology.

Mathematics anxiety reduces default mode network deactivation in response to numerical tasks.

PubMed

Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H

2015-01-01

Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval.

Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

PubMed

Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

2017-02-01

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

Mathematics anxiety reduces default mode network deactivation in response to numerical tasks

PubMed Central

Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert H.

2015-01-01

Mathematics anxiety is negatively related to mathematics performance, thereby threatening the professional success. Preoccupation with the emotional content of the stimuli may consume working memory resources, which may be reflected in decreased deactivation of areas associated with the default mode network (DMN) activated during self-referential and emotional processing. The common problem is that math anxiety is usually associated with poor math performance, so that any group differences are difficult to interpret. Here we compared the BOLD-response of 18 participants with high (HMAs) and 18 participants with low mathematics anxiety (LMAs) matched for their mathematical performance to two numerical tasks (number comparison, number bisection). During both tasks, we found stronger deactivation within the DMN in LMAs compared to HMAs, while BOLD-response in task-related activation areas did not differ between HMAs and LMAs. The difference in DMN deactivation between the HMA and LMA group was more pronounced in stimuli with additional requirement on inhibitory functions, but did not differ between number magnitude processing and arithmetic fact retrieval. PMID:25954179

Low temperature deactivation of Ge heavily n-type doped by ion implantation and laser thermal annealing

NASA Astrophysics Data System (ADS)

Milazzo, R.; Impellizzeri, G.; Piccinotti, D.; De Salvador, D.; Portavoce, A.; La Magna, A.; Fortunato, G.; Mangelinck, D.; Privitera, V.; Carnera, A.; Napolitani, E.

2017-01-01

Heavy doping of Ge is crucial for several advanced micro- and optoelectronic applications, but, at the same time, it still remains extremely challenging. Ge heavily n-type doped at a concentration of 1 × 1020 cm-3 by As ion implantation and melting laser thermal annealing (LTA) is shown here to be highly metastable. Upon post-LTA conventional thermal annealing As electrically deactivates already at 350 °C reaching an active concentration of ˜4 × 1019 cm-3. No significant As diffusion is detected up to 450 °C, where the As activation decreases further to ˜3 × 1019 cm-3. The reason for the observed detrimental deactivation was investigated by Atom Probe Tomography and in situ High Resolution X-Ray Diffraction measurements. In general, the thermal stability of heavily doped Ge layers needs to be carefully evaluated because, as shown here, deactivation might occur at very low temperatures, close to those required for low resistivity Ohmic contacting of n-type Ge.

Solvent effects on the ultrafast nonradiative deactivation mechanisms of thymine in aqueous solution: Excited-state QM/MM molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Nakayama, Akira; Arai, Gaku; Yamazaki, Shohei; Taketsugu, Tetsuya

2013-12-01

On-the-fly excited-state quantum mechanics/molecular mechanics molecular dynamics (QM/MM-MD) simulations of thymine in aqueous solution are performed to investigate the role of solvent water molecules on the nonradiative deactivation process. The complete active space second-order perturbation theory (CASPT2) method is employed for a thymine molecule as the QM part in order to provide a reliable description of the excited-state potential energies. It is found that, in addition to the previously reported deactivation pathway involving the twisting of the C-C double bond in the pyrimidine ring, another efficient deactivation pathway leading to conical intersections that accompanies the out-of-plane displacement of the carbonyl group is observed in aqueous solution. Decay through this pathway is not observed in the gas phase simulations, and our analysis indicates that the hydrogen bonds with solvent water molecules play a key role in stabilizing the potential energies of thymine in this additional decay pathway.

Immobilized glucose oxidase--catalase and their deactivation in a differential-bed loop reactor.

PubMed

Prenosil, J E

1979-01-01

Glucose oxidase containing catalase was immobilized with a copolymer of phenylenediamine and glutaraldehyde on pumice and titania carrier to study the enzymatic oxidation of glucose in a differential-bed loop reactor. The reaction rate was found to be first order with respect to the concentration of limiting oxygen substrate, suggesting a strong external mass-transfer resistance for all the flow rates used. The partial pressure of oxygen was varied from 21.3 up to 202.6 kPa. The use of a differential-bed loop reactor for the determination of the active enzyme concentration in the catalyst with negligible internal pore diffusion resistance is shown. Catalyst deactivation was studied, especially with respect to the presence of catalase. It is believed that the hydrogen peroxide formed in the oxidation reaction deactivates catalase first; if an excess of catalase is present, the deactivation of glucose oxidase remains small. The mathematical model subsequently developed adequately describes the experimental results.

Deactivation Mechanisms of Pt/Pd-based Diesel Oxidation Catalysts

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

Wiebenga, Michelle H.; Kim, Chang H.; Schmieg, Steven J.

2012-04-30

Currently precious metal-based diesel oxidation catalysts (DOC) containing platinum (Pt) and palladium (Pd) are most commonly used for the oxidation of hydrocarbon and NO in diesel exhaust hydrocarbon oxidation. The present work has been carried out to investigate the deactivation mechanisms of the DOC from its real-world vehicle operation by coupling its catalytic activity measurements with surface characterization including x-ray diffraction, transmission electron microscopy, and x-ray photoelectron spectroscopy. A production Pt-Pd DOC was obtained after being aged on a vehicle driven for 135,000 miles in order to study its deactivation behavior. The performance of the vehicle-aged part was correlated withmore » that of the simulated hydrothermal lab aged sample assuming that Pt-Pd sintering plays a major role in irreversible catalyst deactivation. In addition to the hydrothermal sintering, the deterioration of hydrocarbon and NO oxidation performance was caused by surface poisoning. The role of the various aging factors in determining long-term performance in mobile applications will be discussed.« less

The Role of Phosphorus and Soot on the Deactivation of Diesel Oxidation Catalysts

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

Eaton, Scott J; Nguyen, Ke; Bunting, Bruce G

The deactivation of diesel oxidation catalysts (DOCs) by soot contamination and lube-oil derived phosphorus poisoning is investigated. Pt/CeO2/-Al2O3 DOCs aged using three different protocols developed by the authors and six high mileage field-returned DOCs of similar formulation are evaluated for THC and CO oxidation performance using a bench-flow reactor. Collectively, these catalysts exhibit a variety of phosphorus and soot morphologies contributing to performance deactivation. To isolate and examine the contribution of each deactivation mechanism, performance evaluations are carried out for each DOC ''as received'' and after removal of surface carbon in a high-temperature oxidizing environment. In such a manner themore » deactivation contribution of soot contamination is de-convoluted from that of phosphorus poisoning. It will be shown that this is accomplished while preserving phosphorus (and to a lesser degree sulfur, calcium and zinc) chemistries and concentrations within the washcoat. Washcoat contaminant information and materials changes are characterized using electron-probe microanalysis (EPMA), X-ray diffraction (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), BET surface area, oxygen storage capacity (OSC), X-ray fluorescence (XRF) and inductively coupled plasma (ICP) analysis, from which the relative severity of each mechanism can be quantified. Results show that soot contamination from diesel exhaust severely degrades THC and CO oxidation performance by acting as a catalyst surface diffusion barrier. This results in a considerable increase of light-off temperatures. In contrast, phosphorus poisoning, which is considered a significant deactivation mechanism in three-way catalysts, is shown to have minimal effect on DOC oxidation performance for the conditions studied here. Material changes include the formation of both Ce(III-IV) and aluminum phosphates which do not significantly hinder the THC and CO oxidation in lean exhaust. In addition, thermal aging and sulfur poisoning are shown to produce minimal contributions to the overall deactivation. Consequently, performance of aged DOCs after soot removal is observed to be comparable to that of a fresh catalyst under our testing conditions.« less

Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

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

Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

The stability of palladium supported on ceria (Pd/CeO 2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

Psychophysiological changes following auditory subliminal suggestions for activation and deactivation.

PubMed

Borgeat, F; Goulet, J

1983-06-01

This study was to measure eventual psychophysiological changes resulting from auditory subliminal activation or deactivation suggestions. 18 subjects were alternately exposed to a control situation and to 25-dB activating and deactivating suggestions masked by a 40-dB white noise. Physiological measures (EMG, heart rate, skin-conductance levels and responses, and skin temperature) were recorded while subjects listened passively to the suggestions, during a stressing task that followed and after that task. Multivariate analysis of variance showed a significant effect of the activation subliminal suggestions during and following the stressing task. This result is discussed as indicating effects of consciously unrecognized perceptions on psychophysiological responses.

Deactivation of Ceria Supported Palladium through C–C Scission during Transfer Hydrogenation of Phenol with Alcohols

DOE PAGES

Nelson, Nicholas C.; Manzano, J. Sebastián; Slowing, Igor I.

2016-11-21

The stability of palladium supported on ceria (Pd/CeO 2) was studied during liquid flow transfer hydrogenation using primary and secondary alcohols as hydrogen donors. For primary alcohols, the ceria support was reduced to cerium hydroxy carbonate within 14 h and was a contributing factor toward catalyst deactivation. For secondary alcohols, cerium hydroxy carbonate was not observed during the same time period and the catalyst was stable upon prolonged reaction. Regeneration through oxidation/reduction does not restore initial activity likely due to irreversible catalyst restructuring. Lastly, a deactivation mechanism involving C–C scission of acyl and carboxylate intermediates is proposed.

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

Miller, Daniel P.; Tymińska, Nina; Zurek, Eva, E-mail: ezurek@buffalo.edu

Dispersion corrected Density Functional Theory calculations were employed to study the adsorption of benzenes derivatized with functional groups encompassing a large region of the activated/deactivated spectrum to the Ag(111) surface. Benzenes substituted with weak activating or deactivating groups, such as methyl and fluoro, do not have a strong preference for adsorbing to a particular site on the substrate, with the corrugations in the potential energy surface being similar to those of benzene. Strong activating (N(CH{sub 3}){sub 2}) and deactivating (NO{sub 2}) groups, on the other hand, possess a distinct site preference. The nitrogen in the former prefers to lie abovemore » a silver atom (top site), but in the latter a hollow hexagonal-closed-packed (H{sub hcp}) site of the Ag(111) surface is favored instead. Benzenes derivatized with classic activating groups donate electron density from their highest occupied molecular orbital to the surface, and those functionalized with deactivating groups withdraw electron density from the surface into orbitals that are unoccupied in the gas phase. For benzenes functionalized with two substituents, the groups that are strongly activating or deactivating control the site preference and the other groups assume sites that are, to a large degree, dictated by their positions on the benzene ring. The relative stabilities of the ortho, meta, and para positional isomers of disubstituted benzenes can, in some cases, be modified by adsorption to the surface.« less

Reversible deactivation of higher-order posterior parietal areas. II. Alterations in response properties of neurons in areas 1 and 2

PubMed Central

Goldring, Adam B.; Cooke, Dylan F.; Baldwin, Mary K. L.; Recanzone, Gregg H.; Gordon, Adam G.; Pan, Tingrui; Simon, Scott I.

2014-01-01

The role that posterior parietal (PPC) and motor cortices play in modulating neural responses in somatosensory areas 1 and 2 was examined with reversible deactivation by transient cooling. Multiunit recordings from neurons in areas 1 and 2 were collected from six anesthetized adult monkeys (Macaca mulatta) before, during, and after reversible deactivation of areas 5L or 7b or motor cortex (M1/PM), while select locations on the hand and forelimb were stimulated. Response changes were quantified as increases and decreases to stimulus-driven activity relative to baseline and analyzed during three recording epochs: during deactivation (“cool”) and at two time points after deactivation (“rewarm 1,” “rewarm 2”). Although the type of response change observed was variable, for neurons at the recording sites tested >90% exhibited a significant change in response during cooling of 7b while cooling area 5L or M1/PM produced a change in 75% and 64% of sites, respectively. These results suggest that regions in the PPC, and to a lesser extent motor cortex, shape the response characteristics of neurons in areas 1 and 2 and that this kind of feedback modulation is necessary for normal somatosensory processing. Furthermore, this modulation appears to happen on a minute-by-minute basis and may serve as the substrate for phenomena such as somatosensory attention. PMID:25143537

Light-driven transformable optical agent with adaptive functions for boosting cancer surgery outcomes.

PubMed

Qi, Ji; Chen, Chao; Zhang, Xiaoyan; Hu, Xianglong; Ji, Shenglu; Kwok, Ryan T K; Lam, Jacky W Y; Ding, Dan; Tang, Ben Zhong

2018-05-10

Fluorescence and photoacoustic imaging have different advantages in cancer diagnosis; however, combining effects in one agent normally requires a trade-off as the mechanisms interfere. Here, based on rational molecular design, we introduce a smart organic nanoparticle whose absorbed excitation energy can be photo-switched to the pathway of thermal deactivation for photoacoustic imaging, or to allow opposed routes for fluorescence imaging and photodynamic therapy. The molecule is made of a dithienylethene (DTE) core with two surrounding 2-(1-(4-(1,2,2-triphenylvinyl)phenyl)ethylidene)malononitrile (TPECM) units (DTE-TPECM). The photosensitive molecule changes from a ring-closed, for photoacoustic imaging, to a ring-opened state for fluorescence and photodynamic effects upon an external light trigger. The nanoparticles' photoacoustic and fluorescence imaging properties demonstrate the advantage of the switch. The use of the nanoparticles improves the outcomes of in vivo cancer surgery using preoperative photoacoustic imaging and intraoperative fluorescent visualization/photodynamic therapy of residual tumours to ensure total tumour removal.

