Centimeter-scale secondary information on hydraulic conductivity using a hand-held air permeameter on borehole cores

Saturated hydraulic conductivity (Ks) is one of the most important parameters determining groundwater flow and contaminant transport in both unsaturated and saturated porous media. Determining the small-scale variability of this parameter is key to evaluate implications on effective parameters at the larger scale. Moreover, for stochastic simulations of groundwater flow and contaminant transport, accurate models on the spatial variability of Ks are very much needed. While several well-established laboratory methods exist for determining Ks, investigating the small-scale variability remains a challenge. If several tens to hundreds of metres of borehole core has to be hydraulically characterised at the centimetre to decimetre scale, several hundreds to thousands of Ks measurements are required, which makes it very costly and time-consuming should traditional methods be used. With reliable air permeameters becoming increasingly available from the late 80’s, a fast and effective indirect method exists to determine Ks. Therefore, the use of hand-held air permeameter measurements for determining very accurate small-scale heterogeneity about Ks is very appealing. Very little is known, however, on its applicability for borehole cores that typically carry a small sediment volume. Therefore, the method was tested on several borehole cores of different size, originating from the Campine basin, Northern Belgium. The studied sediments are of Miocene to Pleistocene age, with a marine to continental origin, and consist of sand to clayey sand with distinct clay lenses, resulting in a Ks range of 7 orders of magnitude. During previous studies, two samples were taken from borehole cores each two meters for performing constant head lab permeameter tests. This data is now used as a reference for the air permeameter measurements that are performed with a resolution of 5 centimetres. Preliminary results indicate a very good correlation between the previously gathered constant head Ks data and the air permeability measurements, but a systematic bias seems to exist. A geostatistical analysis with cross-validation is performed to assess the predictive uncertainty on Ks, using both types of data. We conclude that performing hand-held air permeameter measurements on undisturbed borehole cores provides a very cost-effective way to obtain very detailed information in the framework of stochastic simulation and conditioning of heterogeneous hydraulic conductivity fields

Conventionalisation and discrimination as competing pressures on continuous speech-like signals

© John Benjamins Publishing Company. Arbitrary communication systems can emerge from iconic beginnings through processes of conventionalisation via interaction. Here, we explore whether this process of conventionalisation occurs with continuous, auditory signals. We conducted an artificial signalling experiment. Participants either created signals for themselves, or for a partner in a communication game. We found no evidence that the speech-like signals in our experiment became less iconic or simpler through interaction. We hypothesise that the reason for our results is that when it is difficult to be iconic initially because of the constraints of the modality, then iconicity needs to emerge to enable grounding before conventionalisation can occur. Further, pressures for discrimination, caused by the expanding meaning space in our study, may cause more complexity to emerge, again as a result of the restrictive signalling modality. Our findings have possible implications for the processes of conventionalisation possible in signed and spoken languages, as the spoken modality is more restrictive than the manual modality

A Synthetic HIV-1 Subtype C Backbone Generates Comparable PR and RT Resistance Profiles to a Subtype B Backbone in a Recombinant Virus Assay

In order to determine phenotypic protease and reverse transcriptase inhibitor-associated resistance in HIV subtype C virus, we have synthetically constructed an HIV-1 subtype C (HIV-1-C) viral backbone for use in a recombinant virus assay. The in silico designed viral genome was divided into 4 fragments, which were chemically synthesized and joined together by conventional subcloning. Subsequently, gag-protease-reverse-transcriptase (GPRT) fragments from 8 HIV-1 subtype C-infected patient samples were RT-PCR-amplified and cloned into the HIV-1-C backbone (deleted for GPRT) using In-Fusion reagents. Recombinant viruses (1 to 5 per patient sample) were produced in MT4-eGFP cells where cyto-pathogenic effect (CPE), p24 and Viral Load (VL) were monitored. The resulting HIV-1-C recombinant virus stocks (RVS) were added to MT4-eGFP cells in the presence of serial dilutions of antiretroviral drugs (PI, NNRTI, NRTI) to determine the fold-change in IC50 compared to the IC50 of wild-type HIV-1 virus. Additionally, viral RNA was extracted from the HIV-1-C RVS and the amplified GPRT products were used to generate recombinant virus in a subtype B backbone. Phenotypic resistance profiles in a subtype B and subtype C backbone were compared. The following observations were made: i) functional, infectious HIV-1 subtype C viruses were generated, confirmed by VL and p24 measurements; ii) their rate of infection was slower than viruses generated in the subtype B backbone; iii) they did not produce clear CPE in MT4 cells; and iv) drug resistance profiles generated in both backbones were very similar, including re-sensitizing effects like M184V on AZT

A comparative analysis of HIV drug resistance interpretation based on short reverse transcriptase sequences versus full sequences

