Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome

Marginal zone B-cell lymphomas (MZLs) have been divided into 3 distinct subtypes (extranodal MZLs of mucosa-associated lymphoid tissue [MALT] type, nodal MZLs, and splenic MZLs). Nevertheless, the relationship between the subtypes is still unclear. We performed a comprehensive analysis of genomic DNA copy number changes in a very large series of MZL cases with the aim of addressing this question. Samples from 218 MZL patients (25 nodal, 57 MALT, 134 splenic, and 2 not better specified MZLs) were analyzed with the Affymetrix Human Mapping 250K SNP arrays, and the data combined with matched gene expression in 33 of 218 cases. MALT lymphoma presented significantly more frequently gains at 3p, 6p, 18p, and del(6q23) (TNFAIP3/A20), whereas splenic MZLs was associated with del(7q31), del(8p). Nodal MZLs did not show statistically significant differences compared with MALT lymphoma while lacking the splenic MZLs-related 7q losses. Gains of 3q and 18q were common to all 3 subtypes. del(8p) was often present together with del(17p) (TP53). Although del(17p) did not determine a worse outcome and del(8p) was only of borderline significance, the presence of both deletions had a highly significant negative impact on the outcome of splenic MZLs.

Maximum flight velocity of blood drops in analysing blood traces

When analysing blood spatters, traces often occur which regarding the collision angle, cannot be allocated to any supposed centre of origin. Drops following highly curved (ballistic) trajectories usually form these types of traces. The reconstruction of such trajectories requires knowledge of the mass, the diameter (of which approximations are known) and the velocity of the blood drops. This article provides an upper range of the velocity in relation to the diameter of the blood drops based on physical laws. This is very helpful in analysing ballistic trajectories.

Magnetic resonance imaging, ultrasonography and histology of the suspensory ligament origin: a comparative study of normal anatomy of warmblood horses

REASONS FOR PERFORMING STUDY: The diagnosis of lameness caused by proximal metacarpal and metatarsal pain can be challenging. Magnetic resonance imaging (MRI) offers the possibility for further diagnosis but there have been no studies on the normal MRI appearance of the origin of the suspensory ligament (OSL) in conjunction with ultrasonography and histology. OBJECTIVES: To describe the MRI appearance of the OSL in fore- and hindlimbs of sound horses and compare it to the ultrasonographic and histological appearance. The findings can be used as reference values to recognise pathology in the OSL. METHODS: The OSL in the fore- and hindlimbs of 6 sound horses was examined by ultrasonography prior to death, and MRI and histology post mortem. Qualitative evaluation and morphometry of the OSL were performed and results of all modalities compared. RESULTS: Muscular tissue, artefacts, variable SL size and shape complicated ultrasonographic interpretation. In MRI and histology the forelimb OSL consisted of 2 portions, the lateral being significantly thicker than medial. The hindlimb SL had a single large area of origin. In fore- and hindlimbs, the amount of muscular tissue was significantly larger laterally than medially. Overall SL measurements using MRI were significantly higher than using histology and ultrasonography and histological higher than ultrasonographic measurements. Morphologically, there was a good correlation between MRI and histology. CONCLUSIONS: MRI provides more detailed information than ultrasonography regarding muscle fibre detection and OSL dimension and correlates morphologically well with histology. Therefore, ultrasonographic results should be regarded with caution. POTENTIAL RELEVANCE: MRI may be a diagnostic aid when other modalities fail to identify clearly the cause of proximal metacarpal and metatarsal pain; and may improve selection of adequate therapy and prognosis for injuries in this region.

Morphometric assessment of normal, suspect and glaucomatous optic discs with Stratus OCT and HRT II

AIMS: To compare morphometric parameters and diagnostic performance of the new Stratus Optical Coherence Tomograph (OCT) Disc mode and the Heidelberg Retina Tomograph (HRT); to evaluate OCT's accuracy in determining optic nerve head (ONH) borders. METHODS: Controls and patients with ocular hypertension, glaucoma-like discs, and glaucoma were imaged with OCT Disc mode, HRT II, and colour disc photography (DISC-PHOT). In a separate session, automatically depicted ONH shape and size in OCT were compared with DISC-PHOT, and disc borders adjusted manually where required. In a masked fashion, all print-outs and photographs were studied and discs classified as normal, borderline, and abnormal. The Cohen kappa method was then applied to test for agreement of classification. Bland-Altman analysis was used for comparison of disc measures. RESULTS: In all, 49 eyes were evaluated. Automated disc margin recognition failed in 53%. Misplaced margin points were more frequently found in myopic eyes, but only 31/187 were located in an area of peripapillary atrophy. Agreement of OCT with photography-based diagnosis was excellent in normally looking ONHs, but moderate in discs with large cups, where HRT performed better. OCT values were consistently larger than HRT values for disc and cup area. Compared with HRT, small rim areas and volumes tended to be minimized by OCT, and larger ones to be magnified. CONCLUSIONS: Stratus OCT Disc protocol performed overall well in differentiating between normal and glaucomatous ONHs. However, failure of disc border recognition was frequently observed, making manual correction necessary. ONH measures cannot be directly compared between HRT and OCT.

Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures--initial experience

PURPOSE: To prospectively compare cartilage T2 values after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) repair procedures. MATERIALS AND METHODS: The study had institutional review board approval by the ethics committee of the Medical University of Vienna; informed consent was obtained. Twenty patients who underwent MFX or MACT (10 in each group) were enrolled. For comparability, patients of each group were matched by mean age (MFX, 40.0 years +/- 15.4 [standard deviation]; MACT, 41.0 years +/- 8.9) and postoperative interval (MFX, 28.6 months +/- 5.2; MACT, 27.4 months +/- 13.1). Magnetic resonance (MR) imaging was performed with a 3-T MR imager, and T2 maps were calculated from a multiecho spin-echo measurement. Global, as well as zonal, quantitative T2 values were calculated within the cartilage repair area and within cartilage sites determined to be morphologically normal articular cartilage. Additionally, with consideration of the zonal organization, global regions of interest were subdivided into deep and superficial areas. Differences between cartilage sites and groups were calculated by using a three-way analysis of variance. RESULTS: Quantitative T2 assessment of normal native hyaline cartilage showed similar results for all patients and a significant trend of increasing T2 values from deep to superficial zones (P < .05). In cartilage repair areas after MFX, global mean T2 was significantly reduced (P < .05), whereas after MACT, mean T2 was not reduced (P > or = .05). For zonal variation, repair tissue after MFX showed no significant trend between different depths (P > or = .05), in contrast to repair tissue after MACT, in which a significant increase from deep to superficial zones (P < .05) could be observed. CONCLUSION: Quantitative T2 mapping seems to reflect differences in repair tissues formed after two surgical cartilage repair procedures. (c) RSNA, 2008.

Localization of Epileptogenic Zone on Pre-surgical Intracranial EEG Recordings: Toward a Validation of Quantitative Signal Analysis Approaches

In patients diagnosed with pharmaco-resistant epilepsy, cerebral areas responsible for seizure generation can be defined by performing implantation of intracranial electrodes. The identification of the epileptogenic zone (EZ) is based on visual inspection of the intracranial electroencephalogram (IEEG) performed by highly qualified neurophysiologists. New computer-based quantitative EEG analyses have been developed in collaboration with the signal analysis community to expedite EZ detection. The aim of the present report is to compare different signal analysis approaches developed in four different European laboratories working in close collaboration with four European Epilepsy Centers. Computer-based signal analysis methods were retrospectively applied to IEEG recordings performed in four patients undergoing pre-surgical exploration of pharmaco-resistant epilepsy. The four methods elaborated by the different teams to identify the EZ are based either on frequency analysis, on nonlinear signal analysis, on connectivity measures or on statistical parametric mapping of epileptogenicity indices. All methods converge on the identification of EZ in patients that present with fast activity at seizure onset. When traditional visual inspection was not successful in detecting EZ on IEEG, the different signal analysis methods produced highly discordant results. Quantitative analysis of IEEG recordings complement clinical evaluation by contributing to the study of epileptogenic networks during seizures. We demonstrate that the degree of sensitivity of different computer-based methods to detect the EZ in respect to visual EEG inspection depends on the specific seizure pattern.

Gastrointestinal ultrasonography of normal Standardbred neonates and frequency of asymptomatic intussusceptions.

BACKGROUND Ultrasonographic appearance of the gastrointestinal (GI) tract of equine neonates has not been completely described. OBJECTIVES To describe (1) sonographic characteristics of the GI segments in normal nonsedated equine neonates, (2) intra- and interobserver variation in wall thickness, and (3) the sonographic appearance of asymptomatic intussusceptions, and (4) to compare age and sonographic findings of foals with and without asymptomatic intussusceptions. ANIMALS Eighteen healthy Standardbred foals ≤5 days of age. METHODS Prospective, cross-sectional blinded study. Gastrointestinal sonograms were performed stall-side. Intraobserver variability in wall thickness measurements was determined by calculating the coefficient of variation (CV). The Bland-Altman method was used to assess interobserver bias. Student's t-test and Fisher's exact test were used to test the association among presence of intussusceptions, age, and selected sonographic findings. RESULTS The reference ranges (95% predictive interval) for wall thickness were 1.6-3.6 mm for the stomach, 1.9-3.2 mm for the duodenum, 1.9-3.1 mm for the jejunum, 1.3-2.2 mm for the colon, and 0.8-2.7 mm for the cecum. Intraobserver wall thickness CV ranged from 8 to 21% for the 2 observers for 5 gastrointestinal segments. The interobserver bias for wall thickness measurements was not significant except for the stomach (0.14 mm, P < .05) and duodenum (0.29 mm, P < .05). Diagnostic images of mural blood flow could not be obtained. Asymptomatic intussusceptions were found in 10/18 neonates. Associations between sonographic variables or age and the presence of intussusceptions were not found. CONCLUSIONS AND CLINICAL IMPORTANCE Sonographic characteristics of the GI tract of normal Standardbred neonates can be useful in evaluating ill foals. Asymptomatic small intestinal intussusceptions occur in normal Standardbred neonates.

