bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Wellbore Stress Change Caused by Drawdown and Depletion: An Analytical Model for a Vertical Well in a Thin Reservoir
Authors: Schutjens Peter , Kuvshinov Boris N.
Published: September 2010

An analytical model is presented to describe the stress change at the wall of a vertical wellbore because of drawdown and reservoir depletion. The model predicts a lower effective tangential stress and higher effective axial stress (at a given drawdown) than the popular model of Risnes, Bratli, and Horsrud (RBH) model (Risnes et al. 1982; Bratli et al. 1983; Fjær et al. 2008). The reason for this difference is that our model is valid for a finite reservoir thickness ("thin reservoir"), whereas the RBH model is constrained by the condition of an infinite reservoir thickness.

We modeled the production-induced stress change in two reservoirs with different rock properties: Reservoir A has a porosity of approximately 20% and a permeability of up to 30 md; Reservoir B has a porosity of approximately 30% and a permeability of a few darcies. Calculated wellbore stress paths were combined with mechanical properties from core deformation experiments to evaluate the risk of drawdown-induced/depletion-induced shear failure. If we consider only the experimental shear-failure data collected on samples from Reservoir A for the shear-failure limit, then, according to the present model, the planned drawdown of 34 MPa will not lead to wellbore shear failure. Even after 34 MPa of depletion, a drawdown of 34 MPa can be applied safely in Reservoir A. For high-permeability Reservoir B, the model predicts that shear failure of the borehole wall will not occur in the first phase of production, when there is only a drawdown of up to 2 MPa and no depletion. Depending on the shear-failure criterion chosen, the model predicts shear failure after 25 to 42 MPa of depletion. Massive sand production was observed only after some 40 MPa of depletion, confirming that elastic-brittle models are conservative in predicting drawdown-induced or depletion-induced shear failure in a borehole, notably in high-porosity rocks. Our examples show their value in qualitative comparative analysis of shear failure and sand-production risk.
Numerical Evaluation of Hydrocarbon Additives to Steam in the SAGD Process
Authors: Mohebati Moslem Hosseininejad , Maini Brij B. , Harding Thomas G.
Published: September 2010

Heavy oil and bitumen are expected to become increasingly important sources of fuel in the coming decades. Steam assisted gravity drainage (SAGD) is a commercially viable and widely used recovery technique for heavy oil and bitumen. However, it remains an expensive technique and requires large energy input in the form of steam. Energy intensity of SAGD, as well as environmental concerns such as fresh water usage and CO2 emission, make it imperative to find new oil extraction technologies. Coinjecting a hydrocarbon additive with steam offers the potential of higher oil rates and recoveries with lower energy and water consumption.

A reservoir simulation study using a 20X12X15 3D Cartesian model and Athabasca fluid and reservoir properties was conducted to evaluate this process. The role of hydrocarbon additive in the steam chamber and its effect on the performance of SAGD was investigated.

Simulation results revealed the parameters that will have the greatest impact on the process performance and indicated the effectiveness of each hydrocarbon additive in improving the performance of SAGD. The results also showed that selecting the most suitable hydrocarbon additive depends on the operating conditions as well as the original reservoir fluid composition.
Investigation of Cyclic Solvent Injection Process for Heavy Oil Recovery
Authors: Ivory John , Chang Jeannine , Coates Roy , Forshner Ken
Published: September 2010

This paper summarizes numerical and experimental simulation results of a cyclic solvent injection process study, which was part of a continuing investigation into the use of solvents as a follow-up process in Cold Lake and Lloydminster reservoirs that have been pressure-depleted by cold heavy oil production with sand (CHOPS). Typically only 5% - 10% of the original oil in place (OOIP) is recovered during cold production; therefore, an effective follow-up process is required.

The cyclic solvent injection (CSI) experiment consisted of primary production followed by six solvent (28% C3H8  - 72% CO2) injection cycles. Oil recovery after primary production and six solvent cycles was 50%, which indicates the potential viability of the CSI process.

Concurrently with the laboratory physical simulation, a numerical simulation model was developed to represent the physical behaviour of the experimental results. A history match of the primary production portion of the experiment was obtained using an Alberta Innovates - Technology Futures (AITF) foamy oil model. This resulted in the characterization (fluid saturations and pressures) of the oil sandpack at the start of the solvent injection process. The history match of the subsequent six solvent injection cycles was used to validate the numerical model of the CSI process developed at AITF.

This model includes nonequilibrium rate equations that simulated the delay in solvent reaching its equilibrium concentration as it dissolves or exsolves in the oil in response to changes in the pressure and/or gas-phase composition. Dissolution of CH4, C3H8 and CO2 in oil and CO2 in water were considered, as was exsolution of CH4, C3H8 and CO2 from oil and CO2 from water. Reduced gas-phase permeabilities resulting from gas exsolution were also included.

The history match simulations indicated that:

The important mechanisms were represented in the simulations.

Significant oil swelling by solvent dissolution occurs during solvent injection periods. This can reduce solvent injectivity and penetration into a heavy oil reservoir during solvent injection periods.

Low oil and gas-phase relative permeabilities are required during production periods to match the experimental oil and gas production during solvent cycles.

