A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components.
We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular-spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8-1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long-lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3-12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6-1 Hz) than under urethane anesthesia (0.3-0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15-30 Hz), relatively short-lasting (15-25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long-lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS)


Can district nurses and care home staff improve bowel care for older people using a clinical benchmarking tool?
A quasi-experimental study tested a clinical benchmarking tool (Essence of Care) to improve bowel-related care for older people living in six care homes. In the intervention care homes, district nurses and care home staff used the clinical benchmarking tool to discuss and plan how to improve bowel care for residents. In the control care homes, staff were provided with detailed information about the residents and continence services contact details. The intervention was acceptable to care home and district nursing staff, and possible to incorporate into existing working patterns. The study did not demonstrate a significant reduction in bowel-related problems, although there was evidence in one care home of reduction in episodes of avoidable faecal incontinence. At an individual level of care, there were observable benefits, and examples of person-centred care were prompted through participating in the intervention and improved staff awareness. Clinical benchmarking tools can be used to structure discussion between district nurses and care home staff to review and plan care for residents. However, it takes time to achieve change and embedding this kind of approach requires either robust pre-existing working relationships or the involvement of a facilitator.


Hepatosplenic T-cell lymphoma: a rare but challenging entity.
Hepatosplenic T-cell lymphoma (HSTCL) is a rare T-cell neoplasm that most commonly arises from a small subset of γ/δ T-cell receptor-expressing lymphocytes. HSTCL is more common in adolescent and young adults and has a rapidly progressive clinical course and poor outcome due to its refractoriness to conventional chemotherapy regimens. Approximately 20% of the cases arise in the background of chronic immunosuppression or immune dysregulation. Patients commonly present with constitutional symptoms, hepatic and liver enlargement, and cytopenias; hematophagocytic syndrome can also occur. The most frequent chromosomal aberrations associated with HSTCL are isochromosome 7q and trisomy 8, and most cases harbor mutations in genes involved in chromatin modification or the JAK/STAT pathway. The rarity of this disease, along with lack of nodal involvement and presenting symptoms that mimic different entities including infectious etiologies, makes this lymphoma a significant diagnostic challenge. In this review, we highlight the clinical and pathologic features of HSTCL. Moreover, we summarize the results of recent molecular studies suggesting potential targets for novel therapeutics strategies.


In-vivo microstructural anatomy of beta-zone parapapillary atrophy in glaucoma.
To assess the microstructural anatomy of clinical β-zone parapapillary atrophy (βPPA) by using Fourier-domain optical coherence tomography (FD-OCT). Color photographs and horizontal cross-sectional FD-OCT images of the optic disc and parapapillary retina were obtained in 24 eyes (24 patients with glaucoma or suspected glaucoma) with βPPA. The distances between the temporal disc margin and parapapillary landmarks (clinical βPPA margin and the edges of the retinal pigment epithelium [RPE], Bruch's membrane [BM], and the photoreceptor inner/outer segment [IS/OS] junction) were measured in 5 equally spaced horizontal meridians (total, 120 meridians). The mean age was 56 ± 13 (SD) years. In the five meridians, the mean distances from the temporal disc margin to the temporal βPPA margin and the edges of RPE, BM, and the IS/OS junction were 388 ± 173, 371 ± 174, 214 ± 204, and 502 ± 167 μm, respectively. The RPE edge corresponded to the βPPA margin in 78 (65%) of 120 meridians and ended within the βPPA in 42 (35%) of 120 meridians. The BM edge corresponded to the RPE edge in 13 (11%) of 120 meridians and was closer to the disc in 107 (89%) of 120 meridians. The disc margin corresponded to the BM edge in 20 (17%) of 120 meridians and to the edge of the border tissue of Elschnig in 100 (83%) of 120 meridians. The IS/OS junction edge was farther from the disc than the temporal βPPA margin was in all 24 eyes. The βPPA was not completely denuded of RPE, and there was a crescent-shaped area of photoreceptor degeneration or atrophy peripheral to the βPPA. The termination of the border tissue of Elschnig constituted the temporal disc margin in most eyes with βPPA.


Isolation of a novel thioflavin S-derived compound that inhibits BAG-1-mediated protein interactions and targets BRAF inhibitor-resistant cell lines.
Protein-protein interactions mediated through the C-terminal Bcl-2-associated athanogene (BAG) domain of BAG-1 are critical for cell survival and proliferation. Thioflavin S (NSC71948)-a mixture of compounds resulting from the methylation and sulfonation of primulin base-has been shown to dose-dependently inhibit the interaction between BAG-1 and Hsc70 in vitro. In human breast cancer cell lines, with high BAG-1 expression levels, Thioflavin S reduces the binding of BAG-1 to Hsc70, Hsp70, or CRAF and decreases proliferation and viability. Here, we report the development of a protocol for the purification and isolation of biologically active constituents of Thioflavin S and the characterization of the novel compound Thio-2. Thio-2 blocked the growth of several transformed cell lines, but had much weaker effects on untransformed cells. Thio-2 also inhibited the proliferation of melanoma cell lines that had become resistant to treatment with PLX4032, an inhibitor of mutant BRAF. In transformed cells, Thio-2 interfered with intracellular signaling at the level of RAF, but had no effect on the activation of AKT. Thio-2 decreased binding of BAG-1 to Hsc70 and to a lesser extent BRAF in vitro and in vivo, suggesting a possible mechanism of action. Given that tumors frequently develop resistance to kinase inhibitors during treatment, Thio-2 and related compounds may offer promising alternative strategies to currently available therapies.


Maternal feeding practices and feeding behaviors of Australian children aged 12-36 months.
To explore parents' perceptions of the eating behaviors and related feeding practices of their young children. Mothers (N=740) of children aged 12-36 months and born in South Australia were randomly selected by birth date in four 6-month age bands from a centralized statewide database and invited to complete a postal questionnaire. Valid completed questionnaires were returned for 374 children (51% response rate; 54% female). Although mothers generally reported being confident and happy in feeding their children, 23% often worried that they gave their child the right amount of food. Based on a checklist of 36 specified items, 15% of children consumed no vegetables in the previous 24 h, 11% no fruit and for a further 8% juice was the only fruit. Of 12 specified high fat/sugar foods and drinks, 11% of children consumed none, 20% one, 26% two, and 43% three or more. Six of eight child-feeding practices that promote healthy eating behaviors were undertaken by 75% parents 'often' or 'all of the time'. However, 8 of 11 practices that do not promote healthy eating were undertaken by a third of mothers at least 'sometimes'. In this representative sample, dietary quality issues emerge early and inappropriate feeding practices are prevalent thus identifying the need for very early interventions that promote healthy food preferences and positive feeding practices. Such programs should focus not just on the 'what', but also the 'how' of early feeding, including the feeding relationship and processes appropriate to developmental stage.


Cross-activating invariant NKT cells and kupffer cells suppress cholestatic liver injury in a mouse model of biliary obstruction.
Both Kupffer cells and invariant natural killer T (iNKT) cells suppress neutrophil-dependent liver injury in a mouse model of biliary obstruction. We hypothesize that these roles are interdependent and require iNKT cell-Kupffer cell cross-activation. Female, wild-type and iNKT cell-deficient C57Bl/6 mice were injected with magnetic beads 3 days prior to bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. On day three post-BDL, the animals were euthanized and the livers dissected. Necrosis was scored; Kupffer cells were isolated and cell surface marker expression (flow cytometry), mRNA expression (qtPCR), nitric oxide (NO (.) ) production (Griess reaction), and protein secretion (cytometric bead-array or ELISAs) were determined. To address the potential role of NO (.) in suppressing neutrophil accumulation, a group of WT mice received 1400W, a specific inducible nitric oxide synthase (iNOS) inhibitor, prior to BDL. To clarify the mechanisms underlying Kupffer cell-iNKT cell cross-activation, WT animals were administered anti-IFN-γ or anti-lymphocyte function-associated antigen (LFA)-1 antibody prior to BDL. Compared to their WT counterparts, Kupffer cells obtained from BDL iNKT cell-deficient mice expressed lower iNOS mRNA levels, produced less NO (.) , and secreted more neutrophil chemoattractants. Both iNOS inhibition and IFN-γ neutralization increased neutrophil accumulation in the livers of BDL WT mice. Anti-LFA-1 pre-treatment reduced iNKT cell accumulation in these same animals. These data indicate that the LFA-1-dependent cross-activation of iNKT cells and Kupffer cells inhibits neutrophil accumulation and cholestatic liver injury.


The epidemiology of Chagas' disease in a hyperendemic area of Cochabamba, Bolivia: a clinical study including electrocardiography, seroreactivity to Trypanosoma cruzi, xenodiagnosis, and domiciliary triatomine distribution.
A clinicoepidemiologic survey of Chagas' disease was conducted in the remote rural village of Tabacal in southcentral Cochabamba, Bolivia. In June and July 1988, we interviewed and examined 153 of 160 villagers > five years old for signs and symptoms of Chagas' disease. All participants had electrocardiograms (EKGs) and serologic analysis performed, and 20 villagers underwent xenodiagnosis. All 40 houses in the village were examined for triatomes, and house construction materials and defects were recorded. Seventy-four percent of all villagers had serologic evidence of Chagas' disease, and were defined as cases. Cases were three and one-half times more likely to have signs and symptoms of heart failure than non-cases (P = 0.2) and were nine times more likely to have EKG conduction abnormalities than non-cases (P = 0.02). Thirty-three percent of all EKG conduction defects occurred in individuals < 35 years of age. All dwellings had evidence of triatome infestation; 72% of the triatomes collected were positive for metacyclic trypanosomes. We conclude that Trypanosoma cruzi infection is highly prevalent in Tabacal and is a common cause of morbidity in that region.


