Algorithm for multi-curve-fitting with shared parameters and a possible application in evoked compound action potential measurements

BACKGROUND: Experimental results are commonly fitted by determining parameter values of suitable mathematical expressions. In case a relation exists between different data sets, the accuracy of the parameters obtained can be increased by incorporating this relationship in the fitting process instead of fitting the recordings separately. METHODS: An algorithm to fit multiple measured curves simultaneously was developed. The method accounts for parameters that are shared by some curves. It can be applied to either linear or nonlinear equations. Simulated noisy "measurement results" were created to compare the introduced method to the "straight forward" way of fitting the curves separately. RESULTS: The analysis of the simulated measurements confirm, that the introduced method yields more accurate parameters compared to the ones gained by fitting the measurements separately. Therefore it needs more computer time. As an example, the new fitting algorithm is applied to the measurements of the evoked compound action potentials (ECAP) of the auditory nerve: This leads to promising ideas to reduce artefacts generated by the measuring process. CONCLUSION: The introduced fitting algorithm uses the relationship between multiple measurement results to increase the accuracy of the parameters. Its application in the field of ECAP measurements is promising and should be further investigated

Schumpeter: Theorist of the Avant-Garde

This paper argues that Schumpeter’s 1911 edition of ‘Theory of Economic Development’ can be fruitfully read as a theory of the avant-garde, in line with such theories developed by artistic avant-garde around the same time, in particular by the Italian Futurists. In particular it will show that both Schumpeter and other avant-garde theorists sought to break with past (1), identify an avant-garde who could force that break (2), find new ways to represent the dynamic world (3), embrace the new and dynamic (4) and promote a perpetual dynamic process, instead of a specific end-state or utopia (5). This new reading helps us to understand the cultural meaning of this seminal text in economics. Secondly it greatly facilitates our understanding of the differences with the later interwar German edition and English edition, which were more cautious in their embrace of the new, less focused on the individual qualities of the entrepreneur and placed more emphasis on historical continuity. Thirdly this reading suggests a different reason for the bifurcation between Schumpeter and the rest of the Austrian school of economics. Traditionally this split is explained by Schumpeter’s affinities with the Lausanne School, this paper instead suggests that the crucial break between Schumpeter on the one hand and Böhm-Bawerk, Wieser and later members of the Austrian School on the other hand is their theory of and attitude toward social change

Earliest Triassic microbialites in the South China Block and other areas; controls on their growth and distribution

Earliest Triassic microbialites (ETMs) and inorganic carbonate crystal fans formed after the end-Permian mass extinction (ca. 251.4 Ma) within the basal Triassic Hindeodus parvus conodont zone. ETMs are distinguished from rarer, and more regional, subsequent Triassic microbialites. Large differences in ETMs between northern and southern areas of the South China block suggest geographic provinces, and ETMs are most abundant throughout the equatorial Tethys Ocean with further geographic variation. ETMs occur in shallow-marine shelves in a superanoxic stratified ocean and form the only widespread Phanerozoic microbialites with structures similar to those of the Cambro-Ordovician, and briefly after the latest Ordovician, Late Silurian and Late Devonian extinctions. ETMs disappeared long before the mid-Triassic biotic recovery, but it is not clear why, if they are interpreted as disaster taxa. In general, ETM occurrence suggests that microbially mediated calcification occurred where upwelled carbonate-rich anoxic waters mixed with warm aerated surface waters, forming regional dysoxia, so that extreme carbonate supersaturation and dysoxic conditions were both required for their growth. Long-term oceanic and atmospheric changes may have contributed to a trigger for ETM formation. In equatorial western Pangea, the earliest microbialites are late Early Triassic, but it is possible that ETMs could exist in western Pangea, if well-preserved earliest Triassic facies are discovered in future work

Development of a peer support intervention to encourage dietary behaviour change towards a Mediterranean diet in adults at high cardiovascular risk.