A parametric simulation study showed that the quantity of gas injected in an injection period was relatively insensitive to the oil-phase diffusion coefficients, but was sensitive to solvent solubility in oil, dissolution rates, gas-phase diffusion coefficients, molar densities in the oil phase, gas-phase relative permeability and capillary pressure. It was shown that oil production is highly dependent on how quickly solvent can dissolve in the oil during injection and exsolve from the oil during production.
Naloxone, but Not Valsartan, Preserves Responses to Hypoglycemia After Antecedent Hypoglycemia
Authors: Poplawski Michal M. , Mastaitis Jason W. , Mobbs Charles V.
Published: September 2010

OBJECTIVE

Hypoglycemia-associated autonomic failure (HAAF) constitutes one of the main clinical obstacles to optimum treatment of type 1 diabetes. Neurons in the ventromedial hypothalamus are thought to mediate counterregulatory responses to hypoglycemia. We have previously hypothesized that hypoglycemia-induced hypothalamic angiotensin might contribute to HAAF, suggesting that the angiotensin blocker valsartan might prevent HAAF. On the other hand, clinical studies have demonstrated that the opioid receptor blocker naloxone ameliorates HAAF. The goal of this study was to generate novel hypothalamic markers of hypoglycemia and use them to assess mechanisms mediating HAAF and its reversal.

RESEARCH DESIGN AND METHODS

Quantitative PCR was used to validate a novel panel of hypothalamic genes regulated by hypoglycemia. Mice were exposed to one or five episodes of insulin-induced hypoglycemia, with or without concurrent exposure to valsartan or naloxone. Corticosterone, glucagon, epinephrine, and hypothalamic gene expression were assessed after the final episode of hypoglycemia.

RESULTS

A subset of hypothalamic genes regulated acutely by hypoglycemia failed to respond after repetitive hypoglycemia. Responsiveness of a subset of these genes was preserved by naloxone but not valsartan. Notably, hypothalamic expression of four genes, including pyruvate dehydrogenase kinase 4 and glycerol 3-phosphate dehydrogenase 1, was acutely induced by a single episode of hypoglycemia, but not after antecedent hypoglycemia; naloxone treatment prevented this failure. Similarly, carnitine palmitoyltransferase-1 was inhibited after repetitive hypoglycemia, and this inhibition was prevented by naloxone. Repetitive hypoglycemia also caused a loss of hypoglycemia-induced elevation of glucocorticoid secretion, a failure prevented by naloxone but not valsartan.

CONCLUSIONS

Based on these observations we speculate that acute hypoglycemia induces reprogramming of hypothalamic metabolism away from glycolysis toward β-oxidation, HAAF is associated with a reversal of this reprogramming, and naloxone preserves some responses to hypoglycemia by preventing this reversal.
Insulin Reciprocally Regulates Glucagon Secretion in Humans
Authors: Cooperberg Benjamin A. , Cryer Philip E.
Published: September 2010

OBJECTIVE

We tested the hypothesis that an increase in insulin per se, i.e., in the absence of zinc, suppresses glucagon secretion during euglycemia and that a decrease in insulin per se stimulates glucagon secretion during hypoglycemia in humans.

RESEARCH DESIGN AND METHODS

We measured plasma glucagon concentrations in patients with type 1 diabetes infused with the zinc-free insulin glulisine on three occasions. Glulisine was infused with clamped euglycemia (∼95 mg/dl [5.3 mmol/l]) from 0 to 60 min on all three occasions. Then, glulisine was discontinued with clamped euglycemia or with clamped hypoglycemia (∼55 mg/dl [3.0 mmol/l]) or continued with clamped hypoglycemia from 60 to 180 min.

RESULTS

Plasma glucagon concentrations were suppressed by −13 ± 3, −9 ± 3, and −12 ± 2 pg/ml (−3.7 ± 0.9, −2.6 ± 0.9, and −3.4 ± 0.6 pmol/l), respectively, (all P < 0.01) during zinc-free hyperinsulinemic euglycemia over the first 60 min. Glucagon levels remained suppressed following a decrease in zinc-free insulin with euglycemia (−14 ± 3 pg/ml [−4.0 ± 0.9 pmol/l]) and during sustained hyperinsulinemia with hypoglycemia (−14 ± 2 pg/ml [−4.0 ± 0.6 pmol/l]) but increased to −3 ± 3 pg/ml (−0.9 ± 0.9 pmol/l) (P < 0.01) following a decrease in zinc-free insulin with hypoglycemia over the next 120 min.

CONCLUSIONS

These data indicate that an increase in insulin per se suppresses glucagon secretion and a decrease in insulin per se, in concert with a low glucose concentration, stimulates glucagon secretion. Thus, they document that insulin is a β-cell secretory product that, in concert with glucose and among other signals, reciprocally regulates α-cell glucagon secretion in humans.
Moral suasion, installed
Authors: Sprinkle R. H.
Published: September 2010

Breeding for virtue is no novelty. Conscientious prospective parents from deepest antiquity have hoped to breed for virtue in mate selection and peri-conceptual regimen. But methods may be changing. Plotting biotechnology's trajectory well beyond today's horizon, Professor Mark Walker asks if virtue is valuable enough to warrant breeding by molecular-genetic means. He presented this question as “Enhancing genetic virtue: A project for twenty-first century humanity?” in the previous issue of POLITICS AND THE LIFE SCIENCES.
Evidence of past migration of the ice divide between the Shirase and Sôya drainage basins derived from chemical characteristics of the marginal ice in the Sôya drainage basin, East Antarctica
Authors: Iizuka Yoshinori , Miura Hideki , Iwasaki Shogo , Maemoku Hideaki , Sawagaki Takanobu , Greve Ralf , Satake Hiroshi , Sasa Kimikazu , Matsushi Yuki
Published: September 2010