Can contextualization increase understanding during man-machine communication? A theory-driven study.
The Internet offers unlimited possibilities for finding health information. However, the user is often faced with the problem of understanding it. Contextualization has a role to play in enhancing the user's comprehension. We report on a study which addresses this issue, using a theoretical model of communication whose central theme is that of context. A randomized controlled experimental design was chosen, using as a test-bed the website SeniorGezond we had previously developed. The study was composed of a pre-test, the intervention with the website and a post-test. Participants (n=40) were randomly assigned to exposure or no exposure to contextualization with the website. Results show that contextualization increases understanding for non-knowledgeable users. Furthermore, the participant's cognitive style was found to be a significant factor on understanding. We also found that participants bring their own contexts such as social context and psychological context to support their understanding.


Worldwide distribution of the conjugative Clostridium perfringens tetracycline resistance plasmid, pCW3.
The aim of this study was to test the hypothesis that all conjugative R-plasmids of Clostridium perfringens are closely related to the previously characterized tetracycline resistance plasmid, pCW3. Fourteen conjugative R-plasmids derived from 11 C. perfringens strains isolated in Australia, the United States, France, Belgium, and Japan were analyzed. Eleven of the plasmids encoded tetracycline resistance while three carried both tetracycline and chloramphenicol resistance. Each of these plasmids was compared, by restriction analysis, to the reference plasmid, pCW3. Seven of the tetracycline resistance plasmids had EcoRI, XbaI, and ClaI restriction profiles that were identical to those of the corresponding pCW3 digests. The seven remaining R-plasmids were different from pCW3. Comparison of partial restriction maps of these plasmids with a complete map of pCW3 indicated that they contained at least 17 kb of DNA that also was present in pCW3. Hybridization analysis confirmed that these plasmids shared substantial homology with pCW3. The three tetracycline and chloramphenicol resistance plasmids frequently lost a 6-kb chloramphenicol resistance segment during conjugation. Cloning experiments showed that the chloramphenicol resistance determinant was expressed in Escherichia coli and that the chloramphenicol resistance gene of one of these plasmids, pIP401, was contained within a 1.5-kb region of the 6-kb deletion segment. Hybridization analysis indicated that the deletion segment of pIP401 was related to those of the other two chloramphenicol resistance plasmids. During the course of this study, conjugative R-plasmids which appear to be identical to pCW3 or closely related to pCW3 were identified from C. perfringens strains from human, animal and environmental sources in five countries. It is concluded that C. perfringens strains in humans and animals throughout the world have overlapping gene pools and that all the conjugative C. perfringens R-plasmids examined probably evolved from a pCW3-like element.


The gene for the ligand binding chain of the human interferon gamma receptor.
In order to characterize the gene encoding the ligand binding (1(st); alpha) chain of the human IFN-gamma receptor, two overlapping cosmid clones were analyzed. The gene spans over 25 kilobases (kb) of the genomic DNA and has seven exons. The extracellular domain is encoded by exons 1 to 5 and by part of exon 6. The transmembrane region is also encoded by exon 6. Exon 7 encodes the intracellular domain and the 3' untranslated portion. The gene was located on chromosome 6q23.1, as determined by in situ hybridization. The 4 kb region upstream (5') of the gene was sequenced and analyzed for promoter activity. No consensus-matching TATA or CAAT boxes in the 5' region were found. Potential binding sites for Sp1, AP-1, AP-2, and CREB nuclear factors were identified. Compatible with the presence of the Sp1/AP-2 sites and the lack of TATA box, S1-nuclease mapping experiments showed multiple transcription initiation sites. Promoter activity of the 5' flanking region was analyzed with two different reporter genes: the Escherichia coli chloramphenicol acetyltransferase and human growth hormone. The smallest 5' region of the gene that still had full promoter activity was 692 base pairs in length. In addition, we found sequences belonging to the oldest family of Alu repeats, 2 - 3 kb upstream of the gene, which could be useful for genetic studies.


Dimensional psychotic experiences in adolescence: Evidence from a taxometric study of a community-based sample.
Psychotic experiences of varying severity levels are common in adolescence. It is not known whether beyond a certain severity in the general population, psychotic experiences represent a categorically distinct phenomena to milder psychotic experiences. We employed taxometric analytic procedures to determine whether psychotic experiences in adolescence are taxonic (i.e. categorical) or dimensional. Six different psychotic experiences were assessed in a community sample of approximately 5000 adolescents. Three taxometric procedures were conducted. Across all procedures, there was no evidence of a taxon (i.e. a separate latent population) underlying psychotic experiences in adolescence. Rather, a dimensional structure was supported. The results support the notion that psychotic experiences are continuously distributed throughout the general population, and there is no clear discontinuity between milder and more severe psychotic experiences. Thus, these findings support the use of dimensional approaches to understanding psychotic experiences in etiological studies. In clinical practice, categorical cut-offs are needed: the present findings show that a 'natural' break point is not present for identifying severe psychotic experiences, and it is likely therefore that other criteria (such as general functioning) might better aid decision-making with regards to identifying individuals with severe psychotic experiences in need of care during adolescence.


Cephalometric evaluation in children presenting adapted swallowing during mixed dentition.
The tongue trust and anterior projection through the dental arcades during swallowing is known as Adapted Swallowing (AS) and is a common finding during mixed dentition. The authors studied the morphologic dentofacial characteristics through cephalometric measures in 38 girls and 35 boys, aged seven to nine years, presenting AS, as determined by the speech therapist evaluation. Cephalometric evaluation was obtained by Radiocef 2.0 software. The measurements studied were the mandibular and maxillary relations to the cranial base, the nasolabial angle, and the upper airway patency, as proposed by McNamara Jr (1984), and the convexity and facial axis angles and maxillary height from Ricketts (1960; 1981). Results, analyzed in relation to sex and racial group, showed an association of Class II facial convexity with the African Brazilian children with dark black skin. This classification does not reflect an abnormality as all African Brazilians studied were classified as class II, due to the fact that the standard measurements are based in the white American population. These findings point to the need of specific racial normative standard for evaluating orofacial and dental structures.


Characterization of the transcriptome of Haloferax volcanii, grown under four different conditions, with mixed RNA-Seq.
Haloferax volcanii is a well-established model species for haloarchaea. Small scale RNomics and bioinformatics predictions were used to identify small non-coding RNAs (sRNAs), and deletion mutants revealed that sRNAs have important regulatory functions. A recent dRNA-Seq study was used to characterize the primary transcriptome. Unexpectedly, it was revealed that, under optimal conditions, H. volcanii contains more non-coding sRNAs than protein-encoding mRNAs. However, the dRNA-Seq approach did not contain any length information. Therefore, a mixed RNA-Seq approach was used to determine transcript length and to identify additional transcripts, which are not present under optimal conditions. In total, 50 million paired end reads of 150 nt length were obtained. 1861 protein-coding RNAs (cdRNAs) were detected, which encoded 3092 proteins. This nearly doubled the coverage of cdRNAs, compared to the previous dRNA-Seq study. About 2/3 of the cdRNAs were monocistronic, and 1/3 covered more than one gene. In addition, 1635 non-coding sRNAs were identified. The highest fraction of non-coding RNAs were cis antisense RNAs (asRNAs). Analysis of the length distribution revealed that sRNAs have a median length of about 150 nt. Based on the RNA-Seq and dRNA-Seq results, genes were chosen to exemplify characteristics of the H. volcanii transcriptome by Northern blot analyses, e.g. 1) the transcript patterns of gene clusters can be straightforward, but also very complex, 2) many transcripts differ in expression level under the four analyzed conditions, 3) some genes are transcribed into RNA isoforms of different length, which can be differentially regulated, 4) transcripts with very long 5'-UTRs and with very long 3'-UTRs exist, and 5) about 30% of all cdRNAs have overlapping 3'-ends, which indicates, together with the asRNAs, that H. volcanii makes ample use of sense-antisense interactions. Taken together, this RNA-Seq study, together with a previous dRNA-Seq study, enabled an unprecedented view on the H. volcanii transcriptome.


Does Nursing Home Ownership Change Affect Family Ratings on Experience with Care?
Person-centeredness may suffer in nursing homes (NHs) with recent ownership changes. This study identifies associations between ownership change and reported care experiences, important measures of person-centered care for long-term residents in Maryland NHs. Care experience measures and ownership change data were collected from Maryland Health Care Commission reports, which reported data on 220 Maryland NHs from 2011 and 2012. Facility and market covariates were obtained from 2011 NH Compare and Area Health Resource Files. Linear regression was used to examine whether ownership change in 2011 was associated with lower care experience ratings reported during April to June 2012. Dependent variables were overall care rating (scale 1-10), percentage of respondents answering that they would recommend the NH, and assessments of five care and resident life domains (scale 1-4). Care experiences reported in 2012 were high; however, after controlling for covariates, ownership change was associated with significant decreases in 6 out of 7 measures, including a 0.39-point decrease in overall care rating (p = .001). NH managers and policy makers should consider strategies to improve patient-centeredness after ownership change.


[Cerebral venous thrombosis imagiologic features in a pregnant woman].
Cerebral venous thrombosis (CVT) is a relatively rare but serious condition potentially reversible upon accurate diagnosis and adequate therapy. The peri-partum state and pregnancy are predisposing factors and TVC accounts for about 6% of maternal deaths. Its clinical symptoms depend on the the thrombus site and extension, and also on the existing collateral vessels network. We present the case of a 33 year-old woman, 13 weeks pregnant, that complained of headaches and whose cranial magnetic resonance imaging revealed a subtotal oclusión of the superior sagittal sinus. We discuss the imaging features of dural venous thrombosis in the acute phase.


Cognitive remediation for treatment-resistant depression: effects on cognition and functioning and the role of online homework.
Neurocognitive impairments are observed in depression and associated with poor functioning. This study examined the efficacy and the effectiveness of cognitive remediation with supplemental Internet-based homework in treatment-resistant depression. Participants were randomized to treatment or wait list control conditions. Treatment consisted of 10 weeks of weekly group sessions and daily online cognitive exercises completed at home. The participants were assessed on cognitive, mood, motivation, and functioning measures. There was a significant time by treatment interaction for attention/processing speed and verbal memory. Changes in functioning were not significant, although improved cognition predicted improvements in functioning. Number of minutes of online exercise was associated with greater cognitive improvements. Cognitive deficits are malleable with behavioral treatment in a mood disorder characterized by severe and persistent symptoms.


Establishing diagnostic criteria and treatment of subsegmental pulmonary embolism: A Delphi analysis of experts.
Improved imaging techniques have increased the incidence of subsegmental pulmonary embolism (ssPE). Indirect evidence is suggesting that ssPE may represent a more benign presentation of venous thromboembolism not necessarily requiring anticoagulant treatment. However, correctly diagnosing ssPE is challenging with reported low interobserver agreement, partly due to the lack of widely accepted diagnostic criteria. We sought to derive uniform diagnostic criteria for ssPE, guided by expert consensus. Based on an extensive literature review and expert opinion of a Delphi steering committee, two surveys including statements regarding diagnostic criteria and management options for ssPE were established. These surveys were conducted electronically among two panels, respectively: expert thoracic radiologists and clinical venous thromboembolism specialists. The Delphi method was used to achieve consensus after multiple survey rounds. Consensus was defined as a level of agreement >70%. Twenty-nine of 40 invited radiologists (73%) and 40 of 51 clinicians (78%) participated. Following two survey rounds by the expert radiologists, consensus was achieved on 15 of 16 statements, including on the established diagnostic criteria for ssPE (96% agreement): a contrast defect in a subsegmental artery, that is, the first arterial branch division of any segmental artery independent of artery diameter, visible in at least two subsequent axial slices, using a computed tomography scanner with a desired maximum collimator width of ≤1 mm. These criteria were approved by 83% of the clinical venous thromboembolism (VTE) specialists. The clinical expert panel favored anticoagulant treatment in case of prior VTE, antiphospholipid syndrome, pregnancy, cancer, and proximal deep vein thrombosis. The results of this analysis provide standard radiological criteria for ssPE that may be applicable in both clinical trials and practice.


Redefining Humicola sensu stricto and related genera in the Chaetomiaceae.
The traditional concept of the genus Humicola includes species that produce pigmented, thick-walled and single-celled spores laterally or terminally on hyphae or minimally differentiated conidiophores. More than 50 species have been described in the genus. Species commonly occur in soil, indoor environments, and compost habitats. The taxonomy of Humicola and morphologically similar genera is poorly understood in modern terms. Based on a four-locus phylogeny, the morphological concept of Humicola proved to be polyphyletic. The type of Humicola, H. fuscoatra, belongs to the Chaetomiaceae. In the Chaetomiaceae, species producing humicola-like thick-walled spores are distributed among four lineages: Humicola sensu stricto, Mycothermus, Staphylotrichum, and Trichocladium. In our revised concept of Humicola, asexual and sexually reproducing species both occur. The re-defined Humicola contains 24 species (seven new and thirteen new combinations), which are described and illustrated in this study. The species in this genus produce conidia that are lateral, intercalary or terminal on/in hyphae, and conidiophores are not formed or are minimally developed (micronematous). The ascospores of sexual Humicola species are limoniform to quadrangular in face view and bilaterally flattened with one apical germ pore. Seven species are accepted in Staphylotrichum (four new species, one new combination). Thick-walled conidia of Staphylotrichum species usually arise either from hyphae (micronematous) or from apically branched, seta-like conidiophores (macronematous). The sexual morph represented by Staphylotrichum longicolleum (= Chaetomium longicolleum) produces ascomata with long necks composed of a fused basal part of the terminal hairs, and ascospores that are broad limoniform to nearly globose, bilaterally flattened, with an apical germ pore. The Trichocladium lineage has a high morphological diversity in both asexual and sexual structures. Phylogenetic analysis revealed four subclades in this lineage. However, these subclades are genetically closely related, and no distinctive phenotypic characters are linked to any of them. Fourteen species are accepted in Trichocladium, including one new species, twelve new combinations. The type species of Gilmaniella, G. humicola, belongs to the polyphyletic family Lasiosphaeriaceae (Sordariales), but G. macrospora phylogenetically belongs to Trichocladium. The thermophilic genus Mycothermus and the type species My. thermophilum are validated, and one new Mycothermus species is described. Phylogenetic analyses show that Remersonia, another thermophilic genus, is sister to Mycothermus and two species are known, including one new species. Thermomyces verrucosus produces humicola-like conidia and is transferred to Botryotrichum based on phylogenetic affinities. This study is a first attempt to establish an inclusive modern classification of Humicola and humicola-like genera of the Chaetomiaceae. More research is needed to determine the phylogenetic relationships of "humicola"-like species outside the Chaetomiaceae.


Morphologic assessment of leukocyte-endothelial cell interactions in mesenteric venules subjected to ischemia and reperfusion.
Intravital microscopic studies of the mesenteric microcirculation have demonstrated that leukocyte adherence and emigration in postcapillary venules are a characteristic feature of tissues exposed to ischemia-reperfusion. The objectives of this study were to determine whether: (1) neutrophils are the predominant leukocytes that adhere and emigrate in postischemic mesenteric venules, and (2) leukocyte adherence and/or emigration are a prerequisite for reperfusion-induced increases in venular permeability. Leukocyte kinetics in cat mesenteric venules (25-35 microns diameter) were evaluated using both intravital microscopy and quantitative morphometry. The intestine and mesentery were exposed to 60 min of ischemia, followed by 60 min reperfusion. Some animals were pretreated with a monoclonal antibody (MoAb IB4) against the leukocyte adhesion glycoprotein, CD11/CD18. Vessels observed by intravital microscopy and adjacent venules of similar diameter were excised and processed for light (LM) and electron microscopy (EM). Horseradish peroxidase (HRP), administered intravenously, was used to assess vascular permeability by EM. By LM, the control (nonischemic) mesentery is sparsely populated by plasma cells, mast cells, and leukocytes; 30-50% of the resident population is neutrophils. Ischemia-reperfusion led to a significant increase in the number of extravascular cells, with neutrophils accounting for greater than 80% of the total cell population. Control and ischemic venules demonstrated no leakage of HRP into the interstitium. However, venules exposed to ischemia and reperfusion demonstrated HRP leakage between endothelial cells and into the surrounding interstitium; neutrophils were adherent to the luminal surface of the endothelium, transmigrating the vessel wall, and in the surrounding interstitium. Animals pretreated with MoAb IB4 presented the same cell profile as nonischemic controls, with no adherent or transmigrating neutrophils. However, some HRP leakage was noted following reperfusion in venules treated with MoAb IB4. The results of this study indicate that: (1) neutrophils are the predominate leukocytes that adhere and emigrate in postischemic venules, and (2) inhibition of leukocyte adhesion does not completely prevent the venular dysfunction associated with ischemia-reperfusion.


Machine-Learning Algorithms to Code Public Health Spending Accounts.
Government public health expenditure data sets require time- and labor-intensive manipulation to summarize results that public health policy makers can use. Our objective was to compare the performances of machine-learning algorithms with manual classification of public health expenditures to determine if machines could provide a faster, cheaper alternative to manual classification. We used machine-learning algorithms to replicate the process of manually classifying state public health expenditures, using the standardized public health spending categories from the Foundational Public Health Services model and a large data set from the US Census Bureau. We obtained a data set of 1.9 million individual expenditure items from 2000 to 2013. We collapsed these data into 147 280 summary expenditure records, and we followed a standardized method of manually classifying each expenditure record as public health, maybe public health, or not public health. We then trained 9 machine-learning algorithms to replicate the manual process. We calculated recall, precision, and coverage rates to measure the performance of individual and ensembled algorithms. Compared with manual classification, the machine-learning random forests algorithm produced 84% recall and 91% precision. With algorithm ensembling, we achieved our target criterion of 90% recall by using a consensus ensemble of ≥6 algorithms while still retaining 93% coverage, leaving only 7% of the summary expenditure records unclassified. Machine learning can be a time- and cost-saving tool for estimating public health spending in the United States. It can be used with standardized public health spending categories based on the Foundational Public Health Services model to help parse public health expenditure information from other types of health-related spending, provide data that are more comparable across public health organizations, and evaluate the impact of evidence-based public health resource allocation.


