Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study.

PubMed

Li, Wei; Dan, Gang; Jiang, Jianqing; Zheng, Yifeng; Zheng, Xiushan; Deng, Dan

2016-09-13

Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1-to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87.4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC.

Local Dependence in an Operational CAT: Diagnosis and Implications

ERIC Educational Resources Information Center

Pommerich, Mary; Segall, Daniel O.

2008-01-01

The accuracy of CAT scores can be negatively affected by local dependence if the CAT utilizes parameters that are misspecified due to the presence of local dependence and/or fails to control for local dependence in responses during the administration stage. This article evaluates the existence and effect of local dependence in a test of…

Sympathetic, sensory, and nonneuronal contributions to the cutaneous vasoconstrictor response to local cooling.

PubMed

Johnson, John M; Yen, Tony C; Zhao, Kun; Kosiba, Wojciech A

2005-04-01

Previous work indicates that sympathetic nerves participate in the vascular responses to direct cooling of the skin in humans. We evaluated this hypothesis further in a four-part series by measuring changes in cutaneous vascular conductance (CVC) from forearm skin locally cooled from 34 to 29 degrees C for 30 min. In part 1, bretylium tosylate reversed the initial vasoconstriction (-14 +/- 6.6% control CVC, first 5 min) to one of vasodilation (+19.7 +/- 7.7%) but did not affect the response at 30 min (-30.6 +/- 9% control, -38.9 +/- 6.9% bretylium; both P < 0.05, P > 0.05 between treatments). In part 2, yohimbine and propranolol (YP) also reversed the initial vasoconstriction (-14.3 +/- 4.2% control) to vasodilation (+26.3 +/- 12.1% YP), without a significant effect on the 30-min response (-26.7 +/- 6.1% YP, -43.2 +/- 6.5% control; both P < 0.05, P > 0.05 between sites). In part 3, the NPY Y1 receptor antagonist BIBP 3226 had no significant effect on either phase of vasoconstriction (P > 0.05 between sites both times). In part 4, sensory nerve blockade by anesthetic cream (Emla) also reversed the initial vasoconstriction (-20.1 +/- 6.4% control) to one of vasodilation (+213.4 +/- 87.0% Emla), whereas the final levels did not differ significantly (-37.7 +/- 10.1% control, -37.2 +/- 8.7% Emla; both P < 0.05, P > 0.05 between treatments). These results indicate that local cooling causes cold-sensitive afferents to activate sympathetic nerves to release norepinephrine, leading to a local cutaneous vasoconstriction that masks a nonneurogenic vasodilation. Later, a vasoconstriction develops with or without functional sensory or sympathetic nerves.

Local control theory using trajectory surface hopping and linear-response time-dependent density functional theory.

PubMed

Curchod, Basile F E; Penfold, Thomas J; Rothlisberger, Ursula; Tavernelli, Ivano

2013-01-01

The implementation of local control theory using nonadiabatic molecular dynamics within the framework of linear-response time-dependent density functional theory is discussed. The method is applied to study the photoexcitation of lithium fluoride, for which we demonstrate that this approach can efficiently generate a pulse, on-the-fly, able to control the population transfer between two selected electronic states. Analysis of the computed control pulse yields insights into the photophysics of the process identifying the relevant frequencies associated to the curvature of the initial and final state potential energy curves and their energy differences. The limitations inherent to the use of the trajectory surface hopping approach are also discussed.

After-action review of the 2009-10 H1N1 Influenza Outbreak Response: Ohio's Public Health System's performance.

PubMed

Mase, William A; Bickford, Beth; Thomas, Casey L; Jones, Shamika D; Bisesi, Michael

In early 2009, H1N1 influenza was identified within the human population. Centers for Disease Control and Prevention (CDC) officials responded with focused assessment, policy development, and assurances. The response was mobilized through efforts including procurement of adequate vaccine supply, local area span of control, materials acquisition, and facilities and resource identification. Qualitative evaluation of the assurance functions specific to the system's ability to assure safe and healthy conditions are reported. The methodology mirrors the Homeland Security Exercise and Evaluation Program used to assess system capability. Findings demonstrate the effectiveness of community responsive disease prevention efforts in partnership with the public health systems mission to unify traditional public sector systems, for-profit systems, and local area systems was accomplished. As a result of this response pharmaceutical industries, healthcare providers, healthcare agencies, police/safety, colleges, and health and human service agencies were united. Findings demonstrate the effectiveness of community response strategies utilizing feedback from system stakeholders. After-action review processes are critical in all-hazards preparedness. This analysis of local health district response to the H1N1 influenza outbreak informs future public health service delivery. Results provide a synthesis of local health department's emergency response strategies, challenges encountered, and future-focused emergency response strategy implementation. A synthesis is provided as to policy and practice developments which have emerged over the past seven years with regard to lessons learned from the 2009-10 H1N1 influenza outbreak and response.

77 FR 50759 - Noise Exposure Map Notice, Orlando Sanford International Airport, Sanford, FL

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

...; Table 13: 2009 and 2016 Local Runway Use Percentages; Figure 1: East Flow Flight Tracks; Figure 2: West Flow Flight Tracks; Figure 3: Local Flight Tracks; Figure 4: Existing Land Use; Figure 5: 2011 NEM... inseparable from the ultimate land use control and planning responsibilities of local government. These local...

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

PubMed Central

2010-01-01

Background Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab. Methods Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation. Results Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively. Conclusion While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial. PMID:21047402

Spatially Probed Plasmonic Photothermic Nanoheater Enhanced Hybrid Polymeric-Metallic PVDF-Ag Nanogenerator.

PubMed

Liow, Chi Hao; Lu, Xin; Tan, Chuan Fu; Chan, Kwok Hoe; Zeng, Kaiyang; Li, Shuzhou; Ho, Ghim Wei

2018-02-01

Surface plasmon-based photonics offers exciting opportunities to enable fine control of the site, span, and extent of mechanical harvesting. However, the interaction between plasmonic photothermic and piezoresponse still remains underexplored. Here, spatially localized and controllable piezoresponse of a hybrid self-polarized polymeric-metallic system that correlates to plasmonic light-to-heat modulation of the local strain is demonstrated. The piezoresponse is associated to the localized plasmons that serve as efficient nanoheaters leading to self-regulated strain via thermal expansion of the electroactive polymer. Moreover, the finite-difference time-domain simulation and linear thermal model also deduce the local strain to the surface plasmon heat absorption. The distinct plasmonic photothermic-piezoelectric phenomenon mediates not only localized external stimulus light response but also enhances dynamic piezoelectric energy harvesting. The present work highlights a promising surface plasmon coordinated piezoelectric response which underpins energy localization and transfer for diversified design of unique photothermic-piezotronic technology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Predictive Multiple Model Switching Control with the Self-Organizing Map

NASA Technical Reports Server (NTRS)

Motter, Mark A.

2000-01-01

A predictive, multiple model control strategy is developed by extension of self-organizing map (SOM) local dynamic modeling of nonlinear autonomous systems to a control framework. Multiple SOMs collectively model the global response of a nonautonomous system to a finite set of representative prototype controls. Each SOM provides a codebook representation of the dynamics corresponding to a prototype control. Different dynamic regimes are organized into topological neighborhoods where the adjacent entries in the codebook represent the global minimization of a similarity metric. The SOM is additionally employed to identify the local dynamical regime, and consequently implements a switching scheme that selects the best available model for the applied control. SOM based linear models are used to predict the response to a larger family of control sequences which are clustered on the representative prototypes. The control sequence which corresponds to the prediction that best satisfies the requirements on the system output is applied as the external driving signal.

Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery

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

Simpson, J.R.; Thawley, S.E.; Matsuba, H.M.

1984-05-01

The recrods of 71 patients with adenoid cystic carcinoma of the salivary glands were reviewed to determine the dose response relationships for this aggressive tumor. Local control after treament was determined for all patients and analyzed with respect to extent of surgery and dose of radiation. Of 70 patients who were available for evaluation of local control, 28 (40%) had a local recurrence and 42 (60%) did not. The highest control rates were found in patients who underwent both radiation therapy and surgery. Patients who received a dose equal to or greater than 6,000 rad (60 Gy) in addition tomore » surgery had significantly higher local control rates than those who received less than 6,000 rad (60 Gy). Distant metastases developed in 50% of patients regardless of local control, with the following distribution: 39% lung, 19% bone, and 10% disseminated soft-tissue metastases.« less

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

Haemodynamic stability during general anaesthesia for intra-ocular surgery: the effect of topical oxybuprocaine.

PubMed

Lytle, J; Thomas, N F

1992-07-01

Local anaesthesia is frequently used in combination with light general anaesthesia to reduce the reflex responses to surgical stimulation. This combination has not previously been evaluated for intra-ocular surgery. During cataract extraction under general anaesthesia, the effect of topical anaesthesia with oxybuprocaine 0.4% on the pressor response was compared with normal saline in a control group. The simple technique of instilling local anaesthetic drops into the conjunctival sac blocked the pain pathway sufficiently to prevent the pressor response to surgical stimulation (p less than 0.001). Higher inspired concentrations of enflurane were required in the control group to achieve and maintain haemodynamic stability (p less than 0.001).

Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

PubMed

van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; Buisman, Anne-Marie

2017-09-01

In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the administration of a fifth diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine. The objective of this study was to investigate possible differences in vaccine antigen-specific immune responses between children with and without a pronounced local AE after the fifth DTaP-IPV vaccination. Blood was sampled in 2 groups of 4-year-olds: a case group reporting pronounced local swelling and/or erythema up to extensive limb swelling at the injection site (n = 30) and a control group (n = 30). Peripheral blood mononuclear cells were stimulated with individual vaccine antigens. Plasma antigen-specific IgG, IgG subclass and total IgE concentrations and T-cell cytokine [interferon-gamma, interleukin (IL)-13, IL-17 and IL-10] production by stimulated peripheral blood mononuclear cells were determined by multiplex bead-based fluorescent multiplex immunoassays. In children with AEs, significantly higher total IgE and vaccine antigen-specific IgG and IgG4 responses as well as levels of the T-helper 2 (Th2) cytokine IL-13 were found after pertussis, tetanus and diphtheria stimulation compared with controls. Children with pronounced local reactions show higher humoral and cellular immune responses. Acellular vaccines are known to skew toward more Th2 responses. The pronounced local AEs may be associated with more Th2 skewing after the fifth DTaP-IPV vaccination, but other biologic factors may also impact the occurrence of these pronounced local reactions.

Evaluation bias in objective response rate and disease control rate between blinded independent central review and local assessment: a study-level pooled analysis of phase III randomized control trials in the past seven years.

PubMed

Zhang, Jianrong; Zhang, Yiyin; Tang, Shiyan; Liang, Hengrui; Chen, Difei; Jiang, Long; He, Qihua; Huang, Yu; Wang, Xinyu; Deng, Kexin; Jiang, Shuhan; Zhou, Jiaqing; Xu, Jiaxuan; Chen, Xuanzuo; Liang, Wenhua; He, Jianxing

2017-12-01

In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), P<0.01, I 2 =11%; exp-DCR: OR=0.90 (0.81-1.01), P=0.07, I 2 =42%] and control arms [con-ORR: OR=0.79 (0.72-0.85), P<0.01, I 2 =17%; con-DCR: OR=0.94 (0.86-1.02), P=0.14, I 2 =12%]. No sign of evaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I 2 =0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I 2 =0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). Blind independent central review remained irreplaceable to monitor local assessment, but its complete-case implementation may be unnecessary.

Nitrogen Starvation and TorC1 Inhibition Differentially Affect Nuclear Localization of the Gln3 and Gat1 Transcription Factors Through the Rare Glutamine tRNACUG in Saccharomyces cerevisiae

PubMed Central

Tate, Jennifer J.; Rai, Rajendra; Cooper, Terrance G.

2015-01-01

A leucine, leucyl-tRNA synthetase–dependent pathway activates TorC1 kinase and its downstream stimulation of protein synthesis, a major nitrogen consumer. We previously demonstrated, however, that control of Gln3, a transcription activator of catabolic genes whose products generate the nitrogenous precursors for protein synthesis, is not subject to leucine-dependent TorC1 activation. This led us to conclude that excess nitrogen-dependent down-regulation of Gln3 occurs via a second mechanism that is independent of leucine-dependent TorC1 activation. A major site of Gln3 and Gat1 (another GATA-binding transcription activator) control occurs at their access to the nucleus. In excess nitrogen, Gln3 and Gat1 are sequestered in the cytoplasm in a Ure2-dependent manner. They become nuclear and activate transcription when nitrogen becomes limiting. Long-term nitrogen starvation and treatment of cells with the glutamine synthetase inhibitor methionine sulfoximine (Msx) also elicit nuclear Gln3 localization. The sensitivity of Gln3 localization to glutamine and inhibition of glutamine synthesis prompted us to investigate the effects of a glutamine tRNA mutation (sup70-65) on nitrogen-responsive control of Gln3 and Gat1. We found that nuclear Gln3 localization elicited by short- and long-term nitrogen starvation; growth in a poor, derepressive medium; Msx or rapamycin treatment; or ure2Δ mutation is abolished in a sup70-65 mutant. However, nuclear Gat1 localization, which also exhibits a glutamine tRNACUG requirement for its response to short-term nitrogen starvation or growth in proline medium or a ure2Δ mutation, does not require tRNACUG for its response to rapamycin. Also, in contrast with Gln3, Gat1 localization does not respond to long-term nitrogen starvation. These observations demonstrate the existence of a specific nitrogen-responsive component participating in the control of Gln3 and Gat1 localization and their downstream production of nitrogenous precursors. This component is highly sensitive to the function of the rare glutamine tRNACUG, which cannot be replaced by the predominant glutamine tRNACAA. Our observations also demonstrate distinct mechanistic differences between the responses of Gln3 and Gat1 to rapamycin inhibition of TorC1 and nitrogen starvation. PMID:25527290

Which one is more effective for analgesia in infratentorial craniotomy? The scalp block or local anesthetic infiltration.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Vehid, Hayriye; Ibısoglu, Lutfiye Serap; Tunali, Yusuf

2017-03-01

The most painful stages of craniotomy are the placement of the pin head holder and the skin incision. The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5% on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies. The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h. This prospective, randomized and placebo controlled study included forty seven patients (ASA I, II and III). The scalp block was performed in the Group S, the local anesthetic infiltration was performed in the Group I and the control group (Group C) only received remifentanil as an analgesic during the intraoperative period. The hemodynamic response to the pin head holder application and the skin incision, as well as postoperative pain intensity, cumulative morphine consumption and opioid related side effects were compared. The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies. The local anesthetic infiltration reduced the hemodynamic response to the skin incision. As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h. Moreover, the pain intensity was lower after scalp block in the early postoperative period. The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration. Copyright © 2017 Elsevier B.V. All rights reserved.

The School Elections: A Critique of the 1969 New York City School Decentralization.

ERIC Educational Resources Information Center

Demas, Boulton H.

When local school board members in New York City assumed office on 31 local school boards in 1969, this should have resulted in more responsive local boards with sufficient power to control local policy; but this was not the actual result. Specific examination of the decentralization bill, the politics of the election, and the election procedures…

Contrasting Municipal Responses to the Provision of Birth Control Services in Halifax and Exeter before 1948

PubMed Central

Dale, Pamela; Fisher, Kate

2010-01-01

Research exploring the development of the birth control movement in Britain continues to reveal new insights. Local case studies highlight the contentious nature of birth control debates and the significant obstacles that had to be overcome before services could be provided. Moving away from a focus on the activities of birth control campaigners and organisations, such as the Family Planning Association, this paper highlights other local actors in the statutory and voluntary sectors to map why clinics emerged when and where they did. The contrasting examples, provided by Exeter and Halifax, demonstrate the importance of multiple points of contact between local authorities and supporters and opponents of birth control. They also suggest that the attitude of local medical and political elites is not sufficient to explain the success or failure of any clinic.

Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

PubMed Central

Kellogg, Dean L; Zhao, Joan L; Wu, Yubo

2008-01-01

The physiological roles of constituitively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constituitively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser–Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mm sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constituitively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo. PMID:18048451

Decentralized control experiments on NASA's flexible grid

NASA Technical Reports Server (NTRS)

Ozguner, U.; Yurkowich, S.; Martin, J., III; Al-Abbass, F.

1986-01-01

Methods arising from the area of decentralized control are emerging for analysis and control synthesis for large flexible structures. In this paper the control strategy involves a decentralized model reference adaptive approach using a variable structure control. Local models are formulated based on desired damping and response time in a model-following scheme for various modal configurations. Variable structure controllers are then designed employing co-located angular rate and position feedback. In this scheme local control forces the system to move on a local sliding mode in some local error space. An important feature of this approach is that the local subsystem is made insensitive to dynamical interactions with other subsystems once the sliding surface is reached. Experiments based on the above have been performed for NASA's flexible grid experimental apparatus. The grid is designed to admit appreciable low-frequency structural dynamics, and allows for implementation of distributed computing components, inertial sensors, and actuation devices. A finite-element analysis of the grid provides the model for control system design and simulation; results of several simulations are reported on here, and a discussion of application experiments on the apparatus is presented.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

PubMed

Bensignor, T; Brouquet, A; Dariane, C; Thirot-Bidault, A; Lazure, T; Julié, C; Nordlinger, B; Penna, C; Benoist, S

2015-06-01

Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Composite polymer systems with control of local substrate elasticity and their effect on cytoskeletal and morphological characteristics of adherent cells.

PubMed

Chou, Szu-Yuan; Cheng, Chao-Min; LeDuc, Philip R

2009-06-01

At the interface between extracellular substrates and biological materials, substrate elasticity strongly influences cell morphology and function. The associated biological ramifications comprise a diversity of critical responses including apoptosis, differentiation, and motility, which can affect medical devices such as stents. The interactions of the extracellular environment with the substrate are also affected by local properties wherein cells sense and respond to different physical inputs. To investigate the effects of having localized elasticity control of substrate microenvironments on cell response, we have developed a method to control material interface interactions with cells by dictating local substrate elasticity. This system is created by generating a composite material system with alternating, linear regions of polymers that have distinct stiffness characteristics. This approach was used to examine cytoskeletal and morphological changes in NIH 3T3 fibroblasts with emphasis on both local and global properties, noting that cells sense and respond to distinct material elasticities. Isolated cells sense and respond to these local differences in substrate elasticity by extending processes along the interface. Also, cells grown on softer elastic regions at higher densities (in contact with each other) have a higher projected area than isolated cells. Furthermore, when using chemical agents such as cytochalasin-D to disrupt the actin cytoskeleton, there is a significant increase in projected area for cells cultured on softer elastic regions This method has the potential to promote understanding of biomaterial-affected responses in a diversity of areas including morphogenesis, mechanotransduction, stents, and stem cell differentiation.

PH and Electrochemical Responsive Materials for Corrosion Smart Coating Applications

NASA Technical Reports Server (NTRS)

Li, Wenyan; Calle, Luz M.

2008-01-01

Corrosion is a costly issue for military operations and civil industries. While most corrosion initiates from localized corrosion form, such as pitting, failure directly caused by localized corrosion is the most dangerous kind, because it is difficult to anticipate and prevent, occurs very suddenly and can be catastrophic. One way of preventing these failures is with a coating that can detect and heal localized corrosion. pH and other electrochemical changes are often associated with localized corrosion, so it is expected that materials that are pH or otherwise electrochemical responsive can be used to detect and control corrosion. This paper will review various pH and electrochemical responsive materials and their potential applications in corrosion smart coatings. Current research results in this field will also be reported.

Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation.

PubMed

Münch, Christian; Harper, J Wade

2016-06-30

The mitochondrial matrix is unique in that it must integrate the folding and assembly of proteins derived from the nuclear and mitochondrial genomes. In Caenorhabditis elegans, the mitochondrial unfolded protein response (UPRmt) senses matrix protein misfolding and induces a program of nuclear gene expression, including mitochondrial chaperonins, to promote mitochondrial proteostasis. While misfolded mitochondrial-matrix-localized ornithine transcarbamylase induces chaperonin expression, our understanding of mammalian UPRmt is rudimentary, reflecting a lack of acute triggers for UPRmt activation. This limitation has prevented analysis of the cellular responses to matrix protein misfolding and the effects of UPRmt on mitochondrial translation to control protein folding loads. Here we combine pharmacological inhibitors of matrix-localized HSP90/TRAP1 (ref. 8) or LON protease, which promote chaperonin expression, with global transcriptional and proteomic analysis to reveal an extensive and acute response of human cells to UPRmt. This response encompasses widespread induction of nuclear genes, including matrix-localized proteins involved in folding, pre-RNA processing and translation. Functional studies revealed rapid but reversible translation inhibition in mitochondria occurring concurrently with defects in pre-RNA processing caused by transcriptional repression and LON-dependent turnover of the mitochondrial pre-RNA processing nuclease MRPP3 (ref. 10). This study reveals that acute mitochondrial protein folding stress activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition, and provides a framework for further dissection of mammalian UPRmt.

Lessons Learned From Implementing an Incident Command System During a Local Multiagency Response to a Legionnaires' Disease Cluster in Sydney, NSW.

PubMed

Quinn, Emma; Johnstone, Travers; Najjar, Zeina; Cains, Toni; Tan, Geoff; Huhtinen, Essi; Nilsson, Sven; Burgess, Stuart; Dunn, Matthew; Gupta, Leena

2017-09-05

The incident command system (ICS) provides a common structure to control and coordinate an emergency response, regardless of scale or predicted impact. The lessons learned from the application of an ICS for large infectious disease outbreaks are documented. However, there is scant evidence on the application of an ICS to manage a local multiagency response to a disease cluster with environmental health risks. The Sydney Local Health District Public Health Unit (PHU) in New South Wales, Australia, was notified of 5 cases of Legionnaires' disease during 2 weeks in May 2016. This unusual incident triggered a multiagency investigation involving an ICS with staff from the PHU, 3 local councils, and the state health department to help prevent any further public health risk. The early and judicious use of ICS enabled a timely and effective response by supporting clear communication lines between the incident controller and field staff. The field team was key in preventing any ongoing public health risk through inspection, sampling, testing, and management of water systems identified to be at-risk for transmission of legionella. Good working relationships between partner agencies and trust in the technical proficiency of environmental health staff aided in the effective management of the response. (Disaster Med Public Health Preparedness. 2017;page 1 of 4).

Energy management and multi-layer control of networked microgrids

NASA Astrophysics Data System (ADS)

Zamora, Ramon

Networked microgrids is a group of neighboring microgrids that has ability to interchange power when required in order to increase reliability and resiliency. Networked microgrid can operate in different possible configurations including: islanded microgrid, a grid-connected microgrid without a tie-line converter, a grid-connected microgrid with a tie-line converter, and networked microgrids. These possible configurations and specific characteristics of renewable energy offer challenges in designing control and management algorithms for voltage, frequency and power in all possible operating scenarios. In this work, control algorithm is designed based on large-signal model that enables microgrid to operate in wide range of operating points. A combination between PI controller and feed-forward measured system responses will compensate for the changes in operating points. The control architecture developed in this work has multi-layers and the outer layer is slower than the inner layer in time response. The main responsibility of the designed controls are to regulate voltage magnitude and frequency, as well as output power of the DG(s). These local controls also integrate with a microgrid level energy management system or microgrid central controller (MGCC) for power and energy balance for. the entire microgrid in islanded, grid-connected, or networked microgid mode. The MGCC is responsible to coordinate the lower level controls to have reliable and resilient operation. In case of communication network failure, the decentralized energy management will operate locally and will activate droop control. Simulation results indicate the superiority of designed control algorithms compared to existing ones.

Changes in Gene Expression Predicting Local Control in Cervical Cancer: Results from Radiation Therapy Oncology Group 0128

PubMed Central

Weidhaas, Joanne B.; Li, Shu-Xia; Winter, Kathryn; Ryu, Janice; Jhingran, Anuja; Miller, Bridgette; Dicker, Adam P.; Gaffney, David

2009-01-01

Purpose To evaluate the potential of gene expression signatures to predict response to treatment in locally advanced cervical cancer treated with definitive chemotherapy and radiation. Experimental Design Tissue biopsies were collected from patients participating in Radiation Therapy Oncology Group (RTOG) 0128, a phase II trial evaluating the benefit of celecoxib in addition to cisplatin chemotherapy and radiation for locally advanced cervical cancer. Gene expression profiling was done and signatures of pretreatment, mid-treatment (before the first implant), and “changed” gene expression patterns between pre- and mid-treatment samples were determined. The ability of the gene signatures to predict local control versus local failure was evaluated. Two-group t test was done to identify the initial gene set separating these end points. Supervised classification methods were used to enrich the gene sets. The results were further validated by leave-one-out and 2-fold cross-validation. Results Twenty-two patients had suitable material from pretreatment samples for analysis, and 13 paired pre- and mid-treatment samples were obtained. The changed gene expression signatures between the pre- and mid-treatment biopsies predicted response to treatment, separating patients with local failures from those who achieved local control with a seven-gene signature. The in-sample prediction rate, leave-one-out prediction rate, and 2-fold prediction rate are 100% for this seven-gene signature. This signature was enriched for cell cycle genes. Conclusions Changed gene expression signatures during therapy in cervical cancer can predict outcome as measured by local control. After further validation, such findings could be applied to direct additional therapy for cervical cancer patients treated with chemotherapy and radiation. PMID:19509178

Local Control After Stereotactic Body Radiation Therapy for Liver Tumors.

PubMed

Ohri, Nitin; Tomé, Wolfgang A; Méndez Romero, Alejandra; Miften, Moyed; Ten Haken, Randall K; Dawson, Laura A; Grimm, Jimm; Yorke, Ellen; Jackson, Andrew

2018-01-06

To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy 10 vs >100 Gy 10 ). Comparisons were made using log-rank testing. Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy 10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy 10 (3-year local control 65%, P < .001). Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy 10 are utilized. Copyright © 2018 Elsevier Inc. All rights reserved.

76 FR 3650 - Renewal and Revision of Information Collection, OMB Control Number 1004-0009

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... collection of information from individuals, State and local governments, and the private sector in... governments, 286 typical responses from the private sector, and 10 complex responses from the private sector... typical responses from the private sector, and 1,200 hours for complex responses from the private sector...

Local feedback control of light honeycomb panels.

PubMed

Hong, Chinsuk; Elliott, Stephen J

2007-01-01

This paper summarizes theoretical and experimental work on the feedback control of sound radiation from honeycomb panels using piezoceramic actuators. It is motivated by the problem of sound transmission in aircraft, specifically the active control of trim panels. Trim panels are generally honeycomb structures designed to meet the design requirement of low weight and high stiffness. They are resiliently mounted to the fuselage for the passive reduction of noise transmission. Local coupling of the closely spaced sensor and actuator was observed experimentally and modeled using a single degree of freedom system. The effect of the local coupling was to roll off the response between the actuator and sensor at high frequencies, so that a feedback control system can have high gain margins. Unfortunately, only relatively poor global performance is then achieved because of localization of reduction around the actuator. This localization prompts the investigation of a multichannel active control system. Globalized reduction was predicted using a model of 12-channel direct velocity feedback control. The multichannel system, however, does not appear to yield a significant improvement in the performance because of decreased gain margin.

Non-operative management of rectal cancer: understanding tumor biology.

PubMed

Wei, Iris H; Garcia-Aguilar, Julio

2018-05-24

The management of locally advanced rectal cancer involves a combination of chemotherapy, chemoradiation, and surgical resection to provide excellent local tumor control and overall survival. However, aspects of this multimodality approach are associated with significant morbidity and longterm sequelae. In addition, there is growing evidence that patients with a clinical complete response to chemotherapy and chemoradiation treatments may be safely offered initial non-operative management in a rigorous surveillance program. Developing effective methods, such as molecular biomarkers, to predict a patient's response to therapies are therefore needed to help guide personalized treatment strategies. The treatment of locally advanced rectal cancer focuses on a multimodality approach of systemic chemotherapy, radiation, and total mesorectal excision to maximize oncologic outcomes. While combined modality treatment for LARC results in excellent local tumor control and patient survival, the treatments are associated with significant morbidity and long-term functional complications that can impair quality of life. In addition, the tumor response to neoadjuvant therapy is quite variable.2 Weighed against the morbidity and significant sequelae of rectal resection, recognizing how to best optimize nonoperative strategies without compromising oncologic outcomes is critical to our understanding and treatment of this disease.

Local auxin production underlies a spatially restricted neighbor-detection response in Arabidopsis

PubMed Central

Michaud, Olivier

2017-01-01

Competition for light triggers numerous developmental adaptations known as the “shade-avoidance syndrome” (SAS). Important molecular events underlying specific SAS responses have been identified. However, in natural environments light is often heterogeneous, and it is currently unknown how shading affecting part of a plant leads to local responses. To study this question, we analyzed upwards leaf movement (hyponasty), a rapid adaptation to neighbor proximity, in Arabidopsis. We show that manipulation of the light environment at the leaf tip triggers a hyponastic response that is restricted to the treated leaf. This response is mediated by auxin synthesized in the blade and transported to the petiole. Our results suggest that a strong auxin response in the vasculature of the treated leaf and auxin signaling in the epidermis mediate leaf elevation. Moreover, the analysis of an auxin-signaling mutant reveals signaling bifurcation in the control of petiole elongation versus hyponasty. Our work identifies a mechanism for a local shade response that may pertain to other plant adaptations to heterogeneous environments. PMID:28652343

Climate fails to predict wood decomposition at regional scales

NASA Astrophysics Data System (ADS)

Bradford, Mark A.; Warren, Robert J., II; Baldrian, Petr; Crowther, Thomas W.; Maynard, Daniel S.; Oldfield, Emily E.; Wieder, William R.; Wood, Stephen A.; King, Joshua R.

2014-07-01

Decomposition of organic matter strongly influences ecosystem carbon storage. In Earth-system models, climate is a predominant control on the decomposition rates of organic matter. This assumption is based on the mean response of decomposition to climate, yet there is a growing appreciation in other areas of global change science that projections based on mean responses can be irrelevant and misleading. We test whether climate controls on the decomposition rate of dead wood--a carbon stock estimated to represent 73 +/- 6 Pg carbon globally--are sensitive to the spatial scale from which they are inferred. We show that the common assumption that climate is a predominant control on decomposition is supported only when local-scale variation is aggregated into mean values. Disaggregated data instead reveal that local-scale factors explain 73% of the variation in wood decomposition, and climate only 28%. Further, the temperature sensitivity of decomposition estimated from local versus mean analyses is 1.3-times greater. Fundamental issues with mean correlations were highlighted decades ago, yet mean climate-decomposition relationships are used to generate simulations that inform management and adaptation under environmental change. Our results suggest that to predict accurately how decomposition will respond to climate change, models must account for local-scale factors that control regional dynamics.

Visual processing during recovery from vegetative state to consciousness: comparing behavioral indices to brain responses.

PubMed

Wijnen, V J M; Eilander, H J; de Gelder, B; van Boxtel, G J M

2014-11-01

Auditory stimulation is often used to evoke responses in unresponsive patients who have suffered severe brain injury. In order to investigate visual responses, we examined visual evoked potentials (VEPs) and behavioral responses to visual stimuli in vegetative patients during recovery to consciousness. Behavioral responses to visual stimuli (visual localization, comprehension of written commands, and object manipulation) and flash VEPs were repeatedly examined in eleven vegetative patients every two weeks for an average period of 2.6months, and patients' VEPs were compared to a healthy control group. Long-term outcome of the patients was assessed 2-3years later. Visual response scores increased during recovery to consciousness for all scales: visual localization, comprehension of written commands, and object manipulation. VEP amplitudes were smaller, and latencies were longer in the patient group relative to the controls. VEPs characteristics at first measurement were related to long-term outcome up to three years after injury. Our findings show the improvement of visual responding with recovery from the vegetative state to consciousness. Elementary visual processing is present, yet according to VEP responses, poorer in vegetative and minimally conscious state than in healthy controls, and remains poorer when patients recovered to consciousness. However, initial VEPs are related to long-term outcome. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Evaluation of the response of concurrent high dose rate intracavitary brachytherapy with external beam radiotherapy in management of early stage carcinoma cervix.

PubMed

Patidar, Arvind Kumar; Kumar, H S; Walke, Rahul V; Hirapara, Pushpendra H; Jakhar, Shankar Lal; Bardia, M R

2012-10-01

To evaluate local disease control and early complications of concomitant brachytherapy with external beam-radiotherapy in early stage carcinoma cervix. Fifty patients of early stage carcinoma cervix (FIGO-IB/IIA) were randomly divided into study group concomitant external beam irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr, HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25 Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared between treatment and at 6-month follow up. Median overall treatment times were 38 and 61 days in the study and the control groups, respectively. Acute skin reactions and diarrhea were more in the study but manageable. At the completion of the study, there were 80 and 68 % complete responses, 16 and 20 % partial responses, 0 and 8 % stable diseases in the study group and the control group, respectively. Response was better in the study group but statistically insignificant. Larger number of patients and longer follow up are required to arrive at concrete conclusion.

Commission on Transportation in the Twenty-first Century, Subcommittee on State and Local Relations

DOT National Transportation Integrated Search

1987-12-07

Phase II of the work of the Commission on Transportation has : focused on the role that local governments in Virginia might play : in financing and controlling transportation networks. In : response to overall goals of the Commission, joint resolutio...

40 CFR 763.84 - General local education agency responsibilities.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.84 General local education... Occupational Safety and Health Administration asbestos standard for construction, the EPA worker protection... exterminators) who may come in contact with asbestos in a school are provided information regarding the...

40 CFR 763.84 - General local education agency responsibilities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.84 General local education... Occupational Safety and Health Administration asbestos standard for construction, the EPA worker protection... exterminators) who may come in contact with asbestos in a school are provided information regarding the...

40 CFR 763.84 - General local education agency responsibilities.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.84 General local education... Occupational Safety and Health Administration asbestos standard for construction, the EPA worker protection... exterminators) who may come in contact with asbestos in a school are provided information regarding the...

40 CFR 763.84 - General local education agency responsibilities.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.84 General local education... Occupational Safety and Health Administration asbestos standard for construction, the EPA worker protection... exterminators) who may come in contact with asbestos in a school are provided information regarding the...

An fMRI-study of locally oriented perception in autism: altered early visual processing of the block design test.

PubMed

Bölte, S; Hubl, D; Dierks, T; Holtmann, M; Poustka, F

2008-01-01

Autism has been associated with enhanced local processing on visual tasks. Originally, this was based on findings that individuals with autism exhibited peak performance on the block design test (BDT) from the Wechsler Intelligence Scales. In autism, the neurofunctional correlates of local bias on this test have not yet been established, although there is evidence of alterations in the early visual cortex. Functional MRI was used to analyze hemodynamic responses in the striate and extrastriate visual cortex during BDT performance and a color counting control task in subjects with autism compared to healthy controls. In autism, BDT processing was accompanied by low blood oxygenation level-dependent signal changes in the right ventral quadrant of V2. Findings indicate that, in autism, locally oriented processing of the BDT is associated with altered responses of angle and grating-selective neurons, that contribute to shape representation, figure-ground, and gestalt organization. The findings favor a low-level explanation of BDT performance in autism.

Network-Cognizant Voltage Droop Control for Distribution Grids

DOE PAGES

Baker, Kyri; Bernstein, Andrey; Dall'Anese, Emiliano; ...

2017-08-07

Our paper examines distribution systems with a high integration of distributed energy resources (DERs) and addresses the design of local control methods for real-time voltage regulation. Particularly, the paper focuses on proportional control strategies where the active and reactive output-powers of DERs are adjusted in response to (and proportionally to) local changes in voltage levels. The design of the voltage-active power and voltage-reactive power characteristics leverages suitable linear approximation of the AC power-flow equations and is network-cognizant; that is, the coefficients of the controllers embed information on the location of the DERs and forecasted non-controllable loads/injections and, consequently, on themore » effect of DER power adjustments on the overall voltage profile. We pursued a robust approach to cope with uncertainty in the forecasted non-controllable loads/power injections. Stability of the proposed local controllers is analytically assessed and numerically corroborated.« less

Network-Cognizant Voltage Droop Control for Distribution Grids

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

Baker, Kyri; Bernstein, Andrey; Dall'Anese, Emiliano

Our paper examines distribution systems with a high integration of distributed energy resources (DERs) and addresses the design of local control methods for real-time voltage regulation. Particularly, the paper focuses on proportional control strategies where the active and reactive output-powers of DERs are adjusted in response to (and proportionally to) local changes in voltage levels. The design of the voltage-active power and voltage-reactive power characteristics leverages suitable linear approximation of the AC power-flow equations and is network-cognizant; that is, the coefficients of the controllers embed information on the location of the DERs and forecasted non-controllable loads/injections and, consequently, on themore » effect of DER power adjustments on the overall voltage profile. We pursued a robust approach to cope with uncertainty in the forecasted non-controllable loads/power injections. Stability of the proposed local controllers is analytically assessed and numerically corroborated.« less

Local Inflammation in Fracture Hematoma: Results from a Combined Trauma Model in Pigs

PubMed Central

Horst, K.; Eschbach, D.; Pfeifer, R.; Hübenthal, S.; Sassen, M.; Steinfeldt, T.; Wulf, H.; Ruchholtz, S.; Pape, H. C.; Hildebrand, F.

2015-01-01

Background. Previous studies showed significant interaction between the local and systemic inflammatory response after severe trauma in small animal models. The purpose of this study was to establish a new combined trauma model in pigs to investigate fracture-associated local inflammation and gain information about the early inflammatory stages after polytrauma. Material and Methods. Combined trauma consisted of tibial fracture, lung contusion, liver laceration, and controlled hemorrhage. Animals were mechanically ventilated and under ICU-monitoring for 48 h. Blood and fracture hematoma samples were collected during the time course of the study. Local and systemic levels of serum cytokines and diverse alarmins were measured by ELISA kit. Results. A statistical significant difference in the systemic serum values of IL-6 and HMGB1 was observed when compared to the sham. Moreover, there was a statistical significant difference in the serum values of the fracture hematoma of IL-6, IL-8, IL-10, and HMGB1 when compared to the systemic inflammatory response. However a decrease of local proinflammatory concentrations was observed while anti-inflammatory mediators increased. Conclusion. Our data showed a time-dependent activation of the local and systemic inflammatory response. Indeed it is the first study focusing on the local and systemic inflammatory response to multiple-trauma in a large animal model. PMID:25694748

Four-dimensional Printing of Liquid Crystal Elastomers.

PubMed

Ambulo, Cedric P; Burroughs, Julia J; Boothby, Jennifer M; Kim, Hyun; Shankar, M Ravi; Ware, Taylor H

2017-10-25

Three-dimensional structures capable of reversible changes in shape, i.e., four-dimensional-printed structures, may enable new generations of soft robotics, implantable medical devices, and consumer products. Here, thermally responsive liquid crystal elastomers (LCEs) are direct-write printed into 3D structures with a controlled molecular order. Molecular order is locally programmed by controlling the print path used to build the 3D object, and this order controls the stimulus response. Each aligned LCE filament undergoes 40% reversible contraction along the print direction on heating. By printing objects with controlled geometry and stimulus response, magnified shape transformations, for example, volumetric contractions or rapid, repetitive snap-through transitions, are realized.

Local Control of Blood Flow

ERIC Educational Resources Information Center

Clifford, Philip S.

2011-01-01

Organ blood flow is determined by perfusion pressure and vasomotor tone in the resistance vessels of the organ. Local factors that regulate vasomotor tone include myogenic and metabolic autoregulation, flow-mediated and conducted responses, and vasoactive substances released from red blood cells. The relative importance of each of these factors…

Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras.

PubMed

Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H

2015-01-01

Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service responsiveness with thoughtful strategies and management practices in the local health systems.

A SIMPLE APPROACH TO ASSESSING COPPER PITTING CORROSION TENDENCIES AND DEVELOPING CONTROL STRATEGIES

EPA Science Inventory

Localized corrosion of copper plumbing in drinking water distribution systems can lead to pinhole leaks, which are a growing problem for many homeowners. Although water quality is one factor that can be responsible for localized copper corrosion, there is not a good approach to ...

Electromagnetic Evidence of Altered Visual Processing in Autism

ERIC Educational Resources Information Center

Neumann, Nicola; Dubischar-Krivec, Anna M.; Poustka, Fritz; Birbaumer, Niels; Bolte, Sven; Braun, Christoph

2011-01-01

Individuals with autism spectrum disorder (ASD) demonstrate intact or superior local processing of visual-spatial tasks. We investigated the hypothesis that in a disembedding task, autistic individuals exhibit a more local processing style than controls, which is reflected by altered electromagnetic brain activity in response to embedded stimuli…

The response of an individual vortex to local mechanical contact

NASA Astrophysics Data System (ADS)

Kremen, Anna; Wissberg, Shai; Shperber, Yishai; Kalisky, Beena

2016-05-01

Recently we reported a new way to manipulate vortices in thin superconducting films by local mechanical contact without magnetic field, current or altering the pinning landscape [1]. We use scanning superconducting interference device (SQUID) microscopy to image the vortices, and a piezo element to push the tip of a silicon chip into contact with the sample. As a result of the stress applied at the contact point, vortices in the proximity of the contact point change their location. Here we study the characteristics of this vortex manipulation, by following the response of individual vortices to single contact events. Mechanical manipulation of vortices provides local view of the interaction between strain and nanomagnetic objects, as well as controllable, effective, localized, and reproducible manipulation technique.

78 FR 12052 - Agency Information Collection Activities: Proposed Collection; Comment Request; Ambient Air...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... pollution control agencies, and tribal entities which collect and report ambient air quality data for the..., documenting episodes and initiating episode controls, air quality trends assessment, and air pollution.... Although the state and local air pollution control agencies and tribal entities are responsible for the...

36 CFR 330.5 - Policy.

Code of Federal Regulations, 2010 CFR

2010-07-01

... reporting requirements and the control of expenditures. (b) Contracts for law enforcement services, as... responsibilities of the State or local law enforcement agencies. (d) Contract law enforcement personnel shall not... regulations shall remain the responsibility of the Corps of Engineers. (e) Contracts for increased law...

Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.

PubMed

Zervantonakis, Ioannis K; Arvanitis, Costas D

2016-05-01

Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. A novel acoustofluidic platform is developed by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS-induced heating triggers local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher cellular drug uptake in the FUS focal region. This differential drug uptake induces locally confined DNA damage and glioblastoma cell death in the 3D environment. The capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response are demonstrated in a 3D in vitro tumor mode. This has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nanoparticle-Hydrogel: A Hybrid Biomaterial System for Localized Drug Delivery

PubMed Central

Gao, Weiwei; Zhang, Yue; Zhang, Qiangzhe; Zhang, Liangfang

2016-01-01

Nanoparticles have offered a unique set of properties for drug delivery including high drug loading capacity, combinatorial delivery, controlled and sustained drug release, prolonged stability and lifetime, and targeted delivery. To further enhance therapeutic index, especially for localized application, nanoparticles have been increasingly combined with hydrogels to form a hybrid biomaterial system for controlled drug delivery. Herein, we review recent progresses in engineering such nanoparticle-hydrogel hybrid system (namely ‘NP-gel’) with a particular focus on its application for localized drug delivery. Specifically, we highlight four research areas where NP-gel has shown great promises, including (1) passively controlled drug release, (2) stimuli-responsive drug delivery, (3) site-specific drug delivery, and (4) detoxification. Overall, integrating therapeutic nanoparticles with hydrogel technologies creates a unique and robust hybrid biomaterial system that enables effective localized drug delivery. PMID:26951462

Dynamic subcellular localization of a respiratory complex controls bacterial respiration

PubMed Central

Alberge, François; Espinosa, Leon; Seduk, Farida; Sylvi, Léa; Toci, René; Walburger, Anne; Magalon, Axel

2015-01-01

Respiration, an essential process for most organisms, has to optimally respond to changes in the metabolic demand or the environmental conditions. The branched character of their respiratory chains allows bacteria to do so by providing a great metabolic and regulatory flexibility. Here, we show that the native localization of the nitrate reductase, a major respiratory complex under anaerobiosis in Escherichia coli, is submitted to tight spatiotemporal regulation in response to metabolic conditions via a mechanism using the transmembrane proton gradient as a cue for polar localization. These dynamics are critical for controlling the activity of nitrate reductase, as the formation of polar assemblies potentiates the electron flux through the complex. Thus, dynamic subcellular localization emerges as a critical factor in the control of respiration in bacteria. DOI: http://dx.doi.org/10.7554/eLife.05357.001 PMID:26077726

Thermal, cardiac and adrenergic responses to repeated local cooling.

PubMed

Janský, L; Matousková, E; Vávra, V; Vybíral, S; Janský, P; Jandová, D; Knízková, I; Kunc, P

2006-01-01

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.

Responsibility without legal authority? Tackling alcohol-related health harms through licensing and planning policy in local government.

PubMed

Martineau, F P; Graff, H; Mitchell, C; Lock, K

2014-09-01

The power to influence many social determinants of health lies within local government sectors that are outside public health's traditional remit. We analyse the challenges of achieving health gains through local government alcohol control policies, where legal and professional practice frameworks appear to conflict with public health action. Current legislation governing local alcohol control in England and Wales is reviewed and analysed for barriers and opportunities to implement effective population-level health interventions. Case studies of local government alcohol control practices are described. Addressing alcohol-related health harms is constrained by the absence of a specific legal health licensing objective and differences between public health and legal assessments of the relevance of health evidence to a specific place. Local governments can, however, implement health-relevant policies by developing local evidence for alcohol-related health harms; addressing cumulative impact in licensing policy statements and through other non-legislative approaches such as health and non-health sector partnerships. Innovative local initiatives-for example, minimum unit pricing licensing conditions-can serve as test cases for wider national implementation. By combining the powers available to the many local government sectors involved in alcohol control, alcohol-related health and social harms can be tackled through existing local mechanisms. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health.

Is Ground Cover Vegetation an Effective Biological Control Enhancement Strategy against Olive Pests?

PubMed Central

Paredes, Daniel; Cayuela, Luis; Gurr, Geoff M.; Campos, Mercedes

2015-01-01

Ground cover vegetation is often added or allowed to generate to promote conservation biological control, especially in perennial crops. Nevertheless, there is inconsistent evidence of its effectiveness, with studies reporting positive, nil or negative effects on pest control. This might arise from differences between studies at the local scale (e.g. orchard management and land use history), the landscape context (e.g. presence of patches of natural or semi-natural vegetation near the focal orchard), or regional factors, particularly climate in the year of the study. Here we present the findings from a long-term regional monitoring program conducted on four pest species (Bactrocera oleae, Prays oleae, Euphyllura olivina, Saissetia oleae) in 2,528 olive groves in Andalusia (Spain) from 2006 to 2012. Generalized linear mixed effect models were used to analyze the effect of ground cover on different response variables related to pest abundance, while accounting for variability at the local, landscape and regional scales. There were small and inconsistent effects of ground cover on the abundance of pests whilst local, landscape and regional variability explained a large proportion of the variability in pest response variables. This highlights the importance of local and landscape-related variables in biological control and the potential effects that might emerge from their interaction with practices, such as groundcover vegetation, implemented to promote natural enemy activity. The study points to perennial vegetation close to the focal crop as a promising alternative strategy for conservation biological control that should receive more attention. PMID:25646778

Optimal control to modelling motorcycle rider steering: local versus global coordinate systems in rider preview

NASA Astrophysics Data System (ADS)

Rowell, S.; Popov, A. A.; Meijaard, J. P.

2010-04-01

The response of a motorcycle is heavily dependent on the rider's control actions, and consequently a means of replicating the rider's behaviour provides an important extension to motorcycle dynamics. The primary objective here is to develop effective path-following simulations and to understand how riders control motorcycles. Optimal control theory is applied to the tracking of roadway by a motorcycle, using a non-linear motorcycle model operating in free control by steering torque input. A path-following controller with road preview is designed by minimising tracking errors and control effort. Tight controls with high weightings on performance and loose controls with high weightings on control power are defined. Special attention is paid to the modelling of multipoint preview in local and global coordinate systems. The controller model is simulated over a standard single lane-change manoeuvre. It is argued that the local coordinates point of view is more representative of the way that a human rider operates and interprets information. The simulations suggest that for accurate path following, using optimal control, the problem must be solved by the local coordinates approach in order to achieve accurate results with short preview horizons. Furthermore, some weaknesses of the optimal control approach are highlighted here.

Weak simulated extratropical responses to complete tropical deforestation

USGS Publications Warehouse

Findell, K.L.; Knutson, T.R.; Milly, P.C.D.

2006-01-01

The Geophysical Fluid Dynamics Laboratory atmosphere-land model version 2 (AM2/LM2) coupled to a 50-m-thick slab ocean model has been used to investigate remote responses to tropical deforestation. Magnitudes and significance of differences between a control run and a deforested run are assessed through comparisons of 50-yr time series, accounting for autocorrelation and field significance. Complete conversion of the broadleaf evergreen forests of South America, central Africa, and the islands of Oceania to grasslands leads to highly significant local responses. In addition, a broad but mild warming is seen throughout the tropical troposphere (<0.2??C between 700 and 150 mb), significant in northern spring and summer. However, the simulation results show very little statistically significant response beyond the Tropics. There are no significant differences in any hydroclimatic variables (e.g., precipitation, soil moisture, evaporation) in either the northern or the southern extratropics. Small but statistically significant local differences in some geopotential height and wind fields are present in the southeastern Pacific Ocean. Use of the same statistical tests on two 50-yr segments of the control run show that the small but significant extratropical differences between the deforested run and the control run are similar in magnitude and area to the differences between nonoverlapping segments of the control run. These simulations suggest that extratropical responses to complete tropical deforestation are unlikely to be distinguishable from natural climate variability.

Hierarchical Decentralized Control Strategy for Demand-Side Primary Frequency Response

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

Lian, Jianming; Hansen, Jacob; Marinovici, Laurentiu D.

The Grid Friendlymore » $$^\\textrm{TM}$$ Appliance~(GFA) controller, developed at Pacific Northwest National Laboratory, was designed for the purpose of autonomously switching off appliances by detecting under-frequency events. In this paper, a new frequency responsive load~(FRL) controller is first proposed by extending the functionality of the original GFA controller. The proposed FRL controller can autonomously switch on (or off) end-use loads by detecting over-frequency (or under-frequency) events through local frequency measurement. Then, a hierarchical decentralized control framework is developed for engaging the end-use loads to provide primary frequency response with the proposed FRL controller. The developed framework has several important features that are desirable in terms of providing primary frequency control. It not only exclusively maintains the autonomous operation of the end-use loads, but also effectively overcomes the stability issue associated with high penetration of FRLs. The simulation results illustrate the effectiveness of the developed hierarchical control framework for providing primary frequency response with the proposed FRL controller.« less

Laser Doppler assessment of dermal circulatory changes in people with coronary artery disease.

PubMed

Agarwal, Sharad C; Allen, John; Murray, Alan; Purcell, Ian F

2012-07-01

Dermal microcirculation provides an easily accessible vasculature bed which can be used to assess endothelial mediated vasodilatation. We studied and compared microcirculatory changes in response to acetylcholine iontophoresis (ACh), local heating of the skin and reactive hyperaemia in patients with coronary artery disease (CAD). Forty eight patients with CAD were studied and compared with 25 age and sex matched control subjects. Vasodilatory changes in the dermal microcirculation were assessed in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia using a laser Doppler flowmeter (LDF). Body mass index (BMI) and systolic BP were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured as absolute in agreement with our previous publish results) in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia, in healthy controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was significantly higher in patients with CAD, 14.1±4.0 vs 10.9±1.7s; p=0.001. There was a small but significant positive correlation between the perfusion change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On ROC curve analysis, perfusion changes with heating had higher sensitivity and specificity in discriminating patients with CAD from the healthy controls with an area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of 77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41% sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88% sensitivity and 60% specificity). Vasodilatation in the dermal microcirculation measured by the three techniques is attenuated in patients with coronary artery disease. Local heating of the skin is a better discriminator of patients with CAD than ACh iontophoresis and reactive hyperaemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Subcellular localization of the Snf1 kinase is regulated by specific β subunits and a novel glucose signaling mechanism

PubMed Central

Vincent, Olivier; Townley, Robert; Kuchin, Sergei; Carlson, Marian

2001-01-01

The Snf1/AMP-activated protein kinase family has broad roles in transcriptional, metabolic, and developmental regulation in response to stress. In Saccharomyces cerevisiae, Snf1 is required for the response to glucose limitation. Snf1 kinase complexes contain the α (catalytic) subunit Snf1, one of the three related β subunits Gal83, Sip1, or Sip2, and the γ subunit Snf4. We present evidence that the β subunits regulate the subcellular localization of the Snf1 kinase. Green fluorescent protein fusions to Gal83, Sip1, and Sip2 show different patterns of localization to the nucleus, vacuole, and/or cytoplasm. We show that Gal83 directs Snf1 to the nucleus in a glucose-regulated manner. We further identify a novel signaling pathway that controls this nuclear localization in response to glucose phosphorylation. This pathway is distinct from the glucose signaling pathway that inhibits Snf1 kinase activity and responds not only to glucose but also to galactose and sucrose. Such independent regulation of the localization and the activity of the Snf1 kinase, combined with the distinct localization of kinases containing different β subunits, affords versatility in regulating physiological responses. PMID:11331606

North American study on contracting snow and ice response : final report.

DOT National Transportation Integrated Search

2017-01-01

Snow and ice control operations are a vital function often conducted by state and local transportation agencies. Many states are choosing to contract snow and ice response services, instead of or in addition to the use of in-house forces, to maintain...

β-adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and non-burned skin under neutral and hot environments in children

PubMed Central

Rivas, Eric; McEntire, Serina J.; Herndon, David N.; Mlcak, Ronald P.; Suman, Oscar E.

2017-01-01

Objective Tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. Methods In a randomized double-blind study, a placebo was given to 8 burned children while propranolol was given to 13 burned children with similar characteristics (mean ± SD: 11.9±3y, 147±20cm, 45±23kg, 56±12% TBSA). Non-burned children (n=13, 11.4±3y, 152±15cm, 52±13kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and non-burned control skin under the two environmental conditions (23°C and 34°C) via laser-Doppler flowmetry. Results Resting SkBF was greater in burned and unburned skin compared to the non-burned control (main effect: skin, P<0.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBFmax). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and non-burned control skin (EC50, P>0.05) under either condition. Conclusion Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. PMID:28071840

β-Adrenergic blockade does not impair the skin blood flow sensitivity to local heating in burned and nonburned skin under neutral and hot environments in children.

PubMed

Rivas, Eric; McEntire, Serina J; Herndon, David N; Mlcak, Ronald P; Suman, Oscar E

2017-05-01

We tested the hypothesis that propranolol, a drug given to burn patients to reduce hypermetabolism/cardiac stress, may inhibit heat dissipation by changing the sensitivity of skin blood flow (SkBF) to local heating under neutral and hot conditions. In a randomized double-blind study, a placebo was given to eight burned children, while propranolol was given to 13 burned children with similar characteristics (mean±SD: 11.9±3 years, 147±20 cm, 45±23 kg, 56±12% Total body surface area burned). Nonburned children (n=13, 11.4±3 years, 152±15 cm, 52±13 kg) served as healthy controls. A progressive local heating protocol characterized SkBF responses in burned and unburned skin and nonburned control skin under the two environmental conditions (23 and 34°C) via laser Doppler flowmetry. Resting SkBF was greater in burned and unburned skin compared to the nonburned control (main effect: skin, P<.0001; 57±32 burned; 38±36 unburned vs 9±8 control %SkBF max ). No difference was found for maximal SkBF capacity to local heating between groups. Additionally, dose-response curves for the sensitivity of SkBF to local heating were not different among burned or unburned skin, and nonburned control skin (EC 50 , P>.05) under either condition. Therapeutic propranolol does not negatively affect SkBF under neutral or hot environmental conditions and further compromise temperature regulation in burned children. © 2017 John Wiley & Sons Ltd.

"Abbott v. Burke" vs. New Jersey: Policy, Politics and Political Economy.

ERIC Educational Resources Information Center

Bader, Beth D.

Local funding and the resultant limited access to quality programs have created disparities in school funding because of disparities in local wealth. Two issues that control policies of New Jersey's school finance are addressed in this paper. The first is the behavior of government, specifically the responses of elected officials and bureaucrats…

75 FR 10552 - Noise Exposure Map Notice for Chandler Municipal Airport, Chandler, AZ

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-08

... shown in Table 6.6. Flight tracks for the existing and the five-year Noise Exposure Maps are found in... from the ultimate land use control and planning responsibilities of local government. These local... those public agencies and planning agencies with which consultation is required under section 47503 of...

76 FR 3890 - Notice of Public Information Collection(s) Being Reviewed by the Federal Communications...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

.... Respondents: State or Local, or Tribal Government. Number of Respondents and Responses: 77 respondents; 77... parties. If a local government seeks a declaratory ruling or a waiver, it must take steps to afford... notice might reasonably have reached. OMB Control Number: 3060-1105. Title: Digital TV Transition Status...

Localized sinonasal mucosal melanoma: Outcomes and associations with stage, radiotherapy, and positron emission tomography response.

PubMed

Samstein, Robert M; Carvajal, Richard D; Postow, Michael A; Callahan, Margaret K; Shoushtari, Alexander N; Patel, Snehal G; Lee, Nancy Y; Barker, Christopher A

2016-09-01

Sinonasal mucosal melanoma is a rare neoplasm with a poor prognosis. Retrospective analysis was conducted on 78 patients with localized sinonasal mucosal melanoma treated at Memorial Sloan Kettering Cancer Center (MSKCC from 1998-2013). Demographic, tumor, imaging, and treatment factors were recorded and survival and disease-control outcomes were analyzed. Median overall survival (OS) and disease-specific survival (DSS) were 32 and 50 months, respectively. Median locoregional recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were 43 and 12 months, respectively. Multivariate analysis demonstrated greater OS in nasal cavity tumors and earlier T classification. Radiotherapy (RT) was associated with significantly greater LRFS (5-years; 35% vs 59%; p = .01), but no difference in OS. Post-RT positron emission tomography (PET) response was associated with greater OS. Distant metastasis is the predominant mode of recurrence in sinonasal mucosal melanoma, but local recurrence remains common. RT is associated with improved local control, but no survival benefit. The prognostic value of post-RT PET imaging warrants further investigation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1310-1317, 2016. © 2016 Wiley Periodicals, Inc.

Implementation of Indian Control of Indian Education. Booklet No. 1. Revised.

ERIC Educational Resources Information Center

Kirkness, Verna J.

The ten questions and their respective answers comprising this booklet illustrate a growing movement toward Indian control of Indian education. This movement is a policy of the National Indian Brotherhood of Canada based on parental responsibility and local control which recognizes that Indian people through their elected councils have the right…

76 FR 5355 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-31

... Grants (1894-0001). OMB Control Number: Pending. Agency Form Number(s): 1810-NEW. Frequency of Responses... Educational Agencies or Local Educational Agencies. Total Estimated Number of Annual Responses: 5. Total... Website at http://edicsweb.ed.gov , by selecting the ``Browse Pending Collections'' link and by clicking...

Constrained tracking control for nonlinear systems.

PubMed

Khani, Fatemeh; Haeri, Mohammad

2017-09-01

This paper proposes a tracking control strategy for nonlinear systems without needing a prior knowledge of the reference trajectory. The proposed method consists of a set of local controllers with appropriate overlaps in their stability regions and an on-line switching strategy which implements these controllers and uses some augmented intermediate controllers to ensure steering the system states to the desired set points without needing to redesign the controller for each value of set point changes. The proposed approach provides smooth transient responses despite switching among the local controllers. It should be mentioned that the stability regions of the proposed controllers could be estimated off-line for a range of set-point changes. The efficiencies of the proposed algorithm are illustrated via two example simulations. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Tumor dose-volume response in image-guided adaptive brachytherapy for cervical cancer: A meta-regression analysis.

PubMed

Mazeron, Renaud; Castelnau-Marchand, Pauline; Escande, Alexandre; Rivin Del Campo, Eleonor; Maroun, Pierre; Lefkopoulos, Dimitri; Chargari, Cyrus; Haie-Meder, Christine

2016-01-01

Image-guided adaptive brachytherapy is a high precision technique that allows dose escalation and adaptation to tumor response. Two monocentric studies reported continuous dose-volume response relationships, however, burdened by large confidence intervals. The aim was to refine these estimations by performing a meta-regression analysis based on published series. Eligibility was limited to series reporting dosimetric parameters according to the Groupe Européen de Curiethérapie-European SocieTy for Radiation Oncology recommendations. The local control rates reported at 2-3 years were confronted to the mean D90 clinical target volume (CTV) in 2-Gy equivalent using the probit model. The impact of each series on the relationships was pondered according to the number of patients reported. An exhaustive literature search retrieved 13 series reporting on 1299 patients. D90 high-risk CTV ranged from 70.9 to 93.1 Gy. The probit model showed a significant correlation between the D90 and the probability of achieving local control (p < 0.0001). The D90 associated to a 90% probability of achieving local control was 81.4 Gy (78.3-83.8 Gy). The planning aim of 90 Gy corresponded to a 95.0% probability (92.8-96.3%). For the intermediate-risk CTV, less data were available, with 873 patients from eight institutions. Reported mean D90 intermediate-risk CTV ranged from 61.7 to 69.1 Gy. A significant dose-volume effect was observed (p = 0.009). The D90 of 60 Gy was associated to a 79.4% (60.2-86.0%) local control probability. Based on published data from a high number of patients, significant dose-volume effect relationships were confirmed and refined between the D90 of both CTV and the probability of achieving local control. Further studies based on individual data are required to develop nomograms including nondosimetric prognostic criteria. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

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

Blanchard, Miran; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota; Shim, Kevin G.

Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responsesmore » capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary combination therapy model that addresses the need for both systemic and local control in oligometastatic melanoma.« less

Effect of large magnetic islands on screening of external magnetic perturbation fields at slow plasma flow

NASA Astrophysics Data System (ADS)

Li, L.; Liu, Y. Q.; Huang, X.; Luan, Q.; Zhong, F. C.

2017-02-01

A toroidal resistive magneto-hydrodynamic plasma response model, involving large magnetic islands, is proposed and numerically investigated, based on local flattening of the equilibrium pressure profile near a rational surface. It is assumed that such islands can be generated near the edge of the tokamak plasma, due to the penetration of the resonant magnetic perturbations, used for the purpose of controlling the edge localized mode. Within this model, it is found that the local flattening of the equilibrium pressure helps to mitigate the toroidal curvature induced screening effect [Glasser et al., Phys. Fluids 7, 875 (1975)]—the so called Glasser-Greene-Johnson screening, when the local toroidal flow near the mode rational surface is very slow (for example, as a result of mode locking associated with the field penetration). The saturation level of the plasma response amplitude is computed, as the plasma rotation frequency approaches zero. The local modification of the plasma resistivity inside the magnetic island is found to also affect the saturation level of the plasma response at vanishing flow.

Mucosal immunity in HIV controllers: the right place at the right time.

