Mesorhizobium ciceri biovar biserrulae, a novel biovar nodulating the pasture legume Biserrula pelecinus L.
Biserrula pelecinus L. is a pasture legume species that forms a highly specific nitrogen-fixing symbiotic interaction with a group of bacteria that belong to Mesorhizobium. These mesorhizobia have >98.8 % sequence similarity to Mesorhizobium ciceri and Mesorhizobium loti for the 16S rRNA gene (1440 bp) and >99.3 % sequence similarity to M. ciceri for the dnaK gene (300 bp), and strain WSM1271 has 100 % sequence similarity to M. ciceri for GSII (600 bp). Strain WSM1271 had 85 % relatedness to M. ciceri LMG 14989(T) and 50 % relatedness to M. loti LMG 6125(T) when DNA-DNA hybridization was performed. WSM1271 also had a similar cellular fatty acid profile to M. ciceri. These results are strong evidence that the Biserrula mesorhizobia and M. ciceri belong to the same group of bacteria. Significant differences were revealed between the Biserrula mesorhizobia and M. ciceri in growth conditions, antibiotic resistance and carbon source utilization. The G+C content of the DNA of WSM1271 was 62.7 mol%, compared to 63-64 mol% for M. ciceri. The Biserrula mesorhizobia contained a plasmid ( approximately 500 bp), but the symbiotic genes were detected on a mobile symbiosis island and considerable variation was present in the symbiotic genes of Biserrula mesorhizobia and M. ciceri. There was <78.6 % sequence similarity for nodA and <66.9 % for nifH between Biserrula mesorhizobia and M. ciceri. Moreover, the Biserrula mesorhizobia did not nodulate the legume host of M. ciceri, Cicer arietinum, and M. ciceri did not nodulate B. pelecinus. These significant differences observed between Biserrula mesorhizobia and M. ciceri warrant the proposal of a novel biovar for Biserrula mesorhizobia within M. ciceri. The name Mesorhizobium ciceri biovar biserrulae is proposed, with strain WSM1271 (=LMG 23838=HAMBI 2942) as the reference strain.


Reduction of aflatoxin B1 dialdehyde by rat and human aldo-keto reductases.
Oxidation of the mycotoxin aflatoxin (AF) B1 yields the 8,9-epoxide, which nonenzymatically hydrolyzes rapidly to a dihydrodiol that in turn undergoes slow, base-catalyzed ring opening to a dialdehyde [Johnson, W. W., Harris, T. M., and Guengerich F. P. (1996) J. Am. Chem. Soc. 118, 8213-8220]. AFB1 dialdehyde does not bind to DNA but can react with protein lysine groups. One enzyme induced by cancer chemopreventive agents is AFB1 aldehyde reductase (AFAR), which catalyzes the NADPH-dependent reduction of the dialdehyde to a dialcohol. AFB1 dialdehyde is known to convert nonenzymatically to AFB1 dihydrodiol at neutral pH, and we reinvestigated the enzymatic reaction by preparing AFB1 dialdehyde at pH 10 and then used this to initiate reactions (at neutral pH) with rat and human AFAR isozymes. Two monoalcohols were identified as products, and their identities were established by NaB2H4 reduction, chemical cleavage, and mass spectrometry. The monoalcohol corresponding to reduction at C-8 formed first in reactions catalyzed by either the rat or the human AFAR. This C-8 monoalcohol was further reduced to AFB1 dialcohol by AFAR. The other monoalcohol (C-6a) was formed but not reduced to the dialcohol rapidly. Steady-state kinetic parameters were estimated for the reduction of AFB1 dialdehyde by rat and human AFAR to the monoalcohols. The apparent k(cat) and K(m) values were not adequate to rationalize the observed DeltaA(340) spectral changes in a kinetic model. Simulation fitting was done and yielded parameters indicative of greater enzyme efficiency. A survey of 12 human liver cytosol samples showed a variation of 2.3-fold in AFAR activity. Rats treated with AFB1 excreted the dialcohol and a monoalcohol in urine. The results of these studies are consistent with a role of (rat and human) AFAR in protection against AFB1 toxicity.


HIGH FREQUENCY GENETIC TRANSFORMATION OF CICHORIUM INTYBUS L. USING nptII GENE AS A SELECTIVE MARKER.
Cichorium intybus L. is an important vegetable crop used as salad (leaf form) and for the production of coffee substitutes (root form). At the same time these plants can also be used in biotechnologies for synthesis of pharmaceutical proteins. Here we report the possibility of high frequency Agrobacterium rhizogenes- or A. tumefaciens-mediated transformation of C. intybus L. for construction of transgenic "hairy" roots and plants. The used plasmids contained target human interferonifn-α2b gene, Mycobacterium tuberculosis ESAT6:Ag85B antigene esxA::fbpB(ΔTMD) fused gene and human telomerase reverse transcriptase h Tert gene. Using of nptII gene as a selective one was preferable to the bar gene for chicory. In this case the frequency of transgenic plants or "hairy" roots formation was significantly higher. Cultivation of explants on the medium with Basta in concentration 1-2 mg/l have led to plants death or to significant reduction of number of shoots formed. Frequency of "hairy" roots formation varied from 5.9 to 42.3% after A. rhizogenes-mediated transformation. Frequency of regeneration of transgenic plants varied from 10 to 86% after A. tumefaciens-mediated transformation. Both A. rhizogenes- and A. tumefaciens-mediated transformation frequency depended on the type of explants, roots or cotyledons, and vector used. Usage of A. tumefaciens carrying pCB064 plasmid (target esxA:fbpB(ΔTMD) fused gene and nptII selective gene) resulted in the most effective regeneration of transgenic plants with regeneration frequency up to 86%. In the case of chicory A. rhizogenes-mediated transformation the highest regeneration frequency up to 42.3% was demonstrated using p CB161 vector with ifn-α2b target gene and nptII selective gene.


Complicated presentations of groin hernias.
Elective repair of simple (uncomplicated) inguinal and femoral hernias avoids incarceration and bowel obstruction (complicated presentations). To identify factors that perturb this strategy, we analyzed the records of 1,859 consecutive nonpediatric patients with groin hernias. Incarceration or bowel obstruction prompted operation in 22 of 77 (29%) women and in 15 of 34 (44%) patients with femoral hernia. Patients presenting with bowel obstruction were significantly older than those with incarceration only and/or uncomplicated presentation, and 13 of 25 (52%) required resection of necrotic bowel. Mortality was limited to five patients of advanced age with groin hernia and bowel obstruction. Four of the five patients had undergone resection of necrotic bowel. Complicated presentations of groin hernias are associated with a higher proportion of women and patients with femoral hernias. Gangrenous bowel was encountered only in those patients with groin hernia and bowel obstruction. Early diagnosis and elective repair of uncomplicated hernias should remain our strategy in patients of all ages.


Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count.
While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB.


Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies.
Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.


Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish.
Germline mutations in PTPN11, encoding Shp2, cause Noonan syndrome (NS) and LEOPARD syndrome (LS), two developmental disorders that are characterized by multiple overlapping symptoms. Interestingly, Shp2 catalytic activity is enhanced by NS mutations and reduced by LS mutations. Defective cardiac development is a prominent symptom of both NS and LS, but how the Shp2 variants affect cardiac development is unclear. Here, we have expressed the most common NS and LS Shp2-variants in zebrafish embryos to investigate their role in cardiac development in vivo. Heart function was impaired in embryos expressing NS and LS variants of Shp2. The cardiac anomalies first occurred during elongation of the heart tube and consisted of reduced cardiomyocyte migration, coupled with impaired leftward heart displacement. Expression of specific laterality markers was randomized in embryos expressing NS and LS variants of Shp2. Ciliogenesis and cilia function in Kupffer's vesicle was impaired, likely accounting for the left/right asymmetry defects. Mitogen-activated protein kinase (MAPK) signaling was activated to a similar extent in embryos expressing NS and LS Shp2 variants. Interestingly, inhibition of MAPK signaling prior to gastrulation rescued cilia length and heart laterality defects. These results suggest that NS and LS Shp2 variant-mediated hyperactivation of MAPK signaling leads to impaired cilia function in Kupffer's vesicle, causing left-right asymmetry defects and defective early cardiac development.


Targeted Sequencing of 10,198 Samples Confirms Abnormalities in Neuronal Activity and Implicates Voltage-Gated Sodium Channels in Schizophrenia Pathogenesis.
Sequencing studies have pointed to the involvement in schizophrenia of rare coding variants in neuronally expressed genes, including activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-D-aspartate receptor (NMDAR) complexes; however, larger samples are required to reveal novel genes and specific biological mechanisms. We sequenced 187 genes, selected for prior evidence of association with schizophrenia, in a new dataset of 5207 cases and 4991 controls. Included among these genes were members of ARC and NMDAR postsynaptic protein complexes, as well as voltage-gated sodium and calcium channels. We performed a rare variant meta-analysis with published sequencing data for a total of 11,319 cases, 15,854 controls, and 1136 trios. While no individual gene was significantly associated with schizophrenia after genome-wide correction for multiple testing, we strengthen the evidence that rare exonic variants in the ARC (p = 4.0 × 10-4) and NMDAR (p = 1.7 × 10-5) synaptic complexes are risk factors for schizophrenia. In addition, we found that loss-of-function variants and missense variants at paralog-conserved sites were enriched in voltage-gated sodium channels, particularly the alpha subunits (p = 8.6 × 10-4). In one of the largest sequencing studies of schizophrenia to date, we provide novel evidence that multiple voltage-gated sodium channels are involved in schizophrenia pathogenesis and confirm the involvement of ARC and NMDAR postsynaptic complexes.


Another look at the foramen magnum in bipedal mammals.
A more anteriorly positioned foramen magnum evolved in concert with bipedalism at least four times within Mammalia: once in macropodid marsupials, once in heteromyid rodents, once in dipodid rodents, and once in hominoid primates. Here, we expand upon previous research on the factors influencing mammalian foramen magnum position (FMP) and angle with four new analyses. First, we quantify FMP using a metric (basioccipital ratio) not previously examined in a broad comparative sample of mammals. Second, we evaluate the potential influence of relative brain size on both FMP and foramen magnum angle (FMA). Third, we assess FMP in an additional rodent clade (Anomaluroidea) containing bipedal springhares (Pedetes spp.) and gliding/quadrupedal anomalures (Anomalurus spp.). Fourth, we determine the relationship between measures of FMP and FMA in extant hominoids and an expanded mammalian sample. Our results indicate that bipedal/orthograde mammals have shorter basioccipitals than their quadrupedal/non-orthograde relatives. Brain size alone has no discernible effect on FMP or FMA. Brain size relative to palate size has a weak influence on FMP in some clades, but effects are not evident in all metrics of FMP and are inconsistent among clades. Among anomaluroids, bipedal Pedetes exhibits a more anterior FMP than gliding/quadrupedal Anomalurus. The relationship between FMA and FMP in hominoids depends on the metric chosen for quantifying FMP, and if modern humans are included in the sample. However, the relationship between FMA and FMP is nonexistent or weak across rodents, marsupials, and, to a lesser extent, strepsirrhine primates. These results provide further evidence that bipedal mammals tend to have more anteriorly positioned foramina magna than their quadrupedal close relatives. Our findings also suggest that the evolution of FMP and FMA in hominins may not be closely coupled.


Rates of dissolution and biodegradation of water-insoluble organic compounds.
We conducted a study of the relationship between the dissolution rates of organic compounds that are sparingly soluble in water and the biodegradation of these compounds by mixed cultures of bacteria. The rates of dissolution of naphthalene and 4-chlorobiphenyl were directly related to their surface areas. The bacteria caused a decline in the concentration of the soluble substrate. The rate of bacterial growth fell abruptly when 4-chlorobiphenyl or naphthalene was no longer detectable in solution. The population continued to increase in media with different surface areas of insoluble 4-chlorobiphenyl, but the final counts were higher in media in which the surface areas of the substrate were larger. The rates of dissolution of palmitic acid, octadecane, di(2-ethylhexyl) phthalate, and 1-naphthyl N-methylcarbamate were determined in the absence of microorganisms. A mixed culture of microorganisms mineralized palmitic acid, di(2-ethylhexyl) phthalate, and Sevin (1-naphthyl N-methylcarbamate) at a logarithmic rate, but octadecane mineralization was linear. The rates of mineralization at the end of the active phase of the biodegradation were lower than the rate of dissolution of palmitic acid but higher than the rate of dissolution of octadecane in the uninoculated medium. We suggest that spontaneous dissolution rates are only one of the factors that govern the rates of biodegradation.


The neural correlates of cognitive effort in anxiety: effects on processing efficiency.
We investigated the neural correlates of cognitive effort/pre-target preparation (Contingent Negative Variation activity; CNV) in anxiety using a mixed antisaccade task that manipulated the interval between offset of instructional cue and onset of target (CTI). According to attentional control theory (Eysenck et al., 2007) we predicted that anxiety should result in increased levels of compensatory effort, as indicated by greater frontal CNV, to maintain comparable levels of performance under competing task demands. Our results showed that anxiety resulted in faster antisaccade latencies during medium compared with short and long CTIs. Accordingly, high-anxious individuals compared with low-anxious individuals showed greater levels of CNV activity at frontal sites during medium CTI suggesting that they exerted greater cognitive effort and invested more attentional resources in preparation for the task goal. Our results are the first to demonstrate the neural correlates of processing efficiency and compensatory effort in anxiety and are discussed within the framework of attentional control theory.


The economic burden of maternal mortality on households: evidence from three sub-counties in rural western Kenya.
This study explores the consequences of a maternal death to households in rural Western Kenya focusing particularly on the immediate financial and economic impacts. Between September 2011 and March 2013 all households in the study area with a maternal death were surveyed. Data were collected on the demographic characteristics of the deceased woman; household socio-economic status; a history of the pregnancy and health care access and utilization; and disruption to household functioning due to the maternal death. These data were supplemented by in-depth and focus group discussions. The health service utilization costs associated with maternal deaths were significantly higher, due to more frequent service utilization as well as due to the higher cost of each visit suggesting more involved treatments and interventions were sought with these women. The already high costs incurred by cases during pregnancy were further increased during delivery and postpartum mainly a result of higher facility-based fees and expenses. Households who experienced a maternal death spent about one-third of their annual per capita consumption expenditure on healthcare access and use as opposed to at most 12% among households who had a health pregnancy and delivery. Funeral costs were often higher than the healthcare costs and altogether forced households to dis-save, liquidate assets and borrow money. What is more, the surviving members of the households had significant redistribution of labor and responsibilities to make up for the lost contributions of the deceased women. Kenya is in the process of instituting free maternity services in all public facilities. Effectively implemented, this policy can lift a major economic burden experienced by a very large number of household who seek maternal health services which can be catastrophic in complicated cases that result in maternal death. There needs to be further emphasis on insurance schemes that can support households through catastrophic health spending.


