bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interaction of the Madden–Julian Oscillation and the Arctic Oscillation
Authors: Zhou Shuntai , Miller Alvin J.
Published: February 2005

Tropical and extratropical interactions on the intraseasonal time scale are studied in the context of the Arctic Oscillation (AO) and the Madden–Julian oscillation (MJO). To simplify the discussion, a high (low) MJO phase is defined as strong (suppressed) convective activity over the Indian Ocean. In the Northern Hemisphere (NH) winter season, a high (low) AO phase is found more likely coupled with a high (low) MJO phase. Based on the regressed patterns and composites of various dynamical fields and quantities, possible mechanisms linking the AO and the MJO are examined. The analysis indicates that the MJO influence on extratropical circulations seems more evident than the AO influence on tropical circulations. The MJO interacts with the AO through meridional dispersion of Rossby waves in the Pacific sector. The geopotential height anomaly center over the North Pacific associated with the MJO can either reinforce or offset the AO Pacific action center. As a result, the AO pattern can be greatly affected by the MJO. When the AO and the MJO are in the same (opposite) phase, the Pacific action center becomes much stronger (weaker) than the Atlantic action center. The eddy momentum transports associated with the MJO in the Pacific sector are closely related to the retraction and extension of tropical Pacific easterlies and the subtropical Asian–Pacific jet. Because of its large scale, this regional effect is also reflected in the zonal mean state of wave transport and wave forcing on zonal wind, which in turn affects the phase of the AO.
The Aleutian Low and Winter Climatic Conditions in the Bering Sea. Part I: Classification*
Authors: Rodionov S. N. , Overland J. E. , Bond N. A.
Published: February 2005

The Aleutian low is examined as a primary determinant of surface air temperature (SAT) variability in the Bering Sea during the winter [December–January–February–March (DJFM)] months. The Classification and Regression Tree (CART) method is used to classify five types of atmospheric circulation for anomalously warm months (W1–W5) and cold months (C1–C5). For the Bering Sea, changes in the position of the Aleutian low are shown to be more important than changes in its central pressure. The first two types, W1 and C1, account for 51% of the “warm” and 37% of the “cold” months. The W1-type pattern is characterized by the anomalously deep Aleutian low shifted west and north of its mean position. In this situation, an increased cyclonic activity occurs in the western Bering Sea. The C1-type pattern represents a split Aleutian low with one center in the northwestern Pacific and the other in the Gulf of Alaska. The relative frequency of the W1 to C1 types of atmospheric circulation varies on decadal time scales, which helps to explain the predominance of fluctuations on these time scales in the weather of the Bering Sea. Previous work has noted the prominence of multidecadal variability in the North Pacific. The present study finds multidecadal variations in frequencies of the W3 and C3 patterns, both of which are characterized by increased cyclonic activity south of 51°N. In general, the CART method is found to be a suitable means for characterizing the wintertime atmospheric circulation of the North Pacific in terms of its impact on the Bering Sea. The results show that similar pressure anomaly patterns for the North Pacific as a whole can actually result in different conditions for the Bering Sea, and that similar weather conditions in the Bering Sea can arise from decidedly different large-scale pressure patterns.
Biophysical Feedbacks in the Tropical Pacific
Authors: Marzeion Ben , Timmermann Axel , Murtugudde Ragu , Jin Fei-Fei
Published: February 2005

This study explores the influence of phytoplankton on the tropical Pacific heat budget. A hybrid coupled model for the tropical Pacific that is based on a primitive equation reduced-gravity multilayer ocean model, a dynamic ocean mixed layer, an atmospheric mixed layer, and a statistical atmosphere is used. The statistical atmosphere relates deviations of the sea surface temperature from its mean to wind stress anomalies and allows for the rectification of the annual cycle and the El Niño–Southern Oscillation (ENSO) phenomenon through the positive Bjerknes feedback. Furthermore, a nine-component ecosystem model is coupled to the physical variables of the ocean. The simulated chlorophyll concentrations can feed back onto the ocean heat budget by their optical properties, which modify solar light absorption in the surface layers. It is shown that both the surface layer concentration as well as the vertical profile of chlorophyll have a significant effect on the simulated mean state, the tropical annual cycle, and ENSO. This study supports a previously suggested hypothesis (Timmermann and Jin) that predicts an influence of phytoplankton concentration of the tropical Pacific climate mean state and its variability. The bioclimate feedback diagnosed here works as follows: Maxima in the subsurface chlorophyll concentrations lead to an enhanced subsurface warming due to the absorption of photosynthetically available shortwave radiation. This warming triggers a deepening of the mixed layer in the eastern equatorial Pacific and eventually a reduction of the surface ocean currents (Murtugudde et al.). The weakened south-equatorial current generates an eastern Pacific surface warming, which is strongly enhanced by the Bjerknes feedback. Because of the deepening of the mixed layer, the strength of the simulated annual cycle is also diminished. This in turn leads to an increase in ENSO variability.
Evaluating an Experimental Intensive Juvenile Probation Program: Supervision and Official Outcomes
Authors: Lane Jodi , Turner Susan , Fain Terry , Sehgal Amber
Published: February 2005