Ice originating near the inland ice divide of the ice sheet can reappear as marginal ice at the surface near the ice terminal in the ablation area. We have analyzed δ18O values and ion concentrations of the Skallen, Skarvsnes and Hamna terminal ice sections, located along the estuary line in the Sôya drainage basin, East Antarctica. The data suggest that the upper part of the Skallen terminal ice section could have originated from inland precipitation on the Shirase drainage basin during marine isotope stage (MIS) 5e, while the upper part of Skarvsnes and Hamna terminal ice sections could have originated from inland precipitation on the Sôya drainage basin. We calculate past elevation maps for the Antarctic ice sheet using the three-dimensional model, SICOPOLIS. This model suggests that the upstream portion of the Sôya drainage basin during the glacial period (MIS 2, 3 or 4) was located to the northeast of its present location. A flow history is proposed wherein ice from the inland Shirase drainage area flowed over the present ice-divide line from the Shirase to the Sôya drainage basin during the glacial period. The ice in the Sôya drainage basin then flowed to the marginal part of the sheet after the ice divide had assumed its present position.
Effects of debris on ice-surface melting rates: an experimental study
Authors: Reznichenko Natalya , Davies Tim , Shulmeister James , McSaveney Mauri
Published: September 2010

Here we report a laboratory study of the effects of debris thickness, diurnally cyclic radiation and rainfall on melt rates beneath rock-avalanche debris and sand (representing typical highly permeable supraglacial debris). Under continuous, steady-state radiation, sand cover >50 mm thick delays the onset of ice-surface melting by >12 hours, but subsequent melting matches melt rates of a bare ice surface. Only when diurnal cycles of radiation are imposed does the debris reduce the longterm rate of ice melt beneath it. This is because debris >50 mm thick never reaches a steady-state heat flux, and heat acquired during the light part of the cycle is partially dissipated to the atmosphere during the nocturnal part of the cycle, thereby continuously reducing total heat flux to the ice surface underneath. The thicker the debris, the greater this effect. Rain advects heat from high-permeability supraglacial debris to the ice surface, thereby increasing ablation where thin, highly porous material covers the ice. In contrast, low-permeability rock-avalanche material slows water percolation, and heat transfer through the debris can cease when interstitial water freezes during the cold/night part of the cycle. This frozen interstitial water blocks heat advection to the ice–debris contact during the warm/day part of the cycle, thereby reducing overall ablation. The presence of metre-deep rock-avalanche debris over much of the ablation zone of a glacier can significantly affect the mass balance, and thus the motion, of a glacier. The length and thermal intensity of the diurnal cycle are important controls on ablation, and thus both geographical location and altitude significantly affect the impact of debris on glacial melting rates; the effect of debris cover is magnified at high altitude and in lower latitudes.
Greenland flow variability from ice-sheet-wide velocity mapping
Authors: Joughin Ian , Smith Ben E. , Howat Ian M. , Scambos Ted , Moon Twila
Published: September 2010

Using RADARSAT synthetic aperture radar data, we have mapped the flow velocity over much of the Greenland ice sheet for the winters of 2000/01 and 2005/06. These maps provide a detailed view of the ice-sheet flow, including that of the hundreds of glaciers draining the interior. The focused patterns of flow at the coast suggest a strong influence of bedrock topography. Differences between our two maps confirm numerous early observations of accelerated outlet glacier flow as well as revealing previously unrecognized changes. The overall pattern is one of speed-up accompanied by terminus retreat, but there are also several instances of surge behavior and a few cases of glacier slowdown. Comprehensive mappings such as these, at regular intervals, provide an important new observational capability for understanding ice-sheet variability.
Ice friction: the effect of thermal conductivity
Authors: Kietzig Anne-Marie , Hatzikiriakos Savvas G. , Englezos Peter
Published: September 2010

The effect of thermal conductivity on ice friction is studied systematically for different metallic slider materials over a wide range of temperatures, and sliding velocities. By thermally insulating the slider with fiberglass, the isolated effect of thermal conductivity on ice friction is investigated. A decrease of the friction coefficient in the boundary friction regime and an earlier onset of the mixed friction regime in terms of sliding velocity are found. Furthermore, the dependence of the ice friction coefficient on sliding velocity is compared for different sliding materials. It is found that the influence and importance of thermal conductivity decreases with increasing sliding velocity.
Snow grain-size profiles deduced from microwave snow emissivities in Antarctica
Authors: Brucker Ludovic , Picard Ghislain , Fily Michel
Published: September 2010

Spaceborne microwave radiometers are an attractive tool for observing Antarctic climate because their measurements are related to the snow temperature. However, the conversion from microwave emission to snow temperature is not simple and strongly depends on the emissivity through snow properties. This difficulty in predicting the snow property profile for Antarctic conditions is the main bottleneck in the retrieval of accurate climate information from microwave radiometers. We attempt to explain the vertically polarized emissivity at 19.3 and 37 GHz derived from brightness temperatures acquired by the Special Sensor Microwave/Imager (SSM/I) and physical temperature from the ERA-40 re-analysis. In Antarctica the snow emissivities at 19.3 and 37 GHz are nearly equal, although a decrease with frequency is expected. To explain this, we consider various profiles of snow grain size and density and predict their emissivity using a dense-medium radiative transfer (DMRT) model. The results show that the emissivities cannot be explained by constant profiles of grain size and density. Heterogeneous snowpacks need to be considered. We first test random variations of snow density and grain radius with depth and then monotonic and continuous variations in the snow grain radius. In both cases, we show that an overall increase of the snow grain radius with depth is required to match the observed emissivity in Antarctica. In addition, two parameters characterizing the snow grain profiles are retrieved and compared with (1) in situ measurements of grain size at various locations in East Antarctica, (2) grain size estimated using visible spaceborne radiometers and (3) a semi-empirical relationship for grain growth.
Grounding-line basal melt rates determined using radar-derived internal stratigraphy
Authors: Catania Ginny , Hulbe Christina , Conway Howard
Published: September 2010

