Evaluating Complexity of Fetal MEG Signals: A Comparison of Different Metrics and Their Applicability.
In this work, we aim to investigate whether information based metrics of neural activity are a useful tool for the quantification of consciousness before and shortly after birth. Neural activity is measured using fetal magnetoencephalography (fMEG) in human fetuses and neonates. Based on recent theories on consciousness, information-based metrics are established to measure brain complexity and to assess different levels of consciousness. Different metrics (measures of entropy, compressibility and fractality) are, thus, explored in a reference population and their usability is evaluated. For comparative analysis, two fMEG channels were selected: one where brain activity was previously detected and one at least 15 cm away, that represented a control channel. The usability of each metric was evaluated and results from the brain and control channel were compared. Concerning the ease of use with fMEG data, Lempel-Ziv-Complexity (LZC) was evaluated as best, as it is unequivocal and needs low computational effort. The fractality measures have a high number of parameters that need to be adjusted prior to analysis and therefore forfeit comparability, while entropy measures require a higher computational effort and more parameters to adjust compared to LZC. Comparison of a channel with brain activity and a control channel in neonatal recordings showed significant differences in most complexity metrics. This clear difference can be seen as proof of concept for the usability of complexity metrics in fMEG. For fetal data, this comparison produced less clear results which can be related to leftover maternal signals included in the control channel. Further work is necessary to conclusively interpret results from the analysis of fetal recordings. Yet this study shows that complexity metrics can be used for fMEG data on early consciousness and the evaluation gives a guidance for future work. The inconsistency of results from different metrics highlights the challenges of working with complexity metrics as neural correlates of consciousness, as well as the caution one should apply to interpret them.


Recurrent Coding Sequence Variation Explains Only A Small Fraction of the Genetic Architecture of Colorectal Cancer.
Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10(-7) and OR = 1.09, P = 7.4 × 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P < 2.90 × 10(-6)). We found an excess of rare, damaging variants in base-excision (P = 2.4 × 10(-4)) and DNA mismatch repair genes (P = 6.1 × 10(-4)) consistent with a recessive mode of inheritance. This study comprehensively explores the contribution of coding sequence variation to CRC risk, identifying associations with coding variation in 4 genes and PCDHG gene cluster and several candidate recessive alleles. However, these findings suggest that recurrent, low-frequency coding variants account for a minority of the unexplained heritability of CRC.


Effects of the mycelial extract of cultured Cordyceps sinensis on in vivo hepatic energy metabolism in the mouse.
Mice were given the extract of cultured Cordyceps sinensis (Cs) (200 mg/kg daily, p.o.) for 3 weeks. In vivo phosphorus-31 nuclear magnetic resonance (NMR) spectra of the liver were acquired at weekly intervals using a surface coil. From 1 to 3 weeks, a consistent increase in the ATP/inorganic phosphate ratio, which represents the high energy state, was observed in the Cs extract-treated mice. The intracellular pH of the Cs extract-treated mice was not significantly different from that of the control mice. No steatosis, necrosis, inflammation or fibrosis were observed in the liver specimens from Cs extract-treated mice.


Impact of male factor infertility on offspring health and development.
Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility.


Targeted introgression of a wheat stem rust resistance gene by DNA marker-assisted chromosome engineering.
Chromosome engineering is a useful strategy for transfer of alien genes from wild relatives into modern crops. However, this strategy has not been extensively used for alien gene introgression in most crops due to low efficiency of conventional cytogenetic techniques. Here, we report an improved scheme of chromosome engineering for efficient elimination of a large amount of goatgrass (Aegilops speltoides) chromatin surrounding Sr39, a gene that provides resistance to multiple stem rust races, including Ug99 (TTKSK) in wheat. The wheat ph1b mutation, which promotes meiotic pairing between homoeologous chromosomes, was employed to induce recombination between wheat chromosome 2B and goatgrass 2S chromatin using a backcross scheme favorable for inducing and detecting the homoeologous recombinants with small goatgrass chromosome segments. Forty recombinants with Sr39 with reduced surrounding goatgrass chromatin were quickly identified from 1048 backcross progenies through disease screening and molecular marker analysis. Four of the recombinants carrying Sr39 with a minimal amount of goatgrass chromatin (2.87-9.15% of the translocated chromosomes) were verified using genomic in situ hybridization. Approximately 97% of the goatgrass chromatin was eliminated in one of the recombinants, in which a tiny goatgrass chromosome segment containing Sr39 was retained in the wheat genome. Localization of the goatgrass chromatin in the recombinants led to rapid development of three molecular markers tightly linked to Sr39. The new wheat lines and markers provide useful resources for the ongoing global effort to combat Ug99. This study has demonstrated great potential of chromosome engineering in genome manipulation for plant improvement.


Investigation of a method for generating synthetic CT models from MRI scans of the head and neck for radiation therapy.
Magnetic resonance (MR) images often provide superior anatomic and functional information over computed tomography (CT) images, but generally are not used alone without CT images for radiotherapy treatment planning and image guidance. This study aims to investigate the potential of probabilistic classification of voxels from multiple MRI contrasts to generate synthetic CT ('MRCT') images. The method consists of (1) acquiring multiple MRI volumes: T1-weighted, T2-weighted, two echoes from a ultra-short echo time (UTE) sequence, and calculated fat and water image volumes using a Dixon method, (2) classifying tissues using fuzzy c-means clustering with a spatial constraint, (3) assigning attenuation properties with weights based on the probability of individual tissue classes being present in each voxel, and (4) generating a MRCT image volume from the sum of attenuation properties in each voxel. The capability of each MRI contrast to differentiate tissues of interest was investigated based on a retrospective analysis of ten patients. For one prospective patient, the correlation of skull intensities between CT and MR was investigated, the discriminatory power of MRI in separating air from bone was evaluated, and the generated MRCT image volume was qualitatively evaluated. Our analyses showed that one MRI volume was not sufficient to separate all tissue types, and T2-weighted images was more sensitive to bone density variation compared to other MRI image types. The short echo UTE image showed significant improvement in contrasting air versus bone, but could not completely separate air from bone without false labeling. Generated MRCT and CT images showed similar contrast between bone and soft/solid tissues. These results demonstrate the potential of the presented method to generate synthetic CT images to support the workflow of radiation oncology treatment planning and image guidance.


Equity - some theory and its policy implications.
This essay seeks to characterise the essential features of an equitable health care system in terms of the classical Aristotelian concepts of horizontal and vertical equity, the common (but ill-defined) language of "need" and the economic notion of cost-effectiveness as a prelude to identifying some of the more important issues of value that policy-makers will have to decide for themselves; the characteristics of health (and what determines it) that can cause policy to be ineffective (or have undesired consequences); the information base that is required to support a policy directed at securing greater equity, and the kinds of research (theoretical and empirical) that are needed to underpin such a policy.


Integrating phylogeography and high-resolution X-ray CT reveals five new cryptic species and multiple hybrid zones among Australian earless dragons.
Cryptic lineages, comprising species complexes with deep genetic structuring across the landscape but without distinct morphological differences, impose substantial difficulties for systematists and taxonomists in determining true species diversity. Here, we present an integrative approach that combines data from phylogeography and geometric morphometric analyses of three-dimensional cranial models to revisit the uncertain taxonomy of earless dragons from southern and central Australia that at one time or another have been included under the name Tympanocryptis lineata. Our approach finds strong support for seven previously described species, and more importantly, five undescribed Tympanocryptis taxa for which we provide a taxonomic treatment. We also find evidence of introgression and hybridization in three discrete contact zones between lineages, supported by mitochondrial and nuclear genes, as well as morphological analyses. With a sampling design that includes at least five individuals for each genetic lineage with corresponding X-ray microcomputed tomography scans, we perform comparative evolutionary analyses to show that there is a significant phylogenetic signal in Tympanocryptis cranial shape. Our results demonstrate the importance of using multiple specimens in each genetic lineage, particularly in cases of potential hybridization, and that geometric morphometrics, when used in an integrative framework, is a powerful tool in species delimitation across cryptic lineages. Our results lay the groundwork for future evolutionary studies in this widespread group across multiple environmental types and identify several species of immediate conservation concern with a focus on T. petersi sp. nov. We suggest that this species has undergone significant population declines and warrants a full conservation assessment.


