[Chronic myelogenous leukemia].

The advent of tyrosine kinase inhibitors (TKI) has improved the prognosis and outcome of patients with chronic myelogenous leukemia (CML) considerably. Compared with imatinib, the first-line use of second-generation inhibitors nilotinib and dasatinib has led to faster and deeper molecular remissions accompanied by a differential adverse effect profile. An essential part of the management of CML patients is the guideline-based application of cytogenetics and standardized polymerase chain reaction techniques to regularly assess the remission status.

Family income, parental education and brain structure in children and adolescents.

Socioeconomic disparities are associated with differences in cognitive development. The extent to which this translates to disparities in brain structure is unclear. We investigated relationships between socioeconomic factors and brain morphometry, independently of genetic ancestry, among a cohort of 1,099 typically developing individuals between 3 and 20 years of age.

Causes of resistance and treatment choices of second- and third-line treatment in chronic myelogenous leukemia patients.

For patients with chronic myelogenous leukemia who fail first-line therapy, several factors should be considered for the decision of the next treatment option. Second-generation tyrosine kinase inhibitors (TKIs) dasatinib, nilotinib, and bosutinib offer improved potency and a high likelihood of success for these patients. Overall, efficacy data are comparable for these agents, and so physicians should consider the BCR-ABL1 mutation profile and the patient's history to make a decision on the best choice.

ERBB4 polymorphism and family history of psychiatric disorders on age-related cortical changes in healthy children.

Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development.

Homogeneous coordinates in motion correction.

Purpose: Prospective motion correction for MRI and other imaging modalities are commonly based on the assumption of affine motion, i.e., rotations, shearing, scaling and translations.

Emergence of a new lineage of dengue virus type 2 identified in travelers entering Western Australia from Indonesia, 2010-2012.

Dengue virus (DENV) transmission is ubiquitous throughout the tropics. More than 70% of the current global dengue disease burden is borne by people who live in the Asia-Pacific region. We sequenced the E gene of DENV isolated from travellers entering Western Australia between 2010-2012, most of whom visited Indonesia, and identified a diverse array of DENV1-4, including multiple co-circulating viral lineages.

Prospective motion correction of segmented diffusion weighted EPI.

Purpose: Recently, a new algorithm was introduced to combine segments of under-sampled diffusion weighted data using multiplexed sensitivity encoding. While the algorithm provides good results in cooperative volunteers, motion during the data acquisition is not accounted for. In this work, the continuous prospective motion correction of a segmented diffusion weighted acquisition is combined with multiplexed sensitivity encoding.

SENSE and simultaneous multislice imaging.

Purpose: Simultaneous multislice (SMS) acquisitions play an important role in the challenge of increasing single-shot imaging speed. We show that sensitivity encoding in two spatial dimensions (two-dimensional sensitivity encoding [2D-SENSE]) can be used to reconstruct SMS acquisitions with periodic but otherwise arbitrary undersampling patterns.

Theory And Methods: By adopting a 3D k-space representation of the SMS sampling process, the accelerated in-plane and slice-encoding directions form a 2D-reconstruction problem that is equivalent to volumetric controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA).

Next-generation deep sequencing improves detection of BCR-ABL1 kinase domain mutations emerging under tyrosine kinase inhibitor treatment of chronic myeloid leukemia patients in chronic phase.

Purpose: Here, we studied whether amplicon next-generation deep sequencing (NGS) could improve the detection of emerging BCR-ABL1 kinase domain mutations in chronic phase chronic myeloid leukemia (CML) patients under tyrosine kinase inhibitor (TKI) treatment and discussed the clinical relevance of such sensitive mutational detection.

Methods: For NGS data evaluation including extraction of biologically relevant low-level variants from background error noise, we established and applied a robust and versatile bioinformatics approach.

Results: Results from a retrospective longitudinal analysis of 135 samples of 15 CML patients showed that NGS could have revealed emerging resistant mutants 2-11 months earlier than conventional sequencing.

A multifaceted intervention package to improve the diagnosis and management of delirium.

ABSTRACT Background: Delirium is a major cause of morbidity and mortality amongst hospital patients. Previous studies have shown that it is often poorly recognized and managed. We wanted to assess the impact of a multifaceted intervention on delirium management.

Comparison of optical and MR-based tracking.

Purpose: The goal of this study was to compare the accuracy of two real-time motion tracking systems in the MR environment: MR-based prospective motion correction (PROMO) and optical moiré phase tracking (MPT).

Methods: Five subjects performed eight predefined head rotations of 8° ± 3° while being simultaneously tracked with PROMO and MPT. Structural images acquired immediately before and after each tracking experiment were realigned with SPM8 to provide a reference measurement.

Molecular-defined clonal evolution in patients with chronic myeloid leukemia independent of the BCR-ABL status.

To study clonal evolution in chronic myeloid leukemia (CML), we searched for BCR-ABL-independent gene mutations in both Philadelphia chromosome (Ph)-negative and Ph-positive clones in 29 chronic-phase CML patients by targeted deep sequencing of 25 genes frequently mutated in myeloid disorders. Ph-negative clones were analyzed in 14 patients who developed clonal cytogenetic abnormalities in Ph-negative cells during treatment with tyrosine kinase inhibitors (TKI). Mutations were detected in 6/14 patients (43%) affecting the genes DNMT3A, EZH2, RUNX1, TET2, TP53, U2AF1 and ZRSR2.

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

Importance: The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders.

Objective: To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth.

Simulation training for geriatric medicine.

