Freehand real-time elastography: impact of scanning parameters on image quality and in vitro intra- and interobserver validations

Real-time elastography is a method for visualization of the elastic properties of soft tissue and may potentially enable differentiation between malignant and benign pathologic lesions. Our aim was to validate the method on a tissue-mimicking (TM) phantom and to evaluate the influence of different scanning parameters and investigator variability. A TM-phantom containing eight spherical inclusions with known storage modulus was examined using two different transducers on an ultrasound (US) scanner equipped with software for real-time elasticity imaging. The ultrasound transducers were moved vertically in a repetitive manner to induce strain. Two investigators performed series of standardized elastography scans applying a 0-4 categorical quality scale to evaluate the influence of seven parameters: dynamic range of elasticity, region-of-interest, frequency of transducer movement, rejection of elastogram noise, frame rate, persistence and smoothing. Subsequently, repeated examinations of four selected inclusions were performed using a visual analog scale (VAS) where investigators marked a 100 mm horizontal line representing the span in image quality based on experience from the first examination. The hardest and softest inclusions were imaged more clearly than the inclusions with elasticity more similar to the background material. Intraobserver agreement on elastogram quality was good (kappa: 0.67 - 0.75) and interobserver agreement average (kappa: 0.55 - 0.56) when using the categorical scale. The subsequent VAS evaluation gave intraclass-correlation coefficients for the two observers of 0.98 and 0.93, respectively, and an interclass-correlation coefficient of 0.93. Real-time elastography adequately visualized isoechoic inclusions with different elastic properties in a TM-phantom with acceptable intra- and interobserver agreement. Dynamic range of elasticity was the parameter with most impact on the elastographic visualization of inclusions.     

Risk analysis of information security in a mobile instant messaging and presence system for healthcare

INTRODUCTION: Instant messaging (IM) is suited for immediate communication because messages are delivered almost in real time. Results from studies of IM use in enterprise work settings make us believe that IM based services may prove useful also within the healthcare sector. However, today's public instant messaging services do not have the level of information security required for adoption of IM in healthcare. We proposed MedIMob, our own architecture for a secure enterprise IM service for use in healthcare. MedIMob supports IM clients on mobile devices in addition to desktop based clients. METHODS: Security threats were identified in a risk analysis of the MedIMob architecture. The risk analysis process consists of context identification, threat identification, analysis of consequences and likelihood, risk evaluation, and proposals for risk treatment. RESULTS: The risk analysis revealed a number of potential threats to the information security of a service like this. Many of the identified threats are general when dealing with mobile devices and sensitive data; others are threats which are more specific to our service and architecture. Individual threats identified in the risks analysis are discussed and possible counter measures presented. DISCUSSION: The risk analysis showed that most of the proposed risk treatment measures must be implemented to obtain an acceptable risk level; among others blocking much of the additional functionality of the smartphone. To conclude on the usefulness of this IM service, it will be evaluated in a trial study of the human-computer interaction. Further work also includes an improved design of the proposed MedIMob architecture.     

Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL.     

A Polyprotein-Expressing Salmonid Alphavirus Replicon Induces Modest Protection in Atlantic Salmon (Salmo Salar) Against Infectious Pancreatic Necrosis

Vaccination is an important strategy for the control and prevention of infectious pancreatic necrosis (IPN) in farmed Atlantic salmon (Salmo salar) in the post-smolt stage in sea-water. In this study, a heterologous gene expression system, based on a replicon construct of salmonid alphavirus (SAV), was used for in vitro and in vivo expression of IPN virus proteins. The large open reading frame of segment A, encoding the polyprotein NH2-pVP2-VP4-VP3-COOH, as well as pVP2, were cloned and expressed by the SAV replicon in Chinook salmon embryo cells (CHSE-214) and epithelioma papulosum cyprini (EPC) cells. The replicon constructs pSAV/polyprotein (pSAV/PP) and pSAV/pVP2 were used to immunize Atlantic salmon (Salmo salar) by a single intramuscular injection and tested in a subsequent IPN virus (IPNV) challenge trial. A low to moderate protection against IPN was observed in fish immunized with the replicon vaccine that encoded the pSAV/PP, while the pSAV/pVP2 construct was not found to induce protection.     