PubMed

Shacklett, Barbara L; Ferre, April L

2011-05-01

The phenomenon of long-term nonprogression in HIV infection has been recognized for some time, and the ability of rare individuals, designated 'elite controllers', to control HIV in the absence of therapy is the focus of numerous ongoing studies. This review focuses on studies of HIV-specific immune responses in mucosal tissues as a potential correlate of immune control, with an emphasis on recently published work. Genetic studies have implicated a role for elements localized to the major histocompatibility complex (MHC) on chromosome 6 in the immune control of HIV infection. In parallel, functional studies have strongly implicated MHC class I-restricted, CD8+ T-cell responses as a major contributor to elite control. In addition, the localization of HIV-specific CD8+ and CD4+ T cells with respect to the major sites of virus replication in the body may be critical in determining clinical outcome. Recent findings suggest that MHC class I-restricted, CD8+ T cells are a major component of immune control in 'elite controllers'. In addition, the presence of these effector cells at or near critical viral reservoirs, such as mucosal tissues, may be critical in determining their effectiveness at limiting viral replication and dissemination.

Joint Force Quarterly. Number 8, Summer 1995

DTIC Science & Technology

1995-06-01

commands. Control of the Bonin and the Marianas Islands was split with MacArthur controlling forces and local facilities, but having no responsibility for...Headquarters” Lieutenant Colonel Joseph H. Daves , USA (Army War College) “American Global Logistics and Peace Operations” Lieutenant Colonel James W. Dowis

Genetic control of rhizomes and genomic localization of a major-effect growth habit QTL in perennial wildrye

USDA-ARS?s Scientific Manuscript database

Subterranean rhizome branches facilitate vegetative dispersal, survival, and regrowth of perennial grasses. Developmental differences between upright, prostrate, and subterranean stem branching patterns may involve auxin-mediated responses to gravity or light, but genetic mechanisms controlling the...

The Effect of Local Violence on Children’s Attention and Impulse Control

PubMed Central

Tirado-Strayer, Nicole; Papachristos, Andrew V.; Raver, C. Cybele

2012-01-01

Objectives. We examined whether the burden of violence in a child’s community environment alters the child’s behavior and functioning in the classroom setting. Methods. To identify the effects of local violence, we exploited variation in the timing of local homicides, based on data from the Chicago Police Department, relative to the timing of interview assessments conducted as part of a randomized controlled trial conducted with preschoolers in Head Start programs from 2004–2006, the Chicago School Readiness Project. We compared children’s scores when exposed to recent local violence with scores when no recent violence had occurred to identify causal effects. Results. When children were assessed within a week of a homicide that occurred near their home, they exhibited lower levels of attention and impulse control and lower preacademic skills. The analysis showed strong positive effects of local violence on parental distress, providing suggestive evidence that parental responses may be a likely pathway by which local violence affects young children. Conclusions. Exposure to homicide generates acute psychological distress among caregivers and impairs children’s self-regulatory behavior and cognitive functioning. PMID:23078491

The Response of a 2D Emulsion to Local Perturbations

NASA Astrophysics Data System (ADS)

Hong, Xia; Orellana, Carlos; Weeks, Eric

2015-03-01

We experimentally perturb a quasi-two-dimensional emulsion packing by inflating an oil droplet into the system in a controlled way. Our samples are oil-in-water emulsion confined between two close-spaced parallel plates, so that the droplets are deformed into pancake shapes. In this system, there is only viscous friction and no static friction between droplets. By imaging the droplets with a video microscopy, we observe rearrangement events induced by the local perturbation. Simultaneously, we measure droplet-droplet contact forces by analyzing the outlines of each droplet in our movies. These allow us to study how the packings with varying degrees of spatial order have different responses to the local perturbation.

Evidence-Based Diabetes Prevention and Control Programs and Policies in Local Health Departments.

PubMed

Zwald, Marissa; Elliott, Lindsay; Brownson, Ross C; Skala, Mahree

2015-12-01

The purpose of this study is to: (1) assess implementation of evidence-based programs and policies (EBPPs) related to diabetes prevention and control in local health departments, (2) assess feasibility of non-implemented diabetes prevention and control EBPPs, and (3) examine individual- and organizational-level factors associated with implementation of diabetes prevention and control EBPPs. An online survey was administered in January 2015 to key representatives of all local health departments in Missouri. Descriptive statistics were used to describe implementation and perceived feasibility of 20 diabetes prevention and control EBPPs. Logistic regression was used to examine the association between individual and organizational factors and diabetes prevention and control EBPP implementation. One hundred local health departments participated (89% response rate) in the online survey. Most frequently implemented diabetes-related EBPPs in local health departments included: nutrition education for agency or community members, increased fruit and vegetable access in community settings, and community-wide campaigns to promote physical activity. Increased encouragement to others in the department to use evidence-based decision making and agency incentives to help employees use evidence-based decision making were positively associated with implementation of diabetes prevention and control EBPPs. Local health departments are on the "front line" of public health, and this study demonstrates the important role these organizations play in implementing diabetes prevention and control EBPPs. Potential leverage points for more widespread adoption of diabetes-related EBPPs in local health departments include education about and encouragement of evidence-based decision making and organizational incentives for employees to integrate evidence-based decision making into their diabetes prevention and control activities. © 2015 The Author(s).

Evidence-based diabetes prevention and control programs and policies in local health departments

PubMed Central

Zwald, Marissa; Elliott, Lindsay; Brownson, Ross C.; Skala, Mahree

2016-01-01

Purpose The purpose of this study is to: (1) assess implementation of evidence-based programs and policies (EBPPs) related to diabetes prevention and control in local health departments; (2) assess feasibility of non-implemented diabetes prevention and control EBPPs; and (3) examine individual- and organizational-level factors associated with implementation of diabetes prevention and control EBPPs. Methods An online survey was administered in January 2015 to key representatives of all local health departments in Missouri. Descriptive statistics were used to describe implementation and perceived feasibility of 20 diabetes prevention and control EBPPs. Logistic regression was used to examine the association between individual and organizational factors and diabetes prevention and control EBPP implementation. Results One hundred local health departments participated (89% response rate) in the online survey. Most frequently implemented diabetes-related EBPPs in local health departments included: nutrition education for agency or community members; increased fruit and vegetable access in community settings; and community-wide campaigns to promote physical activity. Increased encouragement to others in the department to use evidence-based decision making and agency incentives to help employees use evidence-based decision making were positively associated with implementation of diabetes prevention and control EBPPs. Conclusions Local health departments are the “front line” of public health and this study demonstrates the important role these organizations play in implementing diabetes prevention and control EBPPs. Potential leverage points for more widespread adoption of diabetes-related EBPPs in local health departments include education about and encouragement of evidence-based decision making and organizational incentives for employees to integrate evidence-based decision making into their diabetes prevention and control activities. PMID:26297714

Control of the NASA Langley 16-Foot Transonic Tunnel with the Self-Organizing Feature Map

NASA Technical Reports Server (NTRS)

Motter, Mark A.

1998-01-01

A predictive, multiple model control strategy is developed based on an ensemble of local linear models of the nonlinear system dynamics for a transonic wind tunnel. The local linear models are estimated directly from the weights of a Self Organizing Feature Map (SOFM). Local linear modeling of nonlinear autonomous systems with the SOFM is extended to a control framework where the modeled system is nonautonomous, driven by an exogenous input. This extension to a control framework is based on the consideration of a finite number of subregions in the control space. Multiple self organizing feature maps collectively model the global response of the wind tunnel to a finite set of representative prototype controls. These prototype controls partition the control space and incorporate experimental knowledge gained from decades of operation. Each SOFM models the combination of the tunnel with one of the representative controls, over the entire range of operation. The SOFM based linear models are used to predict the tunnel response to a larger family of control sequences which are clustered on the representative prototypes. The control sequence which corresponds to the prediction that best satisfies the requirements on the system output is applied as the external driving signal. Each SOFM provides a codebook representation of the tunnel dynamics corresponding to a prototype control. Different dynamic regimes are organized into topological neighborhoods where the adjacent entries in the codebook represent the minimization of a similarity metric which is the essence of the self organizing feature of the map. Thus, the SOFM is additionally employed to identify the local dynamical regime, and consequently implements a switching scheme than selects the best available model for the applied control. Experimental results of controlling the wind tunnel, with the proposed method, during operational runs where strict research requirements on the control of the Mach number were met, are presented. Comparison to similar runs under the same conditions with the tunnel controlled by either the existing controller or an expert operator indicate the superiority of the method.

Local Populations of Arabidopsis thaliana Show Clear Relationship between Photoperiodic Sensitivity of Flowering Time and Altitude

PubMed Central

Lewandowska-Sabat, Anna M.; Fjellheim, Siri; Olsen, Jorunn E.; Rognli, Odd A.

2017-01-01

Adaptation of plants to local conditions that vary substantially within their geographic range is essential for seasonal timing of flowering, a major determinant of plant reproductive success. This study investigates photoperiodic responses in natural populations of Arabidopsis thaliana from high northern latitudes and their significance for local adaptation. Thirty lineages from ten local A. thaliana populations, representing different locations across an altitudinal gradient (2–850 m a.s.l.) in Norway, were grown under uniform controlled conditions, and used to screen for responses to five different photoperiods. We studied relationships between variation in photoperiodic sensitivity of flowering time, altitude, and climatic factors associated with the sites of origin. We found that variation in response to photoperiod is significantly correlated with altitude and climatic variables associated with the sites of origin of the populations. Populations originating from lower altitudes showed stronger photoperiodic sensitivity than populations from higher altitudes. Our results indicate that the altitudinal climatic gradient generates clinal variation in adaptive traits in A. thaliana. PMID:28659966

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

PubMed

Mignot, Grégoire; Hervieu, Alice; Vabres, Pierre; Dalac, Sophie; Jeudy, Geraldine; Bel, Blandine; Apetoh, Lionel; Ghiringhelli, François

2014-01-01

The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.

Determinants of Health Service Responsiveness in Community-Based Vector Surveillance for Chagas Disease in Guatemala, El Salvador, and Honduras

PubMed Central

Hashimoto, Ken; Zúniga, Concepción; Romero, Eduardo; Morales, Zoraida; Maguire, James H.

2015-01-01

Background Central American countries face a major challenge in the control of Triatoma dimidiata, a widespread vector of Chagas disease that cannot be eliminated. The key to maintaining the risk of transmission of Trypanosoma cruzi at lowest levels is to sustain surveillance throughout endemic areas. Guatemala, El Salvador, and Honduras integrated community-based vector surveillance into local health systems. Community participation was effective in detection of the vector, but some health services had difficulty sustaining their response to reports of vectors from the population. To date, no research has investigated how best to maintain and reinforce health service responsiveness, especially in resource-limited settings. Methodology/Principal Findings We reviewed surveillance and response records of 12 health centers in Guatemala, El Salvador, and Honduras from 2008 to 2012 and analyzed the data in relation to the volume of reports of vector infestation, local geography, demography, human resources, managerial approach, and results of interviews with health workers. Health service responsiveness was defined as the percentage of households that reported vector infestation for which the local health service provided indoor residual spraying of insecticide or educational advice. Eight potential determinants of responsiveness were evaluated by linear and mixed-effects multi-linear regression. Health service responsiveness (overall 77.4%) was significantly associated with quarterly monitoring by departmental health offices. Other potential determinants of responsiveness were not found to be significant, partly because of short- and long-term strategies, such as temporary adjustments in manpower and redistribution of tasks among local participants in the effort. Conclusions/Significance Consistent monitoring within the local health system contributes to sustainability of health service responsiveness in community-based vector surveillance of Chagas disease. Even with limited resources, countries can improve health service responsiveness with thoughtful strategies and management practices in the local health systems. PMID:26252767

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures

NASA Astrophysics Data System (ADS)

Ma, Ji; Franco, Brian; Tapia, Gustavo; Karayagiz, Kubra; Johnson, Luke; Liu, Jun; Arroyave, Raymundo; Karaman, Ibrahim; Elwany, Alaa

2017-04-01

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

Increased Error-Related Negativity (ERN) in Childhood Anxiety Disorders: ERP and Source Localization

ERIC Educational Resources Information Center

Ladouceur, Cecile D.; Dahl, Ronald E.; Birmaher, Boris; Axelson, David A.; Ryan, Neal D.

2006-01-01

Background: In this study we used event-related potentials (ERPs) and source localization analyses to track the time course of neural activity underlying response monitoring in children diagnosed with an anxiety disorder compared to age-matched low-risk normal controls. Methods: High-density ERPs were examined following errors on a flanker task…

Assessing local health department performance in diabetes prevention and control--North Carolina, 2005.

PubMed

Porterfield, Deborah S; Reaves, Janet; Konrad, Thomas R; Weiner, Bryan J; Garrett, Joanne M; Davis, Mary; Dickson, Curtis W; Plescia, Marcus; Alexander, Janet; Baker, Edward L

2009-07-01

To improve the public health system's ability to prevent and control chronic diseases, we must first understand current practice and develop appropriate strategies for measuring performance. The objectives of this study were to measure capacity and performance of local health departments in diabetes prevention and control and to investigate characteristics associated with performance. In 2005, we conducted a cross-sectional mailed survey of all 85 North Carolina local health departments to assess capacity and performance in diabetes prevention and control based on the 10 Essential Public Health Services and adapted from the Local Public Health System Performance Assessment Instrument. We linked survey responses to county-level data, including data from a national survey of local health departments. Local health departments reported a median of 0.05 full-time equivalent employees in diabetes prevention and 0.1 in control. Performance varied across the 10 Essential Services; activities most commonly reported included providing information to the public and to policy makers (76%), providing diabetes education (58%), and screening (74%). The mean score on a 10-point performance index was 3.5. Characteristics associated with performance were population size, health department size and accreditation status, and diabetes-specific external funding. Performance was not better in localities where the prevalence of diabetes was high or availability of primary care was low. Most North Carolina local health departments had limited capacity to conduct diabetes prevention or control programs in their communities. Diabetes is a major cause of illness and death, yet it is neglected in public health practice. These findings suggest opportunities to enhance local public health practice, particularly through targeted funding and technical assistance.

Local Control: Fear or Fantasy?

ERIC Educational Resources Information Center

Fuhrman, Susan H.

1974-01-01

From all existing evidence, there is no inevitability about the relationship between centralized fiscal responsibility and decentralized decisionmaking. He who pays the piper does not necessarily call the tune. (Author)

The influence of mechanical vibration on local and central balance control.

PubMed

Ehsani, Hossein; Mohler, Jane; Marlinski, Vladimir; Rashedi, Ehsan; Toosizadeh, Nima

2018-04-11

Fall prevention has an indispensable role in enhancing life expectancy and quality of life among older adults. The first step to prevent falls is to devise reliable methods to identify individuals at high fall risk. The purpose of the current study was to assess alterations in local postural muscle and central sensory balance control mechanisms due to low-frequency externally applied vibration among elders at high fall risk, in comparison with healthy controls, as a potential tool for assessing fall risk. Three groups of participants were recruited: healthy young (n = 10; age = 23 ± 2 years), healthy elders (n = 10; age = 73 ± 3 years), and elders at high fall risk (n = 10; age = 84 ± 9 years). Eyes-open and eyes-closed upright standing balance performance was measured with no vibration, 30 Hz, and 40 Hz vibration of Gastrocnemius muscles. When vibratory stimulation was applied, changes in local-control performance manifested significant differences among the groups (p < 0.01). On average between conditions, we observed 97% and 92% less change among high fall risk participants when compared to healthy young and older adults, respectively. On the other hand, vibration-induced changes in the central-control performance were not significant between groups (p ≥ 0.19). Results suggest that local-control deficits are responsible for balance behavior alterations among elders at high fall risk and healthy individuals. This observation may be attributable to deterioration of short-latency reflexive loop in elders at high fall risk. On the other hand, we could not ascribe the balance alterations to problems related to central nervous system performance or long-latency responses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Local Transcriptional Control of YUCCA Regulates Auxin Promoted Root-Growth Inhibition in Response to Aluminium Stress in Arabidopsis.

PubMed

Liu, Guangchao; Gao, Shan; Tian, Huiyu; Wu, Wenwen; Robert, Hélène S; Ding, Zhaojun

2016-10-01

Auxin is necessary for the inhibition of root growth induced by aluminium (Al) stress, however the molecular mechanism controlling this is largely unknown. Here, we report that YUCCA (YUC), which encodes flavin monooxygenase-like proteins, regulates local auxin biosynthesis in the root apex transition zone (TZ) in response to Al stress. Al stress up-regulates YUC3/5/7/8/9 in the root-apex TZ, which we show results in the accumulation of auxin in the root-apex TZ and root-growth inhibition during the Al stress response. These Al-dependent changes in the regulation of YUCs in the root-apex TZ and YUC-regulated root growth inhibition are dependent on ethylene signalling. Increasing or disruption of ethylene signalling caused either enhanced or reduced up-regulation, respectively, of YUCs in root-apex TZ in response to Al stress. In addition, ethylene enhanced root growth inhibition under Al stress was strongly alleviated in yuc mutants or by co-treatment with yucasin, an inhibitor of YUC activity, suggesting a downstream role of YUCs in this process. Moreover, ethylene-insensitive 3 (EIN3) is involved into the direct regulation of YUC9 transcription in this process. Furthermore, we demonstrated that PHYTOCHROME INTERACTING FACTOR4 (PIF4) functions as a transcriptional activator for YUC5/8/9. PIF4 promotes Al-inhibited primary root growth by regulating the local expression of YUCs and auxin signal in the root-apex TZ. The Al-induced expression of PIF4 in root TZ acts downstream of ethylene signalling. Taken together, our results highlight a regulatory cascade for YUCs-regulated local auxin biosynthesis in the root-apex TZ mediating root growth inhibition in response to Al stress.

Portal vein thrombosis and arterioportal shunts: Effects on tumor response after chemoembolization of hepatocellular carcinoma

PubMed Central

Vogl, Thomas J; Nour-Eldin, Nour-Eldin; Emad-Eldin, Sally; Naguib, Nagy NN; Trojan, Joerg; Ackermann, Hans; Abdelaziz, Omar

2011-01-01

AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS. PMID:21455325

33 CFR 209.220 - Flood control regulations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the purpose of coordinating the operation of the flood control features of reservoirs constructed... responsible for the maintenance and operation of the reservoir involved after a detailed study of the flood.... Regulations prescribed by the Secretary of the Army for the maintenance and operation of local flood...

33 CFR 209.220 - Flood control regulations.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the purpose of coordinating the operation of the flood control features of reservoirs constructed... responsible for the maintenance and operation of the reservoir involved after a detailed study of the flood.... Regulations prescribed by the Secretary of the Army for the maintenance and operation of local flood...

Development of a traffic control devices and pavement markings manual for Iowa's cities and counties with a survey of common practices.

DOT National Transportation Integrated Search

2001-04-01

Local transportation agencies are responsible for a significant investment in traffic control : devices and pavement markings. Thousands of signs and other inventory items, equipment, : facilities, and staff are all dedicated to the installation and ...

Effect of short-term water restriction in hot season on some blood parameters and immune response to Newcastle disease vaccine of local and commercial layers in the late phase of production.

PubMed

Alamer, M A; Ahmed, A S

2012-08-01

Forty-five Hisex commercial layers and forty-five local Saudi breed layers were used to compare and assess the effect of water restriction under hot conditions on blood constituents and immune response to Newcastle disease (ND) vaccine. The trial was divided into three periods: control (7 day), water restriction (14 day) and rehydration (7 day). During water restriction, layers from each breed were divided into three groups that received 0%, 20% and 40% restriction of drinking water relative to the control period. The immune response against ND was affected by breed; it also declined significantly with 40% water restriction 10 days post-restriction. Water restriction did not affect haematocrit value, plasma total protein, albumin, glucose or osmolality, which may not suggest a reduction in plasma volume. However, plasma creatinine increased in both breeds because of water restriction that remained elevated during rehydration. Water restriction increased plasma urea in the local group, while it decreased in the commercial group. Irrespective of rate of water restriction, it can be concluded that the two breeds can withstand up to 40% water restriction during high environmental temperature. However, the local breed may be superior in water conservation in relation to the commercial layers. © 2011 Blackwell Verlag GmbH.

Radical chemo-irradiation using intensity-modulated radiotherapy for locally advanced head and neck cancer in elderly patients: Experience from a tertiary care center in South India.

PubMed

Chalissery, J R; Sudheeran, P C; Varghese, K M; Venkatesan, K

2016-01-01

To assess the feasibility, tolerance and response of radical chemo irradiation using Intensity modulated Radiotherapy [IMRT] in elderly patients [age >65] with locally advanced head and neck cancer. Patients aged 65 and above [range 65 to 84years] registered in oncology outpatient unit in our institution between December 2011 to 2014, with stage III and IV head and neck cancer were treated with radical dose of radiotherapy using IMRT and concurrent chemotherapy with cisplatin 40mg/sq.m weekly. Response evaluation and toxicity profile assessment was done 6 to 8 weeks after completion of treatment and 3 monthly thereafter with median follow up of 3 years. Total number of patients analysed were 47. 43(91.5%) patients tolerated 66-.70Gy of radiotherapy and 4 or more cycles of weekly chemotherapy with cisplatin. First follow up evaluation at 6 to 8 weeks showed 81% patients having complete loco regional response. Grade III skin reaction and mucositis was noticed in 24% and 47% respectively. No grade III neutropenia observed. Median follow up of 3 years showed a complete local control in 53% and overall survival of 60%. Radical chemo irradiation with IMRT in elderly patients is a feasible option. Long term local control and overall survival benefits needs to be followed up.

Theta dynamics reveal domain-specific control over stimulus and response conflict.

PubMed

Nigbur, Roland; Cohen, Michael X; Ridderinkhof, K Richard; Stürmer, Birgit

2012-05-01

Cognitive control allows us to adjust to environmental changes. The medial frontal cortex (MFC) is thought to detect conflicts and recruit additional resources from other brain areas including the lateral prefrontal cortices. Here we investigated how the MFC acts in concert with visual, motor, and lateral prefrontal cortices to support adaptations of goal-directed behavior. Physiologically, these interactions may occur through local and long-range synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A speeded flanker task allowed us to investigate conflict-type-specific control networks for perceptual and response conflicts. Theta power over MFC was sensitive to both perceptual and response conflict. Interareal theta phase synchrony, however, indicated a selective enhancement specific for response conflicts between MFC and left frontal cortex as well as between MFC and the presumed motor cortex contralateral to the response hand. These findings suggest that MFC theta-band activity is both generally involved in conflict processing and specifically involved in linking a neural network controlling response conflict.

Nematicons and Their Electro-Optic Control: Light Localization and Signal Readdressing via Reorientation in Liquid Crystals

PubMed Central

Piccardi, Armando; Alberucci, Alessandro; Assanto, Gaetano

2013-01-01

Liquid crystals in the nematic phase exhibit substantial reorientation when the molecules are driven by electric fields of any frequencies. Exploiting such a response at optical frequencies, self-focusing supports transverse localization of light and the propagation of self-confined beams and waveguides, namely “nematicons”. Nematicons can guide other light signals and interact with inhomogeneities and other beams. Moreover, they can be effectively deviated by using the electro-optic response of the medium, leading to several strategies for voltage-controlled reconfiguration of light-induced guided-wave circuits and signal readdressing. Hereby, we outline the main features of nematicons and review the outstanding progress achieved in the last twelve years on beam self-trapping and electro-optic readdressing. PMID:24108367

The C2 Workstation and Data Replication over Disadvantaged Tactical Communication Links

DTIC Science & Technology

2007-09-01

person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number...SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU 18. NUMBER OF PAGES 14 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b...PUBLIC RELEASE C2WS Physical Environment Zodiac Network Radio Network Combat Level Node (Vehicle) Radio Local Store Local Store Local Store To Other

Radiotherapy and Hyperthermia for Treatment of Primary Locally Advanced Cervix Cancer: Results in 378 Patients

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

Franckena, Martine; Lutgens, Ludy C.; Koper, Peter C.

2009-01-01

Purpose: To report response rate, pelvic tumor control, survival, and late toxicity after treatment with combined radiotherapy and hyperthermia (RHT) for patients with locally advanced cervical carcinoma (LACC) and compare the results with other published series. Methods and Materials: From 1996 to 2005, a total of 378 patients with LACC (International Federation of Gynecology and Obstetrics Stage IB2-IVA) were treated with RHT. External beam radiotherapy (RT) was applied to 46-50.4 Gy and combined with brachytherapy. The hyperthermia (HT) was prescribed once weekly. Primary end points were complete response (CR) and local control. Secondary end points were overall survival, disease-specific survival,more » and late toxicity. Patient, tumor, and treatment characteristics predictive for the end points were identified in univariate and multivariate analyses. Results: Overall, a CR was achieved in 77% of patients. At 5 years, local control, disease-specific survival, and incidence of late toxicity Common Terminology Criteria for Adverse Events Grade 3 or higher were 53%, 47%, and 12%, respectively. In multivariate analysis, number of HT treatments emerged as a predictor of outcome in addition to commonly identified prognostic factors. Conclusions: The CR, local control, and survival rates are similar to previously observed results of RHT in the randomized Dutch Deep Hyperthermia Trial. Reported treatment results for currently applied combined treatment modalities (i.e., RT with chemotherapy and/or HT) do not permit definite conclusions about which combination is superior. The present results confirm previously shown beneficial effects from adding HT to RT and justify the application of RHT as first-line treatment in patients with LACC as an alternative to chemoradiation.« less

Model based PI power system stabilizer design for damping low frequency oscillations in power systems.

PubMed

Salgotra, Aprajita; Pan, Somnath

2018-05-01

This paper explores a two-level control strategy by blending local controller with centralized controller for the low frequency oscillations in a power system. The proposed control scheme provides stabilization of local modes using a local controller and minimizes the effect of inter-connection of sub-systems performance through a centralized control. For designing the local controllers in the form of proportional-integral power system stabilizer (PI-PSS), a simple and straight forward frequency domain direct synthesis method is considered that works on use of a suitable reference model which is based on the desired requirements. Several examples both on one machine infinite bus and multi-machine systems taken from the literature are illustrated to show the efficacy of the proposed PI-PSS. The effective damping of the systems is found to be increased remarkably which is reflected in the time-responses; even unstable operation has been stabilized with improved damping after applying the proposed controller. The proposed controllers give remarkable improvement in damping the oscillations in all the illustrations considered here and as for example, the value of damping factor has been increased from 0.0217 to 0.666 in Example 1. The simulation results obtained by the proposed control strategy are favourably compared with some controllers prevalent in the literature. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

The development and implementation of a Hospital Emergency Response Team (HERT) for out-of-hospital surgical care.

PubMed

Scott, Christopher; Putnam, Brant; Bricker, Scott; Schneider, Laura; Raby, Stephanie; Koenig, William; Gausche-Hill, Marianne

2012-06-01

Over the past two decades, Los Angeles County has implemented a Hospital Emergency Response Team (HERT) to provide on-scene, advanced surgical care of injured patients as an element of the local Emergency Medical Services (EMS) system. Since 2008, the primary responsibility of the team has been to perform surgical procedures in the austere field setting when prolonged extrication is anticipated. Following the maxim of "life over limb," the team is equipped to provide rapid amputation of an entrapped extremity as well as other procedures and medical care, such as anxiolytics and advanced pain control. This report describes the development and implementation of a local EMS system HERT.

75 FR 17203 - National Rail Plan

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

..., such as roles and responsibilities, including national leadership as well as those of State, and local... considering implementation of high-speed rail and technological advances such as positive train control and...

School Boards as Policy-Makers.

ERIC Educational Resources Information Center

Coleman, Peter

Decision-making in general and policy decisions in particular are the prime responsibility of school boards because policies are control mechanisms by which trustees assert local control. Policy decisions differ from others in their concern with values and purposes and the legitimization of the organization to society at large. Additionally, they…

Temperature offset control system

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

Fried, M.

1987-07-28

This patent describes a temperature offset control system for controlling the operation of both heating and air conditioning systems simultaneously contained within the same premises each of which is set by local thermostats to operate at an appropriate temperature, the offset control system comprising: a central control station having means for presetting an offset temperature range, means for sensing the temperature at a central location, means for comparing the sensed temperature with the offset temperature range, means responsive to the comparison for producing a control signal indicative of whether the sensed temperature is within the offset temperature range or beyondmore » the offset temperature range, and means for transmitting the control signal onto the standard energy lines servicing the premises; and a receiving station respectively associated with each heating and air conditioning system, the receiving stations each comprising means for receiving the same transmitted control signal from the energy lines, and switch means for controlling the energization of the respective system in response to the received control signal. The heating systems and associated local thermostat are disabled by the control signal when the control signal originates from a sensed temperature above the lower end of the offset temperature range. The air conditioning systems and associated thermostats are disabled by the same control signal when the control signal originates from a sensed temperature below the upper end of the offset temperature range.« less

Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis.

PubMed

Thavaneswaran, Subotheni; Kok, Peey Sei; Price, Timothy

2017-10-01

Multimodality treatment of patients with locally advanced rectal cancer (LARC) has significantly improved local disease control, however the unaltered overall survival (OS) implicates an inability to further control micrometastases, providing rationale for intensified systemic treatment. A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC. We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included. Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation. There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed.

Stereotactic body radiation therapy for liver oligometastases: predictive factors of local response by 18F-FDG-PET/CT.

PubMed

Mazzola, Rosario; Fersino, Sergio; Alongi, Pierpaolo; Di Paola, Gioacchino; Gregucci, Fabiana; Aiello, Dario; Tebano, Umberto; Pasetto, Stefano; Ruggieri, Ruggero; Salgarello, Matteo; Alongi, Filippo

2018-05-23

To investigate metabolic parameters as predictive of local response after stereotactic body radiation therapy (SBRT) for liver-oligometastases. Inclusion criteria of the present retrospective study were: (a) liver oligometastases with controlled primary tumor; (b) absence of progressive disease ≥6 months; (c) metastases ≤ 3; (d) evaluation of SBRT-response by means of 18-fludeoxyglucose-PET/CT for at least two subsequent evaluations; (e) Karnofsky performance status >80; (f) life-expectancy >6 months. The following metabolic parameters were defined semi-quantitatively for each metastases: (1) standardized uptake value (SUVmax; (2) SUV-mean; (3) metabolic tumor volume (MTV), tumor volume with a SUV ≥3, threshold 40%; (4) total lesion glycolysis (TLG), i.e. the product of SUV-mean and MTV. Local control was defined as absence of recurrence in the field of irradiation. 41 liver metastases were analyzed. Pre-SBRT, median SUV-max was 8.7 (range, 4.5-23.59), median SUV-mean was 4.6 (range, 3-7.5), median MTV was 5.7 cc (range, 0.9-80.6) and median total lesion glycolysis was 24.1 (range, 3.6-601.5). At statistical analysis, metastases with SUV-mean >5 (p 0.04; odds ratio 4.75, sensitivity = 50%, specificity = 82.6%, area under the curve 0.66) and SUV-max >12 (p 0.02; odds ratio 5.03, sensitivity = 69%, specificity = 70%, area under the curve = 0.69) showed higher rates of infield-failure compared to the remaining lesions. According to current findings, pre-SBRT SUV-max and SUV-mean could be predictable of local response in liver oligometastases. Advances in knowledge: Present findings could support the hypothesis that fludeoxyglucose-PET/CT may be a powerful tool to predict tumor control. Specifically, current results might be helpful for clinicians in the decision-making process regarding liver oligometastatic patient selection as well as the individual therapy stratification distinguishing between slowly local progressing patients and rapidly progressing patients.

Research participation among state and local public health emergency preparedness and response programs.

PubMed

Yusuf, H; Ekperi, L; Groseclose, S; Siegfried, A; Meit, M; Carbone, E

2018-06-01

The objective of our study was to assess whether state and local health staff participated in public health emergency preparedness research activities and what partner organizations they collaborated with on research. This is a cross-sectional study. Data were derived from a 2014 web-based survey of state, territorial, and local health departments conducted by the Centers for Disease Control and Prevention and NORC at the University of Chicago as part of a larger project to assess the public health emergency preparedness and response research priorities of state and local health departments. Overall, 30% of survey respondents indicated that health department staff were involved in public health preparedness and response research-related activities. Thirty-four percent indicated that they were extremely or moderately familiar with emergency preparedness research and literature. Approximately 67% of respondents reported interest in receiving additional information and/or training related to the preparedness research and literature. The most frequently reported partners for collaboration in preparedness research-related activities were schools of public health (34%). Our findings suggest that there is health department interest in learning more about preparedness and response science and that additional efforts are needed to increase health department participation in public health emergency preparedness and response research-related activities. Published by Elsevier Ltd.

Trajectory Control and Optimization for Responsive Spacecraft

DTIC Science & Technology

2012-03-22

Orbital Elements and Local-Vertical-Local-Horizontal Frame 10 2.3 Equinoctial Frame with respect to ECI Frame [17] . . . . . . . . . 14 3.1...position and velocity, classical orbital elements , and equinoctial elements . These methods are detailed in the following sections. 2.1.1 Inertial Position...trajectory. However, if the singularities are unavoidable equinoctial orbital elements could be used. 2.1.3 Equinoctial Elements . Equinoctial

Bioinspired Programmable Polymer Gel Controlled by Swellable Guest Medium.

PubMed

Deng, Heng; Dong, Yuan; Su, Jheng-Wun; Zhang, Cheng; Xie, Yunchao; Zhang, Chi; Maschmann, Matthew R; Lin, Yuyi; Lin, Jian

2017-09-13

Responsive materials with functions of forming three-dimensional (3D) origami and/or kirigami structures have a broad range of applications in bioelectronics, metamaterials, microrobotics, and microelectromechanical (MEMS) systems. To realize such functions, building blocks of actuating components usually possess localized inhomogeneity so that they respond differently to external stimuli. Previous fabrication strategies lie in localizing nonswellable or less-swellable guest components in their swellable host polymers to reduce swelling ability. Herein, inspired by ice plant seed capsules, we report an opposite strategy of implanting swellable guest medium inside nonswellable host polymers to locally enhance the swelling inhomogeneity. Specifically, we adopted a skinning effect induced surface polymerization combined with direct laser writing to control gradient of swellable cyclopentanone (CP) in both vertical and lateral directions of the nonswellable SU-8. For the first time, the laser direct writing was used as a novel strategy for patterning programmable polymer gel films. Upon stimulation of organic solvents, the dual-gradient gel films designed by origami or kirigami principles exhibit reversible 3D shape transformation. Molecular dynamics (MD) simulation illustrates that CP greatly enhances diffusion rates of stimulus solvent molecules in the SU-8 matrix, which offers the driving force for the programmable response. Furthermore, this bioinspired strategy offers unique capabilities in fabricating responsive devices such as a soft gripper and a locomotive robot, paving new routes to many other responsive polymers.

Evaluation of serum concentrations of the selected cytokines in patients with localized scleroderma.

PubMed

Budzyńska-Włodarczyk, Jolanta; Michalska-Jakubus, Małgorzata M; Kowal, Małgorzata; Krasowska, Dorota

2016-02-01

Localized scleroderma is an autoimmune disease primarily affecting the skin. The cause of disease remains unexplained although environmental factors are implicated, which are likely to be responsible for activation of the endothelium and subsequent inflammation leading to excessive synthesis of collagen and extracellular matrix components. To determine concentrations of interleukin (IL)-27, transforming growth factor (TGF)-β1, TGF-β2, IL-6, and sIL-6R in patients with localized scleroderma compared to controls and to assess the relations between their levels and laboratory markers. The study encompassed 17 females with localized scleroderma (aged 25-67). The control group consisted of 30 age-matched healthy women. The blood was sampled from the basilic vein. Serum levels of cytokines were determined using ELISA. The TGF-β2 levels were found to be significantly lower in patients with localized scleroderma compared to controls. Concentrations of TGF-β1 were decreased in scleroderma patients when compared to controls but without statistical significance. There were no significant differences in serum IL-6, sIL-6R and IL-27 levels between patients and the control group; however, we found a significant positive correlation between the level of sIL-6 and ESR among subjects with localized scleroderma. The findings of decreased serum levels of TGF-β1 and TGF-β2 in patients with localized scleroderma demonstrate a possible association of these cytokines with pathogenesis of the disease. The results suggest also that sIL-6R is likely to be involved in inflammation in patients with localized scleroderma.

No evidence of local adaptation of immune responses to Gyrodactylus in three-spined stickleback (Gasterosteus aculeatus).

PubMed

Robertson, Shaun; Bradley, Janette E; MacColl, Andrew D C

2017-01-01

Parasitism represents one of the most widespread lifestyles in the animal kingdom, with the potential to drive coevolutionary dynamics with their host population. Where hosts and parasites evolve together, we may find local adaptation. As one of the main host defences against infection, there is the potential for the immune response to be adapted to local parasites. In this study, we used the three-spined stickleback and its Gyrodactylus parasites to examine the extent of local adaptation of parasite infection dynamics and the immune response to infection. We took two geographically isolated host populations infected with two distinct Gyrodactylus species and performed a reciprocal cross-infection experiment in controlled laboratory conditions. Parasite burdens were monitored over the course of the infection, and individuals were sampled at multiple time points for immune gene expression analysis. We found large differences in virulence between parasite species, irrespective of host, and maladaptation of parasites to their sympatric host. The immune system responded to infection, with a decrease in expression of innate and Th1-type adaptive response genes in fish infected with the less virulent parasite, representing a marker of a possible resistance mechanism. There was no evidence of local adaptation in immune gene expression levels. Our results add to the growing understanding of the extent of host-parasite local adaptation, and demonstrate a systemic immune response during infection with a common ectoparasite. Further immunological studies using the stickleback-Gyrodactylus system can continue to contribute to our understanding of the function of the immune response in natural populations. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Altered soleus responses to magnetic stimulation in pure cerebellar ataxia.

PubMed

Kurokawa-Kuroda, Tomomi; Ogata, Katsuya; Suga, Rie; Goto, Yoshinobu; Taniwaki, Takayuki; Kira, Jun-Ichi; Tobimatsu, Shozo

2007-06-01

Transcranial magnetic stimulation (TMS) over the leg motor area elicits a soleus primary response (SPR) and a soleus late response (SLR). We evaluated the influence of the cerebellofugal pathway on the SPR and SLR in patients with 'pure' cerebellar ataxia. SPRs and SLRs were recorded from 11 healthy subjects and 9 patients with 'pure' cerebellar cortical degeneration; 5 with spinocerebellar ataxia type 6 (SCA6), and 4 with late cortical cerebellar ataxia (LCCA). In addition, three patients with localized cerebellar lesions were tested. The SPR latency was significantly longer in patients than in controls, but primary responses in the tibialis anterior muscle were normal. The frequency of abnormal SLR was 38.9% in the supine position and 83.3% in the standing position. Two out of three patients with localized cerebellar lesions also showed abnormal SLR. Altered SPRs in patients may result from a dysfunction of the primary motor cortex caused by crossed cerebello-cerebral diaschisis. In addition, our results suggest that 'pure' cerebellar degeneration involves the mechanism responsible for evoking SLR which is related to the control of posture. SLR can be a useful neurophysiological parameter for evaluating cerebellofugal function.

Preoperative Capecitabine and Pelvic Radiation in Locally Advanced Rectal Cancer-Is it Equivalent to 5-FU Infusion Plus Leucovorin and Radiotherapy?

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

Chan, Alexander K., E-mail: alexc@cancerboard.ab.c; Wong, Alfred O.; Jenken, Daryl A.

2010-04-15

Purpose: The aim of this retrospective case-matching study was to compare the treatment outcomes and acute toxicity of preoperative radiotherapy (RT) with capecitabine vs. preoperative RT with intermittent 5-fluorouracil (5-FU) infusion, leucovorin, and mitomycin C in rectal cancer. Methods and Materials: We matched 34 patients who were treated with preoperative concurrent capecitabine and 50 Gy of RT by their clinical T stage (T3 or T4) and the tumor location (<=7 cm or >7 cm from the anal verge) with another 68 patients who were treated with preoperative intermittent 5-FU infusion, leucovorin, mitomycin C, and 50 Gy of RT for amore » comparison of the pathologic tumor response, local control, distant failure, and survival rates. Results: The pathologic complete response rate was 21% with capecitabine and 18% with 5-FU and leucovorin (p = 0.72). The rate of T downstaging after chemoradiation was 59% for both groups. The rate of sphincter-sparing resection was 38% after capecitabine plus RT and 43% after 5-FU plus RT (p = 0.67). At 3 years, there was no significant difference in the local control rate (93% for capecitabine and 92% for 5-FU and leucovorin), relapse-free rate (74% for capecitabine and 73% for 5-FU and leucovorin), or disease-specific survival rate (86% for capecitabine and 77% for 5-FU and leucovorin). The acute toxicity profile was comparable, with little Grade 3 and 4 toxicity. Conclusions: When administered with concurrent preoperative RT, both capecitabine and intermittent 5-FU infusion with leucovorin modulation provided comparable pathologic tumor response, local control, relapse-free survival, and disease-specific survival rates in rectal cancer.« less

Distributed traffic signal control using fuzzy logic

NASA Technical Reports Server (NTRS)

Chiu, Stephen

1992-01-01

We present a distributed approach to traffic signal control, where the signal timing parameters at a given intersection are adjusted as functions of the local traffic condition and of the signal timing parameters at adjacent intersections. Thus, the signal timing parameters evolve dynamically using only local information to improve traffic flow. This distributed approach provides for a fault-tolerant, highly responsive traffic management system. The signal timing at an intersection is defined by three parameters: cycle time, phase split, and offset. We use fuzzy decision rules to adjust these three parameters based only on local information. The amount of change in the timing parameters during each cycle is limited to a small fraction of the current parameters to ensure smooth transition. We show the effectiveness of this method through simulation of the traffic flow in a network of controlled intersections.

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures

PubMed Central

Ma, Ji; Franco, Brian; Tapia, Gustavo; Karayagiz, Kubra; Johnson, Luke; Liu, Jun; Arroyave, Raymundo; Karaman, Ibrahim; Elwany, Alaa

2017-01-01

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods. PMID:28429796

Analysis of the peripheral immune response in patients with neurocysticercosis: evidence for T cell reactivity to parasite glycoprotein and vesicular fluid antigens.

PubMed

Restrepo, B I; Aguilar, M I; Melby, P C; Teale, J M

2001-10-01

In neurocysticercosis (NCC), it is thought that the long-term survival of the parasite within the human brain is due in part to the ability of the cestode to suppress the local immune response. When the parasite dies, the immunosuppression is apparently lost and a strong local inflammatory response then develops. In contrast, little is known about the immunologic response that may occur in the peripheral immune system of these patients. In this study, the status of the peripheral (extracerebral) cellular and humoral response was evaluated in patients with a history of NCC. The in vitro proliferation of peripheral blood mononuclear cells to mitogens and foreign antigens was similar in patients and controls. Importantly, a substantive response was elicited by two Taenia solium metacestode antigens. In addition, 8 of 10 patients had a detectable humoral response to the antigenic glycoproteins of the cestode. Considering both the cellular and humoral response, all of the patients with NCC presented an active peripheral immunity.

Dissociative Global and Local Task-Switching Costs Across Younger Adults, Middle-Aged Adults, Older Adults, and Very Mild Alzheimer Disease Individuals

PubMed Central

Huff, Mark J.; Balota, David A.; Minear, Meredith; Aschenbrenner, Andrew J.; Duchek, Janet M.

2015-01-01

A task-switching paradigm was used to examine differences in attentional control across younger adults, middle-aged adults, healthy older adults, and individuals classified in the earliest detectable stage of Alzheimer's disease (AD). A large sample of participants (570) completed a switching task in which participants were cued to classify the letter (consonant/vowel) or number (odd/even) task-set dimension of a bivalent stimulus (e.g., A 14), respectively. A Pure block consisting of single-task trials and a Switch block consisting of nonswitch and switch trials were completed. Local (switch vs. nonswitch trials) and global (nonswitch vs. pure trials) costs in mean error rates, mean response latencies, underlying reaction time distributions, along with stimulus-response congruency effects were computed. Local costs in errors were group invariant, but global costs in errors systematically increased as a function of age and AD. Response latencies yielded a strong dissociation: Local costs decreased across groups whereas global costs increased across groups. Vincentile distribution analyses revealed that the dissociation of local and global costs primarily occurred in the slowest response latencies. Stimulus-response congruency effects within the Switch block were particularly robust in accuracy in the very mild AD group. We argue that the results are consistent with the notion that the impaired groups show a reduced local cost because the task sets are not as well tuned, and hence produce minimal cost on switch trials. In contrast, global costs increase because of the additional burden on working memory of maintaining two task sets. PMID:26652720

Interaural Level Difference Dependent Gain Control and Synaptic Scaling Underlying Binaural Computation

PubMed Central

Xiong, Xiaorui R.; Liang, Feixue; Li, Haifu; Mesik, Lukas; Zhang, Ke K.; Polley, Daniel B.; Tao, Huizhong W.; Xiao, Zhongju; Zhang, Li I.

2013-01-01

Binaural integration in the central nucleus of inferior colliculus (ICC) plays a critical role in sound localization. However, its arithmetic nature and underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC neurons that the contralateral dominance is created by a “push-pull”-like mechanism, with contralaterally dominant excitation and more bilaterally balanced inhibition. Importantly, binaural spiking response is generated apparently from an ipsilaterally-mediated scaling of contralateral response, leaving frequency tuning unchanged. This scaling effect is attributed to a divisive attenuation of contralaterally-evoked synaptic excitation onto ICC neurons with their inhibition largely unaffected. Thus, a gain control mediates the linear transformation from monaural to binaural spike responses. The gain value is modulated by interaural level difference (ILD) primarily through scaling excitation to different levels. The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to dynamically encode interaural sound localization cues while maintaining an invariant representation of other independent sound attributes. PMID:23972599

Placebo use in vaccine trials: Recommendations of a WHO expert panel

PubMed Central

Rid, Annette; Saxena, Abha; Baqui, Abdhullah H.; Bhan, Anant; Bines, Julie; Bouesseau, Marie-Charlotte; Caplan, Arthur; Colgrove, James; Dhai, Ames; Gomez-Diaz, Rita; Green, Shane K.; Kang, Gagandeep; Lagos, Rosanna; Loh, Patricia; London, Alex John; Mulholland, Kim; Neels, Pieter; Pitisuttithum, Punee; Sarr, Samba Cor; Selgelid, Michael; Sheehan, Mark; Smith, Peter G.

2014-01-01

Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of unvaccinated controls (with or without placebo) when an efficacious vaccine already exists. This paper specifies four situations in which placebo use may be acceptable, provided that the study question cannot be answered in an active-controlled trial design; the risks of delaying or foregoing an efficacious vaccine are mitigated; the risks of using a placebo control are justified by the social and public health value of the research; and the research is responsive to local health needs. The four situations are: (1) developing a locally affordable vaccine, (2) evaluating the local safety and efficacy of an existing vaccine, (3) testing a new vaccine when an existing vaccine is considered inappropriate for local use (e.g. based on epidemiologic or demographic factors), and (4) determining the local burden of disease. PMID:24768580

Local variability in long-term care services: local autonomy, exogenous influences and policy spillovers.

PubMed

Fernandez, José-Luis; Forder, Julien

2015-03-01

In many countries, public responsibility over the funding and provision of long-term care services is held at the local level. In such systems, long-term care provision is often characterised by significant local variability. Using a panel dataset of local authorities over the period 2002-2012, the paper investigates the underlying causes of variation in gross social care expenditure for older people in England. The analysis distinguishes between factors outside the direct control of policy makers, local preferences and local policy spillovers. The results indicate that local demand and supply factors, and to a much lesser extent local political preferences and spatial policy spillovers, explain a large majority of the observed variation in expenditure. Copyright © 2015 John Wiley & Sons, Ltd.

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay.

PubMed

Yao, Pan; Hongqian, Chu; Qinghe, Meng; Lanqin, Shang; Jianjun, Jiang; Xiaohua, Yang; Xuetao, Wei; Weidong, Hao

2016-09-15

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and the lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8(+) T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. Copyright © 2016 Elsevier Inc. All rights reserved.

Updates of Topical and Local Anesthesia Agents.

PubMed

Boyce, Ricardo A; Kirpalani, Tarun; Mohan, Naveen

2016-04-01

As described in this article, there are many advances in topical and local anesthesia. Topical and local anesthetics have played a great role in dentistry in alleviating the fears of patients, eliminating pain, and providing pain control. Many invasive procedures would not be performed without the use and advances of topical/local anesthetics. The modern-day dentist has the responsibility of knowing the variety of products on the market and should have at least references to access before, during, and after treatment. This practice ensures proper care with topical and local anesthetics for the masses of patients entering dental offices worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

A community-engaged infection prevention and control approach to Ebola.

PubMed

Marais, Frederick; Minkler, Meredith; Gibson, Nancy; Mwau, Baraka; Mehtar, Shaheen; Ogunsola, Folasade; Banya, Sama S; Corburn, Jason

2016-06-01

The real missing link in Ebola control efforts to date may lie in the failure to apply core principles of health promotion: the early, active and sustained engagement of affected communities, their trusted leaders, networks and lay knowledge, to help inform what local control teams do, and how they may better do it, in partnership with communities. The predominant focus on viral transmission has inadvertently stigmatized and created fear-driven responses among affected individuals, families and communities. While rigorous adherence to standard infection prevention and control (IPC) precautions and safety standards for Ebola is critical, we may be more successful if we validate and combine local community knowledge and experiences with that of IPC medical teams. In an environment of trust, community partners can help us learn of modest adjustments that would not compromise safety but could improve community understanding of, and responses to, disease control protocol, so that it better reflects their 'community protocol' (local customs, beliefs, knowledge and practices) and concerns. Drawing on the experience of local experts in several African nations and of community-engaged health promotion leaders in the USA, Canada and WHO, we present an eight step model, from entering communities with cultural humility, though reciprocal learning and trust, multi-method communication, development of the joint protocol, to assessing progress and outcomes and building for sustainability. Using examples of changes that are culturally relevant yet maintain safety, we illustrate how often minor adjustments can help prevent and treat the most serious emerging infectious disease since HIV/AIDS. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres

NASA Astrophysics Data System (ADS)

Oakes, Patrick W.; Wagner, Elizabeth; Brand, Christoph A.; Probst, Dimitri; Linke, Marco; Schwarz, Ulrich S.; Glotzer, Michael; Gardel, Margaret L.

2017-06-01

Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events.

An Interim Examination of the US Public Health Response to Ebola.

PubMed

Schemm Dwyer, Katherine; Misner, Heather; Chang, Sara; Fajardo, Neyling

From the summer of 2014 to the spring of 2016, the United States was involved in the Ebola response on both the national and international levels. The United States received 2 imported cases from West Africa and had 2 locally hospital-acquired cases, which spurred a massive and unprecedented public health response. As the domestic response stabilized and the epidemic in West Africa slowed, the Association of State and Territorial Health Officials (ASTHO) and the National Association of County and City Health Officials (NACCHO), through a cooperative agreement with the Centers for Disease Control and Prevention (CDC), led an in-progress review to assess the national public health response to Ebola. The goal was to identify opportunities to improve the Ebola response and best practices to inform future responses. To inform the review, NACCHO and ASTHO relied on feedback collected from several sources, including a stakeholder meeting held in August 2015, a series of key informant interviews, ASTHO's and NACCHO's internal response assessments, and perspectives shared by state and local health department members and workgroups and national partner organizations. ASTHO and NACCHO engaged experts and practitioners in public health, health care, emergency management, laboratory sciences, environmental health, occupational health, homeland security, communications, and public works from US federal, state, and local governments, the nonprofit community, and private industry. This article summarizes feedback and lessons learned as shared by these sources. Additionally, this article presents recommendations for federal, state, local, and nongovernment partners to improve current and future preparedness and response efforts to infectious disease threats.

ELM control with RMP: plasma response models and the role of edge peeling response

NASA Astrophysics Data System (ADS)

Liu, Yueqiang; Ham, C. J.; Kirk, A.; Li, Li; Loarte, A.; Ryan, D. A.; Sun, Youwen; Suttrop, W.; Yang, Xu; Zhou, Lina

2016-11-01

Resonant magnetic perturbations (RMP) have extensively been demonstrated as a plausible technique for mitigating or suppressing large edge localized modes (ELMs). Associated with this is a substantial amount of theory and modelling efforts during recent years. Various models describing the plasma response to the RMP fields have been proposed in the literature, and are briefly reviewed in this work. Despite their simplicity, linear response models can provide alternative criteria, than the vacuum field based criteria, for guiding the choice of the coil configurations to achieve the best control of ELMs. The role of the edge peeling response to the RMP fields is illustrated as a key indicator for the ELM mitigation in low collisionality plasmas, in various tokamak devices.

Controllable curvature from planar polymer sheets in response to light.

PubMed

Hubbard, Amber M; Mailen, Russell W; Zikry, Mohammed A; Dickey, Michael D; Genzer, Jan

2017-03-22

The ability to change shape and control curvature in 3D structures starting from planar sheets can aid in assembly and add functionality to an object. Herein, we convert planar sheets of shape memory polymers (SMPs) into 3D objects with controllable curvature by dictating where the sheets shrink. Ink patterned on the surface of the sheet absorbs infrared (IR) light, resulting in localized heating, and the material shrinks locally wherever the temperature exceeds the activation temperature, T a . We introduce two different mechanisms for controlling curvature within SMP sheets. The 'direct' mechanism uses localized shrinkage to induce curvature only in regions patterned with ink. The 'indirect' mechanism uses localized shrinkage in regions patterned with ink to induce curvature in neighboring regions without ink through a balance of internal stresses. Finite element analysis predicts the final shape of the polymer sheets with excellent qualitative agreement with experimental studies. Results from this study show that curvature can be controlled by the distribution and darkness of the ink pattern on the polymer sheet. Additionally, we utilize the direct and indirect curvature mechanisms to demonstrate the formation and actuation of gripper devices, which represent the potential utility of this approach.

Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials

PubMed Central

Manchikanti, Laxmaiah; Nampiaparampil, Devi E.; Manchikanti, Kavita N.; Falco, Frank J.E.; Singh, Vijay; Benyamin, Ramsin M.; Kaye, Alan D.; Sehgal, Nalini; Soin, Amol; Simopoulos, Thomas T.; Bakshi, Sanjay; Gharibo, Christopher G.; Gilligan, Christopher J.; Hirsch, Joshua A.

2015-01-01

Background: The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups. Methods: Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV). Results: A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone. Conclusion: This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone. PMID:26005584

The role of clinical toxicologists and poison control centers in public health.

PubMed

Sutter, Mark E; Bronstein, Alvin C; Heard, Stuart E; Barthold, Claudia L; Lando, James; Lewis, Lauren S; Schier, Joshua G

2010-06-01

Poison control centers and clinical toxicologists serve many roles within public health; however, the degree to which these entities collaborate is unknown. The objective of this survey was to identify successful collaborations of public health agencies with clinical toxicologists and poison control centers. Four areas including outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources were assessed. An online survey was sent to the directors of poison control centers, state epidemiologists, and the most senior public health official in each state and selected major metropolitan areas. This survey focused on three areas: service, structure within the local or state public health system, and remuneration. Questions regarding remuneration and poison control center location within the public health structure were asked to assess if these were critical factors of successful collaborations. Senior state and local public health officials were excluded because of a low response rate. The survey was completed in October 2007. A total of 111 respondents, 61 poison control centers and 50 state epidemiologists, were eligible for the survey. Sixty-nine (62%) of the 111 respondents, completed and returned the survey. Thirty-three (54%) of the 61 poison control centers responded, and 36 of the 50 state epidemiologists (72%) responded. The most frequent collaborations were terrorism preparedness and epidemic illness reporting. Additional collaborations also exist. Important collaborations exist outside of remuneration or poison control centers being a formal part of the public health structure. Poison control centers have expanded their efforts to include outbreak identification, syndromic surveillance, terrorism preparedness, and daily public health responsibilities amenable to poison control center resources. Collaboration in these areas and others should be expanded. Published by Elsevier Inc.

The Greater Southern Area Health Service Tobacco Control Plan 2006-2009.

PubMed

Gow, Andrew J; Weir, Kylie M; Marich, Andrew J N

2008-01-01

In response to the NSW Tobacco Action Plan 2005-2009, Greater Southern Area Health Service (GSAHS) has developed a local plan. This short report describes how activities promoted in the state plan were prioritised and six outcomes identified as the focus for the GSAHS Tobacco Control Plan 2006-2009.

Area-wide management of Aedes albopictus: II. Gauging the efficacy of traditional integrated pest control measures against urban container mosquitoes

USDA-ARS?s Scientific Manuscript database

Aedes (Stegomyia) albopictus (Skuse), the Asian tiger mosquito, is an introduced invasive species in the U.S. responsible for a significant proportion of service requests to local mosquito control programs. This container-utilizing mosquito is refractory to standard mosquito abatement measures in th...

Local C-Reactive Protein Expression in Obliterative Lesions and the Bronchial Wall in Posttransplant Obliterative Bronchiolitis

PubMed Central

Päiväniemi, Outi E.; Maasilta, Paula K.; Vainikka, Tiina L. S.; Alho, Hanni S.; Karhunen, Pekka J.; Salminen, Ulla-Stina

2009-01-01

The local immunoreactivity of C-reactive protein (CRP) was studied in a heterotopic porcine model of posttranplant obliterative bronchiolitis (OB). Bronchial allografts and control autografts were examined serially 2–28 days after subcutaneous transplantation. The autografts stayed patent. In the allografts, proliferation of inflammatory cells (P < .0001) and fibroblasts (P = .02) resulted in occlusion of the bronchial lumens (P < .01). Influx of CD4+ (P < .001) and CD8+ (P < .0001) cells demonstrated allograft immune response. CRP positivity simultaneously increased in the bronchial walls (P < .01), in macrophages, myofibroblasts, and endothelial cells. Local CRP was predictive of features characteristic of OB (R = 0.456–0.879, P < .05−P < .0001). Early obliterative lesions also showed CRP positivity, but not mature, collagen-rich obliterative plugs (P < .05). During OB development, CRP is localized in inflammatory cells, myofibroblasts and endothelial cells probably as a part of the local inflammatory response. PMID:19503785

Localization of virtual sound at 4 Gz.

PubMed

Sandor, Patrick M B; McAnally, Ken I; Pellieux, Lionel; Martin, Russell L

2005-02-01

Acceleration directed along the body's z-axis (Gz) leads to misperception of the elevation of visual objects (the "elevator illusion"), most probably as a result of errors in the transformation from eye-centered to head-centered coordinates. We have investigated whether the location of sound sources is misperceived under increased Gz. Visually guided localization responses were made, using a remotely controlled laser pointer, to virtual auditory targets under conditions of 1 and 4 Gz induced in a human centrifuge. As these responses would be expected to be affected by the elevator illusion, we also measured the effect of Gz on the accuracy with which subjects could point to the horizon. Horizon judgments were lower at 4 Gz than at 1 Gz, so sound localization responses at 4 Gz were corrected for this error in the transformation from eye-centered to head-centered coordinates. We found that the accuracy and bias of sound localization are not significantly affected by increased Gz. The auditory modality is likely to provide a reliable means of conveying spatial information to operators in dynamic environments in which Gz can vary.

Remote activation of a microactuator using a photo-responsive nanoparticle-polymer composite

NASA Astrophysics Data System (ADS)

Zeberoff, Anthony

Stimulus response materials are a class of novel materials that are currently being explored in various technologies, including biomedical devices and components, food packaging, fabrics, energy harvesting and conversion, and other elementary components such as sensors and actuators. Hybrid organic-inorganic materials such as nanoparticle-polymer composites are attractive candidates as their properties can be significantly tuned for particular applications where selectivity and localized responses are critical factors. In this work we developed and optimized a photo-responsive microactuator that can operate selectively to a specific wavelength of light. The photo-responsive microactuator is comprised of monodispersed microspheres that contain gold nanoparticles. Upon irradiation, these microspheres transduce optical energy to thermal energy, driving a localized phase change in the matrix in which they are embedded. Our remotely powered microactuator can be further realized in applications where decoupling the physical connection of the energy/control source from the actuating component is necessary.

Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients

PubMed Central

Vabres, Pierre; Dalac, Sophie; Jeudy, Geraldine; Bel, Blandine; Apetoh, Lionel; Ghiringhelli, François

2014-01-01

Background The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. Methods In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. Results We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. Conclusion Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers. PMID:25170840

Analysis of Control Strategies for Aircraft Flight Upset Recovery

NASA Technical Reports Server (NTRS)

Crespo, Luis G.; Kenny, Sean P.; Cox, David E.; Muri, Daniel G.

2012-01-01

This paper proposes a framework for studying the ability of a control strategy, consisting of a control law and a command law, to recover an aircraft from ight conditions that may extend beyond the normal ight envelope. This study was carried out (i) by evaluating time responses of particular ight upsets, (ii) by evaluating local stability over an equilibrium manifold that included stall, and (iii) by bounding the set in the state space from where the vehicle can be safely own to wings-level ight. These states comprise what will be called the safely recoverable ight envelope (SRFE), which is a set containing the aircraft states from where a control strategy can safely stabilize the aircraft. By safe recovery it is implied that the tran- sient response stays between prescribed limits before converging to a steady horizontal ight. The calculation of the SRFE bounds yields the worst-case initial state corresponding to each control strategy. This information is used to compare alternative recovery strategies, determine their strengths and limitations, and identify the most e ective strategy. In regard to the control law, the authors developed feedback feedforward laws based on the gain scheduling of multivariable controllers. In regard to the command law, which is the mechanism governing the exogenous signals driving the feed- forward component of the controller, we developed laws with a feedback structure that combines local stability and transient response considera- tions. The upset recovery of the Generic Transport Model, a sub-scale twin-engine jet vehicle developed by NASA Langley Research Center, is used as a case study.

Characterization of temperature and light effects on the defense response phenotypes associated with the maize Rp1-D21 gene

USDA-ARS?s Scientific Manuscript database

Rp1 is a complex locus of maize controlling race-specific resistance to the common rust fungus, Puccinia sorghi. The resistance response includes the “Hypersensitive response” (HR) – a rapid localized cell death at the point of pathogen penetration - and the induction of pathogenesis associated gene...

Global-Local Precedence in the Perception of Facial Age and Emotional Expression by Children with Autism and Other Developmental Disabilities

ERIC Educational Resources Information Center

Gross, Thomas F.

2005-01-01

Global information processing and perception of facial age and emotional expression was studied in children with autism, language disorders, mental retardation, and a clinical control group. Children were given a global-local task and asked to recognize age and emotion in human and canine faces. Children with autism made fewer global responses and…

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

PubMed Central

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

Response analysis of curved bridge with unseating failure control system under near-fault ground motions

NASA Astrophysics Data System (ADS)

Zuo, Ye; Sun, Guangjun; Li, Hongjing

2018-01-01

Under the action of near-fault ground motions, curved bridges are prone to pounding, local damage of bridge components and even unseating. A multi-scale fine finite element model of a typical three-span curved bridge is established by considering the elastic-plastic behavior of piers and pounding effect of adjacent girders. The nonlinear time-history method is used to study the seismic response of the curved bridge equipped with unseating failure control system under the action of near-fault ground motion. An in-depth analysis is carried to evaluate the control effect of the proposed unseating failure control system. The research results indicate that under the near-fault ground motion, the seismic response of the curved bridge is strong. The unseating failure control system perform effectively to reduce the pounding force of the adjacent girders and the probability of deck unseating.

Evaluation of piezoceramic actuators for control of aircraft interior noise

NASA Technical Reports Server (NTRS)

Silcox, Richard J.; Lefebvre, Sylvie; Metcalf, Vern L.; Beyer, Todd B.; Fuller, Chris R.

