Influence of Individual Bracket Base Design on the Shear Bond Strength of In-Office 3D Printed Brackets-An In Vitro Study.

(1) Background: Novel high-performance polymers for medical 3D printing enable in-office manufacturing of fully customized brackets. Previous studies have investigated clinically relevant parameters such as manufacturing precision, torque transmission, and fracture stability. The aim of this study is to evaluate different design options of the bracket base concerning the adhesive bond between the bracket and tooth, measured as the shear bond strength (SBS) and maximum force (Fmax) according to DIN 13990. (2) Methods: Three different designs for printed bracket bases were compared with a conventional metal bracket (C). The following configurations were chosen for the base design: Matching of the base to the anatomy of the tooth surface, size of the cross-sectional area corresponding to the control group (C), and a micro- (A) and macro- (B) retentive design of the base surface. In addition, a group with a micro-retentive base (D) matched to the tooth surface and an increased size was studied. The groups were analyzed for SBS, Fmax, and adhesive remnant index (ARI). The Kruskal-Wallis test with a post hoc test (Dunn-Bonferroni) and Mann-Whitney U test were used for statistical analysis (significance level: p < 0.05). (3) Results: The values for SBS and Fmax were highest in C (SBS: 12.0 ± 3.8 MPa; Fmax: 115.7 ± 36.6 N). For the printed brackets, there were significant differences between A and B (A: SBS 8.8 ± 2.3 MPa, Fmax 84.7 ± 21.8 N; B: SBS 12.0 ± 2.1 MPa, Fmax 106.5 ± 20.7 N). Fmax was significantly different for A and D (D: Fmax 118.5 ± 22.8 N). The ARI score was highest for A and lowest for C. (4) Conclusions: This study shows that conventional brackets form a more stable bond with the tooth than the 3D-printed brackets. However, for successful clinical use, the shear bond strength of the printed brackets can be increased with a macro-retentive design and/or enlargement of the base.

Concept for the Treatment of Class III Anomalies with a Skeletally Anchored Appliance Fabricated in the CAD/CAM Process-The MIRA Appliance.

OBJECTIVE: Intermaxillary elastics, anchored skeletally, represent a promising concept for treatment in adolescent patients with skeletal Class III anomalies. A challenge in existing concepts is the survival rate of the miniscrews in the mandible or the invasiveness of the bone anchors. A novel concept, the mandibular interradicular anchor (MIRA) appliance, for improving skeletal anchorage in the mandible, will be presented and discussed. CLINICAL CASE: In a ten-year-old female patient with a moderate skeletal Class III, the novel MIRA concept, combined with maxillary protraction, was applied. This involved the use of a CAD/CAM-fabricated indirect skeletal anchorage appliance in the mandible, with interradicularly placed miniscrews distal to each canine (MIRA appliance), and a hybrid hyrax in the maxilla with paramedian placed miniscrews. The modified alt-RAMEC protocol involved an intermittent weekly activation for five weeks. Class III elastics were worn for a period of seven months. This was followed by alignment with a multi-bracket appliance. DISCUSSION: The cephalometric analysis before and after therapy shows an improvement of the Wits value (+3.8 mm), SNA (+5°), and ANB (+3°). Dentally, a transversal postdevelopment in the maxilla (+4 mm) and a labial tip of the maxillary (+3.4°) and mandibular anterior teeth (+4.7°) with gap formation is observed. CONCLUSION: The MIRA appliance represents a less invasive and esthetic alternative to the existing concepts, especially with two miniscrews in the mandible per side. In addition, MIRA can be selected for complex orthodontic tasks, such as molar uprighting and mesialization.

Precision of slot widths and torque transmission of in-office 3D printed brackets : An in vitro study.