Modelling the Size Effects on the Mechanical Properties of Micro/Nano Structures.
Experiments on micro- and nano-mechanical systems (M/NEMS) have shown that their behavior under bending loads departs in many cases from the classical predictions using Euler-Bernoulli theory and Hooke's law. This anomalous response has usually been seen as a dependence of the material properties on the size of the structure, in particular thickness. A theoretical model that allows for quantitative understanding and prediction of this size effect is important for the design of M/NEMS. In this paper, we summarize and analyze the five theories that can be found in the literature: Grain Boundary Theory (GBT), Surface Stress Theory (SST), Residual Stress Theory (RST), Couple Stress Theory (CST) and Surface Elasticity Theory (SET). By comparing these theories with experimental data we propose a simplified model combination of CST and SET that properly fits all considered cases, therefore delivering a simple (two parameters) model that can be used to predict the mechanical properties at the nanoscale.


Complete Genome Sequence of Caloramator sp. Strain E03, a Novel Ethanologenic, Thermophilic, Obligately Anaerobic Bacterium.
Here, we report the complete genome sequence of Caloramator sp. strain E03, an anaerobic thermophile that was isolated from a hot spring within the Rabbit Creek area of Yellowstone National Park. The assembly contains a single 2,984,770-bp contig with a G+C content of 31.3% and is predicted to encode 2,678 proteins.


Changing conclusions on secondhand smoke in a sudden infant death syndrome review funded by the tobacco industry.
Prenatal and postnatal exposure to tobacco smoke adversely affects maternal and child health. Secondhand smoke (SHS) has been linked causally with sudden infant death syndrome (SIDS) in major health reports. In 1992, the US Environmental Protection Agency (EPA) first noted an association between SHS and SIDS, and both prenatal exposure and postnatal SHS exposure were listed as independent risk factors for SIDS in a 1997 California EPA report (republished in 1999 by the National Cancer Institute) and a 2004 US Surgeon General report. The tobacco industry has used scientific consultants to attack the evidence that SHS causes disease, most often lung cancer. Little is known about the industry's strategies to contest the evidence on maternal and child health. In 2001, a review was published on SIDS that acknowledged funding from the Philip Morris (PM) tobacco company. Tobacco industry documents related to this review were examined to identify the company's influence on the content and conclusions of this review. Tobacco industry documents include 40 million pages of internal memos and reports made available to the public as a result of litigation settlements against the tobacco industry in the United States. Between November 2003 and January 2004, we searched tobacco industry document Internet sites from the University of California Legacy Tobacco Documents Library and the Tobacco Documents Online website. Key terms included "SIDS" and names of key persons. Two authors conducted independent searches with similar key terms, reviewed the documents, and agreed on relevancy through consensus. Thirty documents were identified as relevant. Two drafts (an early version and a final version) of an industry-funded review article on SIDS were identified, and 2 authors independently compared these drafts with the final publication. Formal comments by PM executives made in response to the first draft were also reviewed. We used Science Citation Index in July 2004 to determine citation patterns for the referenced SIDS reviews. PM executives feared that SHS and maternal and child health issues would create a powerful and emotional impetus for smoke-free areas in the home, public areas, and the workplace. In response to the 1992 US EPA report on SHS, the Science and Technology Department of PM's Switzerland subsidiary, Fabriques de Tabac Reunies, searched for "independent" consultants to publish articles addressing SHS. The first industry-funded article was a literature review focusing on smoking and SIDS, conducted by consultant Peter Lee and co-author Allison Thornton, which stated that the association between parental smoking and SIDS could have been attributable to the failure to control fully for confounders. That first review has only been cited once, in the subsequent industry-funded review. In 1997, PM commissioned a consultant, Frank Sullivan, to write a review, with coauthor Susan Barlow, of all possible risk factors for SIDS. The first draft concluded that prenatal and postnatal smoking exposures are both independent risk factors for SIDS. After receiving comments and meeting with PM scientific executives, Sullivan changed his original conclusions on smoking and SIDS. The final draft was changed to emphasize the effects of prenatal maternal smoking and to conclude that postnatal SHS effects were "less well established." Changes in the draft to support this new conclusion included descriptions of Peter Lee's industry-funded review, a 1999 negative but underpowered study of SIDS risk and urinary cotinine levels, and criticisms of the conclusions of the National Cancer Institute report that SHS was causally associated with SIDS. In April 2001, the Sullivan review was published in the United Kingdom journal Paediatric and Perinatal Epidemiology, with a disclosure statement that acknowledged financial support from PM but did not acknowledge contributions from PM executives in the preparation of the review. By 2004, the Sullivan SIDS review had been cited at least 19 times in the medical literature. PM executives responded to corporate concerns about the possible adverse effects of SHS on maternal and child health by commissioning consultants to write review articles for publication in the medical literature. PM executives successfully encouraged one author to change his original conclusion that SHS is an independent risk factor for SIDS to state that the role of SHS is "less well established." These statements are consistent with PM's corporate position that active smoking causes disease but only public health officials conclude the same for SHS. The author's disclosure of industry funding did not reveal the full extent of PM's involvement in shaping the content of the article. This analysis suggests that accepting tobacco industry funds can disrupt the integrity of the scientific process. The background of this SIDS review is relevant for institutions engaged in the debate about accepting or eschewing funding from the tobacco industry. Those who support acceptance of tobacco industry funds argue that academic authors retain the right to publish their work and maintain final approval of the written product, but this argument fails to recognize that the tobacco industry funds work to ensure that messages favorable to the industry are published and disseminated. Clinicians, parents, and public health officials are most vulnerable to the changed conclusions of the SIDS review. The national SIDS "Back to Sleep" campaign has been very successful in reducing SIDS rates. However, estimates of SIDS risk from SHS (odds ratios range from 1.4 to 5.1) have considerable overlap with estimates of risk from prone sleep positioning (odds ratios range from 1.7 to 12.9). With the Back to Sleep campaign well underway, efforts to address parental smoking behavior in both the prenatal and postnatal periods should be intensified. The tobacco industry's disinformation campaign on SHS and maternal and child health can be counteracted within clinicians' offices.


Please get to the point! A cortical correlate of linguistic informativeness.
The production of informative messages is an effortful endeavor that relies on the interaction between microlinguistic (i.e., lexical and grammatical) and macrolinguistic (i.e., pragmatic and discourse) levels of processing. Although the neural correlates of microlinguistic processing have been extensively studied, investigation of the ability to organize the macrolinguistic aspects of message production is scanty. In this article, we show that repetitive TMS of the dorsal portion of the anterior left, but not right, inferior frontal gyrus reduces the levels of lexical informativeness and global coherence of narratives produced by healthy individuals. Interestingly, levels of productivity and microlinguistic processing were unaffected by the stimulation. These results suggest that the dorsal aspect of the anterior left inferior frontal gyrus is an epicenter of a wider neural network subserving the selection of contextually appropriate semantic representations.


