The Midpoint Rule as a Variational--Symplectic Integrator. I. Hamiltonian Systems

Numerical algorithms based on variational and symplectic integrators exhibit special features that make them promising candidates for application to general relativity and other constrained Hamiltonian systems. This paper lays part of the foundation for such applications. The midpoint rule for Hamilton's equations is examined from the perspectives of variational and symplectic integrators. It is shown that the midpoint rule preserves the symplectic form, conserves Noether charges, and exhibits excellent long--term energy behavior. The energy behavior is explained by the result, shown here, that the midpoint rule exactly conserves a phase space function that is close to the Hamiltonian. The presentation includes several examples.Comment: 11 pages, 8 figures, REVTe

Granulomatosis with polyangiitis with obstructive pneumonia progressing to hypertrophic pachymeningitis A case report

Rationale: Bronchial involvement alone is a rare initial manifestation of granulomatosis with polyangiitis (GPA). Herein, we report a case of refractory GPA with obstructive pneumonia caused by bronchial involvement. Patient concerns: A 65-year-old man complained of a 2-week cough and fever. Diagnoses: Considering the presence of opacities and multiple consolidations in both lungs due to obstruction or stenosis on the bronchus, which did not respond to antibiotics, and proteinase-3-antineutrophil cytoplasmic autoantibody positivity, he was diagnosed with GPA. Positron emission tomography- computed tomography scan revealed no abnormal findings in the upper respiratory tract. Interventions: He was treated with prednisolone (PSL, 50 mg/d) and intravenous cyclophosphamide. Outcomes: His general and respiratory symptoms improved. However, 8 weeks after PSL treatment at 20 mg/d, he developed a relapse of vasculitis along with sinusitis and hypertrophic pachymeningitis. Hence, PSL treatment was resumed to 50 mg/d, and weekly administration of rituximab was initiated. Consequently, the symptoms gradually mitigated. Lessons: GPA with bronchial involvement is often intractable and requires careful follow-up, which should include upper respiratory tract and hypertrophic pachymeningitis assessment

Detection of isorhamnetin glycosides in extracts of apples (Malus domestica cv. ‘Brettacher’) by HPLC-DAD and HPLC-APCI-MSy MS.

Extracts of apple fruits (Malus domestica cv. "Brettacher") were analysed by HPLC with photodiode array detection. An unknown peak was monitored displaying the same retention time as isorhamnetin 3-Oglucoside. Preliminary identification of the isorhamnetin aglycone was performed by comparison of UV spectral data of the unknown compound with a reference substance. Using atmospheric pressure chemical ionisation mass spectrometry in the negative ion mode, the presence of an isorhamnetin glycoside was supported by loss of 162 amu from the pseudomolecular ion (m/z 477). MS 2 product ion analysis of the parent ion m/z 477 provided a fragmentation pattern identical to the reference. Collision-induced dissociation of the aglycone (m/z 315) in the MS 3 product ion analysis allowed the differentiation of rhamnetin and isorhamnetin, and unambiguous assignment by comparison with standard compounds. A second isorhamnetin glycoside eluting prior to the glucoside was tentatively identified as isorhamnetin 3-Ogalactoside. To the best of our knowledge, this is the first report of isorhamnetin glycosides in apple fruit extracts. Results are discussed with respect to chemotaxonomic relevance within the genera Malus and Pyrus, and especially in consideration of the control of the authenticity of apple products

The effect of osteopathic medicine on pain in musicians with nonspecific chronic neck pain: a randomized controlled trial

Background: Nonspecific chronic neck pain (cNP) is common in adult violinists and violists and is often treated with osteopathic medicine (OM), although the effectiveness of this treatment has not been determined to date. This study aimed to evaluate the effectiveness and safety of OM in adult violinists and violists with cNP. Methods: In a two-armed randomized controlled single-center open trial, adult violinists and violists, including music students, with cNP (⩾12 weeks) were randomized to either five individualized OM sessions (OM group) or to no intervention (control group, CG) in the outpatient clinic for integrative medicine, Charité - Universitätsmedizin Berlin, Germany. All patients received a musicians’ medicine consultation and paracetamol on demand. The primary outcome parameter was the neck pain intensity on a visual analog scale (VAS, 0– 100 mm, 0 = no pain, 100 = worst imaginable pain) after 12 weeks. Secondary outcomes included neck pain disability (Neck Disability Index, NDI, 0–100%) after 12 weeks. The last follow-up visit was after 52 weeks. Statistical analysis included analysis of covariance adjusted for respective baseline value. Results: Altogether, 62 outpatients were included [OM group (n = 28), CG (n = 34); 81% female; mean age, 41.6 ± 11.1 years; mean baseline neck pain, 55.9 ± 11.6 mm]. After 12 weeks, OM was associated with an improvement in the OM group versus the CG in neck pain on the VAS [14.6 mm (95% confidence interval 8.0; 21.2) versus 40.8 mm (34.7; 46.9), p < 0.001, Cohen’s d = 1.4], and neck pain disability as determined by the NDI [8.8% (6.7; 10.8) versus 17.2% (15.3; 19.1), p < 0.001]. Some improvements were maintained until 52 weeks of follow-up. No serious adverse events were observed. Conclusions: The results of this study suggest that OM might be effective in reducing pain intensity in adult violinists and violists with nonspecific cNP. Further studies should investigate the efficacy of OM in comparison with a sham procedure and with other effective therapy methods in high-quality multicenter trials. Trial registration: WHO Trial Registration https://apps.who.int/trialsearch/NoAccess.aspx?aspxerrorpath=/trialsearch/Trial2.aspx by German Clinical Trials Register DRKS00009258, Universal Trial Number (UTN): U1111-1173- 5943

