bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Cycle of Arsenic Trioxide–Based Consolidation Chemotherapy Spares Anthracycline Exposure in the Primary Management of Acute Promyelocytic Leukemia
Authors: Gore Steven D. , Gojo Ivana , Sekeres Mikkael A. , Morris Lawrence , Devetten Marcel , Jamieson Katarzyna , Redner Robert L. , Arceci Robert , Owoeye Ibitayo , Dauses Tianna , Schachter-Tokarz Esther , Gallagher Robert E.
Published: January 2010

Purpose

Event-free survival following all-trans-retinoic acid (ATRA) –based therapy for acute promyelocytic leukemia (APL) averages 70% at 5 years. While arsenic trioxide (ATO) can induce remissions in 95% of relapsed patients, few studies have addressed the integration of ATO into the primary management of APL. This study examines the efficacy of a single cycle of ATO-based consolidation therapy in a treatment regimen designed to decrease exposure to other cytotoxic agents.

Patients and Methods

After induction with ATRA and daunorubicin (DRN), untreated patients with APL received 3 days of cytarabine and DRN followed by 30 doses of ATO beginning on day 8. Molecular remitters received 2 years of risk-based maintenance therapy.

Results

Forty-one of 45 patients receiving induction therapy achieved remission; four patients died (one before treatment was initiated). Thirty-seven patients received consolidation and maintenance; of these one patient relapsed (CNS) and one died in remission during maintenance therapy (hepatic sickle cell crisis). With a median follow-up of 2.7 years, estimated disease-free survival was 90%; overall survival for all patients was 88%. Despite a total anthracycline dose of only 360 mg/m2, cardiac ejection fraction decreased by ≥ 20% in 20% of patients.

Conclusion

These data, combined with other recent studies using ATO in the primary management of APL, demonstrate the important role that ATO can play in the primary management of this curable disease. Future studies should continue to focus on reducing the toxicity of treatment without increasing the relapse rate.
A method to evaluate interfacial fracture energy on a fibre/matrix interface
Authors: Ni Q-Q
Published: January 2010

A double cleavage drilled compression (DCDC) specimen was analysed using the boundary element method. The DCDC specimen of FRP composites was proposed and used to evaluate the interfacial behaviour and fracture energy in model composites of carbon fibre reinforced polymer (CFRP). As a result, it was confirmed that the DCDC specimen had the mode I stress distribution for the hole offsetting displacement of b = 0, in which the specimen configuration was symmetrical, while it had the mixed-mode stress distribution for b = 0. The approach of calculating the interfacial fracture energy was established using both the analysis and experiments. Furthermore, the bridging fibre DCDC specimen was proposed and the effect of bridging fibres on the loading phase was made clear. It was shown that the DCDC test was a useful method to evaluate the interfacial behaviour of fibre/matrix in composites.
The Digital Eczema Centre Utrecht
Authors: van Os-Medendorp Harmieke , van Veelen Carien , Hover Maaike , Eland-de Kok Petra , Bruijnzeel-Koomen Carla , Sonnevelt Gert-Jan , Mensing Geert , Pasmans Suzanne
Published: January 2010

The University Medical Centre Utrecht (UMC Utrecht) has developed an eczema portal that combines e-consulting, monitoring and self-management training by a dermatology nurse online for patients and parents of young children with atopic dermatitis (AD). Patient satisfaction with the portal was high. It could be extended to become a Digital Eczema Centre for multidisciplinary collaboration between health-care providers from different locations and the patient. Before starting the construction of the Digital Eczema Centre, the feasibility was examined by carrying out a business case analysis. The purposes, strength and weaknesses showed that the Digital Eczema Centre offered opportunities to improve care for patients with AD. The financial analysis resulted in a medium/best case scenario with a positive result of €50–240,000 over a period of five years. We expect that the Digital Eczema Centre will increase the accessibility and quality of care. The web-based patient record and the digital chain-of-care promote the involvement of patients, parents and multidisciplinary teams as well as the continuity and coordination of care.
Patient-initiated online support groups: motives for initiation, extent of success and success factors
Authors: van Uden-Kraan Cornelia F , Drossaert Constance H C , Taal Erik , Seydel Erwin R , van de Laar Mart A F J
Published: January 2010

We studied the success and success factors of online support groups (OSGs) for patients, and the motives and goals of people who start such groups. We interviewed 23 webmasters of OSGs for patients with breast cancer, fibromyalgia and arthritis. The majority were women ( n = 20) and most were patients ( n = 21). Analysis of the interviews revealed that webmasters had altruistic and intrinsic motives for initiating an online support group. They defined success as the fulfilment of the goals they had in mind when they initiated their groups. To be able to make a group successful, decisions about its organization and management need to be coherent with these goals. Most webmasters stressed that promoting the group, keeping it alive and moderating the messages were vital success factors during the evolution stage. Management of the OSGs took up much of the webmasters' time and energy. On average webmasters were occupied with the group for 10–15 hours a week. Our study provides an overview of the pros and cons of differing decisions that have to be made when initiating an OSG.
Adding value to figures: a web-based European public health information system
Authors: van der Wilk Eveline A , Verschuuren Marieke
Published: January 2010