In 1996, California provided funding to 14 county probation agencies to implement multiagency, comprehensive services to keep troubled youths from recommitting crime and progressing farther into the justice system. We report results of a randomized experiment used to evaluate Ventura County’s 4-year demonstration project called the South Oxnard Challenge Project (SOCP). We followed youths for more than 2 years after random assignment to SOCP or routine probation. We found no significant differences between SOCP and routine juvenile probationers on recidivism or other official-record outcomes. Although most youths were rearrested, most did not receive a sustained petition or incarceration. The modest additional services did not affect outcomes.
Public Policy in Bioethics and Inviolable Principles
Authors: Warnock Mary
Published: February 2005

Though religious belief may be the foundation for private morality and therefore supply such morality with inviolable principles, it has no such role in the case of public policy-making, even where the policy is concerned with matters agreed to be matters of morality. It could have such a role only if the certainty of the principles supplied by religion were generally shared, or were held themselves to be enforceable by law (i.e. in a theocratic state).
Time-based gene expression programme following diaphragm injury in a rat model
Authors: Mehiri S. N. , Barreiro E. , Hayot M. , Voyer M. , Comtois A. S. , Grassino A. E. , Czaika G.
Published: February 2005

It was hypothesised that diaphragm injury activates a time-based programme of gene expression in muscle repair.

Gene expression of different substances, such as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos), growth factors (both basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced injury. Injured and noninjured (control) rat hemidiaphragms were excised at different time points (1–240 h).

In injured hemidiaphragms, in comparison with control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were significantly elevated at 72 h PI.

Caffeine-induced diaphragm injury is followed by a time-based expression programme of different genes tailored to meet muscle repair needs.
Epidemiology ofPseudomonas aeruginosain a cystic fibrosis rehabilitation centre
Authors: Van daele S. G. , Franckx H. , Verhelst R. , Schelstraete P. , Haerynck F. , Van Simaey L. , Claeys G. , Vaneechoutte M. , de Baets F.
Published: February 2005

Pseudomonas aeruginosais the leading pathogen in cystic fibrosis (CF) lungs. Since there is great concern about clonal spread in CF centres, this study examined theP. aeruginosagenotypes of colonised residents of a CF rehabilitation centre.

The isolates from the sputum of 76P. aeruginosa-colonised patients were genotyped by fluorescent amplified fragment length polymorphism on arrival and departure.

A total of 71 differentP. aeruginosagenotypes were identified from 749 isolates. Forty-nine patients had one genotype, 20 had two genotypes and seven had three. Forty-four patients had one or more genotypes in common with other patients (i.e.cluster types). Thirty-two patients were colonised by a single genotype not shared by any other patient. Thirty-eight of the 44 patients with a cluster type already carried their cluster type strain(s) on arrival. Patient-to-patient transmission could not be excluded for eight patients. For five of these, this infection was transient. None of the environmentalP. aeruginosaisolates had a genotype similar to the patients' genotypes.

In summary, most patients were colonised by only one or twoP. aeruginosagenotypes and the risk of persistent patient-to-patient transmission was low during the study period (4%). Most patients with a cluster-type strain carried this strain on arrival, indicating that transmission could have happened in the past. No environmental contamination could be established.
Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology
Authors: van Kessel D. A. , van Velzen-Blad H. , van den Bosch J. M. M. , Rijkers G. T.
Published: February 2005

As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections.

When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass.

When analysing differences between the responder (n = 11) and nonresponder (n = 15) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eightversusfive).

In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets.

In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unkown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.
Exhaled nitric oxide in 4-year-old children: relationship with asthma and atopy
Authors: Brussee J. E. , Smit H. A. , Kerkhof M. , Koopman L. P. , Wijga A. H. , Postma D. S. , Gerritsen J. , Grobbee D. E. , Brunekreef B. , de Jongste J. C.
Published: February 2005

Airway inflammation is an early feature of asthma. Early detection and anti-inflammatory treatment may have important therapeutic impact. Exhaled nitric oxide is a noninvasive marker of airway inflammation. The current study investigated the association between exhaled nitric oxide and asthma, wheezing phenotypes, atopy and blood eosinophilia in a large group of 4-yr-old children from the general population.

All children participated in the Prevention and Incidence of Asthma and Mite Allergy study, a birth cohort study of high-risk (atopic mother) and low-risk children in the Netherlands. Nitric oxide levels were successfully determined in 429 children.

Although there was overlap in the distribution of values of children with and without asthma or atopy, mean values were higher in children with atopy or doctor's diagnosed asthma (geometric mean (ppb) 9.4 and 10.0, respectively) as compared to those without (7.7 and 7.9). Values were highest in atopic symptomatic children. Values were not associated with wheezing phenotype or blood eosinophilia.