We use ice-penetrating radar data across grounding lines of Siple Dome and Roosevelt Island, Antarctica, to measure the spatial pattern, magnitude and duration of sub-ice-shelf melting at these locations. Stratigraphic layers across the grounding line show, in places, a large-amplitude downwarp at, or slightly downstream of, the grounding line due to sub-ice-shelf basal melting. Localized downwarping indicates that melting is transient; melt rates, or the grounding line position, have changed within a few hundred years in order to produce the observed stratigraphy. Elsewhere, no melt-related stratigraphic signature is preserved. In part, heterogeneity in the amount of sub-ice-shelf melt is due to regional circulation patterns in the sub-shelf cavity, but local (on the order of tens of kilometers) heterogeneity in the melt pattern may reflect small differences in the shape of the ice-shelf base at the grounding line. We find that all of the grounding lines crossed have been in place for at most ∼400 years.
Coarctation of Aorta Managed by Balloon Angioplasty
Authors: Begum NNF
Published: September 2010

A retrospective study was carried out on 50 patients at Paediatric cardiology unit of Combined MilitaryHospital, Dhaka to analyze the outcome of balloon angioplasty of coarctation of aorta. The study periodextended over two years starting from January 2007. Age of the patient varies from 7 days to 28 years. Twentytwo (44%) patients were female and rests were male. Native coarctation was in 44 cases (88%) and postsurgical re-coarctation was in 5 cases (10%). Neonatal critical coarctation was 19 (38%). Twelve (24%) caseswere detected when they were investigated for hypertension. Abdominal coarctation was found in 6 cases(12%). Multiple coarctations were found in 3 (6%) cases. Two cases (4%) had balloon angioplasty twice asthey developed re-coarctation. No intra-operative or post-operative complication was observed in any cases ofthis series. Data were collected by chart review. No test was performed on any of the subjects as part of studyprotocol. Coarctation balloon angioplasty of coarctation of aorta is a safe and effective measure to treatcoarctation of aorta.Key words: Balloon angioplasty; coarctation of aorta.DOI: 10.3329/jafmc.v6i1.5983Journal of Armed Forces Medical College, Bangladesh Vol.6(1) 2010 p.4-7
Outcome of Scleral Buckling Surgery in Rhegmatogenous Retinal Detachment
Authors: Hossain MI , Hasan MK , Ali MSM
Published: September 2010

A longitudinal study was carried out in the vitreo-retina clinic of the National Institute of Ophthalmology andHospital (NIO&H) on 30 eyes of 25 patients who were treated with scleral buckle (SB) surgery during theperiod of October 2004 to September 2005 of either sex. The aim of this study was to determine the outcome ofSB surgery in Rhegmatogenous retinal detachment (RRD). The main entry criteria for this study wereprimary RRD treated with SB and for which 12 weeks of follow-up were available. The eyes with proliferativevitreoretinopathy or with history of SB surgery, vitrectomy, posterior segment open-globe trauma orsignificant concurrent eye disease e.g. amblyopia, macular disease etc were excluded from this study. Overalltwenty-four eyes (80%) achieved retinal reattachment with one SB procedure (encircling or segmental); themedian 12-week visual acuity was 6/12. Three additional eyes (10%) achieved retinal reattachment with onevitreoretinal procedure; the median 12-week visual acuity was 6/9. Three eyes (10%) never achieved retinalreattachment despite one additional vitreoretinal procedure, and 12-week visual acuity was no perception oflight. It can be concluded that SB for primary RRD achieves anatomical efficacy and preservation of centralvision in the majority of eyes.Key words: Scleral buckle; Rhegmatogenous retinal detachment outcome.DOI: 10.3329/jafmc.v6i1.5987Journal of Armed Forces Medical College, Bangladesh Vol.6(1) 2010 p.21-24
Reactivation of Hepatitis B Virus (HBV) Following Cancer Chemotherapy
Authors: Rahman MM
Published: September 2010