Deactivating the Writing Program.

ERIC Educational Resources Information Center

Strickland, James

A written language learner must be given an environment that enables or fosters writing development. Unfortunately, the typical system of education and the learning strategies that are taught are at times the very things that deactivate, frustrate, and even pervert the writing program. In fact, some of the rules that student writers respond to are…

Split exponential track length estimator for Monte-Carlo simulations of small-animal radiation therapy

NASA Astrophysics Data System (ADS)

Smekens, F.; Létang, J. M.; Noblet, C.; Chiavassa, S.; Delpon, G.; Freud, N.; Rit, S.; Sarrut, D.

2014-12-01

We propose the split exponential track length estimator (seTLE), a new kerma-based method combining the exponential variant of the TLE and a splitting strategy to speed up Monte Carlo (MC) dose computation for low energy photon beams. The splitting strategy is applied to both the primary and the secondary emitted photons, triggered by either the MC events generator for primaries or the photon interactions generator for secondaries. Split photons are replaced by virtual particles for fast dose calculation using the exponential TLE. Virtual particles are propagated by ray-tracing in voxelized volumes and by conventional MC navigation elsewhere. Hence, the contribution of volumes such as collimators, treatment couch and holding devices can be taken into account in the dose calculation. We evaluated and analysed the seTLE method for two realistic small animal radiotherapy treatment plans. The effect of the kerma approximation, i.e. the complete deactivation of electron transport, was investigated. The efficiency of seTLE against splitting multiplicities was also studied. A benchmark with analog MC and TLE was carried out in terms of dose convergence and efficiency. The results showed that the deactivation of electrons impacts the dose at the water/bone interface in high dose regions. The maximum and mean dose differences normalized to the dose at the isocenter were, respectively of 14% and 2% . Optimal splitting multiplicities were found to be around 300. In all situations, discrepancies in integral dose were below 0.5% and 99.8% of the voxels fulfilled a 1%/0.3 mm gamma index criterion. Efficiency gains of seTLE varied from 3.2 × 105 to 7.7 × 105 compared to analog MC and from 13 to 15 compared to conventional TLE. In conclusion, seTLE provides results similar to the TLE while increasing the efficiency by a factor between 13 and 15, which makes it particularly well-suited to typical small animal radiation therapy applications.

What a Successful Solar Market Can Do for You | State, Local, and Tribal

Science.gov Websites

Can Do for You The Solar Technical Assistance Team (STAT) 2012 webinar series was developed for state policymakers and staff. Wednesday, July 18, 2012, 12-1 p.m. MDT This overview of the STAT webinar series gives jobs, air quality, and reduction in grid congestion). The discussion includes examples of jurisdictions

Multiprofessional education to stimulate collaboration: a circular argument and its consequences.

PubMed

Roodbol, Petrie F

2010-01-01

The current developments in healthcare are unprecedented. The organization of health care is complex. Collaboration is essential to meet all the healthcare needs of patients and to achieve coordinated and unambiguous information. Multiprofessional education (MPE) or multidisciplinary training (MDT) seems a logical step to stimulate teamwork. However, collaboration and MPE are wrestling with the same problems: social identity and acceptance.

Herpes simplex virus: 'to disclose or not to disclose.' An exploration of the multi-disciplinary team's role in advising patients about disclosure when diagnosed with genital herpes simplex virus.

PubMed

Caulfield, Pauline; Willis, Diane

2017-07-01

The first UK prosecution for genital herpes simplex virus (HSV) transmission in 2011 attracted strong criticism from medical experts. To address the dearth of research on the topic, this study aimed to explore the nature of advice given to patients by the multidisciplinary team (MDT) in the West of Scotland on HSV disclosure to partners. Ten semi-structured interviews with members of the MDT were conducted and the interviews were analysed using Burnard's Thematic Content Analysis. Four themes emerged which explored practitioners' knowledge of HSV and their feelings regarding the emotional aspects of the diagnosis on clients including the challenges of discussing disclosure. Within this framework, participants' attitudes to the legal prosecution were also surveyed. This study revealed that participants had good knowledge about HSV. Furthermore, participants believed disclosure to be the patient's choice and had not altered their practice to advise disclosure to all partners in accordance with local protocol. However, there was a general consensus that disclosure was not required due to the prevalence of HSV and prevalence was used to dissipate emotional reactions to HSV diagnosis.

Characterization of coke, or carbonaceous matter, formed on CoMo catalysts used in hydrodesulfurization unit in oil refinery

NASA Astrophysics Data System (ADS)

Kimura, Nobuharu; Iwanami, Yoshimu; Koide, Ryutaro; Kudo, Reiko

2017-06-01

When a mixture of light gas oil (LGO) and light cycle oil is fed into an oil refinery’s hydrodesulfurization (HDS) unit to produce diesel fuel, the catalyst in the HDS unit is rapidly deactivated. By contrast, when the feed is LGO mixed with residue desulfurization gas oil, the catalyst is deactivated slowly. Hoping to understand why, the authors focused on the coke formed on the catalysts during the HDS reaction. The result of a comprehensive analysis of the coke suggested that the ways coke formed and grew on the catalysts may differ depending on the feeds used, which in turn could affect the deactivation behaviors of the catalysts.

CATALYTIC STEAM REFORMING OF CHLOROCARBONS: CATALYST DEACTIVATION. (R826694C633)

EPA Science Inventory

Deactivation of 0.5 wt.% Pt/-Al₂O₃ catalysts during trichloroethylene (TCE)–steam reforming was studied with experiments at 700°C, H

77 FR 10406 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... powered by Pratt & Whitney JT9D series engines require installation of a new bracket for stowing the... serviceable stowage bracket for the deactivation pins on all airplanes powered by Pratt & Whitney JT9D series... Pratt & Whitney JT9D series engines require installation of a new bracket for stowing the deactivation...

The Approach of Emotional Deactivation of Prejudice

ERIC Educational Resources Information Center

Boucher, Jean-Nil

2011-01-01

The aim of the approach of emotional deactivation is to help students reduce the prejudice they may feel towards diverse social groups. Be those groups homosexuals, people living with a disability or immigrants, the victims of prejudice are invited to come into classrooms and to confront the preconceptions that students have in their respect.…

Subject specific finite element modeling of periprosthetic femoral fracture using element deactivation to simulate bone failure.

PubMed

Miles, Brad; Kolos, Elizabeth; Walter, William L; Appleyard, Richard; Shi, Angela; Li, Qing; Ruys, Andrew J

2015-06-01

Subject-specific finite element (FE) modeling methodology could predict peri-prosthetic femoral fracture (PFF) for cementless hip arthoplasty in the early postoperative period. This study develops methodology for subject-specific finite element modeling by using the element deactivation technique to simulate bone failure and validate with experimental testing, thereby predicting peri-prosthetic femoral fracture in the early postoperative period. Material assignments for biphasic and triphasic models were undertaken. Failure modeling with the element deactivation feature available in ABAQUS 6.9 was used to simulate a crack initiation and propagation in the bony tissue based upon a threshold of fracture strain. The crack mode for the biphasic models was very similar to the experimental testing crack mode, with a similar shape and path of the crack. The fracture load is sensitive to the friction coefficient at the implant-bony interface. The development of a novel technique to simulate bone failure by element deactivation of subject-specific finite element models could aid prediction of fracture load in addition to fracture risk characterization for PFF. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Effect of pH on subunit association and heat protection of soybean alpha-galactosidase

NASA Technical Reports Server (NTRS)

Porter, J. E.; Sarikaya, A.; Herrmann, K. M.; Ladisch, M. R.; Mitchell, C. A. (Principal Investigator)

1992-01-01

Soybeans contain the enzyme alpha-galactosidase, which hydrolyzes alpha-1, 6 linkages in stachyose and raffinose to give sucrose and galactose. We have found that galactose, a competitive product inhibitor of alpha-galactosidase, strongly promotes the heat stability of the tetrameric form of the enzyme at pH 4.0 and at temperatures of up to 70 degrees C for 60 min. Stachyose and raffinose also protect alpha-galactosidase from denaturation at pH 4.0 although to a lesser extent. Glucose and mannose have little effect. At pH 7.0 the enzyme is a monomer, and galactose has no effect on the heat stability of the enzyme. In the absence of heat protection of the enzyme by added sugars, a series deactivation mechanism was found to describe the deactivation data. In comparison, a unimolecular, non-first order deactivation model applies at pH 4.0, where heat protection effects were observed. At a temperature above 60 degrees C, simple deactivation is a suitable model. The results suggest that alpha-galactosidase conformation and heat stability are directly related.

Lignocellulosic hydrolysate inhibitors selectively inhibit/deactivate cellulase performance.

PubMed

Mhlongo, Sizwe I; den Haan, Riaan; Viljoen-Bloom, Marinda; van Zyl, Willem H

2015-12-01

In this study, we monitored the inhibition and deactivation effects of various compounds associated with lignocellulosic hydrolysates on individual and combinations of cellulases. Tannic acid representing polymeric lignin residues strongly inhibited cellobiohydrolase 1 (CBH1) and β-glucosidase 1 (BGL1), but had a moderate inhibitory effect on endoglucanase 2 (EG2). Individual monomeric lignin residues had little or no inhibitory effect on hydrolytic enzymes. However, coniferyl aldehyde and syringaldehyde substantially decreased the activity of CBH1 and deactivated BGL1. Acetic and formic acids also showed strong inhibition of BGL1 but not CBH1 and EG2, whereas tannic, acetic and formic acid strongly inhibited a combination of CBH1 and EG2 during Avicel hydrolysis. Diminishing enzymatic hydrolysis is largely a function of inhibitor concentration and the enzyme-inhibitor relationship, rather than contact time during the hydrolysis process (i.e. deactivation). This suggests that decreased rates of hydrolysis during the enzymatic depolymerisation of lignocellulosic hydrolysates may be imparted by other factors related to substrate crystallinity and accessibility. Copyright © 2015 Elsevier Inc. All rights reserved.

The human red cell voltage-regulated cation channel. The interplay with the chloride conductance, the Ca(2+)-activated K(+) channel and the Ca(2+) pump.

PubMed

Bennekou, P; Kristensen, B I; Christophersen, P

2003-09-01

The activation/deactivation kinetics of the human erythrocyte voltage-dependent cation channel was characterized at the single-channel level using inside-out patches. It was found that the time dependence for voltage activation after steps to positive membrane potentials was slow ( t(1/2) about 30 s), whereas the deactivation was fast ( t(1/2) about 15 ms). Both activation and deactivation of this channel were also demonstrated in intact red cells in suspension. At very positive membrane potentials generated by suspension in extracellular low Cl(-) concentrations, the cation conductance switched on with a time constant of about 2 min. Deactivation of the cation channel was clearly demonstrated during transient activation of the Gárdos channel elicited by Ca(2+) influx via the cation channel and ensuing efflux via the Ca(2+) pump. Thus, the voltage-dependent cation channel, the Gárdos channel and the Ca(2+) pump constitute a coupled feedback-regulated system that may become operative under physiological conditions.

Learning and recall of form discriminations during reversible cooling deactivation of ventral-posterior suprasylvian cortex in the cat.

PubMed Central

Lomber, S G; Payne, B R; Cornwell, P

1996-01-01

Extrastriate visual cortex of the ventral-posterior suprasylvian gyrus (vPS cortex) of freely behaving cats was reversibly deactivated with cooling to determine its role in performance on a battery of simple or masked two-dimensional pattern discriminations, and three-dimensional object discriminations. Deactivation of vPS cortex by cooling profoundly impaired the ability of the cats to recall the difference between all previously learned pattern and object discriminations. However, the cats' ability to learn or relearn pattern and object discriminations while vPS was deactivated depended upon the nature of the pattern or object and the cats' prior level of exposure to them. During cooling of vPS cortex, the cats could neither learn the novel object discriminations nor relearn a highly familiar masked or partially occluded pattern discrimination, although they could relearn both the highly familiar object and simple pattern discriminations. These cooling-induced deficits resemble those induced by cooling of the topologically equivalent inferotemporal cortex of monkeys and provides evidence that the equivalent regions contribute to visual processing in similar ways. Images Fig. 1 Fig. 3 PMID:8643686

Emotional faces and the default mode network.

PubMed

Sreenivas, S; Boehm, S G; Linden, D E J

2012-01-11

The default-mode network (DMN) of the human brain has become a central topic of cognitive neuroscience research. Although alterations in its resting state activity and in its recruitment during tasks have been reported for several mental and neurodegenerative disorders, its role in emotion processing has received relatively little attention. We investigated brain responses to different categories of emotional faces with functional magnetic resonance imaging (fMRI) and found deactivation in ventromedial prefrontal cortex (VMPFC), posterior cingulate gyrus (PC) and cuneus. This deactivation was modulated by emotional category and was less prominent for happy than for sad faces. These deactivated areas along the midline conformed to areas of the DMN. We also observed emotion-dependent deactivation of the left middle frontal gyrus, which is not a classical component of the DMN. Conversely, several areas in a fronto-parietal network commonly linked with attention were differentially activated by emotion categories. Functional connectivity patterns, as obtained by correlation of activation levels, also varied between emotions. VMPFC, PC or cuneus served as hubs between the DMN-type areas and the fronto-parietal network. These data support recent suggestions that the DMN is not a unitary system but differentiates according to task and even type of stimulus. The emotion-specific differential pattern of DMN deactivation may be explored further in patients with mood disorder, where the quest for biological markers of emotional biases is still ongoing. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

High-intensity erotic visual stimuli de-activate the primary visual cortex in women.