1992-01-01

Results of an experiment to evaluate piezoceramic actuators as the control actuator for active control of interior noise in a large-scale fuselage model are presented. Control was demonstrated for tonal excitation using a time domain least mean squares algorithm. A maximum of four actuator channels and six error signals were used. The actuators were employed for control of noise at frequencies where interior cavity modes were the dominant response and for driven acoustic responses where a structure resonance was dominant. Global reductions of 9 to 12 dB were obtained for the cases examined. The most effective configuration of skin-mounted actuators was found to be a pure in-plane forcing function as opposed to a bending excitation. The frame-mounted actuators were found to be equally effective as the skin-mounted actuators. However, both configurations resulted in local regions of unacceptably high vibration response in the structure.

Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

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

Tsuji, Hiroshi; Ishikawa, Hitoshi; Yanagi, Takeshi

2007-03-01

Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascularmore » glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.« less

Coherent electronic wave packet motion in C(60) controlled by the waveform and polarization of few-cycle laser fields.

PubMed

Li, H; Mignolet, B; Wachter, G; Skruszewicz, S; Zherebtsov, S; Süssmann, F; Kessel, A; Trushin, S A; Kling, Nora G; Kübel, M; Ahn, B; Kim, D; Ben-Itzhak, I; Cocke, C L; Fennel, T; Tiggesbäumker, J; Meiwes-Broer, K-H; Lemell, C; Burgdörfer, J; Levine, R D; Remacle, F; Kling, M F

2015-03-27

Strong laser fields can be used to trigger an ultrafast molecular response that involves electronic excitation and ionization dynamics. Here, we report on the experimental control of the spatial localization of the electronic excitation in the C_{60} fullerene exerted by an intense few-cycle (4 fs) pulse at 720 nm. The control is achieved by tailoring the carrier-envelope phase and the polarization of the laser pulse. We find that the maxima and minima of the photoemission-asymmetry parameter along the laser-polarization axis are synchronized with the localization of the coherent electronic wave packet at around the time of ionization.

Adjoint eigenfunctions of temporally recurrent single-spiral solutions in a simple model of atrial fibrillation.

PubMed

Marcotte, Christopher D; Grigoriev, Roman O

2016-09-01

This paper introduces a numerical method for computing the spectrum of adjoint (left) eigenfunctions of spiral wave solutions to reaction-diffusion systems in arbitrary geometries. The method is illustrated by computing over a hundred eigenfunctions associated with an unstable time-periodic single-spiral solution of the Karma model on a square domain. We show that all leading adjoint eigenfunctions are exponentially localized in the vicinity of the spiral tip, although the marginal modes (response functions) demonstrate the strongest localization. We also discuss the implications of the localization for the dynamics and control of unstable spiral waves. In particular, the interaction with no-flux boundaries leads to a drift of spiral waves which can be understood with the help of the response functions.

Adjoint eigenfunctions of temporally recurrent single-spiral solutions in a simple model of atrial fibrillation

NASA Astrophysics Data System (ADS)

Marcotte, Christopher D.; Grigoriev, Roman O.

2016-09-01

This paper introduces a numerical method for computing the spectrum of adjoint (left) eigenfunctions of spiral wave solutions to reaction-diffusion systems in arbitrary geometries. The method is illustrated by computing over a hundred eigenfunctions associated with an unstable time-periodic single-spiral solution of the Karma model on a square domain. We show that all leading adjoint eigenfunctions are exponentially localized in the vicinity of the spiral tip, although the marginal modes (response functions) demonstrate the strongest localization. We also discuss the implications of the localization for the dynamics and control of unstable spiral waves. In particular, the interaction with no-flux boundaries leads to a drift of spiral waves which can be understood with the help of the response functions.

Transcription factor WRKY23 assists auxin distribution patterns during Arabidopsis root development through local control on flavonol biosynthesis.

PubMed

Grunewald, Wim; De Smet, Ive; Lewis, Daniel R; Löfke, Christian; Jansen, Leentje; Goeminne, Geert; Vanden Bossche, Robin; Karimi, Mansour; De Rybel, Bert; Vanholme, Bartel; Teichmann, Thomas; Boerjan, Wout; Van Montagu, Marc C E; Gheysen, Godelieve; Muday, Gloria K; Friml, Jirí; Beeckman, Tom

2012-01-31

Gradients of the plant hormone auxin, which depend on its active intercellular transport, are crucial for the maintenance of root meristematic activity. This directional transport is largely orchestrated by a complex interaction of specific influx and efflux carriers that mediate the auxin flow into and out of cells, respectively. Besides these transport proteins, plant-specific polyphenolic compounds known as flavonols have been shown to act as endogenous regulators of auxin transport. However, only limited information is available on how flavonol synthesis is developmentally regulated. Using reduction-of-function and overexpression approaches in parallel, we demonstrate that the WRKY23 transcription factor is needed for proper root growth and development by stimulating the local biosynthesis of flavonols. The expression of WRKY23 itself is controlled by auxin through the Auxin Response Factor 7 (ARF7) and ARF19 transcriptional response pathway. Our results suggest a model in which WRKY23 is part of a transcriptional feedback loop of auxin on its own transport through local regulation of flavonol biosynthesis.

Segregating Top-Down Selective Attention from Response Inhibition in a Spatial Cueing Go/NoGo Task: An ERP and Source Localization Study.

PubMed

Hong, Xiangfei; Wang, Yao; Sun, Junfeng; Li, Chunbo; Tong, Shanbao

2017-08-29

Successfully inhibiting a prepotent response tendency requires the attentional detection of signals which cue response cancellation. Although neuroimaging studies have identified important roles of stimulus-driven processing in the attentional detection, the effects of top-down control were scarcely investigated. In this study, scalp EEG was recorded from thirty-two participants during a modified Go/NoGo task, in which a spatial-cueing approach was implemented to manipulate top-down selective attention. We observed classical event-related potential components, including N2 and P3, in the attended condition of response inhibition. While in the ignored condition of response inhibition, a smaller P3 was observed and N2 was absent. The correlation between P3 and CNV during the foreperiod suggested an inhibitory role of P3 in both conditions. Furthermore, source analysis suggested that P3 generation was mainly localized to the midcingulate cortex, and the attended condition showed increased activation relative to the ignored condition in several regions, including inferior frontal gyrus, middle frontal gyrus, precentral gyrus, insula and uncus, suggesting that these regions were involved in top-down attentional control rather than inhibitory processing. Taken together, by segregating electrophysiological correlates of top-down selective attention from those of response inhibition, our findings provide new insights in understanding the neural mechanisms of response inhibition.

Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy

PubMed Central

Mozzillo, Nicola; Simeone, Ester; Benedetto, Lucia; Curvietto, Marcello; Giannarelli, Diana; Gentilcore, Giusy; Camerlingo, Rosa; Capone, Mariaelena; Madonna, Gabriele; Festino, Lucia; Caracò, Corrado; Di Monta, Gianluca; Marone, Ugo; Di Marzo, Massimiliano; Grimaldi, Antonio M; Mori, Stefano; Ciliberto, Gennaro; Ascierto, Paolo A

2015-01-01

Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials. PMID:26155423

Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy.

PubMed

Mozzillo, Nicola; Simeone, Ester; Benedetto, Lucia; Curvietto, Marcello; Giannarelli, Diana; Gentilcore, Giusy; Camerlingo, Rosa; Capone, Mariaelena; Madonna, Gabriele; Festino, Lucia; Caracò, Corrado; Di Monta, Gianluca; Marone, Ugo; Di Marzo, Massimiliano; Grimaldi, Antonio M; Mori, Stefano; Ciliberto, Gennaro; Ascierto, Paolo A

2015-06-01

Melanoma is responsible for most skin cancer-related deaths and is one of the most common cancers diagnosed in young adults. In melanoma, tumors can become established by activation of the negative regulator of cytotoxic T lymphocytes (CTLs), CTL antigen-4 (CTLA-4). Ipilimumab blocks the interaction of CTLA-4 with CD80/CD86 and augments T-cell activation and proliferation. In electrochemotherapy (ECT), local application of short high-voltage pulses renders cell membranes transiently permeable to chemotherapeutic drugs. The combination of ipilimumab and ECT may be beneficial for the treatment of metastatic melanoma; however, no prospective data are available to date. Here, we report the retrospective analysis of patients treated with ipilimumab in an expanded access program (EAP) who also received ECT. Fifteen patients with previously treated metastatic melanoma who received ipilimumab 3 mg/kg every three weeks for four cycles and underwent ECT for local disease control and/or palliation of cutaneous lesions with bleomycin 15 mg/m 2 after the first ipilimumab infusion were included in the analysis. Over the study period, a local objective response was observed in 67% of patients (27% complete response [CR] and 40% partial response [PR]). According to immune-related response criteria, a systemic response was observed in nine patients (five PR and four stable disease [SD]), resulting in a disease control rate of 60%. Evaluation of circulating T-regulatory (T-reg) cells demonstrated significant differences between responders and non-responders. Overall, treatment was well-tolerated and without notable toxicity. In conclusion, the combination of ipilimumab and ECT appears to be beneficial to patients with advanced melanoma, warranting further investigation in prospective trials.

Human Corneal Limbal-Epithelial Cell Response to Varying Silk Film Geometric Topography In Vitro

PubMed Central

Lawrence, Brian D.; Pan, Zhi; Liu, Aihong; Kaplan, David L.; Rosenblatt, Mark I.

2012-01-01

Silk fibroin films are a promising class of biomaterials that have a number of advantages for use in ophthalmic applications due to their transparent nature, mechanical properties and minimal inflammatory response upon implantation. Freestanding silk films with parallel line and concentric ring topographies were generated for in vitro characterization of human corneal limbal-epithelial (HCLE) cell response upon differing geometric patterned surfaces. Results indicated that silk film topography significantly affected initial HCLE culture substrate attachment, cellular alignment, cell-to-cell contact formation, actin cytoskeleton alignment, and focal adhesion (FA) localization. Most notably, parallel line patterned surfaces displayed a 36%–54% increase on average in initial cell attachment, which corresponded to an over 2-fold increase in FA localization when compared to other silk film surfaces and controls. In addition, distinct localization of FA formation was observed along the edges for all patterned silk film topographies. In conclusion, silk film feature topography appears to help direct corneal epithelial cell response and cytoskeleton development, especially in regards to FA distribution, in vitro. PMID:22705042

Postural vascular response in human skin: passive and active reactions to alteration of transmural pressure.

PubMed

Jepsen, H; Gaehtgens, P

1993-09-01

Laser-Doppler (LD) fluxmetry was performed in the palmar finger skin of healthy subjects to study the mechanisms contributing to the postural vascular response. Local transmural pressure in the skin blood vessels of the region studied was altered for 1 min in two experimental series either by passive movement of the arm to different vertical hand positions relative to heart level or by application of external pressure (-120-180 mmHg) to the finger. Heart and respiratory rate, arterial blood pressure, and LD flux in the contralateral finger (kept at heart level) were measured. The measurements suggest a compound reaction of local (myogenic) and systemic (neurogenic) mechanisms: the local regulatory component appears as a graded active vascular response elicited by passive vessel distension or compression. A systemic component, associated with a single deep inspiration, is frequently observed during the actual movement of the arm. In addition, prolonged holding of the test hand in a given vertical position also elicits a delayed vascular response in the control hand at heart level, which may be generated by volume receptors in the intrathoracic low-pressure system.

A Micro-delivery Approach for Studying Microvascular Responses to Localized Oxygen Delivery

PubMed Central

Ghonaim, Nour W.; Lau, Leo W. M.; Goldman, Daniel; Ellis, Christopher G.; Yang, Jun

2011-01-01

In vivo video microscopy has been used to study blood flow regulation as a function of varying oxygen concentration in microcirculatory networks. However, previous studies have measured the collective response of stimulating large areas of the microvascular network at the tissue surface. Objective We aim to limit the area being stimulated by controlling oxygen availability to highly localized regions of the microvascular bed within intact muscle. Design and Method Gas of varying O2 levels was delivered to specific locations on the surface of the Extensor Digitorum Longus muscle of rat through a set of micro-outlets (100 μm diameter) patterned in ultrathin glass using state-of-the-art microfabrication techniques. O2 levels were oscillated and digitized video sequences were processed for changes in capillary hemodynamics and erythrocyte O2 saturation. Results and Conclusions Oxygen saturations in capillaries positioned directly above the micro-outlets were closely associated with the controlled local O2 oscillations. Radial diffusion from the micro-outlet is limited to ~75 μm from the center as predicted by computational modelling and as measured in vivo. These results delineate a key step in the design of a novel micro-delivery device for controlled oxygen delivery to the microvasculature to understand fundamental mechanisms of microvascular regulation of O2 supply. PMID:21914035

Dissociable early attentional control mechanisms underlying cognitive and affective conflicts

PubMed Central

Chen, Taolin; Kendrick, Keith M.; Feng, Chunliang; Sun, Shiyue; Yang, Xun; Wang, Xiaogang; Luo, Wenbo; Yang, Suyong; Huang, Xiaoqi; Valdés-Sosa, Pedro A.; Gong, Qiyong; Fan, Jin; Luo, Yue-Jia

2016-01-01

It has been well documented that cognitive conflict is sensitive to the relative proportion of congruent and incongruent trials. However, few studies have examined whether affective conflict processing is modulated as a function of proportion congruency (PC). To address this question we recorded event-related potentials (ERP) while subjects performed both cognitive and affective face-word Stroop tasks. By varying the proportion of congruent and incongruent trials in each block, we examined the extent to which PC impacts both cognitive and affective conflict control at different temporal stages. Results showed that in the cognitive task an anteriorly localized early N2 component occurred predominantly in the low proportion congruency context, whereas in the affective task it was found to occur in the high proportion congruency one. The N2 effects across the two tasks were localized to the dorsolateral prefrontal cortex, where responses were increased in the cognitive task but decreased in the affective one. Furthermore, high proportions of congruent items produced both larger amplitude of a posteriorly localized sustained potential component and a larger behavioral Stroop effect in cognitive and affective tasks. Our findings suggest that cognitive and affective conflicts engage early dissociable attentional control mechanisms and a later common conflict response system. PMID:27892513

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

PubMed

Weiskopf, Nikolaus; Veit, Ralf; Erb, Michael; Mathiak, Klaus; Grodd, Wolfgang; Goebel, Rainer; Birbaumer, Niels

2003-07-01

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Nitrogen-responsive Regulation of GATA Protein Family Activators Gln3 and Gat1 Occurs by Two Distinct Pathways, One Inhibited by Rapamycin and the Other by Methionine Sulfoximine*

PubMed Central

Georis, Isabelle; Tate, Jennifer J.; Cooper, Terrance G.; Dubois, Evelyne

2011-01-01

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin. PMID:22039046

Nitrogen-responsive regulation of GATA protein family activators Gln3 and Gat1 occurs by two distinct pathways, one inhibited by rapamycin and the other by methionine sulfoximine.

PubMed

Georis, Isabelle; Tate, Jennifer J; Cooper, Terrance G; Dubois, Evelyne

2011-12-30

Nitrogen availability regulates the transcription of genes required to degrade non-preferentially utilized nitrogen sources by governing the localization and function of transcription activators, Gln3 and Gat1. TorC1 inhibitor, rapamycin (Rap), and glutamine synthetase inhibitor, methionine sulfoximine (Msx), elicit responses grossly similar to those of limiting nitrogen, implicating both glutamine synthesis and TorC1 in the regulation of Gln3 and Gat1. To better understand this regulation, we compared Msx- versus Rap-elicited Gln3 and Gat1 localization, their DNA binding, nitrogen catabolite repression-sensitive gene expression, and the TorC1 pathway phosphatase requirements for these responses. Using this information we queried whether Rap and Msx inhibit sequential steps in a single, linear cascade connecting glutamine availability to Gln3 and Gat1 control as currently accepted or alternatively inhibit steps in two distinct parallel pathways. We find that Rap most strongly elicits nuclear Gat1 localization and expression of genes whose transcription is most Gat1-dependent. Msx, on the other hand, elicits nuclear Gln3 but not Gat1 localization and expression of genes that are most Gln3-dependent. Importantly, Rap-elicited nuclear Gln3 localization is absolutely Sit4-dependent, but that elicited by Msx is not. PP2A, although not always required for nuclear GATA factor localization, is highly required for GATA factor binding to nitrogen-responsive promoters and subsequent transcription irrespective of the gene GATA factor specificities. Collectively, our data support the existence of two different nitrogen-responsive regulatory pathways, one inhibited by Msx and the other by rapamycin.

Regulation of phosphate starvation responses in higher plants.

PubMed

Yang, Xiao Juan; Finnegan, Patrick M

2010-04-01

Phosphorus (P) is often a limiting mineral nutrient for plant growth. Many soils worldwide are deficient in soluble inorganic phosphate (P(i)), the form of P most readily absorbed and utilized by plants. A network of elaborate developmental and biochemical adaptations has evolved in plants to enhance P(i) acquisition and avoid starvation. Controlling the deployment of adaptations used by plants to avoid P(i) starvation requires a sophisticated sensing and regulatory system that can integrate external and internal information regarding P(i) availability. In this review, the current knowledge of the regulatory mechanisms that control P(i) starvation responses and the local and long-distance signals that may trigger P(i) starvation responses are discussed. Uncharacterized mutants that have P(i)-related phenotypes and their potential to give us additional insights into regulatory pathways and P(i) starvation-induced signalling are also highlighted and assessed. An impressive list of factors that regulate P(i) starvation responses is now available, as is a good deal of knowledge regarding the local and long-distance signals that allow a plant to sense and respond to P(i) availability. However, we are only beginning to understand how these factors and signals are integrated with one another in a regulatory web able to control the range of responses demonstrated by plants grown in low P(i) environments. Much more knowledge is needed in this agronomically important area before real gains can be made in improving P(i) acquisition in crop plants.

Operational efficiency and sustainability of vector control of malaria and dengue: descriptive case studies from the Philippines

PubMed Central

2012-01-01

Background Analysis is lacking on the management of vector control systems in disease-endemic countries with respect to the efficiency and sustainability of operations. Methods Three locations were selected, at the scale of province, municipality and barangay (i.e. village). Data on disease incidence, programme activities, and programme management were collected on-site through meetings and focus group discussions. Results Adaptation of disease control strategies to the epidemiological situation per barangay, through micro-stratification, brings gains in efficiency, but should be accompanied by further capacity building on local situational analysis for better selection and targeting of vector control interventions within the barangay. An integrated approach to vector control, aiming to improve the rational use of resources, was evident with a multi-disease strategy for detection and response, and by the use of combinations of vector control methods. Collaboration within the health sector was apparent from the involvement of barangay health workers, re-orientation of job descriptions and the creation of a disease surveillance unit. The engagement of barangay leaders and use of existing community structures helped mobilize local resources and voluntary services for vector control. In one location, local authorities and the community were involved in the planning, implementation and evaluation of malaria control, which triggered local programme ownership. Conclusions Strategies that contributed to an improved efficiency and sustainability of vector control operations were: micro-stratification, integration of vector control within the health sector, a multi-disease approach, involvement of local authorities, and empowerment of communities. Capacity building on situational analysis and vector surveillance should be addressed through national policy and guidelines. PMID:22873707

Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control

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

Habr-Gama, Angelita, E-mail: gamange@uol.com.br; University of São Paulo School of Medicine, São Paulo; Gama-Rodrigues, Joaquim

Purpose: To review the risk of local recurrence and impact of salvage therapy after Watch and Wait for rectal cancer with complete clinical response (cCR) after chemoradiation therapy (CRT). Methods and Materials: Patients with cT2-4N0-2M0 distal rectal cancer treated with CRT (50.4-54 Gy + 5-fluorouracil-based chemotherapy) and cCR at 8 weeks were included. Patients with cCR were enrolled in a strict follow-up program with no immediate surgery (Watch and Wait). Local recurrence-free survival was compared while taking into account Watch and Wait strategy alone and Watch and Wait plus salvage. Results: 90 of 183 patients experienced cCR at initial assessment after CRT (49%). Whenmore » early tumor regrowths (up to and including the initial 12 months of follow-up) and late recurrences were considered together, 28 patients (31%) experienced local recurrence (median follow-up time, 60 months). Of those, 26 patients underwent salvage therapy, and 2 patients were not amenable to salvage. In 4 patients, local re-recurrence developed after Watch and Wait plus salvage. The overall salvage rate for local recurrence was 93%. Local recurrence-free survival at 5 years was 69% (all local recurrences) and 94% (after salvage procedures). Thirteen patients (14%) experienced systemic recurrence. The 5-year cancer-specific overall survival and disease-free survival for all patients (including all recurrences) were 91% and 68%, respectively. Conclusions: Local recurrence may develop in 31% of patients with initial cCR when early regrowths (≤12 months) and late recurrences are grouped together. More than half of these recurrences develop within 12 months of follow-up. Salvage therapy is possible in ≥90% of recurrences, leading to 94% local disease control, with 78% organ preservation.« less

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications.

PubMed

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

To address the limitations of traditional drug delivery, TiO 2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future.

Recent advances on smart TiO2 nanotube platforms for sustainable drug delivery applications

PubMed Central

Wang, Qun; Huang, Jian-Ying; Li, Hua-Qiong; Zhao, Allan Zi-Jian; Wang, Yi; Zhang, Ke-Qin; Sun, Hong-Tao; Lai, Yue-Kun

2017-01-01

To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. PMID:28053530

Single-trial decoding of auditory novelty responses facilitates the detection of residual consciousness

PubMed Central

King, J.R.; Faugeras, F.; Gramfort, A.; Schurger, A.; El Karoui, I.; Sitt, J.D.; Rohaut, B.; Wacongne, C.; Labyt, E.; Bekinschtein, T.; Cohen, L.; Naccache, L.; Dehaene, S.

2017-01-01

Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract subject-specific EEG patterns and predict single-trial local or global novelty responses. We first validate our method with 38 high-density EEG, MEG and intracranial EEG recordings. We empirically demonstrate that our approach circumvents the issues associated with multiple comparisons and individual variability while improving the statistics. Moreover, we confirm in control subjects that local responses are robust to distraction whereas global responses depend on attention. We then investigate 104 vegetative state (VS), minimally conscious state (MCS) and conscious state (CS) patients recorded with high-density EEG. For the local response, the proportion of significant decoding scores (M = 60%) does not vary with the state of consciousness. By contrast, for the global response, only 14% of the VS patients' EEG recordings presented a significant effect, compared to 31% in MCS patients' and 52% in CS patients'. In conclusion, single-trial multivariate decoding of novelty responses provides valuable information in non-communicating patients and paves the way towards real-time monitoring of the state of consciousness. PMID:23859924

The Essentials of Local Autonomy: A Contemporary Focus on Control and Responsibility.

ERIC Educational Resources Information Center

Clark, George W.

Legislative and political issues are examined in this study of the forces governing the structure of control shared by the individual institutions of the California community college system (CCC) and various state agencies. The report first summarizes and compares the findings of three earlier studies of the college-state relationship: (1) William…

Decentralized authority, increased enforcement guide Mexico's environmental evolution

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

Ranger, E.M.; Alonzo, A.L.

1994-01-01

Environmental regulation in Mexico is evolving into a decentralized system where local authorities assume responsibility for compliance. Articles 25, 27 and 73 of Mexico's constitution establish federal, state and municipal jurisdictions for environmental protection, and empower the federal congress to promulgate environmental legislation. An established federal and local environmental legislative and normative framework, along with increased enforcement, provide the country with a comprehensive regulatory system to prevent and control industrial pollution.

Quantitative Proteomic Profiling of Low-Dose Ionizing Radiation Effects in a Human Skin Model

PubMed Central

Hengel, Shawna M.; Aldrich, Joshua T.; Waters, Katrina M.; Pasa-Tolic, Ljiljana; Stenoien, David L.

2014-01-01

To assess responses to low-dose ionizing radiation (LD-IR) exposures potentially encountered during medical diagnostic procedures, nuclear accidents or terrorist acts, a quantitative proteomic approach was used to identify changes in protein abundance in a reconstituted human skin tissue model treated with 0.1 Gy of ionizing radiation. To improve the dynamic range of the assay, subcellular fractionation was employed to remove highly abundant structural proteins and to provide insight into radiation-induced alterations in protein localization. Relative peptide quantification across cellular fractions, control and irradiated samples was performing using 8-plex iTRAQ labeling followed by online two-dimensional nano-scale liquid chromatography and high resolution MS/MS analysis. A total of 107 proteins were detected with statistically significant radiation-induced change in abundance (>1.5 fold) and/or subcellular localization compared to controls. The top biological pathways identified using bioinformatics include organ development, anatomical structure formation and the regulation of actin cytoskeleton. From the proteomic data, a change in proteolytic processing and subcellular localization of the skin barrier protein, filaggrin, was identified, and the results were confirmed by western blotting. This data indicate post-transcriptional regulation of protein abundance, localization and proteolytic processing playing an important role in regulating radiation response in human tissues. PMID:28250387

Control and gating of kinesin-microtubule motility on electrically heated thermo-chips.

PubMed

Ramsey, Laurence; Schroeder, Viktor; van Zalinge, Harm; Berndt, Michael; Korten, Till; Diez, Stefan; Nicolau, Dan V

2014-06-01

First lab-on-chip devices based on active transport by biomolecular motors have been demonstrated for basic detection and sorting applications. However, to fully employ the advantages of such hybrid nanotechnology, versatile spatial and temporal control mechanisms are required. Using a thermo-responsive polymer, we demonstrated a temperature controlled gate that either allows or disallows the passing of microtubules through a topographically defined channel. The gate is addressed by a narrow gold wire, which acts as a local heating element. It is shown that the electrical current flowing through a narrow gold channel can control the local temperature and as a result the conformation of the polymer. This is the first demonstration of a spatially addressable gate for microtubule motility which is a key element of nanodevices based on biomolecular motors.

Silicon microring resonators

NASA Astrophysics Data System (ADS)

Tan, Ying; Dai, Daoxin

2018-05-01

Silicon microring resonators (MRRs) are very popular for many applications because of the advantages of footprint compactness, easy scalability, and functional versatility. Ultra-compact silicon MRRs with box-like spectral responses are realized with a very large free-spectral range (FSR) by introducing bent directional couplers. The measured box-like spectral response has an FSR of >30 nm. The permanent wavelength-alignment techniques for MRRs are also presented, including the laser-induced local-oxidation technique as well as the local-etching technique. With these techniques, one can control finely the permanent wavelength shift, which is also large enough to compensate the random wavelength variation due to the random fabrication errors.

Lignocaine ointment and local anaesthesia in preterm infants.

PubMed Central

Barker, D. P.; Rutter, N.

1995-01-01

The ability of topically applied lignocaine ointment to produce surface anaesthesia was examined in 45 preterm infants (gestational age 25 to 35 weeks) at a median age of 2 days. Two strengths of ointment, 5% and 30%, were tested at 30 and 60 minutes after application to the dorsum of the foot. Anaesthesia was assessed by comparing the response to skin stimulation at the test and control sites, using von Frey hairs. In 84% of cases responses indicated that there was no surface anaesthesia. Topically applied lignocaine ointment is not an effective local anaesthetic in preterm infants, presumably due to poor absorption. PMID:7796241

Model reference, sliding mode adaptive control for flexible structures

NASA Technical Reports Server (NTRS)

Yurkovich, S.; Ozguner, U.; Al-Abbass, F.

1988-01-01

A decentralized model reference adaptive approach using a variable-structure sliding model control has been developed for the vibration suppression of large flexible structures. Local models are derived based upon the desired damping and response time in a model-following scheme, and variable structure controllers are then designed which employ colocated angular rate and position feedback. Numerical simulations have been performed using NASA's flexible grid experimental apparatus.

Transition from global to local control of dayside reconnection from ionospheric-sourced mass loading

NASA Astrophysics Data System (ADS)

Zhang, B.; Brambles, O. J.; Cassak, P. A.; Ouellette, J. E.; Wiltberger, M.; Lotko, W.; Lyon, J. G.

2017-09-01

We have conducted a series of controlled numerical simulations to investigate the response of dayside reconnection to idealized, ionosphere-sourced mass loading processes to determine whether they affect the integrated dayside reconnection rate. Our simulation results show that the coupled solar wind-magnetosphere system may exhibit both local and global control behaviors depending on the amount of mass loading. With a small amount of mass loading, the changes in local reconnection rate affects magnetosheath properties only weakly and the geoeffective length in the upstream solar wind is essentially unchanged, resulting in the same integrated dayside reconnection rate. With a large amount of mass loading, however, the magnetosheath properties and the geoeffective length are significantly affected by slowing down the local reconnection rate, resulting in an increase of the magnetic pressure in the magnetosheath, with a significant reduction in the geoeffective length in the upstream solar wind and in the integrated dayside reconnection rate. In this controlled simulation setup, the behavior of dayside reconnection potential is determined by the role of the enhanced magnetic pressure in the magnetospheath due to magnetospheric mass loading. The reconnection potential starts to decrease significantly when the enhanced magnetic pressure alters the thickness of the magnetosheath.

Medulloblastoma. The identification of prognostic subgroups and implications for multimodality management

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

Kopelson, G.; Linggood, R.M.; Kleinman, G.M.

1983-01-15

For 43 medulloblatoma patients who had five-and ten-year actuarial survival rates of 56%, prognostic factors of statistical significance included: T-stage, M-stage and histopathologic tumor score. Posterior fossa local control rates were also function of T-stage and TS. Combining TS with T-stage, patients fell into three prognostic and local control groups, which may have different future management implications: Small (T1,2) tumors of favorable (TS less than or equal to 5) histology had a 92% ten-year actuarial survival rate with 100% (8/8) local control; no change from current management is suggested. For the intermediate prognosis group, increasing the irradiation dose alone maymore » improve survival because these tumors exhibited an irradiation dose-response relationship. However, it is the poor prognosis group which might be suitable for future adjuvant chemotherapy or radiosensitizer trials since there is no evidence that higher irradiation doses improve local control. This article identifies prognostic subgroups based on histologic type and TM staging in medulloblastoma patients which potentially may be utilized to improve therapeutic results, and confirms the value of staging patients with central nervous system malignancies.« less

Linking morphodynamic response with sediment mass balance on the Colorado River in Marble Canyon: issues of scale, geomorphic setting, and sampling design

USGS Publications Warehouse

Grams, Paul E.; Topping, David J.; Schmidt, John C.; Hazel, Joseph E.; Kaplinski, Matt

2013-01-01

Measurements of morphologic change are often used to infer sediment mass balance. Such measurements may, however, result in gross errors when morphologic changes over short reaches are extrapolated to predict changes in sediment mass balance for long river segments. This issue is investigated by examination of morphologic change and sediment influx and efflux for a 100 km segment of the Colorado River in Grand Canyon, Arizona. For each of four monitoring intervals within a 7 year study period, the direction of sand-storage response within short morphologic monitoring reaches was consistent with the flux-based sand mass balance. Both budgeting methods indicate that sand storage was stable or increased during the 7 year period. Extrapolation of the morphologic measurements outside the monitoring reaches does not, however, provide a reasonable estimate of the magnitude of sand-storage change for the 100 km study area. Extrapolation results in large errors, because there is large local variation in site behavior driven by interactions between the flow and local bed topography. During the same flow regime and reach-average sediment supply, some locations accumulate sand while others evacuate sand. The interaction of local hydraulics with local channel geometry exerts more control on local morphodynamic response than sand supply over an encompassing river segment. Changes in the upstream supply of sand modify bed responses but typically do not completely offset the effect of local hydraulics. Thus, accurate sediment budgets for long river segments inferred from reach-scale morphologic measurements must incorporate the effect of local hydraulics in a sampling design or avoid extrapolation altogether.

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

Jeong, J; Deasy, J O

Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-killmore » was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.« less

Testing interactive effects of automatic and conflict control processes during response inhibition - A system neurophysiological study.

PubMed

Chmielewski, Witold X; Beste, Christian

2017-02-01

In everyday life successful acting often requires to inhibit automatic responses that might not be appropriate in the current situation. These response inhibition processes have been shown to become aggravated with increasing automaticity of pre-potent response tendencies. Likewise, it has been shown that inhibitory processes are complicated by a concurrent engagement in additional cognitive control processes (e.g. conflicting monitoring). Therefore, opposing processes (i.e. automaticity and cognitive control) seem to strongly impact response inhibition. However, possible interactive effects of automaticity and cognitive control for the modulation of response inhibition processes have yet not been examined. In the current study we examine this question using a novel experimental paradigm combining a Go/NoGo with a Simon task in a system neurophysiological approach combining EEG recordings with source localization analyses. The results show that response inhibition is less accurate in non-conflicting than in conflicting stimulus-response mappings. Thus it seems that conflicts and the resulting engagement in conflict monitoring processes, as reflected in the N2 amplitude, may foster response inhibition processes. This engagement in conflict monitoring processes leads to an increase in cognitive control, as reflected by an increased activity in the anterior and posterior cingulate areas, while simultaneously the automaticity of response tendencies is decreased. Most importantly, this study suggests that the quality of conflict processes in anterior cingulate areas and especially the resulting interaction of cognitive control and automaticity of pre-potent response tendencies are important factors to consider, when it comes to the modulation of response inhibition processes. Copyright © 2016 Elsevier Inc. All rights reserved.

Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

PubMed

Richardson, R C; Anderson, V L; Voorhees, W D; Blevins, W E; Inskeep, T K; Janas, W; Shupe, R E; Babbs, C F

1984-11-01

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

Atrazine exposure affects the ability of crayfish (Orconectes rusticus) to localize a food odor source.

PubMed

Belanger, Rachelle M; Peters, Tyler J; Sabhapathy, Gita S; Khan, Sana; Katta, Juhi; Abraham, Noor K

2015-05-01

Environmental pollutants, found in aquatic ecosystems, have been shown to have an effect on olfactory-mediated behaviors including feeding, mate attraction, and other important social behaviors. Crayfish are polytrophic, meaning that they feed on and become prey for all levels of the aquatic food web as well as are also important for the transfer of energy between benthic and terrestrial food webs. Because crayfish are a keystone species, it is important to investigate any factors that may affect their population size. Crayfish are active at night and rely heavily on their sensory appendages (e.g., antennulues, maxillipeds, and pereopods) to localize food sources. In this experiment, we investigated the effects of atrazine (ATR) exposure on the chemosensory responses of male and female crayfish to food odors. We exposed crayfish to environmentally relevant, sublethal levels of ATR [80 ppb (µg/L)] for 72 h and then examined the behavioral responses of both ATR-treated and control crayfish to food odor delivered from one end of a test arena. We used Noldus Ethovision XT software to measure odor localization and locomotory behaviors of crayfish in response to food (fish) odor. We found that control crayfish spent more time in the proximal region of the test arena and at the odor source compared with ATR-treated crayfish. Furthermore, there were no differences in the time spent moving and not moving, total distance travelled in the tank, and walking speed (cm/s) when control and ATR-treated crayfish were compared. Overall, this indicates that acute ATR exposure alters chemosensory abilities of crayfish, whereas overall motor function remains unchanged.

Whole-body heat loss during exercise in the heat is not impaired in type 1 diabetes.

PubMed

Stapleton, Jill M; Yardley, Jane E; Boulay, Pierre; Sigal, Ronald J; Kenny, Glen P

2013-09-01

The objective of this study is to determine whether individuals with type 1 diabetes exhibit impairments in local and whole-body heat loss responses that could affect core temperature regulation during exercise in the heat compared with matched, nondiabetic individuals. Twelve otherwise healthy individuals with type 1 diabetes (HbA1c = 7.7% ± 0.3%) and 12 controls matched for age, sex, body surface area, and physical fitness cycled continuously for 60 min at a set rate of metabolic heat production (approximately 400 W) in a whole-body direct calorimeter (35°C and 20% relative humidity). Local sweat rate (ventilated capsule) was measured on the back and skin blood flow (laser Doppler velocimetry) on the forearm. Core (rectal and esophageal) and mean skin temperatures and heart rate were measured continuously. Whole-body heat exchange and change in body heat content were measured using simultaneous direct whole-body and indirect calorimetry. The change (mean ± SE) in body heat content was similar between groups during exercise (diabetes, 409 ± 27 kJ; control, 386 ± 33 kJ; P = 0.584) and recovery (diabetes, -115 ± 16 kJ; control, -93 ± 24 kJ; P = 0.457). Local heat loss responses of sweating (P = 0.783) and skin blood flow (P = 0.078) as well as rectal temperature (diabetes, 37.87°C ± 0.10°C; control, 37.85°C; ± 0.13°C; P = 0.977) and heart rate (diabetes, 130 ± 9 beats·min, vs control, 126 ± 8 beats·min, P = 0.326) were comparable at the end of the exercise period. During light-to-moderate-intensity exercise performed under conditions permitting full sweat evaporation, otherwise healthy type 1 diabetic individuals did not show impaired heat loss responses during heat exposure when compared with matched individuals without diabetes.

Three-dimensional structural damage localization system and method using layered two-dimensional array of capacitance sensors

NASA Technical Reports Server (NTRS)

Curry, Mark A (Inventor); Senibi, Simon D (Inventor); Banks, David L (Inventor)

2010-01-01

A system and method for detecting damage to a structure is provided. The system includes a voltage source and at least one capacitor formed as a layer within the structure and responsive to the voltage source. The system also includes at least one sensor responsive to the capacitor to sense a voltage of the capacitor. A controller responsive to the sensor determines if damage to the structure has occurred based on the variance of the voltage of the capacitor from a known reference value. A method for sensing damage to a structure involves providing a plurality of capacitors and a controller, and coupling the capacitors to at least one surface of the structure. A voltage of the capacitors is sensed using the controller, and the controller calculates a change in the voltage of the capacitors. The method can include signaling a display system if a change in the voltage occurs.

A dynamic response and eye scanning data base useful in the development of theories and methods for the description of control/display relationships

NASA Technical Reports Server (NTRS)

Klein, R.

1972-01-01

A set of specially prepared digital tapes is reported which contain synchronized measurements of pilot scanning behavior, control response, and vehicle response obtained during instrument landing system approaches made in a fixed-base DC-8 transport simulator. The objective of the master tape is to provide a common data base which can be used by the research community to test theories, models, and methods for describing and analyzing control/display relations and interactions. The experimental conditions and tasks used to obtain the data and the detailed format of the tapes are described. Conventional instrument panel and controls were used, with simulated vertical gust and glide slope beam bend forcing functions. Continuous pilot eye fixations and scan traffic on the panel were measured. Both flight director and standard localizer/glide slope types of approaches were made, with both fixed and variable instrument range sensitivities.

Public Health Policy and Experience of the 2009 H1N1 Influenza Pandemic in Pune, India

PubMed Central

Purohit, Vidula; Kudale, Abhay; Sundaram, Neisha; Joseph, Saju; Schaetti, Christian; Weiss, Mitchell G.

2018-01-01

Background: Prior experience and the persisting threat of influenza pandemic indicate the need for global and local preparedness and public health response capacity. The pandemic of 2009 highlighted the importance of such planning and the value of prior efforts at all levels. Our review of the public health response to this pandemic in Pune, India, considers the challenges of integrating global and national strategies in local programmes and lessons learned for influenza pandemic preparedness. Methods: Global, national and local pandemic preparedness and response plans have been reviewed. In-depth interviews were undertaken with district health policy-makers and administrators who coordinated the pandemic response in Pune. Results: In the absence of a comprehensive district-level pandemic preparedness plan, the response had to be improvised. Media reporting of the influenza pandemic and inaccurate information that was reported at times contributed to anxiety in the general public and to widespread fear and panic. Additional challenges included inadequate public health services and reluctance of private healthcare providers to treat people with flu-like symptoms. Policy-makers developed a response strategy that they referred to as the Pune plan, which relied on powers sanctioned by the Epidemic Act of 1897 and resources made available by the union health ministry, state health department and a government diagnostic laboratory in Pune. Conclusion: The World Health Organization’s (WHO’s) global strategy for pandemic control focuses on national planning, but state-level and local experience in a large nation like India shows how national planning may be adapted and implemented. The priority of local experience and requirements does not negate the need for higher level planning. It does, however, indicate the importance of local adaptability as an essential feature of the planning process. Experience and the implicit Pune plan that emerged are relevant for pandemic preparedness and other public health emergencies. PMID:29524939

Follow your nose: Implicit spatial processing within the chemosensory systems.

PubMed

Wudarczyk, Olga A; Habel, Ute; Turetsky, Bruce I; Gur, Raquel E; Kellermann, Thilo; Schneider, Frank; Moessnang, Carolin

2016-11-01

Although most studies agree that humans cannot smell in stereo, it was recently suggested that olfactory localization is possible when assessed implicitly. In a spatial cueing paradigm, lateralized olfactory cues impaired the detection of congruently presented visual targets, an effect contrary to the typical facilitation observed in other sensory domains. Here, we examined the specificity and the robustness of this finding by studying implicit localization abilities in another chemosensory system and by accounting for possible confounds in a modified paradigm. Sixty participants completed a spatial cueing task along with an explicit localization task, using trigeminal (Experiment 1) and olfactory (Experiment 2) stimuli. A control task was implemented to control for residual somatosensory stimulation (Experiment 3). In the trigeminal experiment, stimuli were localized with high accuracy on the explicit level, while the cueing effect in form of facilitation was limited to response accuracy. In the olfactory experiment, responses were slowed by congruent cues on the implicit level, while no explicit localization was observed. Our results point to the robustness of the olfactory interference effect, corroborating the implicit-explicit dissociation of olfactory localization, and challenging the view that humans lost the ability to extract spatial information from smell. The absence of a similar interference for trigeminal cues suggests distinct implicit spatial processing mechanisms within the chemosensory systems. Moreover, the lack of a typical facilitation effect in the trigeminal domain points to important differences from spatial information processing in other, nonchemosensory domains. The possible mechanisms driving the effects are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles

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

Yamaguchi, Kazunori; Hata, Keiko; Wada, Tadashi

2006-07-28

Human ganglioside-specific sialidase, NEU3, localized at cell membranes is thought to regulate various biological processes at cell surfaces. We here explored functional subcellular localization of the sialidase by immunofluorescence and found accumulation at leading edges of cell membranes in the presence of serum in culture. In response to EGF, the sialidase redistributed rapidly to ruffling cell membranes of squamous carcinoma A431 cells and co-localized with Rac-1. NEU3 overexpression enhanced Rac-1 activation and cell migration as compared with controls in HeLa cells as well as in A431 cells. Consistent with co-localization with Rac-1 by immunofluorescence, NEU3 was found to co-precipitate withmore » activated Rac bound to GST-PAK-1 fusion protein. NEU3 silencing by siRNA, in contrast, resulted in inhibition of Rac-1 activation. These results indicate that NEU3 is able to mobilize to membrane ruffles in response to growth stimuli and activate the Rac-1 signaling by co-localization with Rac-1, leading to increased cell motility.« less

Programmable light-controlled shape changes in layered polymer nanocomposites.

PubMed

Zhu, Zhichen; Senses, Erkan; Akcora, Pinar; Sukhishvili, Svetlana A

2012-04-24

We present soft, layered nanocomposites that exhibit controlled swelling anisotropy and spatially specific shape reconfigurations in response to light irradiation. The use of gold nanoparticles grafted with a temperature-responsive polymer (poly(N-isopropylacrylamide), PNIPAM) with layer-by-layer (LbL) assembly allowed placement of plasmonic structures within specific regions in the film, while exposure to light caused localized material deswelling by a photothermal mechanism. By layering PNIPAM-grafted gold nanoparticles in between nonresponsive polymer stacks, we have achieved zero Poisson's ratio materials that exhibit reversible, light-induced unidirectional shape changes. In addition, we report rheological properties of these LbL assemblies in their equilibrium swollen states. Moreover, incorporation of dissimilar plasmonic nanostructures (solid gold nanoparticles and nanoshells) within different material strata enabled controlled shrinkage of specific regions of hydrogels at specific excitation wavelengths. The approach is applicable to a wide range of metal nanoparticles and temperature-responsive polymers and affords many advanced build-in options useful in optically manipulated functional devices, including precise control of plasmonic layer thickness, tunability of shape variations to the excitation wavelength, and programmable spatial control of optical response.

Dose response relationship in anti-stress gene regulatory networks.

PubMed

Zhang, Qiang; Andersen, Melvin E

2007-03-02

To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on the level of local gains, presence of gain-changing events, and degree of feedforward gene activation, this region can appear as superlinear, sublinear, or even J-shaped. The general dose response transition proposed here was further examined in a complex anti-electrophilic stress pathway, which involves multiple genes, enzymes, and metabolic reactions. This work would help biologists and especially toxicologists to better assess and predict the cellular impact brought about by biological stressors.

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

Li Yexiong, E-mail: yexiong@yahoo.com; Wang Hua; Jin Jing

Purpose: This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. Methods and Materials: The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). Results: The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response ratemore » of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. Conclusions: Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.« less

Microfabricated Nanotopological Surfaces for Study of Adhesion-dependent Cell mechanosensitivity**

PubMed Central

Chen, Weiqiang; Sun, Yubing

2014-01-01

Cells display high sensitivity and exhibit diverse responses to the intrinsic nanotopography of the extracellular matrix through their nanoscale cellular sensing machinery. Here, we reported a simple microfabrication method for precise control and spatial patterning of the local nanoroughness on glass surfaces using photolithography and reactive ion etching (RIE). Using RIE-generated nanorough glass surfaces, we demonstrated that local nanoroughness could provide a potent biophysical signal to regulate a diverse array of NIH/3T3 fibroblast behaviors, including cell morphology, adhesion, proliferation and migration. We further showed that cellular responses to nanotopography might be regulated by cell adhesion signaling and actin cytoskeleton remodeling. To further investigate the role of cytoskeleton contractility in nanoroughness sensing, we applied the RIE method to generate nanoroughness on the tops of an array of elastomeric poly-dimethylsiloxane (PDMS) microposts. We utilized the PDMS microposts as force sensors and demonstrated that nanoroughness could indeed regulate the cytoskeleton contractility of NIH/3T3 fibroblasts. Our results suggested that a feedback regulation and mechano-chemical integration mechanism involving adhesion signaling, actin cytoskeleton, and intracellular mechanosensory components might play an important role in regulating mechanosensitive behaviors of NIH/3T3 fibroblasts. The capability to control and further predict cellular responses to nanoroughness might suggest novel methods for developing biomaterials mimicking nanotopographic structures in vivo and suitable local cellular microenvironments for functional tissue engineering. PMID:22887768

Response surface modeling-based source contribution analysis and VOC emission control policy assessment in a typical ozone-polluted urban Shunde, China.

PubMed

You, Zhiqiang; Zhu, Yun; Jang, Carey; Wang, Shuxiao; Gao, Jian; Lin, Che-Jen; Li, Minhui; Zhu, Zhenghua; Wei, Hao; Yang, Wenwei

2017-01-01

To develop a sound ozone (O 3 ) pollution control strategy, it is important to well understand and characterize the source contribution due to the complex chemical and physical formation processes of O 3 . Using the "Shunde" city as a pilot summer case study, we apply an innovative response surface modeling (RSM) methodology based on the Community Multi-Scale Air Quality (CMAQ) modeling simulations to identify the O 3 regime and provide dynamic analysis of the precursor contributions to effectively assess the O 3 impacts of volatile organic compound (VOC) control strategy. Our results show that Shunde is a typical VOC-limited urban O 3 polluted city. The "Jiangmen" city, as the main upper wind area during July 2014, its VOCs and nitrogen oxides (NO x ) emissions make up the largest contribution (9.06%). On the contrary, the contribution from local (Shunde) emission is lowest (6.35%) among the seven neighbor regions. The local VOCs industrial source emission has the largest contribution comparing to other precursor emission sectors in Shunde. The results of dynamic source contribution analysis further show that the local NO x control could slightly increase the ground O 3 under low (10.00%) and medium (40.00%) reduction ratios, while it could start to turn positive to decrease ground O 3 under the high NO x abatement ratio (75.00%). The real-time assessment of O 3 impacts from VOCs control strategies in Pearl River Delta (PRD) shows that the joint regional VOCs emission control policy will effectively reduce the ground O 3 concentration in Shunde. Copyright © 2016. Published by Elsevier B.V.

Ebola virus disease in Africa: epidemiology and nosocomial transmission.

PubMed

Shears, P; O'Dempsey, T J D

2015-05-01

The 2014 Ebola outbreak in West Africa, primarily affecting Guinea, Sierra Leone, and Liberia, has exceeded all previous Ebola outbreaks in the number of cases and in international response. There have been 20 significant outbreaks of Ebola virus disease in Sub-Saharan Africa prior to the 2014 outbreak, the largest being that in Uganda in 2000, with 425 cases and a mortality of 53%. Since the first outbreaks in Sudan and Zaire in 1976, transmission within health facilities has been of major concern, affecting healthcare workers and acting as amplifiers of spread into the community. The lack of resources for infection control and personal protective equipment are the main reasons for nosocomial transmission. Local strategies to improve infection control, and a greater understanding of local community views on the disease, have helped to bring outbreaks under control. Recommendations from previous outbreaks include improved disease surveillance to enable more rapid health responses, the wider availability of personal protective equipment, and greater international preparedness. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Response of melanoma to heat and radiation therapy--a review of the literature and experience from The Prince of Wales Hospital, Sydney.

PubMed

Mameghan, H; Knittel, T

1988-11-07

Our review of the literature indicates that radiotherapy and/or heat therapy can provide local control of recurrent or metastatic melanoma in a large proportion of patients. This has undoubted value in the local palliation of symptoms and, in the absence of disseminated disease, can be curative. At The Prince of Wales Hospital, Sydney, we have studied the response of melanoma lesions to heat and radiation therapy and have assessed the reaction in the adjacent normal skin. Thirty-two melanoma lesions that were measurable in 12 patients received radiotherapy and heat therapy in different combinations and dose schedules (15 lesions received radiotherapy alone, six lesions received heat therapy alone, and 11 lesions received combined radiation and heat therapy). The acute normal skin reaction was compared between lesions that received single modality radiation or heat therapy and those that received the combination of heat and radiation therapy. A moderate or severe reaction developed at six of the 21 sites that were treated by a single modality, and at four of the 11 sites that received combined heat and radiation therapy (P = 0.7), and all healed within a few days. Evaluation of the melanoma response to therapy was possible only in 26 of the 32 lesions that were treated because two patients died soon after therapy and the response of their six lesions was not evaluable. A complete response occurred in 14 (54%) of 26 lesions and a partial response occurred in 10 (38%) of 26 lesions. The objective response by treatment modality was 10 of 15 lesions for radiotherapy, six of six lesions for heat therapy and eight of 11 lesions for both therapies combined. We conclude that radiotherapy and heat therapy, separately or combined, produce acceptably-low damage to normal tissue and highly-satisfactory local control of melanoma.

Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

PubMed

Dai, Min; Wu, Cong; Fang, Hong-Ming; Li, Li; Yan, Jia-Bao; Zeng, Dan-Lin; Zou, Tao

2017-06-01

We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial.

PubMed

Battersby, Nick J; Dattani, Mit; Rao, Sheela; Cunningham, David; Tait, Diana; Adams, Richard; Moran, Brendan J; Khakoo, Shelize; Tekkis, Paris; Rasheed, Shahnawaz; Mirnezami, Alex; Quirke, Philip; West, Nicholas P; Nagtegaal, Iris; Chong, Irene; Sadanandam, Anguraj; Valeri, Nicola; Thomas, Karen; Frost, Michelle; Brown, Gina

2017-08-29

Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy. TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis. The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection. ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.

Two presentations of contact lens-induced papillary conjunctivitis (CLPC) in hydrogel lens wear: local and general.

PubMed

Skotnitsky, Cheryl C; Naduvilath, Thomas J; Sweeney, Deborah F; Sankaridurg, Padmaja R

2006-01-01

The purpose of this study was to confirm that two distinct clinical presentations of contact lens-induced papillary conjunctivitis (CLPC), local and general, occur in hydrogel lens wear. Retrospective analyses of 124 CLPC events were identified. The classification of CLPC was based on location and extent of papillae. CLPC was classified as local if papillae were present in one to two areas of the tarsal conjunctiva and general if papillae occurred in three or more areas. The CLPC events were compared with an asymptomatic control group in prospective clinical trials conducted from 1993 until 2003 at two clinical sites, Australia and India. Two hundred sixteen subjects from Australia and 914 subjects from India wore either high Dk silicone hydrogel or low Dk hydrogel lenses on a 6-night (6N) or 30-night extended-wear (EW) schedule. The physiological responses of the ocular surface, including tarsal conjunctiva redness and roughness, number of papillae present, lens fit and performance, and subjective patient symptoms, were measured during each visit at each site. These variables listed were compared between local CLPC groups and asymptomatic controls and general CLPC groups and asymptomatic controls. Two types of CLPC in hydrogel lens wearers have been confirmed. Of the 124 CLPC events, there were 61 local and 63 general events. Local and general CLPC cases reported significantly greater frequency of symptoms compared with the asymptomatic controls, in particular itching, lens awareness, secretion, and blurred vision (p < 0.1). The classification of CLPC into two types, local and general, in hydrogel lens wear was confirmed based on presentations at both sites. This distribution of papillae between local and general CLPC may indicate separate etiologies involved in the pathogenesis of the condition.

The role of local sea surface temperature pattern changes in shaping climate change in the North Atlantic sector

NASA Astrophysics Data System (ADS)

Hand, Ralf; Keenlyside, Noel S.; Omrani, Nour-Eddine; Bader, Jürgen; Greatbatch, Richard J.

2018-03-01

Beside its global effects, climate change is manifested in many regionally pronounced features mainly resulting from changes in the oceanic and atmospheric circulation. Here we investigate the influence of the North Atlantic SST on shaping the winter-time response to global warming. Our results are based on a long-term climate projection with the Max Planck Institute Earth System Model (MPI-ESM) to investigate the influence of North Atlantic sea surface temperature pattern changes on shaping the atmospheric climate change signal. In sensitivity experiments with the model's atmospheric component we decompose the response into components controlled by the local SST structure and components controlled by global/remote changes. MPI-ESM simulates a global warming response in SST similar to other climate models: there is a warming minimum—or "warming hole"—in the subpolar North Atlantic, and the sharp SST gradients associated with the Gulf Stream and the North Atlantic Current shift northward by a few a degrees. Over the warming hole, global warming causes a relatively weak increase in rainfall. Beyond this, our experiments show more localized effects, likely resulting from future SST gradient changes in the North Atlantic. This includes a significant precipitation decrease to the south of the Gulf Stream despite increased underlying SSTs. Since this region is characterised by a strong band of precipitation in the current climate, this is contrary to the usual case that wet regions become wetter and dry regions become drier in a warmer climate. A moisture budget analysis identifies a complex interplay of various processes in the region of modified SST gradients: reduced surface winds cause a decrease in evaporation; and thermodynamic, modified atmospheric eddy transports, and coastal processes cause a change in the moisture convergence. The changes in the the North Atlantic storm track are mainly controlled by the non-regional changes in the forcing. The impact of the local SST pattern changes on regions outside the North Atlantic is small in our setup.

Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients

PubMed Central

2012-01-01

Background SBRT is a safe and efficient strategy to locally control multiple metastatic sites. While research in the physics domain for Flattening Filter Free Beams (FFF) beams is increasing, there are few clinical data of FFF beams in clinical practice. Here we reported dosimentric and early clinical data of SBRT and FFF delivery in isolated lymph node oligometastatic patients. Methods Between October 2010 and March 2012, 34 patients were treated with SBRT for oligometastatic lymph node metastasis on a Varian TrueBeamTM treatment machine using Volumetric Modulated Arc Therapy (RapidArc). We retrospectively evaluated a total of 25 patients for isolated lymph node metastases in abdomen and/or pelvis treated with SBRT and FFF (28 treatments). Acute toxicity was recorded. Local control evaluation was scored by means of CT scan and/or PET scan. Results All dosimetric results are in line with what published for the same type of stereotactic abdominal lymph node metastases treatments and fractionation, using RapidArc. All 25 FFF SBRT patients completed the treatment. Acute gastrointestinal toxicity was minimal: one patient showed Grade 1 gastrointestinal toxicity. Three other patients presented Grade 2 toxicity. No Grade 3 or higher was recorded. All toxicities were recovered within one week. The preliminary clinical results at the median follow up of 195 days are: complete response in 12 cases, partial response in 11, stable disease in 5, with an overall response rate of 82%; no local progression was recorded. Conclusions Data of dosimetrical findings and acute toxicity are excellent for patients treated with SBRT with VMAT using FFF beams. Preliminary clinical results showed a high rate of local control in irradiated lesion. Further data and longer follow up are needed to assess late toxicity and definitive clinical outcomes. PMID:23216821

Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin.

PubMed

Yamazaki, Fumio; Sone, Ryoko; Zhao, Kun; Alvarez, Guy E; Kosiba, Wojciech A; Johnson, John M

2006-01-01

Local cooling of nonglabrous skin without functional sympathetic nerves causes an initial vasodilation followed by vasoconstriction. To further characterize these responses to local cooling, we examined the importance of the rate of local cooling and the effect of nitric oxide synthase (NOS) inhibition in intact skin and in skin with vasoconstrictor function inhibited. Release of norepinephrine was blocked locally (iontophoresis) with bretylium tosylate (BT). Skin blood flow was monitored from the forearm by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure. Local temperature was controlled over 6.3 cm2 around the sites of LDF measurement. Local cooling was applied at -0.33 or -4 degrees C/min. At -4 degrees C/min, CVC increased (P < 0.05) at BT sites in the early phase. At -0.33 degrees C/min, there was no early vasodilator response, but there was a delay in the onset of vasoconstriction relative to intact skin. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) (intradermal microdialysis) decreased (P < 0.05) CVC by 28.3 +/- 3.8% at untreated sites and by 46.9 +/- 6.3% at BT-treated sites from the value before infusion. Rapid local cooling (-4 degrees C/min) to 24 degrees C decreased (P < 0.05) CVC at both untreated (saline) sites and L-NAME only sites from the precooling levels, but it transiently increased (P < 0.05) CVC at both BT + saline sites and BT + L-NAME sites in the early phase. After 35-45 min of local cooling, CVC decreased at BT + saline sites relative to the precooling levels (P < 0.05), but at BT + L-NAME sites CVC was not reduced below the precooling level (P = 0.29). These findings suggest that the rate of local cooling, but not functional NOS, is an important determinant of the early non-adrenergic vasodilator response to local cooling and that functional NOS, adrenergic nerves, as well as other mechanisms play roles in vasoconstriction during prolonged local cooling of skin.

Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection.

PubMed

Pega, J; Di Giacomo, S; Bucafusco, D; Schammas, J M; Malacari, D; Barrionuevo, F; Capozzo, A V; Rodríguez, L L; Borca, M V; Pérez-Filgueira, M

2015-09-01

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis.

PubMed

Empuku, Shinichiro; Nakajima, Kentaro; Akagi, Tomonori; Kaneko, Kunihiko; Hijiya, Naoki; Etoh, Tsuyoshi; Shiraishi, Norio; Moriyama, Masatsugu; Inomata, Masafumi

2016-05-01

Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.

Disorder-Enhanced Dielectric Response of Nanoscale and Mesoscopic Insulators

NASA Astrophysics Data System (ADS)

Onoda, Shigeki; Chern, Chyh-Hong; Murakami, Shuichi; Ogimoto, Yasushi; Nagaosa, Naoto

2006-12-01

Enhancement of the dielectric response of insulators by disorder is theoretically proposed, where the quantum interference of electronic waves through the nanoscale or mesoscopic system and its change due to external perturbations control the polarization. In the disordered case with all the states being localized, the resonant tunneling, which is topologically protected, plays a crucial role, and enhances the dielectric response by a factor 30 40 compared with the pure case. The realization of this idea with accessible materials or structures is also discussed.

Immune Response Following Photodynamic Therapy For Bladder Cancer

NASA Astrophysics Data System (ADS)

Raymond K.

1989-06-01

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Region VI of cauliflower mosaic virus encodes a host range determinant.

PubMed Central

Schoelz, J; Shepherd, R J; Daubert, S

1986-01-01

A domain of cauliflower mosaic virus (CaMV) which controls systemic spread in two solanaceous hosts (Datura stramonium and Nicotiana bigelovii) was mapped to the first half of open reading frame 6. Whereas ordinary strains of CaMV are unable to infect solanaceous species except to replicate locally in inoculated leaves, a new CaMV strain (D4) induces chlorotic local lesions and systemically infects both D. stramonium and N. bigelovii. To determine which portion of the CaMV genome controls systemic spread of the virus in solanaceous hosts, nine recombinant genomes constructed between D4 and two ordinary strains of the virus were tested for their ability to infect solanaceous hosts. A 496-base-pair DNA segment comprising the first half of open reading frame 6 specified the type of local lesions and systemic spread of the virus in solanaceous hosts. Exchange of this segment of the genome between strains of CaMV converted a compatible host reaction to an incompatible (hypersensitive) one in response to infection. This suggests that the gene VI protein interacts with the plant to suppress hypersensitivity, the normal response of solanaceous hosts to CaMV infection. Images PMID:3785205

Free hemoglobin enhances tumor necrosis factor-alpha production in isolated human monocytes.

PubMed

Carrillo, Eddy H; Gordon, Laura E; Richardson, J David; Polk, Hiram C

2002-03-01

A systemic inflammatory response (SIR) is seen in approximately 75% of patients with complex blunt liver injuries treated nonoperatively. Many feel this response is caused by blood, bile, and necrotic tissue accumulation in the peritoneal cavity. Our current treatment for these patients is a delayed laparoscopic washout of the peritoneal cavity, resulting in a dramatic resolution of the SIR. Spectrophotometric analysis of the intraperitoneal fluid has confirmed the presence of high concentrations of free hemoglobin (Hb). We hypothesize that free Hb enhances the local peritoneal response by increasing tumor necrosis factor-alpha (TNF-alpha) production by monocytes, contributing to the local inflammatory response and SIR. Monocytes from five healthy volunteers were isolated and cultured in RPMI-1640 for 24 hours. Treatment groups included saline controls, lipopolysaccharide ([LPS], 10 ng/mL, from Escherichia coli), human Hb (25 microg/mL), and Hb + LPS. Supernatants were analyzed by enzyme-linked immunosorbent assay. Student's t test with Mann-Whitney posttest was used for statistical analysis with p < or = 0.05 considered significant. Free Hb significantly increased TNF-alpha production 915 +/- 223 pg/mL versus saline (p = 0.02). LPS and Hb + LPS further increased TNF-alpha production (2294 pg/mL and 2501 pg/mL, respectively, p < 0.001) compared with saline controls. These data confirm that free Hb is a proinflammatory mediator resulting in the production of significant amounts of TNF-alpha. These in vitro findings support our clinical data in which timely removal of intraperitoneal free hemoglobin helps prevent its deleterious local and systemic inflammatory effects in patients with complex liver injuries managed nonoperatively.

Real-Time Maps of Fluid Flow Fields in Porous Biomaterials

PubMed Central

Mack, Julia J.; Youssef, Khalid; Noel, Onika D.V.; Lake, Michael P.; Wu, Ashley; Iruela-Arispe, M. Luisa; Bouchard, Louis-S.

2013-01-01

Mechanical forces such as fluid shear have been shown to enhance cell growth and differentiation, but knowledge of their mechanistic effect on cells is limited because the local flow patterns and associated metrics are not precisely known. Here we present real-time, noninvasive measures of local hydrodynamics in 3D biomaterials based on nuclear magnetic resonance. Microflow maps were further used to derive pressure, shear and fluid permeability fields. Finally, remodeling of collagen gels in response to precise fluid flow parameters was correlated with structural changes. It is anticipated that accurate flow maps within 3D matrices will be a critical step towards understanding cell behavior in response to controlled flow dynamics. PMID:23245922

Regulatory T cells in the control of host-microorganism interactions (*).

PubMed

Belkaid, Yasmine; Tarbell, Kristin

2009-01-01

Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review.

PubMed

Ryan, J E; Warrier, S K; Lynch, A C; Ramsay, R G; Phillips, W A; Heriot, A G

2016-03-01

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict pCR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and MeSH search terms: 'rectal neoplasm', 'response', 'neoadjuvant', 'preoperative chemoradiation', 'tumor response'. After review of title and abstracts, 85 articles addressing the prediction of pCR were selected. Clear methods to predict pCR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict pCR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. At present no robust markers of the prediction of pCR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict pCR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

Pro-Inflammatory cytokines increases hepatocellular carcinoma cells thermotolerance: Evidence of how local inflammation may negatively impact radiofrequency ablation local control rates

PubMed Central

Douglas, Wade G.; Wang, Yangping; Gibbs, John F.; Tracy, Erin; Kuvshinoff, Boris; Huntoon, Kristin; Baumann, Heinz

2008-01-01

Background Hepatocellular carcinomas (HCC) associated with inflammation that undergo radiofrequency ablation (RFA) appear to have poorer local control rates. Little is known of how mediators of inflammation influence HCC cellular thermotolerance which in part is mediated by heat shock protein 70 (HSP 70). This study determines how inflammatory mediators effect cellular thermotolerance and provides insight into how associated inflammation may impact HCC RFA local control rates. Methods HepG2 cell lines were cultured in control medium (CM) or CM containing conditioned medium of endotoxin-activated macrophage (CMM). Serial dilutions of CMM established microenvironments approximating low, medium and high CMM. All groups underwent a heat shock challenge (HSC) at 45° C for 10 minutes. Western blot, northern blot, densometric analysis, along with Thymidine and clonagenic assays determined how inflammation influenced multiple biologic endpoints. Results Cells cultured in low CMM, expressed significantly more HSP 70 RNA and protein compared to control cells after HSC. The cells also had a higher proliferative and survival rate after HSC compared to control cells. Medium CMM cultured cells had no significant difference in HSP 70 RNA and protein production or proliferation and survival rates after HSC, compared to CM cultured cells. AT high CMM the inhibitory effects of inflammatory mediators prevailed, all the measured endpoints were significantly less compared to CM cultured cells. Conclusions This study demonstrates that inflammation can alter the responsiveness of HCC cells to a HSC in a dose dependent manner. This study supports the clinical observation that HCC associated with chronic inflammation have worse RFA local control rates. PMID:18262552

Post-1980 shifts in the sensitivity of boreal tree growth to North Atlantic Ocean dynamics and seasonal climate. Tree growth responses to North Atlantic Ocean dynamics

NASA Astrophysics Data System (ADS)

Ols, Clémentine; Trouet, Valerie; Girardin, Martin P.; Hofgaard, Annika; Bergeron, Yves; Drobyshev, Igor

2018-06-01

The mid-20th century changes in North Atlantic Ocean dynamics, e.g. slow-down of the Atlantic meridional overturning thermohaline circulation (AMOC), have been considered as early signs of tipping points in the Earth climate system. We hypothesized that these changes have significantly altered boreal forest growth dynamics in northeastern North America (NA) and northern Europe (NE), two areas geographically adjacent to the North Atlantic Ocean. To test our hypothesis, we investigated tree growth responses to seasonal large-scale oceanic and atmospheric indices (the AMOC, North Atlantic Oscillation (NAO), and Arctic Oscillation (AO)) and climate (temperature and precipitation) from 1950 onwards, both at the regional and local levels. We developed a network of 6876 black spruce (NA) and 14437 Norway spruce (NE) tree-ring width series, extracted from forest inventory databases. Analyses revealed post-1980 shifts from insignificant to significant tree growth responses to summer oceanic and atmospheric dynamics both in NA (negative responses to NAO and AO indices) and NE (positive response to NAO and AMOC indices). The strength and sign of these responses varied, however, through space with stronger responses in western and central boreal Quebec and in central and northern boreal Sweden, and across scales with stronger responses at the regional level than at the local level. Emerging post-1980 associations with North Atlantic Ocean dynamics synchronized with stronger tree growth responses to local seasonal climate, particularly to winter temperatures. Our results suggest that ongoing and future anomalies in oceanic and atmospheric dynamics may impact forest growth and carbon sequestration to a greater extent than previously thought. Cross-scale differences in responses to North Atlantic Ocean dynamics highlight complex interplays in the effects of local climate and ocean-atmosphere dynamics on tree growth processes and advocate for the use of different spatial scales in climate-growth research to better understand factors controlling tree growth.

Gaps in Perspective: Who Should Be Responsible for Tracking Student Progress across Education Institutions? California Education Policy, Student Data, and the Quest to Improve Student Progress, Part I. Policy Brief

ERIC Educational Resources Information Center

Moore, Colleen; Grubb, Brock; Esch, Camille

2016-01-01

Conventional wisdom suggests that local educators tend to be wary of efforts by the state to gather more information from their institutions, due to the burdens that such requests often entail. But California's current education landscape, with its shift from state to local control of funding and accountability in the K-12 system, its massive…

Plasmonics simulations including nonlocal effects using a boundary element method approach

NASA Astrophysics Data System (ADS)

Trügler, Andreas; Hohenester, Ulrich; García de Abajo, F. Javier

2017-09-01

Spatial nonlocality in the photonic response of metallic nanoparticles is actually known to produce near-field quenching and significant plasmon frequency shifts relative to local descriptions. As the control over size and morphology of fabricated nanostructures is truly reaching the nanometer scale, understanding and accounting for nonlocal phenomena is becoming increasingly important. Recent advances clearly point out the need to go beyond the local theory. We here present a general formalism for incorporating spatial dispersion effects through the hydrodynamic model and generalizations for arbitrary surface morphologies. Our method relies on the boundary element method, which we supplement with a nonlocal interaction potential. We provide numerical examples in excellent agreement with the literature for individual and paired gold nanospheres, and critically examine the accuracy of our approach. The present method involves marginal extra computational cost relative to local descriptions and facilitates the simulation of spatial dispersion effects in the photonic response of complex nanoplasmonic structures.

Effect of local anaesthesia on short- and long-term pain induced by two bloodless castration methods in calves.

PubMed

Thüer, Susann; Mellema, Sibylle; Doherr, Marcus G; Wechsler, Beat; Nuss, Karl; Steiner, Adrian

2007-03-01

Behavioural and cortisol responses of calves were used as indicators of pain to assess short- and long-term effects of bloodless castration methods with and without local anaesthesia. Seventy calves, aged 21-28 days, were control handled (20) or castrated using the Burdizzo (25) or rubber ring technique (25). Either 10 mL lidocaine or NaCl were distributed in both spermatic cords and the scrotal neck. The plasma cortisol response was recorded for 72 h, and behavioural and clinical traits monitored over a three month period. Local anaesthesia reduced the level of indicators of acute pain after both the Burdizzo and rubber ring techniques. It did not, however, result in a totally painless castration. As there was evidence of chronic pain lasting for several weeks after rubber ring castration, the Burdizzo method is judged to be preferable to the rubber ring technique.

36 CFR 292.70 - Indemnification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and severally liable in accordance with Federal and State laws for indemnifying the United States for... incurred from fire suppression efforts, and environmental response actions and cleanup and abatement costs... operation. This includes acts or omissions covered by Federal, State, and local pollution control and...

36 CFR 292.70 - Indemnification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and severally liable in accordance with Federal and State laws for indemnifying the United States for... incurred from fire suppression efforts, and environmental response actions and cleanup and abatement costs... operation. This includes acts or omissions covered by Federal, State, and local pollution control and...

Impaired peripheral vasodilation during graded systemic hypoxia in healthy older adults: role of the sympathoadrenal system

PubMed Central

Richards, Jennifer C.; Crecelius, Anne R.; Larson, Dennis G.; Luckasen, Gary J.

2017-01-01

Systemic hypoxia is a physiological and pathophysiological stress that activates the sympathoadrenal system and, in young adults, leads to peripheral vasodilation. We tested the hypothesis that peripheral vasodilation to graded systemic hypoxia is impaired in older healthy adults and that this age-associated impairment is due to attenuated β-adrenergic mediated vasodilation and elevated α-adrenergic vasoconstriction. Forearm blood flow was measured (Doppler ultrasound), and vascular conductance (FVC) was calculated in 12 young (24 ± 1 yr) and 10 older (63 ± 2 yr) adults to determine the local dilatory responses to graded hypoxia (90, 85, and 80% O2 saturations) in control conditions, following local intra-arterial blockade of β-receptors (propranolol), and combined blockade of α- and β-receptors (phentolamine + propranolol). Under control conditions, older adults exhibited impaired vasodilation to hypoxia compared with young participants at all levels of hypoxia (peak ΔFVC at 80% SpO2 = 4 ± 6 vs. 35 ± 8%; P < 0.01). During β-blockade, older adults actively constricted at 85 and 80% SpO2 (peak ΔFVC at 80% SpO2 = −13 ± 6%; P < 0.05 vs. control), whereas the response in the young was not significantly impacted (peak ΔFVC = 28 ± 8%). Combined α- and β-blockade increased the dilatory response to hypoxia in young adults; however, older adults failed to significantly vasodilate (peak ΔFVC at 80% SpO2= 12 ± 11% vs. 58 ± 11%; P < 0.05). Our findings indicate that peripheral vasodilation to graded systemic hypoxia is significantly impaired in older adults, which cannot be fully explained by altered sympathoadrenal control of vascular tone. Thus, the impairment in hypoxic vasodilation is likely due to attenuated local vasodilatory and/or augmented vasoconstrictor signaling with age. NEW & NOTEWORTHY We found that the lack of peripheral vasodilation during graded systemic hypoxia with aging is not mediated by the sympathoadrenal system, strongly implicating local vascular control mechanisms in this impairment. Understanding these mechanisms may lead to therapeutic advances for improving tissue blood flow and oxygen delivery in aging and disease. PMID:28159810

Phosphatidylinositol 3-kinase function at very early symbiont perception: a local nodulation control under stress conditions?

PubMed

Robert, Germán; Muñoz, Nacira; Alvarado-Affantranger, Xochitl; Saavedra, Laura; Davidenco, Vanina; Rodríguez-Kessler, Margarita; Estrada-Navarrete, Georgina; Sánchez, Federico; Lascano, Ramiro

2018-04-09

Root hair curling is an early and essential morphological change required for the success of the symbiotic interaction between legumes and rhizobia. At this stage rhizobia grow as an infection thread within root hairs and are internalized into the plant cells by endocytosis, where the PI3K enzyme plays important roles. Previous observations show that stress conditions affect early stages of the symbiotic interaction, from 2 to 30 min post-inoculation, which we term as very early host responses, and affect symbiosis establishment. Herein, we demonstrated the relevance of the very early host responses for the symbiotic interaction. PI3K and the NADPH oxidase complex are found to have key roles in the microsymbiont recognition response, modulating the apoplastic and intracellular/endosomal ROS induction in root hairs. Interestingly, compared with soybean mutant plants that do not perceive the symbiont, we demonstrated that the very early symbiont perception under sublethal saline stress conditions induced root hair death. Together, these results highlight not only the importance of the very early host-responses on later stages of the symbiont interaction, but also suggest that they act as a mechanism for local control of nodulation capacity, prior to the abortion of the infection thread, preventing the allocation of resources/energy for nodule formation under unfavorable environmental conditions.

Effects of local anaesthesia or local anaesthesia plus a non-steroidal anti-inflammatory drug on the acute cortisol response of calves to five different methods of castration.

PubMed

Stafford, K J; Mellor, D J; Todd, S E; Bruce, R A; Ward, R N

2002-08-01

The cortisol response of calves to different methods of castration (ring, band, surgical, clamp) with or without local anaesthetic, or local anaesthetic plus a non-steroidal anti-inflammatory drug were recorded. All methods of castration caused a significant cortisol response and by inference pain and distress. Band castration caused a greater cortisol response than ring castration but the responses were eliminated by local anaesthetic. The cortisol response to surgical castration, by traction on the spermatic cords or by cutting across them with an emasculator, was not diminished by local anaesthetic but when ketoprofen was given with local anaesthetic the cortisol response was eliminated. Local anaesthetic did reduce the behavioural response to cutting the scrotum and handling the testes. Clamp castration caused the smallest cortisol response which was reduced or eliminated by local anaesthetic or local anesthetic plus ketoprofen respectively, but this method of castration was not always successful.

Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

PubMed Central

Mostaghel, Elahe A.; Nelson, Peter S.; Lange, Paul; Lin, Daniel W.; Taplin, Mary Ellen; Balk, Steven; Ellis, William; Kantoff, Philip; Marck, Brett; Tamae, Daniel; Matsumoto, Alvin M.; True, Lawrence D.; Vessella, Robert; Penning, Trevor; Hunter Merrill, Rachel; Gulati, Roman; Montgomery, Bruce

2014-01-01

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer. PMID:24323034

Human macrophage ATP7A is localized in the trans-Golgi apparatus, controls intracellular copper levels, and mediates macrophage responses to dermal wounds.

PubMed

Kim, Ha Won; Chan, Qilin; Afton, Scott E; Caruso, Joseph A; Lai, Barry; Weintraub, Neal L; Qin, Zhenyu

2012-02-01

The copper transporter ATP7A has attracted significant attention since the discovery of its gene mutation leading to human Menkes disease. We previously reported that ATP7A is highly expressed in the human vasculature and identified a novel vascular function of ATP7A in modulation of the expression and activity of extracellular superoxide dismutase. We recently identified that ATP7A expression in THP-1 cells (a monocyte/macrophage model cell line) plays a role in the oxidation of low density lipoproteins, indicating that it is necessary to further investigate its expression and function in monocytes/macrophages. In the current study, we demonstrated the protein and mRNA expression of ATP7A in human peripheral blood mononuclear cell (PBMC)-derived macrophages and alveolar macrophages. ATP7A was strongly co-localized with the trans-Golgi apparatus in PBMC-derived macrophages. Intracellular copper, detected by synchrotron X-ray fluorescence microscopy, was found to be distributed to the nucleus and cytoplasm in human THP-1 cells. To confirm the role of endogenous ATP7A in macrophage copper homeostasis, we performed inductively coupled plasma mass spectrometry in murine peritoneal macrophages, which showed markedly increased intracellular copper levels in macrophages isolated from ATP7A-deficient mice versus control mice. Moreover, the role of ATP7A in regulating macrophage responses to dermal wounds was studied by introduction of control and ATP7A-downregulated THP-1 cells into dermal wounds of nude mice. Infiltration of THP-1 cells into the wounded area (detected by expression of human macrophage markers MAC2 and CD68) was reduced in response to downregulation of ATP7A, hinting decreased macrophage accumulation subsequent to dermal wounds. In summary, alongside our previous studies, these findings indicate that human macrophage ATP7A is localized in the trans-Golgi apparatus, regulates intracellular copper levels, and mediates macrophage responses to a dermal wound.

Local processes and regional patterns - Interpreting a multi-decadal altimetry record of Greenland Ice Sheet changes

NASA Astrophysics Data System (ADS)

Csatho, B. M.; Schenk, A. F.; Babonis, G. S.; van den Broeke, M. R.; Kuipers Munneke, P.; van der Veen, C. J.; Khan, S. A.; Porter, D. F.

2016-12-01

This study presents a new, comprehensive reconstruction of Greenland Ice Sheet elevation changes, generated using the Surface Elevation And Change detection (SERAC) approach. 35-year long elevation-change time series (1980-2015) were obtained at more than 150,000 locations from observations acquired by NASA's airborne and spaceborne laser altimeters (ATM, LVIS, ICESat), PROMICE laser altimetry data (2007-2011) and a DEM covering the ice sheet margin derived from stereo aerial photographs (1970s-80s). After removing the effect of Glacial Isostatic Adjustment (GIA) and the elastic crustal response to changes in ice loading, the time series were partitioned into changes due to surface processes and ice dynamics and then converted into mass change histories. Using gridded products, we examined ice sheet elevation, and mass change patterns, and compared them with other estimates at different scales from individual outlet glaciers through large drainage basins, on to the entire ice sheet. Both the SERAC time series and the grids derived from these time series revealed significant spatial and temporal variations of dynamic mass loss and widespread intermittent thinning, indicating the complexity of ice sheet response to climate forcing. To investigate the regional and local controls of ice dynamics, we examined thickness change time series near outlet glacier grounding lines. Changes on most outlet glaciers were consistent with one or more episodes of dynamic thinning that propagates upstream from the glacier terminus. The spatial pattern of the onset, duration, and termination of these dynamic thinning events suggest a regional control, such as warming ocean and air temperatures. However, the intricate spatiotemporal pattern of dynamic thickness change suggests that, regardless of the forcing responsible for initial glacier acceleration and thinning, the response of individual glaciers is modulated by local conditions. We use statistical methods, such as principal component analysis and multivariate regression to analyze the dynamic ice-thickness change time series derived by SERAC and to investigate the primary forcings and controls on outlet glacier changes.

Regulated Localization Is Sufficient for Hormonal Control of Regulator of G Protein Signaling Homology Rho Guanine Nucleotide Exchange Factors (RH-RhoGEFs)*

PubMed Central

Carter, Angela M.; Gutowski, Stephen; Sternweis, Paul C.

2014-01-01

The regulator of G protein signaling homology (RH) Rho guanine nucleotide exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are specific GEFs for the monomeric GTPase RhoA. The RH domains interact specifically with the α subunits of G12 heterotrimeric GTPases. Activated Gα13 modestly stimulates the exchange activity of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF. Because all three RH-RhoGEFs can localize to the plasma membrane upon expression of activated Gα13, cellular localization of these RhoGEFs has been proposed as a mechanism for controlling their activity. We use a small molecule-regulated heterodimerization system to rapidly control the localization of RH-RhoGEFs. Acute localization of the proteins to the plasma membrane activates RhoA within minutes and to levels that are comparable with activation of RhoA by hormonal stimulation of G protein-coupled receptors. The catalytic activity of membrane-localized RhoGEFs is not dependent on activated Gα13. We further show that the conserved RH domains can rewire two different RacGEFs to activate Rac1 in response to a traditional activator of RhoA. Thus, RH domains act as independent detectors for activated Gα13 and are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to substrate, membrane-associated RhoA. PMID:24855647

Parametric excitation of multiple resonant radiations from localized wavepackets

PubMed Central

Conforti, Matteo; Trillo, Stefano; Mussot, Arnaud; Kudlinski, Alexandre

2015-01-01

Fundamental physical phenomena such as laser-induced ionization, driven quantum tunneling, Faraday waves, Bogoliubov quasiparticle excitations, and the control of new states of matter rely on time-periodic driving of the system. A remarkable property of such driving is that it can induce the localized (bound) states to resonantly couple to the continuum. Therefore experiments that allow for enlightening and controlling the mechanisms underlying such coupling are of paramount importance. We implement such an experiment in a special optical fiber characterized by a dispersion oscillating along the propagation coordinate, which mimics “time”. The quasi-momentum associated with such periodic perturbation is responsible for the efficient coupling of energy from the localized wave-packets (solitons in anomalous dispersion and shock fronts in normal dispersion) sustained by the fiber nonlinearity, into free-running linear dispersive waves (continuum) at multiple resonant frequencies. Remarkably, the observed resonances can be explained by means of a unified approach, regardless of the fact that the localized state is a soliton-like pulse or a shock front. PMID:25801054

A model for discriminating reinforcers in time and space.

PubMed

Cowie, Sarah; Davison, Michael; Elliffe, Douglas

2016-06-01

Both the response-reinforcer and stimulus-reinforcer relation are important in discrimination learning; differential responding requires a minimum of two discriminably-different stimuli and two discriminably-different associated contingencies of reinforcement. When elapsed time is a discriminative stimulus for the likely availability of a reinforcer, choice over time may be modeled by an extension of the Davison and Nevin (1999) model that assumes that local choice strictly matches the effective local reinforcer ratio. The effective local reinforcer ratio may differ from the obtained local reinforcer ratio for two reasons: Because the animal inaccurately estimates times associated with obtained reinforcers, and thus incorrectly discriminates the stimulus-reinforcer relation across time; and because of error in discriminating the response-reinforcer relation. In choice-based timing tasks, the two responses are usually highly discriminable, and so the larger contributor to differences between the effective and obtained reinforcer ratio is error in discriminating the stimulus-reinforcer relation. Such error may be modeled either by redistributing the numbers of reinforcers obtained at each time across surrounding times, or by redistributing the ratio of reinforcers obtained at each time in the same way. We assessed the extent to which these two approaches to modeling discrimination of the stimulus-reinforcer relation could account for choice in a range of temporal-discrimination procedures. The version of the model that redistributed numbers of reinforcers accounted for more variance in the data. Further, this version provides an explanation for shifts in the point of subjective equality that occur as a result of changes in the local reinforcer rate. The inclusion of a parameter reflecting error in discriminating the response-reinforcer relation enhanced the ability of each version of the model to describe data. The ability of this class of model to account for a range of data suggests that timing, like other conditional discriminations, is choice under the joint discriminative control of elapsed time and differential reinforcement. Understanding the role of differential reinforcement is therefore critical to understanding control by elapsed time. Copyright © 2016 Elsevier B.V. All rights reserved.

Thermodynamic Modeling and Dispatch of Distributed Energy Technologies including Fuel Cell -- Gas Turbine Hybrids

NASA Astrophysics Data System (ADS)

McLarty, Dustin Fogle

Distributed energy systems are a promising means by which to reduce both emissions and costs. Continuous generators must be responsive and highly efficiency to support building dynamics and intermittent on-site renewable power. Fuel cell -- gas turbine hybrids (FC/GT) are fuel-flexible generators capable of ultra-high efficiency, ultra-low emissions, and rapid power response. This work undertakes a detailed study of the electrochemistry, chemistry and mechanical dynamics governing the complex interaction between the individual systems in such a highly coupled hybrid arrangement. The mechanisms leading to the compressor stall/surge phenomena are studied for the increased risk posed to particular hybrid configurations. A novel fuel cell modeling method introduced captures various spatial resolutions, flow geometries, stack configurations and novel heat transfer pathways. Several promising hybrid configurations are analyzed throughout the work and a sensitivity analysis of seven design parameters is conducted. A simple estimating method is introduced for the combined system efficiency of a fuel cell and a turbine using component performance specifications. Existing solid oxide fuel cell technology is capable of hybrid efficiencies greater than 75% (LHV) operating on natural gas, and existing molten carbonate systems greater than 70% (LHV). A dynamic model is calibrated to accurately capture the physical coupling of a FC/GT demonstrator tested at UC Irvine. The 2900 hour experiment highlighted the sensitivity to small perturbations and a need for additional control development. Further sensitivity studies outlined the responsiveness and limits of different control approaches. The capability for substantial turn-down and load following through speed control and flow bypass with minimal impact on internal fuel cell thermal distribution is particularly promising to meet local demands or provide dispatchable support for renewable power. Advanced control and dispatch heuristics are discussed using a case study of the UCI central plant. Thermal energy storage introduces a time horizon into the dispatch optimization which requires novel solution strategies. Highly efficient and responsive generators are required to meet the increasingly dynamic loads of today's efficient buildings and intermittent local renewable wind and solar power. Fuel cell gas turbine hybrids will play an integral role in the complex and ever-changing solution to local electricity production.

First follow-up radiographic response is one of the predictors of local tumor progression and radiation necrosis after stereotactic radiosurgery for brain metastases.

PubMed

Sharma, Mayur; Jia, Xuefei; Ahluwalia, Manmeet; Barnett, Gene H; Vogelbaum, Michael A; Chao, Samuel T; Suh, John H; Murphy, Erin S; Yu, Jennifer S; Angelov, Lilyana; Mohammadi, Alireza M

2017-09-01

Local progression (LP) and radiation necrosis (RN) occur in >20% of cases following stereotactic radiosurgery (SRS) for brain metastases (BM). Expected outcomes following SRS for BM include tumor control/shrinkage, local progression and radiation necrosis. 1427 patients with 4283 BM lesions were treated using SRS at Cleveland Clinic from 2000 to 2012. Clinical, imaging and radiosurgery data were collected from the database. Local tumor progression and RN were the primary end points and correlated with patient and tumor-related variables. 5.7% of lesions developed radiographic RN and 3.6% showed local progression at 6 months. Absence of new extracranial metastasis (P < 0.001), response to SRS at first follow-up scan (local progression versus stable size (P < 0.001), partial resolution versus complete resolution at first follow up [P = 0.009]), prior SRS to the same lesion (P < 0.001), IDL% (≤55; P < 0.001), maximum tumor diameter (>0.9 cm; P < 0.001) and MD/PD gradient index (≤1.8, P < 0.001) were independent predictors of high risk of local tumor progression. Absence of systemic metastases (P = 0.029), good neurological function at 1st follow-up (P ≤ 0.001), no prior SRS to other lesion (P = 0.024), low conformity index (≤1.9) (P = 0.009), large maximum target diameter (>0.9 cm) (P = 0.003) and response to SRS (tumor progression vs. stable size following SRS [P < 0.001]) were independent predictors of high risk of radiographic RN. Complete tumor response at first follow-up, maximum tumor diameter <0.9 cm, tumor volume <2.4 cc and no prior SRS to the index lesion are good prognostic factors with reduced risk of LP following SRS. Complete tumor response to SRS, poor neurological function at first follow-up, prior SRS to other lesions and high conformity index are favorable factors for not developing RN. Stable or partial response at first follow-up after SRS have same impact on local progression and RN compared to those with complete resolution or progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

"A time of fear": local, national, and international responses to a large Ebola outbreak in Uganda.

PubMed

Kinsman, John

2012-06-13

This paper documents and analyses some of the responses to the largest Ebola outbreak on record, which took place in Uganda between September 2000 and February 2001. Four hundred and twenty five people developed clinical symptoms in three geographically distinct parts of the country (Gulu, Masindi, and Mbarara), of whom 224 (53%) died. Given the focus of previous social scientific Ebola research on experiences in communities that have been directly affected, this article expands the lens to include responses to the outbreak in local, national, and international contexts over the course of the outbreak. Responses to the outbreak were gauged through the articles, editorials, cartoons, and letters that were published in the country's two main English language daily national newspapers: the New Vision and the Monitor (now the Daily Monitor). All the relevant pieces from these two sources over the course of the epidemic were cut out, entered onto a computer, and the originals filed. The three a priori codes, based on the local, national, and international levels, were expanded into six, to include issues that emerged inductively during analysis. The data within each code were subsequently worked into coherent, chronological narratives. A total of 639 cuttings were included in the analysis. Strong and varied responses to the outbreak were identified from across the globe. These included, among others: confusion, anger, and serious stigma in affected communities; medical staff working themselves to exhaustion, with some quitting their posts; patients fleeing from hospitals; calls on spiritual forces for protection against infection; a well-coordinated national control strategy; and the imposition of some international travel restrictions. Responses varied both quantitatively and qualitatively according to the level (i.e. local, national, or international) at which they were manifested. The Ugandan experience of 2000/2001 demonstrates that responses to an Ebola outbreak can be very dramatic, but perhaps disproportionate to the actual danger presented. An important objective for any future outbreak control strategy must be to prevent excessive fear, which, it is expected, would reduce stigma and other negative outcomes. To this end, the value of openness in the provision of public information, and critically, of being seen to be open, cannot be overstated.

“A time of fear”: local, national, and international responses to a large Ebola outbreak in Uganda

PubMed Central

2012-01-01

Background This paper documents and analyses some of the responses to the largest Ebola outbreak on record, which took place in Uganda between September 2000 and February 2001. Four hundred and twenty five people developed clinical symptoms in three geographically distinct parts of the country (Gulu, Masindi, and Mbarara), of whom 224 (53%) died. Given the focus of previous social scientific Ebola research on experiences in communities that have been directly affected, this article expands the lens to include responses to the outbreak in local, national, and international contexts over the course of the outbreak. Methods Responses to the outbreak were gauged through the articles, editorials, cartoons, and letters that were published in the country’s two main English language daily national newspapers: the New Vision and the Monitor (now the Daily Monitor). All the relevant pieces from these two sources over the course of the epidemic were cut out, entered onto a computer, and the originals filed. The three a priori codes, based on the local, national, and international levels, were expanded into six, to include issues that emerged inductively during analysis. The data within each code were subsequently worked into coherent, chronological narratives. Results A total of 639 cuttings were included in the analysis. Strong and varied responses to the outbreak were identified from across the globe. These included, among others: confusion, anger, and serious stigma in affected communities; medical staff working themselves to exhaustion, with some quitting their posts; patients fleeing from hospitals; calls on spiritual forces for protection against infection; a well-coordinated national control strategy; and the imposition of some international travel restrictions. Responses varied both quantitatively and qualitatively according to the level (i.e. local, national, or international) at which they were manifested. Conclusions The Ugandan experience of 2000/2001 demonstrates that responses to an Ebola outbreak can be very dramatic, but perhaps disproportionate to the actual danger presented. An important objective for any future outbreak control strategy must be to prevent excessive fear, which, it is expected, would reduce stigma and other negative outcomes. To this end, the value of openness in the provision of public information, and critically, of being seen to be open, cannot be overstated. PMID:22695277

Adenosine receptor inhibition with theophylline attenuates the skin blood flow response to local heating in humans.

PubMed

Fieger, Sarah M; Wong, Brett J

2010-09-01

Mechanisms underlying the robust cutaneous vasodilatation in response to local heating of human skin remain unresolved. Adenosine receptor activation has been shown to induce vasodilatation via nitric oxide, and a substantial portion of the plateau phase to local heating of human skin has been shown to be dependent on nitric oxide. The purpose of this study was to investigate a potential role for adenosine receptor activation in cutaneous thermal hyperaemia in humans. Six subjects were equipped with four microdialysis fibres on the ventral forearm. Sites were randomly assigned to receive one of the following four treatments: (1) lactated Ringer solution to serve as a control; (2) 4 mM theophylline, a competitive, non-selective A(1)/A(2) adenosine receptor antagonist; (3) 10 mM Nomega(-)-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase; or (4) combined 4 mm theophylline + 10 mM L-NAME. Following baseline measurements, each site was locally heated from a baseline temperature of 33 degrees C to 42 degrees C at a rate of 1 degrees C (10 s)(-1), and skin blood flow was monitored via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF divided by mean arterial pressure and normalized to maximal values (CVC(max)) via local heating to 43 degrees C and infusion of 28 mM sodium nitroprusside. The initial peak was significantly reduced in theophylline (68 +/- 2% CVC(max)) and L-NAME sites (54 +/- 5% CVC(max)) compared with control sites (81 +/- 2% CVC(max); P < 0.01 and P < 0.001, respectively). Combined theophylline + L-NAME (52 +/- 5% CVC(max)) reduced the initial peak compared with control and theophylline sites, but was not significantly different compared with L-NAME sites. The secondary plateau was attenuated in theophylline (77 +/- 2% CVC(max)), L-NAME (60 +/- 2% CVC(max)) and theophylline + L-NAME (53 +/- 1% CVC(max)) compared with control sites (94 +/- 2% CVC(max); P < 0.001 for all conditions). The secondary plateau was reduced in L-NAME compared with theophylline sites (P < 0.001), and combined theophylline + L-NAME further reduced the secondary plateau compared with theophylline- (P < 0.001) and L-NAME-only sites (P < 0.05). These data suggest that adenosine receptor activation directly contributes to cutaneous thermal hyperaemia, as evidenced by the reduced initial peak and secondary plateau in theophylline sites. These data further suggest that a portion of the NO response may be explained by adenosine receptor activation; however, a substantial portion of the NO response is independent of adenosine receptor activation.

Cooperation and control: the Tobacco Institute of Australia.

PubMed

Carter, S M

2003-12-01

To describe the history of the Tobacco Institute of Australia (TIA), particularly regarding connections between local and international cigarette manufacturers and tobacco organisations. Analysis of 4541 industry documents from the world wide web. From 1978 to 1983 the TIA built strong international networks via ICOSI/INFOTAB and the US Tobacco Institute, and defended existing industry freedoms. 1983 to 1989 was the TIA's aggressive heyday, led primarily by John Dollisson. From 1989 to 1994, following the decision in Australian Federation of Consumer Organisations vs TIA, local and international industry lawyers assumed control. Between 1994 and 1997 a brief revival led into decline and then dissolution, as previously common ground became commercially competitive issues for the manufacturers. The TIA facilitated interconnectedness: between local manufacturers; via individuals who played multiple roles; to international tobacco organisations; through the industry's local and international counsel; and by acting as a conduit for information. The local tobacco industry was comprehensively informed on issues including smoking and health, and connected to the international industry, via the TIA. The manufacturers were closely involved in the TIA's activities, and cooperated through the TIA in a manner detrimental to Australian consumers. The TIA's conduct was the responsibility of local and international manufacturers and their counsel.

Plasticity of spatial hearing: behavioural effects of cortical inactivation

PubMed Central

Nodal, Fernando R; Bajo, Victoria M; King, Andrew J

2012-01-01

The contribution of auditory cortex to spatial information processing was explored behaviourally in adult ferrets by reversibly deactivating different cortical areas by subdural placement of a polymer that released the GABAA agonist muscimol over a period of weeks. The spatial extent and time course of cortical inactivation were determined electrophysiologically. Muscimol-Elvax was placed bilaterally over the anterior (AEG), middle (MEG) or posterior ectosylvian gyrus (PEG), so that different regions of the auditory cortex could be deactivated in different cases. Sound localization accuracy in the horizontal plane was assessed by measuring both the initial head orienting and approach-to-target responses made by the animals. Head orienting behaviour was unaffected by silencing any region of the auditory cortex, whereas the accuracy of approach-to-target responses to brief sounds (40 ms noise bursts) was reduced by muscimol-Elvax but not by drug-free implants. Modest but significant localization impairments were observed after deactivating the MEG, AEG or PEG, although the largest deficits were produced in animals in which the MEG, where the primary auditory fields are located, was silenced. We also examined experience-induced spatial plasticity by reversibly plugging one ear. In control animals, localization accuracy for both approach-to-target and head orienting responses was initially impaired by monaural occlusion, but recovered with training over the next few days. Deactivating any part of the auditory cortex resulted in less complete recovery than in controls, with the largest deficits observed after silencing the higher-level cortical areas in the AEG and PEG. Although suggesting that each region of auditory cortex contributes to spatial learning, differences in the localization deficits and degree of adaptation between groups imply a regional specialization in the processing of spatial information across the auditory cortex. PMID:22547635

Immuno-modulatory effect of local rhEGF treatment during tissue repair in diabetic ulcers.

PubMed

García-Honduvilla, Natalio; Cifuentes, Alberto; Ortega, Miguel A; Pastor, Marta; Gainza, Garazi; Gainza, Eusebio; Buján, Julia; Álvarez-Mon, Melchor

2018-04-01

Wound healing is a complex process that can be severely impaired due to pathological situations such as diabetes mellitus. Diabetic foot ulcers are a common complication of this pathology and are characterized by an excessive inflammatory response. In this work, the effects of local treatment with recombinant human epidermal growth factor (rhEGF) were studied using a full-thickness wound healing model in streptozotocin-induced diabetic rats. Wound healing process was assessed with different concentrations of rhEGF (0.1, 0.5, 2.0 and 8.0 µg/mL), placebo and both diabetic and non-diabetic controls ( n  = 53). The macroscopic healing observed in treated diabetic rats was affected by rhEGF concentration. Histologically, we also observed an improvement in the epithelialization, granulation tissue formation and maturation in treated groups, finding again the best response at doses of 0.5 and 2.0 µg/mL. Afterwards, the tissue immune response over time was assessed in diabetic rats using the most effective concentrations of rhEGF (0.5 and 2.0 µg/mL), compared to controls. The presence of macrophages, CD4 + T lymphocytes and CD8 + T lymphocytes, in the reparative tissue was quantified, and cytokine expression was measured by quantitative real-time PCR. rhEGF treatment caused a reduction in the number of infiltrating macrophages in the healing tissue of diabetic, as well as diminished activation of these leukocytes. These findings show that local administration of rhEGF improves the healing process of excisional wounds and the quality of the neoformed tissue in a dose-dependent manner. Besides, this treatment reduces the local inflammation associated with diabetic healing, indicating immuno-modulatory properties. © 2018 The authors.

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

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

Ladra, Matthew M.; Mandeville, Henry C.; Niemierko, Andrzej

2015-06-01

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results:more » With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.« less

Radiotherapy of soft tissue sarcomas in dogs.

PubMed

McChesney, S L; Withrow, S J; Gillette, E L; Powers, B E; Dewhirst, M W

1989-01-01

Megavoltage radiotherapy was administered to 42 dogs with soft tissue sarcoma. Acceptable local control of these aggressive tumors was achieved after one year of treatment. Control rates of 48 and 67% were obtained at doses of 45 and 50 gray (Gy), respectively. At 2 years, control rates decreased to 33% at the dose of 50 Gy. Serious complications developed in 4 of 42 dogs at doses of 40 to 50 Gy. The estimated dose with a 50% probability for causing serious complications was 54 Gy, given in 10 fractions. We believe that the large doses per fraction used in this study probably led to an increased probability for necrosis. Hemangiopericytomas seemed to be more responsive than fibrosarcomas. Only 2 of 11 recurrent tumors were controlled with surgery. Good local control was achieved with radiation alone for one year at doses with a low probability for serious complications; however, higher total radiation doses or combined modalities, such as surgery and radiation or radiation and hyperthermia, may be needed for longer-term control.

Investigating neuronal function with optically controllable proteins

PubMed Central

Zhou, Xin X.; Pan, Michael; Lin, Michael Z.

2015-01-01

In the nervous system, protein activities are highly regulated in space and time. This regulation allows for fine modulation of neuronal structure and function during development and adaptive responses. For example, neurite extension and synaptogenesis both involve localized and transient activation of cytoskeletal and signaling proteins, allowing changes in microarchitecture to occur rapidly and in a localized manner. To investigate the role of specific protein regulation events in these processes, methods to optically control the activity of specific proteins have been developed. In this review, we focus on how photosensory domains enable optical control over protein activity and have been used in neuroscience applications. These tools have demonstrated versatility in controlling various proteins and thereby cellular functions, and possess enormous potential for future applications in nervous systems. Just as optogenetic control of neuronal firing using opsins has changed how we investigate the function of cellular circuits in vivo, optical control may yet yield another revolution in how we study the circuitry of intracellular signaling in the brain. PMID:26257603

Modeling lateral geniculate nucleus response with contrast gain control. Part 2: Analysis

PubMed Central

Cope, Davis; Blakeslee, Barbara; McCourt, Mark E.

2014-01-01

Cope, Blakeslee and McCourt (2013) proposed a class of models for LGN ON-cell behavior consisting of a linear response with divisive normalization by local stimulus contrast. Here we analyze a specific model with the linear response defined by a difference-of-Gaussians filter and a circular Gaussian for the gain pool weighting function. For sinusoidal grating stimuli, the parameter region for band-pass behavior of the linear response is determined, the gain control response is shown to act as a switch (changing from “off” to “on” with increasing spatial frequency), and it is shown that large gain pools stabilize the optimal spatial frequency of the total nonlinear response at a fixed value independent of contrast and stimulus magnitude. Under- and super-saturation as well as contrast saturation occur as typical effects of stimulus magnitude. For circular spot stimuli, it is shown that large gain pools stabilize the spot size that yields the maximum response. PMID:24562034

A map of local adaptation in Arabidopsis thaliana.

PubMed

Fournier-Level, A; Korte, A; Cooper, M D; Nordborg, M; Schmitt, J; Wilczek, A M

2011-10-07

Local adaptation is critical for species persistence in the face of rapid environmental change, but its genetic basis is not well understood. Growing the model plant Arabidopsis thaliana in field experiments in four sites across the species' native range, we identified candidate loci for local adaptation from a genome-wide association study of lifetime fitness in geographically diverse accessions. Fitness-associated loci exhibited both geographic and climatic signatures of local adaptation. Relative to genomic controls, high-fitness alleles were generally distributed closer to the site where they increased fitness, occupying specific and distinct climate spaces. Independent loci with different molecular functions contributed most strongly to fitness variation in each site. Independent local adaptation by distinct genetic mechanisms may facilitate a flexible evolutionary response to changing environment across a species range.

Crucial issues of multi-beam feed-back control with ECH/ECCD in fusion plasmas

NASA Astrophysics Data System (ADS)

Cirant, S.; Berrino, J.; Gandini, F.; Granucci, G.; Iannone, F.; Lazzaro, E.; D'Antona, G.; Farina, D.; Koppenburg, K.; Nowak, S.; Ramponi, G.

2005-01-01

Proof of principle of feed-back controlled Electron Cyclotron Heating and Current Drive (ECH/ECCD), aiming at automatic limitation (or suppression) of Neoclassical Tearing Modes amplitude, has been achieved in a number of present machines. In addition to Neoclassical Tearing Mode stabilization, more applications of well-localized ECH/ECCD can be envisaged (saw-tooth crash control, current profile control, thermal barrier control, disruption mitigation). However, in order to be able to take a step forward towards the application of these techniques to burning plasmas, some crucial issues should be more deeply analyzed: multi-beam simultaneous action, control of deposition radii rdep, diagnostic of plasma reaction. So far the Electron Cyclotron Emission has been the most important tool to get localized information on plasma response, essential for both rdep and risland recognition, but its use in very hot burning plasmas within automatic control loops should be carefully verified. Assuming that plasma response is appropriately diagnosed, the next matter to be discussed concerns how to control rdep, since all techniques so far used, or proposed (plasma position, toroidal field, mechanical beam steering, gyrotron frequency tuning) have limitations or drawbacks. Finally, simultaneous multiple actions on many actuators (EC beams), concurring to automatic control of one single parameter (e.g. NTM amplitude) might be a challenging task for the controller, particularly in view of the fact that any effect of each beam becomes visible only when it is positioned very close to the right radius. All these interlinked aspects are discussed in the paper.

Lack of TAK1 in dendritic cells inhibits the contact hypersensitivity response induced by trichloroethylene in local lymph node assay

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

Yao, Pan; Hongqian, Chu; Qinghe, Meng

Trichloroethylene (TCE) is a ubiquitous environmental contaminant. Occupational TCE exposure has been associated with severe, generalized contact hypersensitivity (CHS) skin disorder. The development of CHS depends on innate and adaptive immune functions. Transforming growth factor-β activated kinase-1 (TAK1) controls the survival of dendritic cells (DCs) that affect the immune system homeostasis. We aimed to investigate the role of TAK1 activity in DC on TCE-induced CHS response. Control mice and DC-specific TAK1 deletion mice were treated with 80% (v/v) TCE using local lymph node assay (LLNA) to establish a TCE-induced CHS model. The draining lymph nodes (DLNs) were excised and themore » lymphocytes were measure for proliferation by BrdU-ELISA, T-cell phenotype analysis by flow cytometry and signaling pathway activation by western blot. The ears were harvested for histopathological analysis. Control mice in the 80% TCE group displayed an inflammatory response in the ears, increased lymphocyte proliferation, elevated regulatory T-cell and activated T-cell percentages, and more IFN-γ producing CD8{sup +} T cells in DLNs. In contrast to control mice, DC-specific TAK1 deletion mice in the 80% TCE group showed an abolished CHS response and this was associated with defective T-cell expansion, activation and IFN-γ production. This effect may occur through Jnk and NF-κB signaling pathways. Overall, this study demonstrates a pivotal role of TAK1 in DCs in controlling TCE-induced CHS response and suggests that targeting TAK1 function in DCs may be a viable approach to preventing and treating TCE-related occupational health hazards. - Highlights: • Lack of TAK1 in DC caused an abolished TCE-induced CHS response. • TAK1 in DCs was essential to maintain the homeostasis of T cells in TCE-induced CHS. • Intact TAK1 in DCs was critical to promote T-cell priming in TCE-induced CHS. • DC-specific TAK1 deficiency abolished the TCE-mediated phosphorylation of Jnk.« less

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors.

PubMed

Conde, Sofia; Borrego, Margarida; Teixeira, Tânia; Teixeira, Rubina; Sá, Anabela; Soares, Paula

2012-01-01

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer. There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND). A set of 159 patients with LARC were treated preoperatively. Group A - 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B - 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy. pathologic complete response (pCR) - 18.7%; TD - 55.1%; ND - 76%; loco-regional response - 74.8%. Group B: pCR - 11.4%; TD - 50%; ND - 55.8%; LRR - 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS. Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.

40 CFR 763.99 - Exclusions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.99 Exclusions. (a) A local education agency shall not be... that school. (4) The lead agency responsible for asbestos inspection in a State that has been granted a...

40 CFR 763.99 - Exclusions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.99 Exclusions. (a) A local education agency shall not be... that school. (4) The lead agency responsible for asbestos inspection in a State that has been granted a...

40 CFR 763.99 - Exclusions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.99 Exclusions. (a) A local education agency shall not be... that school. (4) The lead agency responsible for asbestos inspection in a State that has been granted a...

40 CFR 763.99 - Exclusions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.99 Exclusions. (a) A local education agency shall not be... that school. (4) The lead agency responsible for asbestos inspection in a State that has been granted a...

40 CFR 763.99 - Exclusions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT ASBESTOS Asbestos-Containing Materials in Schools § 763.99 Exclusions. (a) A local education agency shall not be... that school. (4) The lead agency responsible for asbestos inspection in a State that has been granted a...

Citizenship, Diversity and Distance Learning: Videoconferencing in Connecticut.

ERIC Educational Resources Information Center

Sembor, Edward C.

1997-01-01

Profiles a videoconference that brought together two seventh-grade classes in Connecticut. Over several days, white, middle-class, rural students discussed topical issues with urban black students. Topics raised included diversity, politics, gun control and local issues. Includes students' responses to the program. (MJP)

Stereotactic body radiotherapy for de novo spinal metastases: systematic review.

PubMed

Husain, Zain A; Sahgal, Arjun; De Salles, Antonio; Funaro, Melissa; Glover, Janis; Hayashi, Motohiro; Hiraoka, Masahiro; Levivier, Marc; Ma, Lijun; Martínez-Alvarez, Roberto; Paddick, J Ian; Régis, Jean; Slotman, Ben J; Ryu, Samuel

2017-09-01

OBJECTIVE The aim of this systematic review was to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases. METHODS The authors performed a systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, of the literature found in a search of Medline, PubMed, Embase, and the Cochrane Library up to March 2015. The search strategy was limited to publications in the English language. RESULTS A total of 14 full-text articles were included in the analysis. All studies were retrospective except for 2 studies, which were prospective. A total of 1024 treated spinal lesions were analyzed. The median follow-up time ranged from 9 to 49 months. A range of dose-fractionation schemes was used, the most common of which were 16-24 Gy/1 fraction (fx), 24 Gy/2 fx, 24-27 Gy/3 fx, and 30-35 Gy/5 fx. In studies that reported crude results regarding in-field local tumor control, 346 (85%) of 407 lesions remained controlled. For studies that reported actuarial values, the weighted average revealed a 90% 1-year local control rate. Only 3 studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases; 2 cases (0.2%) of neurologic injury were reported. CONCLUSION There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review found that SBRT is associated with favorable rates of local control (approximately 90% at 1 year) and complete pain response (approximately 50%), and low rates of serious adverse events were found. Practice guidelines are summarized based on these data and International Stereotactic Radiosurgery Society consensus.

Effect of local wound infiltration with ropivacaine on postoperative pain relief and stress response reduction after open hepatectomy.

PubMed

Sun, Jing-Xian; Bai, Ke-Yun; Liu, Yan-Feng; Du, Gang; Fu, Zhi-Hao; Zhang, Hao; Yang, Jin-Huan; Wang, Ben; Wang, Xiu-Yu; Jin, Bin

2017-09-28

To prospectively evaluate the effect of local wound infiltration with ropivacaine on postoperative pain relief and stress response reduction after open hepatectomy. A total of 56 patients undergoing open hepatectomy were randomly divided into two groups: a ropivacaine group (wound infiltration with ropivacaine solution) and a control group (infiltration with isotonic saline solution). A visual analog scale (VAS) at rest and on movement was used to measure postoperative pain for the first 48 h after surgery. Mean arterial pressure (MAP), heart rate (HR), time to bowel recovery, length of hospitalization after surgery, cumulative sufentanil consumption, and incidence of nausea and vomiting were compared between the two groups. Surgical stress hormones (epinephrine, norepinephrine, and cortisol) were detected using enzyme-linked immunosorbent assay, and the results were compared. VAS scores both at rest and on movement at 24 h and 48 h were similar between the two groups. Significantly lower VAS scores were detected at 0, 6, and 12 h in the ropivacaine group compared with the control group ( P < 0.05 for all). MAP was significantly lower at 6, 12, and 24 h ( P < 0.05 for all); HR was significantly lower at 0, 6, 12, and 24 h ( P < 0.05 for all); time to bowel recovery and length of hospitalization after surgery ( P < 0.05 for both) were significantly shortened; and cumulative sufentanil consumption was significantly lower at 6, 12, 24, and 36 h ( P < 0.05 for all) in the ropivacaine group than in the control group, although the incidence of nausea and vomiting showed no significant difference between the two groups. The levels of epinephrine, norepinephrine, and cortisol were significantly lower in the ropivacaine group than in the control group at 24 and 48 h ( P < 0.01 for all). Local wound infiltration with ropivacaine after open hepatectomy can improve postoperative pain relief, reduce surgical stress response, and accelerate postoperative recovery.

Differential acute and chronic effects of burn trauma on murine skeletal muscle bioenergetics

PubMed Central

Porter, Craig; Herndon, David N.; Bhattarai, Nisha; Ogunbileje, John O.; Szczesny, Bartosz; Szabo, Csaba; Toliver-Kinsky, Tracy; Sidossis, Labros S.

2015-01-01

Altered skeletal muscle mitochondrial function contributes to the pathophysiological stress response to burns. However, the acute and chronic impact of burn trauma on skeletal muscle bioenergetics remains poorly understood. Here, we determined the temporal relationship between burn trauma and mitochondrial function in murine skeletal muscle local to and distal from burn wounds. Male BALB/c mice (8–10 weeks old) were burned by submersion of the dorsum in water (~95°C) to create a full thickness burn on ~30% of the body. Skeletal muscle was harvested from spinotrapezius underneath burn wounds (local) and the quadriceps (distal) of sham and burn treated mice at 3h, 24h, 4d and 10d post-injury. Mitochondrial respiration was determined in permeabilized myofiber bundles by high-resolution respirometry. Caspase 9 and caspase 3 protein concentration were determined by western blot. In muscle local to burn wounds, respiration coupled to ATP production was significantly diminished at 3h and 24h post-injury (P<0.001), as was mitochondrial coupling control (P<0.001). There was a 5- (P<0.05) and 8-fold (P<0.001) increase in respiration in response to cytochrome at 3h and 24h post burn, indicating damage to the outer mitochondrial membranes. Moreover, we also observed greater active caspase 9 and caspase 3 in muscle local to burn wounds, indicating the induction of apoptosis. Distal muscle mitochondrial function was unaltered by burn trauma until 10d post burn, where both respiratory capacity (P<0.05) and coupling control (P<0.05) was significantly lower than sham. These data highlight a differential response in muscle mitochondrial function to burn trauma, where the timing, degree and mode of dysfunction are dependent on whether the muscle is local or distal to the burn wound. PMID:26615714

Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor.

PubMed

Wang, Ling-Wei; Liu, Yen-Wan Hsueh; Chou, Fong-In; Jiang, Shiang-Huei

2018-06-19

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

Statistical evaluation of the Local Lymph Node Assay.

PubMed

Hothorn, Ludwig A; Vohr, Hans-Werner

2010-04-01

In the Local Lymph Node Assay measured endpoints for each animal, such as cell proliferation, cell counts and/or lymph node weight should be evaluated separately. The primary criterion for a positive response is when the estimated stimulation index is larger than a specified relative threshold that is endpoint- and strain-specific. When the lower confidence limit for ratio-to-control comparisons is larger than a relevance threshold, a biologically relevant increase can be concluded according to the proof of hazard. Alternatively, when the upper confidence limit for ratio-to-control comparisons is smaller than a tolerable margin, harmlessness can be concluded according to a proof of safety. Copyright 2009 Elsevier Inc. All rights reserved.

The Role of Working Memory Capacity and Interference Resolution Mechanisms in Task Switching

PubMed Central

Pettigrew, Corinne; Martin, Randi C.

2015-01-01

Theories of task switching have emphasized a number of control mechanisms that may support the ability to flexibly switch between tasks. The present study examined the extent to which individual differences in working memory (WM) capacity and two measures of interference resolution, response-distractor inhibition and resistance to proactive interference (PI), account for variability in task switching, including global costs, local costs, and N-2 repetition costs. 102 young and 60 older adults were tested on a battery of tasks. Composite scores were created for WM capacity, response-distractor inhibition, and resistance to PI; shifting was indexed by rate residual scores which combine response time and accuracy and account for individual differences in processing speed. Composite scores served as predictors of task switching. WM was significantly related to global switch costs. While resistance to PI and WM explained some variance in local costs, these effects did not reach significance. In contrast, none of the control measures explained variance in N-2 repetition costs. Furthermore, age effects were only evident for N-2 repetition costs, with older adults demonstrating larger costs than young adults. Results are discussed within the context of theoretical models of task switching. PMID:26594895

The role of working memory capacity and interference resolution mechanisms in task switching.

PubMed

Pettigrew, Corinne; Martin, Randi C

2016-12-01

Theories of task switching have emphasized a number of control mechanisms that may support the ability to flexibly switch between tasks. The present study examined the extent to which individual differences in working memory (WM) capacity and two measures of interference resolution, response-distractor inhibition and resistance to proactive interference (PI), account for variability in task switching, including global costs, local costs, and N-2 repetition costs. A total of 102 young and 60 older adults were tested on a battery of tasks. Composite scores were created for WM capacity, response-distractor inhibition, and resistance to PI; shifting was indexed by rate residual scores, which combine response time and accuracy and account for individual differences in processing speed. Composite scores served as predictors of task switching. WM was significantly related to global switch costs. While resistance to PI and WM explained some variance in local costs, these effects did not reach significance. In contrast, none of the control measures explained variance in N-2 repetition costs. Furthermore, age effects were only evident for N-2 repetition costs, with older adults demonstrating larger costs than young adults. Results are discussed within the context of theoretical models of task switching.

Quantitative in vivo studies of hyperemia in the course of the tissue response to biomaterial implantation

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

Bouet, T.; Schmitt, M.; Desuzinges, C.

1990-11-01

Hyperemia associated with an inflammatory response has been investigated in rats, by using four different experimental models, i.e., positive and negative polymer implants from the pharmacopea, operative control, and abscess induced by turpentine oil. 133Xenon clearance, infrared thermography and Laser Doppler Flowmetry (LDF) were used to monitor the subcutaneous local hemodynamic changes from 1 to 40 postoperative days. LDF proved to be a sensitive, reproducible method, able to discriminate positive from negative implants already at the 3rd postoperative day and up to 40 days. This increased local blood flow was also visualized at the site of positive implants at themore » 14th and 21st postoperative days by means of 133Xe Clearance. Additional information obtained by infrared thermography allowed discrimination between positive implants and control sites but only at the very early stage (1 to 3 days). The significance of the different data collected by the three techniques was correlated with histological events occurring at the different implant sites. LDF may therefore represent a useful technique for noninvasive semiquantitative assessment of tissue response to biomaterials.« less

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

PubMed Central

Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

2016-01-01

Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

Linear and non-linear responses of vegetation and soils to glacial-interglacial climate change in a Mediterranean refuge.

PubMed

Holtvoeth, Jens; Vogel, Hendrik; Valsecchi, Verushka; Lindhorst, Katja; Schouten, Stefan; Wagner, Bernd; Wolff, George A

2017-08-14

The impact of past global climate change on local terrestrial ecosystems and their vegetation and soil organic matter (OM) pools is often non-linear and poorly constrained. To address this, we investigated the response of a temperate habitat influenced by global climate change in a key glacial refuge, Lake Ohrid (Albania, Macedonia). We applied independent geochemical and palynological proxies to a sedimentary archive from the lake over the penultimate glacial-interglacial transition (MIS 6-5) and the following interglacial (MIS 5e-c), targeting lake surface temperature as an indicator of regional climatic development and the supply of pollen and biomarkers from the vegetation and soil OM pools to determine local habitat response. Climate fluctuations strongly influenced the ecosystem, however, lake level controls the extent of terrace surfaces between the shoreline and mountain slopes and hence local vegetation, soil development and OM export to the lake sediments. There were two phases of transgressional soil erosion from terrace surfaces during lake-level rise in the MIS 6-5 transition that led to habitat loss for the locally dominant pine vegetation as the terraces drowned. Our observations confirm that catchment morphology plays a key role in providing refuges with low groundwater depth and stable soils during variable climate.

Interaction between mantle and crustal detachments: a non-linear system controlling lithospheric extension

NASA Astrophysics Data System (ADS)

Rosenbaum, G.; Regenauer-Lieb, K.; Weinberg, R. F.

2009-12-01

We use numerical modelling to investigate the development of crustal and mantle detachment faults during lithospheric extension. Our models simulate a wide range of rift systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles, which grow in response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation at different levels of the lithosphere. Crustal detachment faults are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW/m2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate (60-70 mW/m2) heat flow. Results show a non-linear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometime unexpected switches in extension modes (e.g. from diffuse rifting to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this non-linearity to result from the interference of doming wavelengths. Disharmony of crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonious crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged rifting history prior to continental breakup.

Interaction between mantle and crustal detachments: A nonlinear system controlling lithospheric extension

NASA Astrophysics Data System (ADS)

Rosenbaum, Gideon; Regenauer-Lieb, Klaus; Weinberg, Roberto F.

2010-11-01

We use numerical modeling to investigate the development of crustal and mantle detachments during lithospheric extension. Our models simulate a wide range of extensional systems with varying values of crustal thickness and heat flow, showing how strain localization in the mantle interacts with localization in the upper crust and controls the evolution of extensional systems. Model results reveal a richness of structures and deformation styles as a response to a self-organized mechanism that minimizes the internal stored energy of the system by localizing deformation. Crustal detachments, here referred as low-angle normal decoupling horizons, are well developed during extension of overthickened (60 km) continental crust, even when the initial heat flow is relatively low (50 mW m-2). In contrast, localized mantle deformation is most pronounced when the extended lithosphere has a normal crustal thickness (30-40 km) and an intermediate heat flow (60-70 mW m-2). Results show a nonlinear response to subtle changes in crustal thickness or heat flow, characterized by abrupt and sometimes unexpected switches in extension modes (e.g., from diffuse extensional deformation to effective lithospheric-scale rupturing) or from mantle- to crust-dominated strain localization. We interpret this nonlinearity to result from the interference of doming wavelengths in the presence of multiple necking instabilities. Disharmonic crust and mantle doming wavelengths results in efficient communication between shear zones at different lithospheric levels, leading to rupturing of the whole lithosphere. In contrast, harmonic crust and mantle doming inhibits interaction of shear zones across the lithosphere and results in a prolonged history of extension prior to continental breakup.

Haemodynamic responses in chronically painful, human trapezius muscle to cold pressor stimulation.

PubMed

Acero, C O; Kuboki, T; Maekawa, K; Yamashita, A; Clark, G T

1999-10-01

The aim was to compare haemodynamic responses in trapezius muscles to cold pressor stimulation in individuals with localized trapezius myalgia and asymptomatic controls. Nine males with chronic localized pain in the trapezius (mean age, 23.2 years) and nine male controls (mean age, 24.6 years) who had no medical history of migraine, hypertension or sustained pain in the trapezius region were investigated. Two experimental (cold pressor and mock) trials were performed in a randomly assigned sequence. In the cold pressor trial the participant's left foot and ankle were immersed in 4 degrees C cold water for 2 min; the mock trial was done without that stimulus. Blood volume was continuously recorded 1 min before, 2 min during, and 5 min after cold pressor stimulation using near-infrared spectroscopy. Each participant's blood-volume data were baseline-corrected and submitted to statistical analysis. Results showed that the individuals with muscle pain exhibited a significantly lower mean blood volume than the controls during cold pressor stimulation (p = 0.0367). Upon withdrawal of that stimulation, the mean blood volume in both groups fell below the baseline. These results suggest that individuals with chronic regional trapezius myalgia have less capacity to vasodilate this muscle during cold pressor stimulation than those without such myalgia. It is not yet known if this difference in the haemodynamic response is a cause or an effect of the myalgia.

Global versus local mechanisms of temperature sensing in ion channels.

PubMed

Arrigoni, Cristina; Minor, Daniel L

2018-05-01

Ion channels turn diverse types of inputs, ranging from neurotransmitters to physical forces, into electrical signals. Channel responses to ligands generally rely on binding to discrete sensor domains that are coupled to the portion of the channel responsible for ion permeation. By contrast, sensing physical cues such as voltage, pressure, and temperature arises from more varied mechanisms. Voltage is commonly sensed by a local, domain-based strategy, whereas the predominant paradigm for pressure sensing employs a global response in channel structure to membrane tension changes. Temperature sensing has been the most challenging response to understand and whether discrete sensor domains exist for pressure and temperature has been the subject of much investigation and debate. Recent exciting advances have uncovered discrete sensor modules for pressure and temperature in force-sensitive and thermal-sensitive ion channels, respectively. In particular, characterization of bacterial voltage-gated sodium channel (BacNa V ) thermal responses has identified a coiled-coil thermosensor that controls channel function through a temperature-dependent unfolding event. This coiled-coil thermosensor blueprint recurs in other temperature sensitive ion channels and thermosensitive proteins. Together with the identification of ion channel pressure sensing domains, these examples demonstrate that "local" domain-based solutions for sensing force and temperature exist and highlight the diversity of both global and local strategies that channels use to sense physical inputs. The modular nature of these newly discovered physical signal sensors provides opportunities to engineer novel pressure-sensitive and thermosensitive proteins and raises new questions about how such modular sensors may have evolved and empowered ion channel pores with new sensibilities.

Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin.

PubMed

Yamazaki, Fumio

2012-05-01

Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.

Flow-Mediated Endothelial Mechanotransduction

PubMed Central

Davies, Peter F.

2011-01-01

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed. PMID:7624393

Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group.