PURPOSE: To investigate a novel in-office three-dimensionally (3D) printed polymer bracket regarding slot precision and torque transmission. METHODS: Based on a 0.022″ bracket system, stereolithography was used to manufacture brackets (N = 30) from a high-performance polymer that met Medical Device Regulation (MDR) IIa requirements. Conventional metal and ceramic brackets were used for comparison. Slot precision was determined using calibrated plug gages. Torque transmission was measured after artificial aging. Palatal and vestibular crown torques were measured from 0 to 20° using titanium-molybdenum (T) and stainless steel (S) wires (0.019â€³â€¯× 0.025″) in a biomechanical experimental setup. The Kruskal-Wallis test with post hoc test (Dunn-Bonferroni) was used for statistical analyses (significance level p < 0.05). RESULTS: The slot sizes of all three bracket groups were within the tolerance range according to DIN 13996 (ceramic [C]: 0.581 ± 0.003 mm; metal [M]: 0.6 ± 0.005 mm; polymer [P]: 0.581 ± 0.010 mm). The maximum torque values of all bracket-arch combinations were above the clinically relevant range of 5-20 Nmm (PS: 30 ± 8.6 Nmm; PT: 27.8 ± 14.2 Nmm; CS: 24 ± 5.6 Nmm; CT: 19.9 ± 3.8 Nmm; MS: 21.4 ± 6.7 Nmm; MT: 16.7 ± 4.6 Nmm). CONCLUSIONS: The novel, in-office manufactured polymer bracket showed comparable results to established bracket materials regarding slot precision and torque transmission. Given its high individualization possibilities as well as enabling an entire in-house supply chain, the novel polymer brackets bear high potential of future usage for orthodontic appliances.

Orthodontic extrusion in the digital age: a technical note.

OBJECTIVE: The aim of this case series was to test various personalized, CAD/CAM-manufactured orthodontic extrusion appliances. The appliances were characterized by high rigidity and manufacturing precision. In addition, the orthodontic force vector could be precisely and three-dimensionally planned. METHOD AND MATERIALS: After a comprehensive diagnosis of three patients with deep fractured teeth by an interdisciplinary team, each patient's personalized extrusion protocol was determined (slow or rapid extrusion). Based on an intraoral scan, the personalized extrusion appliances were then digitally planned and manufactured using selective laser melting. The force vector was also precisely planned during this process. The appliances were inserted, and the force on the teeth to be extruded was precisely applied in accordance with the extrusion protocol. After extrusion, the teeth were retained and, if necessary, permanently restored. RESULTS: The target teeth of all three patients were successfully extruded. Furthermore, good cleanability and high wearing comfort of the appliances were maintained throughout treatment, as was the precise application of force. CONCLUSION: The effectiveness of the tested digital workflow for precise and simplified orthodontic extrusion was clinically proven. The workflow guaranteed the following throughout treatment: precise planning and application of the force system; improved periodontal hygiene; and improved wearing comfort of the appliance, without affecting the patient's existing occlusion.

Mechanical properties of CAD/CAM-fabricated in comparison to conventionally fabricated functional regulator 3 appliances.

Manufacturing of Fränkel's functional regulator 3 (FR3) is complicated and requires extensive knowledge from the dental technician. To determine whether FR3s produced by CAD/CAM techniques (CAD-FR3) meet similar mechanical properties like conventional FR3s (Con-FR3), for each of 10 patient cases, three CAD-FR3 designs (palatal connector cross-section 3 × 3 mm, 4 × 1 mm or 5 × 2 mm) and one Con-FR3 were subjected to cyclic loading and subsequent fracture testing in a universal testing device. Transversal load capacity (Fmax(FR3)) and stiffness were compared among the different CAD-FR3 designs and Con-FR3s using Friedman and Wilcoxon tests with a significance level of α = 0.05. All CAD-FR3 designs had significantly higher mean Fmax(FR3) (p ≤ 0.007) and stiffness (p ≤ 0.005) than the Con-FR3s. The CAD-FR33×3 had the highest mean Fmax(FR3) (98.2 ± 26.2 N) and stiffness (37.1 ± 15.5 N/mm), closely followed by the CAD-FR35×2 (Fmax(FR3): 90.3 ± 24.7 N; stiffness: 30.0 ± 12.3 N/mm). Among the CAD appliances, CAD-FR34×1 had the lowest values (p ≤ 0.007 for all pairwise tests) with Fmax(FR3) of 45.8 ± 17.9 N and stiffness of 12.5 ± 7.3 N/mm. CAD-FR3s have superior mechanical properties in comparison to Con-FR3s if certain design parameters are followed. Further clinical investigations have to examine if they can serve as an alternative in practice.