PubMed

Huynh, Hieu K; Beers, Caroline; Willemsen, Antoon; Lont, Erna; Laan, Ellen; Dierckx, Rudi; Jansen, Monique; Sand, Michael; Weijmar Schultz, Willibrord; Holstege, Gert

2012-06-01

The primary visual cortex, Brodmann's area (BA 17), plays a vital role in basic survival mechanisms in humans. In most neuro-imaging studies in which the volunteers have to watch pictures or movies, the primary visual cortex is similarly activated independent of the content of the pictures or movies. However, in case the volunteers perform demanding non-visual tasks, the primary visual cortex becomes de-activated, although the amount of incoming visual sensory information is the same. Do low- and high-intensity erotic movies, compared to neutral movies, produce similar de-activation of the primary visual cortex? Brain activation/de-activation was studied by Positron Emission Tomography scanning of the brains of 12 healthy heterosexual premenopausal women, aged 18-47, who watched neutral, low- and high-intensity erotic film segments. We measured differences in regional cerebral blood flow (rCBF) in the primary visual cortex during watching neutral, low-intensity erotic, and high-intensity erotic film segments. Watching high-intensity erotic, but not low-intensity erotic movies, compared to neutral movies resulted in strong de-activation of the primary (BA 17) and adjoining parts of the secondary visual cortex. The strong de-activation during watching high-intensity erotic film might represent compensation for the increased blood supply in the brain regions involved in sexual arousal, also because high-intensity erotic movies do not require precise scanning of the visual field, because the impact is clear to the observer. © 2012 International Society for Sexual Medicine.

A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides

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

Du Yuzhe; Song Weizhong; Groome, James R.

2010-08-15

Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivation. Recent studies have begun to reveal sodium channel residues important for pyrethroid binding. However, how pyrethroid binding leads to inhibition of sodium channel deactivation and inactivation remains elusive. In this study, we show that a negatively charged aspartic acid residue at position 802 (D802) located in the extracellular end of transmembrane segment 1 of domain II (IIS1) is critical for both the action ofmore » pyrethroids and the voltage dependence of channel activation. Charge-reversing or -neutralizing substitutions (K, G, or A) of D802 shifted the voltage dependence of activation in the depolarizing direction and reduced channel sensitivity to deltamethrin, a pyrethroid insecticide. The charge-reversing mutation D802K also accelerated open-state deactivation, which may have counteracted the inhibition of sodium channel deactivation by deltamethrin. In contrast, the D802G substitution slowed open-state deactivation, suggesting an additional mechanism for neutralizing the action of deltamethrin. Importantly, Schild analysis showed that D802 is not involved in pyrethroid binding. Thus, we have identified a sodium channel residue that is critical for regulating the action of pyrethroids on the sodium channel without affecting the receptor site of pyrethroids.« less

Molecular basis of slow activation of the human ether-á-go-go related gene potassium channel

PubMed Central

Subbiah, Rajesh N; Clarke, Catherine E; Smith, David J; Zhao, JingTing; Campbell, Terence J; Vandenberg, Jamie I

2004-01-01

The human ether-á-go-go related gene (HERG) encodes the pore forming α-subunit of the rapid delayed rectifier K+ channel which is central to the repolarization phase of the cardiac action potential. HERG K+ channels have unusual kinetics characterized by slow activation and deactivation, yet rapid inactivation. The fourth transmembrane domain (S4) of HERG, like other voltage-gated K+ channels, contains multiple positive charges and is the voltage sensor for activation. In this study, we mutated each of the positively charged residues in this region to glutamine (Q), expressed the mutant and wild-type (WT) channels in Xenopus laevis oocytes and studied them using two-electrode voltage clamp methods. K525Q channels activated at more hyperpolarized potentials than WT, whereas all the other mutant channels activated at more depolarized potentials. All mutants except for R531Q also had a reduction in apparent gating charge associated with activation. Mutation of K525 to cysteine (C) resulted in a less dramatic phenotype than K525Q. The addition of the positively charged MTSET to K525C altered the phenotype to one more similar to K525Q than to WT. Therefore it is not charge per se, but the specific lysine side chain at position 525, that is crucial for stabilizing the closed state. When rates of activation and deactivation for WT and mutant channels were compared at equivalent total (chemical + electrostatic) driving forces, K525Q and R528Q accelerated activation but had no effect on deactivation, R531Q slowed activation and deactivation, R534Q accelerated activation but slowed deactivation and R537Q accelerated deactivation but had no effect on activation. The main conclusions we can draw from these data are that in WT channels K525 stabilizes the closed state, R531 stabilizes the open state and R534 participates in interactions that stabilize pre-open closed states. PMID:15181157

A pilot study on understanding the journey of advanced prostate cancer patients.

PubMed

Wagholikar, Amol; Fung, Maggie; Nelson, Colleen

2011-01-01

To understand the journey of advanced prostate cancer patients for supporting development of an innovative patient journey browser. Prostate cancer is one of the common cancers in Australia. Due to the chronic nature of the disease, it is important to have effective disease management strategy and care model. Multi-disciplinary care is a well-proven approach for chronic disease management. The Multi-disciplinary team (MDT) can function more effectively if all the required information is available for the clinical decision support. The development of innovative technology relies on an accurate understanding of the advanced prostate cancer patient's journey over a prolonged period. This need arises from the fact that advanced prostate cancer patients may follow various treatment paths and change their care providers. As a result of this, it is difficult to understand the actual sources of patient's clinical records and their treatment patterns. The aim of the research is to understand variable sources of clinical records, treatment patterns, alternative therapies, over the counter (OTC) medications of advanced prostate cancer patients. This study provides better and holistic understanding of advanced prostate cancer journey. The study was conducted through an on-line survey developed to seek and analyse the responses from the participants. The on-line questionnaire was carefully developed through consultations with the clinical researchers at the Australian Prostate Cancer Research Centre-Queensland, prostate cancer support group representatives and health informaticians at the Australian E-Health Research Centre. The non-identifying questionnaire was distributed to the patients through prostate cancer support groups in Queensland, Australia. The pilot study was carried out between August 2010 and December 2010. The research made important observations about the advanced prostate cancer journey. It showed that General Practitioner (GP) was the common source of patient's clinical records (41%) followed by Urologist (14%) and other clinicians (14%). The data analysis also showed that selenium was the common complementary supplement (55%) used by the patients and about 48% patients did not use any OTC drugs. The most common OTC used by the patients was Paracetamol (about 45%). The results have provided a foundation to the architecture of the proposed technology solution. The outcomes of this study are incorporated in design of the proposed patient journey browser system. A basic version of the system is currently being used at the advanced prostate cancer MDT meetings.

Progress towards a leprosy-free country: The experience of Oman

PubMed Central

2017-01-01

Introduction The World Health Organization (WHO) released the Global Leprosy Strategy 2016–2020 towards a leprosy-free world. The author described the progress made towards the elimination of leprosy and suggested recommendations for the acceleration towards a Leprosy-free country according to WHO laid out criterion. Methodology Case record review of Leprosy patients managed between the years 1992 to 2015 were registered and analyzed. Data were collected from annual reports of the Ministry of Health including demographics, classification of leprosy new cases, relapse, childhood, grades of disability (GD) and multidrug therapy (MDT) completion rates. Results Leprosy prevalence rate declined from 1.64 to 0.09 per 10,000 population during the period 1992 and 2015 (p<0.0001). Between 2005 and 2015, 77 patients were diagnosed with Leprosy as per definition and 75/77 (98%) had smear or biopsy positive. Of these, 53 (69%) cases were among foreign-born (non-national) (p<0.003) and 19 (25%) were among women. Most of the leprosy cases were notified in Muscat governorate 29 (38%) and among patients between 25–44 years of age 41 (53%), followed by ≥45 years 29 (38%) and 6 (8%) were children age ≤ 14 years. Multi-bacillary (MB) cases reported 60 versus 17 for Pauci-bacillary (PB) (p< 0.01), while MB was highest among both nationals (83%) and foreign-born (75%). MDT completion rate was 100% and no relapse cases were notified among nationals. The rate of new patients diagnosed with leprosy related disability was 2.3 per million population, and grade 2 disability (G2D) rate among nationals was 0.9 per million population. No disability was recorded among women or children less than 14 years within the nationals group from 2013. Almost all the foreign-born patients didn’t complete their treatment in Oman as they left the country shortly after diagnosis of leprosy due to a very short term contract, discretionary employment practices by the employers and prefer to go home to complete their treatment. Conclusion Oman has met the elimination goals and made great strides towards becoming a leprosy-free country. However, challenges such as improving surveillance system efficiency and sensitivity for detecting timely leprosy cases, as well as foreign-born workers are still a major concerns. PMID:29155821

Progress towards a leprosy-free country: The experience of Oman.

PubMed

Al Awaidy, Salah T

2017-11-01

The World Health Organization (WHO) released the Global Leprosy Strategy 2016-2020 towards a leprosy-free world. The author described the progress made towards the elimination of leprosy and suggested recommendations for the acceleration towards a Leprosy-free country according to WHO laid out criterion. Case record review of Leprosy patients managed between the years 1992 to 2015 were registered and analyzed. Data were collected from annual reports of the Ministry of Health including demographics, classification of leprosy new cases, relapse, childhood, grades of disability (GD) and multidrug therapy (MDT) completion rates. Leprosy prevalence rate declined from 1.64 to 0.09 per 10,000 population during the period 1992 and 2015 (p<0.0001). Between 2005 and 2015, 77 patients were diagnosed with Leprosy as per definition and 75/77 (98%) had smear or biopsy positive. Of these, 53 (69%) cases were among foreign-born (non-national) (p<0.003) and 19 (25%) were among women. Most of the leprosy cases were notified in Muscat governorate 29 (38%) and among patients between 25-44 years of age 41 (53%), followed by ≥45 years 29 (38%) and 6 (8%) were children age ≤ 14 years. Multi-bacillary (MB) cases reported 60 versus 17 for Pauci-bacillary (PB) (p< 0.01), while MB was highest among both nationals (83%) and foreign-born (75%). MDT completion rate was 100% and no relapse cases were notified among nationals. The rate of new patients diagnosed with leprosy related disability was 2.3 per million population, and grade 2 disability (G2D) rate among nationals was 0.9 per million population. No disability was recorded among women or children less than 14 years within the nationals group from 2013. Almost all the foreign-born patients didn't complete their treatment in Oman as they left the country shortly after diagnosis of leprosy due to a very short term contract, discretionary employment practices by the employers and prefer to go home to complete their treatment. Oman has met the elimination goals and made great strides towards becoming a leprosy-free country. However, challenges such as improving surveillance system efficiency and sensitivity for detecting timely leprosy cases, as well as foreign-born workers are still a major concerns.

Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study

PubMed Central

Farr, Olivia M.; Tsoukas, Michael A.; Triantafyllou, Georgios; Dincer, Fadime; Filippaios, Andreas; Ko, Byung-Joon; Mantzoros, Christos S.

2016-01-01

Background GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. Basic Procedures Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17 days (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days) of treatment, we also studied changes in fMRI responses to food cues. Main Findings By design, to avoid any confounding by weight changes, subjects were studied for 17 days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control-related thalamus and pre-SMA. Principal Conclusions We demonstrate herein short-term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that would over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials. PMID:27282865

30 CFR 75.1721 - Opening of new underground coal mines, or reopening and reactivating of abandoned or deactivated...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Opening of new underground coal mines, or reopening and reactivating of abandoned or deactivated coal mines, notification by the operator... LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75...

78 FR 9636 - Airworthiness Directives; Cessna Aircraft Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-11

.... We have changed paragraph (k) of the supplemental NPRM (i.e., paragraph (j) of the previous NPRM) to... Limitations, Revision 7, dated April 23, 2012, of the Cessna Model S550 Maintenance Manual. (k) Deactivation..., deactivate the A/C system as specified in paragraph (k)(1), (k)(2), or (k)(3) of this AD, as applicable. (1...

40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

40 CFR Appendix Vi to Part 268 - Recommended Technologies To Achieve Deactivation of Characteristics in Section 268.42

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Pt. 268, App. VI....42 The treatment standard for many characteristic wastes is stated in the § 268.40 Table of Treatment... combination, can achieve the deactivation portion of the treatment standard. Characteristic wastes that are...

The presence of isolated hydrogen donors in heavily carbon-doped GaAs

NASA Astrophysics Data System (ADS)

Fushimi, Hiroshi; Wada, Kazumi

1994-12-01

The deactivation mechanism of carbon acceptors in GaAs has systematically been studied by measuring the annealing behavior and depth profiles of the carrier concentration. It is found that hydrogen impurities dominate carbon deactivation. Their deactivation undergoes two different ways: Hydrogen donors isolated from carbon acceptors compensate carbon and hydrogen impurities neutralize the carbon by forming neutral carbon-hydrogen complexes. The compensating hydrogen donors diffuse out extremely fast at relatively low temperatures. This is, to the best of our knowledge, the first report on the presence of isolated hydrogen donors in heavily carbon-doped GaAs. The dissociation of carbon-hydrogen complexes is much slower than reported. The mechanism is discussed in terms of a hydrogen retrapping effect by carbon.