Reactivation of Hepatitis B virus (HBV) may occur after immunosuppressive therapy and cancerchemotherapy. Some of these cases may develop liver failure in a previously compensated disease. Aim of thiscase report is to make an awareness of this reactivation of HBV in Bangladeshi society after cancerchemotherapy or immunosuppressive therapy. A forty-five-year old lady, mother of one child was found tohave positive Hepatitis B surface antigen (HBsAg) since 1994 when the test was done for vaccination. She wasasymptomatic and clinically unremarkable. She was treated with standard Interferon for 24 weeks in 2000when Alanine aminotransferase (ALT) was high, Hepatitis B envelope antigen (HBeAg) & HBVdeoxyribonucleic acid (DNA) were positive. After treatment HBeAg & HBV DNA were negative and ALT wasnormal. She developed carcinoma of the left breast which was operated in July 2008. Combination cancerchemotherapy started. After 5th cycle of chemotherapy she developed rise of ALT (1200 i.u/L) and HBV DNA(> 105 copies/ml). Patient was treated with tablet Lamivudine 100 mg/day. After one year of follow up she hadno symptoms. HBV DNA and ALT became normal. Reactivation of HBV may occur after cancerchemotherapy or immunosuppressive therapy. At present recommendation of Asian Pacific Association forStudy of Liver (APASL), European Association for the Study of Liver (EASL) and American Association forthe Study of Liver Diseases (AASLD) is to start prophylactic Lamivudine, Entecavir or any other antiviraldrugs in all patients who are positive for HBsAg irrespective of HBeAg, ALT or HBV DNA status beforestarting chemotherapy or immunosuppressive therapy. So, HBsAg and Anti HBc (Hepatitis B core) should betested in all such cases.Key words: Hepatitis B virus reactivation; chemotherapy.DOI: 10.3329/jafmc.v6i1.5991Journal of Armed Forces Medical College, Bangladesh Vol.6(1) 2010 p.34-35
The use of information theory to determine the language character type of Pictish symbols
Authors: Lee Rob
Published: September 2010

Pictish symbols are found on stones, cave walls and portable items (e.g. silver metalwork). A detailed pictorial corpus of all the images found on these materials has been created. Using this pictorial corpus, a catalogue of possible symbol types has been drawn up and a second, comparative visual corpus for each of these symbol types produced. The images in the pictorial corpus were then defined using the different sets of symbol types and analysed with an information theory technique that determines the degree of information expressed by small petroglyph corpuses. This quantitative, statistical technique confirms that the Pictish symbols represent a written language. Analysis indicates that it is highly likely that the symbols are words and that the majority are likely to be names. Some basic syntax and possible lines of enquiry for decipherment of this language are described.
Androgen Deprivation Therapy for Prostate Cancer—Review of Indications in 2010
Authors: Quon H. , Loblaw D. A.
Published: September 2010

The discovery of androgen deprivation therapy (ADT) has been one of the most important advances in the treatment of prostate cancer. Here, the indications for the use of ADT are reviewed, together with the data supporting each indication. The settings for ADT use include cytoreduction; combined ADT and radiotherapy; pathologic node-positive disease; and recurrent, metastatic, or progressive prostate cancer.
The Association Between Disease Activity and Duration in Systemic Sclerosis
Authors: WALKER JENNIFER G. , STEELE RUSSELL J. , SCHNITZER MIREILLE , TAILLEFER SUZANNE , BARON MURRAY ,   Canadian Scleroderma Research Group, HUDSON MARIE
Published: September 2010

Objective.

The absence of a standardized disease activity index has been an important barrier in systemic sclerosis (SSc) research. We applied the newly derived Valentini Scleroderma Disease Activity Index (SDAI) among our cohort of patients with SSc to document changes in disease activity over time and to assess possible differences in activity between limited and diffuse disease.

Methods.

Cross-sectional study of a national cohort of patients enrolled in the Canadian Scleroderma Research Group Registry. Disease activity was measured using the SDAI. Depression scores were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D).

Results.

A total of 326 out of 639 patients had complete datasets at the time of this analysis; 87% were female, of mean age 55.6 years, with mean disease duration 14.1 years. SDAI declined steeply in the first 5 years after disease onset and patients with diffuse disease had 42% higher SDAI scores than patients with limited disease with the same disease duration and depression scores (standardized relative risk 1.42, 95% CI 1.21, 1.65). Patients with higher CES-D scores had higher SDAI scores relative to patients with the same disease duration and disease subset (standardized RR 1.22, 95% CI 1.14, 1.31). Among the 10 components that make up the SDAI, only skin score (standardized OR 0.59, 95% CI 0.43, 0.82) and patient-reported change in skin (standardized OR 0.64, 95% CI 0.45, 0.92) decreased with increasing disease duration. High skin scores (standardized OR 32.2, 95% CI 15.8, 72.0) were more likely and scleredema (standardized OR 0.58, 95% CI 0.37, 0.92) was less likely to be present in patients with diffuse disease. High depression scores were associated with positive responses for patient-reported changes in skin and cardiopulmonary function.

Conclusion.

Disease activity declined with time and patients with diffuse disease had consistently higher SDAI scores. Depression was found to be associated with higher patient activity scores and strongly associated with patient self-response questions. The role of depression should be carefully considered in future applications of the SDAI, particularly as several components of the score rely upon patient recall.
Ultrasonographic Measurements of Joint Cartilage Thickness in Healthy Children: Age- and Sex-Related Standard Reference Values
Authors: SPANNOW ANNE HELENE , PFEIFFER-JENSEN MOGENS , ANDERSEN NIELS T. , HERLIN TROELS , STENBØG ELISABETH
Published: September 2010

Objective.

Loss of joint cartilage may be an early feature of chronic inflammatory joint diseases like juvenile idiopathic arthritis (JIA). Conventional radiography usually detects only late changes such as joint space narrowing and bone erosion rather than early inflammatory changes. Joint cartilage is easily visualized with high-frequency ultrasonography (US), but age- and gender-related normal standard reference values should be established before US measurement of cartilage thickness becomes standard procedure in the clinic.

Methods.

A cross-sectional study of bilateral grey-scale US cartilage thickness of the knee, ankle, wrist, and second metacarpophalangeal (MCP) and second proximal interphalangeal (PIP) joints was performed in 394 (215 boys/179 girls) healthy Danish Caucasian children aged between 7 and 16 years.