Strongly baryon-dominated disk galaxies at the peak of galaxy formation ten billion years ago.

In the cold dark matter cosmology, the baryonic components of galaxies-stars and gas-are thought to be mixed with and embedded in non-baryonic and non-relativistic dark matter, which dominates the total mass of the galaxy and its dark-matter halo. In the local (low-redshift) Universe, the mass of dark matter within a galactic disk increases with disk radius, becoming appreciable and then dominant in the outer, baryonic regions of the disks of star-forming galaxies. This results in rotation velocities of the visible matter within the disk that are constant or increasing with disk radius-a hallmark of the dark-matter model. Comparisons between the dynamical mass, inferred from these velocities in rotational equilibrium, and the sum of the stellar and cold-gas mass at the peak epoch of galaxy formation ten billion years ago, inferred from ancillary data, suggest high baryon fractions in the inner, star-forming regions of the disks. Although this implied baryon fraction may be larger than in the local Universe, the systematic uncertainties (owing to the chosen stellar initial-mass function and the calibration of gas masses) render such comparisons inconclusive in terms of the mass of dark matter. Here we report rotation curves (showing rotation velocity as a function of disk radius) for the outer disks of six massive star-forming galaxies, and find that the rotation velocities are not constant, but decrease with radius. We propose that this trend arises because of a combination of two main factors: first, a large fraction of the massive high-redshift galaxy population was strongly baryon-dominated, with dark matter playing a smaller part than in the local Universe; and second, the large velocity dispersion in high-redshift disks introduces a substantial pressure term that leads to a decrease in rotation velocity with increasing radius. The effect of both factors appears to increase with redshift. Qualitatively, the observations suggest that baryons in the early (high-redshift) Universe efficiently condensed at the centres of dark-matter haloes when gas fractions were high and dark matter was less concentrated.

New approach for a reliable in vitro sun protection factor method - Part II: Practical aspects and implementations.

OBJECTIVE: Our previous paper (Part I: Principle and mathematical aspects) presented a new reliable in vitro sun protection factor (SPF) method and demonstrated it to be reproducible and correlated with the in vivo method. Nevertheless, the relevance of an international method should to be adaptable to all products on the market and demonstrated with a blind test. Thus, the aim of this second article was to focus on the practical aspects and implementation (Part II) of a large population of different commercially available sunscreen formulations to obtain similar in vivo SPF results for the purpose of labelling. METHODS: The method uses the spectroradiometric measurement of residual ultraviolet (UV) through the sample that was applied on a substrate with a robotic appliance. The method has been demonstrated to be highly reliable, and it is based on a multisubstrate solution with a single UV pre-irradiation dose. Furthermore, different categories of the product were studied to identify a reliable and universal in vitro SPF method. RESULTS: Based on different sunscreens products classified into 5 different groups (emulsion, oil, alcohol, stick and powder), it was demonstrated that our method has good reproducibility and accuracy compared with the clinical SPF method. Indeed, the mean coefficient of variation (CV%) was approximately 7%, and the coefficient of correlation reached approximately 0.8-1.0 for different types of tested products. CONCLUSION: Our second paper concludes that the new in vitro SPF method (based on 113 sunscreen products from the Parts I and II) is clearly adaptable for the SPF labelling purpose on any product type because it is non-invasive, less expensive, more practical and more reliable if performed under strict conditions.