7-(4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity.
The effects of 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro-2 (1H)- quinolinone (OPC-14597), a derivative of the dopamine (DA) autoreceptor agonist 7-(3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy)-2(1H)-quinolinone (OPC-4392), on DA receptors were biochemically and behaviorally studied and compared with those of OPC-4392. Both OPC-14597 and OPC-4392 inhibited reserpine- and gamma-butyrolactone (GBL)-induced increase in tyrosine hydroxylase activity in the mouse and rat brain. The effects of OPC-14597 were comparable to those of OPC-4392 and were completely antagonized by haloperidol. OPC-14597, unlike apomorphine, did not evoke postsynaptic DA receptor-stimulating behavioral signs such as hyperlocomotion in the reserpinized mice and contralateral rotation in rats with unilateral striatal 6-hydroxydopamine lesions. Both OPC-14597 and OPC-4392 inhibited such apomorphine-induced postsynaptic behavioral changes as stereotypy and hyperlocomotion in mice and rats and rotation in rats with unilateral striatal kainic acid lesions. The anti-apomorphine effects of OPC-14597 were about 30 to 140 times greater than those of OPC-4392 and were observed at doses that inhibit the increases in tyrosine hydroxylase activity. The affinities of OPC-14597 for 3H-spiperone-labeled D2 receptors in the rat frontal cortex, limbic forebrain and striatum were higher than those of OPC-4392. These results suggest that OPC-14597 is a unique antipsychotic drug candidate, being a DA autoreceptor agonist that has a stronger postsynaptic D2 receptor antagonistic activity than that of OPC-4392.


Managing health impacts of heat in South East Queensland, Australia.
Heatwaves kill more people than any other natural hazard in Australia. Current literature on managing health risks of heatwaves highlights the importance of implementing urban planning measures, and engaging with vulnerable groups on a local level to better understand perceptions of risk and tailor health protection measures. This paper reviews arrangements to reduce heatwave health risks in South East Queensland in response to these themes. A literature search and document analysis, stakeholder interviews, and multi-stakeholder cross-sectoral workshops revealed that although heatwave management is not always considered by local government and disaster management stakeholders, many urban planning measures to minimize urban heat have been pursued. However, greater information from vulnerable groups is still needed to better inform heatwave management measures.


Biological determinants of postural disorders in elderly women.
Postural control impairments and dizziness, which are major health problems with high secondary morbidity and mortality, increase with aging. Elevated homocysteine (Hcy) level is an age-related metabolic disorder, known to be involved in cardiovascular, neurological, and multisensory dysfunctions. Elevated Hcy level might be involved in sensory balance control systems impairment and dizziness occurrence. Dizziness, fitness Instrumental Activity of Daily Living scale (fitness IADL), systolic arterial pressure with ankle-brachial blood pressure index and homocysteinemia were studied in 61 noninstitutionized elderly women. Clinical balance tests (timed "Up and Go", 10-m walking and one-leg balance) and posturography (including sensory conflicting situations [SCS] and cognitive conflicting situations [CCS]) were performed. Clinical balance control was lower in dizzy women who presented particularly poor stability in SCS. Dizziness was related to low fitness IADL scores (odds ratio [OR] 0.452, 95% CI 0.216-0.946) and to elevated Hcy (OR 8.084, 95% CI 1.992-32.810). Elevated Hcy was correlated with balance disorders both in SCS and CCS. Dizziness is associated with a reduced ability in balance control management. Hcy is related both to dizziness and low postural performance. This relation between elevated Hcy levels and balance impairments, resulting in dizziness, may be explained by its angiotoxicity and neurotoxicity.


GATA6 suppression enhances lung specification from human pluripotent stem cells.
The transcription factor GATA6 has been shown to be important for lung development and branching morphogenesis in mouse models, but its role in human lung development is largely unknown. Here, we studied the role of GATA6 during lung differentiation using human pluripotent stem cells. We found that the human stem cell lines most efficient at generating NKX2.1+ lung progenitors express lower endogenous levels of GATA6 during endoderm patterning and that knockdown of GATA6 during endoderm patterning increased the generation of these cells. Complete ablation of GATA6 resulted in the generation of lung progenitors displaying increased cell proliferation with up to a 15-fold expansion compared with control cells, whereas the null cell line displayed a defect in further development into mature lung cell types. Furthermore, transgenic expression of GATA6 at the endoderm anteriorization stage skewed development toward a liver fate at the expense of lung progenitors. Our results suggest a critical dosage effect of GATA6 during human endoderm patterning and a later requirement during terminal lung differentiation. These studies offer an approach of modulating GATA6 expression to enhance the production of lung progenitors from human stem cell sources.


Right ventricular dysfunction.
Until recently the right ventricle's role in myocardial dynamics has not been fully appreciated. This article provides an overview of the pathophysiology, imaging and management of right ventricular dysfunction. That levosimendan may promote right ventricular function opens new avenues for treatment. In addition there are existing therapies such as phosphodiesterase inhibitors and nitric oxide, which offer yet further modalities to improve outcome in right ventricular failure. How these drugs are used, in combination or alone, in conjunction with ventilatory and cardiovascular strategies has not been evaluated in multicentred randomized controlled trials. Acute right ventricular dysfunction is relatively common. There is a lack of convincing evidence in favour of any single treatment modality. Imaging methods now permit a more accurate evaluation of the right ventricle and its function. Combining treatments may offer significant advantages and the imaging and monitoring available allows real-time assessment of the response to intervention. This article illustrates how incomplete our knowledge of this condition and its management within the critical care setting is and reinforces previous calls for suitably designed trials to evaluate and develop guidelines for existing strategies and therapeutic agents.


Short-Term Moderately Elevated Intraocular Pressure Is Associated With Elevated Scotopic Electroretinogram Responses.
Moderately elevated intraocular pressure (IOP) is a risk factor for open-angle glaucoma. Some patients suffer glaucoma despite clinically measured normal IOPs. Fluctuations in IOP may have a significant role since IOPs are higher during sleep and inversion activities. Controlled transient elevations of IOPs in rats over time lead to optic nerve structural changes that are similar to the early changes observed in constant chronic models of glaucoma. Because early intervention decreases glaucoma progression, this study was done to determine if early physiological changes to the retina could be detected with noninvasive electrophysiological and optical imaging tests during moderately elevated IOP. Intraocular pressures were raised to moderately high levels (35 mm Hg) in one eye of Sprague-Dawley rats while the other (control) eye was untreated. One group of rats underwent scotopic threshold response (STR) and electroretinogram (ERG) testing, while another 3 groups underwent optical coherence tomography (OCT) imaging, Western blot, or histologic evaluation. The amplitudes of the STR and ERG responses in eyes with moderately elevated IOPs were enhanced compared to the values before IOP elevation, and compared to untreated contralateral eyes. Structural changes to the optic nerve also occurred during IOP elevation. Although ischemic IOP elevations are well-known to globally reduce components of the scotopic ERG, acute elevation in rats to levels often observed in untreated glaucoma patients caused an increase in these parameters. Further exploration of these phenomena may be helpful in better understanding the mechanisms mediating early retinal changes during fluctuating or chronically elevated IOP.


Environmental stresses can alleviate the average deleterious effect of mutations.
Fundamental questions in evolutionary genetics, including the possible advantage of sexual reproduction, depend critically on the effects of deleterious mutations on fitness. Limited existing experimental evidence suggests that, on average, such effects tend to be aggravated under environmental stresses, consistent with the perception that stress diminishes the organism's ability to tolerate deleterious mutations. Here, we ask whether there are also stresses with the opposite influence, under which the organism becomes more tolerant to mutations. We developed a technique, based on bioluminescence, which allows accurate automated measurements of bacterial growth rates at very low cell densities. Using this system, we measured growth rates of Escherichia coli mutants under a diverse set of environmental stresses. In contrast to the perception that stress always reduces the organism's ability to tolerate mutations, our measurements identified stresses that do the opposite - that is, despite decreasing wild-type growth, they alleviate, on average, the effect of deleterious mutations. Our results show a qualitative difference between various environmental stresses ranging from alleviation to aggravation of the average effect of mutations. We further show how the existence of stresses that are biased towards alleviation of the effects of mutations may imply the existence of average epistatic interactions between mutations. The results thus offer a connection between the two main factors controlling the effects of deleterious mutations: environmental conditions and epistatic interactions.