The genetics of congenital aniridia—a guide for the ophthalmologist

Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications.     

Evidence that compromised K+ spatial buffering contributes to the epileptogenic effect of mutations in the human Kir4.1 gene (KCNJ10)

Mutations in the human Kir4.1 potassium channel gene (KCNJ10) are associated with epilepsy. Using a mouse model with glia-specific deletion of Kcnj10, we have explored the mechanistic underpinning of the epilepsy phenotype. The gene deletion was shown to delay K(+) clearance after synaptic activation in stratum radiatum of hippocampal slices. The activity-dependent changes in extracellular space volume did not differ between Kcnj10 mutant and wild-type mice, indicating that the Kcnj10 gene product Kir4.1 mediates osmotically neutral K(+) clearance. Combined, our K(+) and extracellular volume recordings indicate that compromised K(+) spatial buffering in brain underlies the epilepsy phenotype associated with human KCNJ10 mutations.     

Help-seeking in the Norwegian Police Service

A traditional view is that police officers possess negative attitudes toward seeking professional help. However, few empirical studies have investigated help-seeking behaviour in police services. This study aimed to investigate help-seeking behaviour, gender differences, and the relationship to self-reported physical and mental health problems in the Norwegian police service. Comparisons were made with a sample of the general Norwegian population. A comprehensive nationwide questionnaire survey of 3,272 Norwegian police officers at all hierarchical levels was conducted; measurements included help-seeking, Subjective Health Complaint questionnaire (SHC), the Hospital Anxiety and Depression Scale (HADS), Paykel's Suicidal Feelings in the General Population, alcohol and medication to cope, self reported health, and sick leave. Female police officers contacted nearly all health professionals more than their male counterparts. Help-seeking was largely unaffected by age. Less than 10% of those reporting anxiety or depressive symptoms or serious suicidal ideation had contacted a psychologist or psychiatrist. A chiropractor had been contacted by 14.5% of the sample during the past year, compared with 7% in the general Norwegian population. Anxiety symptoms were associated with seeking a chiropractor (OR 1.9, 95% CI 1.3-2.7). The strongest association with contacting a psychologist or psychiatrist was medication used to cope (OR 5.8, 95% CI 3.0-11.1). The first nationwide study on help-seeking behaviour showed that police officers sought help among specialists in private practice, physiotherapists and chiropractors relatively often. However, they contacted a psychologist or psychiatrist rarely, even when reporting serious suicidal ideation.     

BMP-6 inhibits human bone marrow B lymphopoiesis--upregulation of Id1 and Id3

OBJECTIVE: In mammals, factors produced by bone marrow (BM) stromal cells are instrumental in orchestrating the developmental process of B lymphocytes. Bone morphogenetic proteins (BMPs) are multifunctional cytokines previously found to regulate hematopoietic stem cells. In the present study, we have explored the role of BMP-6 in human B progenitor cells. MATERIALS AND METHODS: In vitro B lymphopoiesis of CD10(+) B progenitor cells from human BM was evaluated in the presence or absence of BMP-6 in short- or long-term coculture on MS-5 stromal cells, by tracking CFSE-labeled CD10(+) B progenitor cells or by quantification of CD19(+) cells. DNA synthesis in the pre-B cell line Nalm-6 was measured by (3)H-thymidine incorporation. BMP-6-induced phosphorylation of Smad1/5/8 was determined by Western blot analysis, whereas elevation of Id1-Id4 mRNA levels and basal BMP-6 mRNA levels were measured by real-time and conventional RT-PCR, respectively. RESULTS: By in vitro coculture of CD10(+) B progenitor cells or monoculture of Nalm-6 cells, we found that BMP-6 inhibited B lymphopoiesis by impeding cell proliferation. Furthermore, in CD10(+) B progenitors as well as in Nalm-6 cells, BMP-6 rapidly induced phosphorylation of Smad1/5/8, followed by an upregulation of Id1 and Id3 mRNA levels. Finally, we demonstrated that human bone marrow stromal cells express BMP-6 mRNA whereas B progenitor cells did not. CONCLUSIONS: We suggest that BMP-6, produced by the BM, may participate to fine-tune the balance between proliferation, apoptosis, and differentiation in human B progenitor cells during BM B lymphopoiesis.