Unpacking Race, Culture, and Class in Rural Alaska: Native and Non-Native Multidisciplinary Professionals' Perceptions of Child Sexual Abuse

ERIC Educational Resources Information Center

Bubar, Roe; Bundy-Fazioli, Kimberly

2011-01-01

The purpose of this study was to unpack notions of class, culture, and race as they relate to multidisciplinary team (MDT) professionals and their perceptions of prevalence in child sexual abuse cases in Native and non-Native rural Alaska communities. Power and privilege within professional settings is significant for all social work professionals…

Booster Test for Space Launch System Rocket

NASA Image and Video Library

2016-06-26

The test area where the second and final qualification motor (QM-2) test for the Space Launch System’s booster is seen through the window of a camera bunker, Sunday, June 26, 2016, at Orbital ATK Propulsion Systems test facilities in Promontory, Utah. The test is scheduled for Tuesday, June 28 at 10:05 a.m. EDT (8:05 a.m. MDT). Photo Credit: (NASA/Bill Ingalls)

Multiprofessional education to stimulate collaboration: a circular argument and its consequences

PubMed Central

Roodbol, Petrie F.

2010-01-01

The current developments in healthcare are unprecedented. The organization of health care is complex. Collaboration is essential to meet all the healthcare needs of patients and to achieve coordinated and unambiguous information. Multiprofessional education (MPE) or multidisciplinary training (MDT) seems a logical step to stimulate teamwork. However, collaboration and MPE are wrestling with the same problems: social identity and acceptance. PMID:21818197

A Comparison of Two Treatment Studies: CBT and MDT with Adolescent Male Sex Offenders with Reactive Conduct Disorder and/or Personality Traits

ERIC Educational Resources Information Center

Apsche, Jack A.; Bass, Christopher K.; Murphy, Christopher J.

2004-01-01

This paper compares the results of two separate published studies regarding adolescent males with conduct disorders and/or personality disorders/traits. Both studies were published in the Behavior Analyst Today, Vol. 3, No. 4, Vol 5, No. 1, respectively. The concept is to evaluate two treatment research studies that represent "the best" practices…

Physiotherapy movement based classification approaches to low back pain: comparison of subgroups through review and developer/expert survey.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Hodges, Paul W

2012-02-20

Several classification schemes, each with its own philosophy and categorizing method, subgroup low back pain (LBP) patients with the intent to guide treatment. Physiotherapy derived schemes usually have a movement impairment focus, but the extent to which other biological, psychological, and social factors of pain are encompassed requires exploration. Furthermore, within the prevailing 'biological' domain, the overlap of subgrouping strategies within the orthopaedic examination remains unexplored. The aim of this study was "to review and clarify through developer/expert survey, the theoretical basis and content of physical movement classification schemes, determine their relative reliability and similarities/differences, and to consider the extent of incorporation of the bio-psycho-social framework within the schemes". A database search for relevant articles related to LBP and subgrouping or classification was conducted. Five dominant movement-based schemes were identified: Mechanical Diagnosis and Treatment (MDT), Treatment Based Classification (TBC), Pathoanatomic Based Classification (PBC), Movement System Impairment Classification (MSI), and O'Sullivan Classification System (OCS) schemes. Data were extracted and a survey sent to the classification scheme developers/experts to clarify operational criteria, reliability, decision-making, and converging/diverging elements between schemes. Survey results were integrated into the review and approval obtained for accuracy. Considerable diversity exists between schemes in how movement informs subgrouping and in the consideration of broader neurosensory, cognitive, emotional, and behavioural dimensions of LBP. Despite differences in assessment philosophy, a common element lies in their objective to identify a movement pattern related to a pain reduction strategy. Two dominant movement paradigms emerge: (i) loading strategies (MDT, TBC, PBC) aimed at eliciting a phenomenon of centralisation of symptoms; and (ii) modified movement strategies (MSI, OCS) targeted towards documenting the movement impairments associated with the pain state. Schemes vary on: the extent to which loading strategies are pursued; the assessment of movement dysfunction; and advocated treatment approaches. A biomechanical assessment predominates in the majority of schemes (MDT, PBC, MSI), certain psychosocial aspects (fear-avoidance) are considered in the TBC scheme, certain neurophysiologic (central versus peripherally mediated pain states) and psychosocial (cognitive and behavioural) aspects are considered in the OCS scheme.

Magnetic particle capture for biomagnetic fluid flow in stenosed aortic bifurcation considering particle-fluid coupling

NASA Astrophysics Data System (ADS)

Bose, Sayan; Banerjee, Moloy

2015-07-01

Magnetic nanoparticles drug carriers continue to attract considerable interest for drug targeting in the treatment of cancer and other pathological conditions. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the basic principle behind the Magnetic Drug Targeting (MDT). It is essential to couple the ferrohydrodynamic (FHD) and magnetohydrodynamic (MHD) principles when magnetic fields are applied to blood as a biomagnetic fluid. The present study is devoted to study on MDT technique by particle tracking in the presence of a non uniform magnetic field in a stenosed aortic bifurcation. The present numerical model of biomagnetic fluid dynamics (BFD) takes into accounts both magnetization and electrical conductivity of blood. The blood flow in the bifurcation is considered to be incompressible and Newtonian. An Eulerian-Lagrangian technique is adopted to resolve the hemodynamic flow and the motion of the magnetic particles in the flow using ANSYS FLUENT two way particle-fluid coupling. An implantable infinitely long cylindrical current carrying conductor is used to create the requisite magnetic field. Targeted transport of the magnetic particles in a partly occluded vessel differs distinctly from the same in a regular unblocked vessel. Results concerning the velocity and temperature field indicate that the presence of the magnetic field influences the flow field considerably and the disturbances increase as the magnetic field strength increases. The insert position is also varied to observe the variation in flow as well as temperature field. Parametric investigation is conducted and the influence of the particle size (dp), flow Reynolds number (Re) and external magnetic field strength (B0) on the "capture efficiency" (CE) is reported. The difference in CE is also studied for different particle loading condition. According to the results, the magnetic field increased the particle concentration in the target region. Analysis shows that there exists an optimum regime of operating parameters for which deposition of the drug carrying magnetic particles in a target zone on the partly occluded vessel wall can be maximized. The results provide useful design bases for in vitro set up for the investigation of MDT in stenosed blood vessels.

Regional long-term production modeling from a single well test, Mount Elbert Gas Hydrate Stratigraphic Test Well, Alaska North Slope

USGS Publications Warehouse

Anderson, B.J.; Kurihara, M.; White, M.D.; Moridis, G.J.; Wilson, S.J.; Pooladi-Darvish, M.; Gaddipati, M.; Masuda, Y.; Collett, T.S.; Hunter, R.B.; Narita, H.; Rose, K.; Boswell, R.

2011-01-01

Following the results from the open-hole formation pressure response test in the BPXA-DOE-USGS Mount Elbert Gas Hydrate Stratigraphic Test Well (Mount Elbert well) using Schlumberger's Modular Dynamics Formation Tester (MDT) wireline tool, the International Methane Hydrate Reservoir Simulator Code Comparison project performed long-term reservoir simulations on three different model reservoirs. These descriptions were based on 1) the Mount Elbert gas hydrate accumulation as delineated by an extensive history-matching exercise, 2) an estimation of the hydrate accumulation near the Prudhoe Bay L-pad, and 3) a reservoir that would be down-dip of the Prudhoe Bay L-pad and therefore warmer and deeper. All of these simulations were based, in part, on the results of the MDT results from the Mount Elbert Well. The comparison group's consensus value for the initial permeability of the hydrate-filled reservoir (k = 0.12 mD) and the permeability model based on the MDT history match were used as the basis for subsequent simulations on the three regional scenarios. The simulation results of the five different simulation codes, CMG STARS, HydrateResSim, MH-21 HYDRES, STOMP-HYD, and TOUGH+HYDRATE exhibit good qualitative agreement and the variability of potential methane production rates from gas hydrate reservoirs is illustrated. As expected, the predicted methane production rate increased with increasing in situ reservoir temperature; however, a significant delay in the onset of rapid hydrate dissociation is observed for a cold, homogeneous reservoir and it is found to be repeatable. The inclusion of reservoir heterogeneity in the description of this cold reservoir is shown to eliminate this delayed production. Overall, simulations utilized detailed information collected across the Mount Elbert reservoir either obtained or determined from geophysical well logs, including thickness (37 ft), porosity (35%), hydrate saturation (65%), intrinsic permeability (1000 mD), pore water salinity (5 ppt), and formation temperature (3.3-3.9 ??C). This paper presents the approach and results of extrapolating regional forward production modeling from history-matching efforts on the results from a single well test. ?? 2010 Elsevier Ltd.

Patients’ Non-Medical Characteristics Contribute to Collective Medical Decision-Making at Multidisciplinary Oncological Team Meetings

PubMed Central

Restivo, Léa; Apostolidis, Thémis; Bouhnik, Anne-Déborah; Garciaz, Sylvain; Aurran, Thérèse; Julian-Reynier, Claire

2016-01-01

Background The contribution of patients’ non-medical characteristics to individual physicians’ decision-making has attracted considerable attention, but little information is available on this topic in the context of collective decision-making. Medical decision-making at cancer centres is currently carried out using a collective approach, at MultiDisciplinary Team (MDT) meetings. The aim of this study was to determine how patients’ non-medical characteristics are presented at MDT meetings and how this information may affect the team’s final medical decisions. Design Observations were conducted at a French Cancer Centre during MDT meetings at which non-standard cases involving some uncertainty were discussed from March to May 2014. Physicians’ verbal statements and predefined contextual parameters were collected with a non-participant observational approach. Non numerical data collected in the form of open notes were then coded for quantitative analysis. Univariate and multivariate statistical analyses were performed. Results In the final sample of patients’ records included and discussed (N = 290), non-medical characteristics were mentioned in 32.8% (n = 95) of the cases. These characteristics corresponded to demographics in 22.8% (n = 66) of the cases, psychological data in 11.7% (n = 34), and relational data in 6.2% (n = 18). The patient’s age and his/her “likeability” were the most frequently mentioned characteristics. In 17.9% of the cases discussed, the final decision was deferred: this outcome was positively associated with the patients’ non-medical characteristics and with uncertainty about the outcome of the therapeutic options available. Limitations The design of the study made it difficult to draw definite cause-and-effect conclusions. Conclusion The Social Representations approach suggests that patients’ non-medical characteristics constitute a kind of tacit professional knowledge that may be frequently mobilised in physicians’ everyday professional practice. The links observed between patients’ attributes and the medical decisions made at these meetings show that these attributes should be taken into account in order to understand how medical decisions are reached in difficult situations of this kind. PMID:27167521

Regional long-term production modeling from a single well test, Mount Elbert Gas Hydrate Stratigraphic Test Well, Alaska North Slope

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

Anderson, Brian J.; Kurihara, Masanori; White, Mark D.

2011-02-01

Following the results from the open-hole formation pressure response test in the BPXA-DOE-USGS Mount Elbert Gas Hydrate Stratigraphic Test Well (Mount Elbert well) using Schlumberger's Modular Dynamics Formation Tester (MDT) wireline tool, the International Methane Hydrate Reservoir Simulator Code Comparison project performed long-term reservoir simulations on three different model reservoirs. These descriptions were based on 1) the Mount Elbert gas hydrate accumulation as delineated by an extensive history-matching exercise, 2) an estimation of the hydrate accumulation near the Prudhoe Bay L-pad, and 3) a reservoir that would be down-dip of the Prudhoe Bay L-pad and therefore warmer and deeper. Allmore » of these simulations were based, in part, on the results of the MDT results from the Mount Elbert Well. The comparison group's consensus value for the initial permeability of the hydrate-filled reservoir (k = 0.12 mD) and the permeability model based on the MDT history match were used as the basis for subsequent simulations on the three regional scenarios. The simulation results of the five different simulation codes, CMG STARS, HydrateResSim, MH-21 HYDRES, STOMP-HYD, and TOUGH+HYDRATE exhibit good qualitative agreement and the variability of potential methane production rates from gas hydrate reservoirs is illustrated. As expected, the predicted methane production rate increased with increasing in situ reservoir temperature; however, a significant delay in the onset of rapid hydrate dissociation is observed for a cold, homogeneous reservoir and it is found to be repeatable. The inclusion of reservoir heterogeneity in the description of this cold reservoir is shown to eliminate this delayed production. Overall, simulations utilized detailed information collected across the Mount Elbert reservoir either obtained or determined from geophysical well logs, including thickness (37 ft), porosity (35%), hydrate saturation (65%), intrinsic permeability (1000 mD), pore water salinity (5 ppt), and formation temperature (3.3–3.9 °C). Finally, this paper presents the approach and results of extrapolating regional forward production modeling from history-matching efforts on the results from a single well test.« less

Transport and Magnetization in Bad Metals Itinerant Ferromagnets

NASA Astrophysics Data System (ADS)

Klein, Lior

1997-03-01

While much attention has been given to the study of itinerant ferromagnets that are good metals (k_Fl >> 1), very little is known about the transport properties of itinerant ferromagnets in the badly metallic limit (k_Fl= \\cal O ). Here we present our study of the pseudo-cubic perovskite SrRuO3 which is in the limit of k_Fl= \\cal O (1) in its purest form (e.g. single crystals) and is also an itinerant ferromagnet with Tc ~ 160 K. We findfootnote L. Klein, J. S. Dodge, C. H. Ahn, G. J. Snyder, T. H. Geballe, M. R. Beasley, and A. Kapitulnik, Phys. Rev. Lett. 77, 2774 (1996); L. Klein, J. S. Dodge, C. H. Ahn, J. W. Reiner, L. Mieville, T. H.Geballe, M. R. Beasley, and A. Kapitulnik, J. Phys. Condens. Matter 8, 10111 (1996). that while the magnetic properties of SrRuO3 in the paramagnetic phase, near the ferromagnetic phase transition and at low temperatures are normal and similar to those of iron or nickel, the transport properties sharply deviate from those of good metallic ferromagnets: a) As Tarrow T_c^+ the temperature derivative of the magnetic part of the resistivity, dρ _m/dT, diverges with an exponent on the order of 1, an order of magnitude larger than the expected specific heat exponent of ~ 0.1. b) While the critical behavior of dρ _m/dT around Tc is usually found to be symmetric, very weak divergence of dρ _m/dT is observed as Tarrow T_c^-. c) At low temperatures ρ rapidly increases in correlation with the magnetization instead of the usually observed T^2 dependence. d) At T < 4 K for low-residual-resistivity films, and at higher temperatures for high-residual-resistivity films, Kondo-like resistivity minima are observed. We conjecture that the distinct transport behavior of SrRuO3 is related to its being a 'bad metal' in the k_Fl= \\cal O (1) limit, and discuss the possible relevance of our results to the unusual transport properties of other 'bad metals' such as high-temperature superconductors, fullerenes and organic conductors.

