Amplified ambivalence: having a sibling with juvenile idiopathic arthritis

Despite increased awareness of family responses to chronic illness and disability, there is still a need to understand experiences of well siblings. We begin to address this by asking “What is it like to have a sibling with juvenile idiopathic arthritis?” (JIA).Eight families with an adolescent diagnosed with JIA participated. Four members of each family, including one healthy sibling, were interviewed and transcripts analyzed using grounded theory. Analysis suggests healthy siblings see their family as different to ‘normal’ families, forfeit time with peers, share vicariously adverse experiences of their ill sibling, and feel inadequately informed. Such experiences amplify the ambivalent nature of sibling relationships and are possibly felt most strongly during late childhood and early adolescence. Support from extended family can reduce these negative experiences and facilitate social and emotional adjustment which also occurs over time as the children mature. These findings have implications for healthcare professionals and voluntary organizations

a cross-sectional study on the association between urbanicity and the acquisition of immunity

Background Malaria incidence has declined considerably over the last decade. This is partly due to a scale-up of control measures but is also attributed to increasing urbanization. This study aimed to analyse the association between malaria and urbanization and the effect of urbanicity on the acquisition of semi-immunity. Methods In 2012, children with fever presenting to St Michael’s Hospital Pramso/Ghana were recruited. The malaria-positive-fraction (MPF) of fever cases was calculated on community-level to approximate the malaria risk. The mean age of malaria cases was calculated for each community to estimate the acquisition of semi-immunity. The level of urbanicity for the communities was calculated and associations between MPF, urbanicity and immunity were modelled using linear regression. Results Twenty-six villages were included into the study with a mean MPF of 35 %. A linear decrease of 5 % (95 % CI: 4–6 %) in MPF with every ten-point increase in urbanicity was identified. The mean age of malaria patients increased by 2.9 months (95 % CI: 1.0–4.8) with every ten-point increase in urbanicity. Discussion The results confirm an association between an increase in urbanicity and declining malaria risk and demonstrate that the acquisition of semi-immunity is heterogeneous on a micro- epidemiological scale and is associated with urbanicity

Collection of occurrence data in foods – The value of the BfR MEAL study in addition to the national monitoring for dietary exposure assessment

Two different data sets of occurrence data are available in Germany at present: the German National Food Monitoring and the BfR MEAL Study. To determine the suitability of each data set for exposure assessment and to develop concepts for a target-oriented selection and application of data, possibilities, limitations and scope of substance as well as food selection is quantitatively compared. The National Monitoring data provides comprehensive information on the variability of substance levels. This enables short- and long-term exposure assessment and consumer-loyal scenarios. The BfR MEAL Study supplements the monitoring data set with > 100 substances or by complementing the food spectrum for substances already included in the National Monitoring. The study design benefits especially the long-term dietary exposure assessment for the German population including the total diet. Using both programmes enables case-dependent selection of the appropriate dataset and in combination both sets can contribute to enhanced consumer safety

The Leu22Pro tumor-associated variant of DNA polymerase beta is dRP lyase deficient

Approximately 30% of human tumors characterized to date express DNA polymerase beta (pol β) variant proteins. Two of the polymerase beta cancer-associated variants are sequence-specific mutators, and one of them binds to DNA but has no polymerase activity. The Leu22Pro (L22P) DNA polymerase beta variant was identified in a gastric carcinoma. Leu22 resides within the 8 kDa amino terminal domain of DNA polymerase beta, which exhibits dRP lyase activity. This domain catalyzes the removal of deoxyribose phosphate during short patch base excision repair. We show that this cancer-associated variant has very little dRP lyase activity but retains its polymerase activity. Although residue 22 has no direct contact with the DNA, we report here that the L22P variant has reduced DNA-binding affinity. The L22P variant protein is deficient in base excision repair. Molecular dynamics calculations suggest that alteration of Leu22 to Pro changes the local packing, the loop connecting helices 1 and 2 and the overall juxtaposition of the helices within the N-terminal domain. This in turn affects the shape of the binding pocket that is required for efficient dRP lyase catalysis