Effects of exogenous proteases without or with carbohydrases on nutrient digestibility and disappearance of non-starch polysaccharides in broiler chickens.
The objective of the current study was to evaluate the effect of a subtilisin protease, without or with inclusion of carbohydrases, on digestibility and retention of energy and protein, as well as the solubilization and disappearance of non-starch polysaccharides (NSP) from corn-soybean meal based diets fed to broiler chickens. Two hundred eighty-eight Ross 308 male broiler chickens were used for the experiment. On d 14, the birds were weighed and allocated to 6 treatments and 8 replicates per treatment with 6 birds per replicate. Treatments were: 1) corn-soybean meal based control diet; 2) control diet plus supplemental protease at 5,000 (P5000) protease units (PU)/kg); 3) control plus 10,000 PU/kg protease (P10000); or control plus an enzyme combination containing xylanase, amylase, and protease (XAP) added to achieve protease activity of: 4) 2,500 PU/kg (XAP2500); 5) 5,000 PU/kg (XAP5000); or 6) 10,000 PU/kg (XAP10000). The enzymes in XAP were combined at fixed ratios of 10:1:25 of xylanase:amylase:protease. Data were analyzed by ANOVA and specific orthogonal contrasts between treatments were performed. Addition of xylanase and amylase increased (P < 0.05) the ileal digestibility of protein by 4.2% and 2.1% at XAP5000 and XAP10000, respectively (relative to P5000 and P10000, respectively), exhibiting a plateau after the XAP5000 dose. Increment (P < 0.05) in AME due to protease was evident, particularly in P10000. At the ileal level, XAP reduced (P < 0.05) the flow of insoluble xylose and arabinose, which indicates an increase in the solubilization of arabinoxylan polymers in the small intestine. Protease on its own reduced (P < 0.05) the flow of insoluble arabinose but did not affect the flow of insoluble xylose. XAP reduced (P < 0.05) the pre-cecal flow of insoluble and total glucose and galactose. It was concluded that whereas protease by itself improved nutrient utilization and increased solubilization of NSP components, at the lower dose, a combination of xylanase, amylase, and protease produced effects greater than those of protease alone.


Semantic representations in the temporal pole predict false memories.
Recent advances in neuroscience have given us unprecedented insight into the neural mechanisms of false memory, showing that artificial memories can be inserted into the memory cells of the hippocampus in a way that is indistinguishable from true memories. However, this alone is not enough to explain how false memories can arise naturally in the course of our daily lives. Cognitive psychology has demonstrated that many instances of false memory, both in the laboratory and the real world, can be attributed to semantic interference. Whereas previous studies have found that a diverse set of regions show some involvement in semantic false memory, none have revealed the nature of the semantic representations underpinning the phenomenon. Here we use fMRI with representational similarity analysis to search for a neural code consistent with semantic false memory. We find clear evidence that false memories emerge from a similarity-based neural code in the temporal pole, a region that has been called the "semantic hub" of the brain. We further show that each individual has a partially unique semantic code within the temporal pole, and this unique code can predict idiosyncratic patterns of memory errors. Finally, we show that the same neural code can also predict variation in true-memory performance, consistent with an adaptive perspective on false memory. Taken together, our findings reveal the underlying structure of neural representations of semantic knowledge, and how this semantic structure can both enhance and distort our memories.


Methodological quality of service learning studies in rehabilitation professions: A systematic review.
Service-learning (SL) has been widely implemented and grown as a pedagogy in the rehabilitation professions. However, assessment on the quality of evidence for the effectiveness of SL related to student learning outcomes and the scope of SL activities related to the occupation of work in the rehabilitation professions is not available. This systematic review was to evaluate the rigor of the methodological quality of SL studies and the scope of SL activities related to the occupation of work in the rehabilitation professions. We performed a systematic on-line electronic literature search of nine bibliographic databases available through the university library system to identify peer-reviewed journal articles on SL provided by the tri-alliance of rehabilitation professional students, with the primary or secondary outcome on the evaluation of student SL experiences. Twenty-two SL articles using experimental design between 1995 and 2016 were extracted as they qualified for the methodological appraisal. Appraisal of each article was performed independently by four investigators using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. In six of the 22 SL studies (27%), service provided by the rehabilitation professional students was related to the occupation of work (i.e., assessment, prevention of illness, injury, and disability, and intervention). There was a significant increase in the number (and percent) of SL studies related to the occupation of work compared to that of a previous systematic review (0%, P = 0.03, Fisher's exact test). Results from the evaluation of the methodological quality of these 22 reviewed articles revealed that all received a global rating score of weak. The low methodological quality rating of the reviewed articles was mainly attributed to not controlling for confounders (22 articles), non-blinding (21), and using outcome measures which did not have evidence to support their validity (14). Inability to control for confounders was related to weak research design as more than 77% of the reviewed articles used quasi-experimental designs without a control group. Non-blinding was related to the self-report nature of the outcome measures. A significant increase in the number of SL studies related to the occupation of work was found, which may provide an indirect indication on an increase in the capacity to provide (work) rehabilitation services. However, selected studies demonstrated high risk of bias which limited firm conclusions to be drawn on reported findings from SL in the tri-alliance of rehabilitation professions curricula.


PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-Day postinfection period.
Borrelia burgdorferi infection in beagle dogs was studied quantitatively with skin punch biopsy samples and blood samples collected at 4- and 2-week intervals, respectively, over a 500-day period. Thereafter, 25 tissue samples of each dog were collected for further analysis. Starting at day 120 after tick challenge, 12 dogs were treated with antibiotics (azithromycin, ceftriaxone, or doxycycline) for 30 consecutive days. Four dogs received no antibiotic therapy. Quantification of B. burgdorferi DNA was done with an ABI Prism 7700 Sequence Detection System with oligonucleotide primers and a fluorescence-labeled probe designed to specifically amplify a fragment of the ospA gene of B. burgdorferi strain N40. All 16 dogs became infected with B. burgdorferi after tick challenge. In skin biopsy samples, spirochete numbers peaked at day 60 postinfection (<1.5 x 10(6) organisms per 100 microgram of extracted DNA), at the same time when clinical signs of arthritis developed in 11 of 16 dogs, and decreased to almost undetectable levels during the following 6 months. The number of B. burgdorferi organisms detected in skin biopsy samples was inversely correlated with the antibody levels measured by enzyme-linked immunosorbent assay. Antibiotic treatment reduced the amount of detectable spirochete DNA in skin tissue by a factor of 1,000 or more. At the end of the experiment, B. burgdorferi DNA was detectable at low levels (10(2) to 10(4) organisms per 100 microgram of extracted DNA) in multiple tissue samples regardless of treatment. However, more tissue samples of untreated dogs than of antibiotic-treated dogs were positive, and tissue samples of untreated dogs also were positive by culture. Only 1.6% of 576 blood samples of all dogs were positive for B. burgdorferi by PCR.


Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.
N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.


The use of proton pump inhibitors in treating and preventing NSAID-induced mucosal damage.
NSAIDs are prescribed widely but have rare serious gastrointestinal side effects. More recently, adverse cardiovascular effects of these drugs have also been recognized, leading to the withdrawal of some agents and continuing uncertainty about the best approach for patients requiring NSAID therapy. Proton pump inhibitors (PPIs) provide potent and long-lasting inhibition of gastric acid secretion and have proven efficacy in healing NSAID-associated ulcers, including those with continued exposure to NSAIDs. PPIs have also shown efficacy in reducing the risk of ulcerations due to NSAID use compared with NSAIDs alone in randomized controlled trials (RCTs) where endoscopic ulcers are used as the primary endpoint, albeit a surrogate marker for clinical ulcers and complications. Large RCT outcome trials comparing patients exposed to NSAIDs with and without PPI co-therapy have not been performed, but adequately powered RCTs in high-risk patients demonstrate that PPI + nonselective NSAID provides similar rates of symptomatic ulcer recurrence rates as the use of a cyclooxygenase (COX)-2 selective inhibitor. A RCT in high-risk patients with previous ulcer complications supports the additive benefit of two risk-reducing strategies, as ulcer complication recurrence was eliminated in high-risk patients who were given a COX-2 selective agent with a PPI. Helicobacter pylori, an independent risk factor for ulcers, should be sought out and eradicated in patients at increased gastrointestinal risk, typically those with an ulcer history. Following H. pylori eradication, however, patients remain at risk and co-therapy with a PPI is recommended. NSAID medication selection should consider both the individual patients' gastrointestinal and cardiovascular risks.


Single file dynamics in soft materials.
The term single file (SF) dynamics refers to the motion of an assembly of particles through a channel with cross-sections comparable to the particles' diameter. Single file diffusion (SFD) is then the diffusion of a tagged particle in a single file, i.e., under the condition that particle passing is not allowed. SFD accounts for a large variety of processes in nature, including diffusion of colloids in synthetic and natural channels, biological motors along molecular chains, electrons in proteins and liquid helium, ions through membranes, just to mention a few examples. Albeit introduced in 1965s, over the last decade the classical notion of SF dynamics has been generalised to account for a more realistic modelling of the particle properties, file geometry, particle-particle and channel-particle interactions, which paves the way to remarkable applications of the SF model, for instance, in the technology of bio-integrated nanodevices. We provide here a comprehensive review of the recent advances in the theory of SF dynamics with the purpose of spurring further experimental work.


Three-dimensionally preserved integument reveals hydrodynamic adaptations in the extinct marine lizard Ectenosaurus (Reptilia, Mosasauridae).
The physical properties of water and the environment it presents to its inhabitants provide stringent constraints and selection pressures affecting aquatic adaptation and evolution. Mosasaurs (a group of secondarily aquatic reptiles that occupied a broad array of predatory niches in the Cretaceous marine ecosystems about 98-65 million years ago) have traditionally been considered as anguilliform locomotors capable only of generating short bursts of speed during brief ambush pursuits. Here we report on an exceptionally preserved, long-snouted mosasaur (Ectenosaurus clidastoides) from the Santonian (Upper Cretaceous) part of the Smoky Hill Chalk Member of the Niobrara Formation in western Kansas, USA, that contains phosphatized remains of the integument displaying both depth and structure. The small, ovoid neck and/or anterior trunk scales exhibit a longitudinal central keel, and are obliquely arrayed into an alternating pattern where neighboring scales overlap one another. Supportive sculpturing in the form of two parallel, longitudinal ridges on the inner scale surface and a complex system of multiple, superimposed layers of straight, cross-woven helical fiber bundles in the underlying dermis, may have served to minimize surface deformation and frictional drag during locomotion. Additional parallel fiber bundles oriented at acute angles to the long axis of the animal presumably provided stiffness in the lateral plane. These features suggest that the anterior torso of Ectenosaurus was held somewhat rigid during swimming, thereby limiting propulsive movements to the posterior body and tail.


ChimPipe: accurate detection of fusion genes and transcription-induced chimeras from RNA-seq data.
Chimeric transcripts are commonly defined as transcripts linking two or more different genes in the genome, and can be explained by various biological mechanisms such as genomic rearrangement, read-through or trans-splicing, but also by technical or biological artefacts. Several studies have shown their importance in cancer, cell pluripotency and motility. Many programs have recently been developed to identify chimeras from Illumina RNA-seq data (mostly fusion genes in cancer). However outputs of different programs on the same dataset can be widely inconsistent, and tend to include many false positives. Other issues relate to simulated datasets restricted to fusion genes, real datasets with limited numbers of validated cases, result inconsistencies between simulated and real datasets, and gene rather than junction level assessment. Here we present ChimPipe, a modular and easy-to-use method to reliably identify fusion genes and transcription-induced chimeras from paired-end Illumina RNA-seq data. We have also produced realistic simulated datasets for three different read lengths, and enhanced two gold-standard cancer datasets by associating exact junction points to validated gene fusions. Benchmarking ChimPipe together with four other state-of-the-art tools on this data showed ChimPipe to be the top program at identifying exact junction coordinates for both kinds of datasets, and the one showing the best trade-off between sensitivity and precision. Applied to 106 ENCODE human RNA-seq datasets, ChimPipe identified 137 high confidence chimeras connecting the protein coding sequence of their parent genes. In subsequent experiments, three out of four predicted chimeras, two of which recurrently expressed in a large majority of the samples, could be validated. Cloning and sequencing of the three cases revealed several new chimeric transcript structures, 3 of which with the potential to encode a chimeric protein for which we hypothesized a new role. Applying ChimPipe to human and mouse ENCODE RNA-seq data led to the identification of 131 recurrent chimeras common to both species, and therefore potentially conserved. ChimPipe combines discordant paired-end reads and split-reads to detect any kind of chimeras, including those originating from polymerase read-through, and shows an excellent trade-off between sensitivity and precision. The chimeras found by ChimPipe can be validated in-vitro with high accuracy.


Measuring cancer survival in populations: relative survival vs cancer-specific survival.
Two main methods of quantifying cancer patient survival are generally used: cancer-specific survival and relative survival. Both techniques are used to estimate survival in a single population, or to estimate differences in survival between populations. Arguments have been made that the relative survival approach is the only valid choice for population-based cancer survival studies because cancer-specific survival estimates may be invalid if there is misclassification of the cause of death. However, there has been little discussion, or evidence, as to how strong such biases may be, or of the potential biases that may result using relative survival techniques, particularly bias arising from the requirement for an external comparison group. In this article we investigate the assumptions underlying both methods of survival analysis. We provide simulations relating to the impact of misclassification of death and non-comparability of expected survival for cause-specific and relative survival approaches, respectively. For cause-specific analyses, bias through misclassification of cause of death resulted in error in descriptive analyses particularly of cancers with moderate or poor survival, but had smaller impact in analyses involving group comparisons. Relative survival ratio (RSR) estimations were robust in relation to non-comparability of comparison populations for single RSR but were less so in group comparisons where there was large variation in survival. Both cause-specific survival and relative survival are potentially valid epidemiological methods in population-based cancer survival studies, and the choice of method is dependent on the likely magnitude and direction of the biases in the specific analyses to be conducted.


Disposition and metabolism of double-labeled [3H and 14C] N-methyl-2-pyrrolidinone in the rat.
The disposition of N-methyl-2-pyrrolidinone (NMP) was studied in the rat using tritium-labeled ([4-3H]NMP) and carbon-14-labeled ([methyl-14C]NMP and [ring-14C]NMP) radioisomers. Male Sprague-Dawley rats were administered a single intravenous dose (45 mg/kg) of 5.0 microCi of 3H or 14C for single-labeled disposition studies or 5.0 microCi of 3H and 2.5 microCi of 14C for double-labeled studies (2:1 ratio, 3H:14C). Plasma levels of intact NMP were analyzed by HPLC through 6 hr after dosing and suggested a rapid distribution phase followed by a slow elimination phase. The half-life for the terminal elimination phase from plasma was about 7 hr for both 14C-isomers and 9.9 hr for the 3H-isomer. The major route of excretion of radioactivity was via the urine and accounted for about 70% of the dose within 12 hr. After 24 hr, cumulative excretion in urine represented about 80% of the dose. The 2:1 ratio of administered 3H:14C was maintained in urine through 6 hr. Measurement of radioactivity in tissues at 6 hr showed the liver and intestines to contain the highest accumulations of radioactivity, representing approximately 2% and 3% of the dose, respectively. Tissue distribution of radioactivity was similar for all three radiolabeled isomers and showed that NMP was extensively distributed to all major organs. Radiomonitored HPLC analyses of urine revealed the presence of one major and two minor metabolites. The major metabolite, representing 70-75% of the administered dose of radioactivity, was found to retain all three radiolabeled positions.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of patients undergoing primary shoulder arthroplasty before and after the age of fifty.
The reported outcomes of shoulder arthroplasty in patients under the age of fifty years are worse than those in patients over fifty. While there are several possible explanations for this finding, we explored the possibility that patients who had a primary shoulder arthroplasty when they were under fifty years of age differed from those who had the procedure when they were over fifty with respect to their pre-arthroplasty self-assessed comfort and function, sex distribution, and specific type of arthritis. The study group consisted of patients with glenohumeral arthritis who were treated with a primary shoulder arthroplasty by the same surgeon between 1990 and 2008. For each decade of age, the sex distribution, the pre-arthroplasty self-assessed shoulder comfort and function, and the prevalence of twelve different diagnoses were documented. We reviewed the series for three potential causes of worse outcomes in patients under fifty years of age as compared with those over fifty years of age: (1) a higher percentage of women, (2) a lower score for pre-arthroplasty self-assessed comfort and function, and (3) more complex pathological conditions. Patients under the age of fifty years were not more likely than those over fifty to be female or to have a lower pre-arthroplasty self-assessed comfort and function score, but they did have more complex pathological conditions, such as capsulorrhaphy arthropathy, rheumatoid arthritis, and posttraumatic arthritis. Only 21% of the younger patients had primary degenerative joint disease, whereas 66% of the older patients had that diagnosis. This difference was significant (p < 0.000000001). Surgeons performing shoulder arthroplasty in individuals under the age of fifty should be prepared to encounter pathological conditions such as capsulorrhaphy arthropathy, rheumatoid arthritis, and posttraumatic arthritis rather than primary osteoarthritis, which is more common in individuals older than fifty. The pathoanatomy in these younger patients may complicate the surgery, the rehabilitation, and the outcome of the shoulder arthroplasty.


Ablation of epicardial premature ventricular contractions in a patient with ischemic cardiomyopathy and implementation of cardiac resynchronization therapy in the same procedure.
Premature ventricular contractions (PVCs) can cause clinical deterioration in patients with heart failure and increase the frequency of shocks delivered by an implantable cardioverter defibrillator (ICD). Epicardial PVC/ventricular tachycardia (VT) is seen less often in ischemic cardiomyopathy. Radiofrequency catheter ablation is the most effective treatment option for the management of PVC/VT and can improve cardiac function. Presently described is a patient with ischemic cardiomyopathy and frequent PVCs and VT runs with multiple ICD therapies who was treated with simultaneous radiofrequency catheter ablation in the anterior interventricular vein and cardiac resynchronization therapy defibrillator upgrade in the same procedure.