In 2008 a prototype, web-based system was launched which provided information for different user groups interested in European public health topics. The EUPHIX system contained scientifically sound data, with presentations as well as textual information. The information was structured according to the European Community Health Indicators (ECHI) shortlist. The information included different types of data presentations (tables, interactive graphs and maps), explanatory texts and overviews of the data sources and the literature used. The content was produced by a network of European experts according to a structured, peer-reviewed editorial process. Thus EUPHIX provided an easily accessible, comprehensive, state-of-the-art information source. To ensure that it will continue, financial support will be needed. Co-ownership by the European Commission and the Member States seems an appropriate solution.
Design and implementation of a secure and user-friendly broker platform supporting the end-to-end provisioning of e-homecare services
Authors: Van Hoecke Sofie , Steurbaut Kristof , Taveirne Kristof , De Turck Filip , Dhoedt Bart
Published: January 2010

We designed a broker platform for e-homecare services using web service technology. The broker allows efficient data communication and guarantees quality requirements such as security, availability and cost-efficiency by dynamic selection of services, minimizing user interactions and simplifying authentication through a single user sign-on. A prototype was implemented, with several e-homecare services (alarm, telemonitoring, audio diary and video-chat). It was evaluated by patients with diabetes and multiple sclerosis. The patients found that the start-up time and overhead imposed by the platform was satisfactory. Having all e-homecare services integrated into a single application, which required only one login, resulted in a high quality of experience for the patients.
Feasibility of web-based decision aids in neurological patients
Authors: van Til Janine A , Drossaert Constance H C , Renzenbrink Gerbert J , Snoek Govert J , Dijkstra Evelien , Stiggelbout Anne M , IJzerman Maarten J
Published: January 2010

Decision aids (DAs) may be helpful in improving patients' participation in medical decision-making. We investigated the potential for web-based DAs in a rehabilitation population. Two self-administered DAs focused on the treatment of acquired ankle-foot impairment in stroke and the treatment of arm-hand function in cervical spinal cord injury (SCI). Data collection comprised a telephone interview and a self-reported paper questionnaire. Of the patients who agreed to participate, 39 stroke patients (44%) and 38 patients with SCI (78%) returned a questionnaire. More than 75% of patients expressed a need for more information about the treatment of disease-related impairment. The DAs were highly appreciated by both patient groups. Nearly all patients expressed a positive attitude towards the use of the web-based DAs in general practice. The DAs had a positive effect on the knowledge about the treatment alternatives in the stroke patients ( P = 0.001), although not in the patients with SCI. The DAs reduced patients' conflict about treatment ( P < 0.05). The effect of the DAs on patients' desired role in decision-making was limited. Web-based aids are feasible in the rehabilitation population with access to a computer and can improve the knowledge gaps in patients.
Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers for the Prevention of Migraines
Authors: Gales Barry J , Bailey Emilee K , Reed Ashley N , Gales Mark A
Published: January 2010

Objective:

To evaluate the literature examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis.

Data Sources:

MEDLINE (1966–October 2009) and International Pharmaceutical Abstracts were searched using the terms migraine, headache, renina-ngiotensin system, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, aldosterone antagonist, and the individual agents in these classes.

Study Selection and Data Extraction:

English-language human clinical trials, case reports, and systematic reviews were evaluated for efficacy and safety data. The references of reviewed articles were examined to identify additional sources.

Data Synthesis:

Preventative trials evaluating ACE inhibitors consist of a case series, 2 open-label trials, and a placebo-controlled trial. Lisinopril reduced headache hours 20%, headache days 17%, and migraine days 21% versus placebo In the controlled trial (p < 0.06). Clinically significant (>50%) reductions in migraine measures were more common (52–66%) in open-label ACE inhibitor trials than in the controlled (32–36%) trial. Preventive trials evaluating ARBs consist of a meta-analysis, an open-label trial, and 2 placebo-controlled trials. Candesartan reduced headache hours 31%, headache days 26%, and migraine days 28% versus placebo in the first controlled trial (p ≤ 0.001). Telmisartan did not reduce any prespecified primary or secondary outcome measures in the second controlled trial. Clinically significant reductions (>50%) in migraine measures were more common (54–88%) in open-label ARB trials than in the controlled (26–38%) trials. A prescription database review found that ACE inhibitor or ARB therapy halved the use of abortive migraine agents compared to diuretic therapy.

Conclusions:

ACE inhibitors and ARBs have migraine prophylaxis activity similar to that of some currently utilized agents. Low-dose lisinopril or candesartan may be reasonable second- or third-line agents, particularly in patients with other indications for ACE inhibitor or ARB therapy. Further controlled clinical trials are needed to delineate the role of these agents in migraine prevention.
A Battery of Cell- and Structure-specific Markers for the Adult Porcine Retina
Authors: Johansson Ulrica Englund , Eftekhari Sajedeh , Warfvinge Karin
Published: January 2010