Rhythm and Melody Tasks for School-Aged Children With and Without Musical Training: Age-Equivalent Scores and Reliability.

PubMed

Ireland, Kierla; Parker, Averil; Foster, Nicholas; Penhune, Virginia

2018-01-01

Measuring musical abilities in childhood can be challenging. When music training and maturation occur simultaneously, it is difficult to separate the effects of specific experience from age-based changes in cognitive and motor abilities. The goal of this study was to develop age-equivalent scores for two measures of musical ability that could be reliably used with school-aged children (7-13) with and without musical training. The children's Rhythm Synchronization Task (c-RST) and the children's Melody Discrimination Task (c-MDT) were adapted from adult tasks developed and used in our laboratories. The c-RST is a motor task in which children listen and then try to synchronize their taps with the notes of a woodblock rhythm while it plays twice in a row. The c-MDT is a perceptual task in which the child listens to two melodies and decides if the second was the same or different. We administered these tasks to 213 children in music camps (musicians, n = 130) and science camps (non-musicians, n = 83). We also measured children's paced tapping, non-paced tapping, and phonemic discrimination as baseline motor and auditory abilities We estimated internal-consistency reliability for both tasks, and compared children's performance to results from studies with adults. As expected, musically trained children outperformed those without music lessons, scores decreased as difficulty increased, and older children performed the best. Using non-musicians as a reference group, we generated a set of age-based z-scores, and used them to predict task performance with additional years of training. Years of lessons significantly predicted performance on both tasks, over and above the effect of age. We also assessed the relation between musician's scores on music tasks, baseline tasks, auditory working memory, and non-verbal reasoning. Unexpectedly, musician children outperformed non-musicians in two of three baseline tasks. The c-RST and c-MDT fill an important need for researchers interested in evaluating the impact of musical training in longitudinal studies, those interested in comparing the efficacy of different training methods, and for those assessing the impact of training on non-musical cognitive abilities such as language processing.

Rhythm and Melody Tasks for School-Aged Children With and Without Musical Training: Age-Equivalent Scores and Reliability

PubMed Central

Ireland, Kierla; Parker, Averil; Foster, Nicholas; Penhune, Virginia

2018-01-01

Measuring musical abilities in childhood can be challenging. When music training and maturation occur simultaneously, it is difficult to separate the effects of specific experience from age-based changes in cognitive and motor abilities. The goal of this study was to develop age-equivalent scores for two measures of musical ability that could be reliably used with school-aged children (7–13) with and without musical training. The children's Rhythm Synchronization Task (c-RST) and the children's Melody Discrimination Task (c-MDT) were adapted from adult tasks developed and used in our laboratories. The c-RST is a motor task in which children listen and then try to synchronize their taps with the notes of a woodblock rhythm while it plays twice in a row. The c-MDT is a perceptual task in which the child listens to two melodies and decides if the second was the same or different. We administered these tasks to 213 children in music camps (musicians, n = 130) and science camps (non-musicians, n = 83). We also measured children's paced tapping, non-paced tapping, and phonemic discrimination as baseline motor and auditory abilities We estimated internal-consistency reliability for both tasks, and compared children's performance to results from studies with adults. As expected, musically trained children outperformed those without music lessons, scores decreased as difficulty increased, and older children performed the best. Using non-musicians as a reference group, we generated a set of age-based z-scores, and used them to predict task performance with additional years of training. Years of lessons significantly predicted performance on both tasks, over and above the effect of age. We also assessed the relation between musician's scores on music tasks, baseline tasks, auditory working memory, and non-verbal reasoning. Unexpectedly, musician children outperformed non-musicians in two of three baseline tasks. The c-RST and c-MDT fill an important need for researchers interested in evaluating the impact of musical training in longitudinal studies, those interested in comparing the efficacy of different training methods, and for those assessing the impact of training on non-musical cognitive abilities such as language processing. PMID:29674984

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, Ana C; Banca, Paula; Pascoal, Augusto G; Cordeiro, Gustavo; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2018-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used a functional magnetic resonance imaging block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction (n = 20, with balanced left/right lesion sites). Results Analysis of 10 right hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right hemispheric stroke. Left hemispheric stroke was, in general, characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts is novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence.

PubMed

Vidal, A Cristina; Banca, Paula; Pascoal, Augusto G; Santo, Gustavo C; Sargento-Freitas, João; Gouveia, Ana; Castelo-Branco, Miguel

2017-01-01

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.

[Ethics in intensive care and euthanasia : With respect to inactivating defibrillators at the end of life in terminally ill patients].

PubMed

Trappe, H-J

2017-04-01

In critically ill patients, intensive care medical procedures allow diseases to be cured or controlled that were considered incurable many years ago. For patients with terminal heart failure or heart disease with other severe comorbidities (cancer, stroke), the questions whether the deactivation of defibrillators is appropriate or must be regarded as active euthanasia may arise. Notable cases from the author's hospital are analyzed. The literature on the topic euthanasia and basic literature regarding defibrillator therapy are discussed. It is undisputed that patients as part of their self-determination have the right to renounce treatment. Active euthanasia and the thereby deliberate induction of death is prohibited by law in Germany and will be prosecuted. Passive euthanasia is the omission or reduction of possibly life-prolonging treatment measures. Passive euthanasia requires the patient's consent and is legally and ethically permissible. Indirect euthanasia takes into account acceleration of death as a side effect of a medication. Unpunishable assisted suicide ("assisted suicide") is the mere assistance of self-controlled and self-determined death. Assisted suicide is fundamentally not a criminal offense in Germany. Deactivation of a defibrillator is a treatment discontinuation, which is only permitted in accordance with the wishes of the patient. It is not a question of passive or active euthanasia. Involvement of a local ethics committee and/or legal consultation is certainly useful and sometimes also allows previously unrecognized questions to be answered.

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

PubMed

Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

2009-09-01

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

Deactivation kinetics of acid-sensing ion channel 1a are strongly pH-sensitive.

PubMed

MacLean, David M; Jayaraman, Vasanthi

2017-03-21

Acid-sensing ion channels (ASICs) are trimeric cation-selective ion channels activated by protons in the physiological range. Recent reports have revealed that postsynaptically localized ASICs contribute to the excitatory postsynaptic current by responding to the transient acidification of the synaptic cleft that accompanies neurotransmission. In response to such brief acidic transients, both recombinant and native ASICs show extremely rapid deactivation in outside-out patches when jumping from a pH 5 stimulus to a single resting pH of 8. Given that the resting pH of the synaptic cleft is highly dynamic and depends on recent synaptic activity, we explored the kinetics of ASIC1a and 1a/2a heteromers to such brief pH transients over a wider [H + ] range to approximate neuronal conditions better. Surprisingly, the deactivation of ASICs was steeply dependent on the pH, spanning nearly three orders of magnitude from extremely fast (<1 ms) at pH 8 to very slow (>300 ms) at pH 7. This study provides an example of a ligand-gated ion channel whose deactivation is sensitive to agonist concentrations that do not directly activate the receptor. Kinetic simulations and further mutagenesis provide evidence that ASICs show such steeply agonist-dependent deactivation because of strong cooperativity in proton binding. This capacity to signal across such a large synaptically relevant bandwidth enhances the response to small-amplitude acidifications likely to occur at the cleft and may provide ASICs with the ability to shape activity in response to the recent history of the synapse.

Brief and Rare Mental "Breaks" Keep You Focused: Deactivation and Reactivation of Task Goals Preempt Vigilance Decrements

ERIC Educational Resources Information Center

Ariga, Atsunori; Lleras, Alejandro

2011-01-01

We newly propose that the vigilance decrement occurs because the cognitive control system fails to maintain active the goal of the vigilance task over prolonged periods of time (goal habituation). Further, we hypothesized that momentarily deactivating this goal (via a switch in tasks) would prevent the activation level of the vigilance goal from…

Holographic monitoring of spatial distributions of singlet oxygen in water

NASA Astrophysics Data System (ADS)

Belashov, A. V.; Bel'tyukova, D. M.; Vasyutinskii, O. S.; Petrov, N. V.; Semenova, I. V.; Chupov, A. S.

2014-12-01

A method for monitoring spatial distributions of singlet oxygen in biological media has been developed. Singlet oxygen was generated using Radachlorin® photosensitizer, while thermal disturbances caused by nonradiative deactivation of singlet oxygen were detected by the holographic interferometry technique. Processing of interferograms yields temperature maps that characterize the deactivation process and show the distribution of singlet oxygen species.

Gamification of Learning Deactivates the Default Mode Network

PubMed Central

Howard-Jones, Paul A.; Jay, Tim; Mason, Alice; Jones, Harvey

2016-01-01

We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated. PMID:26779054

Ligand-specific Deactivation Time Course of GluN1/GluN2D NMDA Receptors

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

K Vance; N Simorowski; S Traynelis

2011-12-31

N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors that mediate a majority of excitatory synaptic transmission. One unique property of GluN1/GluN2D NMDA receptors is an unusually prolonged deactivation time course following the removal of L-glutamate. Here we show, using x-ray crystallography and electrophysiology, that the deactivation time course of GluN1/GluN2D receptors is influenced by the conformational variability of the ligand-binding domain (LBD) as well as the structure of the activating ligand. L-glutamate and L-CCG-IV induce significantly slower deactivation time courses compared with other agonists. Crystal structures of the isolated GluN2D LBD in complex with various ligands revealmore » that the binding of L-glutamate induces a unique conformation at the backside of the ligand-binding site in proximity to the region at which the transmembrane domain would be located in the intact receptors. These data suggest that the activity of the GluN1/GluN2D NMDA receptor is controlled distinctively by the endogenous neurotransmitter L-glutamate.« less

Gamification of Learning Deactivates the Default Mode Network.

PubMed

Howard-Jones, Paul A; Jay, Tim; Mason, Alice; Jones, Harvey

2015-01-01

We hypothesized that embedding educational learning in a game would improve learning outcomes, with increased engagement and recruitment of cognitive resources evidenced by increased activation of working memory network (WMN) and deactivation of default mode network (DMN) regions. In an fMRI study, we compared activity during periods of learning in three conditions that were increasingly game-like: Study-only (when periods of learning were followed by an exemplar question together with its correct answer), Self-quizzing (when periods of learning were followed by a multiple choice question in return for a fixed number of points) and Game-based (when, following each period of learning, participants competed with a peer to answer the question for escalating, uncertain rewards). DMN hubs deactivated as conditions became more game-like, alongside greater self-reported engagement and, in the Game-based condition, higher learning scores. These changes did not occur with any detectable increase in WMN activity. Additionally, ventral striatal activation was associated with responding to questions and receiving positive question feedback. Results support the significance of DMN deactivation for educational learning, and are aligned with recent evidence suggesting DMN and WMN activity may not always be anti-correlated.

The unrested resting brain: sleep deprivation alters activity within the default-mode network.

PubMed

Gujar, Ninad; Yoo, Seung-Schik; Hu, Peter; Walker, Matthew P

2010-08-01

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and the balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity, findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level.

Availability of the basal planes of graphene oxide determines whether it is antibacterial.

PubMed

Hui, Liwei; Piao, Ji-Gang; Auletta, Jeffrey; Hu, Kan; Zhu, Yanwu; Meyer, Tara; Liu, Haitao; Yang, Lihua

2014-08-13

There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of <1% at 200 μg/mL. Supplementing saline with ≤10% Luria-Bertani (LB) broth, however, progressively deactivated its bactericidal activity depending on LB-supplementation ratio. Supplementation of 10% LB made GO completely inactive; instead, ∼100-fold bacterial growth was observed. Atomic force microscopy images showed that certain LB components were adsorbed on GO basal planes. Using bovine serum albumin and tryptophan as well-defined model adsorbates, we found that noncovalent adsorption on GO basal planes may account for the deactivation of GO's bactericidal activity. Moreover, this deactivation mechanism was shown to be extrapolatable to GO's cytotoxicity against mammalian cells. Taken together, our observations suggest that bare GO intrinsically kills both bacteria and mammalian cells and noncovalent adsorption on its basal planes may be a global deactivation mechanism for GO's cytotoxicity.