This study is one of the few large-scale epidemiological studies among 4-yr-old children from the general population showing that children with symptoms of asthma and atopy have higher levels of exhaled nitric oxide than those without.
Drug-susceptibility testing in tuberculosis: methods and reliability of results
Authors: Kim S. J.
Published: February 2005

The demand for reliable drug-susceptibility testing (DST) increases with the expansion of antituberculosis drug-resistance surveillance, and with the need for an appropriate treatment of multidrug-resistant tuberculosis, whose incidence gradually increases in many parts of the world. However, the reliability of DST results obtained through widely used methods does not meet acceptable levels, except for DST to isoniazid and rifampicin.

In general, susceptibility results are highly predictable, while resistance results show low predictive values when the resistance prevalence is <10%. Poor reliability stems from a weak correlation with clinical response and a low reproducibility due to the poor standardisation of the complex and fragile test procedures. Therefore,in vitrocriteria of resistance for susceptibility testing should be carefully determined with representative clinical samples ofMycobacterium tuberculosisisolated from patients never treated with any antituberculosis drug, and from patients having failed treatment with a regimen containing the tested drug; DST should then be carefully standardised to obtain reproducible results.

The critical concentration of some drugs is close to the minimal inhibitory concentration for wild susceptible strains and, thus, drug-susceptibility testing is prone to yield poorly reproducible results. These issues call for physicians' attention when using the results from drug-susceptibility testing for case management.
Bouguer gravity anomalies and occurrence patterns of kimberlite pipes in Narayanpet-Maddur Regions, Andhra Pradesh, India
Authors: Vasanthi A. , Mallick K.
Published: February 2005

The Narayanpet Kimberlite field, that lies southwest of Hyderabad, the capital city of Andhra Pradesh, India, hosts a number of kimberlite pipes. These pipes appear to be randomly positioned. However, based on regional geologic structures revealed by Bouguer gravity anomalies, especially in a regional gravity map, their locations form a definite pattern. In the Narayanpet-Maddur region, regional Bouguer gravity contours exhibit some features of geologic interest: (1) the eastward convex regional contours show an increase in convexity from the Maddur and Kotakonda area on the east to Narayanpet on the west, (2) convexity is maximum in the vicinity of Narayanpet, where a large number of Kimberlite pipes occur nearly parallel to the regional contour, and (3) between Narayanpet and the Maddur-Kotakonda region, kimberlite pipes occur at intersections of three eastward, convex concentric zones with four lineaments, one trending northeast-southwest and the other three nearly east-west. These linear trends are believed to be radial, extensional, deep-fracture zones, through which kimberlite magma erupted about 1100 Ma. Modeling the residual gravity anomaly over one of the four profiles shows fairly good agreement between observed and computed fields. Based on analysis of Bouguer gravity anomalies and modeling of the residual gravity field, likely locations for kimberlite pipes are the contact zones between granite plutons and the country rocks that coincide with the northeast-southwest–trending radial faults that pass through Narayanpet and Kotakonda to the south and through Kazipur to the north.
Full-resolution 3D GPR imaging
Authors: Grasmueck Mark , Weger Ralf , Horstmeyer Heinrich
Published: February 2005

Noninvasive 3D ground-penetrating radar (GPR) imaging with submeter resolution in all directions delineates the internal architecture and processes of the shallow subsurface. Full-resolution imaging requires unaliased recording of reflections and diffractions coupled with 3D migration processing. The GPR practitioner can easily determine necessary acquisition trace spacing on a frequency-wavenumber (f-k) plot of a representative 2D GPR test profile. Quarter-wavelength spatial sampling is a minimum requirement for full-resolution GPR recording. An intensely fractured limestone quarry serves as a test site for a 100-MHz 3D GPR survey with 0.1 m × 0.2 m trace spacing. This example clearly defines the geometry of fractures in four different orientations, including vertical dips to a depth of 20 m. Decimation to commonly used half-wavelength spatial sampling or only 2D migration processing makes most fractures invisible. The extra data-acquisition effort results in image volumes with submeter resolution, both in the vertical and horizontal directions. Such 3D data sets accurately image fractured rock, sedimentary structures, and archeological remains in previously unseen detail. This makes full-resolution 3D GPR imaging a valuable tool for integrated studies of the shallow subsurface.
Estimating the boundary surface between geologic formations from 3D seismic data using neural networks and geostatistics
Authors: Dowd Peter A. , Pardo-Igúzquiza Eulogio
Published: February 2005