The pig is becoming an increasingly used non-primate model in experimental studies of human retinal diseases and disorders. The anatomy, size, and vasculature of the porcine eye and retina closely resemble their human counterparts, which allows for application of standard instrumentation and diagnostics used in the clinic. Despite many reports that demonstrate immunohistochemistry as a useful method for exploring neuropathologi-cal changes in the mammalian central nervous system, including the pig, the porcine retina has been sparsely described. Hence, to facilitate further immunohistochemical analysis of the porcine retina, we report on the successful use of a battery of antibodies for staining of paraformaldehyde-fixed cryosectioned retina. The following antibodies were evaluated for neuronal cells and structures: recoverin (cones and rods), Rho4D2 (rods), transducin-γ (cones), ROM-1 (photoreceptor outer segments), calbindin (horizontal cells), PKC-α (bipolar cells), parvalbumin (amacrine and displaced amacrine cells), and NeuN (ganglion cells and displaced amacrines). For detecting synaptic connections in fiber layers, we used an antibody against synaptobrevin. For detecting retinal pigment epithelium, we studied antibodies against cytokeratin and RPE65, respectively. The glial cell markers used were bFGF (Müller cells and displaced amacrine cells), GFAP (Müller cells and astrocytes), and vimentin (Müller cells). Each staining effect was evaluated with regard to its specificity, sensitivity, and repro-ducibility in the identification of individual cells, specific cell structures, and fiber layers, respectively. The markers parvalbumin and ROM-1 were tested here for the first time for the porcine retina. All antibodies tested resulted in specific staining of high quality. In conclusion, all immunohistochemical protocols presented here will be applicable in fixed, cryosectioned pig retina.
Genetically Defined Inhibitory Neurons in the Mouse Spinal Cord Dorsal Horn: A Possible Source of Rhythmic Inhibition of Motoneurons during Fictive Locomotion
Authors: Wilson Jennifer M. , Blagovechtchenski Evgueni , Brownstone Robert M.
Published: January 2010

To ensure alternation of flexor and extensor muscles during locomotion, the spinal locomotor network provides rhythmic inhibition to motoneurons. The source of this inhibition in mammals is incompletely defined. We have identified a population of GABAergic interneurons located in medial laminae V/VI that express green fluorescent protein (GFP) in glutamic acid decarboxylase-65::GFP transgenic mice. Immunohistochemical studies revealed GFP+ terminals in apposition to motoneuronal somata, neurons in Clarke's column, and in laminae V/VI where they apposed GFP+ interneurons, thus forming putative reciprocal connections. Whole-cell patch-clamp recordings from GFP+ interneurons in spinal cord slices revealed a range of electrophysiological profiles, including sag and postinhibitory rebound potentials. Most neurons fired tonically in response to depolarizing current injection. Calcium transients demonstrated by two-photon excitation microscopy in the hemisected spinal cord were recorded in response to low-threshold dorsal root stimulation, indicating these neurons receive primary afferent input. Following a locomotor task, the number of GFP+ neurons expressing Fos increased, indicating that these neurons are active during locomotion. During fictive locomotion induced in the hemisected spinal cord, two-photon excitation imaging demonstrated rhythmic calcium activity in these interneurons, which correlated with the termination of ventral root bursts. We suggest that these dorsomedial GABAergic interneurons are involved in spinal locomotor networks, and may provide direct rhythmic inhibitory input to motoneurons during locomotion.
Efficient Encoding of Vocalizations in the Auditory Midbrain
Authors: Holmstrom Lars A. , Eeuwes Lonneke B. M. , Roberts Patrick D. , Portfors Christine V.
Published: January 2010

An important question in sensory neuroscience is what coding strategies and mechanisms are used by the brain to detect and discriminate among behaviorally relevant stimuli. There is evidence that sensory systems migrate from a distributed and redundant encoding strategy at the periphery to a more heterogeneous encoding in cortical structures. It has been hypothesized that heterogeneity is an efficient encoding strategy that minimizes the redundancy of the neural code and maximizes information throughput. Evidence of this mechanism has been documented in cortical structures. In this study, we examined whether heterogeneous encoding of complex sounds contributes to efficient encoding in the auditory midbrain by characterizing neural responses to behaviorally relevant vocalizations in the mouse inferior colliculus (IC). We independently manipulated the frequency, amplitude, duration, and harmonic structure of the vocalizations to create a suite of modified vocalizations. Based on measures of both spike rate and timing, we characterized the heterogeneity of neural responses to the natural vocalizations and their perturbed variants. Using information theoretic measures, we found that heterogeneous response properties of IC neurons contribute to efficient encoding of behaviorally relevant vocalizations.
The Place Code of Saccade Metrics in the Lateral Bank of the Intraparietal Sulcus
Authors: Savaki Helen E. , Gregoriou Georgia G. , Bakola Sophia , Raos Vassilis , Moschovakis Adonis K.
Published: January 2010

