Substitutional carbon doping of free-standing and Ru-supported BN sheets: a first-principles study.

The development of spatially homogeneous mixed structures with boron (B), nitrogen (N) and carbon (C) atoms arranged in a honeycomb lattice is highly desirable, as they open the possibility of creating stable two-dimensional materials with tunable band gaps. However, at least in the free-standing form, the mixed BCN system is energetically driven towards phase segregation to graphene and hexagonal BN. It is possible to overcome the segregation when BCN material is grown on a particular metal substrate, for example Ru(0 0 0 1), but the stabilization mechanism is still unknown. With the use of density-functional theory we study the energetics of BN/Ru slabs, with different types of configurations of C substitutional defects introduced to the h-BN overlayer. The results are compared to the energetics of free-standing BCN materials. We found that the substrate facilitates the C substitution process in the h-BN overlayer. Thus, more homogeneous BCN material can be grown, overcoming the segregation into graphene and h-BN. In addition, we investigate the electronic and transport gaps in free-standing BCN structures, and assess their mechanical properties and stability. The band gap in mixed BCN free-standing material depends on the concentration of the constituent elements and ranges from zero in pristine graphene to nearly 5 eV in free-standing h-BN. This makes BCN attractive for application in modern electronics.

Half-integer filling-factor states in quantum dots.

The emergence of half-integer filling-factor states, such as upsilon=5/2 and 7/2, is found in quantum dots by using numerical many-electron methods. These states have interesting similarities and differences with their counterstates found in the two-dimensional electron gas. The upsilon=1/2 states in quantum dots are shown to have high overlaps with the composite fermion states. The lower overlap of the Pfaffian state indicates that electrons might not be paired in quantum dot geometry. The predicted upsilon=5/2 state has a high spin polarization, which may have an impact on the spin transport through quantum dot devices.

Vortex clusters in quantum dots.

We study electronic structures of two-dimensional quantum dots in strong magnetic fields using mean-field density-functional theory and exact diagonalization. Our numerically accurate mean-field solutions show a reconstruction of the uniform-density electron droplet when the magnetic field flux quanta enter one by one the dot in stronger fields. These quanta correspond to repelling vortices forming polygonal clusters inside the dot. We find similar structures in the exact treatment of the problem by constructing a conditional operator for the analysis. We discuss important differences and limitations of the methods used.

Treatment with tumour necrosis factor alpha antagonists in patients with rheumatoid arthritis induces anticardiolipin antibodies.

OBJECTIVE: To determine the frequency and clinical impact of anticardiolipin antibodies (aCL) in patients with rheumatoid arthritis treated with infliximab and etanercept. METHODS: 121 patients from the Stockholm tumour necrosis factor alpha (TNFalpha) follow up registry (STURE) treated with infliximab or etanercept were studied. RESULTS: At baseline 9/65 (14%) infliximab and 10/56 (18%) etanercept treated patients had positive aCL. After 3 months the frequencies of aCL positivity were 29% (p<0.05 compared with baseline) and 27%, respectively, and after 6 months 28% and 25%. Increases were seen for both IgG and IgM aCL. Increasing age, a higher number of prior DMARDs, and higher DAS28 were predictors for the development of aCL. In the infliximab treated patients, 26/30 (87%) aCL(-) but only 7/14 (50%) aCL(+) patients met the ACR20 criteria (p<0.05), and the frequency of treatment limiting infusion reactions in the aCL(+) patients was higher than expected (17%). aCL positivity in the etanercept treated patients did not show such a clinical correlate. Four patients had thromboembolic events, of whom two were aCL(+) and two aCL(-). CONCLUSION: Frequencies of both IgM and IgG aCL positivity increase in patients treated with these TNFalpha antagonists for 3 months or longer. Increasing age, a greater number of prior DMARDs and a greater disease activity at baseline are predictors for the development of aCL. The development of aCL during treatment with infliximab, but not etanercept, is associated with worse clinical results and more frequent serious infusion reactions. aCL are an important class of autoantibodies associated with TNFalpha blocking therapy.

Treatment with infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor alpha blockers can make sense.