Results.

Cartilage thickness differed significantly between sexes (p < 0.001 for all joints), boys having thicker cartilage than girls. Cartilage thickness clearly decreased with increasing age in both sexes. A formula for calculating sex-specific cartilage thickness at different ages in childhood is suggested. No difference between the right and left side of the investigated joints was observed.

Conclusion.

Using US, we established age- and sex-related normal reference intervals for cartilage thickness of the knee, ankle, wrist, and MCP and PIP joints in 7- to 16-year-old children, and designed a formula for calculating hyaline cartilage thickness in all age groups throughout childhood.
Increased Production of a Proliferation-inducing Ligand (APRIL) by Peripheral Blood Mononuclear Cells Is Associated with Antitopoisomerase I Antibody and More Severe Disease in Systemic Sclerosis
Authors: BIELECKI MAREK , KOWAL KRZYSZTOF , LAPINSKA ANNA , BERNATOWICZ PAWEL , CHYCZEWSKI LECH , KOWAL-BIELECKA OTYLIA
Published: September 2010

Objective.

A proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor (TNF) family, plays a crucial role in the survival of peripheral B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of autoimmune phenomena. We evaluated the capacity of peripheral blood mononuclear cells from patients with SSc (SSc-PBMC) to produce APRIL; and investigated correlations between production of APRIL by SSc-PBMC and clinical and laboratory features of the disease.

Methods.

PBMC from 20 patients with SSc and 14 healthy subjects were incubated in fetal calf serum-supplemented RPMI medium. APRIL levels were determined in cell culture supernatants by ELISA.

Results.

PBMC from patients with SSc produced significantly more APRIL (961 ± 151 pg/ml/105cells) than control PBMC (798 ± 219 pg/ml/105cells; p < 0.01). In patients with SSc, increased production of APRIL was associated with the presence of diffuse skin involvement, scleroderma lung disease, peripheral vasculopathy, greater capillary damage on capillaroscopy, and presence of anti-topoisomerase I (anti-topo I) antibodies. Multivariate regression analysis revealed anti-topo I antibodies as the only independent predictor of high production of APRIL by PBMC.

Conclusion.

Production of APRIL is increased in SSc-PBMC and is associated with the presence of anti-topo I antibodies and more severe disease. Targeting the APRIL pathway might represent a therapeutic possibility for treatment of patients with SSc, in particular those with anti-topo I antibodies.
Un pragmatisme ambigu ? « L'en tant que » herméneutique au regard des Recherches philosophiques
Authors: Monod Jean-Claude
Published: September 2010

Résumé Si l’on trouve dans Être et Temps comme dans les Recherches philosophiques un souci commun visant à rendre compte d’un rapport d’usage quotidien aux choses, que la tradition philosophique aurait eu tendance à méconnaître au profit de leur saisie « objective », cette similitude de surface est plutôt vue ici comme le point de départ d’une discussion : cette saisie pré-objective des choses doit-elle être approchée par une généralisation de l’idée d’interprétation-explicitation, ou bien faut-il maintenir une distinction forte entre « voir » et « voir comme » ?
Troubles oppositionnels chez l'enfant : leur compréhension et leurs soins
Authors: de Becker Emmanuel
Published: September 2010

Résumé Les demandes de consultation en psychiatrie infanto-juvénile qui concernent les troubles oppositionnels de l’enfant sont en augmentation. Parallèlement, l’opposition et en corollaire la violence représentent des aspects quotidiennement évoqués au sein de nos sociétés. A partir d’une situation paradigmatique, l’article développe une réflexion sur la compréhension des conduites d’opposition et leur accompagnement thérapeutique. Pour comprendre cette manière d’être, l’auteur parcourt diverses étiologies possibles en reprenant la distinction entre violence et agressivité. Si l’opposition (le « non ») traduit la différenciation et l’individuation, sa persistance au-delà de 30-36 mois indique un « avatar développemental ». Pour expliquer celui-ci, différents facteurs interviennent, qu’ils appartiennent au sujet lui-même, à son environnement ou à la société. Vient ensuite le temps pour soigner ; plusieurs aspects sont alors abordés pour décrire l’accompagnement thérapeutique des troubles oppositionnels : le jeu de la demande, le format et le contenu des rencontres, les aménagements de la vie concrète.
Qui représentent les élus de la « diversité » ?
Authors: Avanza Martina
Published: September 2010

Résumé À l’exception de l’extrême droite, tous les partis politiques disent aujourd’hui vouloir mieux représenter la « diversité » de la société française et ce, à travers l’augmentation d’élus de la « diversité ». Mais pourquoi cette nécessité apparaît-elle aujourd’hui comme une évidence ? S’agit-il de conquérir l’électorat que ces élus sont censés représenter ? Et quel électorat représentent-ils ? À l’inverse, si ces élus sont des élus comme les autres qui n’ont pas vocation à représenter un segment précis de l’électorat, s’agirait-il plutôt de défendre l’égalité d’accès aux fonctions ? Cet article explorera ces différents registres de légitimation. Le succès de la « diversité » étant en grande partie fondé sur le flou de cette catégorie, il s’agira de voir les usages qui en sont faits par les partis mais aussi par les élus ainsi labellisés, et ce, afin d’interroger ce qui se joue, via la « diversité », dans le lien entre représentants et représentés au sein d’un système républicain et universaliste a priori peu enclin à la représentation des minorités.
Latent Membrane Protein 1, the EBV-Encoded Oncogenic Mimic of CD40, Accelerates Autoimmunity in B6.Sle1 Mice
Authors: Peters Anna L. , Stunz Laura L. , Meyerholz David K. , Mohan Chandra , Bishop Gail A.
Published: September 2010

