Adaptive quantification and longitudinal analysis of pulmonary emphysema with a hidden Markov measure field model.

The extent of pulmonary emphysema is commonly estimated from CT scans by computing the proportional area of voxels below a predefined attenuation threshold. However, the reliability of this approach is limited by several factors that affect the CT intensity distributions in the lung. This work presents a novel method for emphysema quantification, based on parametric modeling of intensity distributions and a hidden Markov measure field model to segment emphysematous regions.

Circulating concentrations of soluble receptor for AGE are associated with age and AGER gene polymorphisms in children with newly diagnosed type 1 diabetes.

Objective: We analyzed the relationship among soluble receptor for advanced glycation end products (sRAGEs), the clinical phenotype, HLA genotype, and risk-associated single nucleotide polymorphisms (SNPs) in the AGER gene in a large population of Finnish children with newly diagnosed type 1 diabetes.

Research Design And Methods: Samples from 2,115 clinically phenotyped children <15 years of age in whom type 1 diabetes was diagnosed and 316 control subjects were analyzed for sRAGEs. Three SNPs of AGER, previously associated with HLA-DR/DQ haplotype independent diabetes risk (rs2070600, rs9469089, and rs17493811), were analyzed in 1,390 affected subjects.

Biomechanics of milk extraction during breast-feeding.

How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple-areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant's jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics.

RETROSPECTIVE DETECTION OF INTERLEAVED SLICE ACQUISITION PARAMETERS FROM FMRI DATA.

To minimize slice excitation leakage to adjacent slices, interleaved slice acquisition is nowadays performed regularly in fMRI scanners. In interleaved slice acquisition, the number of slices skipped between two consecutive slice acquisitions is often referred to as the 'interleave parameter'; the loss of this parameter can be catastrophic for the analysis of fMRI data. In this article we present a method to retrospectively detect the interleave parameter and the axis in which it is applied.

Radiation therapy as a backbone of treatment of locally advanced non-small cell lung cancer.

Locally advanced non-small cell lung cancer (LA-NSCLC) is a heterogeneous disease, encompassing stage IIIA, for which surgery in combination with chemotherapy and/or radiation therapy (RT) represents a potential treatment approach for select patients, and stage IIIB, for which chemoradiation represents the standard of care. Recent advances in systemic cytotoxic and molecularly targeted therapies coupled with technologic innovations in radiotherapy have the potential to improve outcomes for this patient population. Many ongoing clinical trials use specific genetic mutations or histologic status to determine the combination of targeted therapies and RT, as well as to determine the optimal chemoradiotherapy platforms.

Regression-based ranking of pathogen strains with respect to their contribution to natural epidemics.

Genetic variation in pathogen populations may be an important factor driving heterogeneity in disease dynamics within their host populations. However, to date, we understand poorly how genetic diversity in diseases impact on epidemiological dynamics because data and tools required to answer this questions are lacking. Here, we combine pathogen genetic data with epidemiological monitoring of disease progression, and introduce a statistical exploratory method to investigate differences among pathogen strains in their performance in the field.

Pharmacological importance of optically active tetrahydro-β-carbolines and synthetic approaches to create the C1 stereocenter.

1,2,3,4-Tetrahydro-β-carbolines (THβCs) are a pharmacologically important group of compounds belonging to the indole alkaloids. C1-Substituted optically active THβCs have been the target of extensive synthetic efforts due to the presence of the scaffold in numerous natural products and synthetic targets. This review briefly summarizes the methods to obtain the C1 stereocenter and concentrates on evaluating the pharmacological importance of optically active C1-substituted THβCs, including their PDE5-inhibitory, antimalarial, antiviral and antitumor activities.

LOCALLY WEIGHTED TOTAL VARIATION DENOISING FOR RINGING ARTIFACT SUPPRESSION IN PET RECONSTRUCTION USING PSF MODELING.

Iterative reconstruction with point spread function (PSF) modeling improves contrast recovery in positron emission tomography (PET) images, but also introduces ringing artifacts and over enhancement that is contrast and object size dependent. Mitigation of these artifacts is crucial for clinical and research purposes. In this work we introduce a new iterative regularized reconstruction method that incorporates locally-weighted total variation denoising designed to suppress artifacts induced by PSF modeling.

A population-based survey of sleep disturbances in middle-aged women--associations with health, health related quality of life and health behavior.

Objective: To evaluate the prevalence of sleep disturbances and the contributing factors in middle-aged women.

Methods: In a cross-sectional design of the long-term, prospective follow-up study project of 1278 families from a random population sample, the mothers of 15 year-olds were asked to fill in a questionnaire about sleep, health, health related quality of life, and health behavior.

Results: Quality of sleep was reported by 32% of women as good, 43% quite good, 12% average, 10% quite poor and 3% as poor.

The impact of spatial scale and habitat configuration on patterns of trait variation and local adaptation in a wild plant parasite.

Theory indicates that spatial scale and habitat configuration are fundamental for coevolutionary dynamics and how diversity is maintained in host-pathogen interactions. Yet, we lack empirical data to translate the theory to natural host-parasite systems. In this study, we conduct a multiscale cross-inoculation study using the specialist wild plant pathogen Podosphaera plantaginis on its host plant Plantago lanceolata.

Ecological and evolutionary implications of spatial heterogeneity during the off-season for a wild plant pathogen.

While recent studies have elucidated many of the factors driving parasite dynamics during the growing season, the ecological and evolutionary dynamics during the off-season (i.e. the period between growing seasons) remain largely unexplored.

Joint learning of ultrasonic backscattering statistical physics and signal confidence primal for characterizing atherosclerotic plaques using intravascular ultrasound.

Intravascular Ultrasound (IVUS) is a predominant imaging modality in interventional cardiology. It provides real-time cross-sectional images of arteries and assists clinicians to infer about atherosclerotic plaques composition. These plaques are heterogeneous in nature and constitute fibrous tissue, lipid deposits and calcifications.

Pathogen life-history trade-offs revealed in allopatry.

Trade-offs in life-history traits is a central tenet in evolutionary biology, yet their ubiquity and relevance to realized fitness in natural populations remains questioned. Trade-offs in pathogens are of particular interest because they may constrain the evolution and epidemiology of diseases. Here, we studied life-history traits determining transmission in the obligate fungal pathogen, Podosphaera plantaginis, infecting Plantago lanceolata.

Resting state inter and intra hemispheric human brain functional connectivity.

Resting-state functional connectivity between neuroanatomical regions has attracted significant attention in recent years. In the process of obtaining the resting-state functional connectivity map of the human brain from blood-oxygen-level-dependent fMRI signals, it is common to average the signals from left and right hemispheres. This averaging can introduce unappreciated complexities and unintended consequences not related to the research question of interest.

Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs.

Anatomical variability predicts individual differences in transcranial electric stimulation motor threshold.

We have proposed that the current amplitude in electroconvulsive therapy (ECT) be lowered to produce stimulation closer to the neural activation threshold and individualized to account for anatomical variability across patients. A novel approach to individualize the ECT current amplitude could be via motor threshold (MT) determination with transcranial electric stimulation (TES) applied through the ECT electrodes instead of the fixed high current approach. This study derives an estimate of the electric field (E-field) neural activation threshold and tests whether individual differences in TES MT are explained by anatomical variability measurements and simulations in individual head models.

Chk1 targeting reactivates PP2A tumor suppressor activity in cancer cells.

Checkpoint kinase Chk1 is constitutively active in many cancer cell types and new generation Chk1 inhibitors show marked antitumor activity as single agents. Here we present a hitherto unrecognized mechanism that contributes to the response of cancer cells to Chk1-targeted therapy. Inhibiting chronic Chk1 activity in cancer cells induced the tumor suppressor activity of protein phosphatase protein phosphatase 2A (PP2A), which by dephosphorylating MYC serine 62, inhibited MYC activity and impaired cancer cell survival.

The HLA-B*39 allele increases type 1 diabetes risk conferred by HLA-DRB1*04:04-DQB1*03:02 and HLA-DRB1*08-DQB1*04 class II haplotypes.

To further characterise the effect of the HLA-B*39 allele on type 1 diabetes risk we assessed its role in different HLA-DR/DQ haplotypes and genotypes using 1764 nuclear families with a diabetic child collected in the framework of the Finnish Paediatric Diabetes Register. HLA assays were based on sequence specific hybridization using lanthanide labelled oligonucleotide probes. Transmissions of major HLA-DR/DQ haplotypes with and without the HLA-B*39 allele to diabetic index cases were analysed by direct haplotype and allele counting.

Hunting for necrosis in the shadows of intravascular ultrasound.

Coronary artery disease leads to failure of coronary circulation secondary to accumulation of atherosclerotic plaques. In adjunction to primary imaging of such vascular plaques using coronary angiography or alternatively magnetic resonance imaging, intravascular ultrasound (IVUS) is used predominantly for diagnosis and reporting of their vulnerability. In addition to plaque burden estimation, necrosis detection is an important aspect in reporting of IVUS.

Patterns of β-cell autoantibody appearance and genetic associations during the first years of life.

We analyzed demographic and genetic differences between children with various diabetes-associated autoantibodies reflecting the autoimmune process. In a prospective birth cohort comprising children with HLA-conferred susceptibility to type 1 diabetes (T1D), the pattern of autoantibody appearance was analyzed in 520 children with advanced β-cell autoimmunity associated with high risk for disease. In 315 cases, a single biochemical autoantibody could be identified in the first positive sample as insulin (insulin autoantibody [IAA]) in 180, as GAD (GAD antibody [GADA]) in 107, and as IA-2 antigen (IA-2 antibody [IA-2A]) in 28.

The role of inflammatory pathways in cancer-associated cachexia and radiation resistance.

Dysregulated inflammatory responses are key contributors to a multitude of chronic ailments, including cancer. Evidence indicates that disease progression in cancer is dependent on the complex interaction between the tumor and the host microenvironment. Most recently, the inflammatory response has been suggested to be critical, as both the tumor and microenvironment compartments produce cytokines that act on numerous target sites, where they foster a complex cascade of biologic outcomes.

The in vivo performance of ferrocenyl tamoxifen lipid nanocapsules in xenografted triple negative breast cancer.

Triple-negative breast cancers (TNBC) represent the most aggressive form of breast cancers and their treatment are challenging due to the tumor heterogeneity. The high death rate and the limited systemic treatment options for TNBC necessitate the search for alternative chemotherapeutics. We previously found that FcOHTAM, an organometallic derivative of hydroxytamoxifen, showed in vitro a strong antiproliferative effect on various breast cancer cell lines, including MDA-MB-231 cells, the archetype of TNBC.

Rapidly fluctuating environments constrain coevolutionary arms races by impeding selective sweeps.

Although pervasive, the impact of temporal environmental heterogeneity on coevolutionary processes is poorly understood. Productivity is a key temporally heterogeneous variable, and increasing productivity has been shown to increase rates of antagonistic arms race coevolution, and lead to the evolution of more broadly resistant hosts and more broadly infectious parasites. We investigated the effects of the grain of environmental heterogeneity, in terms of fluctuations in productivity, on bacteria-phage coevolution.

Transmission disequilibrium analysis of 31 type 1 diabetes susceptibility loci in Finnish families.

Currently more than 50 type 1 diabetes (T1D) loci outside the human leukocyte antigen (HLA)-region have been established in large European and/or North American populations. Our aim was to attempt to replicate these findings in the less heterogenic Finnish population and to explore evidence for genetic heterogeneity. We analyzed 1761 Finnish T1D trio families for association in 31 T1D loci (25 confirmed and 6 have inconsistent prior evidence).