PubMed

Meyer, Emmanuel; Pasquier, David; Bernadou, Guillemette; Calais, Gilles; Maroun, Pierre; Bossi, Alberto; Theodore, Christine; Albiges, Laurence; Stefan, Dinu; Crevoisier, Renaud D E; Hennequin, Christophe; Lagrange, Jean-Léon; Grellard, Jean-Michel; Clarisse, Bénédicte; Licaj, Idlir; Habrand, Jean-Louis; Carrie, Christian; Joly, Florence

2018-06-01

Renal cell carcinoma (RCC) is usually considered radioresistant, but stereotactic radiation therapy (SRT) may increase local disease control. This study aimed to assess the benefit of SRT in the management of metastatic RCC patients. Data of all RCC patients who received SRT between 2008 and 2015 with curative intent were retrospectively collected in six French referral centres. Local control (LC), progression-free survival (PFS), local recurrence-free survival (LRFS), time to systemic therapy (TTS) and overall survival (OS) were assessed. One hundred and eighty-eight patients treated with SRT for 252 RCC metastases (brain [n = 120]; spine [n = 75]; and others [n = 57]) were recensed. SRT was performed for oligoprogressive disease (101 patients), oligometastatic disease (80 patients) or residual tumour after a partial response to systemic treatment (7 patients). The median biologically effective dose was 78 Gy. For the whole population, local control rates at 6, 12 and 24 months were 87.5%, 82.9% and 77.6%, respectively; median PFS, LRFS, TTS and OS were 8.5, 23.2, 13.2 and 29.2 months, respectively. Among patients treated for oligoprogressive/oligometastatic disease, the median PFS, TTS, and OS were 8.6/7.6, 10.5/14.2 and 23.2/33.9 months, respectively. Among the 7 patients treated with SRT after partial response to systemic treatment, no relapse occurred for 3 of them after a median follow-up of 22 months. Acute and late severe toxicities were noted in 5 (2.6%) patients. SRT is effective and safe for oligometastatic and oligoprogressive RCC patients and may delay introduction or change of systemic therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Game Analysis of Water Pollution Control in China’s Watershed

NASA Astrophysics Data System (ADS)

Li, Shu Wen

2018-05-01

Water pollution in the river basin is an important environmental management problem in China. At present, China’s environmental governance has entered the policy game stage centered on related interests. There are two main focus areas. First, it aims to resolve the conflict between the central government, local governments, and enterprises in terms of the utilization of basin resources and the environment. Second, it is responsible for the implementation of environmental policy. By analyzing the relationships between the central government, local governments, and enterprises in the process of water pollution control in the river basin, this study examines the environmental regulation of the central government and the collusion between local governments and enterprises to pollute the environment. To achieve this, game theory is applied from the perspective of information economics. Lastly, the study proposes corresponding policy recommendations in order to get out of the “prisoner’s dilemma”.

Boron nitride nanotubes as vehicles for intracellular delivery of fluorescent drugs and probes.

PubMed

Niskanen, Jukka; Zhang, Issan; Xue, Yanming; Golberg, Dmitri; Maysinger, Dusica; Winnik, Françoise M

2016-01-01

To evaluate the response of cells to boron nitride nanotubes (BNNTs) carrying fluorescent probes or drugs in their inner channel by assessment of the cellular localization of the fluorescent cargo, evaluation of the in vitro release and biological activity of a drug (curcumin) loaded in BNNTs. Cells treated with curcumin-loaded BNNTs and stimulated with lipopolysaccharide were assessed for nitric oxide release and stimulation of IL-6 and TNF-α. The cellular trafficking of two cell-permeant dyes and a non-cell-permeant dye loaded within BNNTs was imaged. BNNTs loaded with up to 13 wt% fluorophores were internalized by cells and controlled release of curcumin triggered cellular pathways associated with the known anti-inflammatory effects of the drug. The overall findings indicate that BNNTs can function as nanocarriers of biologically relevant probes/drugs allowing one to examine/control their local intracellular localization and biochemical effects, leading the way to applications as intracellular nanosensors.

Modulatory compartments in cortex and local regulation of cholinergic tone.

PubMed

Coppola, Jennifer J; Ward, Nicholas J; Jadi, Monika P; Disney, Anita A

2016-09-01

Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms regulating skin immunity and inflammation.

PubMed

Pasparakis, Manolis; Haase, Ingo; Nestle, Frank O

2014-05-01

Immune responses in the skin are important for host defence against pathogenic microorganisms. However, dysregulated immune reactions can cause chronic inflammatory skin diseases. Extensive crosstalk between the different cellular and microbial components of the skin regulates local immune responses to ensure efficient host defence, to maintain and restore homeostasis, and to prevent chronic disease. In this Review, we discuss recent findings that highlight the complex regulatory networks that control skin immunity, and we provide new paradigms for the mechanisms that regulate skin immune responses in host defence and in chronic inflammation.

A Wireless Local Area Network Command and Control System for Explosive Ordnance Disposal Incident Response

DTIC Science & Technology

2001-09-01

43 4. GPS ......................................................................................................44 E. POWER SUPPLY HARDWARE...44 Figure 5.6 Earthmate GPS Receiver ........................................................................................45...and 5Watts at 25 Ft Effective Range Minimum range of wireless link is 5 miles. Positional awareness System requires GPS input to determine

33 CFR 263.23 - Small flood control project authority (Section 205).

Code of Federal Regulations, 2010 CFR

2010-07-01

... operation, except as may result from the normal procedure applying to projects authorized after submission of preliminary examination and survey reports. (b) Non-Federal responsibilities for dam and reservoir project. All new projects under this authority, including dams and reservoirs, are considered local...

33 CFR 263.23 - Small flood control project authority (Section 205).

Code of Federal Regulations, 2011 CFR

2011-07-01

... operation, except as may result from the normal procedure applying to projects authorized after submission of preliminary examination and survey reports. (b) Non-Federal responsibilities for dam and reservoir project. All new projects under this authority, including dams and reservoirs, are considered local...

14 CFR 325.4 - State and local participation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the Documentary Services Division, unless the Department specifies another date. If no response is... point by filing in the Documentary Services Division, five copies of a document titled with the name of... questionnaire. (Approved by the Office of Management and Budget under control number 3024-0037) ...

Stinging nettle and neem enhance antibody response to local killed and imported live infectious bursal disease vaccines in indigenous chicken in Kenya.

PubMed

Bwana, M O; Njagi, L W; Nyaga, P N; Mbuthia, P G; Bebora, L C; Wahome, M W; Mutinda, W U; Kitala, P M

2018-02-01

Immune responses are critical for protection of chickens from infectious bursal disease (IBD). In this study, the antibody response-enhancing effect of drinking water supplementation of 1% stinging nettle and neem on different IBD vaccines and vaccination regimes was evaluated, using 36 (n = 36) specific antibody negative indigenous chicks. The birds were allocated into 3 groups as follows: 1A-C, 2A-C, and 3A-B, while group 3C acted as the unvaccinated non-supplemented control. A local inactivated K1 and imported live attenuated D78 IBD vaccines were given to groups 1A-C and 3A-B at 14 and 28 d of age, respectively. A combination of K1 and D78 vaccines was given 30 d apart to groups 2A and 2B (D78 at 14 and 21 d and K1 at 44 d of age) and on the same d to group 2C at 14 and 28 d of age. Stinging nettle was given in water to groups 1B, 2B, and 2C, and neem to groups 1C, 2A, and 3B. Birds were bled weekly and immune responses monitored using indirect ELISA. Both neem and stinging nettle had antibody response-enhancing effects in groups 1B and 1C, receiving the local inactivated K1 vaccine. There were significant differences (P < 0.05) in antibody titers between groups 1A and 2C. Stinging nettle induced earlier onset of high antibody responses in group 2C and persistent titers (>3.8 log10) from the third week in group 2B. Imported live D78 vaccine induced higher antibody titers compared to the local inactivated K1 vaccine. Groups 2B and 2C receiving a combination of the local K1 and imported live attenuated D78 vaccines had the highest antibody titers. Adoption of stinging nettle supplementation and a prime-boost program involving use of a local virus isolates-derived vaccine is recommended. © 2017 Poultry Science Association Inc.

Effect of medication on microvascular vasodilatation in patients with systemic lupus erythematosus.

PubMed

Bengtsson, Christine; Andersson, Sven E; Edvinsson, Lars; Edvinsson, Marie-Louise; Sturfelt, Gunnar; Nived, Ola

2010-12-01

The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44°C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (≥5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no difference in microvascular endothelium-dependent vasodilatation, other factors such as medication and smoking may affect vasodilatation in SLE patients. © 2010 The Authors. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.

Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway, coincides with the compartmentalization of Rnr2p–Rnr4p

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

Ainsworth, William B.; Hughes, Bridget Todd; Au, Wei Chun

2013-10-04

Highlights: •Hug1p overexpression sensitizes wild-type cells to DNA damage and hydroxyurea (HU). •Expression of Hug1p in response to HU treatment is delayed relative to Rnr3p. •MEC1 pathway genes are required for cytoplasmic localization of Hug1p. •Hug1p subcellular compartmentalization to the cytoplasm coincides with Rnr2p–Rnr4p. -- Abstract: The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest and induction of genes including the RNR (Ribonucleotide reductase) genes and HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage and replication arrest. Rnr complex activity is in part controlled by cytoplasmic localization of the Rnr2p–Rnr4p subunits and inactivation of negative regulatorsmore » Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously showed that a deletion of HUG1 rescues lethality of mec1Δ and suppresses dun1Δ strains. In this study, multiple approaches demonstrate the regulatory response of Hug1p to DNA damage and HU treatment and support its role as a negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1 polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in response to HU treatment. Cell biology and subcellular fractionation experiments show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and coincides with the cytoplasmic localization of Rnr2p–Rnr4p. Taken together, the genetic interactions, gene expression, and localization studies support a novel role for Hug1p as a negative regulator of the MEC1 checkpoint response through its compartmentalization with Rnr2p–Rnr4p.« less

Role of Surgical Margin on Local Recurrence in High Risk Extremity Osteosarcoma: A Case-Controlled Study

PubMed Central

Song, Won Seok; Kong, Chang-Bae; Cho, Wan Hyeong; Cho, Sang Hyun; Lee, Jeong Dong; Lee, Soo-Yong

2013-01-01

Background The relationship between surgical margin and local recurrence (LR) in osteosarcoma patients with poor responses to chemotherapy is unclear. Moreover, the incidences of LR according to three different resection planes (bone, soft tissue, and perineurovascular) are not commonly known. Methods We evaluated the incidence of LR in three areas. To assess whether there is a role of surgical margin on LR in patients resistant to preoperative chemotherapy, we designed a case (35 patients with LR) and control (70 patients without LR) study. Controls were matched for age, location, initial tumor volume, and tumor volume change during preoperative chemotherapy. Results LR occurred at the soft tissues in 18 cases (51.4%), at the perineurovascular tissues in 11 cases (31.4%), and at the bones in six cases (17.2%). The proportion of inadequate perineurovascular margin was higher in the case group than in the control group (p = 0.01). Within case-control group (105 patients), a correlation between each margin status and LR at corresponding area was found in the bone (p < 0.001) and perineurovascular area (p = 0.001). Conclusions LR is most common in soft tissues. In patients showing similar unfavorable responses to chemotherapy, the losses of perineurovascular fat plane on preoperative magnetic resonance imaging may be a valuable finding in predicting LR. PMID:24009908

A Dynamic Response Regulator Protein Modulates G-Protein–Dependent Polarity in the Bacterium Myxococcus xanthus

PubMed Central

Zhang, Yong; Guzzo, Mathilde; Ducret, Adrien; Li, Yue-Zhong; Mignot, Tâm

2012-01-01

Migrating cells employ sophisticated signal transduction systems to respond to their environment and polarize towards attractant sources. Bacterial cells also regulate their polarity dynamically to reverse their direction of movement. In Myxococcus xanthus, a GTP-bound Ras-like G-protein, MglA, activates the motility machineries at the leading cell pole. Reversals are provoked by pole-to-pole switching of MglA, which is under the control of a chemosensory-like signal transduction cascade (Frz). It was previously known that the asymmetric localization of MglA at one cell pole is regulated by MglB, a GTPase Activating Protein (GAP). In this process, MglB specifically localizes at the opposite lagging cell pole and blocks MglA localization at that pole. However, how MglA is targeted to the leading pole and how Frz activity switches the localizations of MglA and MglB synchronously remained unknown. Here, we show that MglA requires RomR, a previously known response regulator protein, to localize to the leading cell pole efficiently. Specifically, RomR-MglA and RomR-MglB complexes are formed and act complementarily to establish the polarity axis, segregating MglA and MglB to opposite cell poles. Finally, we present evidence that Frz signaling may regulate MglA localization through RomR, suggesting that RomR constitutes a link between the Frz-signaling and MglAB polarity modules. Thus, in Myxococcus xanthus, a response regulator protein governs the localization of a small G-protein, adding further insight to the polarization mechanism and suggesting that motility regulation evolved by recruiting and combining existing signaling modules of diverse origins. PMID:22916026

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial

PubMed Central

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan

2015-01-01

Purpose Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. Methods This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m2 intravenously on day 1 plus oral capecitabine 825 mg/m2 twice daily during LDRBT and EBRT. Results The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. Conclusion A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer. PMID:26361613

Efficacy and Safety of Low-Dose-Rate Endorectal Brachytherapy as a Boost to Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Distal Rectal Cancer: A Phase-II Clinical Trial.

PubMed

Omidvari, Shapour; Zohourinia, Shadi; Ansari, Mansour; Ghahramani, Leila; Zare-Bandamiri, Mohammad; Mosalaei, Ahmad; Ahmadloo, Niloofar; Pourahmad, Saeedeh; Nasrolahi, Hamid; Hamedi, Sayed Hasan; Mohammadianpanah, Mohammad

2015-08-01

Despite advances in rectal cancer treatment over the last decade, local control and risk of late side effects due to external beam radiation therapy (EBRT) remain as concerns. The present study aimed to investigate the efficacy and the safety of low-dose-rate endorectal brachytherapy (LDRBT) as a boost to neoadjuvant chemoradiation for use in treating locally advanced distal rectal adenocarcinomas. This phase-II clinical trial included 34 patients (as the study arm) with newly diagnosed, locally advanced (clinical T3-T4 and/or N1/N2, M0) lower rectal cancer. For comparative analysis, 102 matched patients (as the historical control arm) with rectal cancer were also selected. All the patients were treated with LDRBT (15 Gy in 3 fractions) and concurrent chemoradiation (45-50.4 Gy). Concurrent chemotherapy consisted of oxaliplatin 130 mg/m(2) intravenously on day 1 plus oral capecitabine 825 mg/m(2) twice daily during LDRBT and EBRT. The study results revealed a significant differences between the study arm and the control arm in terms in the pathologic tumor size (2.1 cm vs. 3.6 cm, P = 0.001), the pathologic tumor stage (35% T3-4 vs. 65% T3-4, P = 0.003), and the pathologic complete response (29.4% vs. 11.7%, P < 0.028). Moreover, a significantly higher dose of EBRT (P = 0.041) was found in the control arm, and a longer time to surgery was observed in the study arm (P < 0.001). The higher rate of treatment-related toxicities, such as mild proctitis and anemia, in the study arm was tolerable and easily manageable. A boost of LDRBT can optimize the pathologic complete response, with acceptable toxicities, in patients with distal rectal cancer.

Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma

PubMed Central

Kuo, Hsing-Tao; Que, Jenny; Lin, Li-Ching; Yang, Ching-Chieh; Koay, Lok-Beng; Lin, Chia-Hui

2017-01-01

Abstract Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT. Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4–<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed. A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival. SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate. PMID:29390360

Fatal Attraction? Intraguild Facilitation and Suppression among Predators.

PubMed

Sivy, Kelly J; Pozzanghera, Casey B; Grace, James B; Prugh, Laura R

2017-11-01

Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

Fatal attraction? Intraguild facilitation and suppression among predators

USGS Publications Warehouse

Sivy, Kelly J.; Pozzanghera, Casey B.; Grace, James B.; Prugh, Laura R.

2017-01-01

Competition and suppression are recognized as dominant forces that structure predator communities. Facilitation via carrion provisioning, however, is a ubiquitous interaction among predators that could offset the strength of suppression. Understanding the relative importance of these positive and negative interactions is necessary to anticipate community-wide responses to apex predator declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus) control in Alaska as a quasi experiment, we conducted snow track surveys of apex, meso-, and small predators to test for evidence of carnivore cascades (e.g., mesopredator release). We analyzed survey data using an integrative occupancy and structural equation modeling framework to quantify the strengths of hypothesized interaction pathways, and we evaluated fine-scale spatiotemporal responses of nonapex predators to wolf activity clusters identified from radio-collar data. Contrary to the carnivore cascade hypothesis, both meso- and small predator occupancy patterns indicated guild-wide, negative responses of nonapex predators to wolf abundance variations at the landscape scale. At the local scale, however, we observed a near guild-wide, positive response of nonapex predators to localized wolf activity. Local-scale association with apex predators due to scavenging could lead to landscape patterns of mesopredator suppression, suggesting a key link between occupancy patterns and the structure of predator communities at different spatial scales.

Phase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer.

PubMed

Michael, M; Chander, S; McKendrick, J; MacKay, J R; Steel, M; Hicks, R; Heriot, A; Leong, T; Cooray, P; Jefford, M; Zalcberg, J; Bressel, M; McClure, B; Ngan, S Y

2014-11-11

Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.

Muscle cooling delays activation of the muscle metaboreflex in humans.

PubMed

Ray, C A; Hume, K M; Gracey, K H; Mahoney, E T

1997-11-01

Elevation of muscle temperature has been shown to increase muscle sympathetic nerve activity (MSNA) during isometric exercise in humans. The purpose of the present study was to evaluate the effect of muscle cooling on MSNA responses during exercise. Eight subjects performed ischemic isometric handgrip at 30% of maximal voluntary contraction to fatigue followed by 2 min of postexercise muscle ischemia (PEMI), with and without local cooling of the forearm. Local cooling of the forearm decreased forearm muscle temperature from 31.8 +/- 0.4 to 23.1 +/- 0.8 degrees C (P = 0.001). Time to fatigue was not different during the control and cold trials (156 +/- 11 and 154 +/- 5 s, respectively). Arterial pressures and heart rate were not significantly affected by muscle cooling during exercise, although heart rate tended to be higher during the second minute of exercise (P = 0.053) during muscle cooling. Exercise-induced increases in MSNA were delayed during handgrip with local cooling compared with control. However, MSNA responses at fatigue and PEMI were not different between the two conditions. These findings suggest that muscle cooling delayed the activation of the muscle metaboreflex during ischemic isometric exercise but did not prevent its full expression during fatiguing contraction. These results support the concept that muscle temperature can play a role in the regulation of MSNA during exercise.

Linear ideal MHD predictions for n = 2 non-axisymmetric magnetic perturbations on DIII-D

DOE PAGES

Haskey, Shaun R.; Lanctot, Matthew J.; Liu, Y. Q.; ...

2014-02-05

Here, an extensive examination of the plasma response to dominantly n = 2 non-axisymmetric magnetic perturbations (MPs) on the DIII-D tokamak shows the potential to control 3D field interactions by varying the poloidal spectrum of the radial magnetic field. The plasma response is calculated as a function of the applied magnetic field structure and plasma parameters, using the linear magnetohydrodynamic code MARS-F. The ideal, single fluid plasma response is decomposed into two main components: a local pitch-resonant response occurring at rational magnetic flux surfaces, and a global kink response. The efficiency with which the field couples to the total plasmamore » response is determined by the safety factor and the structure of the applied field. In many cases, control of the applied field has a more significant effect than control of plasma parameters, which is of particular interest since it can be modified at will throughout a shot to achieve a desired effect. The presence of toroidal harmonics, other than the dominant n = 2 component, is examined revealing a significant n = 4 component in the perturbations applied by the DIII-D MP coils; however, modeling shows the plasma responses to n = 4 perturbations are substantially smaller than the dominant n = 2 responses in most situations.« less

Impairment in local and global processing and set-shifting in body dysmorphic disorder

PubMed Central

Kerwin, Lauren; Hovav, Sarit; Helleman, Gerhard; Feusner, Jamie D.

2014-01-01

Body dysmorphic disorder (BDD) is characterized by distressing and often debilitating preoccupations with misperceived defects in appearance. Research suggests that aberrant visual processing may contribute to these misperceptions. This study used two tasks to probe global and local visual processing as well as set shifting in individuals with BDD. Eighteen unmedicated individuals with BDD and 17 non-clinical controls completed two global-local tasks. The embedded figures task requires participants to determine which of three complex figures contained a simpler figure embedded within it. The Navon task utilizes incongruent stimuli comprised of a large letter (global level) made up of smaller letters (local level). The outcome measures were response time and accuracy rate. On the embedded figures task, BDD individuals were slower and less accurate than controls. On the Navon task, BDD individuals processed both global and local stimuli slower and less accurately than controls, and there was a further decrement in performance when shifting attention between the different levels of stimuli. Worse insight correlated with poorer performance on both tasks. Taken together, these results suggest abnormal global and local processing for non-appearance related stimuli among BDD individuals, in addition to evidence of poor set-shifting abilities. Moreover, these abnormalities appear to relate to the important clinical variable of poor insight. Further research is needed to explore these abnormalities and elucidate their possible role in the development and/or persistence of BDD symptoms. PMID:24972487

Near-infrared light-controlled systems for gene transcription regulation, protein targeting and spectral multiplexing.

PubMed

Redchuk, Taras A; Kaberniuk, Andrii A; Verkhusha, Vladislav V

2018-05-01

Near-infrared (NIR, 740-780 nm) optogenetic systems are well-suited to spectral multiplexing with blue-light-controlled tools. Here, we present two protocols, one for regulation of gene transcription and another for control of protein localization, that use a NIR-responsive bacterial phytochrome BphP1-QPAS1 optogenetic pair. In the first protocol, cells are transfected with the optogenetic constructs for independently controlling gene transcription by NIR (BphP1-QPAS1) and blue (LightOn) light. The NIR and blue-light-controlled gene transcription systems show minimal spectral crosstalk and induce a 35- to 40-fold increase in reporter gene expression. In the second protocol, the BphP1-QPAS1 pair is combined with a light-oxygen-voltage-sensing (LOV) domain-based construct into a single optogenetic tool, termed iRIS. This dual-light-controllable protein localization tool allows tridirectional protein translocation among the cytoplasm, nucleus and plasma membrane. Both procedures can be performed within 3-5 d. Use of NIR light-controlled optogenetic systems should advance basic and biomedical research.

24 CFR 960.707 - Pet ownership.

Code of Federal Regulations, 2010 CFR

2010-04-01

... maintains each pet: (1) Responsibly; (2) In accordance with applicable State and local public health, animal control, and animal anti-cruelty laws and regulations; and (3) In accordance with the policies established... covered, or both; (2) Limitations on the number of animals in a unit, based on unit size; (3) Prohibitions...

76 FR 76151 - Notice of Submission for OMB Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... Evaluation Systems in the United States will contribute to the Department's work by providing research-based information to aid state and local efforts to plan and implement comprehensive teacher evaluation systems. The... United States. OMB Control Number: Pending. Agency Form Number(s): N/A. Frequency of Responses: Annually...

Creativity and cognitive control: Behavioral and ERP evidence that divergent thinking, but not real-life creative achievement, relates to better cognitive control.

PubMed

Zabelina, Darya L; Ganis, Giorgio

2018-02-13

Two studies used event-related potentials (ERPs) to examine whether and how divergent thinking and creative achievement are linked to attentional flexibility and cognitive control as indexed by response times and by the amplitude of the anterior N2 ERP component. Both experiments used an oddball paradigm in which participants viewed hierarchical letter stimuli and identified target letters in frequent and rare target trials. The successful identification of targets required attentional flexibility when switching levels of attention (from the frequent global to the rare local attentional level, or vice-versa). Divergent thinkers showed smaller switching times on rare target trials, indicating higher levels of attentional flexibility. Furthermore, divergent thinkers engaged cognitive control processes more strongly at the moment of the attentional switch (and before the response), as indicated by a larger N2 difference between frequent and rare targets. In contrast, creative achievement was associated neither with the switching times on rare target trials, nor with a larger N2 difference between frequent and rare targets. All results held when controlling for general intelligence. Results from these studies provide evidence that divergent thinking is associated with higher attentional flexibility and that such attentional flexibility relies on cognitive control processes required when disengaging from one level of attention (e.g., global), and shifting to the other level of attention (e.g., local). Copyright © 2018 Elsevier Ltd. All rights reserved.

Whole-body heating decreases skin vascular response to low orthostatic stress in the lower extremities.

PubMed

Yamazaki, Fumio; Nakayama, Yoshiro; Sone, Ryoko

2006-04-01

To elucidate the influence of heat stress on cutaneous vascular response in the lower extremities during orthostatic stress, a head-up tilt (HUT) test at angles of 15 degrees, 30 degrees, 45 degrees, and 60 degrees for 4 min each was conducted under normothermic control conditions followed by whole-body heat stress produced by a hot water-perfused suit in healthy volunteers. Skin blood flows (SkBF) in the forearm, thigh, and calf were monitored using laser-Doppler flowmetry throughout the experiment. Furthermore, to elucidate the effects of increased core and local skin temperatures on the local vascular response in calf skin under increasing orthostatic stress, the thigh was occluded at 20, 30, 50, 70, and 80 mmHg with a cuff in both the normothermic condition and the whole-body or local heating condition. Significant decreases in forearm SkBF during HUT were observed at an angle of 60 degrees during normothermia and at 30 degrees or more during heating. SkBF in the thigh and calf was decreased significantly by HUT at 15 degrees and above during normothermia, and there was no significant reduction of SkBF in these sites during HUT at the lower angles (15 degrees -45 degrees ) during whole-body heating. Significant decreases of calf SkBF were observed at cuff pressures of 20 mmHg and above during normothermia and of 30 mmHg and above during whole-body and local heating, respectively. These results suggest that SkBF in the lower extremities shows a marked reduction compared with the upper extremities during low orthostatic stress in normothermia, and the enhanced skin vasoconstrictor response in the lower extremities is diminished by both whole-body and local heat stress.

Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis study.

PubMed

Nedvidkova, Jara; Haluzik, Martin; Bartak, Vladimir; Dostalova, Ivana; Vlcek, Petr; Racek, Pavel; Taus, Michal; Behanova, Magdalena; Svacina, Stepan; Alesci, Salvatore; Pacak, Karel

2004-06-01

Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline-stimulated local lipolysis and to determine local concentrations of lipolysis-regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four-fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

Local representation of the electronic dielectric response function

DOE PAGES

Lu, Deyu; Ge, Xiaochuan

2015-12-11

We present a local representation of the electronic dielectric response function, based on a spatial partition of the dielectric response into contributions from each occupied Wannier orbital using a generalized density functional perturbation theory. This procedure is fully ab initio, and therefore allows us to rigorously define local metrics, such as “bond polarizability,” on Wannier centers. We show that the locality of the bare response function is determined by the locality of three quantities: Wannier functions of the occupied manifold, the density matrix, and the Hamiltonian matrix. Furthermore, in systems with a gap, the bare dielectric response is exponentially localized,more » which supports the physical picture of the dielectric response function as a collection of interacting local responses that can be captured by a tight-binding model.« less

Spatial localization deficits and auditory cortical dysfunction in schizophrenia

PubMed Central

Perrin, Megan A.; Butler, Pamela D.; DiCostanzo, Joanna; Forchelli, Gina; Silipo, Gail; Javitt, Daniel C.

2014-01-01

Background Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia. Methods The study compared performance between patients with schizophrenia (n=21) and healthy controls (n=20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30 degrees separation. Results For the sound localization task, patients showed reduced accuracy (p=0.004) and greater overall response variability (p=0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task (p=0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task (p=0.026), but no significant association was found for the spatial discrimination task. Conclusion Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl’s gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning. PMID:20619608

Technical Report for State and Local Public Health Officials and School Administrators on CDC Guidance for School (K-12) Responses to Influenza during the 2009-2010 School Year

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2009

2009-01-01

This Technical Report includes detailed information on the reasons for the strategies presented in the Centers for Disease Control (CDC) "Guidance for School (K-12) Responses to Influenza During the 2009-2010 School Year" and suggestions on how to use them. The guidance is designed to decrease exposure to regular seasonal flu and 2009 H1N1 flu…

The growth and form of plant shoots

NASA Astrophysics Data System (ADS)

Chelakkot, Raghunath; Mahadevan, L.

2015-03-01

Growing plant stems and shoots exhibit a variety of shapes that embody growth in response to various stimuli. We provide a quantitative biophysical theory for these shapes by accounting for the inherent observed passive and active effects: (i) the passive elastic deflection of the shoot due to its own weight, and (ii) the active controllable growth response of the shoot in response to its orientation relative to gravity, and (iii) proprioception, the shoot's growth response to its own observable shape, which is itself determined by its elasticity and weight. A morphospace diagram in terms of two dimensionless parameters representing a scaled local active gravitropic sensitivity, and a scaled passive elastic sag shows how a variety of observed transient and steady morphologies with effective positive, negative and even oscillatory gravitropic behaviors arise in a sentient growing filament naturally, without the need for ad-hoc complex spatio-temporal control strategies.

Age-related immune response to experimental infection with Eimeria ninakohlyakimovae in goat kids.

PubMed

Matos, L; Muñoz, M C; Molina, J M; Rodríguez, F; Pérez, D; López, A M; Hermosilla, C; Taubert, A; Ruiz, A

2018-06-01

Both the immune response developed in ruminants against Eimeria spp. and the ability to bear patent infections seems to be dependent on the age of the host. In the present study we have evaluated the influence of the age in the development of protective immune responses against Eimeria ninakohlyakimovae. For this purpose, 3, 4 and 5-week-old goat kids were infected with sporulated oocysts and subjected to a homologous challenge 3 weeks later. Goat kids primary infected at 6, 7 and 8 weeks of age served as challenge controls, and uninfected animals were used as negative controls. The protective immunity was assessed by clinical, haematological, parasitological, immunological and pathological parameters. Altogether, the results demonstrate that goat kids of either 3, 4 or 5 weeks of age are able to develop patent infections and immunoprotective responses against E. ninakohlyakimovae, as all age groups: (i) released significantly less oocysts after challenge, which was associated to milder clinical signs; (ii) displayed a local immune response, with significant increase of numerous cellular populations; and (iii) had increased levels of IgG and IgM, and mainly of local IgA. Nevertheless, detailed analysis of the data showed some differences between the three age groups, related both to the Eimeria infection outcome and the resulting immune response, suggesting that youngest goat kids are not fully immunocompetent. This finding may be of interest for the design of immunoprophylactic approaches and/or prophylactic/methaphylactic treatments against goat coccidiosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Arabidopsis tandem CCCH zinc finger proteins AtTZF4, 5 and 6 are involved in light-, abscisic acid- and gibberellic acid-mediated regulation of seed germination.

PubMed

Bogamuwa, Srimathi; Jang, Jyan-Chyun

2013-08-01

Tandem CCCH zinc finger proteins (TZFs) are post-transcriptional regulators of gene expression in animals and yeast. Genetic studies indicate that plant TZFs are involved in hormone-mediated developmental and environmental responses. We have demonstrated previously that Arabidopsis AtTZF1 can localize to processing bodies (PBs) and stress granules (SGs), and affects abscisic acid (ABA)- and gibberellic acid (GA)-mediated growth, stress and gene expression responses. Here we show that AtTZF4, 5 and 6 are specifically expressed in seeds. Consistent with the observation that their expression levels decline during seed imbibition, AtTZF4, 5 and 6 are up-regulated by ABA and down-regulated by GA. Mutant analyses indicate that AtTZF4, 5 and 6 act as positive regulators for ABA- and negative regulators for light- and GA-mediated seed germination responses. Results of gene expression analysis indicate that AtTZF4, 5 and 6 affect seed germination by controlling genes critical for ABA and GA response. Furthermore, AtTZF4, 5 and 6 can co-localize with both PB and SG markers in Arabidopsis cells. Specifically, AtTZF6 can be assembled into PBs and SGs in embryos with the induction of stress hormone methyl jasmonate under the control of native AtTZF6 promoter. © 2013 John Wiley & Sons Ltd.

Local Government Implementation of Long-Term Stewardship at Two DOE Facilities

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

John Pendergrass; Roman Czebiniak; Kelly Mott

2003-08-13

The Department of Energy (DOE) is responsible for cleaning up the radioactive and chemical contamination that resulted from the production of nuclear weapons. At more than one hundred sites throughout the country DOE will leave some contamination in place after the cleanup is complete. In order to protect human health and the environment from the remaining contamination DOE, U.S. Environmental Protection Agency (EPA), state environmental regulatory agencies, local governments, citizens and other entities will need to undertake long-term stewardship of such sites. Long-term stewardship includes a wide range of actions needed to protect human health in the environment for asmore » long as the risk from the contamination remains above acceptable levels, such as barriers, caps, and other engineering controls and land use controls, signs, notices, records, and other institutional controls. In this report the Environmental Law Institute (ELI) and the Energy Communities Alliance (ECA) examine how local governments, state environmental agencies, and real property professionals implement long-term stewardship at two DOE facilities, Losa Alamos National Laboratory and Oak Ridge Reservation.« less

Sustained conduction of vasomotor responses in rat mesenteric arteries in a two-compartment in vitro setup.

PubMed

Palao, Teresa; van Weert, Angela; de Leeuw, Anne; de Vos, Judith; Bakker, Erik N T P; van Bavel, Ed

2018-05-21

Conduction of vasomotor responses may contribute to long-term regulation of resistance artery function and structure. Most previous studies have addressed conduction of vasoactivity only during very brief stimulations. We developed a novel setup that allows the local pharmacological stimulation of arteries in vitro for extended periods of time, and studied the conduction of vasomotor responses in rat mesenteric arteries under those conditions. The new in vitro set up was based on the pressure myograph. The superfusion chamber was divided halfway along the vessel into two compartments, allowing an independent superfusion of the arterial segment in each compartment. Local and remote cumulative concentration-response curves were obtained for a range of vasoactive agents. Additional experiments were performed with the gap junction inhibitor 18β-glycyrrhetinic acid and in absence of the endothelium. Phenylephrine-induced constriction and acetylcholine-induced dilation were conducted over a measured distance up to 2.84 mm, and this conduction was maintained for 5 minutes. Conduction of acetylcholine-induced dilation was inhibited by 18β-glycyrrhetinic acid and conduction of phenylephrine-induced constriction was abolished in absence of the endothelium. Constriction in response to high K + was not conducted. Absence of remote stimulation dampened the local response to phenylephrine. This study demonstrates maintained conduction of vasoactive responses to physiological agonists in rat mesenteric small arteries likely via gap junctions and endothelial cells, providing a possible mechanism for the sustained functional and structural control of arterial networks. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of mucosal adjuvants and immunization routes for the induction of systemic and mucosal humoral immune responses in macaques.

PubMed

Veazey, Ronald S; Siddiqui, Asna; Klein, Katja; Buffa, Viviana; Fischetti, Lucia; Doyle-Meyers, Lara; King, Deborah F; Tregoning, John S; Shattock, Robin J

2015-01-01

Delivering vaccine antigens to mucosal surfaces is potentially very attractive, especially as protection from mucosal infections may be mediated by local immune responses. However, to date mucosal immunization has had limited successes, with issues of both safety and poor immunogenicity. One approach to improve immunogenicity is to develop adjuvants that are effective and safe at mucosal surfaces. Differences in immune responses between mice and men have overstated the value of some experimental adjuvants which have subsequently performed poorly in the clinic. Due to their closer similarity, non-human primates can provide a more accurate picture of adjuvant performance. In this study we immunised rhesus macaques (Macaca mulatta) using a unique matrix experimental design that maximised the number of adjuvants screened while reducing the animal usage. Macaques were immunised by the intranasal, sublingual and intrarectal routes with the model protein antigens keyhole limpet haemocyanin (KLH), β-galactosidase (β-Gal) and ovalbumin (OVA) in combination with the experimental adjuvants Poly(I:C), Pam3CSK4, chitosan, Thymic Stromal Lymphopoietin (TSLP), MPLA and R848 (Resiquimod). Of the routes used, only intranasal immunization with KLH and R848 induced a detectable antibody response. When compared to intramuscular immunization, intranasal administration gave slightly lower levels of antigen specific antibody in the plasma, but enhanced local responses. Following intranasal delivery of R848, we observed a mildly inflammatory response, but no difference to the control. From this we conclude that R848 is able to boost antibody responses to mucosally delivered antigen, without causing excess local inflammation.

Estimating the Impacts of Local Policy Innovation: The Synthetic Control Method Applied to Tropical Deforestation

PubMed Central

Sills, Erin O.; Herrera, Diego; Kirkpatrick, A. Justin; Brandão, Amintas; Dickson, Rebecca; Hall, Simon; Pattanayak, Subhrendu; Shoch, David; Vedoveto, Mariana; Young, Luisa; Pfaff, Alexander

2015-01-01

Quasi-experimental methods increasingly are used to evaluate the impacts of conservation interventions by generating credible estimates of counterfactual baselines. These methods generally require large samples for statistical comparisons, presenting a challenge for evaluating innovative policies implemented within a few pioneering jurisdictions. Single jurisdictions often are studied using comparative methods, which rely on analysts’ selection of best case comparisons. The synthetic control method (SCM) offers one systematic and transparent way to select cases for comparison, from a sizeable pool, by focusing upon similarity in outcomes before the intervention. We explain SCM, then apply it to one local initiative to limit deforestation in the Brazilian Amazon. The municipality of Paragominas launched a multi-pronged local initiative in 2008 to maintain low deforestation while restoring economic production. This was a response to having been placed, due to high deforestation, on a federal “blacklist” that increased enforcement of forest regulations and restricted access to credit and output markets. The local initiative included mapping and monitoring of rural land plus promotion of economic alternatives compatible with low deforestation. The key motivation for the program may have been to reduce the costs of blacklisting. However its stated purpose was to limit deforestation, and thus we apply SCM to estimate what deforestation would have been in a (counterfactual) scenario of no local initiative. We obtain a plausible estimate, in that deforestation patterns before the intervention were similar in Paragominas and the synthetic control, which suggests that after several years, the initiative did lower deforestation (significantly below the synthetic control in 2012). This demonstrates that SCM can yield helpful land-use counterfactuals for single units, with opportunities to integrate local and expert knowledge and to test innovations and permutations on policies that are implemented in just a few locations. PMID:26173108

Estimating the Impacts of Local Policy Innovation: The Synthetic Control Method Applied to Tropical Deforestation.

PubMed

Sills, Erin O; Herrera, Diego; Kirkpatrick, A Justin; Brandão, Amintas; Dickson, Rebecca; Hall, Simon; Pattanayak, Subhrendu; Shoch, David; Vedoveto, Mariana; Young, Luisa; Pfaff, Alexander

2015-01-01

Quasi-experimental methods increasingly are used to evaluate the impacts of conservation interventions by generating credible estimates of counterfactual baselines. These methods generally require large samples for statistical comparisons, presenting a challenge for evaluating innovative policies implemented within a few pioneering jurisdictions. Single jurisdictions often are studied using comparative methods, which rely on analysts' selection of best case comparisons. The synthetic control method (SCM) offers one systematic and transparent way to select cases for comparison, from a sizeable pool, by focusing upon similarity in outcomes before the intervention. We explain SCM, then apply it to one local initiative to limit deforestation in the Brazilian Amazon. The municipality of Paragominas launched a multi-pronged local initiative in 2008 to maintain low deforestation while restoring economic production. This was a response to having been placed, due to high deforestation, on a federal "blacklist" that increased enforcement of forest regulations and restricted access to credit and output markets. The local initiative included mapping and monitoring of rural land plus promotion of economic alternatives compatible with low deforestation. The key motivation for the program may have been to reduce the costs of blacklisting. However its stated purpose was to limit deforestation, and thus we apply SCM to estimate what deforestation would have been in a (counterfactual) scenario of no local initiative. We obtain a plausible estimate, in that deforestation patterns before the intervention were similar in Paragominas and the synthetic control, which suggests that after several years, the initiative did lower deforestation (significantly below the synthetic control in 2012). This demonstrates that SCM can yield helpful land-use counterfactuals for single units, with opportunities to integrate local and expert knowledge and to test innovations and permutations on policies that are implemented in just a few locations.

Photosynthetic variation and responsiveness to CO2 in a widespread riparian tree

PubMed Central

Quentin, Audrey; Ivković, Milos; Furbank, Robert T.; Pinkard, Elizabeth

2018-01-01

Phenotypic responses to rising CO2 will have consequences for the productivity and management of the world’s forests. This has been demonstrated through extensive free air and controlled environment CO2 enrichment studies. However intraspecific variation in plasticity remains poorly characterised in trees, with the capacity to produce unexpected trends in response to CO2 across a species distribution. Here we examined variation in photosynthesis traits across 43 provenances of a widespread, genetically diverse eucalypt, E. camaldulensis, under ambient and elevated CO2 conditions. Genetic variation suggestive of local adaptation was identified for some traits under ambient conditions. Evidence of genotype by CO2 interaction in responsiveness was limited, however support was identified for quantum yield (φ). In this case local adaptation was invoked to explain trends in provenance variation in response. The results suggest potential for genetic variation to influence a limited set of photosynthetic responses to rising CO2 in seedlings of E. camaldulensis, however further assessment in mature stage plants in linkage with growth and fitness traits is needed to understand whether trends in φ could have broader implications for productivity of red gum forests. PMID:29293528

A systematic approach to very important person preparedness for a trauma center.

PubMed

Bulson, Julie; Mattice, Connie; Bulson, Timothy

2012-01-01

Hospitals across the United States are more involved in disaster/rapid response planning than ever. This collaboration is often driven by continuing federal and state preparedness and all-hazards planning efforts that provide cooperative agreement and/or grant support. These efforts currently include programs administered by the US assistant secretary for preparedness and response, the US Centers for Disease Control and Prevention, the US Department of Defense, and the US Department of Homeland Security. Beyond legislated support or mandates, key emergency management regulations governing hospital-specific disaster planning and response activities are required of hospitals by The Joint Commission, the largest national hospital accrediting body. Despite this ongoing, heightened awareness and inclusion of health care in local and regional emergency response planning, there is 1 partnership to yet strengthen: the relationship between community trauma centers and US Secret Service staff responsible for White House travel and health care contingency plans. One Michigan hospital system designed a program that has made preevent communications and preparedness for rapid very important person response with the Secret Service as important as other local all-hazards planning; the evolution of this partnership is the focus of this article.

Toward a collaborative model of pandemic preparedness and response: Taiwan's changing approach to pandemics.

PubMed

Schwartz, Jonathan; Yen, Muh-Yong

2017-04-01

Over time, as newly emerging infectious diseases have become increasingly common and more easily spread, it has become clear that traditional response mechanisms have proven inadequate to the task of prevention and control. To explore whether enhanced cooperation with local government and community institutions can effectively supplement traditional state-centric public health epidemic responses. Drawing on Taiwan as a case study, we assess the role of the whole-of-society approach to epidemic response as arises from the collaborative governance literature. The approach calls for enhanced cooperation, trust building, resource sharing and consensus-oriented decision making among multiple levels of government, business, non-profits, and the public in general. The Taiwan case illustrates the benefits of the whole-of-society approach. Enhanced cooperation between state, local government and non-state institutions, particularly neighborhood committees, has resulted in a strengthened, holistic epidemic preparedness and response infrastructure. The Taiwan case provides evidence that by implementing the whole-of-society approach to pandemic preparedness and response governments can enhance their ability to manage future outbreaks. We recommend that governments beyond Taiwan's borders seriously consider adopting this approach. Copyright © 2016. Published by Elsevier B.V.

Photosynthetic variation and responsiveness to CO2 in a widespread riparian tree.

PubMed

Dillon, Shannon; Quentin, Audrey; Ivković, Milos; Furbank, Robert T; Pinkard, Elizabeth

2018-01-01

Phenotypic responses to rising CO2 will have consequences for the productivity and management of the world's forests. This has been demonstrated through extensive free air and controlled environment CO2 enrichment studies. However intraspecific variation in plasticity remains poorly characterised in trees, with the capacity to produce unexpected trends in response to CO2 across a species distribution. Here we examined variation in photosynthesis traits across 43 provenances of a widespread, genetically diverse eucalypt, E. camaldulensis, under ambient and elevated CO2 conditions. Genetic variation suggestive of local adaptation was identified for some traits under ambient conditions. Evidence of genotype by CO2 interaction in responsiveness was limited, however support was identified for quantum yield (φ). In this case local adaptation was invoked to explain trends in provenance variation in response. The results suggest potential for genetic variation to influence a limited set of photosynthetic responses to rising CO2 in seedlings of E. camaldulensis, however further assessment in mature stage plants in linkage with growth and fitness traits is needed to understand whether trends in φ could have broader implications for productivity of red gum forests.

Perceptual conflict during sensorimotor integration processes - a neurophysiological study in response inhibition.

PubMed

Chmielewski, Witold X; Beste, Christian

2016-05-25

A multitude of sensory inputs needs to be processed during sensorimotor integration. A crucial factor for detecting relevant information is its complexity, since information content can be conflicting at a perceptual level. This may be central to executive control processes, such as response inhibition. This EEG study aims to investigate the system neurophysiological mechanisms behind effects of perceptual conflict on response inhibition. We systematically modulated perceptual conflict by integrating a Global-local task with a Go/Nogo paradigm. The results show that conflicting perceptual information, in comparison to non-conflicting perceptual information, impairs response inhibition performance. This effect was evident regardless of whether the relevant information for response inhibition is displayed on the global, or local perceptual level. The neurophysiological data suggests that early perceptual/ attentional processing stages do not underlie these modulations. Rather, processes at the response selection level (P3), play a role in changed response inhibition performance. This conflict-related impairment of inhibitory processes is associated with activation differences in (inferior) parietal areas (BA7 and BA40) and not as commonly found in the medial prefrontal areas. This suggests that various functional neuroanatomical structures may mediate response inhibition and that the functional neuroanatomical structures involved depend on the complexity of sensory integration processes.

Additional 4-week capecitabine during the resting periods after 6-week neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: long-term oncologic outcomes.

PubMed

Park, Sang Woo; Kim, Jin Soo; Kim, Ji Yeon; Lee, Kyung Ha

2018-06-01

The aim of this study was to evaluate the long-term outcome of additional 4-week chemotherapy with capecitabine during the resting periods following a 6-week neoadjuvant chemoradiotherapy (NCRT) regimen, in patients with locally advanced rectal cancer. Radiotherapy was delivered to the whole pelvis at a total dose of 50.4 Gy for 6 weeks. Oral capecitabine was administered at a dose of 825 mg/m 2 twice daily for 10 weeks. Surgery was performed 2-4 weeks following the completion of chemotherapy. Between January 2010 and September 2011, 41 patients completed the scheduled neoadjuvant therapy and surgery. The pathologic complete response rate, 5-year overall survival, and 5-year disease-free survival rates were 22%, 85.4%, and 78.0%, respectively. The 5-year systemic recurrence and 5-year local recurrence rates were 22% and 0%, respectively. Additional 4-week chemotherapy with capecitabine, during the resting periods following a 6-week NCRT regimen, has favorable long-term oncologic outcomes. Further randomized controlled trials are however necessary to evaluate if substantial improvement in local control is achieved with this additional chemotherapy modality for locally advanced rectal cancer.

Oxygen and Perfusion Kinetics in Response to Fractionated Radiation Therapy in FaDu Head and Neck Cancer Xenografts Are Related to Treatment Outcome

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

Hu, Fangyao; Vishwanath, Karthik; Salama, Joseph K.

Purpose: To test whether oxygenation kinetics correlate with the likelihood for local tumor control after fractionated radiation therapy. Methods and Materials: We used diffuse reflectance spectroscopy to noninvasively measure tumor vascular oxygenation and total hemoglobin concentration associated with radiation therapy of 5 daily fractions (7.5, 9, or 13.5 Gy/d) in FaDu xenografts. Spectroscopy measurements were obtained immediately before each daily radiation fraction and during the week after radiation therapy. Oxygen saturation and total hemoglobin concentration were computed using an inverse Monte Carlo model. Results: First, oxygenation kinetics during and after radiation therapy, but before tumor volumes changed, were associated with localmore » tumor control. Locally controlled tumors exhibited significantly faster increases in oxygenation after radiation therapy (days 12-15) compared with tumors that recurred locally. Second, within the group of tumors that recurred, faster increases in oxygenation during radiation therapy (day 3-5 interval) were correlated with earlier recurrence times. An area of 0.74 under the receiver operating characteristic curve was achieved when classifying the local control tumors from all irradiated tumors using the oxygen kinetics with a logistic regression model. Third, the rate of increase in oxygenation was radiation dose dependent. Radiation doses ≤9.5 Gy/d did not initiate an increase in oxygenation, whereas 13.5 Gy/d triggered significant increases in oxygenation during and after radiation therapy. Conclusions: Additional confirmation is required in other tumor models, but these results suggest that monitoring tumor oxygenation kinetics could aid in the prediction of local tumor control after radiation therapy.« less

Cooperation and control: the Tobacco Institute of Australia

PubMed Central

Carter, S

2003-01-01

Objective: To describe the history of the Tobacco Institute of Australia (TIA), particularly regarding connections between local and international cigarette manufacturers and tobacco organisations. Design: Analysis of 4541 industry documents from the world wide web. Results: From 1978 to 1983 the TIA built strong international networks via ICOSI/INFOTAB and the US Tobacco Institute, and defended existing industry freedoms. 1983 to 1989 was the TIA's aggressive heyday, led primarily by John Dollisson. From 1989 to 1994, following the decision in Australian Federation of Consumer Organisations vs TIA, local and international industry lawyers assumed control. Between 1994 and 1997 a brief revival led into decline and then dissolution, as previously common ground became commercially competitive issues for the manufacturers. The TIA facilitated interconnectedness: between local manufacturers; via individuals who played multiple roles; to international tobacco organisations; through the industry's local and international counsel; and by acting as a conduit for information. Conclusion: The local tobacco industry was comprehensively informed on issues including smoking and health, and connected to the international industry, via the TIA. The manufacturers were closely involved in the TIA's activities, and cooperated through the TIA in a manner detrimental to Australian consumers. The TIA's conduct was the responsibility of local and international manufacturers and their counsel. PMID:14645949

Reduced Arteriovenous Shunting Capacity After Local Heating and Redistribution of Baseline Skin Blood Flow in Type 2 Diabetes Assessed With Velocity-Resolved Quantitative Laser Doppler Flowmetry

PubMed Central

Fredriksson, Ingemar; Larsson, Marcus; Nyström, Fredrik H.; Länne, Toste; Östgren, Carl J.; Strömberg, Tomas

2010-01-01

OBJECTIVE To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS The skin blood flow response to local heating (44°C for 20 min) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity × concentration), in a physiologically relevant unit (grams RBC per 100 g tissue × millimeters per second) in a fixed output volume, separated into three velocity regions: v <1 mm/s, v 1–10 mm/s, and v >10 mm/s. RESULTS The increased blood flow occurs in vessels with a velocity >1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v >10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v >10 mm/s, whereas no significant increase was found for v <1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio. PMID:20393143

Community-owned resource persons for malaria vector control: enabling factors and challenges in an operational programme in Dar es Salaam, United Republic of Tanzania

PubMed Central

2011-01-01

Background Community participation in vector control and health services in general is of great interest to public health practitioners in developing countries, but remains complex and poorly understood. The Urban Malaria Control Program (UMCP) in Dar es Salaam, United Republic of Tanzania, implements larval control of malaria vector mosquitoes. The UMCP delegates responsibility for routine mosquito control and surveillance to community-owned resource persons (CORPs), recruited from within local communities via the elected local government. Methods A mixed method, cross-sectional survey assessed the ability of CORPs to detect mosquito breeding sites and larvae, and investigated demographic characteristics of the CORPs, their reasons for participating in the UMCP, and their work performance. Detection coverage was estimated as the proportion of wet habitats found by the investigator which had been reported by CORP. Detection sensitivity was estimated as the proportion of wet habitats found by the CORPS which the investigator found to contain Anopheles larvae that were also reported to be occupied by the CORP. Results The CORPs themselves perceived their role as professional rather than voluntary, with participation being a de facto form of employment. Habitat detection coverage was lower among CORPs that were recruited through the program administrative staff, compared to CORPs recruited by local government officials or health committees (Odds Ratio = 0.660, 95% confidence interval = [0.438, 0.995], P = 0.047). Staff living within their areas of responsibility had > 70% higher detection sensitivity for both Anopheline (P = 0.016) and Culicine (P = 0.012): positive habitats compared to those living outside those same areas. Discussion and conclusions Improved employment conditions as well as involving the local health committees in recruiting individual program staff, communication and community engagement skills are required to optimize achieving effective community participation, particularly to improve access to fenced compounds. A simpler, more direct, less extensive community-based surveillance system in the hands of a few, less burdened, better paid and maintained program personnel may improve performance and data quality. PMID:21955856

Local immunomodulation with Fas ligand-engineered biomaterials achieves allogeneic islet graft acceptance.

PubMed

Headen, Devon M; Woodward, Kyle B; Coronel, María M; Shrestha, Pradeep; Weaver, Jessica D; Zhao, Hong; Tan, Min; Hunckler, Michael D; Bowen, William S; Johnson, Christopher T; Shea, Lonnie; Yolcu, Esma S; García, Andrés J; Shirwan, Haval

2018-06-04

Islet transplantation is a promising therapy for type 1 diabetes. However, chronic immunosuppression to control rejection of allogeneic islets induces morbidities and impairs islet function. T effector cells are responsible for islet allograft rejection and express Fas death receptors following activation, becoming sensitive to Fas-mediated apoptosis. Here, we report that localized immunomodulation using microgels presenting an apoptotic form of the Fas ligand with streptavidin (SA-FasL) results in prolonged survival of allogeneic islet grafts in diabetic mice. A short course of rapamycin treatment boosted the immunomodulatory efficacy of SA-FasL microgels, resulting in acceptance and function of allografts over 200 days. Survivors generated normal systemic responses to donor antigens, implying immune privilege of the graft, and had increased CD4 + CD25 + FoxP3 + T regulatory cells in the graft and draining lymph nodes. Deletion of T regulatory cells resulted in acute rejection of established islet allografts. This localized immunomodulatory biomaterial-enabled approach may provide an alternative to chronic immunosuppression for clinical islet transplantation.

A combined experimental atomic force microscopy-based nanoindentation and computational modeling approach to unravel the key contributors to the time-dependent mechanical behavior of single cells.

PubMed

Florea, Cristina; Tanska, Petri; Mononen, Mika E; Qu, Chengjuan; Lammi, Mikko J; Laasanen, Mikko S; Korhonen, Rami K

2017-02-01

Cellular responses to mechanical stimuli are influenced by the mechanical properties of cells and the surrounding tissue matrix. Cells exhibit viscoelastic behavior in response to an applied stress. This has been attributed to fluid flow-dependent and flow-independent mechanisms. However, the particular mechanism that controls the local time-dependent behavior of cells is unknown. Here, a combined approach of experimental AFM nanoindentation with computational modeling is proposed, taking into account complex material behavior. Three constitutive models (porohyperelastic, viscohyperelastic, poroviscohyperelastic) in tandem with optimization algorithms were employed to capture the experimental stress relaxation data of chondrocytes at 5 % strain. The poroviscohyperelastic models with and without fluid flow allowed through the cell membrane provided excellent description of the experimental time-dependent cell responses (normalized mean squared error (NMSE) of 0.003 between the model and experiments). The viscohyperelastic model without fluid could not follow the entire experimental data that well (NMSE = 0.005), while the porohyperelastic model could not capture it at all (NMSE = 0.383). We also show by parametric analysis that the fluid flow has a small, but essential effect on the loading phase and short-term cell relaxation response, while the solid viscoelasticity controls the longer-term responses. We suggest that the local time-dependent cell mechanical response is determined by the combined effects of intrinsic viscoelasticity of the cytoskeleton and fluid flow redistribution in the cells, although the contribution of fluid flow is smaller when using a nanosized probe and moderate indentation rate. The present approach provides new insights into viscoelastic responses of chondrocytes, important for further understanding cell mechanobiological mechanisms in health and disease.

Deviance sensitivity in the auditory cortex of freely moving rats

PubMed Central

2018-01-01

Deviance sensitivity is the specific response to a surprising stimulus, one that violates expectations set by the past stimulation stream. In audition, deviance sensitivity is often conflated with stimulus-specific adaptation (SSA), the decrease in responses to a common stimulus that only partially generalizes to other, rare stimuli. SSA is usually measured using oddball sequences, where a common (standard) tone and a rare (deviant) tone are randomly intermixed. However, the larger responses to a tone when deviant does not necessarily represent deviance sensitivity. Deviance sensitivity is commonly tested using a control sequence in which many different tones serve as the standard, eliminating the expectations set by the standard ('deviant among many standards'). When the response to a tone when deviant (against a single standard) is larger than the responses to the same tone in the control sequence, it is concluded that true deviance sensitivity occurs. In primary auditory cortex of anesthetized rats, responses to deviants and to the same tones in the control condition are comparable in size. We recorded local field potentials and multiunit activity from the auditory cortex of awake, freely moving rats, implanted with 32-channel drivable microelectrode arrays and using telemetry. We observed highly significant SSA in the awake state. Moreover, the responses to a tone when deviant were significantly larger than the responses to the same tone in the control condition. These results establish the presence of true deviance sensitivity in primary auditory cortex in awake rats. PMID:29874246

Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a fraction isolated from Phoneutria nigriventer (armed spider) venom.

PubMed

Antunes, E; Marangoni, R A; Giglio, J R; Brain, S D; de Nucci, G

1993-11-01

Phoneutria nigriventer venom was fractionated by gel filtration followed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those responsible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradykinin and histamine) were intradermally injected in male New Zealand white rabbits. Local oedema formation was measured as the local accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction XIII was the only fraction assayed which significantly induced oedema formation. Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk, whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that the increased vascular permeability induced by fraction XIII is due to local generation of kinins in response to tissue (but not plasma) kallikrein-kinin system activation.

Interplay of hot electrons from localized and propagating plasmons.

PubMed

Hoang, Chung V; Hayashi, Koki; Ito, Yasuo; Gorai, Naoki; Allison, Giles; Shi, Xu; Sun, Quan; Cheng, Zhenzhou; Ueno, Kosei; Goda, Keisuke; Misawa, Hiroaki

2017-10-03

Plasmon-induced hot-electron generation has recently received considerable interest and has been studied to develop novel applications in optoelectronics, photovoltaics and green chemistry. Such hot electrons are typically generated from either localized plasmons in metal nanoparticles or propagating plasmons in patterned metal nanostructures. Here we simultaneously generate these heterogeneous plasmon-induced hot electrons and exploit their cooperative interplay in a single metal-semiconductor device to demonstrate, as an example, wavelength-controlled polarity-switchable photoconductivity. Specifically, the dual-plasmon device produces a net photocurrent whose polarity is determined by the balance in population and directionality between the hot electrons from localized and propagating plasmons. The current responsivity and polarity-switching wavelength of the device can be varied over the entire visible spectrum by tailoring the hot-electron interplay in various ways. This phenomenon may provide flexibility to manipulate the electrical output from light-matter interaction and offer opportunities for biosensors, long-distance communications, and photoconversion applications.Plasmon-induced hot electrons have potential applications spanning photodetection and photocatalysis. Here, Hoang et al. study the interplay between hot electrons generated by localized and propagating plasmons, and demonstrate wavelength-controlled polarity-switchable photoconductivity.

Where Is Obesity Prevention on the Map? Distribution and Predictors of Local Health Department Prevention Activities in Relation to County-Level Obesity Prevalence in the US

PubMed Central

Stamatakis, Katherine A.; Leatherdale, Scott T.; Marx, Christine; Yan, Yan; Colditz, Graham A.; Brownson, Ross C.

2013-01-01

Context The system of local health departments (LHD) in the US has potential to advance a locally-oriented public health response in obesity control and reduce geographic disparities. However, the extent to which obesity prevention programs correspond to local obesity levels is unknown. Objective This study examines the extent to which LHDs across the US have responded to local levels of obesity by examining the association between jurisdiction level obesity prevalence and the existence of obesity prevention programs. Design Data on LHD organizational characteristics from the Profile Study of Local Health Departments and county-level estimates of obesity from the Behavioral Risk Factor Surveillance System were analyzed (n=2,300). Since local public health systems are nested within state infrastructure, multilevel models were used to examine the relationship between county-level obesity prevalence and LHD obesity prevention programming and to assess the impact of state-level clustering. Setting 2,300 local health department jurisdictions defined with respect to county boundaries Participants Practitioners in local health departments who responded to the 2005 Profile Study of Local Health Departments. Main Outcome Measures Likelihood of having obesity prevention activities and association with area-level obesity prevalence Results The existence of obesity prevention activities was not associated with prevalence of obesity in the jurisdiction. A substantial portion of the variance in LHD activities was explained by state-level clustering. Conclusions This paper identified a gap in the local public health response to the obesity epidemic and underscores the importance of multilevel modeling in examining predictors of LHD performance. PMID:22836530

Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma.

PubMed

Machtay, Mitchell; Paulus, Rebecca; Moughan, Jennifer; Komaki, Ritsuko; Bradley, J Effrey; Choy, Hak; Albain, Kathy; Movsas, Benjamin; Sause, William T; Curran, Walter J

2012-04-01

Local-regional control (LRC) rates for non-small cell lung cancer after chemoradiotherapy were studied (using two different definitions of LRC) for the association between LRC and survival. Seven legacy Radiation Therapy Ooncology Group trials of chemoradiotherapy for locally advanced non-small cell lung cancer were analyzed. Two different definitions of LRC were studied: (1) freedom from local progression (FFLP-LRC), the traditional Radiation Therapy Oncology Group methodology, in which a failure is intrathoracic tumor progression by World Health Oorganization criteria; and (2) response-mandatory (strict-LRC), in which any patient not achieving at least partial response was considered to have failure at day 0. Testing for associations between LRC and survival was performed using a Cox multivariate model that included other potential predictive factors. A total of 1390 patients were analyzed. The LRC rate at 3 years was 38% based on the FFLP-LRC definition and 14% based on the strict-LRC definition. Performance status, concurrent chemotherapy, and radiotherapy dose intensity (biologically equivalent dose) were associated with better LRC (using either definition). With the strict-LRC definition (but not FFLP-LRC), age was also important. There was a powerful association between LRC and overall survival (p, 0.0001) on univariate and multivariate analyses. Age, performance status, chemotherapy sequencing, and biologically equivalent dose were also significantly associated with survival. Histology and gender were also significant if the strict-LRC model was used. LRC is associated with survival. The definition of LRC affects the results of these analyses. A consensus definition of LRC, incorporating functional imaging and/or central review, is needed, with the possibility of using LRC as a surrogate end point in future trials.

Responsive feeding and child interest in food vary when rural Malawian children are fed lipid-based nutrient supplements or local complementary food.

PubMed

Flax, Valerie L; Mäkinen, Samppa; Ashorn, Ulla; Cheung, Yin Bun; Maleta, Kenneth; Ashorn, Per; Bentley, Margaret E

2013-07-01

Caregiver and child behaviours during feeding have been used to measure responsiveness, which has been recognised as important for child growth and development. The aims of this study were to understand how caregiver and child behaviours differ when feeding lipid-based nutrient supplements (LNS) vs. local complementary food and to detect associations between behaviours and child interest in food. Sixteen moderately underweight 6-17-month-old Malawian children receiving 50 g/day of supplementary LNS for 12 weeks were videotaped during LNS (n = 32) and local complementary feeding (n = 28) episodes. Behaviours were coded at the level of the intended bite (1674 total bites). The analysis used regression models adjusted for within-subject correlation. Caregivers were less likely to allow children to self-feed and more likely to use physical pressure during LNS vs. complementary food bites. Positive caregiver verbalization was infrequent and did not differ by type of food. Higher odds of accepting a bite were associated with the bite containing LNS, odds ratio (OR) 3.05; 90% confidence interval (CI) (1.98, 4.71), the child self-feeding, OR 5.70; 90% CI (2.77, 11.69), and positive caregiver verbalization, OR 2.46; 90% CI (1.26, 4.80), while lower odds of acceptance were associated with negative child verbalization during feeding, OR 0.27; 90% CI (0.17, 0.42). In this sample, caregivers used more responsive feeding practices during bites of local complementary food and were more controlling when feeding LNS. Responsive caregiver behaviours predicted child acceptance of food. These results could be used to design interventions in Malawi to improve responsive feeding practices in general and during LNS use. © 2011 John Wiley & Sons Ltd.