EBV infection is associated with development of the autoimmune disease systemic lupus erythematosus (SLE), and EBV can reactivate during SLE flares. Latent membrane protein 1 (LMP1) is an EBV-encoded oncogenic mimic of CD40 that can be re-expressed in PBMCs during SLE flares, as >90% of humans are latently EBV-infected. Whether LMP1 signaling exacerbates SLE is unknown. The phenotype of mice expressing a chimeric molecule with the mouse CD40 extracellular domain and the LMP1 intracellular signaling regions (mCD40-LMP1 transgenic [tg]) includes enhanced autoreactivity, yet these mice do not develop fatal autoimmune disease. We hypothesized that LMP1-mediated activation signals cooperate with and/or amplify events that predispose individuals to development of autoimmunity. To determine which aspects of autoimmunity may be exacerbated by LMP1, we bred mCD40-LMP1tg mice to two lupus-prone strains, B6.Sle1 and B6.Sle3, and analyzed autoimmunity parameters. LMP1+Sle1+/+ mice developed enlarged lymphoid organs containing increased frequencies of germinal center, B cells, CD86+ B cells, and activated and memory T cells compared with non-tg littermates. Anti-histone Abs were elevated in serum of LMP1+Sle1+/+ mice, and they had signs of kidney pathology. LMP1+Sle1+/+ B cells produced increased IL-6 and upregulated CD86 to a higher degree following CD40 stimulation in vitro, suggesting that the in vivo autoimmune exacerbation is B cell intrinsic. In contrast, the LMP1 transgene has no additional effects on autoimmunity on the B6.Sle3 background. These data indicate that LMP1-induced effects can cooperate with distinct subsets of host genes that predispose to autoimmunity and can thus be an exacerbating factor in autoimmune disease via multiple mechanisms.
Surfactant Protein-A Inhibits Mycoplasma-Induced Dendritic Cell Maturation through Regulation of HMGB-1 Cytokine Activity
Authors: Ledford Julie G. , Lo Bernice , Kislan Michele M. , Thomas Joseph M. , Evans Katherine , Cain Derek W. , Kraft Monica , Williams Kristi L. , Wright Jo Rae
Published: September 2010

During pulmonary infections, a careful balance between activation of protective host defense mechanisms and potentially injurious inflammatory processes must be maintained. Surfactant protein A (SP-A) is an immune modulator that increases pathogen uptake and clearance by phagocytes while minimizing lung inflammation by limiting dendritic cell (DC) and T cell activation. Recent publications have shown that SP-A binds to and is bacteriostatic for Mycoplasma pneumoniae in vitro. In vivo, SP-A aids in maintenance of airway homeostasis during M. pneumoniae pulmonary infection by preventing an overzealous proinflammatory response mediated by TNF-α. Although SP-A was shown to inhibit maturation of DCs in vitro, the consequence of DC/SP-A interactions in vivo has not been elucidated. In this article, we show that the absence of SP-A during M. pneumoniae infection leads to increased numbers of mature DCs in the lung and draining lymph nodes during the acute phase of infection and, consequently, increased numbers of activated T and B cells during the course of infection. The findings that glycyrrhizin, a specific inhibitor of extracellular high-mobility group box-1 (HMGB-1) abrogated this effect and that SP-A inhibits HMGB-1 release from immune cells suggest that SP-A inhibits M. pneumoniae-induced DC maturation by regulating HMGB-1 cytokine activity.
The Class A Scavenger Receptor, Macrophage Receptor with Collagenous Structure, Is the Major Phagocytic Receptor for Clostridium sordellii Expressed by Human Decidual Macrophages
Authors: Thelen Tennille , Hao Yibai , Medeiros Alexandra I. , Curtis Jeffrey L. , Serezani Carlos H. , Kobzik Lester , Harris Lisa H. , Aronoff David M.
Published: September 2010

Clostridium sordellii is an emerging pathogen associated with highly lethal female reproductive tract infections following childbirth, abortion, or cervical instrumentation. Gaps in our understanding of the pathogenesis of C. sordellii infections present major challenges to the development of better preventive and therapeutic strategies against this problem. We sought to determine the mechanisms whereby uterine decidual macrophages phagocytose this bacterium and tested the hypothesis that human decidual macrophages use class A scavenger receptors to internalize unopsonized C. sordellii. In vitro phagocytosis assays with human decidual macrophages incubated with pharmacological inhibitors of class A scavenger receptors (fucoidan, polyinosinic acid, and dextran sulfate) revealed a role for these receptors in C. sordellii phagocytosis. Soluble macrophage receptor with collagenous structure (MARCO) receptor prevented C. sordellii internalization, suggesting that MARCO is an important class A scavenger receptor in decidual macrophage phagocytosis of this microbe. Peritoneal macrophages from MARCO-deficient mice, but not wild-type or scavenger receptor AI/II–deficient mice, showed impaired C. sordellii phagocytosis. MARCO-null mice were more susceptible to death from C. sordellii uterine infection than wild-type mice and exhibited impaired clearance of this bacterium from the infected uterus. Thus, MARCO is an important phagocytic receptor used by human and mouse macrophages to clear C. sordellii from the infected uterus.
Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population
Authors: Sidney John , Steen Amiyah , Moore Carrie , Ngo Sandy , Chung Jolan , Peters Bjoern , Sette Alessandro
Published: September 2010