The exact locations of horizons that separate geologic sequences are known only at physically sampled locations (e.g., borehole intersections), which, in general, are very sparse. 3D seismic data, on the other hand, provide complete coverage of a volume of interest with the possibility of detecting the boundaries between formations with, for example, contrasted acoustic impedance. Detection of boundaries is hampered, however, by coarse spatial resolution of the seismic data, together with local variability of acoustic impedance within formations. The authors propose a two-part approach to the problem, using neural networks and geostatistics. First, an artificial neural network is used for boundary detection. The training set for the neural net comprises seismic traces that are collocated with the borehole locations. Once the net is trained, it is applied to the entire seismic grid. Second, output from the neural network is processed geostatistically to filter noise and to assess the uncertainty of the boundary locations. A physical counterpart is interpreted for each structure inferred from the spatial semivariogram. Factorial kriging is used for filtering, and uncertainty in the shape of the boundaries is assessed by geostatistical simulation. In this approach, the boundary locations are interpreted as random functions that can be simulated to incorporate their uncertainty in applications. A case study of boundary detection between sandstone and breccia formations in a highly faulted zone is used to illustrate the methodologies.
BLyS antagonists and peptide tolerance induction
Authors: Merrill J T
Published: February 2005

The major impediment to drug development for systemic lupus erythematosus (SLE) is its heterogeneity. The unpredictable manner in which lupus targets different organs at varying intensity makes the study of new drugs and the optimization of their administration extremely difficult. With the advent of novel, targeted biologic agents for SLE, it can be hoped that more strategic, lupus-relevant immune modulation will lead to safer and more effective treatments. Two alternative new approaches to lupus treatment are reviewed. The first involves selective inhibition of a single protein (BLyS), which may play a central role in host defense and in the pathogenesis of SLE. Although this approach is finely targeted to the inhibition of a single protein which is known to be upregulated in SLE patients, the positioning of BLyS at a critical hub in the immune response suggests that more global adverse repercussions on immunity might still occur. The second strategy is the use of peptides designed to specifically induce tolerance in limited autoreactive immune responses. Immune repercussions might, at least in theory, be almost nonexistent with this kind of approach. Concerns that limited induction of tolerance might have equally limited impact on the complex immune disorder of SLE are not borne out in preliminary murine data. Specific development programs are ongoing using both of these strategies and have recently entered human trials.
Bone mineral density in postmenopausal Chinese patients with systemic lupus erythematosus
Authors: Mok C C , Mak A , Ma K M
Published: February 2005

The objective was to study the bone mineral density (BMD) and its clinical determinants in a cohort of postmenopausal patients with systemic lupus erythematosus (SLE). All postmenopausal SLE patients receiving long term glucocorticoids were identified from our medical clinics. Lumbar and femoral BMDs were measured by dual X-ray absorptiometry. Clinical determinants of BMD were studied by simple and multiple linear regression. Variables evaluated were: age, body mass index, parity, duration of menopause, smoking and alcohol drinking, duration of SLE and steroid treatment, cumulative prednisone dose, clinical and serological profile, disease activity, damage index and the use of medications. In total, 34 patients were studied. The mean age was 52.9 + 4.9 years and the median duration of SLE was 75.5 months. The mean duration of menopause was 5.2 + 3.9 years and the daily maintenance dose of prednisone was 4.0 + 2.5 mg/day. At the lumbar spine, 33% of the patients were osteopenic and 48% were osteoporotic. Two patients had thoracic and lumbar vertebral compression fractures. At the nondominant femoral neck, 74% of patients were osteopenic but only 3% was osteoporotic. In a multivariate model, the current or past use of hydroxychloroquine (HCQ) was associated with a higher spinal BMD. The presence of anti-Sm and the absence of anti-Ro were associated with a higher femoral BMD. It was concluded that osteoporosis, especially at the spine, is a common and serious problem in postmenopausal Chinese SLE patients receiving long term glucocorticoid therapy. Active intervention should be considered. The protective role of HCQ has to be confirmed with further studies.
Giant cell myocarditis: a rare cardiovascular manifestation in a patient with systemic lupus erythematosus
Authors: Chung L , Berry G J , Chakravarty E F
Published: February 2005

Giant cell myocarditis (GCM) is a rare form of myocarditis with a median survival of less than one year. It has been reported to occur in patients with various underlying autoimmune diseases; however, no cases of GCM have been described in patients with clear evidence of underlying systemic lupus erythematosus (SLE). The presentation of GCM may mimic that of lupus myocarditis, including an initial response to immunosuppression. Despite initial clinical similarities, lupus myocarditis and GCM are histologically distinct entities with dramatic differences in prognosis. We report herein a patient with a longstanding history of SLE, who presented acutely with myocarditis, responded well to initial immunosuppression and then subsequently died of progressive heart failure that was found to be due to GCM. Endomyocardial biopsy can help define diagnosis and prognosis of lupus patients presenting with myocarditis, and early referral for cardiac transplantation should be considered in patients diagnosed with GCM.
Methotrexate in systemic lupus erythematosus
Authors: Wong J M , Esdaile J M
Published: February 2005