OBJECTIVE: When one TNFalpha blocker (etanercept or infliximab) has failed, to determine whether it makes sense to treat patients with the other. PATIENTS AND METHODS: Since 1999 patients treated with etanercept or infliximab have been systematically followed up at our institution in the STURE database. We identified 31 patients who had received both agents. RESULTS: Eighteen patients received etanercept first; discontinuation was mostly due to lack of efficacy. DAS28 values had improved only slightly with etanercept, with a mean (SEM) best DAS28 value of 4.8 (0.6). After switching to infliximab, the mean best DAS28 was 3.6 (0.6)-significantly better than the previous result (p<0.05). Similarly, the mean best ACR-N during etanercept treatment was 17.2 (6.65) and during subsequent infliximab treatment 40.4 (10.6) (p = 0.08). Thirteen patients received infliximab first; discontinuation was mainly due to adverse events. The best DAS28 value achieved during etanercept was 3.6 (0.4) compared with 4.1 (0.4) for infliximab (p<0.05), but the change in DAS28 was not different and ACR-N were similar for infliximab and etanercept in this group. CONCLUSION: For patients with insufficient efficacy from etanercept, treatment with infliximab provided better results, suggesting that a trial of infliximab is reasonable for such patients. For patients who discontinued infliximab owing to adverse events, treatment with etanercept gave at least similar clinical efficacy. Taken together, these data provide support for a trial of the reciprocal TNFalpha blocker in patients when one such agent has failed.

Role of interactions in the far-infrared spectrum of a lateral quantum-dot molecule.

We study the effects of electron-electron correlations and confinement potential on the far-infrared spectrum of a lateral two-electron quantum-dot molecule by exact diagonalization. The calculated spectra directly reflect the lowered symmetry of the external confinement potential. Surprisingly, we find interactions to drive the spectrum towards that of a high-symmetry parabolic quantum-dot. We conclude that far-infrared spectroscopy is suitable for probing effective confinement of the electrons in a quantum-dot system, even if interaction effects cannot be resolved in a direct fashion.

Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a genetically complex disease where the response to different treatments varies greatly between different patients. This is the case with the tumour necrosis factor (TNF) blocking agents, where 20-40% of patients have been described as non-responders. No predictive markers exist as yet for the prognosis of response. OBJECTIVE: To analyse whether polymorphisms of several cytokine genes are associated with the responsiveness to TNF blockade with etanercept. METHODS: 123 patients with active RA were treated with etanercept and response rates were determined after three months using American College of Rheumatology (ACR)20 and disease activity score (DAS)28 response criteria. Genotyping was done for TNF (-308 TNFA), interleukin (IL)10 (-1087 IL10), transforming growth factor (TGF)beta1 (codon 25 TGFB1), and IL1 receptor antagonist (intron 2 IL1RN). RESULTS: 24 patients (20%) were defined as non-responders owing to their failure to fulfil any of the ACR20 or DAS28 response criteria. None of the recorded alleles was alone significantly associated with responsiveness to treatment. However, a certain combination of alleles (-308 TNF1/TNF1 and -1087 G/G) was associated with good responsiveness to etanercept (p<0.05). In addition, a combination of alleles influencing interleukin 1 receptor antagonist (IL1Ra) and TGFbeta1 production (A2 allele for IL1RN and rare C allele in codon 25 of TGFB1 gene) was associated with non-responsiveness (p<0.05). CONCLUSION: Genetic polymorphisms, which may influence the balance of pro- and anti-inflammatory cytokines of relevance for the course of RA, are associated with clinical responsiveness to etanercept treatment.

Two-electron quantum dot molecule: composite particles and the spin phase diagram.

We study a two-electron quantum dot molecule in a magnetic field by the direct diagonalization of the Hamiltonian matrix. The ground states of the molecule with the total spin S = 0 and S = 1 provide a possible realization for a qubit of a quantum computer. Switching between the states is best achieved by changing the magnetic field. Based on an analysis of the wave function, we show that the system consists of composite particles formed by an electron and flux quanta attached to it. This picture can also be used to explain the spin phase diagram.

Pollen competition and seed-siring success in Picea abies.

The aim of the present work was to study pollen-tube competition in Picea abies. Controlled crossings were performed with pollen mixtures including pairs of pollen lots with fast and slowly elongating pollen-tubes. Paternity analysis using isozyme markers was performed on the progenies in order to study whether the in vitro pollen-germination vigour corresponds to the proportion of seeds sired by the pollen donor. Paternal success was found to be unequal, 15 out of 23 crossings producing progeny that differed significantly from the hypothetical ratio of 1:1. The paternal contribution in the majority of the crossings was as expected: the pollen parent with more-vigorous in vitro germination sired more seeds than the less-vigorous pollen. In the case of two pollen mixtures, however, the seed-siring success summed over the maternal trees was the opposite to the expected value. Despite these aberrations, the results support the hypothesis that pollen-tube competition is one of the factors contributing to male fitness in P. abies.However, when all the other factors affecting pollination and seed set under natural conditions are taken into account, it is clear that the seed-siring success of a particular paternal genotype cannot be predicted reliably by measuring only the in vitro pollen vigour.

