A thorough characterization of base materials is the prerequisite for further research. In this paper, the characterization data of the reference materials (CEM I 42.5 R, limestone powder, calcined ...clay and a mixture of these three components) used in the second funding phase of the priority program 2005 of the German Research Foundation (DFG SPP 2005) are presented under the aspects of chemical and mineralogical composition as well as physical and chemical properties. The data were collected based on tests performed by up to eleven research groups involved in this cooperative program.
The introduction of tyrosine kinase inhibitors (TKI) in the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) has revolutionized the outcome, but the prognosis of the ...disease is still based on prognostic systems that were developed in the era of conventional chemotherapy and interferon (IFN)-alfa. A new prognostic score including only two variables, spleen size and basophils, was developed for the prediction of complete cytogenetic response (CCyR) and progression-free survival (PFS). The score was based on a large series of patients who were enrolled in prospective multicenter studies of first-line imatinib treatment. The prognostic value of the EUTOS (European Treatment and Outcome Study for CML) score has now been tested in an independent, multicenter, multinational series of 1288 patients who were treated first-line with imatinib outside prospective studies. It was found that also in these patients, the EUTOS prognostic score was predictive for CCyR, PFS and overall survival (OS). In addition, the prognostic value of the score was reported to be significant in seven of the eight other independent studies of almost 2000 patients that were performed in Europe, the Americas and Asia. The EUTOS risk score is a valid tool for the prediction of the therapeutic effects of TKI, particularly imatinib.
A simple, first principles-based model of the oxygen reduction reaction (ORR) is used to determine ORR kinetics on the (111), (100), and (211) facets of eleven transition metals (Au, Ag, Pt, Pd, Ir, ...Cu, Rh, Ni, Ru, Co, Fe). For most metals, the unreconstructed (100) facets are found to have an activity comparable to, or slightly higher than, the (111) facets. In contrast, (211) steps are found to be significantly less active than the terraces, with the exception of the most noble metals. These results are combined with simple models of the geometries of catalytic nanoparticles to estimate the average ORR activity of Pt and Au nanoparticles of various sizes. On Pt, a modest decrease in the activity with decreasing particle size is predicted, while for Au, the opposite trend is found.
We present zero field and transverse field muon spin relaxation experiments on the recently discovered Fe-based superconductor LaFeAsO1-xFx (x=0.075 and x=0.1). The temperature dependence of the ...deduced superfluid density is consistent with a BCS s-wave or a dirty d-wave gap function, while the field dependence strongly evidences unconventional superconductivity. We obtain the in-plane penetration depth of lambda ab(0)=254(2) nm for x=0.1 and lambda ab(0)=364(8) nm for x=0.075. Further evidence for unconventional superconductivity is provided by the ratio of Tc versus the superfluid density, which is close to the Uemura line of high-Tc cuprates.
Social psychiatry in private practice Balmer, R; Handschin, J; Hellmann-Merzbacher, J ...
Schweizer Archiv für Neurologie und Psychiatrie (Zurich, Switzerland : 1985),
1987, Letnik:
138, Številka:
6
Journal Article
Though in general the practice of Community Mental Health (or "Social Psychiatry") is a task of the State, the County or the City governments, the panel discussed two instances of sizeable ...contributions by private practices to the tasks of community mental health, such as crisis intervention or the care of the chronically psychiatrically handicapped, which are not commonly treated in psychiatrists' offices. The "Psychosoziale Arbeitsgemeinschaft" of Basle began in a psychiatric group practice through common sessions with public health nurses, social workers and other community helpers and served a workers' section of the city. In the course of five years several other services could be built up, such as a day-care center for psychically handicapped, a patient visiting program through voluntary helpers and a rehabilitation workshop. Ultimately subsidy from State and Federal funds could be obtained. Another program, in Zurich, started in a nonpsychiatric general practice, also in a workers' section. The physicians of that group hired, at their own expense, a social worker-educator and psychotherapist with a five year experience in community mental health work to care for the social and psychological problems commonly found in every general practice. The costs of her work cannot be generally billed to the health insurance carriers, but it is possible for the therapist to negotiate case by case with the insurance, this with success in a good many cases. The discussion with the audience shows that, in spite of considerable difficulty, it appears that private practice and especially a group practice, can make a valuable contribution to the mental health care of a disadvantaged segment of the population.
BackgroundWhile 2–4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours.MethodsClinical and genomic data were collected from 5945 patients ...with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020.ResultsIn total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I–III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17–6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS).ConclusionsA subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.
Highlights • The adapted technique allows territories of multiple motor units to be obtained with one scan. • Larger and smaller motor units are recruited throughout the depth of the masseter. • ...Heterogeneous recruitment of motor units might functionally stabilize the muscle.
Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be ...associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities.
This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS.
Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range IQR: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening.
OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.
Abstract
Background
Anti-drug antibodies (ADAs) to anti-tumor necrosis factor alpha (anti-TNF) drugs are associated with increased drug clearance and loss of response. We aimed to assess the ...effectiveness of starting an immunomodulator (IM) drug in patients with newly detected ADAs on anti-TNF monotherapy.
Methods
We reviewed the medical records of pediatric patients with inflammatory bowel disease on infliximab or adalimumab monotherapy with first-time detection of significant ADAs between 2014 and 2018. Patients who started an IM within 3 months of ADA detection were compared with those who did not (No-IM). Outcomes included steroid-free clinical and biochemical remission on the same anti-TNF , anti-TNF durability, and ADA reversal.
Results
We identified 89 patients with ADAs: 30 IM patients and 59 No-IM patients. The initial anti-TNF was stopped shortly after ADA detection in 36% of the No-IM patients vs none of the IM patients, driving longer survival on the initial anti-TNF in the IM group (P = 0.005). At 12 months, steroid-free clinical and biochemical remission on the same anti-TNF occurred in 53.9% of the IM group vs 26.8% in the No-IM group (P = 0.025). Drug levels rose higher (P = 0.003) and ADA levels fell farther (P = 0.037) in the IM group than in the No-IM group. Baseline ADA level predicted ADA reversal in the No-IM patients with an area under the receiver operating characteristic of 0.79 (P = 0.006). An ADA level <329 ng/mL had a 76.2% sensitivity and an 83.3% specificity for ADA reversal without IM.
Conclusions
Pediatric patients with inflammatory bowel disease on anti-TNF monotherapy who started an IM for significant ADA levels exhibited longer anti-TNF durability and a higher likelihood of steroid-free clinical and biochemical remission on the same anti-TNF. Patients not treated with an IM were unlikely to reverse ADAs >329 ng/mL.
Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in ...patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-β, desmin, α-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca(2+) response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas.
PDF