A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted by a mosaic sire.
A mechanobullous skin disorder was identified in the progeny of a 3-y-old Friesian-Jersey crossbred bull. The condition presented as loss of skin and mucosa from contact areas and inflammation. Examination of skin samples under light microscopy revealed separation of the epidermis from the dermis. Electron microscopic analysis refined the site of cleavage to above the basement membrane involving lysis of basal keratinocytes. These observations were consistent with the simplex form of epidermolysis bullosa (EB) in humans. Candidate genes based on human gene mutations were assessed, resulting in keratin 5 being identified as the most likely candidate gene. The sequence of bovine keratin 5 was established and sequencing led to identification of a G to A substitution in all affected animals. This mutation leads to an amino acid change of glutamic acid to lysine in the final E (478) of the KLLEGE motif of the protein. The sire carried a de novo mutation and was mosaic, explaining his asymptomatic status and the less than expected frequency of affected offspring. Remarkably, the same mutation has been previously described in EB simplex in humans.


Impaired antiplatelet effects of aspirin associated with hypoxia and ATP release from erythrocytes. Studies in a system with flowing human blood.
We have explored how hypoxic conditions may affect the antiplatelet effects of aspirin. For this purpose, a perfusion system containing a damaged vessel segment was modified in order to induce hypoxia (low Po2) in flowing blood. Blood samples were incubated with 50 mumol L-1 aspirin and divided into two aliquots, one being perfused under standard conditions (normoxic) and the other under hypoxic conditions. The interaction of platelets with the subendothelium was morphometrically evaluated. In studies with untreated blood under normoxic conditions, platelet interaction with the subendothelium was 0.3 +/- 0.1% of contact, 5.3 +/- 1.6% of adhesion, 24.3 +/- 3.3% of thrombus and 29.9 +/- 2.7% of total covered surface. Aspirin-treated blood perfused under normoxic conditions showed a marked decrease in thrombus with a concomitant increase in both platelet adhesion and covered surface percentages. However, when aspirin-treated blood was perfused under hypoxic conditions, platelet interaction was not significantly different from that observed in untreated blood. Hypoxia induced a 10-fold increase in ATP release from erythrocytes in the perfusates. If apyrase was added to the perfusates, ATP release was prevented and aspirin effects were evident again. Our results suggest that, under hypoxic conditions, the presence of aspirin would not help to inhibit further platelet activation.


Health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques: a case study with rice farmers in Vietnam.
Various methods for risk characterization have been developed using probabilistic approaches. Data on Vietnamese farmers are available for the comparison of outcomes for risk characterization using different probabilistic methods. This article addresses the health risk characterization of chlorpyrifos using epidemiological dose-response data and probabilistic techniques obtained from a case study with rice farmers in Vietnam. Urine samples were collected from farmers and analyzed for trichloropyridinol (TCP), which was converted into absorbed daily dose of chlorpyrifos. Adverse health response doses due to chlorpyrifos exposure were collected from epidemiological studies to develop dose-adverse health response relationships. The health risk of chlorpyrifos was quantified using hazard quotient (HQ), Monte Carlo simulation (MCS), and overall risk probability (ORP) methods. With baseline (prior to pesticide spraying) and lifetime exposure levels (over a lifetime of pesticide spraying events), the HQ ranged from 0.06 to 7.1. The MCS method indicated less than 0.05% of the population would be affected while the ORP method indicated that less than 1.5% of the population would be adversely affected. With postapplication exposure levels, the HQ ranged from 1 to 32.5. The risk calculated by the MCS method was that 29% of the population would be affected, and the risk calculated by ORP method was 33%. The MCS and ORP methods have advantages in risk characterization due to use of the full distribution of data exposure as well as dose response, whereas HQ methods only used the exposure data distribution. These evaluations indicated that single-event spraying is likely to have adverse effects on Vietnamese rice farmers.


Safe practice of population-focused nursing care: Development of a public health nursing concept.
Patient safety, a cornerstone of quality nursing care in most healthcare organizations, has not received attention in the specialty of public health nursing, owing to the conceptual challenges of applying this individual level concept to populations. Public health nurses (PHNs), by definition, provide population-focused care. Safe practice of population-focused nursing care involves preventing errors that would affect the health of entire populations and communities. The purpose of this article is to conceptually develop the public health nursing concept of safe practice of population-focused care and calls for related research. Key literature on patient safety is reviewed. Concepts applying to population-focused care are organized based on Donabedian's Framework. Structural, operational and system failures and process errors of omission and commission can occur at the population level of practice and potentially influence outcomes for population-patients. Practice, research and policy implications are discussed. Safe PHN population-focused practice deserves attention.


Metallo-beta-lactamase production by Pseudomonas otitidis: a species-related trait.
Susceptibility to several β-lactams and β-lactamase production was investigated in a collection of 20 strains of Pseudomonas otitidis, a new Pseudomonas species that has been recently recognized in association with otic infections in humans. All strains appeared to be susceptible to piperacillin, cefotaxime, ceftazidime, and aztreonam, while resistance or decreased susceptibility to carbapenems was occasionally observed. All strains were found to express metallo-β-lactamase (MBL) activity and to carry a new subclass B3 MBL gene, named bla(POM), that appeared to be highly conserved in this species. P. otitidis, therefore, is the first example of a pathogenic Pseudomonas species endowed with a resident MBL. The POM-1 protein from P. otitidis type strain MCC10330 exhibits the closest similarity (60 to 64%) to the L1 MBL of Stenotrophomonas maltophilia. Expression in Escherichia coli and Pseudomonas aeruginosa revealed that, similar to L1 and other subclass B3 MBLs, POM-1 confers decreased susceptibility or resistance to carbapenems, penicillins, and cephalosporins but not to aztreonam. Expression of the POM MBL in P. otitidis is apparently constitutive and, in most strains, does not confer a carbapenem-resistant phenotype. However, a strong inoculum size effect was observed for carbapenem MICs, and carbapenem-resistant mutants could be readily selected upon exposure to imipenem, suggesting that carbapenem-based regimens should be considered with caution for P. otitidis infections.


The effects of phonetic similarity and list length on children's sound categorization performance.
Three experiments investigating children's performance on tests of sound categorization are reported. In two experiments, the children had to decide which was the "odd one out" in a sequence of three, four, and five words. In each case the "oddity" judgement required selecting the word which differed in its final consonant, producing a different rime segment. The odd word differed either by one phonetic feature (voice or place) or by both voice and place, from the others in the sequence. Oddity judgements were easier when the odd word was phonetically dissimilar to the background items but, contrary to expectation, performance did not decline as list length increased. Experiment 3 extended these findings by showing that place-only changes were more difficult than voice-only changes. Sound categorization performance correlated with memory span for words, but memory span did not make an independent contribution to sound categorization once age and reading skills had been controlled. The experiments show that the sound categorization task taps individual differences in speech perception mechanisms but that memory load is less crucial to this task than has often been supposed.