Oxidative degradation of silica-supported polyethylenimine for CO2 adsorption: insights into the nature of deactivated species.

PubMed

Ahmadalinezhad, Asieh; Sayari, Abdelhamid

2014-01-28

The oxidative degradation of polyethylenimine-impregnated mesoporous SBA-15 silica for CO2 capture was investigated at the molecular level. The adsorbents were exposed to flowing air at different temperatures, and their degree of deactivation was evaluated through the measurement of CO2 adsorption capacity prior and subsequent to air exposure. A solvent-extraction method was employed to isolate the deactivated species from the silica support. The extracted species were investigated by a variety of 1D and 2D NMR techniques such as (13)C, (1)H, (1)H-(15)N HMBC, (1)H-(13)C HMQC, and (1)H-(13)C HMBC. This in-depth investigation showed that they contain predominantly fragments involving imine and carbonyl groups. Several structural units were conclusively established.

Magnetic nanoparticle-based drug delivery for cancer therapy.

PubMed

Tietze, Rainer; Zaloga, Jan; Unterweger, Harald; Lyer, Stefan; Friedrich, Ralf P; Janko, Christina; Pöttler, Marina; Dürr, Stephan; Alexiou, Christoph

2015-12-18

Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called "magnetic drug targeting", MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting, tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles. Copyright © 2015 Elsevier Inc. All rights reserved.

Variational Data Assimilation for the Global Ocean

DTIC Science & Technology

2013-01-01

ocean includes the Geoid (a fixed gravity equipotential surface ) as well as the MDT, which is not known accurately enough relative to the centimeter...scales, including processes that control the surface mixed layer, the formation of ocean eddies, meandering ocean J.A. Cummings (E3) nography Division...variables. Examples of this in the ocean are integral quantities, such as acous^B travel time and altimeter measures of sea surface height, and direct

Booster Test for Space Launch System Rocket

NASA Image and Video Library

2016-06-26

The quench system arm and nozzle are seen at the test area where the second and final qualification motor (QM-2) test for the Space Launch System’s booster will take place, Sunday, June 26, 2016, at Orbital ATK Propulsion Systems test facilities in Promontory, Utah. The test is scheduled for Tuesday, June 28 at 10:05 a.m. EDT (8:05 a.m. MDT). Photo Credit: (NASA/Bill Ingalls)

Successful strategies in implementing a multidisciplinary team working in the care of patients with cancer: an overview and synthesis of the available literature.

PubMed

Soukup, Tayana; Lamb, Benjamin W; Arora, Sonal; Darzi, Ara; Sevdalis, Nick; Green, James Sa

2018-01-01

In many health care systems globally, cancer care is driven by multidisciplinary cancer teams (MDTs). A large number of studies in the past few years and across different literature have been performed to better understand how these teams work and how they manage patient care. The aim of our literature review is to synthesize current scientific and clinical understanding on cancer MDTs and their organization; this, in turn, should provide an up-to-date summary of the current knowledge that those planning or leading cancer services can use as a guide for service implementation or improvement. We describe the characteristics of an effective MDT and factors that influence how these teams work. A range of factors pertaining to teamwork, availability of patient information, leadership, team and meeting management, and workload can affect how well MDTs are implemented within patient care. We also review how to assess and improve these teams. We present a range of instruments designed to be used with cancer MDTs - including observational tools, self-assessments, and checklists. We conclude with a practical outline of what appears to be the best practices to implement (Dos) and practices to avoid (Don'ts) when setting up MDT-driven cancer care.

Successful strategies in implementing a multidisciplinary team working in the care of patients with cancer: an overview and synthesis of the available literature

PubMed Central

Soukup, Tayana; Lamb, Benjamin W; Arora, Sonal; Darzi, Ara; Sevdalis, Nick; Green, James SA

2018-01-01

In many health care systems globally, cancer care is driven by multidisciplinary cancer teams (MDTs). A large number of studies in the past few years and across different literature have been performed to better understand how these teams work and how they manage patient care. The aim of our literature review is to synthesize current scientific and clinical understanding on cancer MDTs and their organization; this, in turn, should provide an up-to-date summary of the current knowledge that those planning or leading cancer services can use as a guide for service implementation or improvement. We describe the characteristics of an effective MDT and factors that influence how these teams work. A range of factors pertaining to teamwork, availability of patient information, leadership, team and meeting management, and workload can affect how well MDTs are implemented within patient care. We also review how to assess and improve these teams. We present a range of instruments designed to be used with cancer MDTs – including observational tools, self-assessments, and checklists. We conclude with a practical outline of what appears to be the best practices to implement (Dos) and practices to avoid (Don’ts) when setting up MDT-driven cancer care. PMID:29403284

Psychological Features and Their Relationship to Movement-Based Subgroups in People Living With Low Back Pain.

PubMed

Karayannis, Nicholas V; Jull, Gwendolen A; Nicholas, Michael K; Hodges, Paul W

2018-01-01

To determine the distribution of higher psychological risk features within movement-based subgroups for people with low back pain (LBP). Cross-sectional observational study. Participants were recruited from physiotherapy clinics and community advertisements. Measures were collected at a university outpatient-based physiotherapy clinic. People (N=102) seeking treatment for LBP. Participants were subgrouped according to 3 classification schemes: Mechanical Diagnosis and Treatment (MDT), Treatment-Based Classification (TBC), and O'Sullivan Classification (OSC). Questionnaires were used to categorize low-, medium-, and high-risk features based on depression, anxiety, and stress (Depression, Anxiety, and Stress Scale-21 Items); fear avoidance (Fear-Avoidance Beliefs Questionnaire); catastrophizing and coping (Pain-Related Self-Symptoms Scale); and self-efficacy (Pain Self-Efficacy Questionnaire). Psychological risk profiles were compared between movement-based subgroups within each scheme. Scores across all questionnaires revealed that most patients had low psychological risk profiles, but there were instances of higher (range, 1%-25%) risk profiles within questionnaire components. The small proportion of individuals with higher psychological risk scores were distributed between subgroups across TBC, MDT, and OSC schemes. Movement-based subgrouping alone cannot inform on individuals with higher psychological risk features. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Plasma Deactivation of Oral Bacteria Seeded on Hydroxyapatite Disks as Tooth Enamel Analogue

PubMed Central

Blumhagen, Adam; Singh, Prashant; Mustapha, Azlin; Chen, Meng; Wang, Yong; Yu, Qingsong

2014-01-01

Purpose To study the plasma treatment effects on deactivation of oral bacteria seeded on a tooth enamel analogue. Methods A non-thermal atmospheric pressure argon plasma brush was used to treat two different Gram-positive oral bacteria including Lactobacillus acidophilus (L. acidophilus) and Streptococcus mutans (S. mutans). The bacteria were seeded on hydroxyapatite (HA) disks used as tooth enamel analogue with three initial bacterial seeding concentrations: a low inoculum concentration between 2.1×108 and 2.4×108 cfu/mL, a medium inoculum concentration between 9.8×108 and 2.4×109 cfu/mL, and a high inoculum concentration between 1.7×1010 and 3.5×1010 cfu/mL. The bacterial survivability upon plasma exposure was examined in terms of plasma exposure time and oxygen addition into the plasmas. SEM was performed to examine bacterial morphological changes after plasma exposure. Results The experimental data indicated that 13 second plasma exposure time completely killed all the bacteria when initial bacterial seeding density on HA surfaces were less than 6.9×106 cfu/cm2 for L. acidophilus and 1.7×107 cfu/cm2 for S. mutans, which were resulted from low initial seeding inoculum concentration between 2.1×108 and 2.4×108 cfu/mL. Plasma exposure of the bacteria at higher initial bacterial seeding density obtained with high initial seeding inoculum concentration, however, only resulted in ~ 1.5 to 2 log reduction and ~ 2 to 2.5 log reduction for L. acidophilus and S. mutans, respectively. It was also noted that oxygen addition into the argon plasma brush did not affect the plasma deactivation effectiveness. SEM images showed that plasma deactivation mainly occurred with the top layer bacteria, while shadowing effects from the resulting bacterial debris reduced the plasma deactivation of the underlying bacteria. Clinical Significance The experimental results indicate that, with direct contact, nonthermal atmospheric pressure argon plasmas could rapidly and effectively deactivate oral bacteria seeded on HA surfaces and thus could be a promising technique in various dental clinical applications. PMID:25000666

Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution.

PubMed

Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

2011-01-01

The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.

Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

PubMed

Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

2013-12-01

Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

Mechanism of acetaldehyde-induced deactivation of microbial lipases

PubMed Central

2011-01-01

Background Microbial lipases represent the most important class of biocatalysts used for a wealth of applications in organic synthesis. An often applied reaction is the lipase-catalyzed transesterification of vinyl esters and alcohols resulting in the formation of acetaldehyde which is known to deactivate microbial lipases, presumably by structural changes caused by initial Schiff-base formation at solvent accessible lysine residues. Previous studies showed that several lipases were sensitive toward acetaldehyde deactivation whereas others were insensitive; however, a general explanation of the acetaldehyde-induced inactivation mechanism is missing. Results Based on five microbial lipases from Candida rugosa, Rhizopus oryzae, Pseudomonas fluorescens and Bacillus subtilis we demonstrate that the protonation state of lysine ε-amino groups is decisive for their sensitivity toward acetaldehyde. Analysis of the diverse modification products of Bacillus subtilis lipases in the presence of acetaldehyde revealed several stable products such as α,β-unsaturated polyenals, which result from base and/or amino acid catalyzed aldol condensation of acetaldehyde. Our studies indicate that these products induce the formation of stable Michael-adducts at solvent-accessible amino acids and thus lead to enzyme deactivation. Further, our results indicate Schiff-base formation with acetaldehyde to be involved in crosslinking of lipase molecules. Conclusions Differences in stability observed with various commercially available microbial lipases most probably result from different purification procedures carried out by the respective manufacturers. We observed that the pH of the buffer used prior to lyophilization of the enzyme sample is of utmost importance. The mechanism of acetaldehyde-induced deactivation of microbial lipases involves the generation of α,β-unsaturated polyenals from acetaldehyde which subsequently form stable Michael-adducts with the enzymes. Lyophilization of the enzymes from buffer at pH 6.0 can provide an easy and effective way to stabilize lipases toward inactivation by acetaldehyde. PMID:21342514

Anterior Medial Prefrontal Cortex Exhibits Activation during Task Preparation but Deactivation during Task Execution

PubMed Central

Koshino, Hideya; Minamoto, Takehiro; Ikeda, Takashi; Osaka, Mariko; Otsuka, Yuki; Osaka, Naoyuki

2011-01-01

Background The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task. Methodology/Principal Findings Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial. Conclusions/Significance The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing. PMID:21829668

The S4–S5 Linker Acts as a Signal Integrator for hERG K+ Channel Activation and Deactivation Gating

PubMed Central

Ng, Chai Ann; Perry, Matthew D.; Tan, Peter S.; Hill, Adam P.; Kuchel, Philip W.; Vandenberg, Jamie I.

2012-01-01

Human ether-à-go-go-related gene (hERG) K+ channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel. PMID:22359612

Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti-fibrosis effect by inhibition of mammalian target of rapamycin.

PubMed

Shi, Hongbo; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

2017-03-01

A previous study has demonstrated that Ganshuang granule (GSG) plays an anti-fibrotic role partially by deactivation of hepatic stellate cells (HSCs). In HSCs activation, mammalian target of rapamycin (mTOR)-autophagy plays an important role. We attempted to investigate the role of mTOR-autophagy in anti-fibrotic effect of GSG. The cirrhotic mouse model was prepared to demonstrate the anti-fibrosis effect of GSG. High performance liquid chromatography (HPLC) analyses were used to identify the active component of GSG. The primary mouse HSCs were isolated and naringin was added into activated HSCs to observe its anti-fibrotic effect. 3-methyladenine (3-MA) and Insulin-like growth factor-1 (IGF-1) was added, respectively, into fully activated HSCs to explore the role of autophagy and mTOR. GSG played an anti-fibrotic role through deactivation of HSCs in cirrhotic mouse model. The concentration of naringin was highest in GSG by HPLC analyses and naringin markedly suppressed HSCs activation in vitro, which suggested that naringin was the main active component of GSG. The deactivation of HSCs caused by naringin was not because of the autophagic activation but mTOR inhibition, which was supported by the following evidence: first, naringin induced autophagic activation, but when autophagy was blocked by 3-MA, deactivation of HSCs was not attenuated or reversed. Second, naringin inhibited mTOR pathway, meanwhile when mTOR was activated by IGF-1, deactivation of HSCs was reversed. In conclusion, we have demonstrated naringin in GSG suppressed activation of HSCs for anti-fibrosis effect by inhibition of mTOR, indicating a potential therapeutic application for liver cirrhosis. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

17β-estradiol rapidly facilitates lordosis through G protein-coupled estrogen receptor 1 (GPER) via deactivation of medial preoptic nucleus μ-opioid receptors in estradiol primed female rats.

