In-vivo kinetics of inhaled 5-Aminolevulinic acid-Induced Protoporphyrin IX fluorescence in bronchial tissue

BACKGROUND: In the diagnosis of early-stage lung cancer photosensitizer-enhanced fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases sensitivity when compared to white-light bronchoscopy. This investigation was to evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the bronchial mucosa in order to define the time optimum for its application prior to bronchoscopy. METHODS: Patients with known or suspected bronchial carcinoma were randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before flexible fluorescence bronchoscopy was performed. Macroscopically suspicious areas as well as areas with visually detected porphyrin fluorescence and normal control sites were measured spectroscopically. Biopsies for histopathology were obtained from suspicious areas as well as from adjacent normal areas. RESULTS: Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for malignant and premalignant changes (moderate dysplasia) which is almost twice as high as that of white-light bronchoscopy, whereas specificity is reduced. This is due to false-positive inflammatory lesions which also frequently show increased porphyrin fluorescence. Malignant and premalignant alterations produced fluorescence values that are up to 5 times higher than those of normal tissue. According to the pharmacokinetics of porphyrin fluorescence measured by spectroscopy, the optimum time range for 5-ALA application is 80–270 min prior to fluorescence bronchoscopy, with an optimum at 160 min. CONCLUSION: According to our results we propose inhalation of 5-ALA 160 min prior to fluorescence bronchoscopy, suggesting that this time difference provides the best tumor/normal tissue fluorescence ratio

Thermally nucleated magnetic reversal in CoFeB/MgO nanodots

Power consumption is the main limitation in the development of new high performance random access memory for portable electronic devices. Magnetic RAM (MRAM) with CoFeB/MgO based magnetic tunnel junctions (MTJs) is a promising candidate for reducing the power consumption given its non-volatile nature while achieving high performance. The dynamic properties and switching mechanisms of MTJs are critical to understanding device operation and to enable scaling of devices below 30 nm in diameter. Here we show that the magnetic reversal mechanism is incoherent and that the switching is thermally nucleated at device operating temperatures. Moreover, we find an intrinsic thermal switching field distribution arising on the sub-nanosecond time-scale even in the absence of size and anisotropy distributions or material defects. These features represent the characteristic signature of the dynamic properties in MTJs and give an intrinsic limit to reversal reliability in small magnetic nanodevices

Improved lung preservation relates to an increase in tubular myelin-associated surfactant protein A

BACKGROUND: Declining levels of surfactant protein A (SP-A) after lung transplantation are suggested to indicate progression of ischemia/reperfusion (IR) injury. We hypothesized that the previously described preservation-dependent improvement of alveolar surfactant integrity after IR was associated with alterations in intraalveolar SP-A levels. METHODS: Using immuno electron microscopy and design-based stereology, amount and distribution of SP-A, and of intracellular surfactant phospholipids (lamellar bodies) as well as infiltration by polymorphonuclear leukocytes (PMNs) and alveolar macrophages were evaluated in rat lungs after IR and preservation with EuroCollins or Celsior. RESULTS: After IR, labelling of tubular myelin for intraalveolar SP-A was significantly increased. In lungs preserved with EuroCollins, the total amount of intracellular surfactant phospholipid was reduced, and infiltration by PMNs and alveolar macrophages was significantly increased. With Celsior no changes in infiltration or intracellular surfactant phospholipid amount occurred. Here, an increase in the number of lamellar bodies per cell was associated with a shift towards smaller lamellar bodies. This accounts for preservation-dependent changes in the balance between surfactant phospholipid secretion and synthesis as well as in inflammatory cell infiltration. CONCLUSION: We suggest that enhanced release of surfactant phospholipids and SP-A represents an early protective response that compensates in part for the inactivation of intraalveolar surfactant in the early phase of IR injury. This beneficial effect can be supported by adequate lung preservation, as e.g. with Celsior, maintaining surfactant integrity and reducing inflammation, either directly (via antioxidants) or indirectly (via improved surfactant integrity)

Is the beck anxiety inventory a good tool to assess the severity of anxiety? A primary care study in The Netherlands study of depression and anxiety (NESDA)

<p>Abstract</p> <p>Background</p> <p>Appropriate management of anxiety disorders in primary care requires clinical assessment and monitoring of the severity of the anxiety. This study focuses on the Beck Anxiety Inventory (BAI) as a severity indicator for anxiety in primary care patients with different anxiety disorders (social phobia, panic disorder with or without agoraphobia, agoraphobia or generalized anxiety disorder), depressive disorders or no disorder (controls).</p> <p>Methods</p> <p>Participants were 1601 primary care patients participating in the Netherlands Study of Depression and Anxiety (NESDA). Regression analyses were used to compare the mean BAI scores of the different diagnostic groups and to correct for age and gender.</p> <p>Results</p> <p>Patients with any anxiety disorder had a significantly higher mean score than the controls. A significantly higher score was found for patients with panic disorder and agoraphobia compared to patients with agoraphobia only or social phobia only. BAI scores in patients with an anxiety disorder with a co-morbid anxiety disorder and in patients with an anxiety disorder with a co-morbid depressive disorder were significantly higher than BAI scores in patients with an anxiety disorder alone or patients with a depressive disorder alone. Depressed and anxious patients did not differ significantly in their mean scores.</p> <p>Conclusions</p> <p>The results suggest that the BAI may be used as a severity indicator of anxiety in primary care patients with different anxiety disorders. However, because the instrument seems to reflect the severity of depression as well, it is not a suitable instrument to discriminate between anxiety and depression in a primary care population.</p

Genome-Wide Analysis of Copy Number Variation in Type 1 Diabetes

Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D

How is the New Public Management applied in the occupational health care system? - decision-makers' and OH personnel's views in Finland

<p>Abstract</p> <p>Background</p> <p>In many countries occupational health care system is in change. Occupational health studies are mainly focused on occupational health substance and content. This study offers new perspectives on municipal OHS and its operations from management perspective.</p> <p>Aim</p> <p>The aim of this study is to analyse how New Public Management (NPM) doctrines are applied in the Finnish occupational health care system (OHS). The main focus is to describe and compare the views of decision-makers' and OH workers within the framework of NPM.</p> <p>Methods</p> <p>The data were collected by semi-structured interviews from 17 municipal decision-makers' and 26 municipal OH workers. Data was analyzed by examining coded data in a theory-driven way according to Hood's doctrine of NPM.</p> <p>Results</p> <p>The doctrines were not as compatible with the OH personnel view as with the decision-makers' view. Decision-makers and OH personnel highlighted the strict criteria required for operation evaluation. Moreover, decision-makers strongly accentuated professional management in the public sector and the reorganization of public sector units. These were not equally relevant in OH personnel views. In OH personnel views, other doctrines (more attention to performance and accomplishments, emphasizing and augmentation of the competition and better control of public expense and means test) were not similarly in evidence, only weak evidence was observed when their importance viewed as medium by decision-makers. Neither of the respondents group kept the doctrine of management models of the private sector relevant.</p> <p>Conclusions</p> <p>The NPM and Hoods doctrine fitted well with OH research. The doctrine brought out view differences and similarities between decision-makers and OH personnel. For example, policymakers highlighted more strongly the structural change by emphasizing professional management compared to OH personnel. The need for reorganization of municipal OH, regardless of different operational preconditions, was obvious for both decision-makers and OH personnel. The adaptation of more clarify management to a municipal context is not trouble-free. The municipality systemic structure, complex operational environment, and reconciliation of political and officer authority set challenges to management of municipalities.</p

Engineered Models of Metastasis with Application to Study Cancer Biomechanics

Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types