Background: Geriatric medicine encompasses a diverse nature of medical, social and ethical challenges, and requires a multidimensional, interdisciplinary approach. Recent reports have highlighted failings in the care of the elderly, and it is therefore vital that specialist trainees in geriatric medicine are afforded opportunities to develop their skills in managing this complex patient population. Simulation has been widely adopted as a teaching tool in medicine; however, its use in geriatric medicine to date has involved primarily role-play or discrete clinical skills training.

A Bayesian approach to the creation of a study-customized neonatal brain atlas.

Atlas-based image analysis (ABA), in which an anatomical "parcellation map" is used for parcel-by-parcel image quantification, is widely used to analyze anatomical and functional changes related to brain development, aging, and various diseases. The parcellation maps are often created based on common MRI templates, which allow users to transform the template to target images, or vice versa, to perform parcel-by-parcel statistics, and report the scientific findings based on common anatomical parcels. The use of a study-specific template, which represents the anatomical features of the study population better than common templates, is preferable for accurate anatomical labeling; however, the creation of a parcellation map for a study-specific template is extremely labor intensive, and the definitions of anatomical boundaries are not necessarily compatible with those of the common template.

The Memory Aid study: protocol for a randomized controlled clinical trial evaluating the effect of computer-based working memory training in elderly patients with mild cognitive impairment (MCI).

Background: Mild cognitive impairment (MCI) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging, but less severe than dementia. Reduced working memory (WM) is regarded as one of the core symptoms of an MCI condition. Recent studies have indicated that WM can be improved through computer-based training.

Schizophrenia-risk variant rs6994992 in the neuregulin-1 gene on brain developmental trajectories in typically developing children.

The neuregulin-1 (NRG1) gene is one of the best-validated risk genes for schizophrenia, and psychotic and bipolar disorders. The rs6994992 variant in the NRG1 promoter (SNP8NRG243177) is associated with altered frontal and temporal brain macrostructures and/or altered white matter density and integrity in schizophrenic adults, as well as healthy adults and neonates. However, the ages when these changes begin and whether neuroimaging phenotypes are associated with cognitive performance are not fully understood.

Effects of APOE ε4, age, and HIV on glial metabolites and cognitive deficits.

Objective: We aimed to evaluate the combined effects of HIV and APOE ε4 allele(s) on glial metabolite levels, and on known cognitive deficits associated with either condition, across the ages.

Methods: One hundred seventy-seven participants, primarily of white and mixed race (97 seronegative subjects: aged 44.7 ± 1.

Importin-α7 is required for enhanced influenza A virus replication in the alveolar epithelium and severe lung damage in mice.

Influenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism by using various ex vivo imaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-α7 gene-deficient (α7(-/-)) mice with a recombinant H1N1 influenza virus and compared the in vivo viral kinetics with those in wild-type (WT) mice.

Simultaneous Multi-Slice fMRI using spiral trajectories.

Parallel imaging methods using multi-coil receiver arrays have been shown to be effective for increasing MRI acquisition speed. However parallel imaging methods for fMRI with 2D sequences show only limited improvements in temporal resolution because of the long echo times needed for BOLD contrast. Recently, Simultaneous Multi-Slice (SMS) imaging techniques have been shown to increase fMRI temporal resolution by factors of four and higher.

MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure.

In the face of competing tyrosine kinase inhibitors (TKIs), identification of chronic myeloid leukemia (CML) patients expecting favorable response to second-line treatment is warranted. At the time of imatinib resistance, the investigation of multidrug-resistance protein 1 (MDR1) and BCR-ABL yielded the following results: (i) Patients with high MDR1 transcript levels showed superior response at 48 months as compared with low-level MDR1 patients: major molecular response (MMR) in 41% vs 16% (P=0.014), complete cytogenetic response (CCyR) in 58% vs 39% (P=0.

MRI default mode network connectivity is associated with functional outcome after cardiopulmonary arrest.

Background: We hypothesized that the degree of preserved functional connectivity within the DMN during the first week after cardiopulmonary arrest (CPA) would be associated with functional outcome at hospital discharge.

Methods: Initially comatose CPA survivors with indeterminate prognosis at 72 h were enrolled. Seventeen CPA subjects between 4 and 7 days after CPA and 17 matched controls were studied with task-free fMRI.

Outcome in single and twin pregnancies at 20 to 24 weeks gestation: ten years experience in one perinatal center.

Objective: The aim of this investigation was to evaluate the outcome at 20 to 24 weeks gestation of twin and singleton extremely low birth weight infants.

Study Design: The authors conducted a retrospective cohort study of live newborns at 20 to 24 weeks gestation admitted to one neonatal intensive care unit (NICU) from 2000 to 2009. Outcome mortality and predictors of outcome were evaluated.

The KIT D816V expressed allele burden for diagnosis and disease monitoring of systemic mastocytosis.

The activating KIT D816V mutation plays a central role in the pathogenesis, diagnosis, and targeted treatment of systemic mastocytosis (SM). For improved and reliable identification of KIT D816V, we have developed an allele-specific quantitative real-time PCR (RQ-PCR) with an enhanced sensitivity of 0.01-0.

Imaging of the murine biliopancreatic tract at 7 Tesla: technique and results in a model of primary sclerosing cholangitis.

Purpose: To assess the feasibility of a 7 Tesla (T) MR cholangiopancreatography (MRCP) protocol to image the morphology and detect and intraindividually monitor pathological changes of the biliopancreatic tract in a mouse model of primary sclerosing cholangitis (PSC).

Materials And Methods: Six female Mdr2(Abcb)(-/-) mice, a well-established model of PSC, were imaged five times during weeks 10-19. Three wild-type controls were imaged at age 15 weeks.