The most appropriate treatment of moderate, nonorgan threatening disease activity in systemic lupus erythematosus (SLE) remains poorly defined, although methotrexate (MTX) is commonly used. The results of 20 uncontrolled case series and a single retrospective cohort study tend to support its use to treat active skin and joint disease. Unfortunately, three prospective randomized trials have reported conflicting results. Two reported improvement in overall disease activity and decreased corticosteroid requirement with MTX. The third trial showed no benefit from MTX for disease activity, but did report a reduction in corticosteroid requirements. Difficulties in conducting trials in moderately active SLE are discussed.
Efficacy and safety of nadroparin in the treatment of pregnant women with antiphospholipid syndrome: a prospective cohort study
Authors: Ruffatti A , Favaro M , Tonello M , De Silvestro G , Pengo V , Fais G , Suma V , Chiarelli S , Todesco S
Published: February 2005

The optimal therapeutic management of patients with antiphospholipid syndrome (APS) during pregnancy is debatable. In the present prospective cohort study the use of a low molecular weight heparin (LMWH) (nadroparin), administered alone twice daily in 30 pregnant women who were diagnosed with APS on the basis of the current classification criteria, is evaluated. Dosage was adjusted according to anti-Xa levels in the patients as the pregnancies progressed. Three women, in whom an important gradual fall in platelet count in the first trimester did not respond to increased nadroparin doses, were shifted to a second-line treatment protocol. Fetal loss occurred in two of the 27 remaining women (7.40%), while 25 (92.59%) delivered 25 live infants, between the 32nd and 40th weeks of gestation. No fetal problems were registered during pregnancies, while maternal complications occurred in two of the 25 patients (8%). Moreover, there were no thrombotic events in any of the women during the study. Patient compliance was good and only minor side-effects were reported. The results of this study indicate that nadroparin alone is useful and safe in the management of pregnant patients with APS. However, in consideration of the good pregnancy outcome obtained in patients with only pregnancy morbidity when heparin and aspirin were used together, other studies comparing nadroparin twice daily with once daily plus Aspirin would be useful to ascertain which is more effective in these patients.
Maternal and fetal outcome of lupus pregnancy: a prospective study of 29 pregnancies
Authors: Molad Y , Borkowski T , Monselise A , Ben-Haroush A , Sulkes J , Hod M , Feldberg D , Bar J
Published: February 2005

The aim of this study was to analyse pregestational and pregnancy risk factors for adverse fetal and maternal outcome in lupus pregnancy. Twenty women with systemic lupus erythematosus (SLE) (29 pregnancies) were prospectively evaluated.

Mean patient age was 29.5 + 4.7 years, and mean disease duration, 6.3 + 6.5 years. Twenty-two pregnancies (75.9%) ended in live births; preterm delivery occurred in 17.4%, intrauterine growth restriction in 50%, preeclampsia in 3.7%, and gestational hypertension in 8%. Six pregnancies (20.7%) ended in spontaneous abortions. Adverse live-birth outcome was significantly associated with low pregestational serum albumin level, elevated gestational anti-dsDNA antibody, and diabetes mellitus. Spontaneous abortion was directly associated with low levels of pregestational serum albumin, positive anticardiolipin IgA, anti-β2-glycoprotein I IgM, and anti-La antibodies, and inversely associated with number of patients’ children. Postgestational lupus flare-up was noted in six pregnancies. Risk factors included high pregestational SLE Disease Activity Index (SLEDAI), lower serum albumin, elevated serum antibody to dsDNA, proteinuria, and use of prednisone and hydroxychloroquine.

We conclude that despite high rate of obstetrical complications and postpartum lupus flare-up, pregnancy poses low risk for the majority of women with SLE.
Cardio-pulmonary involvement in juvenile systemic lupus erythematosus
Authors: Beresford M W , Cleary A G , Sills J A , Couriel J , Davidson J E
Published: February 2005

Cardio-pulmonary manifestations of systemic lupus erythematosus (SLE) are well recognized in adults. We report the occurrence of clinically significant cardio-pulmonary disease in a cohort of predominantly Caucasian children with SLE. All children with SLE attending the Royal Liverpool Children’s NHS Trust between 1995 and 2003 were reviewed. Of 29 children with SLE, 27 (93%) were Caucasian. Nine (31%) had cardio-respiratory complications: cardiac only (n = 1); respiratory only (n = 4); both cardiac and respiratory manifestations (n = 4). Median (range) duration of follow-up of affected children: four years (six months to 11 years). Six out of eight (75%) presented with respiratory complications before SLE was diagnosed. Three children had pericardial effusions, one requiring pericardiocentesis for tamponade. One had cardiac conduction defects and another significant pulmonary hypertension. Respiratory complications comprised: interstitial lung disease (n = 4), with two showing evidence of pulmonary fibrosis; pleural effusions (n = 2), pulmonary haemorrhage (n = 1) and lupus pneumonitis (n = 1). Disease course was complicated by CMV infection in one child. Lung biopsy was performed in five cases. Seven were treated with cyclophosphamide with significant improvement in symptoms/lung function. Of this predominantly Caucasian paediatric cohort with SLE, 31% had significant cardio-pulmonary involvement. All children with SLE should have regular monitoring of their cardio-respiratory status.
Anti-cytokine therapy in systemic lupus erythematosus
Authors: Smolen J S , Steiner G , Aringer M
Published: February 2005