BACKGROUND: Mediterranean diet (MD) interventions are demonstrated to significantly reduce cardiovascular disease (CVD) risk but are typically resource intensive and delivered by health professionals. There is considerable interest to develop interventions that target sustained dietary behaviour change and that are feasible to scale-up for wider public health benefit. The aim of this paper is to describe the process used to develop a peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk. METHODS: The Medical Research Council (MRC) and Behaviour Change Wheel (BCW) frameworks and the COM-B (Capability, Opportunity, Motivation, Behaviour) theoretical model were used to guide the intervention development process. We used a combination of evidence synthesis and qualitative research with the target population, health professionals, and community health personnel to develop the intervention over three main stages: (1) we identified the evidence base and selected dietary behaviours that needed to change, (2) we developed a theoretical basis for how the intervention might encourage behaviour change towards a MD and selected intervention functions that could drive the desired MD behaviour change, and (3) we defined the intervention content and modelled outcomes. RESULTS: A theory-based, culturally tailored, peer support intervention was developed to specifically target behaviour change towards a MD in the target population. The intervention was a group-based program delivered by trained peer volunteers over 12-months, and incorporated strategies to enhance social support, self-efficacy, problem-solving, knowledge, and attitudes to address identified barriers to adopting a MD from the COM-B analysis. CONCLUSIONS: The MRC and BCW frameworks provided a systematic and complementary process for development of a theory-based peer support intervention to encourage dietary behaviour change towards a MD in non-Mediterranean adults at high CVD risk. The next step is to evaluate feasibility, acceptability, and diet behaviour change outcomes in response to the peer support intervention (change towards a MD and nutrient biomarkers) using a randomized controlled trial design

Breast MRI in nonpalpable breast lesions: a randomized trial with diagnostic and therapeutic outcome – MONET – study

<p>Abstract</p> <p>Background</p> <p>In recent years there has been an increasing interest in MRI as a non-invasive diagnostic modality for the work-up of suspicious breast lesions. The additional value of Breast MRI lies mainly in its capacity to detect multicentric and multifocal disease, to detect invasive components in ductal carcinoma in situ lesions and to depict the tumor in a 3-dimensional image. Breast MRI therefore has the potential to improve the diagnosis and provide better preoperative staging and possibly surgical care in patients with breast cancer. The aim of our study is to assess whether performing contrast enhanced Breast MRI can reduce the number of surgical procedures due to better preoperative staging and whether a subgroup of women with suspicious nonpalpable breast lesions can be identified in which the combination of mammography, ultrasound and state-of-the-art contrast-enhanced Breast MRI can provide a definite diagnosis.</p> <p>Methods/Design</p> <p>The MONET – study (<b><it>M</it></b>R mammography <b><it>O</it></b>f <b><it>N</it></b>onpalpable Br<b><it>E</it></b>ast <b><it>T</it></b>umors) is a randomized controlled trial with diagnostic and therapeutic endpoints. We aim to include 500 patients with nonpalpable suspicious breast lesions who are referred for biopsy. With this number of patients, the expected 12% reduction in surgical procedures due to more accurate preoperative staging with Breast MRI can be detected with a high power (90%). The secondary outcome is the positive and negative predictive value of contrast enhanced Breast MRI. If the predictive values are deemed sufficiently close to those for large core biopsy then the latter, invasive, procedure could possibly be avoided in some women. The rationale, study design and the baseline characteristics of the first 100 included patients are described.</p> <p>Trial registration</p> <p>Study protocol number NCT00302120</p

Habitat-related birdsong divergence: a multi-level study on the influence of territory density and ambient noise in European blackbirds

Song plays an important role in avian communication and acoustic variation is important at both the individual and population level. Habitat-related variation between populations in particular can reflect adaptations to the environment accumulated over generations, but this may not always be the case. In this study, we test whether variation between individuals matches local conditions with respect to noise level and territory density to examine whether short-term flexibility could contribute to song divergence at the population level. We conducted a case study on an urban and forest population of the European blackbird and show divergence at the population level (i.e. across habitats) in blackbird song, anthropogenic noise level and territory density. Unlike in several other species, we found a lack of any correlation at the individual level (i.e. across individuals) between song features and ambient noise. This suggests species-specific causal explanations for noise-dependent song differentiation which are likely associated with variation in song-copying behaviour or feedback constraints related to variable singing styles. On the other hand, we found that at the level of individual territories, temporal features, but not spectral ones, are correlated to territory density and seasonality. This suggests that short-term individual variation can indeed contribute to habitat-dependent divergence at the population level. As this may undermine the potential role for song as a population marker, we conclude that more investigations on individual song flexibility are required for a better understanding of the impact of population-level song divergence on hybridisation and speciation