Knowledge of the binding repertoires and specificities of HLA-DQ molecules is somewhat limited and contradictory, partly because of the scarcity of reports addressing some of the most common molecules and possibly because of the diversity of the techniques used. In this paper, we report the development of high-throughput binding assays for the six most common DQ molecules in the general worldwide population. Using comprehensive panels of single substitution analogs of specific ligands, we derived detailed binding motifs for DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides. In contrast to what has previously been observed for DR and DP molecules, DQ motifs were generally less clearly defined in terms of chemical specificity and, strikingly, had little overlap with each other. However, testing a panel of peptides spanning a set of Phleum pratense Ags, and panels of known DQ epitopes, revealed a surprisingly significant and substantial overlap in the repertoire of peptides bound by these DQ molecules. Although the mechanism underlying these apparently contradictory findings is not clear, it likely reflects the peculiar mode of interaction between DQ (and not DR or DP) molecules and their peptide ligands. Because the DQ molecules studied are found in >85% of the general human population, these findings have important implications for epitope identification studies and monitoring of DQ-restricted immune responses.
Plasticity and Heterogeneity in the Generation of Memory B Cells and Long-Lived Plasma Cells: The Influence of Germinal Center Interactions and Dynamics
Authors: Good-Jacobson Kim L. , Shlomchik Mark J.
Published: September 2010

In the humoral response, short-lived plasmablasts generate an early burst of Ab that probably plays an initial protective role. Simultaneously, another arm of the response is often triggered that leads to delayed effector function but long-term protection. This arm comprises the germinal center response and its products: long-lived memory B (Bmem) cells and plasma cells (PCs). The factors that control the differentiation of PCs and Bmem cells, as well as the composition and function of the memory compartment—how it self-renews while generating rapid secondary effector function—are poorly understood. Recent work in mice and humans is beginning to illuminate these issues. We review this progress, with emphasis on events in the germinal center, especially B–T interactions, which influence the development of memory and PC compartments and on Bmem cell heterogeneity that may underlie flexibility and self-renewal of long-lived humoral immunity.
p300-Mediated Acetylation Stabilizes the Th-Inducing POK Factor
Authors: Zhang Min , Zhang Jiali , Rui Jinxiu , Liu Xiaolong
Published: September 2010

The lineage-specifying factor Th-inducing POK (ThPOK) directs the intrathymic differentiation of CD4 T cells. Although the regulation of ThPOK at the transcription level has been extensively studied, specific posttranslational modifications regulating the activity of ThPOK have not been addressed. In this paper, we show that ThPOK is an unstable protein that is more readily degraded in CD8 T cells compared with CD4 T cells. Among the various proteins that bind ThPOK, acetyltransferase p300 specifically promotes the acetylation of ThPOK at K210, K216, and K339, outcompeting ubiquitination, thereby stabilizing the protein. In CD4 T cells, attenuation of p300-mediated acetylation promotes the degradation of ThPOK. In contrast, mutation of lysines 210, 216, and 339 to arginines stabilizes ThPOK and enhances its ability to suppress the expression of CD8 molecule and cytotoxic effectors in CD8 T cells. Our results reveal an essential role of p300-mediated acetylation in regulating the stability of ThPOK and suggest that such regulation may play a part in CD4/CD8 lineage differentiation.
Discrete TCR Repertoires and CDR3 Features Distinguish Effector and Foxp3+ Regulatory T Lymphocytes in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Allergic Encephalomyelitis
Authors: Nguyen Phuong , Liu Wei , Ma Jing , Manirarora Jean N. , Liu Xin , Cheng Cheng , Geiger Terrence L.
Published: September 2010

Regulatory T lymphocytes (Tregs) expressing the Foxp3 transcription factor are critical modulators of autoimmunity. Foxp3+ Tregs may develop in the thymus as a population distinct from conventional Foxp3− αβ T cells (Tconvs). Alternatively, plasticity in Foxp3 expression may allow for the interconversion of mature Tregs and Tconvs. We examined >160,000 TCR sequences from Foxp3+ or Foxp3− populations in the spleens or CNS of wild-type mice with experimental allergic encephalomyelitis to determine their relatedness and identify distinguishing TCR features. Our results indicate that the CNS-infiltrating Tregs and Tconvs arise predominantly from distinct sources. The repertoires of CNS Treg or Tconv TCRs showed limited overlap with heterologous populations in both the CNS and the spleen, indicating that they are largely unrelated. Indeed, Treg and Tconv TCRs in the CNS were significantly less related than those populations in the spleen. In contrast, CNS Treg and Tconv repertoires strongly intersected those of the homologous cell type in the spleen. High-frequency sequences more likely to be disease associated showed similar results, and some public TCRs demonstrated Treg- or Tconv-specific motifs. Different charge characteristics and amino acid use preferences were identified in the CDR3β of Tregs and Tconvs infiltrating the CNS, further indicating that their repertoires are qualitatively distinct. Therefore, discrete populations of Tregs and Tconvs that do not substantially interconvert respond during experimental allergic encephalomyelitis. Differences in sequence and physical characteristics distinguish Treg and Tconv TCRs and imply dissimilar Ag recognition properties.