In the course of the disease, a wide variety of cytokines is dysregulated, many of which likely influence systemic lupus erythematosus (SLE) autoimmunity and/or lupus tissue inflammation. Proinflammatory cytokines in particular, such as TNF, IL-6, IL-18 or IFN-gamma, may play a major role in propagating the inflammatory processes responsible for tissue damage. These cytokines are overexpressed both systemically and locally, and preliminary results from open-label trials and/or animal studies suggest potential benefits of blocking either of these inflammatory mediators. Since new therapeutic agents may soon offer many ways to influence the process, controlled clinical trials following open-label safety studies are of central importance to arrive at optimized therapies for SLE patients.
Block and tackle: CTLA4Ig takes on lupus
Authors: Davidson A , Diamond B , Wofsy D , Daikh D
Published: February 2005

Blockade of antigen nonspecific costimulatory signals is a promising approach for the treatment of autoimmune diseases including systemic lupus erythematosus (SLE). CTLA4Ig, an antagonist of the CD28/B7 costimulatory interaction, effectively prevents SLE onset in several murine models and, when used in combination with cyclophosphamide, can induce remission of active SLE nephritis. In this review we describe the known mechanisms of action of CTLA4Ig both in normal immunity and in autoimmune disease models and address issues about its activity that still need to be resolved. We discuss the preclinical use of CTLA4Ig in murine SLE models and the rationale for a clinical trial in SLE patients.
An integrated approach to consumer representation and involvement in a multicentre randomized controlled trial
Authors: Langston Anne L , Mccallum Marilyn , Campbell Marion K , Robertson Clare , Ralston Stuart H
Published: February 2005

Although, consumer involvement in individual studies is often limited, their involvement in guiding health research is generally considered to be beneficial. This paper outlines our experiences of an integrated relationship between the organisers of a clinical trial and a consumer organisation. The PRISM trial is a UK multicentre, randomized controlled trial comparing treatment strategies for Paget's disease of the bone. The National Association for the Relief of Paget's Disease (NARPD) is the only UK support group for sufferers of Paget's disease and has worked closely with the PRISM team from the outset. NARPD involvement is integral to the conduct of the trial and specific roles have included: peer-review; trial steering committee membership; provision of advice to participants, and promotion of the trial amongst Paget's disease patients. The integrated relationship has yielded benefits to both the trial and the consumer organisation. The benefits for the trial have included: recruitment of participants via NARPD contacts; well-informed participants; unsolicited patient advocacy of the trial; and interested and pro-active collaborators. For the NARPD and Paget's disease sufferers, benefits have included: increased awareness of Paget's disease; increased access to relevant health research; increased awareness of the NARPD services; and wider transfer of diagnosis and management knowledge to/from health care professionals. Our experience has shown that an integrated approach between a trial team and a consumer organisation is worthwhile. Adoption of such an approach in other trials may yield significant improvements in recruitment and quality of participant information flow. There are, however, resource implications for both parties.
Experimental designs for multicomponent interventions among persons with multifactorial geriatric syndromes
Authors: Allore Heather G , Tinettia Mary E , Gill Thomas M , Peduzzi Peter N
Published: February 2005

This paper discusses issues about the design of clinical trials to test multicomponent interventions for multifactorial health conditions, such as geriatric syndromes in which more than one risk factor is related to the outcome. The issues covered include: identification and selection of modifiable risk factors related to the outcome of interest, selection of intervention components to reduce the deleterious effects of the modifiable risk factors, assignment of components of the intervention, blinding, sample size requirements and estimation of component effects. Each of these issues is explored using examples from nine illustrative multicomponent intervention trials. Statistical and clinical concerns regarding the design of multicomponent interventions are addressed. We also propose elements of multicomponent interventions for multifactorial health conditions that should be reported in publications and areas where future research is needed.
A web-based system for managing and co-ordinating multiple multisite studies
Authors: Winget Marcy , Kincaid Heather , Lin Peter , Li Li , Kelly Sean , Thornquist Mark
Published: February 2005

Efficient and secure collection and management of information is essential in any modern biomedical study. Data management and coordination of multisite studies is a complex process. It involves development of systems for data collection, data cleaning with quality assurance checks, and specimen tracking, as well as development of procedures for conducting the study, training clinical sites, and communicating with sites to answer study questions and resolve and track data inquiries and resolutions. We developed a secure web-based system that is designed to automate evaluation of eligibility criteria and data collection, track specimens, serve as a resource for study-specific information, facilitate communication across sites in multisite studies, track data queries and resolutions, and allow administrative management of studies. The system combines a common framework across studies that defines the internal structure for all the web pages, with a study-specific one that defines the content of each page via a relational database. This combination creates a flexible and efficient environment enabling several multisite studies to be simultaneously or consecutively implemented and managed in a timely manner. We describe the development process, the system and its evaluation, current status, lessons learned, and future development plans.
Shared care for people with mental illness: a GP's perspective
Authors: Lester Helen
Published: February 2005