The lateral intraparietal area (LIP) of monkeys is known to participate in the guidance of rapid eye movements (saccades), but the means it uses to specify movement variables are poorly understood. To determine whether area LIP devotes neural space to encode saccade metrics spatially, we used the quantitative [14C]deoxyglucose method to obtain images of the distribution of metabolic activity in the intraparietal sulcus (IPs) of rhesus monkeys trained to repeatedly execute saccades of the same amplitude and direction for the duration of the experiment. Different monkeys were trained to perform saccades of different sizes and in different directions. A clear topography of saccade metrics was found in the cytoarchitectonically identified area LIP ventral (LIPv) contralateral to the direction of the eye movements. We demonstrate that the representation of the vertical meridian runs parallel to the fundus of the IPs and that it is not orthogonal to the representation of the horizontal meridian. Instead, the latter runs through the middle of LIPv parallel to its border with area LIP dorsal (LIPd). The upper part of oculomotor space is represented rostrally and dorsally relative to the horizontal meridian toward the LIPv–LIPd border, whereas the lower part of oculomotor space is represented caudally and ventrally toward the caudal edge of the IPs. Saccade amplitude is also represented in an orderly manner.
Chromogranin B Gene Ablation Reduces the Catecholamine Cargo and Decelerates Exocytosis in Chromaffin Secretory Vesicles
Authors: Díaz-Vera Jésica , Morales Yézer G. , Hernández-Fernaud Juan R. , Camacho Marcial , Montesinos Mónica S. , Calegari Federico , Huttner Wieland B. , Borges Ricardo , Machado José D.
Published: January 2010

Chromogranins/secretogranins (Cgs) are the major soluble proteins of large dense-core secretory vesicles (LDCVs). We have recently reported that the absence of chromogranin A (CgA) caused important changes in the accumulation and in the exocytosis of catecholamines (CAs) using a CgA-knock-out (CgA-KO) mouse. Here, we have analyzed a CgB-KO mouse strain that can be maintained in homozygosis. These mice have 36% less adrenomedullary epinephrine when compared toChgb+/+[wild type (WT)], whereas the norepinephrine content was similar. The total evoked release of CA was 33% lower than WT mice. This decrease was not due to a lower frequency of exocytotic events but to less secretion per quantum (∼30%) measured by amperometry; amperometric spikes exhibited a slower ascending but a normal decaying phase. Cell incubation withl-DOPA increased the vesicle CA content of WT but not of the CgB-KO cells. Intracellular electrochemistry, using patch amperometry, showed thatl-DOPA overload produced a significantly larger increase in cytosolic CAs in cells from the KO animals than chromaffin cells from the WT. These data indicate that the mechanisms for vesicular accumulation of CAs in the CgB-KO cells were saturated, while there was ample capacity for further accumulation in WT cells. Protein analysis of LDCVs showed the overexpression of CgA as well as other proteins apparently unrelated to the secretory process. We conclude that CgB, like CgA, is a highly efficient system directly involved in monoamine accumulation and in the kinetics of exocytosis from LDCVs.
Knockdown of L Calcium Channel Subtypes: Differential Effects in Neuropathic Pain
Authors: Fossat Pascal , Dobremez Eric , Bouali-Benazzouz Rabia , Favereaux Alexandre , Bertrand Sandrine S. , Kilk Kalle , Léger Claire , Cazalets Jean-René , Langel Ülo , Landry Marc , Nagy Frédéric
Published: January 2010

The maintenance of chronic pain states requires the regulation of gene expression, which relies on an influx of calcium. Calcium influx through neuronal L-type voltage-gated calcium channels (LTCs) plays a pivotal role in excitation–transcription coupling, but the involvement of LTCs in chronic pain remains unclear. We used a peptide nucleic acid (transportan 10-PNA conjugates)-based antisense strategy to investigate the role of the LTC subtypes CaV1.2 and CaV1.3 in long-term pain sensitization in a rat model of neuropathy (spinal nerve ligation). Our results demonstrate that specific knockdown of CaV1.2 in the spinal dorsal horn reversed the neuropathy-associated mechanical hypersensitivity and the hyperexcitability and increased responsiveness of dorsal horn neurons. Intrathecal application of anti-CaV1.2 siRNAs confirmed the preceding results. We also demonstrated an upregulation of CaV1.2 mRNA and protein in neuropathic animals concomitant to specific CaV1.2-dependent phosphorylation of the cAMP response element (CRE)-binding protein (CREB) transcription factor. Moreover, spinal nerve ligation animals showed enhanced transcription of the CREB/CRE-dependent gene COX-2 (cyclooxygenase 2), which also depends strictly on CaV1.2 activation. We propose that L-type calcium channels in the spinal dorsal horn play an important role in pain processing, and that the maintenance of chronic neuropathic pain depends specifically on channels comprising CaV1.2.
Molecular Identity of Periglomerular and Short Axon Cells
Authors: Kiyokage Emi , Pan Yu-Zhen , Shao Zuoyi , Kobayashi Kazuto , Szabo Gabor , Yanagawa Yuchio , Obata Kunihiko , Okano Hideyuki , Toida Kazunori , Puche Adam C. , Shipley Michael T.
Published: January 2010