Acquiring variation in an artificial language: children and adults are sensitive to socially conditioned linguistic variation

Languages exhibit sociolinguistic variation, such that adult native speakers condition the usage of linguistic variants on social context, gender, and ethnicity, among other cues. While the existence of this kind of socially conditioned variation is well-established, less is known about how it is acquired. Studies of naturalistic language use by children provide various examples where children's production of sociolinguistic variants appears to be conditioned on similar factors to adults’ production, but it is difficult to determine whether this reflects knowledge of sociolinguistic conditioning or systematic differences in the input to children from different social groups. Furthermore, artificial language learning experiments have shown that children have a tendency to eliminate variation, a process which could potentially work against their acquisition of sociolinguistic variation. The current study used a semi-artificial language learning paradigm to investigate learning of the sociolinguistic cue of speaker identity in 6-year-olds and adults. Participants were trained and tested on an artificial language where nouns were obligatorily followed by one of two meaningless particles and were produced by one of two speakers (one male, one female). Particle usage was conditioned deterministically on speaker identity (Experiment 1), probabilistically (Experiment 2), or not at all (Experiment 3). Participants were given tests of production and comprehension. In Experiments 1 and 2, both children and adults successfully acquired the speaker identity cue, although the effect was stronger for adults and in Experiment 1. In addition, in all three experiments, there was evidence of regularization in participants' productions, although the type of regularization differed with age: children showed regularization by boosting the frequency of one particle at the expense of the other, while adults regularized by conditioning particle usage on lexical items. Overall, results demonstrate that children and adults are sensitive to speaker identity cues, an ability which is fundamental to tracking sociolinguistic variation, and that children's well-established tendency to regularize does not prevent them from learning sociolinguistically conditioned variation

Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain

Background Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes. Results To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using antibody microarrays and mapped disease-specific molecular networks. Using these networks as seeds we then employed independent genome and transcriptome data sets to corroborate potential pathogenic pathways. Conclusions We identified Growth-Differentiation Factor (GDF) signaling as a novel Alzheimer’s disease-relevant pathway supported by in vivo and in vitro follow-up experiments, demonstrating the existence of a highly informative link between cellular pathology and changes in circulatory signaling proteins

Estimation of Immune Cell Densities in Immune Cell Conglomerates: An Approach for High-Throughput Quantification

Determining the correct number of positive immune cells in immunohistological sections of colorectal cancer and other tumor entities is emerging as an important clinical predictor and therapy selector for an individual patient. This task is usually obstructed by cell conglomerates of various sizes. We here show that at least in colorectal cancer the inclusion of immune cell conglomerates is indispensable for estimating reliable patient cell counts. Integrating virtual microscopy and image processing principally allows the high-throughput evaluation of complete tissue slides.For such large-scale systems we demonstrate a robust quantitative image processing algorithm for the reproducible quantification of cell conglomerates on CD3 positive T cells in colorectal cancer. While isolated cells (28 to 80 microm(2)) are counted directly, the number of cells contained in a conglomerate is estimated by dividing the area of the conglomerate in thin tissues sections (< or =6 microm) by the median area covered by an isolated T cell which we determined as 58 microm(2). We applied our algorithm to large numbers of CD3 positive T cell conglomerates and compared the results to cell counts obtained manually by two independent observers. While especially for high cell counts, the manual counting showed a deviation of up to 400 cells/mm(2) (41% variation), algorithm-determined T cell numbers generally lay in between the manually observed cell numbers but with perfect reproducibility.In summary, we recommend our approach as an objective and robust strategy for quantifying immune cell densities in immunohistological sections which can be directly implemented into automated full slide image processing systems

Influence of ultrasound-assisted par-frying on crust formation and browning during the production of French fries