Catastrophic antiphospholipid syndrome: remission following leg amputation in 2 cases.

OBJECTIVE: The antiphospholipid syndrome is characterized by venous and arterial thrombotic events that are often recurrent, thrombocytopenia, recurrent fetal loss, and elevated titers of antiphospholipid antibodies. A subtype of patients with a particularly overwhelming clinical picture has been termed catastrophic antiphospholipid syndrome (CAPS). In this report, we present 2 patients who exhibited a similar multisystem disorder associated with gangrenous changes in the lower extremities. METHODS: Two patients with CAPS are presented, highlighting the impact of this disorder on the patients and the response to various therapeutic modalities. RESULTS: Both patients had pulmonary, cardiac, cutaneous, and neurologic findings consistent with CAPS. In addition, they had large purulent leg ulcers associated with livedo reticularis. Amputation of the legs in each case induced remission of the systemic illness. CONCLUSIONS: We believe that infection plays a significant role in the pathogenesis and amplification of the antiphospholipid syndrome. In certain patients, this association probably is mediated via immune mechanisms, which also enhance the genesis of atherosclerosis. After the foci of infection (suppurative leg ulcers) were removed, the underlying illness improved. These case studies provide an opportunity to study the interrelationship between several confounding factors that converge and lead to the development of this autoimmune condition.

Development of a pharmaceutical apotransferrin product for iron binding therapy.

High-dose chemotherapy of patients with haematological malignancies results in extracellular iron accumulation and appearance of non-transferrin-bound iron, which is thought to predispose the patients to septic infections and contribute to organ toxicity. We describe the development of a human plasma-derived apotransferrin product for iron binding therapy. The product is purified from Cohn fraction IV of human plasma by two ion exchange chromatography steps and ultrafiltration. The process comprises solvent detergent treatment as the main virus inactivation step and 15 nm virus filtration and polyethylene glycol precipitation as removal steps for physico-chemically resistant infectious agents. Product characterization by electrospray and MALDI-TOF mass spectrometry indicated no other chemical modifications than N-linked glycan chains and disulphide bonds, except minor oxidation. The purity of the product was more than 98%, main impurities being IgG, IgA and hemopexin. The product had intact iron binding capacity and native conformation. A stable liquid formulation for the finished product was developed. The product has proved safe and well tolerated in early clinical trials in iron binding therapy.

[Blockade of TNFalpha--new therapeutic principle in severe rheumatoid arthritis]. / Blockad av TNF alpha--ny behandlingsprincip vid svår reumatoid artrit.

TNF-alpha is a proinflammatory cytokine. It has a key function in the inflammatory cascade both systemically and locally in the inflamed joints of patients affected by rheumatoid arthritis (RA). Treatment with two different "biological" drugs that block the proinflammatory capacity of TNF-alpha has recently been approved by the European drug authorities. This paper discusses experience gained in clinical trials and during the first year of treatment in Sweden using infliximab (anti-TNF-alpha monoclonal antibodies) and etanercept (recombinant TNF-alpha receptor fusion protein).

Rotator cuff calcifications: treatment with ultrasound-guided percutaneous needle aspiration and lavage.

OBJECTIVE: To analyze the results of ultrasound (US)-guided needle puncture, aspiration and lavage in the treatment of symptomatic calcific tendinitis of the rotator cuff. DESIGN AND PATIENTS: Atraumatic pain in 61 shoulders of 58 patients was resistant to conservative therapy. The average age of the treated patients was 42 years (range 26-49 years), follow-up was 12 months, and the mean diameter of the calcifications was 1.6 cm (range 1.1-2.9 cm). With US guidance and local anesthesia, two needles were placed within each calcification. The calcification was punctured 10-15 times and saline solution injected and aspirated using the needles until the aspirate was free of calcific particles. RESULTS AND CONCLUSIONS: Based on radiographs at 1 year follow-up. 74% (45 of 61) of the calcifications decreased, including 28% (17 of 61) which disappeared totally, and 26% (16 of 61) were unchanged. Calcifications with a faint or absent shadow on US proved to be nearly liquid (slurry calcification in 93% (14 of 15) of cases and could be aspirated. Clinical results were excellent in 74% (45 of 61), moderate in 16% (10 of 61) and poor in 10% (6 of 61) of cases. US offers technical advantages over fluoroscopy, and the typical US image of a slurry calcification helps to select the most suitable patients for aspiration treatment. The results are comparable with those using fluoroscopic guidance.

Hill-Sachs lesion: sonographic detection.

