Societal views on orphan drugs: cross sectional survey of Norwegians aged 40 to 67

Objective To determine whether a general societal preference for prioritising treatment of rare diseases over common ones exists and could provide a justification for accepting higher cost effectiveness thresholds for orphan drugs

Sonographic Evaluation for Endometrial Polyps

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135550/1/jum201635112381.pd

Maximum Host Survival at Intermediate Parasite Infection Intensities

BACKGROUND: Although parasitism has been acknowledged as an important selective force in the evolution of host life histories, studies of fitness effects of parasites in wild populations have yielded mixed results. One reason for this may be that most studies only test for a linear relationship between infection intensity and host fitness. If resistance to parasites is costly, however, fitness may be reduced both for hosts with low infection intensities (cost of resistance) and high infection intensities (cost of parasitism), such that individuals with intermediate infection intensities have highest fitness. Under this scenario one would expect a non-linear relationship between infection intensity and fitness. METHODOLOGY/PRINCIPAL FINDINGS: Using data from blue tits (Cyanistes caeruleus) in southern Sweden, we investigated the relationship between the intensity of infection of its blood parasite (Haemoproteus majoris) and host survival to the following winter. Presence and intensity of parasite infections were determined by microscopy and confirmed using PCR of a 480 bp section of the cytochrome-b-gene. While a linear model suggested no relationship between parasite intensity and survival (F = 0.01, p = 0.94), a non-linear model showed a significant negative quadratic effect (quadratic parasite intensity: F = 4.65, p = 0.032; linear parasite intensity F = 4.47, p = 0.035). Visualization using the cubic spline technique showed maximum survival at intermediate parasite intensities. CONCLUSIONS/SIGNIFICANCE: Our results indicate that failing to recognize the potential for a non-linear relationship between parasite infection intensity and host fitness may lead to the potentially erroneous conclusion that the parasite is harmless to its host. Here we show that high parasite intensities indeed reduced survival, but this effect was masked by reduced survival for birds heavily suppressing their parasite intensities. Reduced survival among hosts with low parasite intensities suggests costs of controlling parasite infections; however, the nature of such costs remains to be elucidated

Value of tissue harmonic imaging (THI) and contrast harmonic imaging (CHI) in detection and characterisation of breast tumours

The purpose of this study was to investigate the extent to which tissue harmonic imaging (THI), speckle reduction imaging (SRI), spatial compounding (SC) and contrast can improve detection and differentiation of breast tumours. We examined 38 patients (14 benign, 24 malignant tumours) with different combinations of THI, SRI and SC. The effect on delineation, margin, tissue differentiation and posttumoral phenomena was evaluated with a three-point score. Additionally, 1oo not palpable tumours (diameters: 4–15 mm) were examined by contrast harmonic imaging (CHI) with power Doppler. After bolus injection (0.5 ml Optison), vascularisation and enhancement were observed for 20 min. The best combination for detection of margin, infiltration, echo pattern and posterior lesion boundary was the combination of SRI level 2 with SC low. THI was helpful for lesions OF more than 1 cm depth. In native Power Doppler, vessels were found in 54 of 100 lesions. Within 5 min after contrast medium (CM) injection, marginal and penetrating vessels increased in benign and malignant tumours and central vessels mostly in carcinomas (p<0.05). A diffuse CM accumulation was observed up to 20 min after injection in malignant tumours only (p<0.05). THI, SRI and SC improved delineation and tissue differentiation. Second-generation contrast agent allowed detection of tumour vascularisation with prolonged enhancement

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd

Variation in Phenotype, Parasite Load and Male Competitive Ability across a Cryptic Hybrid Zone

BackgroundMolecular genetic studies are revealing an increasing number of cryptic lineages or species, which are highly genetically divergent but apparently cannot be distinguished morphologically. This observation gives rise to three important questions: 1) have these cryptic lineages diverged in phenotypic traits that may not be obvious to humans; 2) when cryptic lineages come into secondary contact, what are the evolutionary consequences: stable co-existence, replacement, admixture or differentiation and 3) what processes influence the evolutionary dynamics of these secondary contact zones?Methodology/principal findingsTo address these questions, we first tested whether males of the Iberian lizard Lacerta schreiberi from two highly genetically divergent, yet morphologically cryptic lineages on either side of an east-west secondary contact could be differentiated based on detailed analysis of morphology, coloration and parasite load. Next, we tested whether these differences could be driven by pre-copulatory intra-sexual selection (male-male competition). Compared to eastern males, western males had fewer parasites, were in better body condition and were more intensely coloured. Although subtle environmental variation across the hybrid zone could explain the differences in parasite load and body condition, these were uncorrelated with colour expression, suggesting that the differences in coloration reflect heritable divergence. The lineages did not differ in their aggressive behaviour or competitive ability. However, body size, which predicted male aggressiveness, was positively correlated with the colour traits that differed between genetic backgrounds.Conclusions/significanceOur study confirms that these cryptic lineages differ in several aspects that are likely to influence fitness. Although there were no clear differences in male competitive ability, our results suggest a potential indirect role for intra-sexual selection. Specifically, if lizards use the colour traits that differ between genetic backgrounds to assess the size of potential rivals or mates, the resulting fitness differential favouring western males could result in net male-mediated gene flow from west to east across the current hybrid zone.Devi Stuart-Fox, Raquel Godinho, Joëlle Goüy de Bellocq, Nancy R. Irwin, José Carlos Brito, Adnan Moussalli, Pavel Široký, Andrew F. Hugall and Stuart J. E. Bair

Analysing the eosinophil cationic protein - a clue to the function of the eosinophil granulocyte

Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen. In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated. In conditions such as Hypereosinophilic Syndrome (HES) circulating eosinophil levels are even further raised. Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear. The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP). This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions. Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis. ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions. ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections. The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil