Exploring the use of Granger causality for the identification of chemical exposure based on physiological data.

Wearable sensors offer new opportunities for the early detection and identification of toxic chemicals in situations where medical evaluation is not immediately possible. We previously found that continuously recorded physiology in guinea pigs can be used for early detection of exposure to an opioid (fentanyl) or a nerve agent (VX), as well as for differentiating between the two. Here, we investigated how exposure to these different chemicals affects the interactions between ECG and respiration parameters as determined by Granger causality (GC). Features reflecting such interactions may provide additional information and improve models differentiating between chemical agents. Traditional respiration and ECG features, as well as GC features, were extracted from data of 120 guinea pigs exposed to VX (n = 61) or fentanyl (n = 59). Data were divided in a training set (n = 99) and a test set (n = 21). Minimum Redundancy Maximum Relevance (mRMR) and Support Vector Machine (SVM) algorithms were used to, respectively, perform feature selection and train a model to discriminate between the two chemicals. We found that ECG and respiration parameters are Granger-related under healthy conditions, and that exposure to fentanyl and VX affected these relationships in different ways. SVM models discriminated between chemicals with accuracy of 95% or higher on the test set. GC features did not improve the classification compared to traditional features. Respiration features (i.e., peak inspiratory and expiratory flow) were the most important to discriminate between different chemical's exposure. Our results indicate that it may be feasible to discriminate between chemical exposure when using traditional physiological respiration features from wearable sensors. Future research will examine whether GC features can contribute to robust detection and differentiation between chemicals when considering other factors, such as generalizing results across species.

Breast sensibility after mastectomy and implant-based breast reconstruction.

PURPOSE: The aim of the study is to evaluate the level of sensible impairment after mastectomy or implant-based breast reconstruction (IBBR). In addition, factors influencing breast sensibility were evaluated. METHODS: A cross-sectional study was performed in Maastricht University Medical Center between July 2016 and August 2018. Women with unilateral mastectomy with or without IBBR were included. Objective sensory measurements were performed using Semmes-Weinstein monofilaments. Their healthy breast served as control, using a paired t test. Differences between mastectomy with and without IBBR were evaluated using the independent t test. Linear regression was performed to evaluate the association between patient characteristics on breast sensibility. The paired t test was used to evaluate in which part of the breast the sensibility is best preserved. RESULTS: Fifty-one patients were eligible for inclusion. Sixteen patients underwent IBBR after mastectomy. Twenty-three patients received radiotherapy and 35 patients received chemotherapy. Monofilament values were significantly higher in the operated group compared to the reference group (p < 0.001). Linear regression showed a statistically significant association between IBBR and objectively measured impaired sensation (p = 0.008). After mastectomy, the cutaneous protective sensation is only diminished. After IBBR, it is lost in the majority of the breast. The medial part of the breast was significantly more sensitive than the lateral part in all operated breasts (p < 0.001). CONCLUSION: IBBR has a significantly negative impact on the breast sensibility compared to mastectomy alone. This study shows that the protective sensation of the skin in the breast is lost after IBBR. To our knowledge, this is the first study to evaluate the level of sensible impairment after mastectomy or IBBR. More research is necessary to confirm these results.

Sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions: A systematic review.

BACKGROUND: The sensory recovery of the reconstructed breast is an undervalued topic in the field of autologous breast reconstruction. This systematic review aimed to evaluate the available literature on the sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions and to assess the possible benefits of sensory nerve coaptation compared to spontaneous reinnervation of the flap. METHODS: A comprehensive literature search was conducted in PubMed, Embase and the Cochrane Library to identify all eligible studies regarding the sensory recovery of all types of innervated and non-innervated autologous breast reconstructions. RESULTS: The search yielded 334 hits, of which 32 studies concerning 1177 breast reconstructions were included. The amount of heterogeneity between the studies was high, which made the pooling of data difficult. The studies indicated that spontaneous reinnervation of autologous breast reconstructions occurred to a variable extent, depending on how and when it was measured. Despite these variable results, the sensory recovery of innervated flaps, however, was superior, started earlier and gradually improved over time with a higher chance of approaching normal values than non-innervated flaps. There is a lack of studies that assess the return of erogenous sensation and quality of life. CONCLUSION: The current evidence shows that nerve coaptation results in superior sensory recovery of the reconstructed breast compared to spontaneous reinnervation of the flap. This review illustrates that more standardised, high-quality studies with adequate sample sizes are needed to objectively evaluate the sensory recovery of the breast after autologous breast reconstructions.

Energy saving in WWTP: Daily benchmarking under uncertainty and data availability limitations.

Efficient management of Waste Water Treatment Plants (WWTPs) can produce significant environmental and economic benefits. Energy benchmarking can be used to compare WWTPs, identify targets and use these to improve their performance. Different authors have performed benchmark analysis on monthly or yearly basis but their approaches suffer from a time lag between an event, its detection, interpretation and potential actions. The availability of on-line measurement data on many WWTPs should theoretically enable the decrease of the management response time by daily benchmarking. Unfortunately this approach is often impossible because of limited data availability. This paper proposes a methodology to perform a daily benchmark analysis under database limitations. The methodology has been applied to the Energy Online System (EOS) developed in the framework of the project "INNERS" (INNovative Energy Recovery Strategies in the urban water cycle). EOS calculates a set of Key Performance Indicators (KPIs) for the evaluation of energy and process performances. In EOS, the energy KPIs take in consideration the pollutant load in order to enable the comparison between different plants. For example, EOS does not analyse the energy consumption but the energy consumption on pollutant load. This approach enables the comparison of performances for plants with different loads or for a single plant under different load conditions. The energy consumption is measured by on-line sensors, while the pollutant load is measured in the laboratory approximately every 14 days. Consequently, the unavailability of the water quality parameters is the limiting factor in calculating energy KPIs. In this paper, in order to overcome this limitation, the authors have developed a methodology to estimate the required parameters and manage the uncertainty in the estimation. By coupling the parameter estimation with an interval based benchmark approach, the authors propose an effective, fast and reproducible way to manage infrequent inlet measurements. Its use enables benchmarking on a daily basis and prepares the ground for further investigation.

Water jet indentation for local elasticity measurements of soft materials.

We present a novel elastography method for soft materials (100Pa-100kPa) based on indentation by a µm-sized water jet. We show that the jet creates a localized deformation ("cavity") of the material that can be easily visualized. We study experimentally how cavity width and depth depend on jet speed, height, incidence angle and sample elasticity. We describe how to calibrate the indenter using gels of known stiffness. We then demonstrate that the indenter yields quantitative elasticity values within 10% of those measured by shear rheometry. We corroborate our experimental findings with fluid-solid finite-element simulations that quantitatively predict the cavity profile and fluid flow lines. The water jet indenter permits in situ local stiffness measurements of 2D or 3D gels used for cell culture in physiological buffer, is able to assess stiffness heterogeneities with a lateral resolution in the range 50-500µm (at the tissue scale) and can be assembled at low cost with standard material from a biology laboratory. We therefore believe it will become a valuable method to measure the stiffness of a wide range of soft, synthetic or biological materials.

Structural investigation of cell wall polysaccharides of Lactobacillus delbrueckii subsp. bulgaricus 17.

Lactobacilli are valuable strains for commercial (functional) food fermentations. Their cell surface-associated polysaccharides (sPSs) possess important functional properties, such as acting as receptors for bacteriophages (bacterial viruses), influencing autolytic characteristics and providing protection against antimicrobial peptides. The current report provides an elaborate molecular description of several surface carbohydrates of Lactobacillus delbrueckii subsp. bulgaricus strain 17. The cell surface of this strain was shown to contain short chain poly(glycerophosphate) teichoic acids and at least two different sPSs, designated here as sPS1 and sPS2, whose chemical structures were examined by 2D nuclear magnetic resonance spectroscopy and methylation analysis. Neutral branched sPS1, extracted with n-butanol, was shown to be composed of hexasaccharide repeating units (-[α-d-Glcp-(1-3)-]-4-ß-l-Rhap2OAc-4-ß-d-Glcp-[α-d-Galp-(1-3)]-4-α-Rhap-3-α-d-Galp-), while the major component of the TCA-extracted sPS2 was demonstrated to be a linear d-galactan with the repeating unit structure being (-[Gro-3P-(1-6)-]-3-ß-Galf-3-α-Galp-2-ß-Galf-6-ß-Galf-3-ß-Galp-).

Elimination of pharmaceutical residues in biologically pre-treated hospital wastewater using advanced UV irradiation technology: a comparative assessment.

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H2O2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H2O2 as AOP. The "conventional" cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process.

Complete genome sequence of the giant Pseudomonas phage Lu11.

The complete genome sequence of the giant Pseudomonas phage Lu11 was determined, comparing 454 and Sanger sequencing. The double-stranded DNA (dsDNA) genome is 280,538 bp long and encodes 391 open reading frames (ORFs) and no tRNAs. The closest relative is Ralstonia phage ϕRSL1, encoding 40 similar proteins. As such, Lu11 can be considered phylogenetically unique within the Myoviridae and indicates the diversity of the giant phages within this family.

[Genome instability of Pseudomonas aeruginosa phages of the EL species: examination of virulent mutants].

The article continues a study of pseudolysogeny in Pseudominas aeruginosa infected with phiKZ-like phages of the EL species. Analysis was performed for several newly isolated virulent mutants of EL phages (EL and RU) that were virulent (capable of causing lysis of bacteria infected with the wild-type phage) and a lower extent of opalescence of negative colonies (NCs). Wile-type recombinants were detected in crosses of virulent mutants of phages EL and RU to confirm the polygenic control of virulence. Since a deletion mutation was found in one of the virulent EL mutants and high genetic instability was characteristic of another mutant, a mobile genetic element was assumed to play a role in mutagenesis. Pseudolysogeny of bacteria provides for horizontal gene transfer between different bacterial strains. Hence, sequencing of the phage genome and demonstration of the lack of toxic gene products are insufficient for the phage to be included into a therapeutic mixture. To use live phages, it is essential to study in detail the possible consequences of their interaction with host bacteria.

[Drop-out from clinical psychotherapeutic treatment of personality problems]. / Drop-out bij klinisch psychotherapeutische behandeling van persoonlijkheidsproblematiek.

BACKGROUND: Drop-out is a serious problem in psychotherapy. Earlier studies have shown that the main factors associated with drop-out are young age, low socio-economic status and pathological symptoms such as severity of the problems and problematic substance-abuse. AIM: To investigate patient's and pathological characteristics that predict drop-out among patients with predominantly personality problems. METHOD: Patient's characteristics and pathological characteristics of 372 subjects were ascertained via a retrospective study by means of four databases: intake letters, scid-ii personality questionnaires, scid-i and ii interviews and discharge letters. The association between these characteristics and drop-out was tested by means of bivariate and multivariate analysis. results The drop-out rate was 33.3 %. The main predictors of drop-out were young age, a low Global Assessment of Functioning (gaf)-score and the existence of problematic substance-abuse at discharge. The degree and severity of axis i disorders and the nature of personality problems made hardly any contribution to the prediction of drop-out. CONCLUSION: These findings indicate that more attention needs to be given to the existence of substance-abuse before psychotherapy begins. Drop-out is still a problem and is difficult to predict and hard to influence.

Relation between branching patterns and perfusion in stochastic generated coronary arterial trees.

Biological variation in branching patterns is likely to affect perfusion of tissue. To assess the fundamental consequences of branching characteristics, 50 stochastic asymmetrical coronary trees and one non-stochastic symmetrical branching tree were generated. In the stochastic trees, area growth, A, at branching points was varied: A = random; 1.00; 1.10; 1.13 and 1.15 and symmetry, S, was varied: S = random; 1.00; 0.70; 0.58; 0.50 and 0.48. With random S and A values, a large variation in flow and volume was found, linearly related to the number of vessels in the trees. Large A values resulted in high number of vessels and high flow and volume values, indicating vessels connected in parallel. Lowering symmetry values increased the number of vessels, however, without changing flow, indicating a dominant connection of vessels in series. Both large A and small S values gave more realistic gradual pressure drops compared to the symmetrical non-stochastic branching tree. This study showed large variations in tree realizations, which may reflect real biological variations in tree anatomies. Furthermore, perfusion of tissue clearly depends on the branching rules applied.

Passive immunization of guinea pigs with llama single-domain antibody fragments against foot-and-mouth disease.

Foot-and-mouth disease (FMD) is a highly contagious disease that occasionally causes outbreaks in Europe. There is a need for therapies that provide rapid protection against FMD in outbreak situations. We aim to provide such rapid protection by passive immunization with llama single-domain antibody fragments (VHHs). Twenty-four VHHs binding serotype O FMDV in vitro were isolated from immunized llamas by phage display and expressed in bakers yeast for further characterization. They recognized four functionally independent antigenic sites. Six strongly FMDV neutralizing VHHs bound to a peptide representing the GH-loop of viral protein 1 known to be involved in binding to the cellular receptor of FMDV. Clone M8, recognizing this antigenic site, and clone M23, recognizing another antigenic site, showed synergistic in vitro virus neutralization. Three FMDV specific VHHs were PEGylated in order to decrease their rapid blood clearance and thus enable in vivo guinea pig protection experiments. Passive immunization with individual VHHs showed no protection, but a mixture of M8 and M23 showed partial transient protection. The protection afforded by these VHHs was however low as compared to the complete protection afforded by convalescent guinea pig serum. In contrast, these VHHs showed far more efficient in vitro FMDV neutralization than convalescent guinea pig serum. This lack of correlation between in vitro neutralization and in vivo protection lends further credence to the notion that opsonophagocytosis of FMDV is important for protection in vivo.

Non-homogenized ITS regions in the parasitic nematode Cooperia oncophora.

Here, the validity of the assumption of concerted evolution of ribosomal regions in larval and adult Cooperia oncophora was assessed. In each of 4 individuals of this parasitic nematode, at least 78% of the sequences comprised different ITS variants. This implies that concerted evolution is not acting, which is corroborated by the scarcity of signatures of gene conversion and recombination. Mis-incorporation of nucleotides and illegitimate PCR-induced recombination turned out to be unlikely, and positions with substantial frequencies of alternative nucleotides corresponded to ambiguous positions in published ITS2 sequences of this and other Cooperia species based on direct sequencing. The ITS regions of each individual C. oncophora displayed a significant excess of unique mutations in agreement with expansion of the ribosomal gene family. Interesting corollaries of the inferred size changes of this gene family are genomic rearrangements that occur during larval development such as multiple rounds of endoduplication (in Rhabditidae), chromatin diminution (in Ascaris), and non-compensatory mutations on the secondary structure of the ITS2. It is yet unknown which process is important in trichostrongylids. Finally, although it can not be rigorously assessed in Cooperia, the ITS polymorphisms can readily be envisioned to affect phylogenetic reconstructions of closely related nematodes.

Vaccination against the nematode Haemonchus contortus with a thiol-binding fraction from the excretory/secretory products (ES).

Fractionated excretory/secretory products (ES) of adult Haemonchus contortus were evaluated as protective antigens. The proteins were successively eluted from a Thiol Sepharose column using 25 mM cysteine followed by 25 mM Dl-dithiothreitol (DTT). Sheep were vaccinated three times and challenged with 5000 third stage infective larvae (L3) of H. contortus. Highest level of protection was found in sheep vaccinated with the DTT-eluted fraction in which egg output and worm burden were reduced by 52 and 50%, respectively, compared to the adjuvant control group. There was a positive correlation between fecundity (number of eggs per female) and the cumulative EPG or worm burden. Serum and mucus antibody levels of ES-specific immunoglobulins increased after immunizations and after challenge for IgG, IgA and IgE. The harvesting of H. contortus from animals clustered per group revealed the presence of cysteine protease activity in the ES of all groups but in addition to that, metalloprotease activity was also detected in the groups vaccinated with the DTT-eluted fraction, total ES and adjuvant only, in contrast to previous batches of ES (completely inhibited by E64) obtained from non vaccinated animals.

In situ analysis of coronary terminal arteriole diameter responses: technical report of a new experimental model.

INTRODUCTION: To date, investigation of coronary arteriole vasomotor activity has been limited to arterioles >30- 40 microm. Here, we introduce a new experimental model to allow for in situ microscopy of terminal coronary arterioles. METHODS: Rat hearts were perfused in a closed loop system (priming volume 20 ml) which was placed on a computer-controlled microscope stage. FITC-dextran and tetrodotoxin (TTX, 50 microM) were added. Tilting of the microscope by 90 degrees allowed for visual access to the ventricular surface. Arterioles were identified by the flow direction of fluorescent beads (1 microm). Images were recorded on video tape, and arteriole diameters were measured offline. Stability of the preparation and maintenance of coronary flow reserve were analyzed. Responses of coronary flow and arteriole diameters to the vasodilators papaverine and Na-nitroprusside were recorded. RESULTS: In TTX-arrested control hearts coronary flow and terminal arteriole diameters were stable for 2 h. Administration of papaverine and Na-nitroprusside increased coronary flow from 6.4 +/- 0.7 to 13.3 +/- 1.3 ml/min, decreasing coronary resistance by 52 +/- 3%. Terminal coronary arteriole diameters increased from 12.0 +/- 0.9 to 13.6 +/- 1.0 microm, decreasing hindrance of this vessel segment by 45 +/- 11%. CONCLUSION: Preservation of coronary terminal arteriolar tone and adequate responsiveness to vasodilators in the TTX-arrested isolated heart were demonstrated. Thus, this model may serve to complement our understanding of coronary microvascular control mechanisms by extending observations to the terminal arteriolar bed.

Effects of locally injected interferon-beta on palatal mucoperiosteal wound healing.

BACKGROUND: Wound contraction and scar formation in the palatal mucoperiosteum after cleft palate surgery impair maxillary growth. The aim of this study was to determine the effects of IFN-beta on palatal mucoperiosteal wound healing in growing rats. METHODS: Standardized wounds were made in the palatal mucoperiosteum of young rats. Either IFN-beta or vehicle were injected at the wound site between 4 and 29 days after wounding. The results were compared with control wounds. Tissue samples were collected at 8, 15, 30, and 60 days PW for biochemical and microscopic analysis. RESULTS: IFN-beta stimulated re-epithelialization but did not reduce the number of myofibroblasts or scar tissue formation. Surprisingly, the injection of vehicle alone delayed the healing process. CONCLUSION: IFN-beta might be suitable to stimulate re-epithelialization but it does not reduce scar tissue formation in rat palatal wound healing. The injection of agents into palatal wounds might severely impair the healing process.

Polyphasic typing of Cryptosporidium baileyi: a suggested model for characterization of cryptosporidia.

The present study was undertaken to characterize the oocyst morphology, host specificity, organ location, virulence, and sequences of the small subunit ribosomal RNA, 70-kDa heat shock protein, and oocyst wall protein genes of Cryptosporidium baileyi, and to compare this strain with other Cryptosporidium species. This study also aims to serve as a model for polyphasic (phenetic and genetic) characterization of Cryptosporidium species and strains. On the basis of these results, further genetic and phenetic characterization of an avian isolate is needed if the difference between the length or width, or both, of oocysts of an isolate and of C. baileyi is > or = 10% or if the difference between the oocyst shape index of the isolate and of C. baileyi is > or = 3% (or both). The isolate is infectious for mammals or lower vertebrates, or the host range is narrow, i.e., infectious only for some bird species; after oral or intratracheal inoculation, the parasites are not located in the cloaca and in the bursa of Fabricius or the respiratory tract; clinical disease or weight gain reduction can be observed after oral inoculation; the genetic distance for the examined gene between C. baileyi and the isolate is similar in magnitude to that observed between most closely related Cryptosporidium species.