Sunscreen sun protection factor claim based on in vivo interlaboratory variability.

OBJECTIVE: The SPF (sun protection factor) is the best known reference in the world for expressing UVB protection. The SPF is used for labelling purposes for consumer guidance. The determination of the SPF is often accomplished using an in vivo method that has been standardized. Only one in vivo SPF value from one laboratory is required for claiming an SPF value. The aim of this study was to determine the relevance of the in vivo SPF value in terms of interlaboratory variability for claiming purposes and to determine whether some minimum number of different in vivo SPF values from different laboratories would improve the reliability of the final SPF claimed. METHODS: A large population of 44 different commercially available sunscreen formulations from the European market has been investigated, covering various product types. The majority of the SPF values claimed ranged from 15 to 50+. For each product, at least three different in vivo SPF values tested in different laboratories have been gathered, and a variety of statistical analyses have been performed. RESULTS: For each SPF category from the average of all samples, the minimum and maximum in vivo-measured SPF values from the different laboratories would lead to labels claiming different levels of SPF for the same product. Indeed, with coefficients of variation for in vivo SPF determinations that exceed 50% in some cases, as an example, the same product could in reality be claimed to be SPF 30, SPF 50 or SPF 50+. CONCLUSION: In this study, the authors demonstrated that using only one in vivo SPF value from one laboratory may actually challenge the reliability of the final SPF claim significantly. To reduce the consumer health risk by ensuring the reliability of the SPF claim, an average from at least 3 (ideally 4) different in vivo SPF values should be compulsory.

New approach for a reliable in vitro sun protection factor method Part I: Principle and mathematical aspects.

OBJECTIVE: Development of an international harmonized in vitro method for sun protection factor (SPF) assessment is currently in progress because of the lack of both reproducibility and accuracy in the current methodology. The aim of this article was to focus on the principle and mathematical aspects (Part I) of a new approach for a reproducible and correlated in vitro test method to obtain results similar to the in vivo SPF for labelling purposes. METHODS: The currently used in vitro test is based on the spectroradiometric measurement of the residual ultraviolet (UV) transmitted through a thin layer of sunscreen spread on a substrate. To reach the goals of reproducibility and accuracy, the specifications of the key parameters and different steps of the procedure are clearly described in this study. RESULTS: Once reproducibility is obtained with an ad hoc procedure, the accuracy of the SPF values for a large number of products can be demonstrated with the prerequisite of a single UV irradiation dose and a multisubstrate solution. Using a total of 27 samples, the mean coefficient of variation was found to be <10% and the coefficient of correlation with the SPF clinical value reached approximately 0.81. CONCLUSION: The first part of the article revealed a relevant tool for the in vitro SPF assessment that can be closely correlated to the in vivo SPF for labelling purposes. The second part study will focus on the practical aspects and implementation (Part II) achieved using the present method, will validate the robustness of the models and demonstrate the need to have different product categories to reach a reliable in vitro SPF method adaptable for all products available in the market.

Competitive mode and site of interaction of ticagrelor at the human platelet P2Y12 -receptor.