Within glomeruli, the initial sites of synaptic integration in the olfactory pathway, olfactory sensory axons terminate on dendrites of projection and juxtaglomerular (JG) neurons. JG cells form at least two major circuits: the classic intraglomerular circuit consisting of external tufted (ET) and periglomerular (PG) cells and an interglomerular circuit comprised of the long-range connections of short axon (SA) cells. We examined the projections and the synaptic inputs of identified JG cell chemotypes using mice expressing green fluorescent protein (GFP) driven by the promoter for glutamic acid decarboxylase (GAD) 65 kDa, 67 kDa, or tyrosine hydroxylase (TH). Virtually all (97%) TH+ cells are also GAD67+ and are thus DAergic–GABAergic neurons. Using a combination of retrograde tracing, whole-cell patch-clamp recording, and single-cell three-dimensional reconstruction, we show that different JG cell chemotypes contribute to distinct microcircuits within or between glomeruli. GAD65+ GABAergic PG cells ramify principally within one glomerulus and participate in uniglomerular circuits. DAergic–GABAergic cells have extensive interglomerular projections. DAergic–GABAergic SA cells comprise two subgroups. One subpopulation contacts 5–12 glomeruli and is referred to as “oligoglomerular.” Approximately one-third of these oligoglomerular DAergic SA cells receive direct olfactory nerve (ON) synaptic input, and the remaining two-thirds receive input via a disynaptic ON→ET→SA circuit. The second population of DAergic–GABAergic SA cells also disynaptic ON input and connect tens to hundreds of glomeruli in an extensive “polyglomerular” network. Although DAergic JG cells have traditionally been considered PG cells, their interglomerular connections argue that they are more appropriately classified as SA cells.
Motor Cortical Representation of Hand Translation and Rotation during Reaching
Authors: Wang Wei , Chan Sherwin S. , Heldman Dustin A. , Moran Daniel W.
Published: January 2010

Previous studies have shown that hand translation is well represented by neuronal activity in the proximal arm area of primary motor cortex (M1). However, little is known about cortical representation of hand rotation in M1. In this study, single-unit activity was recorded from monkeys while they performed a “center-out with rotation” task. When reaching for a target, subjects had to match four separate kinematic parameters: three-dimensional location and one-dimensional orientation of the target. Among the 512 neurons modulated by hand movement, 446 were tuned to hand translation, 326 were tuned to hand rotation, and 260 neurons were tuned to both hand translation and hand rotation. Approximately half of the neurons that encoded both translation and rotation did so in a nonlinear manner. This nonlinear interaction can be modeled as a gain-field type of encoding whereby hand rotational velocity modulated the hand translational cosine tuning curves in a multiplicative manner. Furthermore, this study demonstrated that both hand translation and hand rotation can be decoded simultaneously from a population of motor cortical neurons.
Lack of Medial Prefrontal Cortex Activation Underlies the Immediate Extinction Deficit
Authors: Kim Seok Chan , Jo Yong Sang , Kim Il Hwan , Kim Hyun , Choi June-Seek
Published: January 2010

We conducted a series of experiments to investigate the neural basis of the immediate extinction deficit, the lack of extinction when the interval between fear memory acquisition and extinction is short. In experiment 1, rats were given extinction training composed of 15 conditioned stimuli (CSs) either 15 min (immediate extinction: I-EXT) or 24 h (delayed extinction: D-EXT) after five tone–shock pairings. In the retention test performed 48 h after conditioning, I-EXT group exhibited significantly higher freezing than D-EXT group. In experiment 2, functional activation in the medial prefrontal cortex (mPFC) was detected usingc-fosimmunoreactivity. The number of Fos-positive neurons in the mPFC was significantly lower in I-EXT group than in D-EXT group. In experiment 3, rats received immediate extinction with microstimulation of the infralimbic region (IL) of the mPFC, either contingently paired or unpaired with the CS. In a subsequent retention test, the paired stimulation group exhibited decreased freezing relative to the unpaired stimulation group. Together, our results suggest that the immediate extinction deficit may be linked to the lack of neuronal activity in the IL.
Transient Overexpression of α-Ca2+/Calmodulin-Dependent Protein Kinase II in the Nucleus Accumbens Shell Enhances Behavioral Responding to Amphetamine
Authors: Loweth Jessica A. , Singer Bryan F. , Baker Lorinda K. , Wilke Georgia , Inamine Hidetoshi , Bubula Nancy , Alexander John K. , Carlezon William A. , Neve Rachael L. , Vezina Paul
Published: January 2010

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to contribute to the expression of psychostimulant sensitization by regulating dopamine (DA) overflow from DA neuron terminals in the nucleus accumbens (NAcc). The present experiments explored the contribution of CaMKII in NAcc neurons postsynaptic to these terminals where it is known to participate in a number of signaling pathways that regulate responding to psychostimulant drugs. Exposure to amphetamine transiently increased αCaMKII levels in the shell but not the core of the NAcc. Thus, HSV (herpes simplex viral) vectors were used to transiently overexpress αCaMKII in NAcc neurons in drug-naive rats, and behavioral responding to amphetamine was assessed. Transiently overexpressing αCaMKII in the NAcc shell led to long-lasting enhancement of amphetamine-induced locomotion and self-administration manifested when αCaMKII levels were elevated and persisting long after they had returned to baseline. Enhanced locomotion was not observed after infection in the NAcc core or sites adjacent to the NAcc. Transient elevation of NAcc shell αCaMKII levels also enhanced locomotor responding to NAcc AMPA and increased phosphorylation levels of GluR1 (Ser831), a CaMKII site, both soon and long after infection. Similar increases in pGluR1 (Ser831) were observed both soon and long after exposure to amphetamine. These results indicate that the transient increase in αCaMKII observed in neurons of the NAcc shell after viral-mediated gene transfer and likely exposure to amphetamine leads to neuroadaptations in AMPA receptor signaling in this site that may contribute to the long-lasting maintenance of behavioral and incentive sensitization by psychostimulant drugs like amphetamine.
A Molecular Mechanism for Ibuprofen-Mediated RhoA Inhibition in Neurons
Authors: Dill John , Patel Ankur R. , Yang Xiao-Li , Bachoo Robert , Powell Craig M. , Li Shuxin
Published: January 2010