<p>Abstract</p> <p>Background</p> <p>As second-line antiretroviral treatment (ART) becomes more accessible in resource-limited settings (RLS), the need for more affordable monitoring tools such as point-of-care viral load assays and simplified genotypic HIV drug resistance (HIVDR) tests increases substantially. The prohibitive expenses of genotypic HIVDR assays could partly be addressed by focusing on a smaller region of the HIV reverse transcriptase gene (RT) that encompasses the majority of HIVDR mutations for people on ART in RLS. In this study, an <it>in silico </it>analysis of 125,329 RT sequences was performed to investigate the effect of submitting short RT sequences (codon 41 to 238) to the commonly used virco^®TYPE and Stanford genotype interpretation tools.</p> <p>Results</p> <p>Pair-wise comparisons between full-length and short RT sequences were performed. Additionally, a non-inferiority approach with a concordance limit of 95% and two-sided 95% confidence intervals was used to demonstrate concordance between HIVDR calls based on full-length and short RT sequences.</p> <p>The results of this analysis showed that HIVDR interpretations based on full-length versus short RT sequences, using the Stanford algorithms, had concordance significantly above 95%. When using the virco^®TYPE algorithm, similar concordance was demonstrated (>95%), but some differences were observed for d4T, AZT and TDF, where predictions were affected in more than 5% of the sequences. Most differences in interpretation, however, were due to shifts from fully susceptible to reduced susceptibility (d4T) or from reduced response to minimal response (AZT, TDF) or vice versa, as compared to the predicted full RT sequence. The virco^®TYPE prediction uses many more mutations outside the RT 41-238 amino acid domain, which significantly contribute to the HIVDR prediction for these 3 antiretroviral agents.</p> <p>Conclusions</p> <p>This study illustrates the acceptability of using a shortened RT sequences (codon 41-238) to obtain reliable genotype interpretations by virco^®TYPE and Stanford algorithms. Implementation of this simplified protocol could significantly reduce the cost of both resistance testing and ARV treatment monitoring in RLS.</p

Chefs in Future Integrated Healthcare - Current State and Innovation Needs: A First Overview of the NECTAR Project (aN Eu Curriculum for Chef gasTro-Engineering in Primary Food Care)

: People in need of care, chronic or acute, often present problematic food intake and special nutritional needs. Integrated, person-centred and pro-active food and nutritional care delivery has been proven effective for people in health care. However, skills mismatches have been reported in different professions involved, which also applies to the role of chefs in healthcare. The EU funded project NECTAR aims at closing this gap by creating a new job profile, called Chef Gastro-Engineering (CGE). The current publication summarizes the status quo in hospitals and gives a perspective on the future role of chefs in integrated healthcare delivery

Heart Failure, Female Sex, and Atrial Fibrillation Are the Main Drivers of Human Atrial Cardiomyopathy: Results From the CATCH ME Consortium

Background: Atrial cardiomyopathy (atCM) is an emerging prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy, and capillary density are hallmarks of atCM. The contribution of etiological factors and atrial fibrillation (AF) to the development of differential atCM phenotypes has not been quantified. This study aimed to evaluate the association between histological features of atCM and the clinical phenotype. Methods and results: We examined left atrial (LA, n=95) and right atrial (RA, n=76) appendages from a European cohort of patients undergoing cardiac surgery. Quantification of histological atCM features was performed following wheat germ agglutinin/CD31/vimentin staining. The contributions of AF, heart failure, sex, and age to histological characteristics were determined with multiple linear regression models. Persistent AF was associated with increased endomysial fibrosis (LA: +1.13±0.47 μm, P=0.038; RA: +0.94±0.38 μm, P=0.041), whereas total extracellular matrix content was not. Men had larger cardiomyocytes (LA: +1.92±0.72 μm, P<0.001), while women had more endomysial fibrosis (LA: +0.99±0.56 μm, P=0.003). Patients with heart failure showed more endomysial fibrosis (LA: +1.85±0.48 μm, P<0.001) and extracellular matrix content (LA: +3.07±1.29%, P=0.016), and a higher capillary density (LA: +0.13±0.06, P=0.007) and size (LA: +0.46±0.22 μm, P=0.044). Fuzzy k-means clustering of histological features identified 2 subtypes of atCM: 1 characterized by enhanced endomysial fibrosis (LA: +3.17 μm, P<0.001; RA: +2.86 μm, P<0.001), extracellular matrix content (LA: +3.53%, P<0.001; RA: +6.40%, P<0.001) and fibroblast density (LA: +4.38%, P<0.001), and 1 characterized by cardiomyocyte hypertrophy (LA: +1.16 μm, P=0.008; RA: +2.58 μm, P<0.001). Patients with fibrotic atCM were more frequently female (LA: odds ratio [OR], 1.33, P=0.002; RA: OR, 1.54, P=0.004), with persistent AF (LA: OR, 1.22, P=0.036) or heart failure (LA: OR, 1.62, P<0.001). Hypertrophic features were more common in men (LA: OR=1.33, P=0.002; RA: OR, 1.54, P=0.004). Conclusions: Fibrotic atCM is associated with female sex, persistent AF, and heart failure, while hypertrophic features are more common in men

Management in non-traumatic arm, neck and shoulder complaints: differences between diagnostic groups

Arm, neck and/or shoulder complaints are common in western societies. In the Netherlands, general practice guidelines are issued on shoulder pain and epicondylitis only. Little is known about actual management of the total range of diagnoses. The objectives of the study are: to determine management in patients consulting the GP with a new episode of non-traumatic arm neck and shoulder complaints up to 6 months after the first consultation. To evaluate differences in management between patients with specific diagnoses versus non-specific diagnoses and between specific diagnostic groups. In a prospective cohort study in general practice. We recruited 682 eligible patients. Data on diagnosis, management, patient- and complaint-characteristics were collected. Co-occurrence of treatment options was presented in scaled rectangles. After 6 months, additional diagnostic tests had been performed in 18% of the patients, mainly radiographic examination (14%). Further, 49% had been referred for physiotherapy and 12% to the medical specialist. Patients with specific diagnoses were more frequently referred for specialist treatment, and patients with non-specific diagnoses for physiotherapy. Corticosteroid injections (17%) were mainly applied specific diagnoses (e.g. impingement syndrome, frozen shoulder, carpal tunnel and M. Quervain). Frequencies of prescribed medication (51%) did not differ between specific and non-specific