PubMed

Long, Nathan; Serey, Chhorvann; Sinchak, Kevin

2014-09-01

In female rats sexual receptivity (lordosis) can be induced with either a single large dose of estradiol benzoate (EB), or a priming dose of EB that does not induce sexual receptivity followed by 17β-estradiol (E2). Estradiol priming initially inhibits lordosis through a multi-synaptic circuit originating in the arcuate nucleus of the hypothalamus (ARH) that activates and internalizes μ-opioid receptors (MOR) in medial preoptic nucleus (MPN) neurons. Lordosis is facilitated when MPN MOR are deactivated after the initial estradiol-induced activation. We tested the hypothesis that E2 given 47.5 h post EB acts rapidly through G protein-coupled estrogen receptor 1 (GPER) in the ARH to deactivate MPN MOR and facilitate lordosis. Ovariectomized Long Evans rats implanted with a third ventricle cannula were primed with 2 μg EB. DMSO control, E2, or G1 (GPER selective agonist) was infused 47.5 h later, and rats were tested for sexual receptivity. E2 and G1 infusions significantly increased levels of sexual receptivity compared to DMSO controls and pretreatment with G15 (GPER antagonist) blocked the facilitation of sexual receptivity. Brains were processed for MPN MOR immunohistochemistry to measure MPN MOR activation levels. E2 and G1 both significantly reduced MPN MOR activation compared to DMSO controls, while pretreatment with G15 blocked MPN MOR deactivation. In another group of EB treated ovariectomized rats, GPER immunofluorescence positive staining was observed throughout the ARH. Together these data indicate that in the 2 μg EB primed rat, E2 rapidly signals through GPER in the ARH to deactivate MPN MOR and facilitate lordosis. Published by Elsevier Inc.

Safe and Effective Deactivation of Metallic Sodium Filled Scrap and Cold Traps From Sodium-cooled Nuclear Reactor D and D - 12176

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

Nester, Dean; Crocker, Ben; Smart, Bill

2012-07-01

As part of the Plateau Remediation Project at US Department of Energy's Hanford, Washington site, CH2M Hill Plateau Remediation Company (CHPRC) contracted with IMPACT Services, LLC to receive and deactivate approximately 28 cubic meters of sodium metal contaminated debris from two sodium-cooled research reactors (Enrico Fermi Unit 1 and the Fast Flux Test Facility) which had been stored at Hanford for over 25 years. CHPRC found an off-site team composed of IMPACT Services and Commodore Advanced Sciences, Inc., with the facilities and technological capabilities to safely and effectively perform deactivation of this sodium metal contaminated debris. IMPACT Services provided themore » licensed fixed facility and the logistical support required to receive, store, and manage the waste materials before treatment, and the characterization, manifesting, and return shipping of the cleaned material after treatment. They also provided a recycle outlet for the liquid sodium hydroxide byproduct resulting from removal of the sodium from reactor parts. Commodore Advanced Sciences, Inc. mobilized their patented AMANDA unit to the IMPACT Services site and operated the unit to perform the sodium removal process. Approximately 816 Kg of metallic sodium were removed and converted to sodium hydroxide, and the project was accomplished in 107 days, from receipt of the first shipment at the IMPACT Services facility to the last outgoing shipment of deactivated scrap metal. There were no safety incidents of any kind during the performance of this project. The AMANDA process has been demonstrated in this project to be both safe and effective for deactivation of sodium and NaK. It has also been used in other venues to treat other highly reactive alkali metals, such as lithium (Li), potassium (K), NaK and Cesium (Cs). (authors)« less

Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase.

PubMed

Duan, Wenjuan; Zhou, Juefei; Li, Wei; Zhou, Teng; Chen, Qianqian; Yang, Fuyu; Wei, Taotao

2013-04-01

The activation and deactivation of Ca(2+)- and calmodulindependent neuronal nitric oxide synthase (nNOS) in the central nervous system must be tightly controlled to prevent excessive nitric oxide (NO) generation. Considering plasma membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present investigation aims to determine the key events involved in nNOS deactivation of by PMCA in living cells to maintain its cellular context. Using time-resolved Förster resonance energy transfer (FRET), we determined the occurrence of Ca(2+)-induced protein-protein interactions between plasma membrane calcium ATPase 4b (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the intracellular Ca(2+) concentrations ([Ca(2+)]i), which deactivates nNOS and slowdowns NO synthesis. Under the basal [Ca(2+)]i caused by PMCA activation, no protein-protein interactions were observed between PMCA4b and nNOS. Furthermore, both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential for the protein-protein interaction. The involvement of lipid raft microdomains on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA isoforms, PMCA4 was relatively more concentrated in the raft fractions. Disruption of lipid rafts altered the intracellular localization of PMCA4b and affected the interaction between PMCA4b and nNOS, which suggest that the unique lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for rapid nNOS deactivation.

Comparison of mounting methods for the evaluation of fibers by phase contrast microscopy.

PubMed

Lee, Eun Gyung; Pang, Thomas W S; Nelson, John; Andrew, Mike; Harper, Martin

2011-07-01

The objectives of this study were to evaluate mounting methods for fiber examination of air sample filters by phase contrast microscopy (PCM) and to evaluate differences in fiber counts that might be due to fiber movement. Acetone/triacetin (AT) with various amounts of triacetin and acetone/Euparal (AE) where the mounting medium was placed between the cleared filter wedge and the coverslip were tested as a function of time. Field sample slides collected from a taconite iron-ore processing mill, a tremolitic talc-ore processing mill, and from around a crusher in a meta-basalt stone quarry were prepared with relocatable coverslips to revisit the same field areas on the slides. For each slide, three or four field areas were randomly selected and pictures were taken every 2 weeks to determine any sign of fiber movement over time. For 11 AT slides (named as AT-3.5) prepared with 3.5 μl of the mounting medium according to the NIOSH 7400 method, no fiber movements were detected over 59 weeks. On the other hand, AT slides prepared with larger quantities (10, 15, and 20 μl) of the mounting medium (named as AT-10) and AE slides prepared with ∼10 μl mounting medium showed fiber movement from the eighth day at the earliest. Fiber movement began earlier for the slides mounted with excess triacetin than for those mounted with Euparal. The sample slide storage method, either vertically or horizontally, did not seem to accelerate fiber movement. Additionally, two other modified methods, dimethylformamide solution/Euparal (mDE) and dimethylformamide solution/triacetin (mDT), were also prepared where the mounting medium was placed between the cleared filter wedge and the glass slide. The findings of fiber movements were similar; when 3.5 μl of triacetin was used for the mDT slides, fiber movements were not detected, while fibers on slides prepared with 10 μl triacetin (mDT-10) moved around. No fiber movements were observed for the mDE slides at any time during 59 weeks. Once fiber movement started, fibers moved over distances measured from 4 μm and up to >1000 μm within 22 weeks. However, since then, no further fiber movements have been observed in any field sample slides. Additional sample slides, two Amosite and two chrysotile, were prepared from Union for International Cancer Control (UICC) samples using the AT method with 5 μl triacetin mounting medium. Fiber movements were also observed in these samples; chrysotile fibers began to migrate in 3 weeks, while Amosite fiber movement started after 3 months. Although fiber movement was observed for the AT-10, AE, and mDT-10 sample slides, fiber counts were not significantly different from AT-3.5 and mDE samples that exhibited no fiber movement. Although fiber counts would not be significantly changed by fiber movement, the type and amount of mounting medium for sample slide preparation remains critical for issues such as quality assurance and training of analysts by revisiting the same fibers.

Kinetic deuterium isotope effects in glucocorticoid receptor activation

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

Aranyi, P.

1984-01-01

Activation and deactivation of the chick thymus glucocorticoid receptor protein was studied in ordinary and heavy water by DNA-cellulose binding of the tritiated triamcinolone acetonide-receptor complex. Activation was significantly slower in heavy water if it was promoted by incubation at elevated temperature in buffers of low ionic strength. In the presence of 300 mM KC1 or after separation from the low molecular weight cytosol constituents, the complex was activated at the same rate in both solvents. Deactivation (time dependent loss of DNA-binding capacity) was much faster in ordinary than in heavy water regardless of gel filtration or the presence ofmore » KC1. A model of receptor activation-deactivation was constructed on the basis of these data that accounts for the observed kinetic deuterium isotope effects and reveals some submolecular details of the process.« less

Photosensitized singlet oxygen luminescence from the protein matrix of Zn-substituted myoglobin.

PubMed

Lepeshkevich, Sergei V; Parkhats, Marina V; Stasheuski, Alexander S; Britikov, Vladimir V; Jarnikova, Ekaterina S; Usanov, Sergey A; Dzhagarov, Boris M

2014-03-13

A nanosecond laser near-infrared spectrometer was used to study singlet oxygen ((1)O2) emission in a protein matrix. Myoglobin in which the intact heme is substituted by Zn-protoporphyrin IX (ZnPP) was employed. Every collision of ground state molecular oxygen with ZnPP in the excited triplet state results in (1)O2 generation within the protein matrix. The quantum yield of (1)O2 generation was found to be equal to 0.9 ± 0.1. On the average, six from every 10 (1)O2 molecules succeed in escaping from the protein matrix into the solvent. A kinetic model for (1)O2 generation within the protein matrix and for a subsequent (1)O2 deactivation was introduced and discussed. Rate constants for radiative and nonradiative (1)O2 deactivation within the protein were determined. The first-order radiative rate constant for (1)O2 deactivation within the protein was found to be 8.1 ± 1.3 times larger than the one in aqueous solutions, indicating the strong influence of the protein matrix on the radiative (1)O2 deactivation. Collisions of singlet oxygen with each protein amino acid and ZnPP were assumed to contribute independently to the observed radiative as well as nonradiative rate constants.

Modification of a three-way catalyst washcoat by aging: A study along the longitudinal axis

NASA Astrophysics Data System (ADS)

Granados, M. López; Galisteo, F. Cabello; Mariscal, R.; Alifanti, M.; Gurbani, A.; Fierro, J. L. G.; Fernández-Ruíz, R.

2006-10-01

This work reports the research carried out by studying aliquots extracted at different axial coordinates from Three Way Catalyst (TWC) monoliths aged under real traffic conditions. Our study focused on the catalytic properties and on several chemical and physical effects caused in the Front and Rear monolith washcoat surfaces by vehicle aging after 60,000 km. Regarding the catalytic properties, all the used aliquots showed poorer activity than their corresponding fresh counterparts. The strongest deactivation was detected for NO and hydrocarbon conversion. CO conversion was less affected and the Rear monolith was as deactivated as the Front one. The characterisation techniques (TXRF, N 2 adsorption-desorption isotherms, XRD and H 2-TPR) detected - (i) the deposition of P, Zn and Pb; (ii) the formation of CePO 4 on account of the Ce from the washcoat; (iii) thermal sintering; (iv) inhibition of the reducibility of Ce oxides - as the main effects brought about by vehicle aging conditions. The deactivation observed at the beginning of the Front monolith was the result of a combination of the former effects. When moving downstream to higher axial coordinates, Pb accumulation and the loss of specific area appeared to be the only probable sources of deactivation.

Rapid localized deactivation of self-assembled monolayers by propagation-controlled laser-induced plasma and its application to self-patterning of electronics and biosensors

NASA Astrophysics Data System (ADS)

Kim, Jongsu; Kwon, Seung-Gab; Back, Seunghyun; Kang, Bongchul

2018-03-01

We present a novel laser-induced surface treatment process to rapidly control the spatial wettabilities of various functional solutions with submicron to micron resolutions. Ultrathin hydrophobic self-assembled monolayers (SAMs) that little absorb typical laser lights due to short penetration depth were selectively deactivated by instantaneous interaction with laser-induced metallic plasmas. The spatial region of the deactivated SAM, which corresponds to process resolution, is adjustable by controlling the spatial propagation of the plasma. This method leads to the parallel formation of hydrophilic functional solutions on glass substrates with a minimum resolution on the submicron scale. To show its feasibility in device engineering fields, this method was applied to the cost-effective fabrication of electronics and biosensors. Rapid self-patterning of electronic and biological functional solutions (silver nanoparticle solution and streptavidin protein solution) was successfully realized by selective deactivation of two different SAMs (tridecafluoro-1,1,2,2-tetrahydrooctyltrichlorosilane (FOTS) for electronics and the hetero-hybrid SAM (octadecyltrichlorosilane (OTS)/2-[methoxy(polyethyleneoxy)propyl] trichlorosilane (PEG)) for biosensors). As a result, this method can be exploited for the rapid and low-cost fabrication of various thin film devices such as electronics, biosensors, energy, displays, and photonics.

Receiving and use of streams of monodisperse ice granules for cleaning and deactivation of surfaces

NASA Astrophysics Data System (ADS)

Boukharov, A.; Balashov, A.; Timohin, A.; Ivanov, A.; Holin, B.

2017-11-01

The most generally useful methods for cleaning and processing of surfaces are the sand-jets and shot blasting jets. Installations of this kind are used for cleaning of corrosion surfaces, the oil-dirt deposits, paint coatings. However the use of these installations follows to high investment and operational expenditure, larger risk of operators disease, the negative affect for a environment. These problems can be solved with the use of new cleaning method through application of mono-disperse (identical by the size and the form) ice granules of 300 - 1000 microns, accelerated by air stream in the nozzle device to the speed of 10 - 100 m/s. In view of the extreme complexity of the receiving such particles by means of cooling and the subsequent freezing of water drops are necessary additional experimental researches. For study of thermal processes of receiving mono-disperse ice granules the experimental installation was created and experiments on deactivation and cleaning of surfaces with pollution of various types are made. Experiments showed that by means of a stream of the accelerated ice granules it is rather successfully possible to delete oil-dirt deposits, outdated paint coats and rust. Besides, efficient deactivation of radioactive surfaces is possible. The coefficient deactivation of γ activity is highest.