Post-radiation changes in oral tissues - An analysis of cancer irradiation cases.
Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC) using special stains. The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months), and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining), fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.


The role of autoregulation of the hepatic glucose production in man. Response to a physiologic decrement in plasma glucose.
In man, a decrease in plasma glucose concentration results in a compensatory increase in hepatic glucose release. Studies in vitro have suggested that a low glucose concentration per se may directly stimulate hepatic glucose release, an effect often referred to as autoregulation. Whether autoregulation occurs in man in response to a physiologic decrement in blood glucose is not known. Therefore, seven healthy, nonobese subjects were studied on two occasions to determine the role of autoregulation in mediating the increase in glucose production that accompanies a physiologic decrement in plasma glucose concentration. On both occasions, plasma glucose concentrations were clamped successively at 95, 65, and 95 mg/dl for 2 h each. Insulin (approximately 14 microU/ml) and glucagon (approximately 70 pg/ml) were maintained constant on both occasions by an infusion of somatostatin and insulin. Phentolamine and propranolol also were infused on one occasion to produce combined alpha- and beta-adrenergic blockade. In the absence of adrenergic blockade, glucose production increased by approximately 1.3 mg/kg X min when the plasma glucose concentration was decreased from 95 to 65 mg/dl and decreased by approximately 1.5 mg/kg X min when glucose was increased from 65 to 95 mg/dl. In the presence of adrenergic blockade, the increase and decrease in glucose production averaged 0 and 0.5 mg/kg X min, respectively, representing 70-100% inhibition. We conclude that, in the presence of low physiologic insulin concentrations, autoregulation is not a major contributor to the hepatic response to a physiologic decrement in plasma glucose concentration in man.


Recognising the forest, but not the trees: an effect of colour on scene perception and recognition.
Colour has been shown to facilitate the recognition of scene images, but only when these images contain natural scenes, for which colour is 'diagnostic'. Here we investigate whether colour can also facilitate memory for scene images, and whether this would hold for natural scenes in particular. In the first experiment participants first studied a set of colour and greyscale natural and man-made scene images. Next, the same images were presented, randomly mixed with a different set. Participants were asked to indicate whether they had seen the images during the study phase. Surprisingly, performance was better for greyscale than for coloured images, and this difference is due to the higher false alarm rate for both natural and man-made coloured scenes. We hypothesized that this increase in false alarm rate was due to a shift from scrutinizing details of the image to recognition of the gist of the (coloured) image. A second experiment, utilizing images without a nameable gist, confirmed this hypothesis as participants now performed equally on greyscale and coloured images. In the final experiment we specifically targeted the more detail-based perception and recognition for greyscale images versus the more gist-based perception and recognition for coloured images with a change detection paradigm. The results show that changes to images are detected faster when image-pairs were presented in greyscale than in colour. This counterintuitive result held for both natural and man-made scenes (but not for scenes without nameable gist) and thus corroborates the shift from more detailed processing of images in greyscale to more gist-based processing of coloured images.


Rapid classification of phenotypic mutants of Arabidopsis via metabolite fingerprinting.
We evaluated the application of gas chromatography-mass spectrometry metabolic fingerprinting to classify forward genetic mutants with similar phenotypes. Mutations affecting distinct metabolic or signaling pathways can result in common phenotypic traits that are used to identify mutants in genetic screens. Measurement of a broad range of metabolites provides information about the underlying processes affected in such mutants. Metabolite profiles of Arabidopsis (Arabidopsis thaliana) mutants defective in starch metabolism and uncharacterized mutants displaying a starch-excess phenotype were compared. Each genotype displayed a unique fingerprint. Statistical methods grouped the mutants robustly into distinct classes. Determining the genes mutated in three uncharacterized mutants confirmed that those clustering with known mutants were genuinely defective in starch metabolism. A mutant that clustered away from the known mutants was defective in the circadian clock and had a pleiotropic starch-excess phenotype. These results indicate that metabolic fingerprinting is a powerful tool that can rapidly classify forward genetic mutants and streamline the process of gene discovery.


Common and low-frequency variants associated with genome-wide recombination rate.
Meiotic recombination contributes to genetic diversity by yielding new combinations of alleles. Individuals vary with respect to the genome-wide recombination counts in their gametes. Exploiting data resources in Iceland, we compiled a data set consisting of 35,927 distinct parents and 71,929 parent-offspring pairs. Within this data set, we called over 2.2 million recombination events and imputed variants with sequence-level resolution from 2,261 whole genome-sequenced individuals into the parents to search for variants influencing recombination rate. We identified 13 variants in 8 regions that are associated with genome-wide recombination rate, 8 of which were previously unknown. Three of these variants associate with male recombination rate only, seven variants associate with female recombination rate only and three variants affect both. Two are low-frequency variants with large effects, one of which is estimated to increase the male and female genetic maps by 111 and 416 cM, respectively. This variant, located in an intron, would not be found by exome sequencing.


Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase.
A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression.


Poly(acrylic acid)-bearing photoreactive azido groups for stabilizing multilayer films.
In this article, we have demonstrated a universal method for improving the stability of polyelectrolyte multilayer films by designing a photoreactive polyanion as the building block for layer-by-layer (LbL) self-assembly. By grafting an azido group into poly(acrylic acid), we synthesized a photoreactive polyanion, which can induce the photo-crosslinking between the azido group and polymeric backbone under UV irradiation. Our results show that after photocross-linking, the stability of the polyelectrolyte multilayer is greatly improved. Considering that the polyanion-bearing azido group is highly reactive, we have shown that it can be used to stabilize different LbL films. Moreover, by taking advantage of the different stability before and after UV irradiation, a patterned surface can be fabricated, which could be used as a template for selective adsorption.


Assessment of the metabolic capabilities of Haemophilus influenzae Rd through a genome-scale pathway analysis.
The annotated full DNA sequence is becoming available for a growing number of organisms. This information along with additional biochemical and strain-specific data can be used to define metabolic genotypes and reconstruct cellular metabolic networks. The first free-living organism for which the entire genomic sequence was established was Haemophilus influenzae. Its metabolic network is reconstructed herein and contains 461 reactions operating on 367 intracellular and 84 extracellular metabolites. With the metabolic reaction network established, it becomes necessary to determine its underlying pathway structure as defined by the set of extreme pathways. The H. influenzae metabolic network was subdivided into six subsystems and the extreme pathways determined for each subsystem based on stoichiometric, thermodynamic, and systems-specific constraints. Positive linear combinations of these pathways can be taken to determine the extreme pathways for the complete system. Since these pathways span the capabilities of the full system, they could be used to address a number of important physiological questions. First, they were used to reconcile and curate the sequence annotation by identifying reactions whose function was not supported in any of the extreme pathways. Second, they were used to predict gene products that should be co-regulated and perhaps co-expressed. Third, they were used to determine the composition of the minimal substrate requirements needed to support the production of 51 required metabolic products such as amino acids, nucleotides, phospholipids, etc. Fourth, sets of critical gene deletions from core metabolism were determined in the presence of the minimal substrate conditions and in more complete conditions reflecting the environmental niche of H. influenzae in the human host. In the former case, 11 genes were determined to be critical while six remained critical under the latter conditions. This study represents an important milestone in theoretical biology, namely the establishment of the first extreme pathway structure of a whole genome.


Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.
This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.


Advances in glaucoma therapeutics.
Glaucoma is a major cause of irreversible blindness in the world. The prevalence of glaucomatous loss in vision will continue to grow as our populations age. Ocular hypertension is a major risk factor for the development of glaucoma and current glaucoma therapy is directed at lowering intraocular pressure. Several new ocular hypotensive agents have been introduced in the past several years providing a variety of treatment options. In addition, various classes of neuroprotective agents demonstrating activity in a wide variety of animal models have been proposed as potential new glaucoma therapeutics. Although these approaches will slow the progression of vision loss, they do not directly intervene in the disease process(es). Advances have been made attempting to understand the pathogenic pathways involved in glaucomatous damage to the eye and in methods to clinically measure glaucoma damage. An increased understanding of the pathophysiology of glaucoma will lead to the development of new therapeutic agents that intervene and perhaps even reverse glaucomatous damage to the eye. There also is a need to develop new methods to clinically measure glaucoma damage because, currently, considerable damage occurs before glaucoma is diagnosed and glaucoma remains underdiagnosed in the general population.


Peptostreptococcus asaccharolyticus renal abscess: a rare cause of fever of unknown origin.
Renal abscess is uncommon in pediatrics and is rarely a cause of fever of unknown origin. We recently cared for a patient who presented with a 3-week history of fever. An indium scan ultimately led to the diagnosis of a renal abscess. Aspiration yielded Peptostreptococcus asaccharolyticus. This unusual case prompted a review of the clinical and microbiologic features of renal abscess in pediatric patients at our hospital over the past 10 years. Seven additional patients with a discharge diagnosis of renal abscess were identified. Only 2 of the patients had identifiable risk factors (diabetes mellitus and polycystic kidneys). Staphylococcus aureus or Enterobacteriaceae were responsible for most infections, consistent with hematogenous and urinary tract sources, respectively. No other cases of anaerobic abscess were identified. This case highlights the importance of considering a renal abscess in the differential diagnosis of fever of unknown origin and of processing specimens for both aerobic and anaerobic organisms.


Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos.
N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10-12 h. One hundred percent mortality was observed at concentrations≥50 µM. At sub-lethal concentrations (10-30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%-40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.


Factors associated with preschool workers' willingness to continue working.
In industrialized countries, the turnover rate of preschool workers is extremely high and now represents a social problem. Consequently, it has become important to promote stable early care and educational environments for this population. Several factors related to working environments are known to affect turnover intention; however, the specific factors related to turnover intention among preschool workers have not yet been identified. Considering this, the objective of the present study was to determine factors associated with preschool workers' willingness to continue working.The participants of this study were 1137 preschool workers based in Nagasaki Prefecture, Japan. Multivariate logistic regression analysis was used to analyze the participants' data, with willingness to continue working for 5 years or more set as the dependent variable.Analysis of the results for all subjects clearly showed that male sex, older age, good mental health, high number of social supports, and good work engagement have a positive effect on willingness to continue working. Further, stratifying the participants in terms of age revealed that for preschool workers under 39 years, male sex, good mental health, high number of social supports, and good work engagement act positively in regard to willingness to continue working. Meanwhile, for those over 40 years, it was found that permanent employment and good work engagement act positively in this regard. Thus, work engagement was the only common factor between preschool workers under 39 and over 40.The findings of this cross-sectional study demonstrate that the factors associated with willingness to continue working among preschool workers differ between younger and older professionals. These findings underline the importance of considering age categories when attempting to maximize such professionals' willingness to continue working.


[Psychiatric disorders in velo-cardio-facial syndrome].
Velo-cardio-facial syndrome (vcfs) is a congenital disorder with a markedly variable clinical expression. The majority of those affected have cognitive-behavioural symptoms and psychiatric problems. Most of the somatic characteristics can be treated effectively. The quality of life of patients with vcfs is therefore determined largely by cognitive and behavioural symptoms, including the increased risk of psychiatric disorders. On the basis of a case-study featuring a 41-year-old vcfs patient and by reviewing the literature we describe the psychiatric disorders that can occur in conjunction with this syndrome.


Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea.
Sound pressure fluctuations striking the ear are conveyed to the cochlea, where they vibrate the basilar membrane on which sit hair cells, the mechanoreceptors of the inner ear. Recordings of hair cell electrical responses have shown that they transduce sound via submicrometer deflections of their hair bundles, which are arrays of interconnected stereocilia containing the mechanoelectrical transducer (MET) channels. MET channels are activated by tension in extracellular tip links bridging adjacent stereocilia, and they can respond within microseconds to nanometer displacements of the bundle, facilitated by multiple processes of Ca2+-dependent adaptation. Studies of mouse mutants have produced much detail about the molecular organization of the stereocilia, the tip links and their attachment sites, and the MET channels localized to the lower end of each tip link. The mammalian cochlea contains two categories of hair cells. Inner hair cells relay acoustic information via multiple ribbon synapses that transmit rapidly without rundown. Outer hair cells are important for amplifying sound-evoked vibrations. The amplification mechanism primarily involves contractions of the outer hair cells, which are driven by changes in membrane potential and mediated by prestin, a motor protein in the outer hair cell lateral membrane. Different sound frequencies are separated along the cochlea, with each hair cell being tuned to a narrow frequency range; amplification sharpens the frequency resolution and augments sensitivity 100-fold around the cell's characteristic frequency. Genetic mutations and environmental factors such as acoustic overstimulation cause hearing loss through irreversible damage to the hair cells or degeneration of inner hair cell synapses. © 2017 American Physiological Society. Compr Physiol 7:1197-1227, 2017.


Cultivation of autotrophic ammonia-oxidizing archaea from marine sediments in coculture with sulfur-oxidizing bacteria.
The role of ammonia-oxidizing archaea (AOA) in nitrogen cycling in marine sediments remains poorly characterized. In this study, we enriched and characterized AOA from marine sediments. Group I.1a crenarchaea closely related to those identified in marine sediments and "Candidatus Nitrosopumilus maritimus" (99.1 and 94.9% 16S rRNA and amoA gene sequence identities to the latter, respectively) were substantially enriched by coculture with sulfur-oxidizing bacteria (SOB). The selective enrichment of AOA over ammonia-oxidizing bacteria (AOB) is likely due to the reduced oxygen levels caused by the rapid initial growth of SOB. After biweekly transfers for ca. 20 months, archaeal cells became the dominant prokaryotes (>80%), based on quantitative PCR and fluorescence in situ hybridization analysis. The increase of archaeal 16S rRNA gene copy numbers was coincident with the amount of ammonia oxidized, and expression of the archaeal amoA gene was observed during ammonia oxidation. Bacterial amoA genes were not detected in the enrichment culture. The affinities of these AOA to oxygen and ammonia were substantially higher than those of AOB. [(13)C]bicarbonate incorporation and the presence and activation of genes of the 3-hydroxypropionate/4-hydroxybutyrate cycle indicated autotrophy during ammonia oxidation. In the enrichment culture, ammonium was oxidized to nitrite by the AOA and subsequently to nitrate by Nitrospina-like bacteria. Our experiments suggest that AOA may be important nitrifiers in low-oxygen environments, such as oxygen-minimum zones and marine sediments.


On elastic nanoindentation of coated half-spaces by point indenters of non-ideal shapes.
The elastic contact of non-ideal conical and Berkovich indenters with bi-layer half-spaces is investigated. Blunted tips are simulated as smooth surfaces. The boundary element method is employed to carry out the numerical simulations of nanoindentation. An analytical analysis of the influence of the coating thickness and the tip bluntness magnitude on the nanoindentation loading curve is realized. The dimensionless compression force is introduced in order to describe the nanoindentation at different approaches between the indenter and the coated half-space. A practical technique for determining the Young's modulus of coatings is proposed. The technique is based on the modelling of indentation of the blunted indenter tip into the coating/substrate composite. This technique is applied to the nanoindentation study of nanocrystalline Cr coatings on silicon and glass substrates being tested by a diamond Berkovich indenter with a blunted tip.


The distributional impact of taxing sugar-sweetened beverages: findings from an extended cost-effectiveness analysis in South Africa.
Facing increasing obesity prevalence and obesity-related disease burden, South Africa has devised an obesity prevention strategy that includes a recently implemented tax on the sugar content of sugar-sweetened beverages (SSB). We assess the potential distributional impact (across socioeconomic groups) of this tax on type 2 diabetes mellitus (T2DM) incidence and associated mortality and its financial burden on households. We conducted an extended cost-effectiveness analysis of the new 10% tax on SSBs in South Africa, and estimated: the averted premature deaths related to T2DM, the financial benefits to households (out-of-pocket (OOP) medical costs and indirect costs due to productivity losses averted), the increased government tax revenues and healthcare savings for the government, all across income quintiles. A 10% SSB tax increase would avert an estimated 8000 T2DM-related premature deaths over 20 years, with most deaths averted among the third and fourth income quintiles. The government would save about South African rand (ZAR) 2 billion (US$140 million) in subsidised healthcare over 20 years; and would raise ZAR6 billion (US$450 million) in tax revenues per annum. The bottom two quintiles would bear the smallest tax burden increase (36% of the additional taxes). The bottom two income quintiles would also have the lowest savings in OOP payments due to significant subsidisation provided by government healthcare. Lastly, an estimated 32 000 T2DM-related cases of catastrophic expenditures and 12 000 cases of poverty would be averted. SSB taxation would have a substantial distributional impact on obesity-related premature deaths, cost savings to the government and the financial outcomes of South Africa's population.