Ibuprofen is a nonsteroidal anti-inflammatory drug widely used to relieve pain and inflammation in many disorders via inhibition of cyclooxygenases. Recently, we have demonstrated that ibuprofen inhibits intracellular signaling of RhoA and promotes significant axonal growth and functional recovery following spinal cord lesions in rodents. In addition, another study suggests that ibuprofen reduces generation of amyloid-β42 peptide via inactivation of RhoA signaling, although it may also regulate amyloid-β42 formation by direct inhibition of the γ-secretase complex. The molecular mechanisms by which ibuprofen inhibits the RhoA signal in neurons, however, remain unclear. Here, we report that the transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is essential for coupling ibuprofen to RhoA inhibition and subsequent neurite growth promotion in neurons. Ibuprofen activates PPARγ in neuron-like PC12 and B104 cells. Activation of PPARγ with traditional agonists mimics the RhoA-inhibiting properties of ibuprofen in PC12 cells and, like ibuprofen, promotes neurite elongation in primary cultured neurons exposed to axonal growth inhibitors. Protein knockdown with small interfering RNA specific for PPARγ blocks RhoA suppression of PPARγ agonists in PC12 cells. Moreover, the effect of ibuprofen on RhoA activity and neurite growth in neuronal cultures is prevented by selective PPARγ inhibition. These findings support that PPARγ plays an essential role in mediating the RhoA-inhibiting effect of ibuprofen. Elucidation of the novel molecular mechanisms linking ibuprofen to RhoA inhibition may provide additional therapeutic targets to the disorders characterized by RhoA activation, including spinal cord injuries and Alzheimer's disease.
Doctors’ perceptions of personal boundaries to primary care interactions: A qualitative investigation
Authors: Cocksedge Simon , May Carl
Published: January 2010

Definitions of professional roles and appropriate care are increasingly inclusive in primary care but many subjective factors influence the care that is actually delivered. One such factor is the boundary a clinician puts on his or her self in interactions with patients. This qualitative study investigated doctors’ perceptions of personal boundaries to primary care consultations by exploring two examples: touch and spiritual care. Respondents reported clear but contrasting boundaries: some neither used touch nor explored spiritual care; others regularly undertook both. Some interviewees deliberately varied these boundaries, irrespective of their own views, if they felt this was in their patients’ best interests. Such subjective limits may affect the quality of primary health care offered to some patients and contrast with theoretical definitions which assume both all-encompassing primary care, and doctors’ conscious awareness of themselves and their personal boundaries. The existence of these boundaries, and some doctors’ lack of awareness of them, has educational implications if patient-centred professional role definitions are to be realistically delivered in everyday primary care.
Oral communication skills of international medical graduates: Assessing empathy in discourse
Authors: Cordella Marisa , Musgrave Simon
Published: January 2010

We examine a dataset consisting of 11 International Medical Graduates (IMGs) performing an Objective Structured Clinical Examination (OSCE). Our aim is to address questions about the linguistic realization of empathy in the clinical discourse of IMGs and the extent to which OSCE examiners are sensitive to relevant features of the discourse. We analyse three aspects of the dataset as manifestations of empathy: sequential organization to provide reassurance; responsiveness to the simulated patient's lexical choices for emotionally charged words; and the organization of turn taking in the interaction. Our analysis suggests that in each of these areas it is possible to identify discourse strategies which realize empathy. These strategies are used by IMGs who are good communicators and not used by poor communicators. Our evidence suggests that of the features we examine, the most salient for the examiner is a greater than normal occurrence of transition pauses. We argue that it is only in the area of the organization of conversation that the problems displayed by some IMGs are due to differences in cultural background, and it is therefore significant that the feature we identify as salient comes from this area.
Interactional positions and the production of identities: Negotiating fatherhood in family therapy talk
Authors: Suoninen Eero , Wahlström Jarl
Published: January 2010

Participants in a conversation may, even within the same basic role staging, create different cooperation settings. To describe these cooperative settings, we employ the concept of interactional position as a basic analytical tool. From our understanding of identity as a conversational achievement, we demonstrate how evolving interactional positions frame the construction of client identities in family therapy meetings. We focus particularly on how constructions of fatherhood identity are negotiated in the meetings. The methodological perspective of our study draws on social psychological discourse analysis, conversation analysis and social constructionism, and the data consists of video recordings of six family therapy meetings dealing with a single case. The analysis demonstrates the large variety of combinations of interactional positions that are possible in family therapy conversation and explicates how strongly the construction of the client's identity depends on the position combinations allowed in a therapy session.
Integrated and Optimized Approach to Full Field Modeling For an Offshore Gas Field
Authors: Tyagi Vipin , Sinha Shaurya K. , Dasgupta Ayan , Gopinath B
Published: January 2010

An integrated production system model is an important tool for optimizing gas field planning and mitigating risks. It combines reservoir performance, well inflow and outflow, the surface gathering system and the production host into a single model in which operating envelopes and constraints are captured. Using the tool, representative system production forecasts can be generated to test alternative development decisions against a range of reservoir outcomes, allowing optimum solutions to be identified.