Insulin Sensitivity Is Reflected by Characteristic Metabolic Fingerprints - A Fourier Transform Mass Spectrometric Non-Targeted Metabolomics Approach

BACKGROUND: A decline in body insulin sensitivity in apparently healthy individuals indicates a high risk to develop type 2 diabetes. Investigating the metabolic fingerprints of individuals with different whole body insulin sensitivity according to the formula of Matsuda, et al. (ISI(Matsuda)) by a non-targeted metabolomics approach we aimed a) to figure out an unsuspicious and altered metabolic pattern, b) to estimate a threshold related to these changes based on the ISI, and c) to identify the metabolic pathways responsible for the discrimination of the two patterns. METHODOLOGY AND PRINCIPAL FINDINGS: By applying infusion ion cyclotron resonance Fourier transform mass spectrometry, we analyzed plasma of 46 non-diabetic subjects exhibiting high to low insulin sensitivities. The orthogonal partial least square model revealed a cluster of 28 individuals with alterations in their metabolic fingerprints associated with a decline in insulin sensitivity. This group could be separated from 18 subjects with an unsuspicious metabolite pattern. The orthogonal signal correction score scatter plot suggests a threshold of an ISI(Matsuda) of 15 for the discrimination of these two groups. Of note, a potential subgroup represented by eight individuals (ISI(Matsuda) value between 8.5 and 15) was identified in different models. This subgroup may indicate a metabolic transition state, since it is already located within the cluster of individuals with declined insulin sensitivity but the metabolic fingerprints still show some similarities with unaffected individuals (ISI >15). Moreover, the highest number of metabolite intensity differences between unsuspicious and altered metabolic fingerprints was detected in lipid metabolic pathways (arachidonic acid metabolism, metabolism of essential fatty acids and biosynthesis of unsaturated fatty acids), steroid hormone biosyntheses and bile acid metabolism, based on data evaluation using the metabolic annotation interface MassTRIX. CONCLUSIONS: Our results suggest that altered metabolite patterns that reflect changes in insulin sensitivity respectively the ISI(Matsuda) are dominated by lipid-related pathways. Furthermore, a metabolic transition state reflected by heterogeneous metabolite fingerprints may precede severe alterations of metabolism. Our findings offer future prospects for novel insights in the pathogenesis of the pre-diabetic phase

Cyanobacterial Diversity and a New Acaryochloris-Like Symbiont from Bahamian Sea-Squirts

Symbiotic interactions between ascidians (sea-squirts) and microbes are poorly understood. Here we characterized the cyanobacteria in the tissues of 8 distinct didemnid taxa from shallow-water marine habitats in the Bahamas Islands by sequencing a fragment of the cyanobacterial 16S rRNA gene and the entire 16S–23S rRNA internal transcribed spacer region (ITS) and by examining symbiont morphology with transmission electron (TEM) and confocal microscopy (CM). As described previously for other species, Trididemnum spp. mostly contained symbionts associated with the Prochloron-Synechocystis group. However, sequence analysis of the symbionts in Lissoclinum revealed two unique clades. The first contained a novel cyanobacterial clade, while the second clade was closely associated with Acaryochloris marina. CM revealed the presence of chlorophyll d (chl d) and phycobiliproteins (PBPs) within these symbiont cells, as is characteristic of Acaryochloris species. The presence of symbionts was also observed by TEM inside the tunic of both the adult and larvae of L. fragile, indicating vertical transmission to progeny. Based on molecular phylogenetic and microscopic analyses, Candidatus Acaryochloris bahamiensis nov. sp. is proposed for this symbiotic cyanobacterium. Our results support the hypothesis that photosymbiont communities in ascidians are structured by host phylogeny, but in some cases, also by sampling location

Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair

Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70-/- cells and ku80 -/- cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase β (Pol β). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80-/- mice had a shorter life span than dna-pkcs-/- mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. © 2014 Choi et al