Shared care in mental health is now a policy imperative in England and Wales, yet its meaning, form and function are still open to debate. In this article, I discuss the benefits of and barriers to a shared care approach, explain how policy is currently driving practice in this area, discuss recent shared care initiatives and highlight some of the tensions inherent in the approach, particularly from the viewpoint of patients. I also give some of the key factors that need to be in place within a ‘whole systems' approach to ensure that shared care moves from the rhetoric of the statute book to everyday practice.
Alcohol dependence and driving: A survey of patients' knowledge of DVLA regulations and possible clinical implications
Authors: Culshaw Martin , Wootton Lisa , Wylie Scott
Published: February 2005

Aims and Method

A survey of 58 patients with alcohol dependence was carried out to ascertain how much knowledge such patients have about the Driver and Vehicle Licensing Agency (DVLA) regulations. Patients completed a questionnaire about whether they follow DVLA regulations, what information health professionals had given to them and whether they would still seek treatment if they knew doctors might inform the DVLA.

Results

The majority of patients surveyed were continuing to drive. Very few had any knowledge of DVLA regulations regarding alcohol dependence. With the knowledge that doctors have a duty to notify the DVLA in certain circumstances, a significant proportion said they would be less likely to seek treatment or would stop attending for treatment.

Clinical Implications

Health professionals may be avoiding discussions of the DVLA regulations with patients suffering from alcohol dependence in an attempt to preserve the doctor–patient relationship.
Cbl-mediated ubiquitination of α5 integrin subunit mediates fibronectin-dependent osteoblast detachment and apoptosis induced by FGFR2 activation
Authors: Kaabeche Karim , Guenou Hind , Bouvard Daniel , Didelot Nadège , Listrat Antoine , Marie Pierre J.
Published: February 2005

Fibroblast growth factor receptor signaling is an important mechanism regulating osteoblast function. To gain an insight into the regulatory role of FGF receptor-2 (FGFR2) signaling in osteoblasts, we investigated integrin-mediated attachment and cell survival in human calvarial osteoblasts expressing activated FGFR2. FGFR2 activation reduced osteoblast attachment on fibronectin. This was associated with reduced expression of the α5 integrin subunit normally expressed in human calvarial osteoblasts in vivo. Treatment with lactacystin, a potent inhibitor of proteasome, restored α5 integrin levels in FGFR2 mutant osteoblasts. Immunoprecipitation analysis showed that α5 integrin interacts with both the E3 ubiquitin ligase Cbl and ubiquitin. Immunocytochemistry revealed that α5 integrin colocalizes with FGFR2 and Cbl at the leading edge in membrane ruffle regions. Transfection with the 70Z-Cbl mutant lacking the RING domain required for Cbl-ubiquitin interaction, or with the G306E Cbl mutant that abolishes the binding ability of Cbl phosphotyrosine-binding domain restored α5 integrin levels. This suggests that Cbl-mediated ubiquitination plays an essential role in α5 integrin proteasome degradation induced by FGFR2 activation. Reduced α5 integrin expression was associated with an increased Bax/Bcl-2 ratio and increased caspase-9 and -3 activities in FGFR2 mutant osteoblasts. Forced expression of α5 integrin rescued cell attachment and corrected both the Bax/Bcl-2 ratio and caspase-3 and caspase-9 activities in FGFR2 mutant osteoblasts. We show that Cbl recruitment induced by FGFR2 activation triggers α5 integrin degradation by the proteasome, which results in reduced osteoblast attachment on fibronectin and caspase-dependent apoptosis. This identifies a functional role of the α5 integrin subunit in the induction of apoptosis triggered by FGFR2 activation in osteoblasts, and reveals that a Cbl-dependent mechanism is involved in the coordinated regulation of cell apoptosis induced by α5 integrin degradation.
Effect of moving surface on the aerodynamic drag of road vehicles
Authors: Singh S N , Rai L , Puri P , Bhatnagar A
Published: February 2005

The effect on aerodynamic drag using a model of a truck has been investigated by controlling the boundary layer separation by the momentum injection method using a rotating cylinder. It involves the use of experiments coupled with computational fluid dynamics (CFD) analysis to validate the theory of momentum injection. Modelling of the truck has been done on the software GAMBIT©. The best suitable turbulence model was selected by comparing the results with the experimental results. The rotational speed and radius of the cylinder are varied to establish the effect of momentum injection on aerodynamic drag. The coefficient of drag reduces by approximately 35 per cent from an initial value of 0.51-0.32 for a cylinder of radius 1 cm with rotational speed of 4000 r/min.
A diesel particulate filter regeneration model with a multi-step chemical reaction scheme
Authors: Law M C , Clarke A , Garner C P
Published: February 2005

Diesel particulate filters (DPFs) are considered necessary in order to meet future global diesel engine emissions legislation. Various regeneration methods have been developed to clean DPFs by periodic oxidation of trapped particulate matter (soot). To achieve this goal, it is important to understand the fundamentals of the regeneration process. Previous soot oxidation regeneration models relied on tunable chemical kinetic parameters to achieve agreement between model and experimental results. In the work reported in this paper, a multistep chemical reaction scheme is incorporated in a model to study the thermal regeneration process. The regeneration model does not require tunable parameters and its results compare well with experimental findings. The effects on regeneration of various gas species are also studied, in addition to O2 and N2, such as CO and H2O that are present in the exhaust gas. The model is also used to demonstrate the effects of quenching the regeneration process and its impact on partial filter regeneration.
Experimental verification using a driving simulator of the effect of simultaneous optimal distribution of tyre forces for active vehicle handling control
Authors: Mokhiamar O , Abe M
Published: February 2005

Both theoretical and experimental studies are carried out in order to prove the effect of the simultaneous optimum distribution of lateral and longitudinal tyre forces on enhancement of vehicle handling and stability assuming that all four wheels can be independently steered and driven/braked. A driving simulator is used as an experimental instrument to investigate the effect of the optimum tyre force distribution control. The inputs to the optimization process are the driver's commands (steering wheel angle and foot brake pressure/accelerator pedal pressure), while the outputs are lateral and longitudinal forces on all four wheels. Lateral and longitudinal tyre forces cannot be chosen arbitrarily, but must satisfy certain specified equality constraints. The equality constraints are related to the required total longitudinal force, total lateral force and total yaw moment to achieve a given vehicle motion. The total lateral force and total moment required are introduced using the model responses of side-slip angle and yaw rate to the driver's steering input, while the total longitudinal force is computed according to the driver's command (traction/braking). The results of either computer simulation or a driving simulator show that the influence of the proposed optimum tyre force distribution control on vehicle performance enhancement is significantly apparent. Furthermore, driving simulator results show very good agreement with the computer simulation results presented.
Study on combustion and emission characteristics of a vehicle engine fuelled with dimethyl ether
Authors: Ying Wang , Longbao Zhou , Zhongji Yang , Hongyi Dong
Published: February 2005

This paper reports on basic investigations into identifying the optimum parameters of a fuel system for a four-cylinder, direct-injection diesel engine with dimethyl ether (DME) as fuel—such as nozzle opening pressure, nozzle type, etc. Combustion and emission characteristics of the DME engine are studied experimentally. Smokeless emission can be realized under all operating conditions; in addition, NOx, HC, CO and particulate matter (PM) emissions of the CA498 DME engine can meet Euro 3 regulations by using an oxidation catalytic converter. It is also indicated that NO x emissions can reduce by about 40 per cent at larger exhaust gas recirculation ratios with less penalty on the brake thermal e ffi ciency of the DME engine. A DME-powered vehicle has been developed and is operating successfully on the highway. The maximum speed and accelerating performance are equivalent to those of diesel operation; the noise of the vehicle is lower than that of diesel vehicles. Very promising results with respect to emission, e ffi ciency, durability, and combustion noise can be achieved in a DME engine.
On-line control for optimal ignition timing using the pseudolinear radial basis function and the local linear model tree
Authors: Beham M , Yu D L
Published: February 2005

A new generation of engines demands new control strategies. The increased number of control variables of variable valve timing engines results in complexity of conventional control structures. This necessitates the integration of new technologies for optimal control of the ignition timing. This paper presents a neural network controller for ignition timing that uses two recently proposed new neural network structures—a pseudolinear radial basis function (PLRBF) network and a local linear model tree (LOLIMOT) network. Tests showed that the relative load signal is not necessary to evaluate the ignition angle, and therefore no air mass meter is necessary. The two neural networks are compared with a conventional look-up table control structure. The network controller improves the conventional look-up table method for calibration by comparison with bilateral look-up tables. The neural controller is implemented and tested in a research car. Experimental results show that the neural networks are very effective in mapping non-linearity. The design of the neural network controller simplifies the structure drastically.
Iminium Alkaloids from Marine Invertebrates: Structure, Biological Activity, and Biogenesis
Authors: Kita Masaki , Uemura Daisuke
Published: February 2005

The discovery of new natural products frequently triggers a breakthrough in basic sciences. This review features marine iminium alkaloids, which control biologically and physiologically intriguing phenomena. Pinnatoxins, potent shellfish poisons purified from the Okinawan bivalve Pinna muricata, activate Ca2+ channels. Norzoanthamine hydrochloride, isolated from the colonial zoanthid Zoanthus sp., suppresses decreases in bone weight and strength in ovariectomized mice. Symbioimine, an amphoteric iminium metabolite from the dinoflagellate Symbiodinium sp., inhibits osteoclast differentiation. The latter two compounds are good candidates for antiosteoporotic drugs.