Protection studies with recombinant excretory/secretory proteins of Haemonchus contortus.

The efficacy of two recombinant proteins of Haemonchus contortus was studied in both adult sheep and young lambs. These 15 and 24 kDa excretory/secretory proteins were given combined, either supplemented or not with a glycan-rich insect cell extract. In 9-month-old sheep (trial 1), faecal egg output and worm burden were reduced by 49% and 55%, respectively, after vaccination with rec15/24, and by 46% and 65% after vaccination with rec15/24 and glycan extract. No reduction in egg output or number of worms was found in young lambs using the above recombinant proteins plus glycan-rich extract (trial 2). When trial 1 was repeated (trial 3), the protection could not be reproduced, possibly due to differences in batches of recombinant proteins. In all sheep, independent of their age, rec15/24-specific immunoglobulin (Ig)G1 and IgA titres were present, but 9-month-old protected sheep had significantly higher IgA titres than the lambs. Addition of glycans resulted in lower rec15/24-specific IgG1 and IgA in 9-month-old sheep after challenge. This did not affect the level of protection. A significant negative correlation was found between IgA and worm numbers in protected sheep immunized with rec15/24 supplemented with glycans. Total IgE and rec15/24 specific IgE titres were low. The number of eosinophils, mast cells, sheep mast cell protease (SMCP)+ cells and IgA+ cells did not differ between the protected and unprotected sheep, but the lambs had significantly fewer mast cells independent of their immunization.

A method using sustainability indicators to compare conventional and animal-friendly egg production systems.

The objective of this paper was to describe a method that enables a comparison of egg production systems for their contribution to sustainable development of egg production, using data from the Netherlands for demonstration purposes. One conventional system, the battery cage system, and two animal-friendly systems, the deep-litter and the aviary systems, illustrate this method. The method is based on a three-phase framework that identifies relevant issues regarding sustainable development (Phase 1), translates issues into sustainability indicators (Phase 2), and assesses the contribution of sustainability indicators to sustainable development (Phase 3). Phases 1 and 2 are based on analysis of literature and consultation with experts. Phase 3 is based on graphical and numerical comparisons. A graphical comparison presents the relative deviation between actual and target values for each sustainability indicator. A numerical comparison combines the relative deviation for each sustainability indicator into an overall contribution of an egg production system to sustainable development. Sustainability indicators selected include economic performance, ammonia emission, energy use, hen welfare, farmer welfare, and egg quality. Based on equal importance of these indicators, the battery cage system shows the least negative contribution to sustainable development. The aviary system is considered a better animal-friendly alternative for a battery cage system when compared with a deep-litter system. The aviary system especially needs to improve economic performance and farmer welfare. The conclusion can only be tentative, however, because methodological aspects such as selection and weighting of sustainability indicators will need careful attention and further research.

Evidence for stretch-induced resistance increase of proximal coronary microcirculation.

We investigated the influence of stretch on regional hemodynamic parameters of the septal circulation. We used a similar experimental setup and mathematical model, as described previously (14). Five ventricular septa were isolated from anesthetized dogs, sutured to a biaxial stretching apparatus, and perfused with an oxygenated perfluorochemical emulsion at maximal vasodilation. Under unloaded and biaxially stretched conditions, flow and septal thickness (to index vascular volume) were measured continuously. Pressure was varied sinusoidally at 30, 50, and 70 mmHg with amplitude of 7.5 mmHg over frequencies ranging between 0.015 and 7 Hz. Admittance (flow/pressure) and capacitance (thickness/pressure) transfer functions were calculated and interpreted in terms of a two-compartmental model with volume-dependent resistances. Parameter estimation showed that the proximal resistance and compliance were unaffected, whereas the resistance of the proximal part of the microcirculation, including the small arterioles, increased with stretch. The effect of stretch on the distal resistance and capacitance, however, could not be determined unequivocally.