Identifying Core Competencies of Infection Control Nurse Specialists in Hong Kong.

PubMed

Chan, Wai Fong; Bond, Trevor G; Adamson, Bob; Chow, Meyrick

2016-01-01

To confirm a core competency scale for Hong Kong infection control nurses at the advanced nursing practice level from the core competency items proposed in a previous phase of this study. This would serve as the foundation of competency assurance in Hong Kong hospitals. A cross-sectional survey design was used. All public and private hospitals in Hong Kong. All infection control nurses in hospitals of Hong Kong. The 83-item proposed core competency list established in an earlier study was transformed into a questionnaire and sent to 112 infection control nurses in 48 hospitals in Hong Kong. They were asked to rate the importance of each infection prevention and control item using Likert-style response categories. Data were analyzed using the Rasch model. The response rate of 81.25% was achieved. Seven items were removed from the proposed core competency list, leaving a scale of 76 items that fit the measurement requirements of the unidimensional Rasch model. Essential core competency items of advanced practice for infection control nurses in Hong Kong were identified based on the measurement criteria of the Rasch model. Several items of the scale that reflect local Hong Kong contextual characteristics are distinguished from the overseas standards. This local-specific competency list could serve as the foundation for education and for certification of infection control nurse specialists in Hong Kong. Rasch measurement is an appropriate analytical tool for identifying core competencies of advanced practice nurses in other specialties and in other locations in a manner that incorporates practitioner judgment and expertise.

Monte Carlo Solution to Find Input Parameters in Systems Design Problems

NASA Astrophysics Data System (ADS)

Arsham, Hossein

2013-06-01

Most engineering system designs, such as product, process, and service design, involve a framework for arriving at a target value for a set of experiments. This paper considers a stochastic approximation algorithm for estimating the controllable input parameter within a desired accuracy, given a target value for the performance function. Two different problems, what-if and goal-seeking problems, are explained and defined in an auxiliary simulation model, which represents a local response surface model in terms of a polynomial. A method of constructing this polynomial by a single run simulation is explained. An algorithm is given to select the design parameter for the local response surface model. Finally, the mean time to failure (MTTF) of a reliability subsystem is computed and compared with its known analytical MTTF value for validation purposes.

Angiotensin II type 2 receptor (AT2R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons

PubMed Central

Anand, U; Facer, P; Yiangou, Y; Sinisi, M; Fox, M; McCarthy, T; Bountra, C; Korchev, YE; Anand, P

2013-01-01

Background The angiotensin II (AngII) receptor subtype 2 (AT2R) is expressed in sensory neurons and may play a role in nociception and neuronal regeneration. Methods We used immunostaining with characterized antibodies to study the localization of AT2R in cultured human and rat dorsal root ganglion (DRG) neurons and a range of human tissues. The effects of AngII and AT2R antagonist EMA401 on capsaicin responses in cultured human and rat (DRG) neurons were measured with calcium imaging, on neurite length and density with Gap43 immunostaining, and on cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. Results AT2R expression was localized in small-/medium-sized cultured neurons of human and rat DRG. Treatment with the AT2R antagonist EMA401 resulted in dose-related functional inhibition of capsaicin responses (IC50 = 10 nmol/L), which was reversed by 8-bromo-cAMP, and reduced neurite length and density; AngII treatment significantly enhanced capsaicin responses, cAMP levels and neurite outgrowth. The AT1R antagonist losartan had no effect on capsaicin responses. AT2R was localized in sensory neurons of human DRG, and nerve fibres in peripheral nerves, skin, urinary bladder and bowel. A majority sub-population (60%) of small-/medium-diameter neuronal cells were immunopositive in both control post-mortem and avulsion-injured human DRG; some very small neurons appeared to be intensely immunoreactive, with TRPV1 co-localization. While AT2R levels were reduced in human limb peripheral nerve segments proximal to injury, they were preserved in painful neuromas. Conclusions AT2R antagonists could be particularly useful in the treatment of chronic pain and hypersensitivity associated with abnormal nerve sprouting. PMID:23255326

Proteome analysis of yeast response to various nutrient limitations

PubMed Central

Kolkman, Annemieke; Daran-Lapujade, Pascale; Fullaondo, Asier; Olsthoorn, Maurien M A; Pronk, Jack T; Slijper, Monique; Heck, Albert J R

2006-01-01

We compared the response of Saccharomyces cerevisiae to carbon (glucose) and nitrogen (ammonia) limitation in chemostat cultivation at the proteome level. Protein levels were differentially quantified using unlabeled and 15N metabolically labeled yeast cultures. A total of 928 proteins covering a wide range of isoelectric points, molecular weights and subcellular localizations were identified. Stringent statistical analysis identified 51 proteins upregulated in response to glucose limitation and 51 upregulated in response to ammonia limitation. Under glucose limitation, typical glucose-repressed genes encoding proteins involved in alternative carbon source utilization, fatty acids β-oxidation and oxidative phosphorylation displayed an increased protein level. Proteins upregulated in response to nitrogen limitation were mostly involved in scavenging of alternative nitrogen sources and protein degradation. Comparison of transcript and protein levels clearly showed that upregulation in response to glucose limitation was mainly transcriptionally controlled, whereas upregulation in response to nitrogen limitation was essentially controlled at the post-transcriptional level by increased translational efficiency and/or decreased protein degradation. These observations underline the need for multilevel analysis in yeast systems biology. PMID:16738570

The Neuroanatomical Correlates of Training-Related Perceptuo-Reflex Uncoupling in Dancers

PubMed Central

Nigmatullina, Yuliya; Hellyer, Peter J.; Nachev, Parashkev; Sharp, David J.; Seemungal, Barry M.

2015-01-01

Sensory input evokes low-order reflexes and higher-order perceptual responses. Vestibular stimulation elicits vestibular-ocular reflex (VOR) and self-motion perception (e.g., vertigo) whose response durations are normally equal. Adaptation to repeated whole-body rotations, for example, ballet training, is known to reduce vestibular responses. We investigated the neuroanatomical correlates of vestibular perceptuo-reflex adaptation in ballet dancers and controls. Dancers' vestibular-reflex and perceptual responses to whole-body yaw-plane step rotations were: (1) Briefer and (2) uncorrelated (controls' reflex and perception were correlated). Voxel-based morphometry showed a selective gray matter (GM) reduction in dancers' vestibular cerebellum correlating with ballet experience. Dancers' vestibular cerebellar GM density reduction was related to shorter perceptual responses (i.e. positively correlated) but longer VOR duration (negatively correlated). Contrastingly, controls' vestibular cerebellar GM density negatively correlated with perception and VOR. Diffusion-tensor imaging showed that cerebral cortex white matter (WM) microstructure correlated with vestibular perception but only in controls. In summary, dancers display vestibular perceptuo-reflex dissociation with the neuronatomical correlate localized to the vestibular cerebellum. Controls' robust vestibular perception correlated with a cortical WM network conspicuously absent in dancers. Since primary vestibular afferents synapse in the vestibular cerebellum, we speculate that a cerebellar gating of perceptual signals to cortical regions mediates the training-related attenuation of vestibular perception and perceptuo-reflex uncoupling. PMID:24072889

Analysis of TMT primary mirror control-structure interaction

NASA Astrophysics Data System (ADS)

MacMynowski, Douglas G.; Thompson, Peter M.; Sirota, Mark J.

2008-07-01

The primary mirror control system (M1CS) keeps the 492 segments of the Thirty Meter Telescope primary mirror aligned in the presence of disturbances. A global position control loop uses feedback from inter-segment edge sensors to three actuators behind each segment that control segment piston, tip and tilt. If soft force actuators are used (e.g. voice-coil), then in addition to the global position loop there will be a local servo loop to provide stiffness. While the M1 control system at Keck compensates only for slow disturbances such as gravity and thermal variations, the M1CS for TMT will need to provide some compensation for higher frequency wind disturbances in order to meet stringent error budget targets. An analysis of expected high-wavenumber wind forces on M1 suggests that a 1Hz control bandwidth is required for the global feedback of segment edge-sensorbased position information in order to minimize high spatial frequency segment response for both seeing-limited and adaptive optics performance. A much higher bandwidth is required from the local servo loop to provide adequate stiffness to wind or acoustic disturbances. A related paper presents the control designs for the local actuator servo loops. The disturbance rejection requirements would not be difficult to achieve for a single segment, but the structural coupling between segments mounted on a flexible mirror cell results in controlstructure interaction (CSI) that limits the achievable bandwidth. Using a combination of simplified modeling to build intuition and the full telescope finite element model for verification, we present designs and analysis for both the local servo loop and global loop demonstrating sufficient bandwidth and resulting wind-disturbance rejection despite the presence of CSI.

A malaria transmission-directed model of mosquito life cycle and ecology

PubMed Central

2011-01-01

Background Malaria is a major public health issue in much of the world, and the mosquito vectors which drive transmission are key targets for interventions. Mathematical models for planning malaria eradication benefit from detailed representations of local mosquito populations, their natural dynamics and their response to campaign pressures. Methods A new model is presented for mosquito population dynamics, effects of weather, and impacts of multiple simultaneous interventions. This model is then embedded in a large-scale individual-based simulation and results for local elimination of malaria are discussed. Mosquito population behaviours, such as anthropophily and indoor feeding, are included to study their effect upon the efficacy of vector control-based elimination campaigns. Results Results for vector control tools, such as bed nets, indoor spraying, larval control and space spraying, both alone and in combination, are displayed for a single-location simulation with vector species and seasonality characteristic of central Tanzania, varying baseline transmission intensity and vector bionomics. The sensitivities to habitat type, anthropophily, indoor feeding, and baseline transmission intensity are explored. Conclusions The ability to model a spectrum of local vector species with different ecologies and behaviours allows local customization of packages of interventions and exploration of the effect of proposed new tools. PMID:21999664

Self-organization of grafted polyelectrolyte layers via the coupling of chemical equilibrium and physical interactions.

PubMed

Tagliazucchi, Mario; de la Cruz, Mónica Olvera; Szleifer, Igal

2010-03-23

The competition between chemical equilibrium, for example protonation, and physical interactions determines the molecular organization and functionality of biological and synthetic systems. Charge regulation by displacement of acid-base equilibrium induced by changes in the local environment provides a feedback mechanism that controls the balance between electrostatic, van der Waals, steric interactions and molecular organization. Which strategies do responsive systems follow to globally optimize chemical equilibrium and physical interactions? We address this question by theoretically studying model layers of end-grafted polyacids. These layers spontaneously form self-assembled aggregates, presenting domains of controlled local pH and whose morphologies can be manipulated by the composition of the solution in contact with the film. Charge regulation stabilizes micellar domains over a wide range of pH by reducing the local charge in the aggregate at the cost of chemical free energy and gaining in hydrophobic interactions. This balance determines the boundaries between different aggregate morphologies. We show that a qualitatively new form of organization arises from the coupling between physical interactions and protonation equilibrium. This optimization strategy presents itself with polyelectrolytes coexisting in two different and well-defined protonation states. Our results underline the need of considering the coupling between chemical equilibrium and physical interactions due to their highly nonadditive behavior. The predictions provide guidelines for the creation of responsive polymer layers presenting self-organized patterns with functional properties and they give insights for the understanding of competing interactions in highly inhomogeneous and constrained environments such as those relevant in nanotechnology and those responsible for biological cells function.

Relocation and the characteristics of hospital and hostel regimes.

PubMed

Booth, T; Simons, K; Booth, W

1991-01-01

Drawing on evidence from a research evaluation of a local community care programme, this paper explores whether relocation from a British National Health Service mental handicap hospital into local authority hostels (supervised residential facilities) brought about a qualitative change in the residential environment of movers towards less restrictive management practices and caring routines, more responsive attitudes towards their rights and needs as individuals, and greater control over their own lives. The conclusions point to the existence of a substantial measure of overlap in the fundamental characteristics of the hospital and hostel regimes.

Medical anthropology and Ebola in Congo: cultural models and humanistic care.

PubMed

Hewlett, B S; Epelboin, A; Hewlett, B L; Formenty, P

2005-09-01

Seldom have medical anthropologists been involved in efforts to control high mortality diseases such as Ebola hemorrhagic fever (EHF) This paper describes the results of two distinct but complementary interventions during the first phases of an outbreak in the Republic of Congo in 2003. The first approach emphasized understanding local peoples cultural models and political-economic explanations for the disease while the second approach focused on providing more humanitarian care of patients by identifying and incorporating local beliefs and practices into patient care and response efforts.

Magnetoelectric force microscopy based on magnetic force microscopy with modulated electric field.

PubMed

Geng, Yanan; Wu, Weida

2014-05-01

We present the realization of a mesoscopic imaging technique, namely, the Magnetoelectric Force Microscopy (MeFM), for visualization of local magnetoelectric effect. The basic principle of MeFM is the lock-in detection of local magnetoelectric response, i.e., the electric field-induced magnetization, using magnetic force microscopy. We demonstrate MeFM capability by visualizing magnetoelectric domains on single crystals of multiferroic hexagonal manganites. Results of several control experiments exclude artifacts or extrinsic origins of the MeFM signal. The parameters are tuned to optimize the signal to noise ratio.

Morphogenesis Is Not Required for Candida albicans-Staphylococcus aureus Intra-Abdominal Infection-Mediated Dissemination and Lethal Sepsis

PubMed Central

Nash, Evelyn E.; Peters, Brian M.; Palmer, Glen E.; Fidel, Paul L.

2014-01-01

Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An established experimental mouse model of Staphylococcus aureus-Candida albicans intra-abdominal infection results in ∼60% mortality within 48 h postinoculation, concomitant with amplified local inflammatory responses, while monomicrobial infections are avirulent. The purpose of this study was to characterize early local and systemic innate responses during coinfection and determine the role of C. albicans morphogenesis in lethality, a trait involved in virulence and physical interaction with S. aureus. Local and systemic proinflammatory cytokines were significantly elevated during coinfection at early time points (4 to 12 h) compared to those in monoinfection. In contrast, microbial burdens in the organs and peritoneal lavage fluid were similar between mono- and coinfected animals through 24 h, as was peritoneal neutrophil infiltration. After optimizing the model for 100% mortality within 48 h, using 3.5 × 107 C. albicans (5× increase), coinfection with C. albicans yeast-locked or hypha-locked mutants showed similar mortality, dissemination, and local and systemic inflammation to the isogenic control. However, coinfection with the yeast-locked C. albicans mutant given intravenously (i.v.) and S. aureus given intraperitoneally (i.p.) failed to induce mortality. These results suggest a unique intra-abdominal interaction between the host and C. albicans-S. aureus that results in strong inflammatory responses, dissemination, and lethal sepsis, independent of C. albicans morphogenesis. PMID:24891104

Sex and race differences in young people's responsiveness to price and tobacco control policies

PubMed Central

Chaloupka, F.; Pacula, R. L.

1999-01-01

OBJECTIVE—To determine if there are differences in young people's responsiveness to price and tobacco control policies for population subgroups and to examine whether or not these differences, if they exist, can explain sex and racial differences in trends in the prevalence of smoking in young people in the United States.
DESIGN—Use cross-sectional and intertemporal variation in local and state tobacco control policies and prices to calculate demand responses to these policies using regression analysis techniques.
SUBJECTS—A nationally representative sample of American eighth grade (ages 13-14 years), 10th grade (15-16 years) and 12th grade (17-18 years) students obtained from the 1992-1994 Monitoring the Future surveys.
MAIN OUTCOME MEASURE—Thirty-day smoking prevalence.
RESULTS—Young men are much more responsive to changes in the price of cigarettes than young women. The prevalence elasticity for young men is almost twice as large as that for young women. Smoking rates of young black men are significantly more responsive to changes in price than young white men. Significant differences in responsiveness to particular tobacco control policies also exist. These differences, however, explain relatively little of the differences in smoking prevalence among young population subgroups.
CONCLUSIONS—Policymakers need to keep in mind that there is not a "one-size fits all" strategy for discouraging smoking among young people.


Keywords: adolescents; tobacco control policies; price; sex differences; racial differences PMID:10629242

Granular metamaterials for vibration mitigation

NASA Astrophysics Data System (ADS)

Gantzounis, G.; Serra-Garcia, M.; Homma, K.; Mendoza, J. M.; Daraio, C.

2013-09-01

Acoustic metamaterials that allow low-frequency band gaps are interesting for many practical engineering applications, where vibration control and sound insulation are necessary. In most prior studies, the mechanical response of these structures has been described using linear continuum approximations. In this work, we experimentally and theoretically address the formation of low-frequency band gaps in locally resonant granular crystals, where the dynamics of the system is governed by discrete equations. We investigate the quasi-linear behavior of such structures. The analysis shows that a stopband can be introduced at about one octave lower frequency than in materials without local resonances. Broadband and multi-frequency stopband characteristics can also be achieved by strategically tailoring the non-uniform local resonance parameters.

Increased atherosclerosis in mice with increased vascular biglycan content.

PubMed

Thompson, Joel C; Tang, Tao; Wilson, Patricia G; Yoder, Meghan H; Tannock, Lisa R

2014-07-01

The response to retention hypothesis of atherogenesis proposes that atherosclerosis is initiated via the retention of atherogenic lipoproteins by vascular proteoglycans. Co-localization studies suggest that of all the vascular proteoglycans, biglycan is the one most closely co-localized with LDL. The goal of this study was to determine if over-expression of biglycan in hyperlipidemic mice would increase atherosclerosis development. Transgenic mice were developed by expressing biglycan under control of the smooth muscle actin promoter, and were crossed to the LDL receptor deficient (C57BL/6 background) atherosclerotic mouse model. Biglycan transgenic and non-transgenic control mice were fed an atherogenic Western diet for 4-12 weeks. LDL receptor deficient mice overexpressing biglycan under control of the smooth muscle alpha actin promoter had increased atherosclerosis development that correlated with vascular biglycan content. Increased vascular biglycan content predisposes to increased lipid retention and increased atherosclerosis development. Published by Elsevier Ireland Ltd.

Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy

NASA Technical Reports Server (NTRS)

Ingber, D. E.

1992-01-01

Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in response to these stimuli in the local tissue microenvironment. Analysis of this local control mechanism has revealed that ECM molecules switch capillary endothelial cells between differentiation and growth by both binding specific transmembrane integrin receptors and physically resisting cell-generated mechanical loads that are applied to these receptors. Control of capillary endothelial cell form and function therefore may be exerted by altering the mechanical properties of the ECM as well as its chemical composition. Understanding of this mechanochemical control mechanism has led to the development of new angiogenesis inhibitors that may be useful for the treatment of cancer.

Rapid control of male typical behaviors by brain-derived estrogens

PubMed Central

Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

2012-01-01

Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

Simple robot suggests physical interlimb communication is essential for quadruped walking

PubMed Central

Owaki, Dai; Kano, Takeshi; Nagasawa, Ko; Tero, Atsushi; Ishiguro, Akio

2013-01-01

Quadrupeds have versatile gait patterns, depending on the locomotion speed, environmental conditions and animal species. These locomotor patterns are generated via the coordination between limbs and are partly controlled by an intraspinal neural network called the central pattern generator (CPG). Although this forms the basis for current control paradigms of interlimb coordination, the mechanism responsible for interlimb coordination remains elusive. By using a minimalistic approach, we have developed a simple-structured quadruped robot, with the help of which we propose an unconventional CPG model that consists of four decoupled oscillators with only local force feedback in each leg. Our robot exhibits good adaptability to changes in weight distribution and walking speed simply by responding to local feedback, and it can mimic the walking patterns of actual quadrupeds. Our proposed CPG-based control method suggests that physical interaction between legs during movements is essential for interlimb coordination in quadruped walking. PMID:23097501

Simple robot suggests physical interlimb communication is essential for quadruped walking.

PubMed

Owaki, Dai; Kano, Takeshi; Nagasawa, Ko; Tero, Atsushi; Ishiguro, Akio

2013-01-06

Quadrupeds have versatile gait patterns, depending on the locomotion speed, environmental conditions and animal species. These locomotor patterns are generated via the coordination between limbs and are partly controlled by an intraspinal neural network called the central pattern generator (CPG). Although this forms the basis for current control paradigms of interlimb coordination, the mechanism responsible for interlimb coordination remains elusive. By using a minimalistic approach, we have developed a simple-structured quadruped robot, with the help of which we propose an unconventional CPG model that consists of four decoupled oscillators with only local force feedback in each leg. Our robot exhibits good adaptability to changes in weight distribution and walking speed simply by responding to local feedback, and it can mimic the walking patterns of actual quadrupeds. Our proposed CPG-based control method suggests that physical interaction between legs during movements is essential for interlimb coordination in quadruped walking.

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer

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

Gee, Harriet E., E-mail: harriet.gee@sydney.edu.au; The Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW; Central Clinical School, Sydney Medical School, University of Sydney, NSW

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series ofmore » 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers—TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1—were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy–treated patients but not in untreated matched control individuals (n=107; P<.05). Conclusions: Biomarkers of DNA repair and cell cycle control can identify patients at high risk of treatment failure in those receiving radiation therapy for early breast cancer in independent cohorts. These should be further investigated prospectively, especially TOP2A and SKP2, for which targeted therapies are available.« less

Regulation of SOBIR1 accumulation and activation of defense responses in bir1-1 by specific components of ER quality control.

PubMed

Sun, Tongjun; Zhang, Qian; Gao, Minghui; Zhang, Yuelin

2014-03-01

Receptor-like kinases play diverse roles in plant biology. Arabidopsis BAK1-INTERACTING RECEPTOR-LIKE KINASE 1 (BIR1) functions as a negative regulator of plant immunity. bir1-1 mutant plants display spontaneous cell death and constitutive defense responses that are dependent on SUPPRESSOR OF BIR1,1 (SOBIR1) and PHYTOALEXIN DEFICIENT4 (PAD4). Here we report that mutations in three components of ER quality control, CALRETICULIN3 (CRT3), ER-LOCALIZED DnaJ-LIKE PROTEIN 3b (ERdj3b) and STROMAL-DERIVED FACTOR-2 (SDF2), also suppress the spontaneous cell death and constitutive defense responses in bir1-1. Further analysis revealed that accumulation of the SOBIR1 protein is reduced in crt3-1 and erdj3b-1 mutant plants. These data suggest that ER quality control plays important roles in the biogenesis of SOBIR1, and is required for cell death and defense responses in bir1-1. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Implementation of a workplace smoking ban in bars: the limits of local discretion.

PubMed

Montini, Theresa; Bero, Lisa A

2008-12-08

In January 1998, the California state legislature extended a workplace smoking ban to bars. The purpose of this study was to explore the conditions that facilitate or hinder compliance with a smoking ban in bars. We studied the implementation of the smoking ban in bars by interviewing three sets of policy participants: bar employers responsible for complying with the law; local government officials responsible for enforcing the law; and tobacco control activists who facilitated implementation. We transcribed the interviews and did a qualitative analysis of the text. The conditions that facilitated bar owners' compliance with a smoking ban in bars included: if the cost to comply was minimal; if the bars with which they were in competition were in compliance with the smoking ban; and if there was authoritative, consistent, coordinated, and uniform enforcement. Conversely, the conditions that hindered compliance included: if the law had minimal sanctions; if competing bars in the area allowed smoking; and if enforcement was delayed or inadequate. Many local enforcers wished to forfeit their local discretion and believed the workplace smoking ban in bars would be best implemented by a state agency. The potential implication of this study is that, given the complex nature of local politics, smoking bans in bars are best implemented at a broader provincial or national level.

Local Support for Alcohol Control Policies and Perceptions of Neighborhood Issues in Two College Communities

PubMed Central

Fairlie, Anne M.; DeJong, William; Wood, Mark D.

2014-01-01

Background Although valuable, national opinion surveys on alcohol policy may be less informative for policy development at the local level. Using samples of adult residents in two college communities, the present study: 1) measured public support for local alcohol control policies to stem underage drinking and alcohol over-service in on-premise outlets; 2) assessed residents' opinions regarding neighborhood problems; and 3) identified factors associated with strong policy support. Methods We administered random-sample telephone surveys to residents ages 21 years and older in college communities located in Community 1 (N = 501; mean age = 57.4 years, SD = 14.7) and Community 2 (N = 505; mean age = 56.0 years, SD = 15.2). The response rates were typical of telephone surveys (Community 1: 33.5%; Community 2: 29.9%). We assessed support for 16 alcohol control policies and the occurrence of specific types of neighborhood incidents (e.g., witnessing intoxicated people). We used multiple regression analyses to determine factors associated with policy support. Results Residents in Community 1 reported significantly higher weekly alcohol use, a greater number of witnessed neighborhood incidents, and a higher level of perceived neighborhood problems than did residents in Community 2. Residents in Community 1 perceived local alcohol control policies and their enforcement to be significantly stricter. Overall, policy support was high and did not differ between the communities. In both communities, higher policy support was significantly associated with being female, being older, less weekly alcohol use, and lower perceived strictness of alcohol control policies and enforcement. Conclusions It is important for campus officials and community leaders to be aware of and publicize favorable public opinion when advocating for policy change, especially at the local level. Information on residents' perceptions of the neighborhood issues they face can also inform local policy and enforcement efforts. PMID:25085566

Integrating Health into Local Climate Response: Lessons from the U.S. CDC Climate-Ready States and Cities Initiative

PubMed Central

Fox, Mary A.; Kaye, Charlotte; Resnick, Beth

2017-01-01

Summary: Public health has potential to serve as a frame to convey the urgency of behavior change needed to adapt to a changing climate and reduce greenhouse gas emissions. Local governments form the backbone of climate-related public health preparedness. Yet local health agencies are often inadequately prepared and poorly integrated into climate change assessments and plans. We reviewed the climate health profiles of 16 states and two cities participating in the U.S. Centers for Disease Control and Prevention (CDC)’s Climate-Ready States and Cities Initiative (CRSCI) that aims to build local capacity to assess and respond to the health impacts of climate change. Following recommendations from a recent expert panel strategic review, we present illustrations of emerging promising practice and future directions. We found that CRSCI has strengthened climate preparedness and response in local public health agencies by identifying critical climate-health impacts and vulnerable populations, and has helped integrate health more fully into broader climate planning. Promising practice was found in all three recommendation areas identified by the expert panel (leveraging partnerships, refining assessment methodologies and enhancing communications), particularly with regard to health impacts of extreme heat. Vast needs remain, however, suggesting the need to disseminate CRSCI experience to non-grantees. In conclusion, the CRSCI program approach and selected activities illustrate a way forward toward robust, targeted local preparedness and response that may serve as a useful example for public health departments in the United States and internationally, particularly at a time of uncertain commitment to climate change agreements at the national level. https://doi.org/10.1289/EHP1838 PMID:28934724

Metabolic Mapping of the Brain's Response to Visual Stimulation: Studies in Humans.

ERIC Educational Resources Information Center

Phelps, Michael E.; Kuhl, David E.

1981-01-01

Studies demonstrate increasing glucose metabolic rates in human primary (PVC) and association (AVC) visual cortex as complexity of visual scenes increase. AVC increased more rapidly with scene complexity than PVC and increased local metabolic activities above control subject with eyes closed; indicates wide range and metabolic reserve of visual…

Fluvial processes in Puget Sound rivers and the Pacific Northwest [Chapter 3

Treesearch

John M. Buffington; Richard D. Woodsmith; Derek B. Booth; David R. Montgomery

2003-01-01

The variability of topography, geology, climate; vegetation, and land use in the Pacific Northwest creates considerable spatial and temporal variability of fluvial processes and reach-scale channel type. Here we identify process domains of typical Pacific Northwest watersheds and examine local physiographic and geologic controls on channel processes and response...

Record of Decision for the First Air National Guard F-35A Operational Base

DTIC Science & Technology

2013-12-02

Air Quality • Employ fugitive dust control and soil retention practices including: - Water trucks or sprinkler systems to keep all areas of vehicle...with local fire departments on F-35A crash response procedures. Soils and Water • Sequence construction activities to limit the soil exposure for

7 CFR Appendix D to Subpart E of... - Alcohol Production Facilities Planning, Performing, Development and Project Control

Code of Federal Regulations, 2012 CFR

2012-01-01

... (CONTINUED) GENERAL Business and Industrial Loan Program Pt. 1980, Subpt. E, App. D Appendix D to Subpart E... designed utilizing accepted engineering practices and are conformed to applicable Federal, State and local... this appendix. (II) Technical Services. (A) The borrower is responsible for selecting engineering...

Backing into the Future: Motatau Bilingual School.

ERIC Educational Resources Information Center

Robust, Te Tuhi

2000-01-01

Describes the struggles and triumphs of a Maori community in the Bay of Islands (New Zealand) as it took local control of its rural school and made it fully bilingual. A series of government reforms have made the Maori people responsible for administering the school with insufficient funds while the government maintains power over the curriculum…

Well-Prepared Teachers Inspire Student Learning

ERIC Educational Resources Information Center

Pecheone, Raymond L.; Whittaker, Andrea

2016-01-01

This is an era of transformation in the preparation, induction, and assessment of prospective teachers. The tension between local and state control is at the heart of the debate. States should be responsible for establishing performance standards that ensure that new teachers are well-prepared, competent, and ready to teach. This is why the…

The Quiet Revolution in Land Use Control.

ERIC Educational Resources Information Center

Bosselman, Fred; Callies, David

The Council on Environmental Quality commissioned this report on the innovative land use laws of several states to learn how some of the most complex land use issues and problems of re-allocating responsibilities between state and local governments are being addressed. Many of the laws analyzed are designed to deal with problems that are treated…

Area-wide management of Aedes albopictus: choice of study sites based on geospatial characteristics, socioeconomic factors, and mosquito populations

USDA-ARS?s Scientific Manuscript database

Aedes (Stegomyia) albopictus (Skuse), the Asian tiger mosquito, is an introduced invasive species in the U.S. responsible for a significant proportion of service requests to local mosquito control programs. This container-utilizing mosquito is refractory to standard mosquito abatement measures in th...

High-throughput microfluidics to control and measure signaling dynamics in single yeast cells

PubMed Central

Hansen, Anders S.; Hao, Nan; O'Shea, Erin K.

2015-01-01

Microfluidics coupled to quantitative time-lapse fluorescence microscopy is transforming our ability to control, measure, and understand signaling dynamics in single living cells. Here we describe a pipeline that incorporates multiplexed microfluidic cell culture, automated programmable fluid handling for cell perturbation, quantitative time-lapse microscopy, and computational analysis of time-lapse movies. We illustrate how this setup can be used to control the nuclear localization of the budding yeast transcription factor Msn2. Using this protocol, we generate oscillations of Msn2 localization and measure the dynamic gene expression response of individual genes in single cells. The protocol allows a single researcher to perform up to 20 different experiments in a single day, whilst collecting data for thousands of single cells. Compared to other protocols, the present protocol is relatively easy to adopt and higher-throughput. The protocol can be widely used to control and monitor single-cell signaling dynamics in other signal transduction systems in microorganisms. PMID:26158443

Community-Centered Responses to Ebola in Urban Liberia: The View from Below

PubMed Central

Abramowitz, Sharon Alane; McLean, Kristen E.; McKune, Sarah Lindley; Bardosh, Kevin Louis; Fallah, Mosoka; Monger, Josephine; Tehoungue, Kodjo; Omidian, Patricia A.

2015-01-01

Background The West African Ebola epidemic has demonstrated that the existing range of medical and epidemiological responses to emerging disease outbreaks is insufficient, especially in post-conflict contexts with exceedingly poor healthcare infrastructures. In this context, community-based responses have proven vital for containing Ebola virus disease (EVD) and shifting the epidemic curve. Despite a surge in interest in local innovations that effectively contained the epidemic, the mechanisms for community-based response remain unclear. This study provides baseline information on community-based epidemic control priorities and identifies innovative local strategies for containing EVD in Liberia. Methodology/Principal Findings This study was conducted in September 2014 in 15 communities in Monrovia and Montserrado County, Liberia – one of the epicenters of the Ebola outbreak. Findings from 15 focus group discussions with 386 community leaders identified strategies being undertaken and recommendations for what a community-based response to Ebola should look like under then-existing conditions. Data were collected on the following topics: prevention, surveillance, care-giving, community-based treatment and support, networks and hotlines, response teams, Ebola treatment units (ETUs) and hospitals, the management of corpses, quarantine and isolation, orphans, memorialization, and the need for community-based training and education. Findings have been presented as community-based strategies and recommendations for (1) prevention, (2) treatment and response, and (3) community sequelae and recovery. Several models for community-based management of the current Ebola outbreak were proposed. Additional findings indicate positive attitudes towards early Ebola survivors, and the need for community-based psychosocial support. Conclusions/Significance Local communities’ strategies and recommendations give insight into how urban Liberian communities contained the EVD outbreak while navigating the systemic failures of the initial state and international response. Communities in urban Liberia adapted to the epidemic using multiple coping strategies. In the absence of health, infrastructural and material supports, local people engaged in self-reliance in order to contain the epidemic at the micro-social level. These innovations were regarded as necessary, but as less desirable than a well-supported health-systems based response; and were seen as involving considerable individual, social, and public health costs, including heightened vulnerability to infection. PMID:25856072

Community-centered responses to Ebola in urban Liberia: the view from below.

PubMed

Abramowitz, Sharon Alane; McLean, Kristen E; McKune, Sarah Lindley; Bardosh, Kevin Louis; Fallah, Mosoka; Monger, Josephine; Tehoungue, Kodjo; Omidian, Patricia A

2015-04-01

The West African Ebola epidemic has demonstrated that the existing range of medical and epidemiological responses to emerging disease outbreaks is insufficient, especially in post-conflict contexts with exceedingly poor healthcare infrastructures. In this context, community-based responses have proven vital for containing Ebola virus disease (EVD) and shifting the epidemic curve. Despite a surge in interest in local innovations that effectively contained the epidemic, the mechanisms for community-based response remain unclear. This study provides baseline information on community-based epidemic control priorities and identifies innovative local strategies for containing EVD in Liberia. This study was conducted in September 2014 in 15 communities in Monrovia and Montserrado County, Liberia--one of the epicenters of the Ebola outbreak. Findings from 15 focus group discussions with 386 community leaders identified strategies being undertaken and recommendations for what a community-based response to Ebola should look like under then-existing conditions. Data were collected on the following topics: prevention, surveillance, care-giving, community-based treatment and support, networks and hotlines, response teams, Ebola treatment units (ETUs) and hospitals, the management of corpses, quarantine and isolation, orphans, memorialization, and the need for community-based training and education. Findings have been presented as community-based strategies and recommendations for (1) prevention, (2) treatment and response, and (3) community sequelae and recovery. Several models for community-based management of the current Ebola outbreak were proposed. Additional findings indicate positive attitudes towards early Ebola survivors, and the need for community-based psychosocial support. Local communities' strategies and recommendations give insight into how urban Liberian communities contained the EVD outbreak while navigating the systemic failures of the initial state and international response. Communities in urban Liberia adapted to the epidemic using multiple coping strategies. In the absence of health, infrastructural and material supports, local people engaged in self-reliance in order to contain the epidemic at the micro-social level. These innovations were regarded as necessary, but as less desirable than a well-supported health-systems based response; and were seen as involving considerable individual, social, and public health costs, including heightened vulnerability to infection.

Network model of top-down influences on local gain and contextual interactions in visual cortex.

PubMed

Piëch, Valentin; Li, Wu; Reeke, George N; Gilbert, Charles D

2013-10-22

The visual system uses continuity as a cue for grouping oriented line segments that define object boundaries in complex visual scenes. Many studies support the idea that long-range intrinsic horizontal connections in early visual cortex contribute to this grouping. Top-down influences in primary visual cortex (V1) play an important role in the processes of contour integration and perceptual saliency, with contour-related responses being task dependent. This suggests an interaction between recurrent inputs to V1 and intrinsic connections within V1 that enables V1 neurons to respond differently under different conditions. We created a network model that simulates parametrically the control of local gain by hypothetical top-down modification of local recurrence. These local gain changes, as a consequence of network dynamics in our model, enable modulation of contextual interactions in a task-dependent manner. Our model displays contour-related facilitation of neuronal responses and differential foreground vs. background responses over the neuronal ensemble, accounting for the perceptual pop-out of salient contours. It quantitatively reproduces the results of single-unit recording experiments in V1, highlighting salient contours and replicating the time course of contextual influences. We show by means of phase-plane analysis that the model operates stably even in the presence of large inputs. Our model shows how a simple form of top-down modulation of the effective connectivity of intrinsic cortical connections among biophysically realistic neurons can account for some of the response changes seen in perceptual learning and task switching.

MAppERS experience: natural processes and preparedness in the societal context

NASA Astrophysics Data System (ADS)

Frigerio, Simone; Schenato, Luca; Bossi, Giulia; Mantovani, Matteo; Marcato, Gianluca; Pasuto, Alessandro

2016-04-01

Within natural processes responsibilities from central authorities to local levels as first actors of civil protection is a changing pattern. Prevention and preparedness in natural hazards are long-term goals based on capacities of professional volunteers, and improving the awareness of the citizens as local inhabitants. Local people have impacts on their lives but training and involvement towards specific techniques change their role within risk communication and emergency preparedness. A collaborative user environment is useful for emergency response and support in the wake of disasters, feeding updated information on the ground directly to on-site responders. MAppERS (Mobile Application for Emergency Response and Support) is a funded project (2013-2015 Humanitarian Aid and Civil Protection, ECHO A5) based on human role as "crowd-sourced mappers" through smart phone application able to share GPS-localised and detailed parameters. The feedback from testing and the training courses aim to raising public awareness and participation in a networked disaster response. The project implies design and test of smart phone linked with a real-time dashboard platform for rescue services citizens and volunteers of civil protection. Two pilot sites, including trainings on modules functioning control usability and quality of the product. The synchronized platform offers the activity of cloud data collection with a central data dashboard. Information is collected in a context of floods processes, with crowdsourcing action from local population, for proper awareness with own personal flood plan and long-term preparedness. A second context tested pre-emergency actions on field with rescue team, collecting state-of-art and condition of hazards.

Decision support for evidence-based integration of disease control: A proof of concept for malaria and schistosomiasis

PubMed Central

Graeden, Ellie; Kerr, Justin; Sorrell, Erin M.; Katz, Rebecca

2018-01-01

Managing infectious disease requires rapid and effective response to support decision making. The decisions are complex and require understanding of the diseases, disease intervention and control measures, and the disease-relevant characteristics of the local community. Though disease modeling frameworks have been developed to address these questions, the complexity of current models presents a significant barrier to community-level decision makers in using the outputs of the most scientifically robust methods to support pragmatic decisions about implementing a public health response effort, even for endemic diseases with which they are already familiar. Here, we describe the development of an application available on the internet, including from mobile devices, with a simple user interface, to support on-the-ground decision-making for integrating disease control programs, given local conditions and practical constraints. The model upon which the tool is built provides predictive analysis for the effectiveness of integration of schistosomiasis and malaria control, two diseases with extensive geographical and epidemiological overlap, and which result in significant morbidity and mortality in affected regions. Working with data from countries across sub-Saharan Africa and the Middle East, we present a proof-of-principle method and corresponding prototype tool to provide guidance on how to optimize integration of vertical disease control programs. This method and tool demonstrate significant progress in effectively translating the best available scientific models to support practical decision making on the ground with the potential to significantly increase the efficacy and cost-effectiveness of disease control. Author summary Designing and implementing effective programs for infectious disease control requires complex decision-making, informed by an understanding of the diseases, the types of disease interventions and control measures available, and the disease-relevant characteristics of the local community. Though disease modeling frameworks have been developed to address these questions and support decision-making, the complexity of current models presents a significant barrier to on-the-ground end users. The picture is further complicated when considering approaches for integration of different disease control programs, where co-infection dynamics, treatment interactions, and other variables must also be taken into account. Here, we describe the development of an application available on the internet with a simple user interface, to support on-the-ground decision-making for integrating disease control, given local conditions and practical constraints. The model upon which the tool is built provides predictive analysis for the effectiveness of integration of schistosomiasis and malaria control, two diseases with extensive geographical and epidemiological overlap. This proof-of-concept method and tool demonstrate significant progress in effectively translating the best available scientific models to support pragmatic decision-making on the ground, with the potential to significantly increase the impact and cost-effectiveness of disease control. PMID:29649260

Image quality prediction - An aid to the Viking lander imaging investigation on Mars

NASA Technical Reports Server (NTRS)

Huck, F. O.; Wall, S. D.

1976-01-01

Image quality criteria and image quality predictions are formulated for the multispectral panoramic cameras carried by the Viking Mars landers. Image quality predictions are based on expected camera performance, Mars surface radiance, and lighting and viewing geometry (fields of view, Mars lander shadows, solar day-night alternation), and are needed in diagnosis of camera performance, in arriving at a preflight imaging strategy, and revision of that strategy should the need arise. Landing considerations, camera control instructions, camera control logic, aspects of the imaging process (spectral response, spatial response, sensitivity), and likely problems are discussed. Major concerns include: degradation of camera response by isotope radiation, uncertainties in lighting and viewing geometry and in landing site local topography, contamination of camera window by dust abrasion, and initial errors in assigning camera dynamic ranges (gains and offsets).

Skin microdialysis coupled with laser speckle contrast imaging to assess microvascular reactivity.

PubMed

Cracowski, J L; Gaillard-Bigot, F; Cracowski, C; Roustit, M; Millet, C

2011-11-01

Laser speckle contrast imaging (LSCI) can be used to assess real-time responses of skin microcirculation to pharmacological interventions. The main objective of this study was to determine whether intradermal or subdermal microdialysis fiber insertion, coupled with skin flux recording using LSCI, can be used to assess baseline cutaneous flux and the post-occlusive reactive hyperemic response. The microdialysis sites were compared to control area without microdialysis fibers. One dermal and two subdermal microdialysis fibers were randomly inserted in the right forearm skin of six healthy volunteers. We performed consecutively tests of post-occlusive hyperemia, infusion of 29 mM sodium nitroprusside (SNP), local thermal hyperemia at 43°C and a second 29 mM SNP infusion at the end of the experiment. Two hours after fiber insertion, cutaneous vascular conductances (CVC) at the subdermal fiber sites were not different from their respective control regions of interest, while at the dermal site CVC remained higher (0.48+/-0.15 versus 0.37+/-0.1 PU.mm Hg(-1), P=0.003). The peak CVC and area under the curve observed during post-occlusive reactive hyperemia were similar at all fiber sites and their respective controls. We observed a similar increase in CVC using 29 mM SNP infusion, 40 min local heating at 43°C, and their combination. Finally, physiological and pharmacological responses of the subdermal sites were reproducible in terms of amplitude, whether expressed as raw CVC or as % CVCmax. We showed that studying skin microvascular physiological or pharmacological responses using inserted subdermal microdialysis fibers coupled with LSCI is feasible and reproducible, and provides two-dimensional information. This technique will be useful for future mechanistic studies of skin microcirculation. Copyright © 2011 Elsevier Inc. All rights reserved.

Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas.

PubMed

Silveira, Edna Aparecida; Siman, Fabiana Dayse Magalhães; de Oliveira Faria, Thaís; Vescovi, Marcos Vinícius Altoé; Furieri, Lorena Barros; Lizardo, Juliana Hott Fúcio; Stefanon, Ivanita; Padilha, Alessandra Simão; Vassallo, Dalton Valentim

2014-02-01

Chronic lead exposure induces hypertension affecting endothelial function. We investigated whether low-concentration lead exposure alters blood pressure and vascular reactivity, focusing on the roles of NO, oxidative stress, cyclooxygenase-derived vasoconstrictor prostanoids, and the local angiotensin-renin system. Aortic rings from 3-month-old Wistar rats were treated daily with lead acetate (first dose 4mg/100g, subsequent doses 0.05mg/100g, im) or vehicle for 30 days. Treatment increased lead blood levels (12μg/dl), blood pressure, and aortic ring contractile response to phenylephrine (1nM-100mM). Contractile response after L-NAME administration increased in both groups but was higher after lead treatment. Lead effects on Rmax decreased more after apocynin and superoxide dismutase administration compared to control. Indomethacin reduced phenylephrine response more after lead treatment than in controls. The selective COX-2 inhibitor NS398, thromboxane A2/prostaglandin H2 receptor antagonist SQ 29,548, TXA2 synthase inhibitor furegrelate, EP1 receptor antagonist SC 19220, and ACE inhibitor and AT1 receptor antagonist losartan reduced phenylephrine responses only in vessels from lead-treated rats. Basal and stimulated NO release was reduced and local O2(-) liberation increased in the lead-treated group compared to controls. eNOS, iNOS, and AT1 receptor protein expression increased with lead exposure, but COX-2 protein expression decreased. This is the first demonstration that blood Pb(2+) (12µg/dl) concentrations below the WHO-established values increased systolic blood pressure and vascular phenylephrine reactivity. This effect was associated with reduced NO bioavailability, increased reactive oxygen species production, increased participation of COX-derived contractile prostanoids, and increased renin-angiotensin system activity. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Polarization Control with Plasmonic Antenna Tips: A Universal Approach to Optical Nanocrystallography and Vector-Field Imaging

NASA Astrophysics Data System (ADS)

Park, Kyoung-Duck; Raschke, Markus B.

2018-05-01

Controlling the propagation and polarization vectors in linear and nonlinear optical spectroscopy enables to probe the anisotropy of optical responses providing structural symmetry selective contrast in optical imaging. Here we present a novel tilted antenna-tip approach to control the optical vector-field by breaking the axial symmetry of the nano-probe in tip-enhanced near-field microscopy. This gives rise to a localized plasmonic antenna effect with significantly enhanced optical field vectors with control of both \\textit{in-plane} and \\textit{out-of-plane} components. We use the resulting vector-field specificity in the symmetry selective nonlinear optical response of second-harmonic generation (SHG) for a generalized approach to optical nano-crystallography and -imaging. In tip-enhanced SHG imaging of monolayer MoS$_2$ films and single-crystalline ferroelectric YMnO$_3$, we reveal nano-crystallographic details of domain boundaries and domain topology with enhanced sensitivity and nanoscale spatial resolution. The approach is applicable to any anisotropic linear and nonlinear optical response, and provides for optical nano-crystallographic imaging of molecular or quantum materials.

An Investigation of Land-Atmosphere Coupling from Local to Regional Scales

NASA Astrophysics Data System (ADS)

Brunsell, N. A.; Van Vleck, E.; Rahn, D. A.

2017-12-01

The exchanges of mass and energy between the surface and atmosphere have been shown to depend upon both local and regional climatic influences. However, the degree of control exerted by the land surface on the coupling metrics is not well understood. In particular, we lack an understanding of the relationship between the local microclimate of a site and the regional forces responsible for land-atmosphere coupling. To address this, we investigate a series of metrics calculated from eddy covariance data and ceilometer data, land surface modeling and remotely sensed observations in the central United States to diagnose these interactions and predict the change from one coupling regime (e.g. wet/dry coupling) to another state. The stability of the coupling is quantified using a Lyapunov exponent based methodology. Through the use of a wavelet information theoretic approach, we isolate the roles local energy partitioning, as well as the temperature and moisture gradients on controlling and changing the coupling regime. Taking a multi-scale observational approach, we first examine the relationship at the tower scale. Using land surface models, we quantify to what extent current models are capable of properly diagnosing the dynamics of the coupling regime. In particular, we focus on the role of the surface moisture and vegetation to initiate and maintain precipitation feedbacks. We extend this analysis to the regional scale by utilizing reanalysis and remotely sensed observations. Thus, we are able to quantify the changes in observed coupling patterns with linkages to local interactions to address the question of the local control that the surface exerts over the maintenance of land-atmosphere coupling.

Local domains of motor cortical activity revealed by fiber-optic calcium recordings in behaving nonhuman primates.

PubMed

Adelsberger, Helmuth; Zainos, Antonio; Alvarez, Manuel; Romo, Ranulfo; Konnerth, Arthur

2014-01-07

Brain mapping experiments involving electrical microstimulation indicate that the primary motor cortex (M1) directly regulates muscle contraction and thereby controls specific movements. Possibly, M1 contains a small circuit "map" of the body that is formed by discrete local networks that code for specific movements. Alternatively, movements may be controlled by distributed, larger-scale overlapping circuits. Because of technical limitations, it remained unclear how movement-determining circuits are organized in M1. Here we introduce a method that allows the functional mapping of small local neuronal circuits in awake behaving nonhuman primates. For this purpose, we combined optic-fiber-based calcium recordings of neuronal activity and cortical microstimulation. The method requires targeted bulk loading of synthetic calcium indicators (e.g., OGB-1 AM) for the staining of neuronal microdomains. The tip of a thin (200 µm) optical fiber can detect the coherent activity of a small cluster of neurons, but is insensitive to the asynchronous activity of individual cells. By combining such optical recordings with microstimulation at two well-separated sites of M1, we demonstrate that local cortical activity was tightly associated with distinct and stereotypical simple movements. Increasing stimulation intensity increased both the amplitude of the movements and the level of neuronal activity. Importantly, the activity remained local, without invading the recording domain of the second optical fiber. Furthermore, there was clear response specificity at the two recording sites in a trained behavioral task. Thus, the results provide support for movement control in M1 by local neuronal clusters that are organized in discrete cortical domains.

Modeling Elevation and Aspect Controls on Emerging Ecohydrologic Processes and Ecosystem Patterns Using the Component-based Landlab Framework

NASA Astrophysics Data System (ADS)

Nudurupati, S. S.; Istanbulluoglu, E.; Adams, J. M.; Hobley, D. E. J.; Gasparini, N. M.; Tucker, G. E.; Hutton, E. W. H.

2014-12-01

Topography plays a commanding role on the organization of ecohydrologic processes and resulting vegetation patterns. In southwestern United States, climate conditions lead to terrain aspect- and elevation-controlled ecosystems, with mesic north-facing and xeric south-facing vegetation types; and changes in biodiversity as a function of elevation from shrublands in low desert elevations, to mixed grass/shrublands in mid elevations, and forests at high elevations and ridge tops. These observed patterns have been attributed to differences in topography-mediated local soil moisture availability, micro-climatology, and life history processes of plants that control chances of plant establishment and survival. While ecohydrologic models represent local vegetation dynamics in sufficient detail up to sub-hourly time scales, plant life history and competition for space and resources has not been adequately represented in models. In this study we develop an ecohydrologic cellular automata model within the Landlab component-based modeling framework. This model couples local vegetation dynamics (biomass production, death) and plant establishment and competition processes for resources and space. This model is used to study the vegetation organization in a semiarid New Mexico catchment where elevation and hillslope aspect play a defining role on plant types. Processes that lead to observed plant types across the landscape are examined by initializing the domain with randomly assigned plant types and systematically changing model parameters that couple plant response with soil moisture dynamics. Climate perturbation experiments are conducted to examine the plant response in space and time. Understanding the inherently transient ecohydrologic systems is critical to improve predictions of climate change impacts on ecosystems.

Formation of a physiological complex between TRPV2 and RGA protein promotes cell surface expression of TRPV2.

PubMed

Stokes, Alexander J; Wakano, Clay; Del Carmen, Kimberly A; Koblan-Huberson, Murielle; Turner, Helen

2005-03-01

The transient receptor potential, sub-family Vanilloid (TRPV)(2) cation channel is activated in response to extreme temperature elevations in sensory neurons. However, TRPV2 is widely expressed in tissues with no sensory function, including cells of the immune system. Regulation of GRC, the murine homolog of TRPV2 has been studied in insulinoma cells and myocytes. GRC is activated in response to certain growth factors and neuropeptides, via a mechanism that involves regulated access of the channel to the plasma membrane. This is likely to be an important primary control mechanism for TRPV2 outside the CNS. Here, we report that a regulated trafficking step controls the access of TRPV2 to the cell surface in mast cells. In mast cells, elevations in cytosolic cAMP are sufficient to drive plasma membrane localization of TRPV2. We have previously proposed that the recombinase gene activator protein (RGA), a four-transmembrane domain, intracellular protein, associates with TRPV2 during the biosynthesis and early trafficking of the channel. We use a polyclonal antibody to RGA to confirm the formation of a physiological complex between RGA and TRPV2. Finally, we show that over-expression of the RGA protein potentiates the basal surface localization of TRPV2. We propose that trafficking and activation mechanisms intersect for TRPV2, and that cAMP mobilizing stimuli may regulate TRPV2 localization in non-sensory cells. RGA participates in the control of TRPV2 surface levels, and co-expression of RGA may be a key component of experimental systems that seek to study TRPV2 physiology.

System identification for Space Station Freedom using observer/Kalman filter Markov parameters. M.S. Thesis

NASA Technical Reports Server (NTRS)

Papadopoulos, Michael; Tolson, Robert H.

1993-01-01

The Modal Identification Experiment (MIE) is a proposed experiment to define the dynamic characteristics of Space Station Freedom. Previous studies emphasized free-decay modal identification. The feasibility of using a forced response method (Observer/Kalman Filter Identification (OKID)) is addressed. The interest in using OKID is to determine the input mode shape matrix which can be used for controller design or control-structure interaction analysis, and investigate if forced response methods may aid in separating closely spaced modes. A model of the SC-7 configuration of Space Station Freedom was excited using simulated control system thrusters to obtain acceleration output. It is shown that an 'optimum' number of outputs exists for OKID. To recover global mode shapes, a modified method called Global-Local OKID was developed. This study shows that using data from a long forced response followed by free-decay leads to the 'best' modal identification. Twelve out of the thirteen target modes were identified for such an output.

Utilization of Local Law Enforcement Aerial Resources in Consequence Management (CM) Response

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

Wasiolek, Piotr T.; Malchow, Russell L.

2013-03-12

During the past decade the U.S. Department of Homeland Security (DHS) was instrumental in enhancing the nation’s ability to detect and prevent a radiological or nuclear attack in the highest risk cities. Under the DHS Securing the Cities initiative, nearly 13,000 personnel in the New York City region have been trained in preventive radiological and nuclear detection operations, and nearly 8,500 pieces of radiological detection equipment have been funded. As part of the preventive radiological/nuclear detection (PRND) mission, several cities have received funding to purchase commercial aerial radiation detection systems. In 2008, the U.S. Department of Energy, National Nuclear Securitymore » Administration Aerial Measuring System (AMS) program started providing Mobile Aerial Radiological Surveillance (MARS) training to such assets, resulting in over 150 HAZMAT teams’ officers and pilots from 10 law enforcement organizations and fire departments being trained in the aerial radiation detection. From the beginning, the MARS training course covered both the PRND and consequence management (CM) missions. Even if the law enforcement main focus is PRND, their aerial assets can be utilized in the collection of initial radiation data for post-event radiological CM response. Based on over 50 years of AMS operational experience and information collected during MARS training, this presentation will focus on the concepts of CM response using aerial assets as well as utilizing law enforcement/fire department aerial assets in CM. Also discussed will be the need for establishing closer relationships between local jurisdictions’ aerial radiation detection capabilities and state and local radiation control program directors, radiological health department managers, etc. During radiological events these individuals may become primary experts/advisers to Incident Commanders for radiological emergency response, especially in the early stages of a response. The knowledge of the existence, specific capabilities, and use of local aerial radiation detection systems would be critical in planning the response, even before federal assets arrive on the scene. The relationship between local and federal aerial assets and the potential role for the further use of the MARS training and expanded AMS Reachback capabilities in facilitating such interactions will be discussed.« less

THE ABSCOPAL EFFECT OF X IRRADIATION ON BONE GROWTH IN RATS

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

Pappas, A.M.; Cohen, J.

1963-06-01

The abscopal effect of irradiation (that which is evident at a distance from the irradiated volume but within the same organism) was investigated in rats. It was possible to demonstrate the effects on growth locally and abscopally when x-ray doses of 400 and 800 r were delivered to the lower extremity and when 800 r was delivered to the knee alone. A distinction between abscopal effects after local irradiation and systemic effects after whole-body irradiation is discussed. The weights of control and irradiated animals were similar for the first 21 days, during which period they did not exhibit any untowardmore » effects of irradiation. However, after 21 days there was a decrease in weight gain, which persisted until the 72nd day. Group A (controls) was the heaviest group, with a mean weight of 412 g. Group B (800 r to the left hind extremity) had a mean weight of 378. Group C (400 r to the left hind extremity) and Group D (800 r to the left knee) exhibited mean weights of 391 and 394 g, respectively. Roentgenographic measurements revealed that all animals receiving irradiation had retardation in the growth of the irradiated tibiae, which were shorter than both the control and the contralateral (unirradiated) tibiae. Only the animals that had received 800 r to their leff hind extremity showed significant differences in the lengths of their unirradiated bones compared with the bones of the control animals of Group A, that is, a significant abscopal growth retardation. Although the abscopal effect appeared to be associated with the volume of tissue irradiated, the way this effect is mediated is not known. The weight gains of the animals demonstrated a strong association between decrease in weight gain, the volume of tissue irradiated, and the dose administered. The impaired weight gsin roughly paralleled the abscopal retardation of bone growth. The animals which received the highest dose of irradiation, 800 r, to the largest volume of tissue, 10% of the body volume, revealed the greatest deviation from the control group. It is concluded that irradiation effects in animals are composites of the responses of the whole organism to the injury, of the responses of local tissues, and vessels at their level of tissue organization, and of the responses of individual cells. All of these responses may be interdependent. The evidence indicates that a systemic inhibition of all bone growth and weight gain occurs when a sufficient volume of tissue is irradiated at a sufficiently high dosage. (BBB)« less

Localized direction selective responses in the dendrites of visual interneurons of the fly

PubMed Central

2010-01-01

Background The various tasks of visual systems, including course control, collision avoidance and the detection of small objects, require at the neuronal level the dendritic integration and subsequent processing of many spatially distributed visual motion inputs. While much is known about the pooled output in these systems, as in the medial superior temporal cortex of monkeys or in the lobula plate of the insect visual system, the motion tuning of the elements that provide the input has yet received little attention. In order to visualize the motion tuning of these inputs we examined the dendritic activation patterns of neurons that are selective for the characteristic patterns of wide-field motion, the lobula-plate tangential cells (LPTCs) of the blowfly. These neurons are known to sample direction-selective motion information from large parts of the visual field and combine these signals into axonal and dendro-dendritic outputs. Results Fluorescence imaging of intracellular calcium concentration allowed us to take a direct look at the local dendritic activity and the resulting local preferred directions in LPTC dendrites during activation by wide-field motion in different directions. These 'calcium response fields' resembled a retinotopic dendritic map of local preferred directions in the receptive field, the layout of which is a distinguishing feature of different LPTCs. Conclusions Our study reveals how neurons acquire selectivity for distinct visual motion patterns by dendritic integration of the local inputs with different preferred directions. With their spatial layout of directional responses, the dendrites of the LPTCs we investigated thus served as matched filters for wide-field motion patterns. PMID:20384983

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

PubMed

Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

2017-03-01

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells

NASA Technical Reports Server (NTRS)

Boyd, Nolan L.; Park, Heonyong; Yi, Hong; Boo, Yong Chool; Sorescu, George P.; Sykes, Michelle; Jo, Hanjoong

2003-01-01

Caveolae are plasmalemmal domains enriched with cholesterol, caveolins, and signaling molecules. Endothelial cells in vivo are continuously exposed to shear conditions, and their caveolae density and location may be different from that of static cultured cells. Here, we show that chronic shear exposure regulates formation and localization of caveolae and caveolin-1 in bovine aortic endothelial cells (BAEC). Chronic exposure (1 or 3 days) of BAEC to laminar shear increased the total number of caveolae by 45-48% above static control. This increase was due to a rise in the luminal caveolae density without changing abluminal caveolae numbers or increasing caveolin-1 mRNA and protein levels. Whereas some caveolin-1 was found in the plasma membrane in static-cultured cells, it was predominantly localized in the Golgi. In contrast, chronic shear-exposed cells showed intense caveolin-1 staining in the luminal plasma membrane with minimum Golgi association. The preferential luminal localization of caveolae may play an important role in endothelial mechanosensing. Indeed, we found that chronic shear exposure (preconditioning) altered activation patterns of two well-known shear-sensitive signaling molecules (ERK and Akt) in response to a step increase in shear stress. ERK activation was blunted in shear preconditioned cells, whereas the Akt response was accelerated. These results suggest that chronic shear stimulates caveolae formation by translocating caveolin-1 from the Golgi to the luminal plasma membrane and alters cell signaling responses.

Preventing malaria in the Peruvian Amazon: a qualitative study in Iquitos, Peru.

PubMed

Newell, Ian; Wiskin, Connie; Anthoney, James; Meza, Graciela; de Wildt, Gilles

2018-01-16

In Peru, despite decades of concerted control efforts, malaria remains a significant public health burden. Peru has recently exhibited a dramatic rise in malaria incidence, impeding South America's progress towards malaria elimination. The Amazon basin, in particular the Loreto region of Peru, has been identified as a target for the implementation of intensified control strategies, aiming for elimination. No research has addressed why vector control strategies in Loreto have had limited impact in the past, despite vector control elsewhere being highly effective in reducing malaria transmission. This study employed qualitative methods to explore factors limiting the success of vector control strategies in the region. Twenty semi-structured interviews were conducted among adults attending a primary care centre in Iquitos, Peru, together with 3 interviews with key informants (health care professionals). The interviews focussed on how local knowledge, together with social and cultural attitudes, determined the use of vector control methods. Five themes emerged. (a) Participants believed malaria to be embedded within their culture, and commonly blamed this for a lack of regard for prevention. (b) They perceived a shift in mosquito biting times to early evening, rendering night-time use of bed nets less effective. (c) Poor preventive practices were compounded by a consensus that malaria prevention was the government's responsibility, and that this reduced motivation for personal prevention. (d) Participants confused the purpose of space-spraying. (e) Participants' responses also exposed persisting misconceptions, mainly concerning the cause of malaria and best practices for its prevention. To eliminate malaria from the Americas, region-specific strategies need to be developed that take into account the local social and cultural contexts. In Loreto, further research is needed to explore the potential shift in biting behaviour of Anopheles darlingi, and how this interacts with the population's social behaviours and current use of preventive measures. Attitudes concerning personal responsibility for malaria prevention and long-standing misconceptions as to the cause of malaria and best preventive practices also need to be addressed.

Suppression of epidemic spreading in complex networks by local information based behavioral responses.

PubMed

Zhang, Hai-Feng; Xie, Jia-Rong; Tang, Ming; Lai, Ying-Cheng

2014-12-01

The interplay between individual behaviors and epidemic dynamics in complex networks is a topic of recent interest. In particular, individuals can obtain different types of information about the disease and respond by altering their behaviors, and this can affect the spreading dynamics, possibly in a significant way. We propose a model where individuals' behavioral response is based on a generic type of local information, i.e., the number of neighbors that has been infected with the disease. Mathematically, the response can be characterized by a reduction in the transmission rate by a factor that depends on the number of infected neighbors. Utilizing the standard susceptible-infected-susceptible and susceptible-infected-recovery dynamical models for epidemic spreading, we derive a theoretical formula for the epidemic threshold and provide numerical verification. Our analysis lays on a solid quantitative footing the intuition that individual behavioral response can in general suppress epidemic spreading. Furthermore, we find that the hub nodes play the role of "double-edged sword" in that they can either suppress or promote outbreak, depending on their responses to the epidemic, providing additional support for the idea that these nodes are key to controlling epidemic spreading in complex networks.

Suppression of epidemic spreading in complex networks by local information based behavioral responses

NASA Astrophysics Data System (ADS)

Zhang, Hai-Feng; Xie, Jia-Rong; Tang, Ming; Lai, Ying-Cheng

2014-12-01

The interplay between individual behaviors and epidemic dynamics in complex networks is a topic of recent interest. In particular, individuals can obtain different types of information about the disease and respond by altering their behaviors, and this can affect the spreading dynamics, possibly in a significant way. We propose a model where individuals' behavioral response is based on a generic type of local information, i.e., the number of neighbors that has been infected with the disease. Mathematically, the response can be characterized by a reduction in the transmission rate by a factor that depends on the number of infected neighbors. Utilizing the standard susceptible-infected-susceptible and susceptible-infected-recovery dynamical models for epidemic spreading, we derive a theoretical formula for the epidemic threshold and provide numerical verification. Our analysis lays on a solid quantitative footing the intuition that individual behavioral response can in general suppress epidemic spreading. Furthermore, we find that the hub nodes play the role of "double-edged sword" in that they can either suppress or promote outbreak, depending on their responses to the epidemic, providing additional support for the idea that these nodes are key to controlling epidemic spreading in complex networks.

Bipedal vs. unipedal: a comparison between one-foot and two-foot driving in a driving simulator.

PubMed

Wang, Dong-Yuan Debbie; Richard, F Dan; Cino, Cullen R; Blount, Trevin; Schmuller, Joseph

2017-04-01

Is it better to drive with one foot or with two feet? Although two-foot driving has fostered interminable debate in the media, no scientific and systematic research has assessed this issue and federal and local state governments have provided no answers. The current study compared traditional unipedal (one-foot driving, using the right foot to control the accelerator and the brake pedal) with bipedal (two-foot driving, using the right foot to control the accelerator and the left foot to control the brake pedal) responses to a visual stimulus in a driving simulator study. Each of 30 undergraduate participants drove in a simulated driving scenario. They responded to a STOP sign displayed on the centre of the screen by bringing their vehicle to a complete stop. Brake RT was shorter under the bipedal condition, while throttle RT showed advantage under the unipedal condition. Stopping time and distance showed a bipedal advantage, however. We discuss further limitations of the current study and implications in a driving task. Before drawing any conclusions from the simulator study, further on-road driving tests are necessary to confirm these obtained bipedal advantages. Practitioner Summary: Traditional unipedal (using the right foot to control the accelerator and the brake pedal) with bipedal (using the right foot to control the accelerator and the left foot to control the brake pedal) responses to a visual stimulus in a driving simulator were compared. Our results showed a bipedal advantage. Promotion: Although two-foot driving has fostered interminable debate in the media, no scientific and systematic research has assessed this issue and federal and local state governments have provided no answers. Traditional (one-foot driving, using the right foot to control the accelerator and the brake pedal) with bipedal (using the right foot to control the accelerator and the left foot to control the brake pedal) responses to a visual stimulus in a simulated driving study were compared. Throttle reaction time was faster in the unipedal condition whereas brake reaction time, stopping time and stopping distance showed a bipedal advantage. We discuss further theoretical issues and implications in a driving task.

Actin-based gravity-sensing mechanisms in unicellular plant model systems

NASA Astrophysics Data System (ADS)

Braun, Markus; Limbach, Christoph

2005-08-01

Considerable progress has been made in the understanding of the molecular and cellular mechanisms underlying gravity sensing and gravity-oriented polarized growth in single-celled rhizoids and protonemata of the characean algae. It is well known that the actin cytoskeleton plays a key role in these processes. Numerous actin-binding proteins control apical actin polymerization and the dynamic remodeling of the actin arrangement. An actomyosin-based system mediates the delivery and incorporation of secretory vesicles at the growing tip and coordinates the tip-high gradient of cytoplasmic free calcium which is required for local exocytosis. Additionally, the actomyosin system precisely controls the position of statoliths and, upon a change in orientation relative to the gravity vector, directs sedimenting statoliths to the confined graviperception sites of the plasma membrane where gravitropic signalling is initiated. The upward growth response of protonemata is preceded by an actin-dependent relocalization of the Ca2+-gradient to the upper flank. The downward growth response of rhizoids, however, is caused by differential growth of the opposite flankes due to a local reduction of cytoplasmic free calcium limited to the plasma membrane area where statoliths are sedimented. Thus, constant actin polymerization in the growing tip and the spatiotemporal control of actin remodeling are essential for gravity sensing and gravity-oriented polarized growth of characean rhizoids and protonemata.

Multimodal nonlinear nanophotonics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kivshar, Yuri S.

2017-05-01

Nonlinear nanophotonics is a rapidly developing field of research with many potential applications for the design of nonlinear nanoantennas, light sources, nanolasers, and ultrafast miniature metadevices. A tight confinement of the local electromagnetic fields in resonant photonic nanostructures can boost nonlinear optical effects, thus offering versatile opportunities for the subwavelength control of light. To achieve the desired functionalities, it is essential to gain flexible control over the near- and far-field properties of nanostructures. To engineer nonlinear scattering from resonant nanoscale elements, both modal and multipolar control of the nonlinear response are widely exploited for enhancing the near-field interaction and optimizing the radiation directionality. Motivated by the recent progress of all-dielectric nanophotonics, where the electric and magnetic multipolar contributions may become comparable, here we review the advances in the recently emerged field of multipolar nonlinear nanophotonics, starting from earlier relevant studies of metallic and metal-dielectric structures supporting localized plasmonic resonances to then discussing the latest results for all-dielectric nanostructures driven by Mie-type multipolar resonances and optically induced magnetic response. These recent developments suggest intriguing opportunities for a design of nonlinear subwavelength light sources with reconfigurable radiation characteristics and engineering large effective optical nonlinearities at the nanoscale, which could have important implications for novel nonlinear photonic devices operating beyond the diffraction limit.

Local health department 2009 H1N1 influenza vaccination clinics-CDC staffing model comparison and other best practices.

PubMed

Porter, Dayna; Hall, Mark; Hartl, Brian; Raevsky, Cathy; Peacock, Roberta; Kraker, David; Walls, Sandra; Brink, Gail

2011-01-01

Mass vaccination clinic staffing models, such as the Centers for Disease Control and Prevention Large-Scale Vaccination Clinic Output and Staff Estimates: An Example, provide guidance on appropriate roles and number of staff for successful mass vaccination clinics within local and state health departments. The Kent County Health Department used this model as a starting point for mass vaccination clinics in response to 2009 H1N1 influenza. In addition to discussion of successful modification of the Centers for Disease Control and Prevention model to maximize local health department mass vaccination clinic efficiency, additional best practices including use of the Incident Command System and a reservation system are provided. Use of the provided modified staffing model and additional best practices will increase the success of health department mass vaccination clinics, and should be considered not only for future public health emergencies, but also for seasonal influenza vaccination campaigns.

Walking patterns induced by learned odors in the honeybee, Apis mellifera L.

PubMed

Yamashita, Toshiya; Haupt, S Shuichi; Ikeno, Hidetoshi; Ai, Hiroyuki

2016-01-01

The odor localization strategy induced by odors learned via differential conditioning of the proboscis extension response was investigated in honeybees. In response to reward-associated but not non-reward-associated odors, learners walked longer paths than non-learners and control bees. When orange odor reward association was learned, the path length and the body turn angles were small during odor stimulation and greatly increased after stimulation ceased. In response to orange odor, bees walked locally with alternate left and right turns during odor stimulation to search for the reward-associated odor source. After odor stimulation, bees walked long paths with large turn angles to explore the odor plume. For clove odor, learning-related modulations of locomotion were less pronounced, presumably due to a spontaneous preference for orange in the tested population of bees. This study is the first to describe how an odor-reward association modulates odor-induced walking in bees. © 2016. Published by The Company of Biologists Ltd.

A Conserved Dopamine-Cholecystokinin Signaling Pathway Shapes Context–Dependent Caenorhabditis elegans Behavior

PubMed Central

Bhattacharya, Raja; Touroutine, Denis; Barbagallo, Belinda; Climer, Jason; Lambert, Christopher M.; Clark, Christopher M.; Alkema, Mark J.; Francis, Michael M.

2014-01-01

An organism's ability to thrive in changing environmental conditions requires the capacity for making flexible behavioral responses. Here we show that, in the nematode Caenorhabditis elegans, foraging responses to changes in food availability require nlp-12, a homolog of the mammalian neuropeptide cholecystokinin (CCK). nlp-12 expression is limited to a single interneuron (DVA) that is postsynaptic to dopaminergic neurons involved in food-sensing, and presynaptic to locomotory control neurons. NLP-12 release from DVA is regulated through the D1-like dopamine receptor DOP-1, and both nlp-12 and dop-1 are required for normal local food searching responses. nlp-12/CCK overexpression recapitulates characteristics of local food searching, and DVA ablation or mutations disrupting muscle acetylcholine receptor function attenuate these effects. Conversely, nlp-12 deletion reverses behavioral and functional changes associated with genetically enhanced muscle acetylcholine receptor activity. Thus, our data suggest that dopamine-mediated sensory information about food availability shapes foraging in a context-dependent manner through peptide modulation of locomotory output. PMID:25167143

Spinning Reserve From Hotel Load Response: Initial Progress

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

Kueck, John D; Kirby, Brendan J

2008-11-01

This project was motivated by the fundamental match between hotel space conditioning load response capability and power system contingency response needs. As power system costs rise and capacity is strained demand response can provide a significant system reliability benefit at a potentially attractive cost. At ORNL s suggestion, Digital Solutions Inc. adapted its hotel air conditioning control technology to supply power system spinning reserve. This energy saving technology is primarily designed to provide the hotel operator with the ability to control individual room temperature set-points based upon occupancy (25% to 50% energy savings based on an earlier study [Kirby andmore » Ally, 2002]). DSI added instantaneous local load shedding capability in response to power system frequency and centrally dispatched load shedding capability in response to power system operator command. The 162 room Music Road Hotel in Pigeon Forge Tennessee agreed to host the spinning reserve test. The Tennessee Valley Authority supplied real-time metering equipment in the form of an internet connected Dranetz-BMI power quality meter and monitoring expertise to record total hotel load during both normal operations and test results. The Sevier County Electric System installed the metering. Preliminary testing showed that hotel load can be curtailed by 22% to 37% depending on the outdoor temperature and the time of day. These results are prior to implementing control over the common area air conditioning loads. Testing was also not at times of highest system or hotel loading. Full response occurred in 12 to 60 seconds from when the system operator s command to shed load was issued. The load drop was very rapid, essentially as fast as the 2 second metering could detect, with all units responding essentially simultaneously. Load restoration was ramped back in over several minutes. The restoration ramp can be adjusted to the power system needs. Frequency response testing was not completed. Initial testing showed that the units respond very quickly. Problems with local power quality generated false low frequency signals which required testing to be stopped. This should not be a problem in actual operation since the frequency trip points will be staggered to generate a droop curve which mimics generator governor response. The actual trip frequencies will also be low enough to avoid power quality problems. The actual trip frequencies are too low to generate test events with sufficient regularity to complete testing in a reasonable amount of time. Frequency response testing will resume once the local power quality problem is fully understood and reasonable test frequency settings can be determined. Overall the preliminary testing was extremely successful. The hotel response capability matches the power system reliability need, being faster than generation response and inherently available when the power system is under the most stress (times of high system and hotel load). Periodic testing is scheduled throughout the winter and spring to characterize hotel response capability under a full range of conditions. More extensive testing will resume when summer outdoor temperatures are again high enough to fully test hotel response.« less

Long term results after fractionated stereotactic radiotherapy (FSRT) in patients with craniopharyngioma: maximal tumor control with minimal side effects.

PubMed

Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E

2014-09-16

There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6-70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 - 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 - 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one's initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

PubMed

Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

2009-03-17

The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory parameters is not yet helpful in diagnostic and follow-up of CRPS I.

Brassinosteroid and gibberellin control of seedling traits in maize (Zea mays L.).

PubMed

Hu, Songlin; Sanchez, Darlene L; Wang, Cuiling; Lipka, Alexander E; Yin, Yanhai; Gardner, Candice A C; Lübberstedt, Thomas

2017-10-01

In this study, we established two doubled haploid (DH) libraries with a total of 207 DH lines. We applied BR and GA inhibitors to all DH lines at seedling stage and measured seedling BR and GA inhibitor responses. Moreover, we evaluated field traits for each DH line (untreated). We conducted genome-wide association studies (GWAS) with 62,049 genome wide SNPs to explore the genetic control of seedling traits by BR and GA. In addition, we correlate seedling stage hormone inhibitor response with field traits. Large variation for BR and GA inhibitor response and field traits was observed across these DH lines. Seedling stage BR and GA inhibitor response was significantly correlate with yield and flowering time. Using three different GWAS approaches to balance false positive/negatives, multiple SNPs were discovered to be significantly associated with BR/GA inhibitor responses with some localized within gene models. SNPs from gene model GRMZM2G013391 were associated with GA inhibitor response across all three GWAS models. This gene is expressed in roots and shoots and was shown to regulate GA signaling. These results show that BRs and GAs have a great impact for controlling seedling growth. Gene models from GWAS results could be targets for seeding traits improvement. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-Term Citalopram Treatment Alters the Stress Responses of the Cortical Dopamine and Noradrenaline Systems: the Role of Cortical 5-HT1A Receptors

PubMed Central

Kaneko, Fumi; Kishikawa, Yuki; Hanada, Yuuki; Yamada, Makiko; Kakuma, Tatsuyuki; Kawahara, Hiroshi; Nishi, Akinori

2016-01-01

Background: Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants. Methods: The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis. Results: Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and α2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response. Conclusions: Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress. PMID:27029212

Negative index of refraction in a four-level system with magnetoelectric cross coupling and local field corrections

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

Bello, F.

2011-07-15

This research focuses on a coherently driven four-level atomic medium with the aim of inducing a negative index of refraction while taking into consideration local field corrections as well as magnetoelectric cross coupling (i.e.,chirality) within the material's response functions. Two control fields are used to render the medium transparent for a probe field which simultaneously couples to an electric and a magnetic dipole transition, thus allowing one to test the permittivity and permeability of the material at the same time. Numerical simulations show that a negative index of refraction with low absorption can be obtained for a range of probemore » detunings while depending on number density and the ratio between the intensities of the control fields.« less

Biocontrol in an impulsive predator-prey model.

PubMed

Terry, Alan J

2014-10-01

We study a model for biological pest control (or "biocontrol") in which a pest population is controlled by a program of periodic releases of a fixed yield of predators that prey on the pest. Releases are represented as impulsive increases in the predator population. Between releases, predator-pest dynamics evolve according to a predator-prey model with some fairly general properties: the pest population grows logistically in the absence of predation; the predator functional response is either of Beddington-DeAngelis type or Holling type II; the predator per capita birth rate is bounded above by a constant multiple of the predator functional response; and the predator per capita death rate is allowed to be decreasing in the predator functional response and increasing in the predator population, though the special case in which it is constant is permitted too. We prove that, when the predator functional response is of Beddington-DeAngelis type and the predators are not sufficiently voracious, then the biocontrol program will fail to reduce the pest population below a particular economic threshold, regardless of the frequency or yield of the releases. We prove also that our model possesses a pest-eradication solution, which is both locally and globally stable provided that predators are sufficiently voracious and that releases occur sufficiently often. We establish, curiously, that the pest-eradication solution can be locally stable whilst not being globally stable, the upshot of which is that, if we delay a biocontrol response to a new pest invasion, then this can change the outcome of the response from pest eradication to pest persistence. Finally, we state a number of specific examples for our model, and, for one of these examples, we corroborate parts of our analysis by numerical simulations. Copyright © 2014 Elsevier Inc. All rights reserved.

Laminar circuit organization and response modulation in mouse visual cortex

PubMed Central

Olivas, Nicholas D.; Quintanar-Zilinskas, Victor; Nenadic, Zoran; Xu, Xiangmin

2012-01-01

The mouse has become an increasingly important animal model for visual system studies, but few studies have investigated local functional circuit organization of mouse visual cortex. Here we used our newly developed mapping technique combining laser scanning photostimulation (LSPS) with fast voltage-sensitive dye (VSD) imaging to examine the spatial organization and temporal dynamics of laminar circuit responses in living slice preparations of mouse primary visual cortex (V1). During experiments, LSPS using caged glutamate provided spatially restricted neuronal activation in a specific cortical layer, and evoked responses from the stimulated layer to its functionally connected regions were detected by VSD imaging. In this study, we first provided a detailed analysis of spatiotemporal activation patterns at specific V1 laminar locations and measured local circuit connectivity. Then we examined the role of cortical inhibition in the propagation of evoked cortical responses by comparing circuit activity patterns in control and in the presence of GABAa receptor antagonists. We found that GABAergic inhibition was critical in restricting layer-specific excitatory activity spread and maintaining topographical projections. In addition, we investigated how AMPA and NMDA receptors influenced cortical responses and found that blocking AMPA receptors abolished interlaminar functional projections, and the NMDA receptor activity was important in controlling visual cortical circuit excitability and modulating activity propagation. The NMDA receptor antagonist reduced neuronal population activity in time-dependent and laminar-specific manners. Finally, we used the quantitative information derived from the mapping experiments and presented computational modeling analysis of V1 circuit organization. Taken together, the present study has provided important new information about mouse V1 circuit organization and response modulation. PMID:23060751

Extrinsic polarization-controlled optical anisotropy in plasmon-black phosphorus coupled system

NASA Astrophysics Data System (ADS)

Liu, Zizhuo; Wells, Spencer A.; Butun, Serkan; Palacios, Edgar; Hersam, Mark C.; Aydin, Koray

2018-07-01

Two-dimensional black phosphorus (BP) has drawn extensive research interest due to its promising anisotropic photonic and electronic properties. Here, we study anisotropic optical absorption and photoresponse of exfoliated BP flakes at visible frequencies. We enhance this intrinsic optical anisotropy in BP flakes by coupling plasmonic rectangular nanopatch arrays that support localized surface plasmon resonances. In particular, by combining extrinsic anisotropic plasmonic nanostructures lithographically aligned with intrinsically anisotropic BP flakes, we demonstrate for the first time a combined anisotropic plasmonic-semiconductor coupling that provides significant control over the polarization-dependent optical properties of the plasmon-BP hybrid material system, enhancing polarization-sensitive responses to a larger degree. This hybrid material system not only unveils the plasmon-enhanced mechanisms in BP, but also provides novel controllable functionalities in optoelectronic device applications involving polarization-sensitive optical and electrical responses.

Extrinsic polarization-controlled optical anisotropy in plasmon-black phosphorus coupled system.

PubMed

Liu, Zizhuo; Wells, Spencer A; Butun, Serkan; Palacios, Edgar; Hersam, Mark C; Aydin, Koray

2018-07-13

Two-dimensional black phosphorus (BP) has drawn extensive research interest due to its promising anisotropic photonic and electronic properties. Here, we study anisotropic optical absorption and photoresponse of exfoliated BP flakes at visible frequencies. We enhance this intrinsic optical anisotropy in BP flakes by coupling plasmonic rectangular nanopatch arrays that support localized surface plasmon resonances. In particular, by combining extrinsic anisotropic plasmonic nanostructures lithographically aligned with intrinsically anisotropic BP flakes, we demonstrate for the first time a combined anisotropic plasmonic-semiconductor coupling that provides significant control over the polarization-dependent optical properties of the plasmon-BP hybrid material system, enhancing polarization-sensitive responses to a larger degree. This hybrid material system not only unveils the plasmon-enhanced mechanisms in BP, but also provides novel controllable functionalities in optoelectronic device applications involving polarization-sensitive optical and electrical responses.

Experiences of an Engineer working in Reactor Safety and Emergency Response

NASA Astrophysics Data System (ADS)

Osborn, Douglas

2015-04-01

The U.S. Department of Energy's Federal Radiological Monitoring and Assessment Center Consequence Management Home Team (FRMAC/CMHT) Assessment Scientist's roles, responsibilities incorporate the FRMAC with other federal, state, and local agencies during a nuclear/radiological emergency. Before the Consequence Management Response Team arrives on-site, the FRMAC/CMHT provides technical and logistical support to the FRMAC and to state, local, and tribal authorities following a nuclear/radiological event. The FRMAC/CMHT support includes analyzing event data, evaluating hazards that relate to protection of the public, and providing event information and data products to protective action decision makers. The Assessment Scientist is the primary scientist responsible for performing calculations and analyses and communicating results to the field during any activation of the FRMAC/CMHT assets. As such, the FRMAC/CMHT Assessment Scientist has a number of different roles and responsibilities to fill depending upon the type of response that is required. Additionally, the Sandia National Laboratories (SNL) Consequence Assessment Team (CAT) Consequence Assessor roles, responsibilities involve hazardous materials operational emergency at SNL New Mexico facilities (SNL/NM) which include loss of control over radioactive, chemical, or explosive hazardous materials. When a hazardous materials operational emergency occurs, key decisions must be made in order to regain control over the hazards, protect personnel from the effects of the hazards, and mitigate impacts on operations, facilities, property, and the environment. Many of these decisions depend in whole or in part on the evaluation of potential consequences from a loss of control over the hazards. As such, the CAT has a number of different roles and responsibilities to fill depending upon the type of response that is required. Primary consequence-based decisions supported by the CAT during a hazardous materials operational emergency at SNL/NM include: (1) Onsite Protective Actions (2) Offsite Protective Action Recommendations (3) Event categorization (4) Event classification Other consequence-based decisions supported by the CAT include: (1) Response planning and operations (2) Event termination (3) Reentry planning and operations (4) Recovery planning and operations Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration.

Non-Uniform Thickness Electroactive Device

NASA Technical Reports Server (NTRS)

Su, Ji (Inventor); Harrison, Joycelyn S. (Inventor)

2006-01-01

An electroactive device comprises at least two layers of material, wherein at least one layer is an electroactive material and wherein at least one layer is of non-uniform thickness. The device can be produced in various sizes, ranging from large structural actuators to microscale or nanoscale devices. The applied voltage to the device in combination with the non-uniform thickness of at least one of the layers (electroactive and/or non-electroactive) controls the contour of the actuated device. The effective electric field is a mathematical function of the local layer thickness. Therefore, the local strain and the local bending/ torsion curvature are also a mathematical function of the local thickness. Hence the thinnest portion of the actuator offers the largest bending and/or torsion response. Tailoring of the layer thicknesses can enable complex motions to be achieved.

The Banana Fruit SINA Ubiquitin Ligase MaSINA1 Regulates the Stability of MaICE1 to be Negatively Involved in Cold Stress Response.

PubMed

Fan, Zhong-Qi; Chen, Jian-Ye; Kuang, Jian-Fei; Lu, Wang-Jin; Shan, Wei

2017-01-01

The regulation of ICE1 protein stability is important to ensure effective cold stress response, and is extensively studied in Arabidopsis . Currently, how ICE1 stability in fruits under cold stress is controlled remains largely unknown. Here, we reported the possible involvement of a SEVEN IN ABSENTIA (SINA) ubiquitin ligase MaSINA1 from banana fruit in affecting MaICE1 stability. MaSINA1 was identified based on a yeast two-hybrid screening using MaICE1 as bait. Further yeast two-hybrid, pull-down, bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (CoIP) assays confirmed that MaSINA1 interacted with MaICE1. The expression of MaSINA1 was repressed by cold stress. Subcellular localization analysis in tobacco leaves showed that MaSINA1 was localized predominantly in the nucleus. In vitro ubiquitination assay showed that MaSINA1 possessed E3 ubiquitin ligase activity. More importantly, in vitro and semi- in vivo experiments indicated that MaSINA1 can ubiquitinate MaICE1 for the 26S proteasome-dependent degradation, and therefore suppressed the transcriptional activation of MaICE1 to MaNAC1, an important regulator of cold stress response of banana fruit. Collectively, our data reveal a mechanism in banana fruit for control of the stability of ICE1 and for the negative regulation of cold stress response by a SINA E3 ligase via the ubiquitin proteasome system.

Rate and extent of protein localization is controlled by peptide-binding domain association kinetics and morphology.

PubMed

Mills, Evan; Truong, Kevin

2009-06-01

Protein localization is an important regulatory mechanism in many cell signaling pathways such as cytoskeletal organization and genetic regulation. The specific mechanism of protein localization determines the kinetics and morphological constraints of protein translocation, and thus affects the rate and extent of localization. To investigate the affect of localization kinetics and morphology on protein localization, we designed a protein localization system based on Ca(2+)-calmodulin and Src homology 3 domain binding peptides that can translocate between specific localizations in response to a Ca(2+) signal. We used a stochastic biomolecular simulator to predict that such a protein localization system will exhibit slower and less complete translocations when the association kinetics of a binding domain and peptide are reduced. As well, we predicted that increasing the diffusion resistance by manipulating the morphology of the system would similarly impair translocation speed and completeness. We then constructed a network of synthetic fusion proteins and showed that these predictions could be qualitatively confirmed in vitro. This work provides a basis for explaining the different characteristics (rate and extent) of protein transport and localization in cells as a consequence of the kinetics and morphology of the transport mechanism.

A heating-superfusion platform technology for the investigation of protein function in single cells.

PubMed

Xu, Shijun; Ainla, Alar; Jardemark, Kent; Jesorka, Aldo; Jeffries, Gavin D M

2015-01-06

Here, we report on a novel approach for the study of single-cell intracellular enzyme activity at various temperatures, utilizing a localized laser heating probe in combination with a freely positionable microfluidic perfusion device. Through directed exposure of individual cells to the pore-forming agent α-hemolysin, we have controlled the membrane permeability, enabling targeted delivery of the substrate. Mildly permeabilized cells were exposed to fluorogenic substrates to monitor the activity of intracellular enzymes, while adjusting the local temperature surrounding the target cells, using an infrared laser heating system. We generated quantitative estimates for the intracellular alkaline phosphatase activity at five different temperatures in different cell lines, constructing temperature-response curves of enzymatic activity at the single-cell level. Enzymatic activity was determined rapidly after cell permeation, generating five-point temperature-response curves within just 200 s.

Reproducibility of flow mediated skin fluorescence to assess microvascular function.

PubMed

Hellmann, Marcin; Tarnawska, Maria; Dudziak, Maria; Dorniak, Karolina; Roustit, Matthieu; Cracowski, Jean-Luc

2017-09-01

Recent technical developments enable skin fluorescence to be quantified in vivo in humans. The present study aimed at determining whether flow mediated skin fluorescence was reproducible, sensitive to changes within an individual, and if it could differ between patients with coronary artery disease and healthy volunteers. First, forearm flow mediated skin fluorescence recorded during and after brachial artery occlusion was assessed following successive forearm occlusion periods (1, 2, 3 and 5min) and expressed as ischemic and hyperemic responses (as % of baseline). Secondly, 3min flow mediated skin fluorescence was assessed before and after 10min local cooling to 15°C. In a third protocol, the inter-day reproducibility of ischemic and hyperemic responses to 3min occlusion was tested at an interval of 7days, and compared between healthy controls and patients with coronary artery disease (CAD). In the first protocol, we observed a time dependent increase in the ischemic and hyperemic responses to occlusion. Next, we observed a lower hyperemic response after local cooling (9.8±4.2 versus 17.8±2.5% respectively, P<0.001), while in contrast, the ischemic response was higher and exhibited greater variability (23±15 versus 11.8±6.4%; P=0.028). In the third protocol, the inter-day reproducibility of flow mediated skin fluorescence for a 3min occlusion period was excellent. The ischemic response was significantly lower in CAD patients than in healthy controls (6.7±4.8% vs 14.7±6.8% respectively, P<0.001). Similarly, the hyperemic response was significantly decreased in the CAD group compared to healthy controls (11.6±3.6% vs 19.5±5.4% respectively, P<0.001). We show that quantifying the ischemic and hyperemic flow mediated skin fluorescence is feasible, reproducible, sensitive to acute changes in skin blood flow, and distinguishes patients populations. However, more data are needed to evaluate the correlation with other methods or specific biochemical endothelial markers. Copyright © 2017 Elsevier Inc. All rights reserved.

U.S. Geological Survey Ground-Water Climate Response Network

USGS Publications Warehouse

,

2007-01-01

The U.S. Geological Survey serves the Nation by providing reliable hydrologic information used by others to manage the Nation's water resources. The U.S. Geological Survey (USGS) measures more than 20,000 wells each year for a variety of objectives as part of Federal programs and in cooperation with State and local agencies. Water-level data are collected using consistent data-collection and quality-control methods. A small subset of these wells meets the criteria necessary to be included in a 'Climate Response Network' of wells designed to illustrate the response of the ground-water system to climate variations nationwide. The primary purpose of the Climate Response Network is to portray the effect of climate on ground-water levels in unconfined aquifers or near-surface confined aquifers that are minimally affected by pumping or other anthropogenic stresses. The Climate Response Network Web site (http://groundwaterwatch.usgs.gov/) is the official USGS Web site for illustrating current ground-water conditions in the United States and Puerto Rico. The Climate Response Network Web pages provide information on ground-water conditions at a variety of scales. A national map provides a broad overview of water-table conditions across the Nation. State maps provide a more local picture of ground-water conditions. Site pages provide the details about a specific well.

Ramp - Metering Algorithms Evaluated within Simplified Conditions

NASA Astrophysics Data System (ADS)

Janota, Aleš; Holečko, Peter; Gregor, Michal; Hruboš, Marián

2017-12-01

Freeway networks reach their limits, since it is usually impossible to increase traffic volumes by indefinitely extending transport infrastructure through adding new traffic lanes. One of the possible solutions is to use advanced intelligent transport systems, particularly ramp metering systems. The paper shows how two particular algorithms of local and traffic-responsive control (Zone, ALINEA) can be adapted to simplified conditions corresponding to Slovak freeways. Both control strategies are modelled and simulated using PTV Vissim software, including the module VisVAP. Presented results demonstrate the properties of both control strategies, which are compared mutually as well as with the initial situation in which no control strategy is applied

Radiotherapy in the treatment of solitary plasmacytoma.

PubMed

Jyothirmayi, R; Gangadharan, V P; Nair, M K; Rajan, B

1997-05-01

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

The Role of the Independent Sector in a Modern Democratic Society. An European View.

ERIC Educational Resources Information Center

Mason, Peter

This document discusses the shift in democratic countries toward the allocation of responsibility for the organization and control of education in the public system by decentralization from the center to the local community and beyond, to the governing bodies of individual schools, and to the parents who are represented on school councils. This…

Priority setting for government investment in forestry conservation schemes-an example from New Zealand

Treesearch

Colin L. O' Loughlin

1991-01-01

In New Zealand responsibility for funding flood protection and erosion prevention and control projects rests largely with local regional authorities. However, in 1988 Central Government decided to provide direct funding for a major forestry conservation scheme in the erosion-susceptible East Coast region. Government's investment decision was influenced by a number...

The Great Balancing Act: Financial Equity and Local Control. Can Vermont's Act 60 Do It?

ERIC Educational Resources Information Center

Jimerson, Lorna

Vermont's Equal Educational Opportunity Act of 1997 (Act 60) has attracted attention because of its funding and quality components, and the highly publicized responses to its implementation. A key feature is its "recapture" provision in which property-wealthy towns contribute to a state educational fund that helps support education in…

EPA'S CONTROL TECHNOLOGY APPROACH TO ASSISTING STATES AND REGIONS WITH AIR TOXICS PROBLEMS: FIVE CASE STUDIES

EPA Science Inventory

The paper discusses a new U.S. strategy to reduce public exposure to toxic air pollutants in the ambient air. he strategy calls for state and local authorities to take on more of the lead regulatory role. he shift in emphasis and responsibility prompted EPA's Offices of Research ...

Stability of spanwise-modulated flows behind backward-facing steps

NASA Astrophysics Data System (ADS)

Boiko, A. V.; Dovgal, A. V.; Sorokin, A. M.

2017-10-01

An overview and synthesis of researches on development of local vortical disturbances in laminar separated flows downstream of backward-facing steps, in which the velocity field depends essentially on two variables are given. Peculiarities of transition to turbulence in such spatially inhomogeneous separated zones are discussed. The experimental data are supplemented by the linear stability characteristics of model velocity profiles of the separated flow computed using both the classical local formulation and the nonlocal approach based on the Floquet theory for partial differential equations with periodic coefficients. The results clarify the response of the local separated flows to their modulation with stationary geometrical and temperature inhomogeneities. The results can be useful for the development of new methods of laminar separation control.

Escherichia coli infection induces distinct local and systemic transcriptome responses in the mammary gland.

PubMed

Mitterhuemer, Simone; Petzl, Wolfram; Krebs, Stefan; Mehne, Daniel; Klanner, Andrea; Wolf, Eckhard; Zerbe, Holm; Blum, Helmut

2010-02-25

Coliform bacteria are the most common etiologic agents in severe mastitis of cows. Escherichia coli infections are mostly restricted to a single udder quarter whereas neighboring quarters stay clinically inapparent, implicating the presence of a systemic defense reaction. To address its underlying mechanism, we performed a transcriptome study of mammary tissue from udder quarters inoculated with E. coli (6 h and 24 h post infection), from neighboring quarters of the same animals, and from untreated control animals. After 6 h 13 probe sets of differentially expressed genes (DEG) were detected in infected quarters versus control animals. Eighteen hours later 2154 and 476 DEG were found in infected and in neighboring quarters vs. control animals. Cluster analysis revealed DEG found only in infected quarters (local response) and DEG detected in both infected and neighboring quarters (systemic response). The first group includes genes mainly involved in immune response and inflammation, while the systemic reaction comprises antigen processing and presentation, cytokines, protein degradation and apoptosis. Enhanced expression of antimicrobial genes (S100A8, S100A9, S100A12, CXCL2, GNLY), acute phase genes (LBP, SAA3, CP, BF, C6, C4BPA, IF), and indicators of oxidative stress (GPX3, MT1A, MT2A, SOD2) point to an active defense reaction in infected and neighboring healthy quarters. Its early onset is indicated by increased transcription of NFIL3 at 6 h. NFIL3 is a predicted regulator of many genes of the systemic response at 24 h. The significance of our transcriptome study was evidenced by some recent findings with candidate gene based approaches. The discovery and holistic analysis of an extensive systemic reaction in the mammary gland significantly expands the knowledge of host-pathogen interactions in mastitis which may be relevant for the development of novel therapies and for genetic selection towards mastitis resistance.

Case report: Irreversible electroporation for locally advanced pancreatic cancer.

PubMed

Orcutt, Sonia; Kis, Bela; Malafa, Mokenge

2017-01-01

For patients with pancreatic adenocarcinoma who are not candidates for surgical resection, long-term survival is poor, even with currently available systemic and radiation therapy options. However, for those with locally advanced disease who do not have distant metastasis, locoregional control of the tumor has the potential to improve long-term outcomes. A newly developed technology, irreversible electroporation, has advantages over traditional thermal ablation with unresectable cancers in this location. In our case report, we describe the first patient treated with irreversible electroporation at our institution for locally advanced pancreatic cancer. The patient is a 63-year-old man who had a partial response to standard chemotherapy and radiation, but was found on operative assessment to have persistently unresectable disease. He therefore underwent irreversible electroporation to the pancreatic mass. His postoperative course was complicated by delayed gastric emptying and wound infection. Three months after surgery, he had no evidence of distant or recurrent disease. Irreversible electroporation for locally advanced pancreatic cancer is an emerging technique which attempts to improve local control of locally advanced, non-metastatic pancreatic cancer. Early data have demonstrated the potential for improved long-term survival in these patients, although further studies are needed to confirm safety and efficacy of this technique. While there is a positive outlook for the use of irreversible electroporation for locally advanced pancreas cancer, there remain some uncertainties surrounding this therapy, which underscores the importance of future research in this area. Copyright © 2017. Published by Elsevier Ltd.

Improving infection control in general practice.

PubMed

Farrow, S C; Zeuner, D; Hall, C

1999-03-01

Infection control measures in the health care setting should protect patients and staff from cross-infection. The prevention of harm is an essential part of good medical practice and failure might result in professional misconduct proceedings by the General Medical Council (GMC) and prosecution under the Health and Safety at Work legislation, as well as civil liability. For a health authority, overall responsibility for public health includes arrangements for the control of communicable diseases and infection in hospital and the community (NHS Management Executive, 1993), a function usually led by the Consultant in Communicable Disease Control (CCDC). This paper describes one district's collaborative approach between public health and GPs to assess and improve local infection control standards.

Climate change and local public health in the United States: preparedness, programs and perceptions of local public health department directors.

PubMed

Maibach, Edward W; Chadwick, Amy; McBride, Dennis; Chuk, Michelle; Ebi, Kristie L; Balbus, John

2008-07-30

While climate change is inherently a global problem, its public health impacts will be experienced most acutely at the local and regional level, with some jurisdictions likely to be more burdened than others. The public health infrastructure in the U.S. is organized largely as an interlocking set of public agencies at the federal, state and local level, with lead responsibility for each city or county often residing at the local level. To understand how directors of local public health departments view and are responding to climate change as a public health issue, we conducted a telephone survey with 133 randomly selected local health department directors, representing a 61% response rate. A majority of respondents perceived climate change to be a problem in their jurisdiction, a problem they viewed as likely to become more common or severe over the next 20 years. Only a small minority of respondents, however, had yet made climate change adaptation or prevention a top priority for their health department. This discrepancy between problem recognition and programmatic responses may be due, in part, to several factors: most respondents felt personnel in their health department--and other key stakeholders in their community--had a lack of knowledge about climate change; relatively few respondents felt their own health department, their state health department, or the Centers for Disease Control and Prevention had the necessary expertise to help them create an effective mitigation or adaptation plan for their jurisdiction; and most respondents felt that their health department needed additional funding, staff and staff training to respond effectively to climate change. These data make clear that climate change adaptation and prevention are not currently major activities at most health departments, and that most, if not all, local health departments will require assistance in making this transition. We conclude by making the case that, through their words and actions, local health departments and their staff can and should play a role in alerting members of their community about the prospect of public health impacts from climate change in their jurisdiction.

Climate Change and Local Public Health in the United States: Preparedness, Programs and Perceptions of Local Public Health Department Directors

PubMed Central

Maibach, Edward W.; Chadwick, Amy; McBride, Dennis; Chuk, Michelle; Ebi, Kristie L.; Balbus, John

2008-01-01

While climate change is inherently a global problem, its public health impacts will be experienced most acutely at the local and regional level, with some jurisdictions likely to be more burdened than others. The public health infrastructure in the U.S. is organized largely as an interlocking set of public agencies at the federal, state and local level, with lead responsibility for each city or county often residing at the local level. To understand how directors of local public health departments view and are responding to climate change as a public health issue, we conducted a telephone survey with 133 randomly selected local health department directors, representing a 61% response rate. A majority of respondents perceived climate change to be a problem in their jurisdiction, a problem they viewed as likely to become more common or severe over the next 20 years. Only a small minority of respondents, however, had yet made climate change adaptation or prevention a top priority for their health department. This discrepancy between problem recognition and programmatic responses may be due, in part, to several factors: most respondents felt personnel in their health department–and other key stakeholders in their community–had a lack of knowledge about climate change; relatively few respondents felt their own health department, their state health department, or the Centers for Disease Control and Prevention had the necessary expertise to help them create an effective mitigation or adaptation plan for their jurisdiction; and most respondents felt that their health department needed additional funding, staff and staff training to respond effectively to climate change. These data make clear that climate change adaptation and prevention are not currently major activities at most health departments, and that most, if not all, local health departments will require assistance in making this transition. We conclude by making the case that, through their words and actions, local health departments and their staff can and should play a role in alerting members of their community about the prospect of public health impacts from climate change in their jurisdiction. PMID:18665266

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

PubMed Central

Pettipher, E. R.; Labasi, J. M.; Salter, E. D.; Stam, E. J.; Cheng, J. B.; Griffiths, R. J.

1996-01-01

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice indicating that rolipram can cause adrenal stimulation in vivo. 6. In summary, these data indicate that systemic production of TNF alpha in response to high dose endotoxin is controlled differently from the local production of TNF alpha in response to low dose endotoxin. The systemic production of TNF alpha is regulated by catecholamines, but not by corticosterone, while the local production of TNF alpha in the peritoneal cavity is not regulated by basal levels of either catecholamines or corticosterone. 7. These data also show that the ability of rolipram to inhibit the local production of TNF alpha is dependent on the release of corticosterone from the adrenal glands. PMID:8730750

Regulation of tumour necrosis factor production by adrenal hormones in vivo: insights into the antiinflammatory activity of rolipram.

PubMed

Pettipher, E R; Labasi, J M; Salter, E D; Stam, E J; Cheng, J B; Griffiths, R J

1996-04-01

1. The role of adrenal hormones in the regulation of the systemic and local production of tumour necrosis factor (TNF alpha) was examined in male Balb/c mice. 2. Intraperitoneal injection of 0.3 mg E. coli lipopolysaccharide (LPS, 0111:B4) led to high levels of circulating TNF alpha without stimulating TNF alpha production in the peritoneal cavity. Systemic production of TNF alpha in response to LPS was increased in adrenalectomized animals and in normal animals treated with the beta-adrenoceptor antagonist, propranolol. The glucocorticoid antagonist, RU 486, did not modify systemic TNF alpha production. These results indicate that systemic TNF alpha production is regulated by adrenaline but not by corticosterone. 3. When mice were primed with thioglycollate, TNF alpha was produced in the peritoneal cavity in response to low dose LPS (1 micrograms). The levels of TNF alpha in the peritoneal cavity were not enhanced by adrenalectomy or by treatment with either propranolol or RU 486, indicating local production of TNF alpha in the peritoneal cavity is not regulated by adrenaline or corticosterone. 4. The phosphodiesterase type IV (PDE-IV) inhibitor, rolipram, inhibited both the systemic production of TNF alpha in response to high dose endotoxin (ED50 = 1.3 mg kg-1) and the local production of TNF alpha in the peritoneal cavity in response to low dose endotoxin (ED50 = 9.1 mg kg-1). In adrenalectomized mice there was a slight reduction in the ability of rolipram to inhibit the systemic production of TNF alpha (ED50 = 3.3 mg kg-1) while the ability of rolipram to inhibit the local production of TNF alpha in the peritoneal cavity was virtually abolished (24% inhibition at 30 mg kg-1). The glucocorticoid antagonist, RU 486, also reduced the ability of rolipram to inhibit local TNF alpha production while propranolol was without effect. 5. Systemic treatment with rolipram increased the plasma concentrations of corticosterone in normal mice but not in adrenalectomized mice indicating that rolipram can cause adrenal stimulation in vivo. 6. In summary, these data indicate that systemic production of TNF alpha in response to high dose endotoxin is controlled differently from the local production of TNF alpha in response to low dose endotoxin. The systemic production of TNF alpha is regulated by catecholamines, but not by corticosterone, while the local production of TNF alpha in the peritoneal cavity is not regulated by basal levels of either catecholamines or corticosterone. 7. These data also show that the ability of rolipram to inhibit the local production of TNF alpha is dependent on the release of corticosterone from the adrenal glands.

Robotic Attention Processing And Its Application To Visual Guidance

NASA Astrophysics Data System (ADS)

Barth, Matthew; Inoue, Hirochika

1988-03-01

This paper describes a method of real-time visual attention processing for robots performing visual guidance. This robot attention processing is based on a novel vision processor, the multi-window vision system that was developed at the University of Tokyo. The multi-window vision system is unique in that it only processes visual information inside local area windows. These local area windows are quite flexible in their ability to move anywhere on the visual screen, change their size and shape, and alter their pixel sampling rate. By using these windows for specific attention tasks, it is possible to perform high speed attention processing. The primary attention skills of detecting motion, tracking an object, and interpreting an image are all performed at high speed on the multi-window vision system. A basic robotic attention scheme using the attention skills was developed. The attention skills involved detection and tracking of salient visual features. The tracking and motion information thus obtained was utilized in producing the response to the visual stimulus. The response of the attention scheme was quick enough to be applicable to the real-time vision processing tasks of playing a video 'pong' game, and later using an automobile driving simulator. By detecting the motion of a 'ball' on a video screen and then tracking the movement, the attention scheme was able to control a 'paddle' in order to keep the ball in play. The response was faster than that of a human's, allowing the attention scheme to play the video game at higher speeds. Further, in the application to the driving simulator, the attention scheme was able to control both direction and velocity of a simulated vehicle following a lead car. These two applications show the potential of local visual processing in its use for robotic attention processing.

Nucleotide-oligomerizing domain-1 (NOD1) receptor activation induces pro-inflammatory responses and autophagy in human alveolar macrophages.

PubMed

Juárez, Esmeralda; Carranza, Claudia; Hernández-Sánchez, Fernando; Loyola, Elva; Escobedo, Dante; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; Torres, Martha; Sada, Eduardo

2014-09-25

Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic receptor involved in recognizing bacterial peptidoglycan fragments that localize to the cytosol. NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages. NOD1 mediates intracellular pathogen clearance in the lungs of mice; however, little is known about NOD1's role in human alveolar macrophages (AMs) or its involvement in Mycobacterium tuberculosis (Mtb) infection. AMs, monocytes (MNs), and monocyte-derived macrophages (MDMs) from healthy subjects were assayed for NOD1 expression. Cells were stimulated with the NOD1 ligand Tri-DAP and cytokine production and autophagy were assessed. Cells were infected with Mtb and treated with Tri-DAP post-infection. CFUs counting determined growth control, and autophagy protein recruitment to pathogen localization sites was analyzed by immunoelectron microscopy. NOD1 was expressed in AMs, MDMs and to a lesser extent MNs. Tri-DAP stimulation induced NOD1 up-regulation and a significant production of IL1β, IL6, IL8, and TNFα in AMs and MDMs; however, the level of NOD1-dependent response in MNs was limited. Autophagy activity determined by expression of proteins Atg9, LC3, IRGM and p62 degradation was induced in a NOD1-dependent manner in AMs and MDMs but not in MNs. Infected AMs could be activated by stimulation with Tri-DAP to control the intracellular growth of Mtb. In addition, recruitment of NOD1 and the autophagy proteins IRGM and LC3 to the Mtb localization site was observed in infected AMs after treatment with Tri-DAP. NOD1 is involved in AM and MDM innate responses, which include proinflammatory cytokines and autophagy, with potential implications in the killing of Mtb in humans.

[11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy.

PubMed

Schwarzenböck, Sarah M; Knieling, Anna; Souvatzoglou, Michael; Kurth, Jens; Steiger, Katja; Eiber, Matthias; Esposito, Irene; Retz, Margitta; Kübler, Hubert; Gschwend, Jürgen E; Schwaiger, Markus; Krause, Bernd J; Thalgott, Mark

2016-09-27

Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

The use of plastic optical fibres and shape memory alloys for damage assessment and damping control in composite materials

NASA Astrophysics Data System (ADS)

Kuang, K. S. C.; Cantwell, W. J.

2003-08-01

This paper reports the use of a plastic fibre sensor for detecting impact damage in carbon fibre epoxy cantilever beams by monitoring their damping response under free vibration loading conditions. The composite beams were impacted at impact energies up to 8 J. The residual strengths and stiffnesses of the damaged laminates were measured in order to relate reductions in their mechanical properties to changes in their damping characteristics. Here, optical fibre sensors were surface bonded to carbon fibre composite beams which were subjected to free vibration tests to monitor their dynamic response. In the second part of this study, Ni-Ti shape memory alloy (SMA) wires were employed to control and modify the damping response of a composite beam. The SMA wires were initially trained to obtain the desired shape when activated. Here, the trained SMA wires were heated locally using a nickel/chromium wire that was wrapped around the trained region of the SMA. By using this method to activate the SMA wire (as opposed to direct electrical heating), it is possible to obtain localized actuation without heating the entire length of the wire. This procedure minimizes any damage to the host material that may result from local heat transfer between the SMA wire and the composite structure. In addition, the reduction in power requirements to achieve SMA activation permits the use of small-size power packs which can in turn lead to a potential weight reduction in weight-critical applications. The findings of this study demonstrate that a trained SMA offers a superior damping capability to that exhibited by an 'as-supplied' flat-annealed wire.

Perioperative pain control: a strategy for management.

PubMed

Cohen, Mitchell Jay; Schecter, William P

2005-12-01

A thorough understanding of the anatomy and neurophysiology of the pain response is necessary for the effective treatment of perioperative pain. This article describes the mechanisms that produce pain,including those related to inflammation. Other topics include the pharmacologies of nonopioid and opioid analgesics. Nonopioid analgesics can be separated into two categories: nonsteroidal anti-inflammatory drugs, such as salicylates, and acetaminophen. Opioids include morphine, fentanyl, and meperidine. The pharmacology of local anesthesia is discussed. The six major adverse reactions to local anesthetics are cardiac arrhythmias, hypertension, direct tissue toxicity, central nervous system toxicity, methemoglobinemia and allergic reactions. Methods for measuring pain are described.

Finite-time synchronization control of a class of memristor-based recurrent neural networks.

PubMed

Jiang, Minghui; Wang, Shuangtao; Mei, Jun; Shen, Yanjun

2015-03-01

This paper presents a global and local finite-time synchronization control law for memristor neural networks. By utilizing the drive-response concept, differential inclusions theory, and Lyapunov functional method, we establish several sufficient conditions for finite-time synchronization between the master and corresponding slave memristor-based neural network with the designed controller. In comparison with the existing results, the proposed stability conditions are new, and the obtained results extend some previous works on conventional recurrent neural networks. Two numerical examples are provided to illustrate the effective of the design method. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor response and negative distal resection margins of rectal cancer after hyperthermochemoradiation therapy.

PubMed

Tsutsumi, Soichi; Tabe, Yuichi; Fujii, Takaaki; Yamaguchi, Satoru; Suto, Toshinaga; Yajima, Reina; Morita, Hiroki; Kato, Toshihide; Shioya, Mariko; Saito, Jun-Ichi; Asao, Takayuki; Nakano, Takashi; Kuwano, Hiroyuki

2011-11-01

The safety of regional hyperthermia has been tested in locally advanced rectal cancer. The aim of this study was to assess the effects of shorter distal margins on local control and survival in rectal cancer patients who were treated with preoperative hyperthermochemoradiation therapy (HCRT) and underwent rectal resection by using the total mesorectal excision (TME) method. Ninety-three patients with rectal adenocarcinoma who received neoadjuvant HCRT (total radiation: 50 Gy) were included in this study. Surgery was performed 8 weeks after HCRT, and each resected specimen was evaluated histologically. Length of distal surgical margins, status of circumferential margins, pathological response, and tumor node metastasis stage were examined for their effects on recurrence and survival. Fifty-eight (62.4%) patients had tumor regression, and 20 (21.5%) had a pathological complete response. Distal margin length ranged from 1 to 55 mm (median, 21 mm) and did not correlate with local recurrence (p=0.57) or survival (p=0.75) by univariate analysis. Kaplan-Meier estimates of recurrence-free survival and local recurrence for the <10 mm versus ≥10 mm groups were not significantly different. Positive circumferential margins and failure of tumors to respond were unfavorable factors in survival. Distal resection margins that are shorter than 10 mm but are not positive appear to be equivalent to longer margins in patients who undergo HCRT followed by rectal resection with TME. To improve the down-staging rate, additional studies are needed.

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex.

PubMed

Seok, Seung-Hyeon; Lee, Woojong; Jiang, Li; Molugu, Kaivalya; Zheng, Aiping; Li, Yitong; Park, Sanghyun; Bradfield, Christopher A; Xing, Yongna

2017-05-23

The aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomain interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. These observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands.

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

PubMed Central

Lee, Woojong; Jiang, Li; Molugu, Kaivalya; Zheng, Aiping; Li, Yitong; Park, Sanghyun; Bradfield, Christopher A.; Xing, Yongna

2017-01-01

The aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR–ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomain interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. These observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands. PMID:28396409

Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex

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

Seok, Seung-Hyeon; Lee, Woojong; Jiang, Li

he aryl hydrocarbon receptor (AHR) belongs to the PAS (PER-ARNT-SIM) family transcription factors and mediates broad responses to numerous environmental pollutants and cellular metabolites, modulating diverse biological processes from adaptive metabolism, acute toxicity, to normal physiology of vascular and immune systems. The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. We determined the crystal structure of the mammalian AHR–ARNT heterodimer in complex with the DRE, in which ARNT curls around AHR into a highly intertwined asymmetric architecture, with extensive heterodimerization interfaces and AHR interdomainmore » interactions. Specific recognition of the DRE is determined locally by the DNA-binding residues, which discriminates it from the closely related hypoxia response element (HRE), and is globally affected by the dimerization interfaces and interdomain interactions. Changes at the interdomain interactions caused either AHR constitutive nuclear localization or failure to translocate to nucleus, underlying an allosteric structural pathway for mediating ligand-induced exposure of nuclear localization signal. These observations, together with the global higher flexibility of the AHR PAS-A and its loosely packed structural elements, suggest a dynamic structural hierarchy for complex scenarios of AHR activation induced by its diverse ligands.« less

Mechanisms underlying the control of responses to predator odours in aquatic prey.

PubMed

Mitchell, Matthew D; Bairos-Novak, Kevin R; Ferrari, Maud C O

2017-06-01

In aquatic systems, chemical cues are a major source of information through which animals are able to assess the current state of their environment to gain information about local predation risk. Prey use chemicals released by predators (including cues from a predator's diet) and other prey (such as alarm cues and disturbance cues) to mediate a range of behavioural, morphological and life-history antipredator defences. Despite the wealth of knowledge on the ecology of antipredator defences, we know surprisingly little about the physiological mechanisms that control the expression of these defensive traits. Here, we summarise the current literature on the mechanisms known to specifically mediate responses to predator odours, including dietary cues. Interestingly, these studies suggest that independent pathways may control predator-specific responses, highlighting the need for greater focus on predator-derived cues when looking at the mechanistic control of responses. Thus, we urge researchers to tease apart the effects of predator-specific cues (i.e. chemicals representing a predator's identity) from those of diet-mediated cues (i.e. chemicals released from a predator's diet), which are known to mediate different ecological endpoints. Finally, we suggest some key areas of research that would greatly benefit from a more mechanistic approach. © 2017. Published by The Company of Biologists Ltd.

A case study of development and application of a streamlined control and response modeling system for PM2.5 attainment assessment in China.

PubMed

Long, Shicheng; Zhu, Yun; Jang, Carey; Lin, Che-Jen; Wang, Shuxiao; Zhao, Bin; Gao, Jian; Deng, Shuang; Xie, Junping; Qiu, Xuezhen

2016-03-01

This article describes the development and application of a streamlined air control and response modeling system with a novel response surface modeling-linear coupled fitting method and a new module to provide streamlined model data for PM2.5 attainment assessment in China. This method is capable of significantly reducing the dimensions required to establish a response surface model, as well as capturing more realistic response of PM2.5 to emission changes with a limited number of model simulations. The newly developed module establishes a data link between the system and the Software for Model Attainment Test-Community Edition (SMAT-CE), and has the ability to rapidly provide model responses to emission control scenarios for SMAT-CE using a simple interface. The performance of this streamlined system is demonstrated through a case study of the Yangtze River Delta (YRD) in China. Our results show that this system is capable of reproducing the Community Multi-Scale Air Quality (CMAQ) model simulation results with maximum mean normalized error<3.5%. It is also demonstrated that primary emissions make a major contribution to ambient levels of PM2.5 in January and August (e.g., more than 50% contributed by primary emissions in Shanghai), and Shanghai needs to have regional emission control both locally and in its neighboring provinces to meet China's annual PM2.5 National Ambient Air Quality Standard. The streamlined system provides a real-time control/response assessment to identify the contributions of major emission sources to ambient PM2.5 (and potentially O3 as well) and streamline air quality data for SMAT-CE to perform attainment assessments. Copyright © 2015. Published by Elsevier B.V.

Washing and changing uniforms: is guidance being adhered to?

PubMed

Potter, Yvonne Camilla; Justham, David

To allay public apprehension regarding the risk of nurses' uniforms transmitting healthcare-associated infections (HCAI), national and local guidelines have been issued to control use, laundry and storage. This paper aims to measure the knowledge of registered nurses (RNs) and healthcare assistants (HCAs) working within a rural NHS foundation Trust and their adherence to the local infection prevention and control (IPC) standard regarding uniforms through a Trust-wide audit. Stratified random sampling selected 597 nursing staff and 399 responded (67%) by completing a short questionnaire based on the local standard. Responses were coded and transferred to SPSS (v. 17) for analysis. The audit found that nursing staff generally adhere to the guidelines, changing their uniforms daily and immediately upon accidental soiling, and wearing plastic aprons where indicated. At home, staff normally machine-wash and then iron their uniforms at the hottest setting. Nevertheless, few observe the local direction to place their newly-laundered uniforms in protective covers. This paper recommends a re-audit to compare compliance rates with baseline figures and further research into the reasons why compliance is lacking to sanction interventions for improvement, such as providing relevant staff education and re-introducing appropriate changing facilities.

Putting the public (back) into public health: leadership, evidence and action.

PubMed

South, J; Connolly, A M; Stansfield, J A; Johnstone, P; Henderson, G; Fenton, K A

2018-03-13

There is a strong evidence-based rationale for community capacity building and community empowerment as part of a strategic response to reduce health inequalities. Within the current UK policy context, there are calls for increased public engagement in prevention and local decision-making in order to give people greater control over the conditions that determine health. With reference to the challenges and opportunities within the English public health system, this essay seeks to open debate about what is required to mainstream community-centred approaches and ensure that the public is central to public health. The essay sets out the case for a reorientation of public health practice in order to build impactful action with communities at scale leading to a reduction in the health gap. National frameworks that support local practice are described. Four areas of challenge that could potentially drive an implementation gap are discussed: (i) achieving integration and scale, (ii) effective community mobilization, (iii) evidencing impact and (iv) achieving a shift in power. The essay concludes with a call to action for developing a contemporary public health practice that is rooted in communities and offers local leadership to strengthen local assets, increase community control and reduce health inequalities.

Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics.

PubMed

Huang, Wenwen; Rollett, Alexandra; Kaplan, David L

2015-05-01

Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications. The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.

Parametric manipulation of the conflict signal and control-state adaptation.

PubMed

Forster, Sarah E; Carter, Cameron S; Cohen, Jonathan D; Cho, Raymond Y

2011-04-01

Mechanisms by which the brain monitors and modulates performance are an important focus of recent research. The conflict-monitoring hypothesis posits that the ACC detects conflict between competing response pathways which, in turn, signals for enhanced control. The N2, an ERP component that has been localized to ACC, has been observed after high conflict stimuli. As a candidate index of the conflict signal, the N2 would be expected to be sensitive to the degree of response conflict present, a factor that depends on both the features of external stimuli and the internal control state. In the present study, we sought to explore the relationship between N2 amplitude and these variables through use of a modified Eriksen flankers task in which target-distracter compatibility was parametrically varied. We hypothesized that greater target-distracter incompatibility would result in higher levels of response conflict, as indexed by both behavior and the N2 component. Consistent with this prediction, there were parametric degradations in behavioral performance and increases in N2 amplitudes with increasing incompatibility. Further, increasingly incompatible stimuli led to the predicted parametric increases in control on subsequent incompatible trials as evidenced by enhanced performance and reduced N2 amplitudes. These findings suggest that the N2 component and associated behavioral performance are finely sensitive to the degree of response conflict present and to the control adjustments that result from modulations in conflict.

Allogeneic mesenchymal stem cell transplantation in healthy equine superficial digital flexor tendon: A study of the local inflammatory response.

PubMed

Brandão, Jaqueline Souza; Alvarenga, Marina Landim; Pfeifer, João Pedro Hubbe; Dos Santos, Vitor Hugo; Fonseca-Alves, Carlos Eduardo; Rodrigues, Mirian; Laufer-Amorim, Renée; Castillo, José Antonio Lucas; Alves, Ana Liz Garcia

2018-06-01

The superficial digital flexor tendon (SDFT) is a structure frequently affected by injuries in high-performance athletic horses, and there are limited therapeutic options. Regenerative medicine has evolved significantly in treating different illnesses. However, understanding the cellular behaviour during mesenchymal stem cell (MSC) transplantation in healthy tissues is not fully known yet. To address the inflammatory response induced by allogeneic MSC transplantation, this study evaluated the local inflammatory response after the application of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) in the equine tendon compared to an autologous transplant and the control group. Eighteen thoracic limbs (TL) in nine animals were divided into three groups and subjected to the application of AT-MSCs in the healthy tendon. In the allogeneic group (Gallog), the animals received an allogeneic AT-MSC application in the TL. The autologous group (Gauto) received an application of autologous cells in the TL, and in the control group (Gcont), phosphate-buffered saline (PBS) was applied. There were no significant differences among the evaluated groups in the physical, morphological, thermography, and ultrasonography analyses. A higher number of CD3-positive lymphocytes was observed in the Gauto group compared to the control (P < 0.05). Additionally, we did not observe different expressions of CD172 and microvascular density among the groups. The allogeneic transplantation of AT-MSCs did not result in an adverse or inflammatory reaction that compromised the use of these cells in this experiment. Their behaviour was similar to that of autologous transplantation. Copyright © 2018. Published by Elsevier Ltd.

Plasticity and stress tolerance override local adaptation in the responses of Mediterranean holm oak seedlings to drought and cold.

PubMed

Gimeno, Teresa E; Pías, Beatriz; Lemos-Filho, José P; Valladares, Fernando

2009-01-01

Plant populations of widely distributed species experience a broad range of environmental conditions that can be faced by phenotypic plasticity or ecotypic differentiation and local adaptation. The strategy chosen will determine a population's ability to respond to climate change. To explore this, we grew Quercus ilex (L.) seedlings from acorns collected at six selected populations from climatically contrasting localities and evaluated their response to drought and late season cold events. Maximum photosynthetic rate (A(max)), instantaneous water use efficiency (iWUE), and thermal tolerance to freeze and heat (estimated from chlorophyll fluorescence versus temperature curves) were measured in 5-month-old seedlings in control (no stress), drought (water-stressed), and cold (low suboptimal temperature) conditions. The observed responses were similar for the six populations: drought decreased A(max) and increased iWUE, and cold reduced A(max) and iWUE. All the seedlings maintained photosynthetic activity under adverse conditions (drought and cold), and rapidly increased their iWUE by closing stomata when exposed to drought. Heat and freeze tolerances were similarly high for seedlings from all the populations, and they were significantly increased by drought and cold, respectively; and were positively related to each other. Differences in seedling performance across populations were primarily induced by maternal effects mediated by seed size and to a lesser extent by idiosyncratic physiologic responses to drought and low temperatures. Tolerance to multiple stresses together with the capacity to physiologically acclimate to heat waves and cold snaps may allow Q. ilex to cope with the increasingly stressful conditions imposed by climate change. Lack of evidence of physiologic seedling adaptation to local climate may reflect opposing selection pressures to complex, multidimensional environmental conditions operating within the distribution range of this species.

Vasopressin V1a receptors are present in the carotid body and contribute to the control of breathing in male Sprague-Dawley rats.