This paper describes the integrated production system modeling approach taken during feasibility studies for areally extensive offshore gas field. Examples of the development decisions tested using the model were the type and size of production host, the type and phasing of wells and the flow assurance strategy.

Key learnings were the need to be systematic about data inputs across disciplines, quality assurance of forecast results and understanding the level of refinement of the model and what development decisions it can reliably be used for. Many gas field development decisions are inter-related and the integrated system model serves as a useful tool for alignment and consistency across the project team.
Reservoir Flow Simulation Study for a Sector in Main Pay-South Rumaila Oil Field
Authors: Mohammed W. J. , Al-Jawad M. S. , Al-Shamma D. A.
Published: January 2010

A reservoir simulator called "SimBest II" has been used in the present study. The oil field under study is a sector of South Rumaila oil field/ main pay. The simulator has been used to study the fluid flow in the reservoir and predict the future behavior of the reservoir. SimBest II consists of two parts: Initialization and Simulation. The validity of the model is achieved by comparing its results with historical performance of the reservoir.

The validity of initialization results has been adjusted according to the actual initial oil in place and the initial pressure and water saturation distributions. Also good matching has been adopted in the simulation part according to average reservoir pressure, well pressure, the time of water breakthrough, and the depths of oil-water contact. Three types of contour maps were plotted at the end of simulation time for all layers of the sector under study which are Pressure contour map (isobaric map), Permeability times sand thickness (capacity) contour map, Oil saturation times porosity (hydrocarbon porosity) contour map. These contour maps are the best indicator for determining the trapped oil zone. The treatment method of water influx at the flow boundary that used in the current study is the Carter-Tracy method. This method yields an influx of water that moves across the flow boundaries.
Influence of Relevant Parameters on Hole Cleaning and Pipe String Erosion in Air Drilling
Authors: Zhu Hongjun , Lin Yuanhua , Meng Yingfeng , Zhao Sijun , Liu Deping , Faqian Luo
Published: January 2010

Air drilling has many advantages over mud drilling in increasing penetration rate, decreasing formation damage, eliminating lost circulation, reducing pressure differential sticking and so on. Hole cleaning and pipe erosion failure are the two key problems for air drilling. Hence proper injecting parameters should not only meet the requirement of carrying cuttings, but also avoid the erosion of drillpipe. For example, if the standpipe pressure was much larger, high-speed air flow with cuttings would cause the erosion of drillpipe and destroy its internal coating, which is the main reason of shorting service time of drillpipe. Other parameters such as drillpipe rotational speed, borehole deviation, eccentricity, cutting size and cutting density also affect the cuttings transportation and pipe erosion. Previous published papers are limited to physical model dimensions and operating parameters, or no exact calculation results due to too many assumptions.

In this paper, a model of gas-solid two-phase flow was built and a new approach to determine the injecting parameters was introduced. Based on the computational fluid dynamics and aerodynamics theory, the flow properties in 311.5mm wellbore, 1500m long, with 127mm drillpipe had been simulated with variable parameters. Then the distributions of pressure, velocity and cuttings volumetric concentration were obtained in drillstring and annulus. By analyzing multi-group calculation results, injecting parameters were optimized to meet the needs of the drilling job. Calculation results coincided well with the actual field data, and had been used to guide air drilling in Da-Wan 3 well, Lao-Jun 1 well, and Qing-Xi 1 well for Chuanqing Drilling and Exploration Corp.
New Completion Methodology to Improve Oil Recovery and Minimize Water Intrusion in Reservoirs Subject to Water Injection
Authors: Sierra Leopoldo , East Loyd , Kulakofsky David
Published: January 2010

Water injection during the early stage of a new reservoir’s development is gaining popularity around the world. This is especially true in Saudi Arabia where water injection is used to improve oil recovery and for pressure maintenance by placing short or long horizontal water-injection wells around the reservoir flanks.

For cases where water-injection wells are placed in reservoir flanks, some of the producing wells are perforated transversally oriented to the water-injection wells to improve the oil recovery around the involved areas. For this specific exploitation strategy, there is a potential risk of water channeling from the injector to the producing well toe which, once it happens, might jeopardize recovery efficiency.

For the referenced exploitation strategy, a new completion methodology considering the placement of a fracture barrier at the toe of the producing well to delay water intrusion and improve recovery efficiency is proposed. This paper discusses the process to create the fracture barrier and the benefits of the completion methodology supported with extensive simulations for the different scenarios.
Effect of Acid Type on Initial Response and Sustenance of Production in Acid Fracturing Treatment: A Field Treatment Evaluation
Authors: Sarma Dilip Kumar , Roy Sharmila , Roul Niranjan , Yadav N. , Singhal C. P.
Published: January 2010

The primary objective of acid fracturing is to generate a conductive flow path between wellbore and reservoir. The factors that governed the effectiveness of acid fracturing treatments are etched fracture penetration and its conductivity. The effective fracture length and its conductivity usually depend on (a) acid convection to the rock surface, b) acid reaction rate and (c) acid leak-off into the reservoir. The etched fracture length is limited by the distance traveled by acid along the fracture. This limit is a greater problem especially in high temperature reservoirs, as the reaction rate is very high with conventional acid systems. Excessive fluid leak-off is another factor that limits fracture extension and etched penetration.