Long-term efficacy of Internet-based cognitive behavior therapy for obsessive-compulsive disorder with or without booster: a randomized controlled trial.
As relapse after completed cognitive behavior therapy (CBT) for obsessive-compulsive disorder (OCD) is common, many treatment protocols include booster programs to improve the long-term effects. However, the effects of booster programs are not well studied. In this study, we investigated the long-term efficacy of Internet-based CBT (ICBT) with therapist support for OCD with or without an Internet-based booster program. A total of 101 participants were included in the long-term follow-up analysis of ICBT. Of these, 93 were randomized to a booster program or no booster program. Outcome assessments were collected at 4, 7, 12 and 24 months after receiving ICBT. The entire sample had sustained long-term effects from pre-treatment to all follow-up assessments, with large within-group effect sizes (Cohen's d = 1.58-2.09). The booster group had a significant mean reduction in OCD symptoms compared to the control condition from booster baseline (4 months) to 7 months, but not at 12 or 24 months. Participants in the booster group improved significantly in terms of general functioning at 7, 12 and 24 months, and had fewer relapses. Kaplan-Meier analysis also indicated a significantly slower relapse rate in the booster group. The results suggest that ICBT has sustained long-term effects and that adding an Internet-based booster program can further improve long-term outcome and prevent relapse for some OCD patients.


Variations in risk attitude across race, gender, and education.
Significant disparities in health care utilization exist across gender and race. Little is known about the patient-specific factors that may contribute to this variation. This study examined variations in risk attitude across major sociodemographic groups. A survey elicited utility measures for health states under risk-insensitive and risk-sensitive conditions (time tradeoff and standard gamble methods, respectively). Risk attitude was modeled assuming constant proportional risk posture, thus the utility function used was a power function. A multivariable linear regression model was used to examine the relationship between risk attitude and sociodemographic factors. Of the 62 study subjects, the mean age was 47.6 years, 47% were female, and 33% were African American. Overall, 37% of respondents were decidedly risk averse, 37% moderately risk averse, 15% moderately risk seeking, and 11% decidedly risk seeking. Significant predictors of increasing risk aversion in multivariate modeling were white race (P < 0.01) and lower education (P < 0.05). Women also tended to be more risk averse (P = 0.07). This study found significant differences in risk attitude across race and educational status, with a smaller difference across gender. Further research is needed to validate these findings and clarify their contribution to racial and gender variations in health care utilization and their future role in decision and cost-effectiveness analyses.


Endothelial cell-specific molecule 2 (ECSM2) localizes to cell-cell junctions and modulates bFGF-directed cell migration via the ERK-FAK pathway.
Despite its first discovery by in silico cloning of novel endothelial cell-specific genes a decade ago, the biological functions of endothelial cell-specific molecule 2 (ECSM2) have only recently begun to be understood. Limited data suggest its involvement in cell migration and apoptosis. However, the underlying signaling mechanisms and novel functions of ECSM2 remain to be explored. A rabbit anti-ECSM2 monoclonal antibody (RabMAb) was generated and used to characterize the endogenous ECSM2 protein. Immunoblotting, immunoprecipitation, deglycosylation, immunostaining and confocal microscopy validated that endogenous ECSM2 is a plasma membrane glycoprotein preferentially expressed in vascular endothelial cells (ECs). Expression patterns of heterologously expressed and endogenous ECSM2 identified that ECSM2 was particularly concentrated at cell-cell contacts. Cell aggregation and transwell assays showed that ECSM2 promoted cell-cell adhesion and attenuated basic fibroblast growth factor (bFGF)-driven EC migration. Gain or loss of function assays by overexpression or knockdown of ECSM2 in ECs demonstrated that ECSM2 modulated bFGF-directed EC motility via the FGF receptor (FGFR)-extracellular regulated kinase (ERK)-focal adhesion kinase (FAK) pathway. The counterbalance between FAK tyrosine phosphorylation (activation) and ERK-dependent serine phosphorylation of FAK was critically involved. A model of how ECSM2 signals to impact bFGF/FGFR-driven EC migration was proposed. ECSM2 is likely a novel EC junctional protein. It can promote cell-cell adhesion and inhibit bFGF-mediated cell migration. Mechanistically, ECSM2 attenuates EC motility through the FGFR-ERK-FAK pathway. The findings suggest that ECSM2 could be a key player in coordinating receptor tyrosine kinase (RTK)-, integrin-, and EC junctional component-mediated signaling and may have important implications in disorders related to endothelial dysfunction and impaired EC junction signaling.


Why have microsaccades become larger? Investigating eye deformations and detection algorithms.
The reported size of microsaccades is considerably larger today compared to the initial era of microsaccade studies during the 1950s and 1960s. We investigate whether this increase in size is related to the fact that the eye-trackers of today measure different ocular structures than the older techniques, and that the movements of these structures may differ during a microsaccade. In addition, we explore the impact such differences have on subsequent analyzes of the eye-tracker signals. In Experiment I, the movement of the pupil as well as the first and fourth Purkinje reflections were extracted from series of eye images recorded during a fixation task. Results show that the different ocular structures produce different microsaccade signatures. In Experiment II, we found that microsaccade amplitudes computed with a common detection algorithm were larger compared to those reported by two human experts. The main reason was that the overshoots were not systematically detected by the algorithm and therefore not accurately accounted for. We conclude that one reason to why the reported size of microsaccades has increased is due to the larger overshoots produced by the modern pupil-based eye-trackers compared to the systems used in the classical studies, in combination with the lack of a systematic algorithmic treatment of the overshoot. We hope that awareness of these discrepancies in microsaccade dynamics across eye structures will lead to more generally accepted definitions of microsaccades.


p53 codon 72 polymorphism and human papillomavirus associated skin cancer.
Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC. Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV. The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant differences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts. These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer.


High-speed scanning stroboscopic fringe-pattern projection technology for three-dimensional shape precision measurement.
A high-speed scanning stroboscopic fringe-pattern projection system is designed. A high-speed rotating polygon mirror and a line-structured laser cooperate to produce stable and unambiguous stroboscopic fringe patterns. The system combines the rapidity of the grating projection with the high accuracy of the line-structured laser light source. The fringe patterns have fast frame rate, great density, high precision, and high brightness, with convenience and accuracy in adjusting brightness, frequency, linewidth, and the amount of phase shift. The characteristics and the stability of this system are verified by experiments. Experimental results show that the finest linewidth can reach 40 μm and that the minimum fringe cycle is 80 μm. Circuit modulation makes the light source system flexibly adjustable, easy to control in real time, and convenient to project various fringe patterns. Combined with different light intensity adjustment algorithms and 3D computation models, the 3D topography with high accuracy can be obtained for objects measured under different environments or objects with different sizes, morphologies, and optical properties. The proposed system shows a broad application prospect for fast 3D shape precision measurements, particularly in the industrial field of 3D online detection for precision devices.


In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment.
Rabbit antithrombin III (AT), purified by heparin-agarose, was labeled with iodine-131 by either the glucose oxidase-lactoperoxidase or iodine monochloride techniques. When intravenously injected, the disappearance of the 131I-AT from plasma was characterized by rapid initial decreases, and three-exponential equations were required for best fit of the plasma disappearance curves. This rapid 131I-AT removal was not caused by denaturation, as shown by comparison with results obtained when 131I-AT was biologically screened (injected into a first rabbit, and then transferred 16 h later in whole plasma to a second for kinetic evaluation) before injection. Thus, the same rapid initial loss of plasma 131I-AT was observed with screened preparations, and the plasma fractional catabolic rates of 0.716 +/- 0.048 and 0.673 +/- 0.051 day-1 for unscreened and screened 131I-AT were not significantly different. These results support the hypothesis that a vascular-endothelial AT compartment is present in rabbit. The fractions of the total-body AT in the plasma, the vascular-endothelial and the extravascular compartments were 0.337 +/- 0.031, 0.178 +/- 0.056, and 0.485 +/- 0.069, respectively. Two three-compartment kinetic models are discussed. The first pictures AT as distributing independently between plasma and two other compartments, and the second sees AT as first passing to the vascular-endothelial compartment, and then directly into the extravascular compartment. The plasma 131I-AT kinetic data was consistent with both models, but the sizes of the vascular-endothelial compartments were best predicted by the second. If AT catabolism was assigned to the plasma, both models generally underpredicted the whole-body radioactivities, while assignment of breakdown to the extravascular compartment generally resulted in overpredictions. This suggests that AT catabolism occurs from both plasma and extravascular compartments.


Three-dimensional analysis of optical forces generated by an active tractor beam using radial polarization.
We theoretically study the three-dimensional behavior of nanoparticles in an active optical conveyor. To do this, we solved the Langevin equation when the forces are generated by a focusing system at the near field. Analytical expressions for the optical forces generated by the optical conveyor were obtained by solving the Richards and Wolf vectorial diffraction integrals in an approximated form when a mask of two annular pupils is illuminated by a radially polarized Hermite-Gauss beam. Trajectories, in both the transverse plane and the longitudinal direction, are analyzed showing that the behavior of the optical conveyor can be optimized by conveniently choosing the configuration of the mask of the two annular pupils (inner and outer radius of the two rings) in order to trap and transport all particles at the focal plane.


Programming an Artificial Neural Network Tool for Spatial Interpolation in GIS - A Case Study for Indoor Radio Wave Propagation of WLAN.
Wireless communication networks offer subscribers the possibilities of free mobility and access to information anywhere at any time. Therefore, electromagnetic coverage calculations are important for wireless mobile communication systems, especially in Wireless Local Area Networks (WLANs). Before any propagation computation is performed, modeling of indoor radio wave propagation needs accurate geographical information in order to avoid the interruption of data transmissions. Geographic Information Systems (GIS) and spatial interpolation techniques are very efficient for performing indoor radio wave propagation modeling. This paper describes the spatial interpolation of electromagnetic field measurements using a feed-forward back-propagation neural network programmed as a tool in GIS. The accuracy of Artificial Neural Networks (ANN) and geostatistical Kriging were compared by adjusting procedures. The feedforward back-propagation ANN provides adequate accuracy for spatial interpolation, but the predictions of Kriging interpolation are more accurate than the selected ANN. The proposed GIS ensures indoor radio wave propagation model and electromagnetic coverage, the number, position and transmitter power of access points and electromagnetic radiation level. Pollution analysis in a given propagation environment was done and it was demonstrated that WLAN (2.4 GHz) electromagnetic coverage does not lead to any electromagnetic pollution due to the low power levels used. Example interpolated electromagnetic field values for WLAN system in a building of Yildiz Technical University, Turkey, were generated using the selected network architectures to illustrate the results with an ANN.


Joint Measurements of Terahertz Wave Generation and High-Harmonic Generation from Aligned Nitrogen Molecules Reveal Angle-Resolved Molecular Structures.
We report the synchronized measurements of terahertz wave generation and high-harmonic generation from aligned nitrogen molecules in dual-color laser fields. Both yields are found to be alignment dependent, showing the importance of molecular structures in the generation processes. By calibrating the angular ionization rates with the terahertz yields, we present a new way of retrieving the angular differential photoionization cross section (PICS) from the harmonic signals which avoids specific model calculations or separate measurements of the alignment-dependent ionization rates. The measured PICS is found to be consistent with theoretical predications, although some discrepancies exist. This all-optical method provides a new alternative for investigating molecular structures.


Treat patient, not just the disease: holistic needs assessment for haematological cancer patients.
Haematological malignancies can have devastating effects on the patients' physical, emotional, psycho-sexual, educational and economic health. With the improvement of therapies patients with these malignancies are living longer, however significant proportion these patient show poor quality of life (QoL) due to various physical and psychological consequences of the disease and the treatments. Health-related QoL (HRQoL) is multi-dimensional and temporal, relating to a state of functional, physical, psychological and social/family well-being. Compared with the general population, HRQoL of these patients is worse in most dimensions. However without routine holistic need assessment (HNA), clinicians are unlikely to identify patients with clinically significant distress. Surviving cancer is a chronic life-altering condition with several factors negatively affecting their QoL, such as psychological problems, including depression and excessive fear of recurrence, as well as social aspects, such as unemployment and social isolation. These need to be adequately understood and addressed in the healthcare of long-term survivors of haematological cancer. Applying a holistic approach to patient care has many benefits and yet, only around 25% of cancer survivors in the UK receive a holistic needs assessment. The efforts of the last decade have established the importance of ensuring access to psychosocial services for haematological cancer survivors. We need to determine the most effective practices and how best to deliver them across diverse settings. Distress, like haematological cancer, is not a single entity, and one treatment does not fit all. Psychosocialoncology needs to increase its research in comparative effectiveness.


Bacterial multidrug efflux transporters.
Infections caused by bacteria are a leading cause of death worldwide. Although antibiotics remain a key clinical therapy, their effectiveness has been severely compromised by the development of drug resistance in bacterial pathogens. Multidrug efflux transporters--a common and powerful resistance mechanism--are capable of extruding a number of structurally unrelated antimicrobials from the bacterial cell, including antibiotics and toxic heavy metal ions, facilitating their survival in noxious environments. Transporters of the resistance-nodulation-cell division (RND) superfamily typically assemble as tripartite efflux complexes spanning the inner and outer membranes of the cell envelope. In Escherichia coli, the CusCFBA complex, which mediates resistance to copper(I) and silver(I) ions, is the only known RND transporter specific to heavy metals. Here, we describe the current knowledge of individual pump components of the Cus system, a paradigm for efflux machinery, and speculate on how RND pumps assemble to fight diverse antimicrobials.


Phylogeography and population history of the crab-eating fox (Cerdocyon thous).
The crab-eating fox is a medium-sized Neotropical canid with generalist habits and a broad distribution in South America. We have investigated its genetic diversity, population structure and demographic history across most of its geographic range by analysing 512 base pairs (bp) of the mitochondrial DNA (mtDNA) control region, 615 bp of the mtDNA cytochrome b gene and 1573 total nucleotides from three different nuclear fragments. MtDNA data revealed a strong phylogeographic partition between northeastern Brazil and other portions of the species' distribution, with complete separation between southern and northern components of the Atlantic Forest. We estimated that the two groups diverged from each other c. 400,000-600,000 years ago, and have had contrasting population histories. A recent demographic expansion was inferred for the southern group, while northern populations seem to have had a longer history of large population size. Nuclear sequence data did not support this north-south pattern of subdivision, likely due at least in part to secondary male-mediated historical gene flow, inferred from multilocus coalescent-based analyses. We have compared the inferred phylogeographic patterns to those observed for other Neotropical vertebrates, and report evidence for a major north-south demographic discontinuity that seems to have marked the history of the Atlantic Forest biota.


Local control of acetylcholinesterase gene expression in multinucleated skeletal muscle fibers: individual nuclei respond to signals from the overlying plasma membrane.
Nuclei in multinucleated skeletal muscle fibers are capable of expressing different sets of muscle-specific genes depending on their locations within the fiber. Here we test the hypothesis that each nucleus can behave autonomously and responds to signals generated locally on the plasma membrane. We used acetylcholinesterase (AChE) as a marker because its transcripts and protein are concentrated at the neuromuscular and myotendenous junctions. First, we show that tetrodotoxin (TTX) reversibly suppresses accumulation of cell surface AChE clusters, whereas veratridine or scorpion venom (ScVn) increase them. AChE mRNA levels are also regulated by membrane depolarization. We then designed chambered cultures that allow application of sodium channel agonists or antagonists to restricted regions of the myotube surface. When a segment of myotube is exposed to TTX, AChE cluster formation is suppressed only on that region. Conversely, ScVn increases AChE cluster formation only where in contact with the muscle surface. Likewise, both the synthesis and secretion of AChE are shown to be locally regulated. Moreover, using in situ hybridization, we show that the perinuclear accumulation of AChE transcripts also depends on signals that each nucleus receives locally. Thus AChE can be up- and downregulated in adjacent regions of the same myotubes. These results indicate that individual nuclei are responding to locally generated signals for cues regulating gene expression.


Opinions of veterinarians on antimicrobial use in farm animals in Flanders and the Netherlands.
Veterinarians play an important role in the reduction of antimicrobial use in farm animals. This study aims to quantify opinions of veterinarians from the Netherlands and Flanders regarding antimicrobial use and resistance issues in farm animals. An online survey was sent out to 678 and 1100 farm animal veterinarians in Flanders and the Netherlands, of which 174 and 437 were returned respectively. Suboptimal climate conditions were regarded as the most important cause for high antimicrobial use in farm animals. Flemish veterinarians also regarded insufficient biosecurity measures and farmers' mentality as important determinants, while the Dutch respondents ranked insufficient immunity of young animals and economic considerations of farmers as major causes. The majority of Dutch respondents (63.8 per cent) supported the existing national policy, which aimed to halve veterinary antimicrobial use, while the Flemish (32.9 per cent) were less supportive of such a policy. Improvements in housing and climate conditions, biosecurity measures and strict control of specific infectious diseases were seen as important and promising measures to reduce antimicrobial use. To reduce antimicrobial use in farm animals, some shared approaches might be applicable in both countries. However, cultural, political and societal differences between Flanders and the Netherlands require differentiated approaches to reduce veterinary antimicrobial use.


Pharmacological treatment of schizophrenia with comorbid substance use disorder.
While antipsychotics remain the cornerstone of treatment for schizophrenic patients with comorbid substance use disorder (SUD), such treatment is nonetheless complicated by frequent medical comorbidity and poor adherence to medication. Randomised controlled trials (RCTs) on the efficacy of antipsychotics for the treatment of schizophrenic patients with comorbid SUD are reviewed and analysed on the basis of a systematic literature search (PubMed) ranging from 1985 to 2015. On the same basis, findings from RCTs on the efficacy of psychotropic and other medications used for primary SUD are summarised, and the main issues liable to influence treatment choice are discussed, including pharmacodynamic as well as pharmacokinetic interactions, adherence, medical comorbidity and the impact on brain structure. As far as the treatment of schizophrenic patients with SUD is concerned, direct and indirect evidence tends to stand in favour of the use of second-generation antipsychotics (SGAs), and particularly those with lower metabolic, cardiovascular and extrapyramidal side effects, as well as those with a depot formulation. A few of the usual medications for the treatment of primary SUD, such as naltrexone and disulfiram for alcohol use and bupropion for tobacco cessation, can also be safely and efficiently administered to schizophrenic patients with SUD.


Tuberculosis infection among people with severe mental illness.
In a study of the prevalence of tuberculosis infection and risk factors for infection among people with severe mental illness, 71 participants in a psychiatric day program were given a tuberculin skin test. Twelve of the 71 subjects (17 percent) had positive results. None had active tuberculosis. Those with tuberculosis infection were more likely to be immigrants and to be above the study group's median age of 32. Eleven of the 12 infected subjects had experienced at least one of seven risk factors for tuberculosis infection, which suggests that more clinical attention should be placed on tuberculosis infection in this population.


Effect of temperature on the development and survival of the Argentine ant, Linepithema humile.
The influence of temperature on the developmental times and survival of insects can largely determine their distribution. For invasive species, like the Argentine ant, Linepithema humile Mayr (Hymenoptera: Formicidae), these data are essential for predicting their potential range based on mechanistic models. In the case of this species, such data are too scarce and incomplete to make accurate predictions based on its physiological needs. This research provides comprehensive new data about brood survival and developmental times at a wide range of temperatures under laboratory conditions. Temperature affected both the complete brood development from egg to adult worker and each of the immature stages separately. The higher the temperature, the shorter the development times. Brood survival from egg to adult was low, with the maximum survival rate being only 16% at 26 degrees C. Temperature also affected survival of each of the immature stages differently: eggs were negatively affected by high temperatures, while larvae were negatively affected by low temperatures, and the survival of pupae was apparently independent of environmental temperature. At 32 degrees C no eggs survived, while at 18 degrees C less than 2% of the eggs hatched into larva. The data from the present study are essential for developing prediction models about the distribution range of this tramp species based on its physiological needs in relation to temperature.


Mapping carbon accumulation potential from global natural forest regrowth.
To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy.


Sweet potato [Ipomoea batatas (L.) Lam. "Tainong 57"] starch improves insulin sensitivity in high-fructose diet-fed rats by ameliorating adipocytokine levels, pro-inflammatory status, and insulin signaling.
The aim of this study was to investigate the effects of low-glycemic index (GI) sweet potato starch on adipocytokines, pro-inflammatory status, and insulin signaling in the high-fructose diet-induced insulin-resistant rat. We randomly divided 24 insulin-resistant rats and 16 normal rats into two groups fed a diet containing 575 g/kg of starch: a low-GI sweet potato starch (S) or a high-GI potato starch (P). The four experimental groups were labeled as follows: insulin-resistant P (IR-P), insulin-resistant S (IR-S), normal P (N-P) and normal S (N-S). After 4 wk on the experimental diets, an intraperitoneal glucose tolerance test (IPGTT) was conducted, and the homeostasis model assessment (HOMA), adipocytokines, pro-inflammatory cytokines levels, and insulin signaling-related protein expression were measured. The homeostasis model assessment values were significantly lower in the IR-S than in the IR-P group, suggesting that insulin sensitivity was improved among sweet potato starch-fed rats. Levels of tumor necrosis factor-α, interleukin-6, resistin, and retinol binding protein-4 were significantly lower in the IR-S versus the IR-P group, indicating an improvement of pro-inflammatory status in sweet potato starch-fed rats. The sweet potato starch diet also significantly enhanced the protein expression of phospho-Tyr-insulin receptor substrate-1 and improved the translocation of glucose transporter 4 in the skeletal muscle. Our results illustrated that sweet potato starch feeding for 4 wk can improve insulin sensitivity in insulin-resistant rats, possibly by improving the adipocytokine levels, pro-inflammatory status, and insulin signaling.


Missing covariate data within cancer prognostic studies: a review of current reporting and proposed guidelines.
Prognostic models play a crucial role in the clinical decision-making process. Unfortunately, missing covariate data impede the construction of valid and reliable models, potentially introducing bias, if handled inappropriately. The extent of missing covariate data within reported cancer prognostic studies, the current handling and the quality of reporting this missing covariate data are unknown. Therefore, a review was conducted of 100 articles reporting multivariate survival analyses to assess potential prognostic factors, published within seven cancer journals in 2002. Missing covariate data is a common occurrence in studies performing multivariate survival analyses, being apparent in 81 of the 100 articles reviewed. The percentage of eligible cases with complete data was obtainable in 39 articles, and was <90% in 17 of these articles. The methods used to handle incomplete covariates were obtainable in 32 of the 81 articles with known missing data and the most commonly reported approaches were complete case and available case analysis. This review has highlighted deficiencies in the reporting of missing covariate data. Guidelines for presenting prognostic studies with missing covariate data are proposed, which if followed should clarify and standardise the reporting in future articles.


Potential sperm contributions to the murine zygote predicted by in silico analysis.
Paternal contributions to the zygote are thought to extend beyond delivery of the genome and paternal RNAs have been linked to epigenetic transgenerational inheritance in different species. In addition, sperm-egg fusion activates several downstream processes that contribute to zygote formation, including PLC zeta-mediated egg activation and maternal RNA clearance. Since a third of the preimplantation developmental period in the mouse occurs prior to the first cleavage stage, there is ample time for paternal RNAs or their encoded proteins potentially to interact and participate in early zygotic activities. To investigate this possibility, a bespoke next-generation RNA sequencing pipeline was employed for the first time to characterise and compare transcripts obtained from isolated murine sperm, MII eggs and pre-cleavage stage zygotes. Gene network analysis was then employed to identify potential interactions between paternally and maternally derived factors during the murine egg-to-zygote transition involving RNA clearance, protein clearance and post-transcriptional regulation of gene expression. Our in silico approach looked for factors in sperm, eggs and zygotes that could potentially interact co-operatively and synergistically during zygote formation. At least five sperm RNAs (Hdac11, Fbxo2, Map1lc3a, Pcbp4 and Zfp821) met these requirements for a paternal contribution, which with complementary maternal co-factors suggest a wider potential for extra-genomic paternal involvement in the developing zygote.


Hemp (Cannabis sativa L.) Protein Hydrolysates Promote Anti-Inflammatory Response in Primary Human Monocytes.
Hemp seeds have a wide variety of chemical compounds which present biological activity. Specifically, the focus on proteins and bioactive peptides are increasing as alternative sources of nutraceutical uses. In the literature, hemp protein products (HPPs) have reported antioxidant and anti-inflammatory properties. This study aimed to determine the inflammation-related modulatory effects of HPPs on lipopolysaccharide (LPS)-activated primary human monocytes. CD14+ cells were immunomagnetically isolated from buffy coats and the anti-inflammatory activity of hemp protein isolate (HPI) and hydrolysates (HPHs) was evaluated on LPS-stimulated human primary monocytes. The specific markers of inflammation, polarization, and chemoattraction were measured by RT-qPCR and ELISA assays. Our results showed that HPPs decreased the pro-inflammatory mediators (TNFα, IL-1β, and IL-6) and increased the anti-inflammatory mediators (IL-10 and IL-4). In addition, M1 polarization marker gene expression (CCR7 and iNOS) was downregulated by HPPs and, M2 polarization marker gene expression (CD200R and MRC1) was upregulated. Finally, the mRNA expression of chemotaxis genes (CCR2 and CCL2) was downregulated by HPPs. In conclusion, this study suggests that HPPs may improve chronic inflammatory states and promote regenerative processes by reprogramming monocytes toward M2 polarization phenotype.


Diversity and structure of bacterial communities in Arctic versus Antarctic pack ice.
A comprehensive assessment of bacterial diversity and community composition in arctic and antarctic pack ice was conducted through cultivation and cultivation-independent molecular techniques. We sequenced 16S rRNA genes from 115 and 87 pure cultures of bacteria isolated from arctic and antarctic pack ice, respectively. Most of the 33 arctic phylotypes were >97% identical to previously described antarctic species or to our own antarctic isolates. At both poles, the alpha- and gamma-proteobacteria and the Cytophaga-Flavobacterium group were the dominant taxonomic bacterial groups identified by cultivation as well as by molecular methods. The analysis of 16S rRNA gene clone libraries from multiple arctic and antarctic pack ice samples revealed a high incidence of closely overlapping 16S rRNA gene clone and isolate sequences. Simultaneous analysis of environmental samples with fluorescence in situ hybridization (FISH) showed that approximately 95% of 4',6'-diamidino-2-phenylindole (DAPI)-stained cells hybridized with the general bacterial probe EUB338. More than 90% of those were further assignable. Approximately 50 and 36% were identified as gamma-proteobacteria in arctic and antarctic samples,respectively. Approximately 25% were identified as alpha-proteobacteria, and 25% were identified as belonging to the Cytophaga-Flavobacterium group. For the quantification of specific members of the sea ice community, new oligonucleotide probes were developed which target the genera Octadecabacter, Glaciecola, Psychrobacter, Marinobacter, Shewanella, and Polaribacter: High FISH detection rates of these groups as well as high viable counts corroborated the overlap of clone and isolate sequences. A terrestrial influence on the arctic pack ice community was suggested by the presence of limnic phylotypes.