Femoro-popliteal bypass above knee with saphenous vein vs synthetic graft.
There is still debate whether sintethic graft (polytetrafluoroethylene or Dacron) is equivalent to vein as bypass graft material for the above-knee femoropopliteal bypass. Therefore, we performed prospective randomized trial to compare vein with polytetrafluoroethylene/dacron for femoropopliteal bypasses with the distal anastomosis above the knee. Between January 2000 and June 2003, 121 femoropopliteal bypasses were performed. The indications for operation were severe claudication in 96 cases, rest pain in 16 cases, and ulceration in 9 cases. After randomization, 60 reversed saphenous venous bypasses and 61 polytetrafluoroethylene/dacron bypasses were performed. No perioperative mortality was seen, and 5% of the patients had minor infections of the wound, not resulting in loss of the bypass, the limb, or life. After 5 years, 37% of the patients had died and 7% were lost to follow-up. Only once saphenous vein was necessary for coronary artery bypass grafting. Primary patency rates after 5 years were 76,6% for venous bypass grafts and 59,1% for polytetrafluoroethylene/dacron grafts (p=0,035). Secondary patency rates were 83,3% for vein and 69,2% for polytetrafluoroethylene/dacron bypasses (p = 0,036). In the venous group, 10 bypasses failed, leading to four new bypasses. In the polytetrafluoroethylene group, 22 bypasses failed, leading to 12 reinterventions. After 5 years of follow-up, we conclude that a bypass with saphenous vein has better patency rates at all intervals and needs fewer reoperations. Saphenous vein should be the graft material of choice for above-knee femoropopliteal bypasses and should not be preserved for reinterventions. Polytetrafluoroethylene/dacron is an acceptable alternative if the saphenous vein is not available.


Effect of inhaled fluticasone propionate on airway responsiveness in treatment-naive individuals--a lesser benefit in females.
A randomized double-blind placebo-controlled parallel group study with inhaled fluticasone propionate over 6 weeks, designed to quantify the beneficial effect on airway responsiveness, and so assess whether short pulses of intermittent prophylactic treatment might serve as an alternative means of managing mild asthma, is reported. The 20-50-yr-old participants, who were recruited from an epidemiological study of the general population, had never knowingly received any regular treatment for asthma. Fluticasone propionate at the maximum recommended dose level (2,000 microg daily) and placebo were administered via metered-dose inhalers, and airway responsiveness was quantified conventionally by the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PD20) at 2-week intervals during the treatment phase and at various intervals subsequently. Compared with placebo fluticasone propionate was associated with a highly significant decrease in airway responsiveness (1.9 doublings of the geometric mean PD20), which was maximal at the end of the 6-week treatment period. No persisting benefit was detectable at the next measurement 2 weeks later, or thereafter. Multiple linear regression analysis showed that the magnitude of the fluticasone propionate effect was significantly greater in males than in females (3.2 versus 1.2 doublings respectively of the geometric mean PD20), but was uninfluenced by current smoking, age or FEV1. In conclusion, in the absence of any possibility of tachyphylaxis, inhaled fluticasone propionate at this dose causes a steadily increasing improvement in airway responsiveness over a 6-week period, which is modified by sex but lost almost immediately on treatment cessation. Short pulses of intermittent prophylactic treatment would not, therefore, be useful as a means of managing mild asthma.


Local Anaesthetic Systemic Toxicity in a Patient under General Anaesthesia (GA): A Diagnostic Challenge.
Local anaesthetic systemic toxicity (LAST) is one of the most dreadful complications after local anaesthetic (LA) use and it is very difficult to manage. The diagnosis of LAST is purely clinical and its presentation is usually obscured in a sedated or anaesthetized patient. A 25-year-old male patient undergoing laparotomy for acute duodenal perforation under general anaesthesia developed seizures after epidural administration of 0.5% bupivacaine. All other possible causes of seizures were ruled out. Seizures were controlled with antiepileptic drugs and patient recovered fully after withholding LA administration. Although, lipid rescue is recommended for LAST, our patient was managed without its use. We, therefore, recommend that utmost care and vigilance should be exercised while using local anesthetics as there is no perfectly accurate method to rule out intravascular administration of LA. Even, if LA is correctly used, LA is detected in plasma due to its systemic absorption from injection site.


Evaluation of Salmon (Salmo salar) and Rainbow Trout (Oncorhynchus mykiss) pin bones using textural analysis and micro X-ray computational tomography.
Industrially, common problems arise with the deboning pin bone process, where Atlantic Salmon (Salmo salar) and Rainbow Trout (Oncorhynchus mykiss) fillets, post rigor, are subjected to a pulling process to remove the pin bones from the fillet. This study measured the length of pin bones from two species of fish and two different industrial graded weights, and then used a texture analyser and µCT X-ray to measure the pulling force, break point and volume of the pin bones of both species of fish. Results showed that salmon pin bones required significantly higher pulling force to remove pin bones from the fish fillet when compared with Trout pin bones. Interestingly Trout pin bones were significantly longer and stronger than Salmon pin bones, but had significantly lower volume. This research has progressed the issues surrounding pin boning industrially, however, more studies are required in order to understand if these differences affect the overall deboning pin bone process.


Estimating maternal mortality: the sisterhood method.
This paper describes a new indirect technique for deriving population-based estimates of maternal mortality. The technique, called the "sisterhood method," is relevant to developing countries where the alternative data sources and approaches to estimation are often inadequate and inappropriate. The sisterhood method uses the proportions of adult sisters dying during pregnancy, childbirth, or the puerperium reported by adults during a census or survey, to derive a variety of indicators of maternal mortality. The first field trial of the method was carried out in the North Bank Division of The Gambia, West Africa, in 1987. The results indicate a lifetime risk of maternal mortality of 0.0584, or 1 in 17, approximating a maternal mortality ratio of 1,005 per 100,000 live births, which is consistent with previous estimates for this region.


Frequency of extreme precipitation increases extensively with event rareness under global warming.
The intensity of the heaviest extreme precipitation events is known to increase with global warming. How often such events occur in a warmer world is however less well established, and the combined effect of changes in frequency and intensity on the total amount of rain falling as extreme precipitation is much less explored, in spite of potentially large societal impacts. Here, we employ observations and climate model simulations to document strong increases in the frequencies of extreme precipitation events occurring on decadal timescales. Based on observations we find that the total precipitation from these intense events almost doubles per degree of warming, mainly due to changes in frequency, while the intensity changes are relatively weak, in accordance to previous studies. This shift towards stronger total precipitation from extreme events is seen in observations and climate models, and increases with the strength - and hence the rareness - of the event. Based on these results, we project that if historical trends continue, the most intense precipitation events observed today are likely to almost double in occurrence for each degree of further global warming. Changes to extreme precipitation of this magnitude are dramatically stronger than the more widely communicated changes to global mean precipitation.


LEAVES (optimizing the mentaL health and resiliencE of older Adults that haVe lost thEir spouSe via blended, online therapy): Proposal for an Online Service Development and Evaluation.
Loss of a spouse is a frequent occurrence in later life. While most older adults successfully process this loss and will return to a normal life, about 10% of the individuals are unable to cope, and progress to prolonged grief (PG). PG, in turn, can result in mental and physical problems including poor sleep, cardiovascular problems, depression, and suicidal tendencies. LEAVES (optimizing the mentaL health and resiliencE of older Adults that haVe lost thEir spouSe via blended, online therapy) is an online bereavement program that will support the prevention and treatment of PG, so that elderly mourners can continue to lead an active, meaningful, and dignified life. LEAVES will cater to secondary end users (eg, family, informal caregivers) by reducing stress. LEAVES will help older adults to process the loss of a spouse in an online environment, which consists of (1) an existing online grief self-help program LIVIA, (2) the Before You Leave program that allows for storing personal memories, (3) a virtual agent platform, and (4) an accessible front-end design. LEAVES can detect persons at risk for complications, reveal negative trends in their emotional life, and act to counter such trends. The service relies on online support whenever possible but is blended with telephone or face-to-face counseling when necessary. The project will take place between February 2020 and January 2023 and includes a real-life evaluation in which 315 end users will use the service across 3 countries (the Netherlands, Portugal, and Switzerland). The evaluation of LEAVES will focus on clinical effect, its business case, and technology acceptance. The results will pave the way for smooth integration into existing care paths and reimbursement schemes. The LEAVES service aims to soften the mourning process, prevents depression or social isolation, strengthens widow(er)s resilience and well-being, and quickens one's return to societal participation. DERR1-10.2196/19344.


Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro.
Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.


Diagnostic and prognostic value of low density lipoprotein-containing circulating immune complexes in atherosclerosis.
Recently, it has been shown that increased level of LDL-containing circulating immune complexes (LDL-CIC) possess high diagnostic significance in clinically manifested atherosclerosis, but little is known about its diagnostic and prognostic significance in early atherosclerosis. Two-years prospective study was performed in 98 asymptomatic men aged 40-74. The rate of atherosclerosis progression was estimated by high-resolution B-mode ultrasonography as the increase in intima-media thickness (IMT) of common carotid arteries. The patients with elevated baseline levels of LDL-CIC were characterized by significantly higher levels of total and LDL cholesterol as well as significantly increased mean IMT of common carotid arteries. Among all baseline lipid parameters, only LDL-CIC and LDL cholesterol were contingent with the extent of early carotid atherosclerosis (p = 0.042 and p = 0.049, respectively) and had the highest levels of relative risk and odds ratio. During the follow up, significant IMT increase was registered in 53.1 % (n = 52) patients, IMT significant reduction was observed in 21.4 % (n = 21) patients. The increased levels of LDL-CIC, total serum cholesterol and LDL cholesterol had similar prognostic significance with the respect of atherosclerosis progression. The normal level of LDL-CIC (below than 16.0 μg/ml) was the only lipid parameter that predicted the absence of carotid atherosclerosis progression for two following years at prognostic value of 78.3 %. The results of the study allow assuming that LDL-CIC level may be employed not only as a marker of early atherosclerosis, but also has a sufficient prognostic value for clinical implications.


Single-photon sensitive light-in-fight imaging.
The ability to record images with extreme temporal resolution enables a diverse range of applications, such as fluorescence lifetime imaging, time-of-flight depth imaging and characterization of ultrafast processes. Recently, ultrafast imaging schemes have emerged, which require either long acquisition times or raster scanning and have a requirement for sufficient signal that can only be achieved when light is reflected off an object or diffused by a strongly scattering medium. Here we present a demonstration of the potential of single-photon detector arrays for visualization and rapid characterization of events evolving on picosecond time scales. The single-photon sensitivity, temporal resolution and full-field imaging capability enables the observation of light-in-flight in air, as well as the measurement of laser-induced plasma formation and dynamics in its natural environment. The extreme sensitivity and short acquisition times pave the way for real-time imaging of ultrafast processes or visualization and tracking of objects hidden from view.


Referral of patients with chronic obstructive pulmonary disease to pulmonary rehabilitation: a qualitative study of barriers and enablers for primary healthcare practitioners.
Pulmonary rehabilitation (PR) is a cost-effective, internationally recommended intervention for patients with chronic obstructive pulmonary disease (COPD). Referral is predominately led by primary healthcare practitioners (PHCPs), but referral and patient uptake is poor. To understand barriers and enablers for PHCPs when considering patient referral to PR, to explore the influence of patient characteristics, and to understand how referral rates may be increased. PHCPs who care for and refer patients with COPD to PR were purposively selected from general practices across Cambridgeshire and Peterborough, and the West Midlands. A qualitative study. Semi-structured interviews were undertaken to theme saturation, exploring PR referral. Images depicting patients with varying COPD severity were used to stimulate memory and associative recall. Interviews were recorded, transcribed verbatim, and analysed using rapid qualitative analysis. A total of 19 PHCPs were interviewed. Barriers to PR referral included limited awareness of the clinical benefits, little knowledge of local PR providers, consultation time constraints, and presumed low patient motivation. While practice nurses had the greatest knowledge, they still described difficulty in promoting PR. PHCPs frequently described assessing patient suitability based on presumed accessibility, social, and disease-specific characteristics rather than the clinical benefits of PR. Referrals were facilitated by financial incentives for the practice and positive feedback from patients and providers. There were more barriers to PR referral than enablers. Providers must engage better with PHCPs, patients with COPD, and carers, and actively promote PR. Increasing PHCPs' awareness of the benefits of PR, financial incentives, and alternative referral pathways should be considered.


Oomycete Species Associated with Soybean Seedlings in North America-Part II: Diversity and Ecology in Relation to Environmental and Edaphic Factors.
Soybean (Glycine max (L.) Merr.) is produced across a vast swath of North America, with the greatest concentration in the Midwest. Root rot diseases and damping-off are a major concern for production, and the primary causal agents include oomycetes and fungi. In this study, we focused on examination of oomycete species distribution in this soybean production system and how environmental and soil (edaphic) factors correlate with oomycete community composition at early plant growth stages. Using a culture-based approach, 3,418 oomycete isolates were collected from 11 major soybean-producing states and most were identified to genus and species using the internal transcribed spacer region of the ribosomal DNA. Pythium was the predominant genus isolated and investigated in this study. An ecology approach was taken to understand the diversity and distribution of oomycete species across geographical locations of soybean production. Metadata associated with field sample locations were collected using geographical information systems. Operational taxonomic units (OTU) were used in this study to investigate diversity by location, with OTU being defined as isolate sequences with 97% identity to one another. The mean number of OTU ranged from 2.5 to 14 per field at the state level. Most OTU in this study, classified as Pythium clades, were present in each field in every state; however, major differences were observed in the relative abundance of each clade, which resulted in clustering of states in close proximity. Because there was similar community composition (presence or absence) but differences in OTU abundance by state, the ordination analysis did not show strong patterns of aggregation. Incorporation of 37 environmental and edaphic factors using vector-fitting and Mantel tests identified 15 factors that correlate with the community composition in this survey. Further investigation using redundancy analysis identified latitude, longitude, precipitation, and temperature as factors that contribute to the variability observed in community composition. Soil parameters such as clay content and electrical conductivity also affected distribution of oomycete species. The present study suggests that oomycete species composition across geographical locations of soybean production is affected by a combination of environmental and edaphic conditions. This knowledge provides the basis to understand the ecology and distribution of oomycete species, especially those able to cause diseases in soybean, providing cues to develop management strategies.


Views from Within a Narrative: Evaluating Long-Term Human-Robot Interaction in a Naturalistic Environment Using Open-Ended Scenarios.
This article describes the prototyping of human-robot interactions in the University of Hertfordshire (UH) Robot House. Twelve participants took part in a long-term study in which they interacted with robots in the UH Robot House once a week for a period of 10 weeks. A prototyping method using the narrative framing technique allowed participants to engage with the robots in episodic interactions that were framed using narrative to convey the impression of a continuous long-term interaction. The goal was to examine how participants responded to the scenarios and the robots as well as specific robot behaviours, such as agent migration and expressive behaviours. Evaluation of the robots and the scenarios were elicited using several measures, including the standardised System Usability Scale, an ad hoc Scenario Acceptance Scale, as well as single-item Likert scales, open-ended questionnaire items and a debriefing interview. Results suggest that participants felt that the use of this prototyping technique allowed them insight into the use of the robot, and that they accepted the use of the robot within the scenario.