Frying is a key processing step during the production of French fries and important for end product quality and sensory attributes. It is governed by heat and mass transfer between the frying oil and the potato strips. Crust and color of the French fries are key quality parameters and important in consumer perception. Crust formation is a result of combined heat and mass transfer effects. Convective heat transfer from frying oil to potato strips and heat conduction within the tissue cause water evaporation. Mass transfer occurs in the form of water vapor release to the frying oil and oil absorption in the outer layers of the potato strips. Browning of French fries is related to Maillard reactions between reducing sugars and amino acids. High contents of reducing sugars are often related to an undesired dark color and bitter taste of French fries. High-intensity ultrasound transmitted to liquid media causes cavitation and microstreaming, which can influence boundary layers and cell structures and result in improved heat and mass transfer. The influence of an ultrasound treatment of potato strips during the par-frying step was investigated in order to determine the effect on the resulting changes in product quality. Improved heat transfer at the product surface due to micro-streaming in the oil and a facilitated release of vapor from the product surface was observed. A faster crust formation was found at the initial phase of frying but the crust was found to become softer at longer sonication times due to persistent mechanical ultrasound effects. French fries from ultrasound assisted par-frying had a lighter color after finish-frying in comparison to the conventionally par-fried samples due to an improved release of reducing sugars from the tissue. Ultrasound-assisted par-frying showed to be effective in modifying heat and mass transfer with an impact on crust formation and browning of French fries. Further work is required regarding the optimization of parameters and sonication times

Sharing vocabularies: towards horizontal alignment of values-driven business functions

This paper highlights the emergence of different ‘vocabularies’ that describe various values-driven business functions within large organisations and argues for improved horizontal alignment between them. We investigate two established functions that have long-standing organisational histories: Ethics and Compliance (E&C) and Corporate Social Responsibility (CSR). By drawing upon research on organisational alignment, we explain both the need for and the potential benefit of greater alignment between these values-driven functions. We then examine the structural and socio-cultural dimensions of organisational systems through which E&C and CSR horizontal alignment can be coordinated to improve synergies, address tensions, and generate insight to inform future research and practice in the field of Business and Society. The paper concludes with research questions that can inform future scholarly research and a practical model to guide organizations’ efforts towards inter-functional, horizontal alignment of values-driven organizational practice

Development of a Continuous Pulsed Electric Field (PEF) Vortex-Flow Chamber for Improved Treatment Homogeneity Based on Hydrodynamic Optimization

Pulsed electric fields (PEF) treatment is an effective process for preservation of liquid products in food and biotechnology at reduced temperatures, by causing electroporation. It may contribute to increase retention of heat-labile constituents with similar or enhanced levels of microbial inactivation, compared to thermal processes. However, especially continuous PEF treatments suffer from inhomogeneous treatment conditions. Typically, electric field intensities are highest at the inner wall of the chamber, where the flow velocity of the treated product is lowest. Therefore, inhomogeneities of the electric field within the treatment chamber and associated inhomogeneous temperature fields emerge. For this reason, a specific treatment chamber was designed to obtain more homogeneous flow properties inside the treatment chamber and to reduce local temperature peaks, therefore increasing treatment homogeneity. This was accomplished by a divided inlet into the chamber, consequently generating a swirling flow (vortex). The influence of inlet angles on treatment homogeneity was studied (final values: radial angle α = 61°; axial angle β = 98°), using computational fluid dynamics (CFD). For the final design, the vorticity, i.e., the intensity of the fluid rotation, was the lowest of the investigated values in the first treatment zone (1002.55 1/s), but could be maintained for the longest distance, therefore providing an increased mixing and most homogeneous treatment conditions. The new design was experimentally compared to a conventional co-linear setup, taking into account inactivation efficacy of Microbacterium lacticum as well as retention of heat-sensitive alkaline phosphatase (ALP). Results showed an increase in M. lacticum inactivation (maximum Δlog of 1.8 at pH 7 and 1.1 at pH 4) by the vortex configuration and more homogeneous treatment conditions, as visible by the simulated temperature fields. Therefore, the new setup can contribute to optimize PEF treatment conditions and to further extend PEF applications to currently challenging products