The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. Comparison of all 10 variable exons between mouse, human, and rat.
The human CD44 cell surface glycoprotein family which has been implicated in lymphocyte homing, tumor metastasis, and extracellular matrix attachment consists of a large number of related isoforms that derive from the differential splicing of a single CD44 gene transcript. Recent mapping of the CD44 locus in man indicated the presence of at least nine alternative exons within the region of the gene encoding the variable membrane proximal extracellular domain. Here we report the identification of a 10th alternative exon (termed V1) in the mouse, human, and rat CD44 genes. We demonstrate tissue-specific patterns of expression for transcripts containing exons V1-V10 in the mouse and a highly restricted usage of exon V1 in transcripts from mouse gastric tissue. Close sequence homology between exons V1-V10 from mouse rat and human points to a specific functional role rather than a purely structural role for the membrane proximal extracellular domain of the CD44 molecule.


Microbial synthesis of pinene.
The volumetric heating values of today's biofuels are too low to power energy-intensive aircraft, rockets, and missiles. Recently, pinene dimers were shown to have a volumetric heating value similar to that of the tactical fuel JP-10. To provide a sustainable source of pinene, we engineered Escherichia coli for pinene production. We combinatorially expressed three pinene synthases (PS) and three geranyl diphosphate synthases (GPPS), with the best combination achieving ~28 mg/L of pinene. We speculated that pinene toxicity was limiting production; however, toxicity should not be limiting at current titers. Because GPPS is inhibited by geranyl diphosphate (GPP) and to increase flux through the pathway, we combinatorially constructed GPPS-PS protein fusions. The Abies grandis GPPS-PS fusion produced 32 mg/L of pinene, a 6-fold improvement over the highest titer previously reported in engineered E. coli. Finally, we investigated the pinene isomer ratio of our pinene-producing microbe and discovered that the isomer profile is determined not only by the identity of the PS used but also by the identity of the GPPS with which the PS is paired. We demonstrated that the GPP concentration available to PS for cyclization alters the pinene isomer ratio.


Analysis of a widely tunable long-period grating by use of an ultrathin cladding layer and higher-order cladding mode coupling.
A widely tunable long-period grating in single-mode fiber is analyzed by use of an ultrathin cladding layer and higher-order cladding mode coupling. The numerical simulation shows that a 225-nm tuning range in the newly designed ultrathin long-period grating (cladding thickness, 35 microm) with third-order cladding mode coupling can be obtained. The analyzed tuning range is seven times wider than those of the other known long-period gratings. We believe that the proposed highly sensitive long-period grating will be widely used as a gain-flattening filter for ultrawideband optical amplifiers and fast tunable filters in dynamic optical communication systems.


Optical and electrical properties of Vanadium doped Indium oxide thin films.
A new transparent conducting indium vanadium oxide (IVO) thin film is developed by using a modification-specific reactive thermal coevaporation method. Electrical and optical characteristics of IVO films were studied with different vanadium doping concentration, which shows good optical transmittance in the visible spectra range and a minimum electrical resistivity of 7.95 x 10(-4) Omega.cm corresponding to a carrier density of 2.28 x 10(20) cm(-3) and a Hall mobility of 34.5 cm(2) V(-1) s(-1), respectively. Using IVO film as the anode, OLED shows a reduced turn-on voltage and significantly enhanced luminance and electroluminescence efficiency with respect to the device with an ITO anode. Our results indicate that IVO is a promising transparent conducting oxide material, and a suitable electrical contact for hole injection in OLEDs.


Effect of xenon and dexmedetomidine as adjuncts for general anesthesia on postoperative emergence delirium after elective cardiac catheterization in children: study protocol for a randomized, controlled, pilot trial.
Emergence delirium, a manifestation of acute postoperative brain dysfunction, is frequently observed after pediatric anesthesia and has been associated with the use of sevoflurane. Both xenon and dexmedetomidine possess numerous desirable properties for the anesthesia of children with congenital heart disease, including hemodynamic stability, lack of neurotoxicity, and a reduced incidence of emergence delirium. Combining both drugs has never been studied as a balanced-anesthesia technique. This combination allows the provision of anesthesia without administering anesthetic drugs against which the Food and Drug Administration (FDA) issued a warning for the use in young children. In this phase-II, mono-center, prospective, single-blinded, randomized, controlled pilot trial, we will include a total of 80 children aged 0-3 years suffering from congenital heart disease and undergoing general anesthesia for elective diagnostic and/or interventional cardiac catheterization. Patients are randomized into two study groups, receiving either a combination of xenon and dexmedetomidine or mono-anesthesia with sevoflurane for the maintenance of anesthesia. The purpose of this study is to estimate the effect size for xenon-dexmedetomidine versus sevoflurane anesthesia with respect to the incidence of emergence delirium in children. We will also describe group differences for a variety of secondary outcome parameters including peri-interventional hemodynamics, emergence characteristics, incidence of postoperative vomiting, and the feasibility of a combined xenon-dexmedetomidine anesthesia in children. Sevoflurane is the most frequently used anesthetic in young children, but has been indicated as an independent risk factor in the development of emergence delirium. Xenon and dexmedetomidine have both been associated with a reduction in the incidence of emergence delirium. Combining xenon and dexmedetomidine has never been described as a balanced-anesthesia technique in children. Our pilot study will therefore deliver important data required for future prospective clinical trials. EudraCT, 2018-002258-56. Registered on 20 August 2018. https://www.clinicaltrialsregister.eu.


Landfill sustainability and aftercare completion criteria.
Although many countries are increasing their efforts to recycle and to re-use waste materials, landfilling will still be needed in order to dispose of wastes which cannot be recycled or treated in other ways. Since landfills will most probably be present for a long time, measures will have to be taken to reduce their (long-term) emissions. The European Commission has delegated the competent authorities to decide to end aftercare and several member states have provided regulations for this purpose. However, there is currently no guidance for long-term risk assessment to support an aftercare completion procedure for landfills. The aim of this study is to provide examples of current regulations and to demonstrate an alternative approach for a quantitative risk assessment of landfill leachate. The presented modelling approach clearly demonstrates the added value of site specific risk assessments of the long-term emissions from landfills and might provide a basis for application when the acceptance criteria for landfill will be revisited in the future. In addition, the modelling approach can be used as one of the toolboxes to perform assessments of the long-term emissions from landfill leachates and might help the competent authorities to decide whether the remaining emission potential is acceptable or not. Moreover, the results imply that local environmental conditions contribute to the acceptability of landfill emissions and are important factors in choosing a landfill location.


Imaging and biomarkers for Alzheimer's disease.
The development of acetyl-cholinesterase inhibitors, and the prospect of future therapies to prevent, or modify, the course of Alzheimer's disease necessitates greater accuracy in diagnosis of this heterogeneous disease. Current diagnosis is based on clinical criteria and neuropathology. This is not always sufficient, and the development of sensitive and specific biomarkers would enable earlier and more accurate diagnosis. Genetic markers, such as Apolipoprotein E4, and cerebrospinal fluid markers such as beta-amyloid and tau, support a diagnosis of Alzheimer's disease. The latter can also predict conversion from mild cognitive impairment to dementia. Imaging markers improve diagnostic accuracy by reflecting brain function or aspects of in vivo pathological changes. In order for such biomarkers to become clinically useful, however, effective treatments need to become available, and long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes for the longitudinal natural history of the disease.


Expression and characterization of the JAK kinase and STAT protein from brine shrimp, Artemia franciscana.
In this study, we isolated and characterized both JAK and STAT genes from Artemia, Artemia franciscana. Although AfJAK showed only 19% identity (33% similarity) to the Drosophila Hop protein, AfJAK contained the characteristic JAK homology domain (JH domain) from JH1 to JH7. On the other hand, AfSTAT showed higher identity (30%) to Drosophila STAT (STAT92E). The low identities of AfJAK and AfSTAT to Drosophila Hop and STAT92E suggest that JAK and STAT proteins are unique in each different species of invertebrate. RT-PCR analysis showed that both AfJAK and AfSTAT transcripts were ubiquitously expressed in the embryo, which is similar to the expression patterns of Drosophila Hop and STAT92E mRNAs during development. In addition, we generated a constitutively active form of AfSTAT by fusing the JH1 domain of AfJAK to the C-terminal end of AfSTAT. This fusion protein, AfSTAT-HA-JH1, autophosphorylated on its tyrosine residue and was able to bind to specific DNA motifs including the STAT-binding motifs in the Drosophila Raf promoter. Both AfJAK and AfSTAT proteins elicited the transactivation potential toward the fly Raf promoter in Sf9 cells. However, tyrosine phosphorylation of AfSTAT was not detected, which is consistent with the cellular localization analysis that most AfSTAT proteins were in the cytoplasm. Our results demonstrate that both JAK and STAT are present in the genome of Artemia, which can serve as the basis for further investigations to explore the role of the JAK/STAT signal pathway in the development and immune response of brine shrimp.


Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension.
Exercise is an effective intervention for treating hypertension and arterial stiffness, but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects. Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients. Sixty-five patients with hypertension were randomized to 16 weeks of continuous exercise training (n=26), interval training (n=26) or a sedentary routine (n=13). The training was conducted in two 40-min sessions a week. Assessment of arterial stiffness by carotid-femoral pulse wave velocity (PWV) measurement and 24-h ambulatory blood pressure monitoring (ABPM) were performed before and after the 16 weeks of training. At the end of the study, ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality. PWV had declined significantly only after interval training from 9.44+/-0.91 to 8.90+/-0.96 m s(-1), P=0.009 (continuous from 10.15+/-1.66 to 9.98+/-1.81 m s(-1), P=ns; control from 10.23+/-1.82 to 10.53+/-1.97 m s(-1), P=ns). Continuous and interval exercise training were beneficial for blood pressure control, but only interval training reduced arterial stiffness in treated hypertensive subjects.