After treatment, the etched non-smooth fracture surfaces leave open pathways, in addition to the wormholes and channels created from the fracture to the formation. The induced fracture tends to close due the effect of in-situ stresses and decline the conductivity. Factors that contribute to the reduction in fracture conductivity upon completion of an acid fracturing treatment are (a) elastic response, (b) compressive failure of the asperities and (c) creeping effect. Therefore, in most of the cases, the initial response of acid fracturing treatment is highly encouraging. However, the sustenance of production may not be adequate because of either insufficient extension of fracture or closure of fractures under the effect of in-situ stresses. Type of acid and treatment methodologies viz. injection rate, leak-off control measures etc. are having significant impact on success of treatments.

To address the issues, different combinations of acid systems were applied in various low producer wells in a tight carbonate reservoir of an offshore field. This paper will present the treatment design, methodology and impact of various acid systems on effectiveness of acid fracturing treatments from field application results.
Spoolable Connector Allows Coiled Tubing Operations Offshore India
Authors: Effiong G. , Dean G. , Nayak S. , Satyarthi R.S.
Published: January 2010

Available footprint on offshore platforms can be a significant challenge for Coiled Tubing (CT) operations. Many times a smaller CT unit is deployed for work that would be faster and operationally easier with CT of larger diameter. Often the platform’s crane capacity dictates the size of CT to be used, which in turn reduces the working envelope of the CT.

Some wells offshore India are completed horizontally and require intervention utilizing larger sizes of CT in order to gain horizontal reach and manipulate sliding sleeves. When CT is used for these operations, the weight of the CT reel itself is critical to the effectiveness of the overall operation and requires proper management. Traditional methods of managing / reducing CT reel weight involve spooling the CT string from a boat to the platform or joining CT sections by butt welding them together on the platform. Bringing the required length of CT onboard in two or more sections and joining them together utilizing the spoolable connector provides significant benefits over the traditional methods. The use of just one spoolable connector can reduce the maximum CT reel lifting weight by typically 30-40%, while increasing the CT size easily by one or two gauge sizes.

This paper describes the results of a feasibility study performed to address typical challenges and presents actual case histories in which a spoolable connector was used to connect two CT strings. Required equipment was built and mobilized so that two separate strings could be joined on the platform with the aid of a connecting jig. Several trips were safely performed without the need to change the spoolable connector. Specific benefits of the spoolable connector over the traditional methods are explained. Methods to monitor the usable life of the spoolable connector while tripping in and out of the well will also be discussed, as well as new developments currently underway.
Dry-tree Support Semi-Submersible for Drilling and Production From Deepwater of East Coast India
Authors: Srinivasan Nagan , Sundaravadivelu R. , Selvakumar R. , Kaundinya V.P.K.
Published: January 2010

The most reliable floating structure for the unexpected storm conditions of east coast India deepwater is presented in this paper. Dry-tree support due to very low heave response in 100 yrs return strom attracted this vessel solution to be cost effective in ultra deepwater. Several advantages are inbuilt including self installation of the vessel. The key design features that would enhance the applications of the semi-submersible design for deepwater are vessel motion characteristics, heave natural period, high air-gap, large deck-area, large deck pay-load, reduced mooring load, large riser pull-down load, feasibility for dynamic positioning, self-installation, quay-side top side integration and float-over installation. This paper presents the design of dry-tree support semisubmersible for drilling and production from deepwater of east coast India. The displacement of the vessel is 82500T, payload is 15000T, free board is 19.85m and the keel tank size is 91.5m by 91.5m by 6.1m. The ballast in the keel tank is 28000T.The hydrodynamic response of the vessel obtained by the experimental study for the retracted condition is used to validate the numerical results. The numerical study on the dry-tree submersible with keel tank in retracted (draft=39.62m) and telescopic condition (draft=65.25m) is carried out and the results are used to demonstrate the application of dry-tree support semi submersible for deep waters of east coast of India.
Middle East Field Water Production Mechanisms
Authors: Al-Ghanim Jassim A. , Al-Nufaili Subhi A.
Published: January 2010

The control of water production has always been one of the most critical challenges in Middle East oil fields. Good evaluation of water production mechanism results in a proper control on water, since there is a different job design for different mechanism. In general, water coning and/or multilayer channeling is the most production problem mechanisms in Middle East oil fields. The purpose of this work is to apply water control diagnostic plots technique to identify excessive water production mechanism.

This method was applied for wells in Middle East sandstone oil reservoirs using actual production history data to generate log- log plots of WOR (water oil ratio) and dWOR/dt (simple time derivative of water oil ratio) vs. time.

The plots were found to be effective in differentiating whether the well is experiencing water coning (negative slope) or multilayer channeling (positive slope for the time derivative of water oil ratio curve).

The diagnostic plots applied in this study provide a handy method for quick evaluation of excessive water production mechanisms in order to select wells candidates for water control treatment.