Unpacking the key components of a programme to improve the timeliness of hip-fracture care: a mixed-methods case study.
Delay to surgery for patients with hip fracture is associated with higher incidence of post-operative complications, prolonged recovery and length of stay, and increased mortality. Therefore, many health care organisations launch improvement programmes to reduce the wait for surgery. The heterogeneous application of similar methods, and the multifaceted nature of the interventions, constrain the understanding of which method works, when, and how. In complex acute care settings, another concern is how changes for one patient group influence the care for other groups. We therefore set out to analyse how multiple components of hip-fracture improvement efforts aimed to reduce the time to surgery influenced that time both for hip-fracture patients and for other acute surgical orthopaedic inpatients. This study is an observational mixed-methods single case study of improvement efforts at a Swedish acute care hospital, which triangulates control chart analysis of process performance data over a five year period with interview, document, and non-participant observation data. The improvement efforts led to an increase in the monthly percentage of hip-fracture patients operated within 24 h of admission from an average of 47% to 83%, with performance predictably ranging between 67% and 98% if the process continues unchanged. Meanwhile, no significant changes in lead time to surgery for other acute surgical orthopaedic inpatients were observed. Interview data indicated that multiple intervention components contributed to making the process more reliable. The triangulation of qualitative and quantitative data, however, indicated that key changes that improved performance were the creation of a process improvement team and having an experienced clinician coordinate demand and supply of surgical services daily and enhance pre-operative patient preparation. Timeliness of surgery for patients with hip fracture in a complex hospital setting can be substantially improved without displacing other patient groups, by involving staff in improvement efforts and actively managing acute surgical procedures.


Erysipelas or cellulitis with a prosthetic joint in situ.
We describe a case of a 60-year old male who developed an acute prosthetic joint infection (PJI) of the knee, secondary to erysipelas of the lower leg due to beta-hemolytic Group G streptococci. As it is unknown how often this phenomenon occurs in patients with prosthetic implants and which patients are most prone to develop this complication, we analyzed: i) the incidence of the development of a PJI in these patients and ii) the clinical characteristics of streptococcal PJI during an episode of erysipelas/cellulitis. Based on a retrospective analysis of patients with a prosthetic implant in situ presenting at the emergency department with erysipelas/cellulitis, 1 out of 10 patients developed a PJI. An additional analysis within a multicenter cohort on streptococcal PJI demonstrated in 22 patients that a secondary PJI due to erysipelas/cellulitis mostly develops in young implants (<5 years old). In 20 cases (91%), the skin infection was in the same limb as the joint prosthesis suggesting contiguous spread of bacteria. These data emphasizes the importance of preventive measures to reduce the occurrence of skin infections in patients with prosthetic implants, and if an erysipelas or cellulitis does occur, to monitor patients carefully.


GloPID-R report on Chikungunya, O'nyong-nyong and Mayaro virus, part I: Biological diagnostics.
The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) Chikungunya (CHIKV), O'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group is investigating the natural history, epidemiology and medical management of infection by these viruses, to identify knowledge gaps and to propose recommendations for direct future investigations and rectification measures. Here, we present the first report dedicated to diagnostic aspects of CHIKV, ONNV and MAYV. Regarding diagnosis of the disease at the acute phase, molecular assays previously described for the three viruses require further evaluation, standardized protocols and the availability of international standards representing the genetic diversity of the viruses. Detection of specific IgM would benefit from further investigations to clarify the extent of cross-reactivity among the three viruses, the sensitivity of the assays, and the possible interfering role of cryoglobulinaemia. Implementation of reference panels and external quality assessments for both molecular and serological assays is necessary. Regarding sero-epidemiological studies, there is no reported high-throughput assay that can distinguish among these different viruses in areas of potential co-circulation. New specific tools and/or improved standardized protocols are needed to enable large-scale epidemiological studies of public health relevance to be performed. Considering the high risk of future CHIKV, MAYV and ONNV outbreaks, the Working Group recommends that a major investigation should be initiated to fill the existing diagnostic gaps.


Raising the thermoelectric performance of p-type PbS with endotaxial nanostructuring and valence-band offset engineering using CdS and ZnS.
We have investigated in detail the effect of CdS and ZnS as second phases on the thermoelectric properties of p-type PbS. We report a ZT of ~1.3 at 923 K for 2.5 at.% Na-doped p-type PbS with endotaxially nanostructured 3.0 at.% CdS. We attribute the high ZT to the combination of broad-based phonon scattering on multiple length scales to reduce (lattice) thermal conductivity and favorable charge transport through coherent interfaces between the PbS matrix and metal sulfide nanophase precipitates, which maintains the requisite high carrier conductivity and the associated power factor. Similar to large ionically bonded metal sulfides (ZnS, CaS, and SrS), the covalently bonded CdS can also effectively reduce the lattice thermal conductivity in p-type PbS. The presence of ubiquitous nanostructuring was confirmed by transmission electron microscopy. Valence and conduction band energy levels of the NaCl-type metal sulfides, MS (M = Pb, Cd, Zn, Ca, and Sr) were calculated from density functional theory to gain insight into the band alignment between PbS and the second phases in these materials. The hole transport is controlled by band offset minimization through the alignment of valence bands between the host PbS and the embedded second phases, MS (M = Cd, Zn, Ca, and Sr). The smallest valence band offset of about 0.13 eV at 0 K was found between PbS and CdS which is diminished further by thermal band broadening at elevated temperature. This allows carrier transport between the endotaxially aligned components (i.e., matrix and nanostructure), thus minimizing significant deterioration of the hole mobility and power factor. We conclude the thermoelectric performance of the PbS system and, by extension, other systems can be enhanced by means of a closely coupled phonon-blocking/electron-transmitting approach through embedding endotaxially nanostructured second phases.


Continuous-flow column study of reductive dehalogenation of PCE upon bioaugmentation with the Evanite enrichment culture.
A continuous-flow anaerobic column experiment was conducted to evaluate the reductive dechlorination of tetrachloroethene (PCE) in Hanford aquifer material after bioaugmentation with the Evanite (EV) culture. An influent PCE concentration of 0.09 mM was transformed to vinyl chloride (VC) and ethene (ETH) within a hydraulic residence time of 1.3 days. The experimental breakthrough curves were described by the one-dimensional two-site-nonequilibrium transport model. PCE dechlorination was observed after bioaugmentation and after the lactate concentration was increased from 0.35 to 0.67 mM. At the onset of reductive dehalogenation, cis-dichloroethene (c-DCE) concentrations in the column effluent exceeded the influent PCE concentration indicating enhanced PCE desorption and transformation. When the lactate concentration was increased to 1.34 mM, c-DCE reduction to vinyl chloride (VC) and ethene (ETH) occurred. Spatial rates of PCE and VC transformation were determined in batch-incubated microcosms constructed with aquifer samples obtained from the column. PCE transformation rates were highest in the first 5 cm from the column inlet and decreased towards the column effluent. Dehalococcoides cell numbers dropped from approximately 73.5% of the total Bacterial population in the original inocula, to about 0.5% to 4% throughout the column. The results were consistent with estimates of electron donor utilization, with 4% going towards dehalogenation reactions.


Systematic review of proposed definitions of nocturnal polyuria and population-based evidence of their diagnostic accuracy.
Background Evidence of diagnostic accuracy for proposed definitions of nocturnal polyuria is currently unclear. Purpose Systematic review to determine population-based evidence of the diagnostic accuracy of proposed definitions of nocturnal polyuria based on data from frequency-volume charts. Methods Seventeen pre-specified search terms identified 351 unique investigations published from 1990 to 2016 in BIOSIS, Embase, Embase Alerts, International Pharmaceutical Abstract, Medline, and Cochrane. Thirteen original communications were included in this review based on pre-specified exclusion criteria. Data were extracted from each paper regarding subject age, sex, ethnicity, health status, sample size, data collection methods, and diagnostic discrimination of proposed definitions including sensitivity, specificity, positive and negative predictive value. Results The sample size of study cohorts, participant age, sex, ethnicity, and health status varied considerably in 13 studies reporting on the diagnostic performance of seven different definitions of nocturnal polyuria using frequency-volume chart data from 4968 participants. Most study cohorts were small, mono-ethnic, including only Caucasian males aged 50 or higher with primary or secondary polyuria that were compared to a control group of healthy men without nocturia in prospective or retrospective settings. Proposed definitions had poor discriminatory accuracy in evaluations based on data from subjects independent from the original study cohorts with findings being similar regarding the most widely evaluated definition endorsed by ICS. Conclusions Diagnostic performance characteristics for proposed definitions of nocturnal polyuria show poor to modest discrimination and are not based on sufficient level of evidence from representative, multi-ethnic population-based data from both females and males of all adult ages.