PubMed

Żera, Tymoteusz; Przybylski, Jacek; Grygorowicz, Tomasz; Kasarełło, Kaja; Podobińska, Martyna; Mirowska-Guzel, Dagmara; Cudnoch-Jędrzejewska, Agnieszka

2018-04-01

Vasopressin (AVP) maintains body homeostasis by regulating water balance, cardiovascular system and stress response. AVP inhibits breathing through central vasopressin 1a receptors (V1aRs). Chemoreceptors within carotid bodies (CBs) detect chemical and hormonal signals in the bloodstream and provide sensory input to respiratory and cardiovascular centers of the brainstem. In the study we investigated if CBs contain V1aRs and how the receptors are involved in the regulation of ventilation by AVP. We first immunostained CBs for V1aRs and tyrosine hydroxylase, a marker of chemoreceptor type I (glomus) cells. In urethane-anesthetized adult Sprague-Dawley male rats, we then measured hemodynamic and respiratory responses to systemic (intravenous) or local (carotid artery) administration of AVP prior and after systemic blockade of V1aRs. Immunostaining of CBs showed colocalization of V1aRs and tyrosine hydroxylase within glomus cells. Systemic administration of AVP increased mean arterial blood pressure (MABP) and decreased respiratory rate (RR) and minute ventilation (MV). Local administration of AVP increased MV and RR without significant changes in MABP or heart rate. Pretreatment with V1aR antagonist abolished responses to local and intravenous AVP administration. Our findings show that chemosensory cells within CBs express V1aRs and that local stimulation of the CB with AVP increases ventilation, which is contrary to systemic effects of AVP manifested by decreased ventilation. The responses are mediated by V1aRs, as blockade of the receptors prevents changes in ventilation. We hypothesize that excitatory effects of AVP within the CB provide a counterbalancing mechanism for the inhibitory effects of systemically acting AVP on the respiration. Copyright © 2018 Elsevier Inc. All rights reserved.

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment.

PubMed

Wang, Y; Li, Y; Xia, L; Niu, K; Chen, X; Lu, D; Kong, R; Chen, Z; Sun, J

2018-03-01

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

Demonstration of subcellular migration of CK2α localization from nucleus to sarco(endo)plasmic reticulum in mammalian cardiomyocytes under hyperglycemia.

PubMed

Bitirim, Ceylan Verda; Tuncay, Erkan; Turan, Belma

2018-06-01

The cellular control of glucose uptake and glycogen metabolism in mammalian tissues is in part mediated through the regulation of protein-serine/threonine kinases including CK2. Although it participates to several cellular signaling processes, however, its subcellular localization is not well-defined while some documents mentioned its localization change under pathological conditions. The activation/phosphorylation of some proteins including Zn 2+ -transporter ZIP7 in cardiomyocytes is controlled with CK2α, thereby, inducing changes in the level of intracellular free Zn 2+ ([Zn 2+ ] i ). In this regard, we aimed to examine cellular localization of CK2α in cardiomyocytes and its possible subcellular migration under hyperglycemia. Our confocal imaging together with biochemical analysis in isolated sarco(endo)plasmic reticulum [S(E)R] and nuclear fractions from hearts have shown that CK2α localized highly to S(E)R and Golgi and weakly to nuclear fractions in physiological condition. However, it can migrate from nuclear fractions to S(E)R under hyperglycemia. This migration can further underlie phosphorylation of a target protein ZIP7 as well as some endogenous kinases and phosphatases including PKA, CaMKII, and PP2A. We also have shown that CK2α activation is responsible for hyperglycemia-associated [Zn 2+ ] i increase in diabetic heart. Therefore, our present data demonstrated, for the first time, the physiological relevance of CK2α in cellular control of Zn 2+ -distribution via inducing ZIP7 phosphorylation and activation of these above endogenous actors in hyperglycemia/diabetes-associated cardiac dysfunction. Moreover, our present data also emphasized the multi-subcellular compartmental localizations of CK2α and a tightly regulation of these localizations in cardiomyocytes. Therefore, taken into consideration of all data, one can emphasize the important role of the subcellular localization of CK2α as a novel target-pathway for understanding of diabetic cardiomyopathy.

LHP1 Regulates H3K27me3 Spreading and Shapes the Three-Dimensional Conformation of the Arabidopsis Genome

PubMed Central

Ariel, Federico; Latrasse, David; Mariappan, Kiruthiga Gayathri; Kim, Soon-Kap; Crespi, Martin; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cécile; Benhamed, Moussa

2016-01-01

Precise expression patterns of genes in time and space are essential for proper development of multicellular organisms. Dynamic chromatin conformation and spatial organization of the genome constitute a major step in this regulation to modulate developmental outputs. Polycomb repressive complexes (PRCs) mediate stable or flexible gene repression in response to internal and environmental cues. In Arabidopsis thaliana, LHP1 co-localizes with H3K27me3 epigenetic marks throughout the genome and interacts with PRC1 and PRC2 members as well as with a long noncoding RNA. Here, we show that LHP1 is responsible for the spreading of H3K27me3 towards the 3’ end of the gene body. We also identified a subset of LHP1-activated genes and demonstrated that LHP1 shapes local chromatin topology in order to control transcriptional co-regulation. Our work reveals a general role of LHP1 from local to higher conformation levels of chromatin configuration to determine its accessibility to define gene expression patterns. PMID:27410265

The direction of restructuring of a Korea field epidemiology training program through questionnaire survey among communicable disease response staff in Korea.

PubMed

Lee, Moo-Sik; Lee, Kwan; Park, Ji-Hyuk; Hong, Jee-Young; Jang, Min Young; Jeon, Byoung-Hak; Cho, Sang Yun; Choi, Sun Ja; Hong, Jeong Ik

2017-01-01

We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.

Radiofrequency ablation of liver tumors (I): biological background.

PubMed

Vanagas, Tomas; Gulbinas, Antanas; Pundzius, Juozas; Barauskas, Giedrius

2010-01-01

Majority of patients suffering from liver tumors are not candidates for surgery. Currently, minimal invasive techniques have become available for local destruction of hepatic tumors. Radiofrequency ablation is based on biological response to tissue hyperthermia. The aim of this article is to review available biological data on tissue destruction mechanisms. Experimental evidence shows that tissue injury following thermal ablation occurs in two distinct phases. The initial phase is direct injury, which is determined by energy applied, tumor biology, and tumor microenvironment. The temperature varies along the ablation zone and this is reflected by different morphological changes in affected tissues. The local hyperthermia alters metabolism, exacerbates tissue hypoxia, and increases thermosensitivity. The second phase - indirect injury - is observed after the cessation of heat stimulus. This phase represents a balance of several promoting and inhibiting mechanisms, such as induction of apoptosis, heat shock proteins, Kupffer cell activation, stimulation of the immune response, release of cytokines, and ischemia-reperfusion injury. A deeper understanding of the underlying mechanisms may possibly lead to refinements in radiofrequency ablation technology, resulting in advanced local tumor control and prolonged overall survival.

[Influence of local anaesthesia on short- and long-term pain induced in calves by three bloodless castration methods].

PubMed

Thüer, S; Doherr, M G; Wechsler, B; Mellema, S C; Nuss, K; Kirchhofer, M; Steiner, A

2007-05-01

Behavioural and cortisol responses of calves were used as indicators of pain to assess short- and long-term effects of three bloodless castration methods with and without local anaesthesia. Eighty calves, aged 21 to 28 days, were control handled (20) or castrated by Burdizzo (25), rubber ring (25), or crushing technique (10). Either a total volume of 10 ml of Lidocaine or NaCl was distributed in both spermatic cords and the scrotal neck. The plasma cortisol response was monitored for 72 hours, and behavioural and clinical traits over a three-month period. Castration success was assessed by degree of atrophy and histological tissue examination. The crushing technique cannot be recommended due to incomplete castration success, and the evaluation was stopped after 10 animals. Local anaesthesia reduced the level of indicators of acute pain after Burdizzo and rubber ring technique. It did, however, not result in a totally painless castration. When castration is performed at the age of 3 to 4 weeks, the rubber ring but not the Burdizzo method showed evidence of chronic pain lasting for several weeks.

Implementation of a workplace smoking ban in bars: The limits of local discretion

PubMed Central

Montini, Theresa; Bero, Lisa A

2008-01-01

Background In January 1998, the California state legislature extended a workplace smoking ban to bars. The purpose of this study was to explore the conditions that facilitate or hinder compliance with a smoking ban in bars. Methods We studied the implementation of the smoking ban in bars by interviewing three sets of policy participants: bar employers responsible for complying with the law; local government officials responsible for enforcing the law; and tobacco control activists who facilitated implementation. We transcribed the interviews and did a qualitative analysis of the text. Results The conditions that facilitated bar owners' compliance with a smoking ban in bars included: if the cost to comply was minimal; if the bars with which they were in competition were in compliance with the smoking ban; and if there was authoritative, consistent, coordinated, and uniform enforcement. Conversely, the conditions that hindered compliance included: if the law had minimal sanctions; if competing bars in the area allowed smoking; and if enforcement was delayed or inadequate. Conclusion Many local enforcers wished to forfeit their local discretion and believed the workplace smoking ban in bars would be best implemented by a state agency. The potential implication of this study is that, given the complex nature of local politics, smoking bans in bars are best implemented at a broader provincial or national level. PMID:19063716

Thermoregulatory responses to heat and vibration in men

NASA Technical Reports Server (NTRS)

Spaul, W. A.; Spear, R. C.; Greenleaf, J. E.

1986-01-01

The effect of vibration on thermoregulatory responses was studied in heat-acclimated men exposed suddenly to simultaneous heat and whole body vibrations (WBVs) at two intensity levels, each at graded frequencies between 5 and 80 Hz. The mean rectal temperature (Tre) became elevated more quickly in the WBV exposures than in the controls (heat exposure alone). Both intensity- and frequency-dependent WBV relationships were recorded in localized blood flows and in sweat rates. Thus, vibration appears to reduce the efficiency of the cooling mechanisms during a heat exposure.

Nonspiking local interneurons in insect leg motor control. I. Common layout and species-specific response properties of femur-tibia joint control pathways in stick insect and locust.

PubMed

Büschges, A; Wolf, H

1995-05-01

1. Locusts (Locusta migratoria) and stick insects (Carausius morosus) exhibit different strategies for predator avoidance. Locusts rely primarily on walking and jumping to evade predators, whereas stick insects become cataleptic, catalepsy forming a major component of the twig mimesis exhibited by this species. The neuronal networks that control postural leg movements in locusts and stick insects are tuned differently to their specific behavioral tasks. An important prerequisite for the production of catalepsy in the stick insect is the marked velocity dependency of the control network, which appears to be generated at the level of nonspiking local interneurons. We examined interneuronal pathways in the network controlling the femur-tibia joint of the locust middle leg and compared its properties with those described for the stick insect middle leg. It was our aim to identify possible neural correlates of the species-specific behavior with regard to postural leg motor control. 2. We obtained evidence that the neuronal networks that control the femur-tibia joints in the two species consist of morphologically and physiologically similar--and thus probably homologous--interneurons. Qualitatively, these interneurons receive the same input from the femoral chordotonal organ receptors and they drive the same pools of leg motoneurons in both species. 3. Pathways that contribute to the control of the femur-tibia joint include interneurons that support both "resisting" and "assisting" responses with respect to the motoneuron activity that is actually elicited during reflex movements. Signal processing via parallel, antagonistic pathways therefore appears to be a common principle in insect leg motor control. 4. Differences between the two insect species were found with regard to the processing of velocity information provided by the femoral chordotonal organ. Interneuronal pathways are sensitive to stimulus velocity in both species. However, in the locust there is no marked velocity dependency of the interneuronal responses, whereas in the same interneurons of the stick insect it is pronounced. This characteristic was maintained at the level of the motoneurons controlling the femur-tibia joint. Pathways for postural leg motor control in the locust thus lack an important prerequisite for the generation of catalepsy, that is, a marked velocity dependency.

Prospective study of neoadjuvant chemoradiotherapy using intensity-modulated radiotherapy and 5 fluorouracil for locally advanced rectal cancer - toxicities and response assessment.

PubMed

Simson, David K; Mitra, Swarupa; Ahlawat, Parveen; Saxena, Upasna; Sharma, Manoj Kumar; Rawat, Sheh; Singh, Harpreet; Bansal, Babita; Sripathi, Lalitha Kameshwari; Tanwar, Aditi

2018-01-01

The past 2 decades witnessed the strengthening of evidence favoring the role of neoadjuvant chemoradiation (CHRT) in the treatment of locally advanced rectal cancer. The study aims to evaluate the response and acute toxicities to neoadjuvant CHRT using intensity-modulated radiotherapy (IMRT) in the treatment of rectal cancer. Predictive factors to achieve pathological complete response (pCR) were analyzed, as a secondary endpoint. All consecutive patients who underwent IMRT as part of neoadjuvant CHRT in the treatment of rectal cancer between August 2014 and December 2016 at a tertiary cancer care center were accrued for the study. The cohort underwent CHRT with IMRT technique at a dose of 50.4 Gy in 28 fractions concurrent with continuous infusion of 5 fluorouracil during the first and the last 4 days of CHRT. Surgery was performed 6 weeks later and the pathological response to CHRT was noted. Forty-three subjects were accrued for the study. Radiation dermatitis and diarrhea were the only observed grade ≥3 acute toxicities. Sphincter preservation rate (SPR) was 43.3%. pCR was observed in 32.6%. Univariate and multivariate logistic regression showed that carcinoembryonic antigen was the only independent predictive factor to achieve pCR. IMRT as part of neoadjuvant CHRT in the treatment of locally advanced rectal cancer is well tolerated and gives comparable results with respect to earlier studies in terms of pathological response and SPR. Further randomized controlled studies are needed to firmly state that IMRT is superior to 3-dimensional conformal radiotherapy.

Community Assessment for Public Health Emergency Response (CASPER): An Innovative Emergency Management Tool in the United States.

PubMed

Schnall, Amy; Nakata, Nicole; Talbert, Todd; Bayleyegn, Tesfaye; Martinez, DeAndrea; Wolkin, Amy

2017-09-01

To demonstrate how inclusion of the Centers for Disease Control and Prevention's Community Assessment for Public Health Emergency Response (CASPER) as a tool in Public Health Preparedness Capabilities: National Standards for State and Local Planning can increase public health capacity for emergency response. We reviewed all domestic CASPER activities (i.e., trainings and assessments) between fiscal years 2012 and 2016. Data from these CASPER activities were compared with respect to differences in geographic distribution, type, actions, efficacy, and usefulness of training. During the study period, the Centers for Disease Control and Prevention conducted 24 domestic in-person CASPER trainings for 1057 staff in 38 states. On average, there was a marked increase in knowledge of CASPER. Ninety-nine CASPERs were conducted in the United States, approximately half of which (53.5%) assessed preparedness; the others were categorized as response or recovery (27.2%) or were unrelated to a disaster (19.2%). CASPER trainings are successful in increasing disaster epidemiology skills. CASPER can be used by Public Health Emergency Preparedness program awardees to help build and sustain preparedness and response capabilities.

NK cells influence both innate and adaptive immune responses after mucosal immunisation with antigen and mucosal adjuvant*

PubMed Central

Hall, Lindsay J; Clare, Simon; Dougan, Gordon

2012-01-01

NK cells were found to be recruited in a temporally controlled manner to the nasal-associated lymphoid tissue and the cervical lymph nodes of mice following intranasal immunisation with Ag85B-ESAT6 antigen from Mycobacterium tuberculosis mixed with Escherichia coli heat-labile toxin as adjuvant. These NK cells were activated and they secreted a diverse range of cytokines and other immunmodulators. Using antibody depletion targeting anti-asialo GM1, we found evidence for altered trafficking, impaired activation and cytokine secretion of dendritic cells, macrophages and neutrophils in immunised NK cell depleted mice compared to control animals. Analysis of antigen-specific immune responses revealed an attenuated antibody and cytokine response in immunised NK cell depleted animals. Systemic administration of rIL-6 but not rIFN-γ significantly restored immune responses in mice depleted of NK cells. In conclusion, cytokine production, particularly IL-6, via NK cells and NK cell activated immune populations, plays an important role in the establishment of local innate immune responses and the consequent development of adaptive immunity after mucosal immunisation. PMID:20220095

Correlation between local hemodynamics and lesion distribution in a novel aortic regurgitation murine model of atherosclerosis.

PubMed

Hoi, Yiemeng; Zhou, Yu-Qing; Zhang, Xiaoli; Henkelman, R Mark; Steinman, David A

2011-05-01

Following surgical induction of aortic valve regurgitation (AR), extensive atherosclerotic plaque development along the descending thoracic and abdominal aorta of Ldlr⁻/⁻ mice has been reported, with distinct spatial distributions suggestive of a strong local hemodynamic influence. The objective of this study was to test, using image-based computational fluid dynamics (CFD), whether this is indeed the case. The lumen geometry was reconstructed from micro-CT scanning of a control Ldlr⁻/⁻ mouse, and CFD simulations were carried out for both AR and control flow conditions derived from Doppler ultrasound measurements and literature data. Maps of time-averaged wall shear stress magnitude (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were compared against the spatial distributions of plaque stained with oil red O, previously acquired in a group of AR and control mice. Maps of OSI and RRT were found to be consistent with plaque distributions in the AR mice and the absence of plaque in the control mice. TAWSS was uniformly lower under control vs. AR flow conditions, suggesting that levels (> 100 dyn/cm²) exceeded those required to alone induce a pro-atherogenic response. Simulations of a straightened CFD model confirmed the importance of anatomical curvature for explaining the spatial distribution of lesions in the AR mice. In summary, oscillatory and retrograde flow induced in the AR mice, without concomitant low shear, may exacerbate or accelerate lesion formation, but the distinct anatomical curvature of the mouse aorta is responsible for the spatial distribution of lesions.

Effects of irradiation combined with cis-diamminedichloroplatinum (CDDP) suppository in rabbit VX2 rectal tumors.

PubMed

Wakatsuki, Kazuo; Oda, Kenji; Koda, Keiji; Seike, Kazuhiro; Takiguchi, Nobuhiro; Saito, Norio; Miyazaki, Masaru

2005-03-01

To decrease local recurrence and increase disease free survival, various preoperative therapies for patients with advanced rectal cancer have been studied. Cis-diamminedichloroplatinum (II) (CDDP) has become one of the most widely used cancer chemotherapeutic drugs. It has also been found to have radiosensitizing properties. In this experimental study, the efficacy of chemoradiotherapy using a novel CDDP suppository, and one with mixed micelles, was examined in a rabbit VX2 rectal tumor model. Rabbits were divided into four groups: control group, irradiation (R) group, CDDP suppository plus irradiation (CR) group, and mixed micelles plus CDDP suppository plus irradiation (CMR) group. Tumor growth ratios were reduced significantly in the CR and CMR groups as compared with the ratio in the control group. Microscopically, response rates of main tumors were 0%, 33.3%, 70.0%, and 91. 7%, respectively. The number of metastatic lymph nodes in the CR and CMR groups decreased significantly compared to the control group and the R group. The microscopic response rates of metastatic lymph nodes were 0%, 11.1%, 40.0%, and 41.7%, respectively. Lung metastases were observed in three rabbits in the R group, and in one rabbit in the CMR group. Tissue platinum concentrations both in tumors and in regional lymph nodes increased significantly when mixed micelles were used. Chemoradiotherapy using the CDDP suppository and mixed micelles was effective for local control in the rabbit VX2 rectal tumor model.

Interpretation of hydraulic tests performed at a carbonate rock site for CO2 storage

NASA Astrophysics Data System (ADS)

María Gómez Castro, Berta; Fernández López, Sheila; Carrera, Jesús; de Simone, Silvia; Martínez, Lurdes; Roetting, Tobias; Soler, Joaquim; Ortiz, Gema; de Dios, Carlos; Huber, Christophe

2014-05-01

Interpretation of hydraulic tests performed at a carbonate rock site for CO2 storage Berta Gómez, Sheila Fernández, Tobias Roetting, Lurdes Martínez, Silvia de Simone, Joaquim Soler, Jesus Carrera, Gema Ortiz, Christophe Huber, Carlos de Dios Proper design of CO2 geological storage facilities requires knowledge of the reservoir hydraulic parameters. Specifically, permeability controls the flux of CO2, the rate at which it dissolves, local and regional pressure buildup and the likelihood of induced seismicity. Permeability is obtained from hydraulic tests, which may yield local permeability, which controls injectivity, and large scale permeability, which controls pressure buildup at the large scale. If pressure response measurements are obtained at different elevations, hydraulic tests may also yield vertical permeability, which controls the rate at which CO2 dissolves. The objective of this work is to discuss the interpretation of hydraulic tests at deep reservoirs and the conditions under which these permeabilities can be obtained. To achieve this objective, we have built a radially symmetric model, including a skin and radial as well as vertical heterogeneity. We use this model to simulate hydraulic tests with increasing degrees of complexity about the medium response. We start by assuming Darcy flow, then add coupled mechanical effects (fractures opening) and, finally, we add thermal effects. We discuss how these affect the conventional interpretation of the tests and how to identify their presence. We apply these findings to the interpretation of hydraulic tests at Hontomin.

Immunomodulatory Effects of Levofloxacin on Patients with Pneumonia in Assiut University Hospitals.

PubMed

Badari, Mohamed S; Elgendy, Sherein G; Mohamed, Asmaa S; Hassan, Alaa T

2015-01-01

The immunomodulatory effects of antibiotics could influence the degree of systemic and local responses to infection, so investigation of their intrinsic influence on the host's inflammatory response appears to be essential. Fluoroquinolones are known to exert modulatory activity on immune responses to microbial infection. However the mechanism of this immunmodulation has not been well elucidated. The aim of the work, is to assess the immunomodulatory effects of a levofloxacin, through examining its effect on the concentrations of tumor necrosis factor α (TNF-α) and Interleukin - 10 (IL-10) in serum of pneumonic patients. After following local research ethics committee approval and informed consent. This study included 40 patients with different types of pneumonia, admitted to department of Chest Diseases, Faculty of Medicine, Assiut University Hospitals, Egypt. Also, 10 healthy volunteers served as randomized controls. Both patients and controls received levofloxacin (750 mg once daily for 10 days). Serum levels of TNF-α and IL-10 were measured in patients and control before and after levofloxacin administration (750 mg once daily for 10 days) using human TNF-α and IL-10 ELISA kits respectively. Levofloxacin caused a statistically significant decrease in the mean level of TNF-α in both patients (20.82 ± 1.31 pg/ml) (P < 0.009) and control group (17.12 ± 0.84 pg/ml) (P < 0.004). In contrast, there was statistically significant increase (P < 0.000) in the mean level of IL-1 0 in patients (61.75 ± 2.85 pg/ml) while statistically significant decrease (P < 0.005) in control group (28.57 ± 1.37 pg/ml). In conclusion, our study demonstrates that treatment with levofloxacin affects production of TNF-α as a pro-inflammatory cytokine and IL-10 as an anti-inflammatory cytokines which may provide additional benefits in treatment of respiratory tract infections that are independent of its antibacterial properties.

The effect of glutathione as chain transfer agent in PNIPAAm-based thermo-responsive hydrogels for controlled release of proteins.

PubMed

Drapala, Pawel W; Jiang, Bin; Chiu, Yu-Chieh; Mieler, William F; Brey, Eric M; Kang-Mieler, Jennifer J; Pérez-Luna, Victor H

2014-03-01

To control degradation and protein release using thermo-responsive hydrogels for localized delivery of anti-angiogenic proteins. Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA-Acry) were synthesized via free radical polymerization in the presence of glutathione, a chain transfer agent (CTA) added to modulate their degradation and release properties. Immunoglobulin G (IgG) and the recombinant proteins Avastin® and Lucentis® were encapsulated in these hydrogels and their release was studied. The encapsulation efficiency of IgG was high (75-87%) and decreased with CTA concentration. The transition temperature of these hydrogels was below physiological temperature, which is important for minimally invasive therapies involving these materials. The toxicity from unreacted monomers and free radical initiators was eliminated with a minimum of three buffer extractions. Addition of CTA accelerated degradation and resulted in complete protein release. Glutathione caused the degradation products to become solubilized even at 37°C. Hydrogels prepared without glutathione did not disintegrate nor released protein completely after 3 weeks at 37°C. PEGylation of IgG postponed the burst release effect. Avastin® and Lucentis® released from degraded hydrogels retained their biological activity. These systems offer a promising platform for the localized delivery of proteins.

Local disturbance cycles and the maintenance of heterogeneity across scales in marine metapopulations.

PubMed

Gouhier, Tarik C; Guichard, Frédéric

2007-03-01

In marine systems, the occurrence and implications of disturbance-recovery cycles have been revealed at the landscape level, but only in demographically open or closed systems where landscape-level dynamics are assumed to have no feedback effect on regional dynamics. We present a mussel metapopulation model to elucidate the role of landscape-level disturbance cycles for regional response of mussel populations to onshore productivity and larval transport. Landscape dynamics are generated through spatially explicit rules, and each landscape is connected to its neighbor through unidirectional larval dispersal. The role of landscape disturbance cycles in the regional system behavior is elucidated (1) in demographically open vs. demographically coupled systems, in relation to (2) onshore reproductive output and (3) the temporal scale of landscape disturbance dynamics. By controlling for spatial structure at the landscape and metapopulation levels, we first demonstrate the interaction between landscape and oceanographic connectivity. The temporal scale of disturbance cycles, as controlled by mussel colonization rate, plays a critical role in the regional behavior of the system. Indeed, fast disturbance cycles are responsible for regional synchrony in relation to onshore reproductive output. Slow disturbance cycles, however, lead to increased robustness to changes in productivity and to demographic coupling. These testable predictions indicate that the occurrence and temporal scale of local disturbance-recovery dynamics can drive large-scale variability in demographically open systems, and the response of metapopulations to changes in nearshore productivity.

Assessing the effectiveness of sustainable land management policies for combating desertification: A data mining approach.

PubMed

Salvati, L; Kosmas, C; Kairis, O; Karavitis, C; Acikalin, S; Belgacem, A; Solé-Benet, A; Chaker, M; Fassouli, V; Gokceoglu, C; Gungor, H; Hessel, R; Khatteli, H; Kounalaki, A; Laouina, A; Ocakoglu, F; Ouessar, M; Ritsema, C; Sghaier, M; Sonmez, H; Taamallah, H; Tezcan, L; de Vente, J; Kelly, C; Colantoni, A; Carlucci, M

2016-12-01

This study investigates the relationship between fine resolution, local-scale biophysical and socioeconomic contexts within which land degradation occurs, and the human responses to it. The research draws on experimental data collected under different territorial and socioeconomic conditions at 586 field sites in five Mediterranean countries (Spain, Greece, Turkey, Tunisia and Morocco). We assess the level of desertification risk under various land management practices (terracing, grazing control, prevention of wildland fires, soil erosion control measures, soil water conservation measures, sustainable farming practices, land protection measures and financial subsidies) taken as possible responses to land degradation. A data mining approach, incorporating principal component analysis, non-parametric correlations, multiple regression and canonical analysis, was developed to identify the spatial relationship between land management conditions, the socioeconomic and environmental context (described using 40 biophysical and socioeconomic indicators) and desertification risk. Our analysis identified a number of distinct relationships between the level of desertification experienced and the underlying socioeconomic context, suggesting that the effectiveness of responses to land degradation is strictly dependent on the local biophysical and socioeconomic context. Assessing the latent relationship between land management practices and the biophysical/socioeconomic attributes characterizing areas exposed to different levels of desertification risk proved to be an indirect measure of the effectiveness of field actions contrasting land degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51 Is Immunogenic, but Causes Sterile Abscesses and Unacceptable Reactogenicity

PubMed Central

Graham, Barney S.; McElrath, M. Juliana; Keefer, Michael C.; Rybczyk, Kyle; Berger, David; Weinhold, Kent J.; Ottinger, Janet; Ferarri, Guido; Montefiori, David C.; Stablein, Don; Smith, Carol; Eldridge, John; Duerr, Ann; Fast, Pat; Haynes, Barton F.

2010-01-01

Background A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA). Methods Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in16 vaccine recipients and two placebo recipients after the 2nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, 51Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens. Results 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions. Conclusions The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events. Trial Registration ClinicalTrials.gov NCT00000886 PMID:20706632

Strengthening of Top-Down Frontal Cognitive Control Networks Underlying the Development of Inhibitory Control: An fMRI Effective Connectivity Study

PubMed Central

Hwang, Kai; Velanova, Katerina; Luna, Beatriz

2010-01-01

The ability to voluntarily inhibit responses to task irrelevant stimuli, which is a fundamental component of cognitive control, has a protracted development through adolescence. Prior human developmental imaging studies have found immaturities in localized brain activity in children and adolescents. However, little is known about how these regions integrate with age to form the distributed networks known to support cognitive control. In the present study, we used Granger Causality analysis to characterize developmental changes in effective connectivity underlying inhibitory control (antisaccade task) compared to reflexive responses (prosaccade task) in human participants. By childhood few top-down connectivity were evident with increased parietal interconnectivity. By adolescence connections from prefrontal cortex increased and parietal interconnectivity decreased in number. From adolescence to adulthood there was evidence of increased number and strength of frontal connections to cortical regions as well as subcortical regions. Taken together, results suggest that developmental improvements in inhibitory control may be supported by age related enhancements in top-down effective connectivity between frontal, oculomotor and subcortical regions. PMID:21084608

Temporal and spatial adaptation of transient responses to local features

PubMed Central

O'Carroll, David C.; Barnett, Paul D.; Nordström, Karin

2012-01-01

Interpreting visual motion within the natural environment is a challenging task, particularly considering that natural scenes vary enormously in brightness, contrast and spatial structure. The performance of current models for the detection of self-generated optic flow depends critically on these very parameters, but despite this, animals manage to successfully navigate within a broad range of scenes. Within global scenes local areas with more salient features are common. Recent work has highlighted the influence that local, salient features have on the encoding of optic flow, but it has been difficult to quantify how local transient responses affect responses to subsequent features and thus contribute to the global neural response. To investigate this in more detail we used experimenter-designed stimuli and recorded intracellularly from motion-sensitive neurons. We limited the stimulus to a small vertically elongated strip, to investigate local and global neural responses to pairs of local “doublet” features that were designed to interact with each other in the temporal and spatial domain. We show that the passage of a high-contrast doublet feature produces a complex transient response from local motion detectors consistent with predictions of a simple computational model. In the neuron, the passage of a high-contrast feature induces a local reduction in responses to subsequent low-contrast features. However, this neural contrast gain reduction appears to be recruited only when features stretch vertically (i.e., orthogonal to the direction of motion) across at least several aligned neighboring ommatidia. Horizontal displacement of the components of elongated features abolishes the local adaptation effect. It is thus likely that features in natural scenes with vertically aligned edges, such as tree trunks, recruit the greatest amount of response suppression. This property could emphasize the local responses to such features vs. those in nearby texture within the scene. PMID:23087617

Temporal dynamics of contrast gain in single cells of the cat striate cortex.

PubMed

Bonds, A B

1991-03-01

The response amplitude of cat striate cortical cells is usually reduced after exposure to high-contrast stimuli. The temporal characteristics and contrast sensitivity of this phenomenon were explored by stimulating cortical cells with drifting gratings in which contrast sequentially incremented and decremented in stepwise fashion over time. All responses showed a clear hysteresis, in which contrast gain dropped on average 0.36 log unit and then returned to baseline values within 60 s. Noticeable gain adjustments were seen in as little as 3 s and with peak contrasts as low as 3%. Contrast adaptation was absent in responses from LGN cells. Adaptation was found to depend on temporal frequency of stimulation, with greater and more rapid adaptation at higher temporal frequencies. Two different tests showed that the mechanism controlling response reduction was influenced primarily by stimulus contrast rather than response amplitude. These results support the existence of a rapid and sensitive cortically based system that normalizes the output of cortical cells as a function of local mean contrast. Control of the adaptation appears to arise at least in part across a population of cells, which is consistent with the idea that the gain control serves to limit the information converging from many cells onto subsequent processing areas.

Successful malaria elimination in the Ecuador-Peru border region: epidemiology and lessons learned.

PubMed

Krisher, Lyndsay K; Krisher, Jesse; Ambuludi, Mariano; Arichabala, Ana; Beltrán-Ayala, Efrain; Navarrete, Patricia; Ordoñez, Tania; Polhemus, Mark E; Quintana, Fernando; Rochford, Rosemary; Silva, Mercy; Bazo, Juan; Stewart-Ibarra, Anna M

2016-11-28

In recent years, malaria (Plasmodium vivax and Plasmodium falciparum) has been successfully controlled in the Ecuador-Peru coastal border region. The aim of this study was to document this control effort and to identify the best practices and lessons learned that are applicable to malaria control and to other vector-borne diseases. A proximal outcome evaluation was conducted of the robust elimination programme in El Oro Province, Ecuador, and the Tumbes Region, Peru. Data collection efforts included a series of workshops with local public health experts who played central roles in the elimination effort, review of epidemiological records from Ministries of Health, and a review of national policy documents. Key programmatic and external factors are identified that determined the success of this eradication effort. From the mid 1980s until the early 2000s, the region experienced a surge in malaria transmission, which experts attributed to a combination of ineffective anti-malarial treatment, social-ecological factors (e.g., El Niño, increasing rice farming, construction of a reservoir), and political factors (e.g., reduction in resources and changes in management). In response to the malaria crisis, local public health practitioners from El Oro and Tumbes joined together in the mid-1990s to forge an unofficial binational collaboration for malaria control. Over the next 20 years, they effectively eradicated malaria in the region, by strengthening surveillance and treatment strategies, sharing of resources, operational research to inform policy, and novel interventions. The binational collaboration at the operational level was the fundamental component of the successful malaria elimination programme. This unique relationship created a trusting, open environment that allowed for flexibility, rapid response, innovation and resilience in times of crisis, and ultimately a sustainable control programme. Strong community involvement, an extensive microscopy network and ongoing epidemiologic investigations at the local level were also identified as crucial programmatic strategies. The results of this study provide key principles of a successful malaria elimination programme that can inform the next generation of public health professionals in the region, and serve as a guide to ongoing and future control efforts of other emerging vector borne diseases globally.

Periadolescent exposure to the NMDA antagonist MK-801 impairs the functional maturation of local GABAergic circuits in the adult prefrontal cortex

PubMed Central

Thomases, Daniel R.; Cass, Daryn K.; Tseng, Kuei Y.

2012-01-01

A developmental disruption of prefrontal cortical (PFC) inhibitory circuits is thought to contribute to the adolescent onset of cognitive deficits observed in schizophrenia. However, the developmental mechanisms underlying such a disruption remain elusive. The goal of this study is to examine how repeated exposure to the NMDA receptor antagonist dizocilpine maleate (MK-801) during periadolescence (from postnatal days -PD- 35-40) impacts the normative development of local prefrontal network response in rats. In vivo electrophysiological analyses revealed that MK-801 administration during periadolescence elicits an enduring disinhibited prefrontal local field potential response to ventral hippocampal stimulation at 20Hz (beta) and 40Hz (gamma) in adulthood (PD65-85). Such a disinhibition was not observed when MK-801 was given during adulthood, indicating that the periadolescent transition is indeed a sensitive period for the functional maturation of prefrontal inhibitory control. Accordingly, the pattern of prefrontal local field potential disinhibition induced by periadolescent MK-801 treatment resembles that observed in the normal PD30-40 PFC. Further pharmacological manipulations revealed that these developmentally immature prefrontal responses can be mimicked by single microinfusion of the GABA-A receptor antagonist picrotoxin into the normal adult PFC. Importantly, acute administration of the GABA-A positive allosteric modulator Indiplon into the PFC reversed the prefrontal disinhibitory state induced by periadolescent MK-801 to normal levels. Together, these results indicate a critical role of NMDA receptors in regulating the periadolescent maturation of GABAergic networks in the PFC, and that pharmacologically-induced augmentation of local GABA-A receptor-mediated transmission is sufficient to overcome the disinhibitory prefrontal state associated with the periadolescent MK-801 exposure. PMID:23283319

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer.

PubMed

Guckenberger, Matthias; Klement, Rainer Johannes; Allgäuer, Michael; Appold, Steffen; Dieckmann, Karin; Ernst, Iris; Ganswindt, Ute; Holy, Richard; Nestle, Ursula; Nevinny-Stickel, Meinhard; Semrau, Sabine; Sterzing, Florian; Wittig, Andrea; Andratschke, Nicolaus; Flentje, Michael

2013-10-01

To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC). This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs). There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20). Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A feasibility study of [sup 252]Cf neutron brachytherapy, cisplatin + 5-FU chemo-adjuvant and accelerated hyperfractionated radiotherapy for advanced cervical cancer

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

Murayama, Y.; Wierzbicki, J.; Bowen, M.G.

The purpose was to evaluate the feasibility and toxicity of [sup 252]Cf neutron brachytherapy combined with hyperaccelerated chemoradiotherapy for Stage III and IV cervical cancers. Eleven patients with advanced Stage IIIB-IVA cervical cancers were treated with [sup 252]Cf neutron brachytherapy in an up-front schedule followed by cisplatin (CDDP; 50 mg/m[sup 2]) chemotherapy and hyperfractionated accelerated (1.2 Gy bid) radiotherapy given concurrently with intravenous infusion of 5-Fluorouracil (5-FU) (1000 mg/m[sup 2]/day [times] 4 days) in weeks 1 and 4 with conventional radiation (weeks 2, 3, 5, and 6). Total dose at a paracervical point A isodose surface was 80-85 Gy-eq bymore » external and intracavitary therapy and 60 Gy at the pelvic sidewalls. Patients tolerated the protocol well. There was 91% compliance with the chemotherapy and full compliance with the [sup 252]Cf brachytherapy and the external beam radiotherapy. There were no problems with acute chemo or radiation toxicity. One patient developed a rectovaginal fistula (Grade 3-4 RTOG criteria) but no other patients developed significant late cystitis, proctitis or enteritis. There was complete response (CR) observed in all cases. With mean follow-up to 26 months, local control has been achieved with 90% actuarial 3-year survival with no evidence of disease (NED). [sup 252]Cf neutrons can be combined with cisplatin and 5-FU infusion chemotherapy plus hyperaccelerated chemoradiotherapy without unusual side effects or toxicity and with a high local response and tumor control rate. Further study of [sup 252]Cf neutron-chemoradiotherapy for advanced and bulky cervical cancer are indicated. The authors found chemotherapy was more effective with the improved local tumor control. 18 refs., 2 tabs.« less

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria.

PubMed

Vargo, John A; Boisen, Michelle M; Comerci, John T; Kim, Hayeon; Houser, Christopher J; Sukumvanich, Paniti; Olawaiye, Alexander B; Kelley, Joseph L; Edwards, Robert P; Huang, Marilyn; Courtney-Brooks, Madeleine; Beriwal, Sushil

2014-11-01

For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response. Copyright © 2014 Elsevier Inc. All rights reserved.

Auditory P3a and P3b neural generators in schizophrenia: An adaptive sLORETA P300 localization approach.

PubMed

Bachiller, Alejandro; Romero, Sergio; Molina, Vicente; Alonso, Joan F; Mañanas, Miguel A; Poza, Jesús; Hornero, Roberto

2015-12-01

The present study investigates the neural substrates underlying cognitive processing in schizophrenia (Sz) patients. To this end, an auditory 3-stimulus oddball paradigm was used to identify P3a and P3b components, elicited by rare-distractor and rare-target tones, respectively. Event-related potentials (ERP) were recorded from 31 Sz patients and 38 healthy controls. The P3a and P3b brain-source generators were identified by time-averaging of low-resolution brain electromagnetic tomography (LORETA) current density images. In contrast with the commonly used fixed window of interest (WOI), we proposed to apply an adaptive WOI, which takes into account subjects' P300 latency variability. Our results showed different P3a and P3b source activation patterns in both groups. P3b sources included frontal, parietal and limbic lobes, whereas P3a response generators were localized over bilateral frontal and superior temporal regions. These areas have been related to the discrimination of auditory stimulus and to the inhibition (P3a) or the initiation (P3b) of motor response in a cognitive task. In addition, differences in source localization between Sz and control groups were observed. Sz patients showed lower P3b source activity in bilateral frontal structures and the cingulate. P3a generators were less widespread for Sz patients than for controls in right superior, medial and middle frontal gyrus. Our findings suggest that target and distractor processing involves distinct attentional subsystems, both being altered in Sz. Hence, the study of neuroelectric brain information can provide further insights to understand cognitive processes and underlying mechanisms in Sz. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential for broad-scale transmission of Ebola virus disease during the West Africa crisis: lessons for the Global Health security agenda.

PubMed

Undurraga, Eduardo A; Carias, Cristina; Meltzer, Martin I; Kahn, Emily B

2017-12-01

The 2014-2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola. Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission (based on late 2014 air travel patterns). We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure (e.g. laboratory capacity), and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola. The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak.

Lionfish envenomations in an urban wilderness.

PubMed

Aldred, B; Erickson, T; Lipscomb, J

1996-11-01

Marine envenomations are commonly encountered along coastal regions of the United States. Although less frequent, marine bites and stings do occur in landlocked locales, such as the Midwest, because of an increased interest in keeping these exotic creatures as pets. We report 33 cases of envenomations by captive lionfish (Pterois volitans) called to a regional Chicago poison control center over a 2-year period. All stings were accidental, and 10 (30%) were treated in an emergency department. The wounds were uniformly on the hand, and all presented with local, intense pain. The majority of envenomations were responsive to prompt immersion in nonscalding water within 90 min, and all were advised on tetanus prophylaxis and local wound care. Two patients (6%) required hospitalization. In all cases, those patients envenomated recovered without permanent sequelae. As a result of increasing encounters with lionfish as pets, health care providers. regardless of their locale, should be familiar with the current treatment recommendations.

Effects of a social accountability approach, CARE's Community Score Card, on reproductive health-related outcomes in Malawi: A cluster-randomized controlled evaluation.

PubMed

Gullo, Sara; Galavotti, Christine; Sebert Kuhlmann, Anne; Msiska, Thumbiko; Hastings, Phil; Marti, C Nathan

2017-01-01

Social accountability approaches, which emphasize mutual responsibility and accountability by community members, health care workers, and local health officials for improving health outcomes in the community, are increasingly being employed in low-resource settings. We evaluated the effects of a social accountability approach, CARE's Community Score Card (CSC), on reproductive health outcomes in Ntcheu district, Malawi using a cluster-randomized control design. We matched 10 pairs of communities, randomly assigning one from each pair to intervention and control arms. We conducted two independent cross-sectional surveys of women who had given birth in the last 12 months, at baseline and at two years post-baseline. Using difference-in-difference (DiD) and local average treatment effect (LATE) estimates, we evaluated the effects on outcomes including modern contraceptive use, antenatal and postnatal care service utilization, and service satisfaction. We also evaluated changes in indicators developed by community members and service providers in the intervention areas. DiD analyses showed significantly greater improvements in the proportion of women receiving a home visit during pregnancy (B = 0.20, P < .01), receiving a postnatal visit (B = 0.06, P = .01), and overall service satisfaction (B = 0.16, P < .001) in intervention compared to control areas. LATE analyses estimated significant effects of the CSC intervention on home visits by health workers (114% higher in intervention compared to control) (B = 1.14, P < .001) and current use of modern contraceptives (57% higher) (B = 0.57, P < .01). All 13 community- and provider-developed indicators improved, with 6 of them showing significant improvements. By facilitating the relationship between community members, health service providers, and local government officials, the CSC contributed to important improvements in reproductive health-related outcomes. Further, the CSC builds mutual accountability, and ensures that solutions to problems are locally-relevant, locally-supported and feasible to implement.

Additive manufacturing of hierarchical injectable scaffolds for tissue engineering.

PubMed

Béduer, A; Piacentini, N; Aeberli, L; Da Silva, A; Verheyen, C A; Bonini, F; Rochat, A; Filippova, A; Serex, L; Renaud, P; Braschler, T

2018-06-05

We present a 3D-printing technology allowing free-form fabrication of centimetre-scale injectable structures for minimally invasive delivery. They result from the combination of 3D printing onto a cryogenic substrate and optimisation of carboxymethylcellulose-based cryogel inks. The resulting highly porous and elastic cryogels are biocompatible, and allow for protection of cell viability during compression for injection. Implanted into the murine subcutaneous space, they are colonized with a loose fibrovascular tissue with minimal signs of inflammation and remain encapsulation-free at three months. Finally, we vary local pore size through control of the substrate temperature during cryogenic printing. This enables control over local cell seeding density in vitro and over vascularization density in cell-free scaffolds in vivo. In sum, we address the need for 3D-bioprinting of large, yet injectable and highly biocompatible scaffolds and show modulation of the local response through control over local pore size. This work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

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

Pichon, Baptiste; Campion, Loïc; Delpon, Grégory

Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence ofmore » spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.« less

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

DTIC Science & Technology

2008-08-01

SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

Local control rates of metastatic renal cell carcinoma (RCC) to the bone using stereotactic body radiation therapy: Is RCC truly radioresistant?

PubMed

Amini, Arya; Altoos, Basel; Bourlon, Maria T; Bedrick, Edward; Bhatia, Shilpa; Kessler, Elizabeth R; Flaig, Thomas W; Fisher, Christine M; Kavanagh, Brian D; Lam, Elaine T; Karam, Sana D

2015-01-01

We report the radiographic and clinical response rate of stereotactic body radiation therapy (SBRT) compared with conventional fractionated external beam radiation therapy (CF-EBRT) for renal cell carcinoma (RCC) bone lesions treated at our institution. Forty-six consecutive patients were included in the study, with 95 total lesions treated (50 SBRT, 45 CF-EBRT). We included patients who had histologic confirmation of primary RCC and radiographic evidence of metastatic bone lesions. The most common SBRT regimen used was 27 Gy in 3 fractions. Median follow-up was 10 months (range, 1-64 months). Median time to symptom control between SBRT and CF-EBRT were 2 (range, 0-6 weeks) and 4 weeks (range, 0-7 weeks), respectively. Symptom control rates with SBRT and CF-EBRT were significantly different (P = .020) with control rates at 10, 12, and 24 months of 74.9% versus 44.1%, 74.9% versus 39.9%, and 74.9% versus 35.7%, respectively. The median time to radiographic failure and unadjusted pain progression was 7 months in both groups. When controlling for gross tumor volume, dose per fraction, smoking, and the use of systemic therapy, biologically effective dose ≥80 Gy was significant for clinical response (hazard ratio [HR], 0.204; 95% confidence interval [CI], 0.043-0.963; P = .046) and radiographic (HR, 0.075; 95% CI, 0.013-0.430; P = .004). When controlling for gross tumor volume and total dose, biologically effective dose ≥80 Gy was again predictive of clinical local control (HR, 0.140; 95% CI, 0.025-0.787; P = .026). Toxicity rates were low and equivalent in both groups, with no grade 4 or 5 toxicity reported. SBRT is both safe and effective for treating RCC bone metastases, with rapid improvement in symptoms after treatment and more durable clinical and radiographic response rate. Future prospective trials are needed to further define efficacy and toxicity of treatment, especially in the setting of targeted agents. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Searching for the most cost-effective strategy for controlling epidemics spreading on regular and small-world networks

PubMed Central

Kleczkowski, Adam; Oleś, Katarzyna; Gudowska-Nowak, Ewa; Gilligan, Christopher A.

2012-01-01

We present a combined epidemiological and economic model for control of diseases spreading on local and small-world networks. The disease is characterized by a pre-symptomatic infectious stage that makes detection and control of cases more difficult. The effectiveness of local (ring-vaccination or culling) and global control strategies is analysed by comparing the net present values of the combined cost of preventive treatment and illness. The optimal strategy is then selected by minimizing the total cost of the epidemic. We show that three main strategies emerge, with treating a large number of individuals (global strategy, GS), treating a small number of individuals in a well-defined neighbourhood of a detected case (local strategy) and allowing the disease to spread unchecked (null strategy, NS). The choice of the optimal strategy is governed mainly by a relative cost of palliative and preventive treatments. If the disease spreads within the well-defined neighbourhood, the local strategy is optimal unless the cost of a single vaccine is much higher than the cost associated with hospitalization. In the latter case, it is most cost-effective to refrain from prevention. Destruction of local correlations, either by long-range (small-world) links or by inclusion of many initial foci, expands the range of costs for which the NS is most cost-effective. The GS emerges for the case when the cost of prevention is much lower than the cost of treatment and there is a substantial non-local component in the disease spread. We also show that local treatment is only desirable if the disease spreads on a small-world network with sufficiently few long-range links; otherwise it is optimal to treat globally. In the mean-field case, there are only two optimal solutions, to treat all if the cost of the vaccine is low and to treat nobody if it is high. The basic reproduction ratio, R0, does not depend on the rate of responsive treatment in this case and the disease always invades (but might be stopped afterwards). The details of the local control strategy, and in particular the optimal size of the control neighbourhood, are determined by the epidemiology of the disease. The properties of the pathogen might not be known in advance for emerging diseases, but the broad choice of the strategy can be made based on economic analysis only. PMID:21653570

Searching for the most cost-effective strategy for controlling epidemics spreading on regular and small-world networks.

PubMed

Kleczkowski, Adam; Oleś, Katarzyna; Gudowska-Nowak, Ewa; Gilligan, Christopher A

2012-01-07

We present a combined epidemiological and economic model for control of diseases spreading on local and small-world networks. The disease is characterized by a pre-symptomatic infectious stage that makes detection and control of cases more difficult. The effectiveness of local (ring-vaccination or culling) and global control strategies is analysed by comparing the net present values of the combined cost of preventive treatment and illness. The optimal strategy is then selected by minimizing the total cost of the epidemic. We show that three main strategies emerge, with treating a large number of individuals (global strategy, GS), treating a small number of individuals in a well-defined neighbourhood of a detected case (local strategy) and allowing the disease to spread unchecked (null strategy, NS). The choice of the optimal strategy is governed mainly by a relative cost of palliative and preventive treatments. If the disease spreads within the well-defined neighbourhood, the local strategy is optimal unless the cost of a single vaccine is much higher than the cost associated with hospitalization. In the latter case, it is most cost-effective to refrain from prevention. Destruction of local correlations, either by long-range (small-world) links or by inclusion of many initial foci, expands the range of costs for which the NS is most cost-effective. The GS emerges for the case when the cost of prevention is much lower than the cost of treatment and there is a substantial non-local component in the disease spread. We also show that local treatment is only desirable if the disease spreads on a small-world network with sufficiently few long-range links; otherwise it is optimal to treat globally. In the mean-field case, there are only two optimal solutions, to treat all if the cost of the vaccine is low and to treat nobody if it is high. The basic reproduction ratio, R(0), does not depend on the rate of responsive treatment in this case and the disease always invades (but might be stopped afterwards). The details of the local control strategy, and in particular the optimal size of the control neighbourhood, are determined by the epidemiology of the disease. The properties of the pathogen might not be known in advance for emerging diseases, but the broad choice of the strategy can be made based on economic analysis only.

Hip proprioceptors preferentially modulate reflexes of the leg in human spinal cord injury

PubMed Central

Onushko, Tanya; Hyngstrom, Allison

2013-01-01

Stretch-sensitive afferent feedback from hip muscles has been shown to trigger long-lasting, multijoint reflex responses in people with chronic spinal cord injury (SCI). These reflexes could have important implications for control of leg movements during functional activities, such as walking. Because the control of leg movement relies on reflex regulation at all joints of the limb, we sought to determine whether stretch of hip muscles modulates reflex activity at the knee and ankle and, conversely, whether knee and ankle stretch afferents affect hip-triggered reflexes. A custom-built servomotor apparatus was used to stretch the hip muscles in nine chronic SCI subjects by oscillating the legs about the hip joint bilaterally from 10° of extension to 40° flexion. To test whether stretch-related feedback from the knee or ankle would be affected by hip movement, patellar tendon percussions and Achilles tendon vibration were delivered when the hip was either extending or flexing. Surface electromyograms (EMGs) and joint torques were recorded from both legs. Patellar tendon percussions and Achilles tendon vibration both elicited reflex responses local to the knee or ankle, respectively, and did not influence reflex responses observed at the hip. Rather, the movement direction of the hip modulated the reflex responses local to the joint. The patellar tendon reflex amplitude was larger when the perturbation was delivered during hip extension compared with hip flexion. The response to Achilles vibration was modulated by hip movement, with an increased tonic component during hip flexion compared with extension. These results demonstrate that hip-mediated sensory signals modulate activity in distal muscles of the leg and appear to play a unique role in modulation of spastic muscle activity throughout the leg in SCI. PMID:23615544

Feeling stretched or compressed? The multiple mechanosensitive responses of wood formation to bending.

PubMed

Roignant, Jeanne; Badel, Éric; Leblanc-Fournier, Nathalie; Brunel-Michac, Nicole; Ruelle, Julien; Moulia, Bruno; Decourteix, Mélanie

2018-05-11

Trees constantly experience wind, perceive resulting mechanical cues, and modify their growth and development accordingly. Previous studies have demonstrated that multiple bending treatments trigger ovalization of the stem and the formation of flexure wood in gymnosperms, but ovalization and flexure wood have rarely been studied in angiosperms, and none of the experiments conducted so far has used multidirectional bending treatments at controlled intensities. Assuming that bending involves tensile and compressive strain, we hypothesized that different local strains may generate specific growth and wood differentiation responses. Basal parts of young poplar stems were subjected to multiple transient controlled unidirectional bending treatments during 8 weeks, which enabled a distinction to be made between the wood formed under tensile or compressive flexural strains. This set-up enabled a local analysis of poplar stem responses to multiple stem bending treatments at growth, anatomical, biochemical and molecular levels. In response to multiple unidirectional bending treatments, poplar stems developed significant cross-sectional ovalization. At the tissue level, some aspects of wood differentiation were similarly modulated in the compressed and stretched zones (vessel frequency and diameter of fibres without a G-layer), whereas other anatomical traits (vessel diameter, G-layer formation, diameter of fibres with a G-layer and microfibril angle) and the expression of fasciclin-encoding genes were differentially modulated in the two zones. This work leads us to propose new terminologies to distinguish the 'flexure wood' produced in response to multiple bidirectional bending treatments from wood produced under transient tensile strain (tensile flexure wood; TFW) or under transient compressive strain (compressive flexure wood; CFW). By highlighting similarities and differences between tension wood and TFW and by demonstrating that plants could have the ability to discriminate positive strains from negative strains, this work provides new insight into the mechanisms of mechanosensitivity in plants.

Function of beta 2-adrenergic receptors in chronic localized myalgia.

PubMed

Maekawa, Kenji; Kuboki, Takuo; Inoue, Eitoku; Inoue-Minakuchi, Mami; Suzuki, Koji; Yatani, Hirofumi; Clark, Glenn T

2003-01-01

To investigate alteration of beta 2-adrenergic receptor (beta 2 AR) function in chronic localized myalgia subjects by evaluating levels of the beta 2 AR second messenger, cyclic adenosine monophosphate (cAMP), in mononuclear cells after beta AR-agonist stimulation. Eleven chronic localized myalgia subjects and 21 matched healthy controls participated in this study. Peripheral blood (30 cc) was drawn from the subjects' anterocubital vein. Mononuclear cells were isolated from the total blood by using the Ficoll-Hypaque gradient technique. Basal and stimulated intracellular cAMP levels were determined by enzyme immunoassay using a commercially available kit. Aliquots of 5 x 10(6) cells were incubated with or without stimulation of the beta AR-agonist isoproterenol for 5 minutes. Five different concentrations of isoproterenol (10(-3) M to 10(-7) M) were utilized. cAMP levels in both groups were tested statistically by a 2-way repeated-measures ANOVA with 2 predictors, group difference and isoproterenol concentration difference. As with isoproterenol stimulation, the cAMP responses to forskolin, which activates adenylyl cyclase directly and produces cAMP, bypassing the cell surface receptors were also measured. The basal cAMP levels in both groups (myalgia: 0.33 +/- 0.02 pmol/5 x 10(6) cells; control: 0.43 +/- 0.10 pmol/5 x 10(6) cells) were almost identical, and isoproterenol-produced cAMP levels increased dose-dependently in both groups. No significant differences in the mean cAMP levels were observed between the groups (P = .909). Significant increases were observed according to the isoproterenol concentration increase (P < .0001). The cAMP responses to forskolin stimulation also showed no significant group difference (P = .971). These results suggest that beta 2 AR function is not different between localized myalgia subjects and healthy individuals.

Collaborative Public Health Investigation of Clenbuterol-Adulterated Heroin Outbreak-Richmond, Virginia, March-April 2015.

PubMed

Gleason, Brigette; West, Angela; Avula, Danny; Utah, Okey; Vogt, Marshall; Cumpston, Kirk; Kelly, Michael; Brasler, Paul; Wyatt, Shane; Forlano, Laurie

In March 2015, the Virginia Department of Health (VDH) was alerted by the Virginia Poison Center of a 6-patient cluster treated for severe clinical presentations after using heroin. Patients' symptoms were atypical for heroin use, and concern existed that patients were exposed to heroin that had been adulterated with or replaced by another substance. To understand the extent and characterization of the outbreak and implement response measures to prevent further cases. The purpose of this report is to highlight the collaborative nature of a public health investigation among a diverse group of stakeholders. Active surveillance and retrospective case finding. Richmond metro area community and hospitals. Regional poison centers, the Division of Consolidated Laboratory Services, the Department of Behavioral Health and Developmental Services, community partners, local law enforcement, and multiple VDH divisions. Outbreak investigation, communication to public health professionals, clinicians, and the community, and liaising with the local law enforcement. Outbreak control. Laboratory confirmation of clenbuterol in clinical specimens implicated it as the heroin adulterant. Thirteen patients met clinical and epidemiologic criteria for exposure to clenbuterol-adulterated heroin. All patients were associated with a localized area within Richmond, and patient interviews elucidated heroin supplier information. VDH collaborated with local law enforcement agents who investigated and arrested the supplier, leading to cessation of the outbreak. This outbreak highlights the value of policies and practices that support an integrated outbreak response among public health practitioners, poison center staff, laboratorians, clinicians, law enforcement agents, community groups, and other agencies. Collaboration enabled implementation of effective control measures-including those outside the purview of the health department-and should be standard practice in future outbreaks involving illicit substances.

Image-guided percutaneous cryotherapy for the management of gynecologic cancer metastases.

PubMed

Solomon, Leigh A; Munkarah, Adnan R; Vorugu, Vinaya R; Deppe, Gunter; Adam, Barbara; Malone, John M; Littrup, Peter J

2008-11-01

To report the clinical response to image-guided percutaneous cryotherapy (IPC) for the palliative management of localized metastases in patients with gynecologic malignancies. Institutional review board approval and patient consent were obtained. Gynecologic oncology patients were identified from our institution's cryotherapy database from August 2003 to August 2007. Cryotherapy was performed with 2.4 mm diameter probes (Endocare, Irvine, CA) with ultrasound or computerized tomography (CT) guidance under conscious sedation and local anesthesia. Follow-up was conducted by imaging studies and clinical encounters, using Response Evaluation Criteria in Solid Tumors (RECIST criteria). Twenty-eight ablation sessions were performed for 41 metastatic foci in 15 patients with gynecologic malignancies. Twelve patients had prior chemotherapy and 5 patients had prior radiation. Median follow-up was 317.5 days (range 95-1189). Median post-procedure pain score: 3/10 (range 0-5). Mean initial tumor size was 2.6 cm in maximal diameter. Median reduction in tumor diameter at 1 month was 21.4% (range 2-67.4%), at 3 months was 43.6% (range 16-80.4%), at 6 months was 54.7% (range (16.6-88.9%) and at 9 months was 58.2% (range 32-88.9%). Ten patients received concurrent chemotherapy, 8 had progression of disease at other sites and 2 had stable disease, while the cryotherapy site improved. One of 5 patients who had cryotherapy in the previously irradiated zone had recurrence. A liver capsule hematoma developed as an immediate complication in one patient and an enterocutaneous fistula developed in another. IPC is a well-tolerated, effective tool for local control of isolated metastatic foci as a single-modality treatment and for local control of symptomatic metastases in select patients undergoing systemic therapy for the management of gynecologic malignancies.

Effects of ACE inhibition and ANG II stimulation on renal Na-Cl cotransporter distribution, phosphorylation, and membrane complex properties

PubMed Central

Lee, Donna H.; Maunsbach, Arvid B.; Riquier-Brison, Anne D.; Nguyen, Mien T. X.; Fenton, Robert A.; Bachmann, Sebastian; Yu, Alan S.

2013-01-01

The renal distal tubule Na-Cl cotransporter (NCC) reabsorbs <10% of the filtered Na+ but is a key control point for blood pressure regulation by angiotensin II (ANG II), angiotensin-converting enzyme inhibitors (ACEI), and thiazide diuretics. This study aimed to determine whether NCC phosphorylation (NCCp) was regulated by acute (20–30 min) treatment with the ACEI captopril (12 μg/min × 20 min) or by a sub-pressor dose of ANG II (20 ng·kg−1·min−1) in Inactin-anesthetized rats. By immuno-EM, NCCp was detected exclusively in or adjacent to apical plama membranes (APM) in controls and after ACEI or ANG II treatment, while NCC total was detected in both APM and subapical cytoplasmic vesicles (SCV) in all conditions. In renal homogenates, neither ACEI nor ANG II treatment altered NCCp abundance, assayed by immunoblot. However, by density gradient fractionation we identified a pool of low-density APM in which NCCp decreased 50% in response to captopril and was restored during ANG II infusion, and another pool of higher-density APM that responded reciprocally, indicative of regulated redistribution between two APM pools. In both pools, NCCp was preferentially localized to Triton-soluble membranes. Blue Native gel electrophoresis established that APM NCCp localized to ∼700 kDa complexes (containing γ-adducin) while unphosphorylated NCC in intracellular membranes primarily localized to ∼400 kDa complexes: there was no evidence for native monomeric or dimeric NCC or NCCp. In summary, this study demonstrates that phosphorylated NCC, localized to multimeric complexes in the APM, redistributes in a regulated manner within the APM in response to ACEI and ANG II. PMID:23114965

Challenges to conservation: land use change and local participation in the Al Reem Biosphere Reserve, West Qatar

PubMed Central

2010-01-01

One response to humanity's unsustainable use of natural resources and consequent degradation, even destruction of the environment, is to establish conservation areas to protect Nature and preserve biodiversity at least in selected regions. In Qatar, the government has shown strong support for this approach, confronted by the environmental consequences of oil and gas extraction and rapid urban development, by designating about one-tenth of the country a conservation area. Located in the west of the peninsula, it comprises the Al Reem Reserve, subsequently declared a UNESCO Biosphere Reserve. Several approaches have figured in conservation, currently popular is co-management featuring participation of the local population, which recognises that people's activities often contribute to today's environment, with the promotion of bio-cultural diversity. However, these assumptions may not hold where rapid social and cultural change occurs, as in Qatar. We explore the implications of such change, notably in land use. We detail changes resulting with the move from nomadic to sedentary lifestyles: in land access, which now features tribal-state control, and herding strategies, which now feature migrant labour and depend on imported fodder and water, underwritten by the country's large gas and oil revenues. Current stocking arrangements - animals herded in much smaller areas than previously - are thought responsible for the degradation of natural resources. The place of animals, notably camels, in Qatari life, has also changed greatly, possibly further promoting overstocking. Many local people disagree. What are the implications of such changes for the participatory co-management of conservation areas? Do they imply turning the clock back to centrally managed approaches that seek to control access and local activities? PMID:20964818

Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy.

PubMed

Palta, Manisha; Patel, Pretesh; Broadwater, Gloria; Willett, Christopher; Pepek, Joseph; Tyler, Douglas; Zafar, S Yousuf; Uronis, Hope; Hurwitz, Herbert; White, Rebekah; Czito, Brian

2012-05-01

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.