TREATMENT OF WEGENER'S GRANULOMATOSIS

Treatment of Wegener's granulomatosis, often a life-threatening disease, has greatly improved, considering that before corticosteroids and immunosuppressives were available, the average survival time of patients amounted to no more than 5 months. The management of Wegener's granulomatosis can be divided in two stages: induction of remission and maintenance of remission. The standard regimen for the induction of remission consists of cyclophosphamide, 2 mg/kg/day orally, in combination with prednisone, 1mg/Kg/day orally, with a gradual tapering once remission has been obtained. To lower the overall cumulative dose, monthly intravenous pulses of cyclophosphamide have been evaluated. Other alternative treatments as high doses of corticosteroids, methotrexate, or plasmapheresis have been proposed, together as prophylaxis with trimethoprim-sulfamethoxazole. To minimize toxicity, for maintenance therapy other drugs are also used such as methotrexate, azathioprine, cyclosporine. Frequent therapeutic changes are needed due to the great variability of the disease; while important aspects are the recognition and treatment of relapse, and include not only the management of resistant disease, but also some particular aspects such as disease in chronic dialysis, renal transplant, pregnancy. Other cytotoxic drugs like leflunomide or mycofenolic mofetil appear to be promising, while new efforts to identify more effective and less toxic therapies include biologic products, such as high-dose immunoglobulin, TNF antagonists and other monoclonal antibodies. Many different kind of clinical trials are going on to better evaluate the real efficacy and safety of these treatments in Wegener's granulomatosis

Two cases of lymphoepithelial cyst of the pancreas

A 35-year-old man was found to have a cystic mass in the pancreatic body on a routine health examination ; high serum CA19-9 was also detected. The enucleated cyst was diagnosed as a lymphoepithelial cyst (LEC). A 74-year-old man found to have a cystic mass in the pancreatic head by computer tomography as well as high serum CA19-9 was suspected of a cystic neoplasm of the pancreas (IPMN), and pylorus-preserving pancreaticoduodenectomy (PPPD) was performed. Pathologically, the cyst was found to be LEC. It is often difficult to diagnose pancreatic cyst as LEC preoperatively. Care should be taken not to do over-surgery for benign disease LEC

Effects of glucocorticoids on weight change during the treatment of Wegener's granulomatosis

Objective Weight gain is a side effect of glucocorticoid (GC) use, but the natural history and health implications of changes in weight that occur during the treatment of inflammatory disease are not understood. Methods We evaluated data from the Wegener's Granulomatosis Etanercept Trial. Patients were categorized according to clinical outcome at 1 year: remission (no disease flares), single flare, or multiple flares. Risk factors for gaining ≥10 kg were examined in multivariate models. Results Weights at baseline and 1 year were available for 157 (93%) of the 168 patients analyzed. During year 1, the mean cumulative prednisone dosage in the multiple flares subgroup was 7.9 gm, compared with 6.0 gm and 3.9 gm in the single flare and remission subgroups, respectively ( P 10 kg in the first year of treatment. The quantity of weight gained by patients during treatment has potential future health implications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58632/1/23561_ftp.pd

Assessment of health‐related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's)

Objective To assess a generic measure of health‐related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA). Methods Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC‐LS). HRQOL was assessed with the Short Form 36 (SF‐36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). Results The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC‐LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC‐LS. In both arms of the WGET study, SF‐36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission ( P = 0.005). Conclusion HRQOL, as measured by the SF‐36, is reduced among patients with GPA. SF‐36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90377/1/20649_ftp.pd