Potassium and the excitability properties of normal human motor axons in vivo.

Hyperkalemia is an important cause of membrane depolarization in renal failure. A recent theoretical model of axonal excitability explains the effects of potassium on threshold electrotonus, but predicts changes in superexcitability in the opposite direction to those observed. To resolve this contradiction we assessed the relationship between serum potassium and motor axon excitability properties in 38 volunteers with normal potassium levels. Most threshold electrotonus measures were strongly correlated with potassium, and superexcitability decreased at higher potassium levels (P = 0.016), contrary to the existing model. Improved modelling of potassium effects was achieved by making the potassium currents obey the constant-field theory, and by making the potassium permeabilities proportional to external potassium, as has been observed in vitro. This new model also accounted well for the changes in superexcitability and other excitability measures previously reported in renal failure. These results demonstrate the importance of taking potassium levels into account when assessing axonal membrane dysfunction by excitability testing, and provide evidence that potassium currents are activated by external potassium in vivo.

Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

UNLABELLED Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. RESULTS (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Impact of normal and shear stresses due to wheel slip on hydrological properties of an agricultural clay loam: Experimental and new computerized approach

The main purpose of this study was to evaluate the effect that mechanical stresses acting under the slipping driving wheels of agricultural equipment have on the soil’s pore system and water flow process (surface runoff generation during extreme event). The field experiment simulated low slip (1%) and high slip (27%) on a clay loam. The stress on the soil surface and changes in the amounts of water flowing from macropores were simulated using the Tires/tracks And Soil Compaction (TASC) tool and the MACRO model, respectively. Taking a 65 kW tractor on a clay loam as a reference, results showed that an increase in slip of the rear wheels from 1% to 27% caused normal stress to increase from 90.6 kPa to 104.4 kPa at the topsoil level, and the maximum shear contact stress to rise drastically from 6.0 kPa to 61.6 kPa. At 27% slip, topsoil was sheared and displaced over a distance of 0.35 m. Excessive normal and shear stress values with high slip caused severe reductions of the soil’s macroporosity, saturated hydraulic conductivity, and water quantities flowing from topsoil macropores. Assuming that, under conditions of intense rainfall on sloping land, a loss in vertical water flow would mean an increase in surface runoff, we calculated that a rainfall intensity of 100 mm h-1 and a rainfall duration of 1 h would increase the runoff coefficient to 0.79 at low slip and to 1.00 at high slip, indicating that 100% of rainwater would be transformed into surface runoff at high slip. We expect that these effects have a significant impact on soil erosion and floods in steeper terrain (slope > 15°) and across larger surface areas (> 16 m2) than those included in our study.

Intravitreal ranibizumab monotherapy to treat retinopathy of prematurity zone II, stage 3 with plus disease.

BACKGROUND Treatment of retinopathy of prematurity (ROP) stage 3 plus with bevacizumab is still very controversial. We report the outcome of 6 eyes of 4 premature infants with ROP stage 3 plus disease treated with ranibizumab monotherapy. METHODS Six eyes of 4 premature infants with threshold ROP 3 plus disease in zone II, were treated with one intravitreal injection of 0.03 ml ranibizumab. No prior laser or other intravitreal therapy was done. Fundus examination was performed prior to the intervention and at each follow-up visit. Changes in various mean vital parameters one week post intervention compared to one week pre-intervention were assessed. RESULTS The gestational age (GA) of patient 1, 2, 3, and 4 at birth was 24 5/7, 24 5/7, 24 4/7, and 26 1/7 weeks, respectively. The birth weight was 500 grams, 450 grams, 665 grams, and 745 grams, respectively. The GA at the date of treatment ranged from 34 3/7 to 38 6/7 weeks. In one infant, upper air way infection was observed 2 days post injection of the second eye. Three eyes required paracentesis to reduce the intraocular pressure after injection and to restore central artery perfusion. After six months, all eyes showed complete retinal vascularisation without any signs of disease recurrence. CONCLUSIONS Treatment of ROP 3 plus disease with intravitreal ranibizumab was effective in all cases and should be considered for treatment. One infant developed an upper air way infection suspicious for nasopharyngitis, which might be a possible side effect of ranibizumab. Another frequent complication was intraocular pressure rise after injection. More patients with longer follow-up duration are mandatory to confirm the safety and efficacy of this treatment. TRIAL REGISTRATION NUMBER NCT02164604 ; Date of registration: 13.06.2014.