The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.
Previous work has demonstrated that the character of mouse cortical interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic origin and the character of mature interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical interneurons. Here, we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific interneuron subtypes. Removal of this gene at distinct neurogenic time points results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.


Using home equity to finance long-term care.
A majority of elderly Americans have the bulk of their assets tied up in the houses they own. Reverse mortgages could tap this home equity, providing loan disbursements without requiring older homeowners to make monthly payments on principal and interest. In this paper we analyze the potential of using home equity to finance long-term care of the elderly, including payments for home care and for long-term care insurance. We first estimate each homeowner's risk of need for care (and risk of institutionalization) and then calculate the degree to which home equity could be used to cover the costs of home care (or of insurance premiums). Special emphasis is placed on those in the highest risk group and on those with the lowest incomes, who often turn out to be the same people.


Modulation of Dormancy and Growth Responses in Reproductive Buds of Temperate Trees.
During autumn perennial trees cease growth and form structures called buds in order to protect meristems from the unfavorable environmental conditions, including low temperature and desiccation. In addition to increased tolerance to these abiotic stresses, reproductive buds modulate developmental programs leading to dormancy induction to avoid premature growth resumption, and flowering pathways. Stress tolerance, dormancy, and flowering processes are thus physically and temporarily restricted to a bud, and consequently forced to interact at the regulatory level. We review recent genomic, genetic, and molecular contributions to the knowledge of these three processes in trees, highlighting the role of epigenetic modifications, phytohormones, and common regulatory factors. Finally, we emphasize the utility of transcriptomic approaches for the identification of key structural and regulatory genes involved in bud processes, illustrated with our own experience using peach as a model.


Time-lapse imaging of mitosis after siRNA transfection.
Changes in cellular organization and chromosome dynamics that occur during mitosis are tightly coordinated to ensure accurate inheritance of genomic and cellular content. Hallmark events of mitosis, such as chromosome movement, can be readily tracked on an individual cell basis using time-lapse fluorescence microscopy of mammalian cell lines expressing specific GFP-tagged proteins. In combination with RNAi-based depletion, this can be a powerful method for pinpointing the stage(s) of mitosis where defects occur after levels of a particular protein have been lowered. In this protocol, we present a basic method for assessing the effect of depleting a potential mitotic regulatory protein on the timing of mitosis. Cells are transfected with siRNA, placed in a stage-top incubation chamber, and imaged using an automated fluorescence microscope. We describe how to use software to set up a time-lapse experiment, how to process the image sequences to make either still-image montages or movies, and how to quantify and analyze the timing of mitotic stages using a cell-line expressing mCherry-tagged histone H2B. Finally, we discuss important considerations for designing a time-lapse experiment. This strategy is complementary to other approaches and offers the advantages of 1) sensitivity to changes in kinetics that might not be observed when looking at cells as a population and 2) analysis of mitosis without the need to synchronize the cell cycle using drug treatments. The visual information from such imaging experiments not only allows the sub-stages of mitosis to be assessed, but can also provide unexpected insight that would not be apparent from cell cycle analysis by FACS.


A Developmental Process Analysis of Cross-Generational Continuity in Educational Attainment.
In this prospective longitudinal study (N = 585) we examined intergenerational links in level of educational attainment. Of particular interest was whether family background characteristics, parenting in early childhood and early adolescence, and school adjustment and performance in middle childhood accounted for (i.e., mediated) continuity and amplified or attenuated (i.e., moderated) continuity. Family background data, including mother education level, were collected when the children were age 5 years; parenting was assessed at ages 5 and 12; and school adjustment data (behavior problems, peer acceptance, academic performance) were collected in the first four years of elementary school. Cross-generational continuity in educational attainment was moderate (r = .38) and largely indirect via children's academic performance in elementary school and mothers' academic involvement in early adolescence. Moderator analyses indicated greater cross-generational continuity in single-parent families; in families low in proactive teaching, monitoring, and academic involvement; and in families with lower-IQ children who performed poorly in school and were disliked by peers, These findings suggest that distal and proximal family and child characteristics may serve as crucial processes in the intergenerational transmission of low educational attainment.


Half-sandwich Os(ii) and Ru(ii) bathophenanthroline complexes: anticancer drug candidates with unusual potency and a cellular activity profile in highly invasive triple-negative breast cancer cells.
There is an urgent need to discover new, selective compounds to add to the limited arsenal of chemotherapeutics displaying selective toxicity for aggressive triple-negative breast cancer (TNBC) cells. The effect of two, recently developed metal-based half-sandwich complexes [Os(η6-pcym)(bphen)(dca)]PF6 (Os-dca) and [Ru(η6-pcym)(bphen)(dca)]PF6 (Ru-dca) [pcym = 1-methyl-4-(propan-2-yl)benzene (p-cymene); bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline); dca = dichloroacetate] on triple-negative breast cancer cells MDA-MB-231 is reported. The complexes display selective toxicity in several tumor cells (at submicromolar concentrations), and a prominent effect is observed against highly progressive triple negative breast cancer MDA-MB-231 cells for Os-dca. The lower potency of Ru-dca in comparison with Os-dca is apparently connected with a relatively quick release of the dca ligand due to the hydrolysis of Ru-dca before this complex enters the cells. Remarkably, both Os-dca and Ru-dca reduce successfully metastasis-related properties of the triple-negative breast cancer cells such as migration, invasion, and re-adhesion. The anti-metastatic effects of Os-dca and Ru-dca are associated with their ability to suppress matrix metalloproteinase activity and/or production and reduce the expression of aquaporins. Further detailed mechanistic studies reveal that Os-dca reverses Warburg's effect and oncosis seems to be a prominent mode of cell death that predominates over apoptosis. As such, Os-dca can efficiently overcome the resistance of cancer cells to clinically-used apoptotic inducers cisplatin and carboplatin. The cytostatic and anti-metastatic properties of Os-dca in MDA-MB-231 provide a strong impetus for the development of new metal-based compounds to target hardly treatable human TNBC cells and displaying different modes of action compared to the antitumor metallodrugs in clinical use.


Clinical experiences with radiation induced thyroid cancer after chernobyl.
The risk of developing thyroid cancer increases considerably after exposure to external or internal radiation, especially in children below the age of 10. After the Chernobyl reactor accident, the yearly incidence of childhood thyroid cancer in Belarus increased to approximately 40 per 1.000.000 in girls and to roughly 20 per 1.000.000 in boys compared to approximately 0.5 cases per 1.000.000 prior to the accident. Typically, young children with thyroid cancer after radiation exposure present in ≈95% of the cases as papillary cancers, in ≈50% as invasive tumors growing outside the thyroid capsule, in ≈65% with lymph node metastases and in ≈15% with distant metastases. A joint Belarusian-German project starting in April 1993 that combined treatment with surgery and radioiodine was organized in 237 selected children from Belarus who were exposed to the Chernobyl fallout and had advanced stages of thyroid cancer. The study group included 141 girls and 96 boys. Their median age at the time of the accident was 1.7 years; whereas the median age at the time of diagnosis was 12.4 years. With the exception of two cases with follicular histology, the majority of the patients had been diagnosed with papillary thyroid cancers. In 63%, the tumor had grown outside the thyroid capsule and invaded the tissue of the neck (pT4). Nearly all of the selected cases (96%) showed-up with lymph node metastases (pN1) and 43% of the patients with distant metastases mainly to the lungs (pM1). In 58% of the children, complete remissions of thyroid cancer could be achieved until December 31st 2010 and in 34% of the children, stable partial remissions; in the remaining 8% of the patients, partial remissions were observed. The risk of radiation-induced thyroid cancer increased considerably in children and adolescents who were affected by the Chernobyl reactor accident. In spite of the fact, that thyroid cancers in young children seem to behave more aggressively than in older patients, the results of combined treatment with thyroidectomy, radioiodine therapy and thyroid hormone replacement are excellent.


Consumer evaluations of food risk management quality in Europe.
In developing and implementing appropriate food risk management strategies, it is important to understand how consumers evaluate the quality of food risk management practices. The aim of this study is to model the underlying psychological factors influencing consumer evaluations of food risk management quality using structural equation modeling techniques (SEM), and to examine the extent to which the influence of these factors is country-specific (comparing respondents from Denmark, Germany, Greece, Slovenia, and the United Kingdom). A survey was developed to model the factors that drive consumer evaluations of food risk management practices and their relative importance (n= 2,533 total respondents). The measurement scales included in the structural model were configurally and metrically invariant across countries. Results show that some factors appear to drive perceptions of effective food risk management in all the countries studied, such as proactive consumer protection, which was positively related to consumers' evaluation of food risk management quality, while opaque and reactive risk management was negatively related to perceived food risk management quality. Other factors appeared to apply only in certain countries. For example, skepticism in risk assessment and communication practices was negatively related to food risk management quality, particularly so in the UK. Expertise of food risk managers appeared to be a key factor in consumers' evaluation of food risk management quality in some countries. However, trust in the honesty of food risk managers did not have a significant effect on food risk management quality. From the results, policy implications for food risk management are discussed and important directions for future research are identified.