OBJECTIVE: To determine the value of ultrasonography (US) in the detection of Hill-Sachs lesion of the humerus in comparison with double-contrast computed tomographic arthrography (CTA) and with arthroscopy. DESIGN AND PATIENTS: US and CTA were performed on 92 patients, 86 of whom subsequently underwent arthroscopy. The findings of US, CTA and arthroscopy in these 86 patients in the diagnosis of Hill-Sachs lesion were analyzed. RESULTS AND CONCLUSIONS: In the detection of Hill-Sachs lesion US showed a sensitivity of 91% (21 of 23), a specificity of 95% (60 of 63) and an accuracy of 94% (81 of 86) when compared with CTA, and a sensitivity of 94% (18 of 19), specificity of 91% (61 of 67) and accuracy of 91% (79 of 86) when compared with arthroscopy. In only 2% (2 of 86) of patients was there reduced visualization because of restriction of movement. Hill-Sachs lesion and its relationship to the humeral head can be reliably diagnosed with US.

Prevention of fatal pulmonary embolism with warfarin after total hip replacement.

We studied retrospectively the efficacy of low-dose warfarin for the prevention of fatal pulmonary embolism in 1140 patients (1280 hips) undergoing total hip replacement between 1972 and 1989. The first dose, 10-20 mg, was given the night before operation and the regime was continued for 2 weeks after the procedure. Anticoagulation was aimed at achieving a therapeutic level in 4 to 5 days. All the patients were followed for 3 months. Seven died during this period and autopsy showed that 2 (0.16%) died from pulmonary embolism, one at 3 days and the other 10 days after operation. Pulmonary embolism causing symptoms, but which was not fatal, occurred in 32 patients (2.5%). Symptomatic deep vein thrombosis was present in 45 patients (3.5%). There were 14 (1.1%) massive postoperative haematoma, and 7 needed operative treatment. Low-dose warfarin can be recommended as a safe and efficient method of achieving an acceptably low incidence of postoperative thrombo-embolic complications after total hip replacement.

Effect of birch (Betula pendula) bark and food protein level on root voles (Microtus oeconomus): I. food consumption, growth, and mortality.

The effect of protein and birch bark powder (BBP) content of forage on food consumption and growth of root voles (Microtus oeconomus) was studied by feeding young voles with eight different diets for two weeks. Voles ate more when the protein content of forage was moderate (6%) or low (3%), and when BBP was added to the diets, as compared to a high (12%) protein diet without BBP addition. On high and moderate protein diets voles gained weight, whereas on low protein diets they lost weight. Addition of BBP caused reduced growth or weight loss. Consuming a diet with moderate (6%) protein and high BBP (20%) resulted in high mortality (9 of 10 died). These results show that root voles need at least 6% protein for growth and that the effect of birch bark depends on the protein content of the forage.

Effect of birch (Betula pendula) bark and food protein level on root voles (Microtus oeconomus): II. detoxification capacity.

The effect of protein and birch bark powder (BBP) content of forage on detoxification capacity of root voles (Microtus oeconomus) was studied. Young voles were fed with eight different diets for two weeks. Individuals on low (3%) protein diets had significantly lighter livers and kidneys than those on moderate (6%) or high (12%) protein diets. Birch bark powder addition did not have significant effect on organ weight. Detoxification was significantly induced, apparently due to secondary compounds in BBP. The activity of ethoxyresorufin-O-dealkylase (EROD) was high when protein content or BBP concentration in forage was high as compared to low protein diets or diets containing no BBP. Glucuronidation, on the other hand, was not induced by BBP. High BBP content caused serious physiological stress to the voles. The only individuals surviving were those capable of sufficiently allocating energy and protein to detoxification.

Medial displacement of the biceps brachii tendon: evaluation with dynamic sonography during maximal external shoulder rotation.

PURPOSE: To determine the value of the sonographic subluxation test--dynamic scanning of a shoulder during maximal external rotation--in the evaluation of medial displacement of the biceps tendon. MATERIALS AND METHODS: The subluxation test was performed during shoulder sonography in 1,210 patients, 284 of whom subsequently underwent surgery (152 men and 132 women aged 24-77 years [mean, 52 years]). Subluxation or displacement of the biceps tendon was surgically confirmed in 21 of the 284 patients (16 men and five women aged 35-57 years [mean, 48 years]). The sonographic and surgical findings in these 21 patients were analyzed. RESULTS: The subluxation test helped detect 12 of 14 (86%) cases of subluxation. Static scanning (without the subluxation test) depicted six of seven (86%) cases of dislocation. The test failed or could not be performed in 18 of the 284 (6%) patients; however, no false-positive findings occurred. CONCLUSION: The subluxation test is reliable in the diagnosis of subluxation of the biceps tendon and should be performed during shoulder sonography.