BACKGROUND: The G-protein-coupled P2Y12 -receptor plays a crucial role in platelet aggregation. Recently, ticagrelor was licensed as the first perorally active and reversible P2Y12 -receptor antagonist. OBJECTIVE: The present study investigated the site and the antagonistic mode of action of ticagrelor at wild-type or mutant human P2Y12 -receptors. METHODS: Recombinant wild-type or mutant human P2Y12 -receptors were stably expressed in Chinese hamster ovary Flp-In cells. Receptor function was assessed by quantification of ADP- and 2-methylthio-ADP-mediated inhibition of forskolin-induced cellular cAMP production either using a [(3) H]cAMP-radioaffinity assay or a cAMP response element-driven luciferase reporter gene assay. RESULTS: The natural agonist ADP inhibited forskolin-induced cAMP formation at the wild-type P2Y12 -receptor with a lower potency (EC50 209 nm) than the synthetic agonist 2-methylthio-ADP (EC50 1.0 nm). Ticagrelor shifted the concentration-response curves of both agonists in a parallel and surmountable manner to the right. Increasing concentrations of ticagrelor caused increasing shifts. Schild-plot analysis revealed pA2 values of 8.85 for ticagrelor against ADP, and 8.69 against 2-methylthio-ADP, and slopes of the regression lines not different from unity. In cells expressing a recombinant C194A(5.43) -mutant P2Y12 -receptor construct, ticagrelor lost antagonistic potency when tested against ADP or 2-methylthio-ADP. CONCLUSIONS: The experiments reveal a surmountable and competitive mode of antagonism of ticagrelor at P2Y12 -receptors activated by either the natural agonist ADP or the synthetic agonist 2-methylthio-ADP. Cys194(5.43) is likely to be involved in the interaction of ticagrelor with ADP and 2-methylthio-ADP. The data give new insights into the site and mode of action of ticagrelor at the human P2Y12 -receptor.

Loss of innocence: Albert Moll, Sigmund Freud and the invention of childhood sexuality around 1900.

This paper analyses how, prior to the work of Sigmund Freud, an understanding of infant and childhood sexuality emerged during the nineteenth century. Key contributors to the debate were Albert Moll, Max Dessoir and others, as fin-de-siècle artists and writers celebrated a sexualised image of the child. By the beginning of the twentieth century, most paediatricians, sexologists, psychologists, psychiatrists, psychoanalysts and pedagogues agreed that sexuality formed part of a child's 'normal' development. This paper argues that the main disagreements in discourses about childhood sexuality related to different interpretations of children's sexual experiences. On the one hand stood an explanation that argued for a homology between children's and adults' sexual experiences, on the other hand was an understanding that suggested that adults and children had distinct and different experiences. Whereas the homological interpretation was favoured by the majority of commentators, including Moll, Freud, and to some extent also by C.G. Jung, the heterological interpretation was supported by a minority, including childhood psychologist Charlotte Bühler.

Microtechnology meets systems biology: the small molecules of metabolome as next big targets.

One of the key objectives of systems biology is to study and control biological processes in terms of interactions of components at different molecular levels. Advances in genome sequencing, transcriptomics and proteomics have paved the way for a systemic analysis of cellular processes at gene and protein levels. However, tools are still missing for a reliable and systemic analysis of the small molecules inside cells, the so-called metabolome. Due to the generally very low concentration, high turn-over rate and chemical diversity of metabolites their quantification under physiological, in vivo and dynamic conditions presents major challenges and the missing link for a real systems biology approach on the way from genome to cellular function. To this end, microfluidics can play an important role owing to its unique characteristics such as highly spatial and temporal resolution of sample treatment and analysis. Despite impressive progresses in microtechnology in recent years, many of the microfluidic studies or devices remain at the level of proof-of-principle and have been seldom applied to the real world of metabolomic analysis. In this review article, we first present the major obstacles and challenges for determining in vivo metabolite dynamics in complex biological systems. The progresses in microfluidics, their characteristics and possible applications to solving some of the compelling problems in metabolomic analysis are then discussed. Emphases are put on pinpointing the deficits of the presently available devices and technologies and directions for further development to fulfill the special need of systems biology.

High molecular gas fractions in normal massive star-forming galaxies in the young Universe.

Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly. Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars, and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today's massive spiral galaxies. The slow decrease between z approximately 2 and z approximately 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.

Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology.

BACKGROUND: Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable. MATERIALS AND METHODS: We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders (n = 156), myelodysplastic syndromes (MDS, n = 241), acute myeloid leukaemia (AML, n = 317), systemic mastocytosis (SM, n = 81), non-Hodgkin's lymphoma (n = 59) and acute lymphoblastic leukaemia (n = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects. RESULTS: In healthy subjects, the median serum tryptase was 5.2 ng mL(-1). Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL(-1)) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL(-1), were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found. CONCLUSIONS: In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology.