Community-oriented primary care: historical perspective.
Community-oriented primary care (COPC) is a systematic approach to health care based upon principles derived from epidemiology, primary care, preventive medicine, and health promotion. We describe the development of COPC from an historical perspective. A critical assessment of current trends and implication for physician education and practice of COPC will be discussed in a companion article in the next issue of The Journal. MEDLINE was searched using the key phrase "community-oriented primary care" Other sources of information included books and other documents. In the 1950s, Sydney Kark showed dramatic positive changes in the health status of the population of Pholela, South Africa, using this approach. Similar approaches showed positive change in the health status of poor and underserved populations in the United States. The results were so impressive that the Institute of Medicine recommended widespread application of COPC in the United States. Successful COPC practices, however, have historically required considerable external funding from private and government sources. Thus, controversy about the feasibility of implementation of COPC in mainstream primary care practices developed. Schools of medicine and the discipline of family medicine have struggled to implement effective training in COPC within traditional medical school and residency structures. Yet, the societal need for recognition of and intervention in community health problems and coordination of community health resources continues.


Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.
4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.


Daily physical activity predicts degree of insulin resistance: a cross-sectional observational study using the 2003-2004 National Health and Nutrition Examination Survey.
This study examined the independent association of objectively measured physical activity on insulin resistance while controlling for confounding variables including: cardiorespiratory fitness, adiposity, sex, age, and smoking status. Data were obtained from National Health and Nutrition Examination Survey 2003-2004, a cross-sectional observational study conducted by the National Center for Health Statistics of the Centers for Disease Control that uses a stratified, multistage probability design to obtain a nationally representative sample of the U.S. population. The analysis included 402 healthy U.S. adults with valid accelerometer, cardiorespiratory fitness, and fasting plasma glucose and insulin concentrations. After controlling for relevant confounding variables we performed a multiple linear regression to predict homeostatic model of insulin resistance (HOMA-IR) based on average daily minutes of moderate-to-vigorous physical activity (MVPA). In our bivariate models, MVPA, cardiorespiratory fitness and body fat percentage were all significantly correlated with log HOMA-IR. In the complete model including MVPA and relevant confounding variables, there were strong and significant associations between MVPA and log HOMA-IR (β= -0.1607, P=0.004). In contrast the association between cardiorespiratory fitness and log HOMA-IR was not significant. When using an objective measure of physical activity the amount of time engaged in daily physical activity was associated with lower insulin resistance, whereas higher cardiorespiratory fitness was not. These results suggest that the amount of time engaged in physical activity may be an important determinant for improving glucose metabolism.


Aluminum plasmonics: optimization of plasmonic properties using liquid-prism-coupled ellipsometry.
We have established a method to quantify and optimize the plasmonic behavior of aluminum thin films by coupling spectroscopic ellipsometry into surface plasmon polaritons using a liquid prism cell in a modified Otto configuration. This procedure was applied to Al thin films deposited by four different methods, as well as to single crystal Al substrates, to determine the broadband optical constants and calculate plasmonic figures of merit. The best performance was achieved with Al films that have been sputter-deposited at high temperatures of 350°C, followed by chemical mechanical polishing. This combination of temperature and post-processing produced aluminum films with both large grain size and low surface roughness. Comparing these figures of merit with literature values of gold, silver, and copper shows that at blue and ultraviolet wavelengths, optimized aluminum has the highest figure of merit of all materials studied. We further employ the Ashcroft and Sturm theory of optical conductivity to extract the electron scattering times for the Drude and effective interband transitions, interband transition energies, and the optical mass of electrons.


Human essential fatty acid deficiency: treatment by topical application of linoleic acid.
An essential fatty acid (EFA) deficiency developed in a 19-year-old man who was being maintained on a long-term regimen of fat-free, intravenous hyperalimentation fluids. The EFA deficiency was reversed after 21 days by daily, topical application of linoleic acid to the patient's skin. The ratio of eicosatrienoic acid (20:3, n-9) to eicosatetraenoic acid (20:4, n-6) decreased to normal levels in the skin and serum with clinical improvement of the EFA deficiency syndrome. The cutaneous manifestations (scalp dermatitis, alopecia, and depigmentation of hair) were reversed with continued, topical application of safflower oil, which contains 60% to 70% linoleic acid.


Fuzzily Connected Multimodel Systems Evolving Autonomously From Data Streams.
A general framework and a holistic concept are proposed in this paper that combine computationally light machine learning from streaming data with the online identification and adaptation of dynamic systems in regard to their structure and parameters. According to this concept, the system is assumed to be decomposable into a set of fuzzily connected simple local models. The main thrust of this paper is in the development of an original approach for the self-design, self-monitoring, self-management, and self-learning of such systems in a dynamic manner from data streams which automatically detect and react to the shift in the data distribution by evolving the system structure. Novelties of this contribution lie in the following: 1) the computationally simple approach (simpl_e_Clustering-simplified evolving Clustering) to data space partitioning by recursive evolving clustering based on the relative position of the new data sample to the mean of the overall data, 2) the learning technique for online structure evolution as a reaction to the shift in the data distribution, 3) the method for online system structure simplification based on utility and inputs/feature selection, and 4) the novel graphical illustration of the spatiotemporal evolution of the data stream. The application domain for this computationally efficient technique ranges from clustering, modeling, prognostics, classification, and time-series prediction to pattern recognition, image segmentation, vector quantization, etc., to more general problems in various application areas, e.g., intelligent sensors, mobile robotics, advanced manufacturing processes, etc.


Cereal-based oral rehydration therapy. I. Clinical studies.
Studies of "improved" oral rehydration solutions, in which glucose polymers (starch) derived from rice or other cereals were added to improve cotransport of sodium and to promote sodium and water absorption, have been reported. These solutions were administered to decrease diarrhea volume and duration, reduce vomiting, and replace volume loss in stools. In clinical trials of children and adults with high-output diarrhea, such as in cases of cholera, the use of cereal-based oral rehydration solutions (ORS) compared with glucose-based ORS produced significant (20% to 53%) reductions in stool volumes. In one study the duration of diarrhea was shortened by 30%. In noncholera diarrhea in children, cereal-based ORS was as effective as glucose-based ORS. Although the amino acid transport systems were intact in patients with cholera, the addition of glycine to glucose-based or rice-based ORS did not reduce stool volume or duration of diarrhea. The exception was alanine, which reduced stool output and ORS requirements. More research is needed to determine the optimal mix of starch, amino acids, oligopeptides, and proteins that would utilize the absorptive active transport systems maximally to reduce fluid losses and duration of diarrhea.


Mate-sampling costs and sexy sons.
Costly female mating preferences for purely Fisherian male traits (i.e. sexual ornaments that are genetically uncorrelated with inherent viability) are not expected to persist at equilibrium. The indirect benefit of producing 'sexy sons' (Fisher process) disappears: in some models, the male trait becomes fixed; in others, a range of male trait values persist, but a larger trait confers no net fitness advantage because it lowers survival. Insufficient indirect selection to counter the direct cost of producing fewer offspring means that preferences are lost. The only well-cited exception assumes biased mutation on male traits. The above findings generally assume constant direct selection against female preferences (i.e. fixed costs). We show that if mate-sampling costs are instead derived based on an explicit account of how females acquire mates, an initially costly mating preference can coevolve with a male trait so that both persist in the presence or absence of biased mutation. Our models predict that empirically detecting selection at equilibrium will be difficult, even if selection was responsible for the location of the current equilibrium. In general, it appears useful to integrate mate sampling theory with models of genetic consequences of mating preferences: being explicit about the process by which individuals select mates can alter equilibria.


A multivariate approach to assess habitat integrity in urban streams using benthic macroinvertebrate metrics.
Benthic macroinvertebrates are widely used as indicators of the health of freshwater ecosystems, responding both to water quality and to the hydromorphological integrity. In urban streams, evaluations can be tricky for the synergistic effects of multiple stressors and confounding factors. In these situations, the most broadly used multimetric indices can be used to assess the overall damage to the invertebrate community and, thus, the overall anthropogenic pressure, but they do not allow to understand the specific causal effects. Particularly, habitat loss due to morphological alterations can be difficult to evaluate, especially due to the often concurrent disturbance caused by water pollution. We used a multivariate approach to focus on the characteristics of the streams and rivers in an urban district and to define which macroinvertebrate metrics should be used to assess the influence of the different kinds of alteration in a severely damaged environment. Some metrics enabling the assessment of habitat loss (ratio of oligochaeta, ratio of filterers) were identified. These metrics may help to raise a better awareness in the evaluation of river restoration success and, thus, in the support of decision-making processes.