Ionic liquids as silica deactivating agents in gas chromatography for direct analysis of primary amines in water.

PubMed

Krzyżaniak, Agnieszka; Weggemans, Wilko; Schuur, Boelo; de Haan, André B

2011-12-16

Analysis of primary amines in aqueous samples remains a challenging analytical issue. The preferred approach by gas chromatography is hampered by interactions of free silanol groups with the highly reactive amine groups, resulting in inconsistent measurements. Here, we report a method for direct analysis of aliphatic amines and diamines in aqueous samples by gas chromatography (GC) with silanol deactivation using ionic liquids (ILs). ILs including trihexyl(tetradecyl)phosphonium bis 2,4,4-(trimethylpentyl)phosphinate (Cyphos IL-104), 1-methyl-3-propylimidazolium bis(trifluoromethylsulfonyl)imide [pmim][Tf(2)N] and N″-ethyl-N,N,N',N'-tetramethylguanidinium tris(pentafluoroethyl)trifluorophosphate [etmg][FAP] were tested as deactivating media for the GC liner. Solutions of these ILs in methanol were injected in the system prior to the analysis of primary amines. Butane-1,4-diamine (putrescine, BDA) was used as a reference amine. The best results were obtained using the imidazolium IL [pmim][Tf(2)N]. With this deactivator, excellent reproducibility of the analysis was achieved, and the detection limit of BDA was as low as 1mM. The applicability of the method was proven for the analysis of two different primary amines (C4-C5) and pentane-1,5-diamine. Copyright © 2011 Elsevier B.V. All rights reserved.

Inter-costal Liver Ablation Under Real Time MR-Thermometry With Partial Activation Of A HIFU Phased Array Transducer

NASA Astrophysics Data System (ADS)

Quesson, Bruno; Merle, Mathilde; Köhler, Max; Mougenot, Charles; Roujol, Sebastien; de Senneville, Baudouin Denis; Moonen, Chrit

2010-03-01

HIFU ablation of tumours located inside the liver is hampered by the rib cage, which partially obstructs the beam path and may create adverse effects such as skin burns. This study presents a method for selectively deactivating the transducer elements causing undesired temperature increases near the bones. A manual segmentation of the bones visualized on 3D anatomical MR images acquired prior to sonication was performed to identify the beam obstruction. The resulting mask was projected (ray tracing starting from the focal point) on the transducer and elements with more than 50% obstruction of their active surface were deactivated. The effectiveness of the method for HIFU ablations is demonstrated ex vivo and in vivo in the liver of pigs with real-time MR thermometry, using the proton resonant frequency (PRF) method. For both ex vivo and in vivo experiments, the temperature increase near the bones was significantly reduced when the elements located in front of the ribs were deactivated. The temperature evolution at the focal point were similar, indicative of the absence of loss of heating efficacy when the elements were deactivated. This method is simple, rapid and reliable and allows to perform intercostal MRgHIFU ablation of the liver while sparing the ribs.

Reversible deactivation of higher-order posterior parietal areas. I. Alterations of receptive field characteristics in early stages of neocortical processing

PubMed Central

Cooke, Dylan F.; Goldring, Adam B.; Baldwin, Mary K. L.; Recanzone, Gregg H.; Chen, Arnold; Pan, Tingrui; Simon, Scott I.

2014-01-01

Somatosensory processing in the anesthetized macaque monkey was examined by reversibly deactivating posterior parietal areas 5L and 7b and motor/premotor cortex (M1/PM) with microfluidic thermal regulators developed by our laboratories. We examined changes in receptive field size and configuration for neurons in areas 1 and 2 that occurred during and after cooling deactivation. Together the deactivated fields and areas 1 and 2 form part of a network for reaching and grasping in human and nonhuman primates. Cooling area 7b had a dramatic effect on receptive field size for neurons in areas 1 and 2, while cooling area 5 had moderate effects and cooling M1/PM had little effect. Specifically, cooling discrete locations in 7b resulted in expansions of the receptive fields for neurons in areas 1 and 2 that were greater in magnitude and occurred in a higher proportion of sites than similar changes evoked by cooling the other fields. At some sites, the neural receptive field returned to the precooling configuration within 5–22 min of rewarming, but at other sites changes in receptive fields persisted. These results indicate that there are profound top-down influences on sensory processing of early cortical areas in the somatosensory cortex. PMID:25143546

Towards a Delamination Fatigue Methodology for Composite Materials

NASA Technical Reports Server (NTRS)

OBrien, Thomas K.

2007-01-01

A methodology that accounts for both delaminaton onset and growth in composite structural components is proposed for improved fatigue life prediction to reduce life cycle costs and improve accept/reject criteria for manufacturing flaws. The benefits of using a Delamination Onset Threshold (DOT) approach in combination with a Modified Damage Tolerance (MDT) approach is highlighted. The use of this combined approach to establish accept/reject criteria, requiring less conservative initial manufacturing flaw sizes, is illustrated.

Implications of Subliminal Classical Conditioning for Defeating the Use of Countermeasures in the Detection of Deception: Subliminal Evaluation

DTIC Science & Technology

1993-08-01

presented emotional stimuli than for subliminally presented neutral stimuli. Emotional stimuli consisted of sexually charged photographs, and the neutral...behavior. In addition to research using visual stimuli, some 13 studies have been conducted using subliminal (masked by 40 dB white noise) auditory ...deactivating suggestions masked by a 40-dB white noise signal. For the deactivating subliminal auditory messages, suggestions of heaviness and warmth

Highly catalytic asymmetric addition of deactivated alkyl grignard reagents to aldehydes.

PubMed

Da, Chao-Shan; Wang, Jun-Rui; Yin, Xiao-Gang; Fan, Xin-Yuan; Liu, Yi; Yu, Sheng-Li

2009-12-17

Generally used and highly reactive RMgBr reagents were effectively deactivated by bis[2-(N,N-dimethylamino)ethyl] ether and then were employed in the highly enantioselective addition of Grignard reagents to aldehydes. The reaction was catalyzed by the complex of commercially available (S)-BINOL and Ti(O(i-)Pr)(4) under mild conditions. Compared with the other observed Grignard reagents, alkyl Grignard reagents showed higher enantioselectivity and they achieved >99% ee.

Boosting functionality of synthetic DNA circuits with tailored deactivation

PubMed Central

Montagne, Kevin; Gines, Guillaume; Fujii, Teruo; Rondelez, Yannick

2016-01-01

Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems. The function of molecular circuits is deeply related to their topological structure, but dynamical features (rate laws) also play a critical role. Here we introduce a mechanism to tune the nonlinearities associated with individual nodes of a synthetic network. This mechanism is based on programming deactivation laws using dedicated saturable pathways. We demonstrate this approach through the conversion of a single-node homoeostatic network into a bistable and reversible switch. Furthermore, we prove its generality by adding new functions to the library of reported man-made molecular devices: a system with three addressable bits of memory, and the first DNA-encoded excitable circuit. Specific saturable deactivation pathways thus greatly enrich the functional capability of a given circuit topology. PMID:27845324

Age-related increase in brain activity during task-related and -negative networks and numerical inductive reasoning.

PubMed

Sun, Li; Liang, Peipeng; Jia, Xiuqin; Qi, Zhigang; Li, Kuncheng

2014-01-01

Recent neuroimaging studies have shown that elderly adults exhibit increased and decreased activation on various cognitive tasks, yet little is known about age-related changes in inductive reasoning. To investigate the neural basis for the aging effect on inductive reasoning, 15 young and 15 elderly subjects performed numerical inductive reasoning while in a magnetic resonance (MR) scanner. Functional magnetic resonance imaging (fMRI) analysis revealed that numerical inductive reasoning, relative to rest, yielded multiple frontal, temporal, parietal, and some subcortical area activations for both age groups. In addition, the younger participants showed significant regions of task-induced deactivation, while no deactivation occurred in the elderly adults. Direct group comparisons showed that elderly adults exhibited greater activity in regions of task-related activation and areas showing task-induced deactivation (TID) in the younger group. Our findings suggest an age-related deficiency in neural function and resource allocation during inductive reasoning.

AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate.

PubMed

Partin, K M; Fleck, M W; Mayer, M L

1996-11-01

AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate. Point mutations from Ser to Asn, Ala, Asp, Gly, Gln, Met, Cys, Thr, Leu, Val, and Tyr were constructed in GluRAflip. The last four of these mutants were not functional; S750D was active only in the presence of cyclothiazide, and the remaining mutants exhibited altered rates of deactivation and desensitization for control responses to glutamate, and showed differential modulation by cyclothiazide and aniracetam. Results from kinetic analysis are consistent with aniracetam and cyclothiazide acting via distinct mechanisms. Our experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3-M4 extracellular loop.

Kinetic model of 1,3-specific triacylglycerols alcoholysis catalyzed by lipases.

PubMed

Pilarek, Maciej; Szewczyk, Krzysztof W

2007-01-20

A new model of enzymatic 1,3-specific alcoholysis of triacylglycerols has been developed. The irreversibility of the acyl bounds cleavage in glycerides, a reversible monoglycerides isomerization and an irreversible enzyme deactivation have been assumed. The Ping Pong Bi Bi mechanism with competitive inhibition by alcohol has been applied to describe rates of acyl bonds cleavage. The enzymatic propanolysis and iso-propanolysis of triacetin and tricaprylin catalyzed by immobilized lipase B from Candida antarctica (Novozym 435) have been investigated to verify the model. Good agreement between experimental data and calculations has been obtained. It was shown that the rate of tricaprylin alcoholysis is higher than the triacetin alcoholysis and that the rate of iso-propanolysis reactions are higher than propanolysis. The irreversible enzyme deactivation affects the conversion of glycerides whereas the competitive alcohol inhibition may be neglected. Empirical correlations of rates for monoglycerides isomerization and enzyme deactivation have been proposed.

Epidemics in Adaptive Social Networks with Temporary Link Deactivation

NASA Astrophysics Data System (ADS)

Tunc, Ilker; Shkarayev, Maxim S.; Shaw, Leah B.

2013-04-01

Disease spread in a society depends on the topology of the network of social contacts. Moreover, individuals may respond to the epidemic by adapting their contacts to reduce the risk of infection, thus changing the network structure and affecting future disease spread. We propose an adaptation mechanism where healthy individuals may choose to temporarily deactivate their contacts with sick individuals, allowing reactivation once both individuals are healthy. We develop a mean-field description of this system and find two distinct regimes: slow network dynamics, where the adaptation mechanism simply reduces the effective number of contacts per individual, and fast network dynamics, where more efficient adaptation reduces the spread of disease by targeting dangerous connections. Analysis of the bifurcation structure is supported by numerical simulations of disease spread on an adaptive network. The system displays a single parameter-dependent stable steady state and non-monotonic dependence of connectivity on link deactivation rate.

Effect of phenolic compounds from pretreated sugarcane bagasse on cellulolytic and hemicellulolytic activities.

PubMed

Michelin, Michele; Ximenes, Eduardo; de Lourdes Teixeira de Moraes Polizeli, Maria; Ladisch, Michael R

2016-01-01

This work shows both cellulases and hemicellulases are inhibited and deactivated by water-soluble and acetone extracted phenolics from sugarcane bagasse pretreated at 10% (w/v) for 30 min in liquid hot water at 180 or 200°C. The dissolved phenolics in vacuum filtrate increased from 1.4 to 2.4 g/L as temperature increased from 180 to 200°C. The suppression of cellulose and hemicellulose hydrolysis by phenolics is dominated by deactivation of the β-glucosidase or β-xylosidase components of cellulase and hemicellulase enzyme by acetone extract at 0.2-0.65 mg phenolics/mg enzyme protein and deactivation of cellulases and hemicellulases by the water soluble components in vacuum filtrate at 0.05-2mg/mg. Inhibition was a function of the type of enzyme and the manner in which the phenolics were extracted from the bagasse. Copyright © 2015 Elsevier Ltd. All rights reserved.

Photocatalytic acceptorless alkane dehydrogenation: scope, mechanism, and conquering deactivation with carbon dioxide.

PubMed

Chowdhury, Abhishek Dutta; Julis, Jennifer; Grabow, Kathleen; Hannebauer, Bernd; Bentrup, Ursula; Adam, Martin; Franke, Robert; Jackstell, Ralf; Beller, Matthias

2015-01-01

Alkane dehydrogenation is of special interest for basic science but also offers interesting opportunities for industry. The existing dehydrogenation methodologies make use of heterogeneous catalysts, which suffer from harsh reaction conditions and a lack of selectivity, whereas homogeneous methodologies rely mostly on unsolicited waste generation from hydrogen acceptors. Conversely, acceptorless photochemical alkane dehydrogenation in the presence of trans-Rh(PMe3 )2 (CO)Cl can be regarded as a more benign and atom efficient alternative. However, this methodology suffers from catalyst deactivation over time. Herein, we provide a detailed investigation of the trans-Rh(PMe3 )2 (CO)Cl-photocatalyzed alkane dehydrogenation using spectroscopic and theoretical investigations. These studies inspired us to utilize CO2 to prevent catalyst deactivation, which leads eventually to improved catalyst turnover numbers in the dehydrogenation of alkanes that include liquid organic hydrogen carriers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.