Pretransplant risk assessment in renal allograft recipients using virtual crossmatching.

Preformed donor-specific HLA-antibodies antibodies (DSA) are a major risk for early antibody-mediated rejection (AMR). This prospective study evaluated the accuracy of pretransplant risk assessment using virtual crossmatching (virtualXM) (i.e. comparing HLA-typing of the donor with the recipient's HLA-antibody specificities determined by flow-beads). Sixty-five consecutive patients were stratified according to virtualXM results: patients without DSA (n= 56) were considered low risk and received standard immunosuppression; patients with DSA (n= 9) were considered high risk and received additional induction with anti-T-lymphocyte-globulin (ATG) and intravenous immunoglobulins. Despite induction therapy 4 of 9 patients with DSA (44%) had clinical/subclinical AMR, whereas only 2 of 56 patients without DSA (4%) (p = 0.002). Notably, one of these two patients had early AMR likely induced by non-HLA-antibodies; the other had subclinical AMR at month 6 consistent with de novo DSA. The results of virtualXM and retrospectively obtained flow-cytometric crossmatches (FCXM) (n= 59) were concordant in 51 patients (86%), four patients (7%) were virtualXM-/FCXM+ and none had AMR, four patients (7%) were virtualXM+/FCXM- and one had AMR. VirtualXM can accurately define absence or presence of DSA and may become an invaluable tool for organ allocation and pretransplant risk assessment. However, further studies need to address whether all HLA-antibodies detected by flow-beads are clinically relevant.

In vitro assessment of water resistance of sun care products: a reproducible and optimized in vitro test method.

The aim of the study was to develop a simple reproducible and reliable in vitro water resistance (WR) method to assess the sun care products. This paper is the result of a scientific collaboration between seven different international industrial laboratories and testing institutes. The same group has already achieved an in vitro protocol for the sun protection factor (SPF) determination [1]. The in vitro WR of sunscreens was tested by applying the same principle as in vivo, which determines the percentage of retention of sunscreen products by assessing the SPF before and after water immersion. Special care was taken to study the parameters influencing the WR and the possibility to follow the kinetics of sunscreen retention during water immersion. The influence of different water qualities has been tested, and osmosed water (1-3 microS cm(-1)) was chosen for the main ring study. Measurement was carried out after 5, 20 and 40 min of immersion. Histograms of selected products demonstrate the percentage of WR at all measuring times and centres, and the regression coefficient to the in vivo determination was shown and statistical calculations clearly demonstrate the reproducibility of the results between the different evaluation centres. The presented method is a practical, convenient and relevant tool for WR screening of sun care and skin care products. It even has the potential to be the starting point for the replacement of the in vivo method in future.

The rapid formation of a large rotating disk galaxy three billion years after the Big Bang.

Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

[Item response theory and its application in neurology. Measurement of activity limitations in neurologic patients]. / Item-response-Theorie und deren Anwendung in der Neurologie Messung von Aktivitätseinschränkungen neurologischer Patienten.

This article is concerned with the measurement of activity limitations in neurologic patients and with the application of the item response theory (IRT), especially the Rasch analysis, in analyzing activity ratings. Activity limitations of 166 patients with different neurologic disorders (e.g., stroke, traumatic brain injury) were assessed with the Functional Independence Measure (FIM) during their stay in a rehabilitation hospital. Data analysis was performed with the Rasch model, which allows testing the psychometric qualities of the FIM. Results indicate that the FIM has good psychometric qualities. However, results also show that the 18 FIM items define two statistically and clinically different indicators. Thirteen items define disability in motor functions. Five items define disability in cognitive functions. Separate analyses of the two scales help to improve the psychometric quality of the FIM.

Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.