Dispersion enhancement of the nonlinear electro-optical effect.
It is proposed for the first time how an electrically poled chirped Bragg grating in an optical fiber may be used for creating efficient, electrically controllable optical fiber delay lines. The tunable range for the delay can be chosen by fixing the chirp rate of the Bragg grating. Additionally, strain and temperature may be used to change the centre wavelength of the delay line. Dispersion may also be used to increase phase-modulation in nonlinear optical fibers.


Longitudinal dimensionality of adolescent psychopathology: testing the differentiation hypothesis.
The differentiation hypothesis posits that the underlying liability distribution for psychopathology is of low dimensionality in young children, inflating diagnostic comorbidity rates, but increases in dimensionality with age as latent syndromes become less correlated. This hypothesis has not been adequately tested with longitudinal psychiatric symptom data. Confirmatory factor analyses of DSM-IV symptoms from seven common Axis I syndromes--major depression, generalized anxiety, separation anxiety, social anxiety, attention deficient hyperactivity, conduct, and oppositional defiant disorders--were conducted longitudinally, from ages 9 to 16, using the general-population Great Smoky Mountains Study sample. An eight-syndrome model fit well at all ages, and in both genders. It included social anxiety, separation anxiety, oppositional defiant, and conduct syndromes, along with a multidimensional attention deficit-hyperactivity syndrome (i.e., inattention, hyperactivity, and impulsivity) and a unidimensional major depression/generalized anxiety syndrome. A high degree of measurement invariance across age was found for all syndromes, except for major depression/generalized anxiety. Major depression and generalized anxiety syndromes slightly diverged at age 14-16, when they also began to explain more symptom variance. Additionally, correlations between some emotional and disruptive syndromes showed slight differentiation. Marked developmental differentiation of psychopathology, as implied by the orthogenetic principle, is not a prominent cause of preadolescent and adolescent psychiatric comorbidity.


Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species.
Two cyp51-related genes (cyp51A and cyp51B) encoding 14-alpha sterol demethylase-like enzymes were identified in the opportunistic human pathogen Aspergillus fumigatus. PCR amplification using degenerate oligonucleotides based on conserved areas of cytochrome P450 demethylases of other filamentous fungi and yeasts allowed the cloning and sequencing of two different homologue genes in A. fumigatus. Southern analysis confirmed that both genes hybridized to distinct genomic loci and that both are represented as single copies in the genome. Comparison of the deduced Cyp51A and Cyp51B proteins with the CYP51 proteins from Penicillium italicum, Aspergillus nidulans, Erysiphe graminis, Uncinula necator, Botrytis cinerea, Ustilago maydis, Cryptococcus neoformans, Candida albicans, Saccharomyces cerevisiae, Candida tropicalis, and Candida glabrata showed that the percentages of identity of the amino acid sequences (range, 40 to 70%) were high enough to consider Cyp51A and Cyp51B to be members of the fungal CYP51 family. Fragments from both genes were also cloned from other Aspergillus spp. (A. flavus, A. nidulans, and A. terreus). Phylogenetic analysis showed that, at least in the most pathogenic species of Aspergillus, there are two fungal CYP51 proteins. This is the first report of the existence of two homologue genes coding for 14-alpha sterol demethylase in the fungal kingdom. This finding could provide insights into the azole resistance mechanisms operating in fungi. The primers used here may be useful molecular tools for facilitating the cloning of novel 14-alpha sterol demethylase genes in other filamentous fungi.


Drug use and HIV risk--related sex behaviors: a street outreach study of black adults.
Our street outreach project investigated the relationship between use of noninjecting drugs (alcohol, marijuana, cocaine) and human immunodeficiency virus (HIV) risk-related sex behaviors of black adults. The study focused on three HIV-related risks: multiple sex partners, unprotected sex, and drugs during sex. Data for this study were collected in a street outreach community survey for a drug abuse and HIV intervention study in Birmingham, Ala. A total of 780 black men and women completed the survey. High-risk sex behaviors were far more prevalent among cocaine users than marijuana or alcohol users. A greater number of cocaine users reported having multiple sex partners, not using condoms, and using drugs during sex. Female cocaine users showed the same risk level for HIV infection as male cocaine users. Increased risk of HIV infection through sexual transmission is associated with use of noninjecting cocaine for both men and women. Condom use should be considered as a major component of HIV prevention programs.


Validation of Subjective Well-Being Measures Using Item Response Theory.
Background: Subjective well-being refers to the extent to which a person believes or feels that her life is going well. It is considered as one of the best available proxies for a broader, more canonical form of well-being. For over 30 years, one important distinction in the conceptualization of subjective well-being is the contrast between more affective evaluations of biological emotional reactions and more cognitive evaluations of one's life in relation to a psychologically self-imposed ideal. More recently, researchers have suggested the addition of harmony in life, comprising behavioral evaluations of how one is doing in a social context. Since measures used to assess subjective well-being are self-reports, often validated only using Classical Test Theory, our aim was to focus on the psychometric properties of the measures using Item Response Theory. Method: A total of 1000 participants responded to the Positive Affect Negative Affect Schedule. At random, half of the participants answered to the Satisfaction with Life Scale or to the Harmony in life Scale. First, we evaluate and provide enough evidence of unidimensionality for each scale. Next, we conducted graded response models to validate the psychometric properties of the subjective well-being scales. Results: All scales showed varied frequency item distribution, high discrimination values (Alphas), and had different difficulty parameters (Beta) on each response options. For example, we identified items that respondents found difficult to endorse at the highest/lowest point of the scales (e.g., "Proud" for positive affect; item 5, "If I could live my life over, I would change almost nothing," for life satisfaction; and item 3, "I am in harmony," for harmony in life). In addition, all scales could cover a good portion of the range of subjective well-being (Theta): -2.50 to 2.30 for positive affect, -1.00 to 3.50 for negative affect, -2.40 to 2.50 for life satisfaction, and -2.40 to 2.50 for harmony in life. Importantly, for all scales, there were weak reliability for respondents with extreme latent scores of subjective well-being. Conclusion: The affective component, especially low levels of negative affect, were less accurately measured, while both the cognitive and social component were covered to an equal degree. There was less reliability for respondents with extreme latent scores of subjective well-being. Thus, to improve reliability at the level of the scale, at the item level and at the level of the response scale for each item, we point out specific items that need to be modified or added. Moreover, the data presented here can be used as normative data for each of the subjective well-being constructs.


Sapropterin dihydrochloride treatment in Turkish hyperphenylalaninemic patients under age four.
Sapropterin enhances phenylalanine hydroxylase activity, thus lowering blood phenylalanine (Phe) concentration while increasing protein tolerance in sapropterin-responsive patients. Initiation of sapropterin treatment in responsive patients as early as possible, especially during the time when brain development is fastest, allows intake of more natural protein as well as micro- and macronutrients. Initiation of sapropterin treatment in the newborn period can make exclusive breastfeeding possible. Reports on the efficacy and safety of sapropterin in phenylketonuria (PKU) children under age four are limited in the literature. The purpose of this study is to evaluate the efficacy and safety of sapropterin treatment in infants and children with hyperphenylalaninemia (HPA) and to assess whether genotype analyses are of help in the prediction of responsiveness in these children. Clinical features as well as dietary characteristics were examined in 44 patients undergoing sapropterin treatment. Molecular genetic analysis was performed in 28 of these patients. Phe tolerance increased a median of 2.26-fold (0.88-4.23), from a median of 47.5 mg/kg/day to a median of 114 mg/kg/day (p<0.001). Phe levels could not be kept within normal limits in 5 patients, and thus treatment was stopped due to unsatisfactory metabolic control. In 9 patients, sapropterin treatment was started prior to the initiation of a Phe-restricted diet. Sapropterin treatment was found to be safe and efficacious in patients under age four. Although the BH4 loading test and molecular genetic analysis proved to be useful in detecting responsive patients, these analyses did not enable us to make predictions as to long-term responsiveness.


Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression.
Proteinase 3 (PR3) is a major autoantigen in anti-neutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis (AASV), and the proportion of neutrophils expressing PR3 on their membrane (mPR3+) is increased in AASV. We have shown recently that mPR3 and CD177 are expressed on the same cells in healthy individuals. In this study we try to elucidate mechanisms behind the increased mPR3 expression in AASV and its relationship to CD177. All neutrophils in all individuals were either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils was increased significantly in AASV and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells was not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. AASV patients had normal levels of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Pro-PR3 was found to constitute 10% of circulating PR3 but none of the mPR3. We found increased mRNA levels of both PR3 and CD177 in AASV, but they did not correlate with the proportion of double-positive cells. In cells sorted based on membrane expression, CD177-mRNA was several-fold higher in mPR3+ cells. When exogenous PR3 was added to CD177-transfected U937 cells, only CD177+ cells bound PR3 to their membrane. In conclusion, the increased membrane expression of PR3 found in AASV is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene.


Community-based palliative care: the natural evolution for palliative care delivery in the U.S.
Palliative care in the U.S. has evolved from a system primarily reliant on community-based hospices to a combined model that includes inpatient services at most large hospitals. However, these two dominant approaches leave most patients needing palliative care-those at home (including nursing homes) but not yet ready for hospice-unable to access the positive impacts of the palliative care approach. We propose a community-based palliative care (CPC) model that spans the array of inpatient and outpatient settings in which palliative care is provided and links seamlessly to inpatient care; likewise, it would span the full trajectory of advanced illness rather than focusing on the period just before death. Examples of CPC programs are developing organically across the U.S. As our understanding of CPC expands, standardization is needed to ensure replicability, consistency, and the ability to relate intervention models to outcomes. A growing body of literature examining outpatient palliative care supports the role of CPC in improving outcomes, including reduction in symptom burden, improved quality of life, increased survival, better satisfaction with care, and reduced health care resource utilization. Furthermore the examination of how to operationalize CPC is needed before widespread implementation can be realized. This article describes the key characteristics of CPC, highlighting its role in longitudinal care across patient transitions. Distinguishing features include consistent care across the disease trajectory independent of diagnosis and prognosis; inclusion of inpatient, outpatient, long-term care, and at-home care delivery; collaboration with other medical disciplines, nursing, and allied health; and full integration into the health care system (rather than parallel delivery).


Phytosanitation Methods Influence Posttreatment Colonization of Juglans nigra Logs by Pityophthorus juglandis (Coleoptera: Curculionidae: Scolytinae).
Several North American walnut species (Juglans spp.) are threatened by thousand cankers disease which is caused by the walnut twig beetle (Pityophthorus juglandis Blackman) and its associated fungal plant pathogen, Geosmithia morbida M. Kolarík, E. Freeland, C. Utley and N. Tisserat sp. nov. Spread of this disease may occur via movement of infested black walnut (Juglans nigra L.) wood. This study evaluated the ability of P. juglandis to colonize J. nigra wood previously treated with various phytosanitation methods. Steam-heated and methyl bromide-fumigated J. nigra logs, as well as kiln-dried natural wane J. nigra lumber (with and without bark) were subsequently exposed to P. juglandis colonization pressure in two exposure scenarios. Following a pheromone-mediated, high-pressure scenario in the canopy of infested trees, beetles readily colonized the bark of steam-heated and methyl bromide-fumigated logs, and were also recovered from kiln-dried lumber on which a thin strip of bark was retained. In the simulated lumberyard exposure experiment, during which samples were exposed to lower P. juglandis populations, beetles were again recovered from bark-on steam-heated logs, but were not recovered from kiln-dried bark-on lumber. These data suggest logs and bark-on lumber treated with phytosanitation methods should not be subsequently exposed to P. juglandis populations. Further beetle exclusion efforts for phytosanitized, bark-on walnut wood products transported out of quarantined areas may be necessary to ensure that these products do not serve as a pathway for the spread of P. juglandis and thousand cankers disease.


Flotation of diamond in mantle melt at high pressure.
Experiments show that diamond floats in a primitive mantle melt at around 20 gigapascals and 2360 degrees C and in a melt formed by partial melting of the transition zone at about 16 gigapascals and 2270 degrees C. These observations constrain magma densities at high pressure. Diamond precipitated or trapped in a silicate melt at the base of the transition zone or the lower mantle floats and has been accumulating in the transition zone since early in Earth's history. Thus, the transition zone could be a reservoir of diamond.


Systemic clearance and demethylation of caffeine in sheep and cattle.
Pharmacokinetics of caffeine have been studied in sheep and cattle treated with caffeine (5 mg/kg) by intravenous injection. Terminal-phase elimination half-lives were 8.9 hr in sheep and 8.1 hr in cattle. Noncompartmental analyses of data collected from individual animals indicate that neither terminal-phase rate constants (beta) nor mean residence times of caffeine in plasma differed between species. Each of the three possible N-demethylated primary metabolites of caffeine was detected in plasma from each species, with theophylline predominating in sheep and paraxanthine predominating in cattle. These data indicate that hepatic capacity to clear caffeine from the systemic circulation is similar between sheep and cattle, but that the preferred routes of metabolism differ. Expression of cytochromes P4501A (CYP1A subfamily) may differ between these species.


Exposure of firefighters to particulates and polycyclic aromatic hydrocarbons.
Firefighting continues to be among the most hazardous yet least studied occupations in terms of exposures and their relationship to occupational disease. Exposures are complex, involving mixtures of particles and chemicals such as polycyclic aromatic hydrocarbons (PAHs). Adverse health effects associated with these agents include elevated incidences of coronary heart disease and several cancers. PAHs have been detected at fire scenes, and in the firehouse rest area and kitchen, routinely adjoining the truck bay, and where firefighters spend a major part of each shift. An academic-community partnership was developed with the Cincinnati Fire Department with the goal of understanding active firefighters' airborne and dermal PAH exposure. PAHs were measured in air and particulates, and number and mass concentrations, respectively, of submicron (0.02-1 μm) and PM2.5 (2.5 μm diameter and less) particles during overhaul events in two firehouses and a University of Cincinnati administrative facility as a comparison location. During overhaul firefighters evaluate partially combusted materials for re-ignition after fire extinguishment and commonly remove Self-Contained Breathing Apparatus (SCBA). Face and neck wipes were also collected at a domestic fire scene. Overhaul air samples had higher mean concentrations of PM2.5 and submicron particles than those collected in the firehouse, principally in the truck bay and kitchen. Among the 17 PAHs analyzed, only naphthalene and acenaphthylene were generally detectable. Naphthalene was present in 7 out of 8 overhaul activities, in 2 out of 3 firehouse (kitchen and truck bay) samples, and in none collected from the control site. In firefighter face and neck wipes a greater number of PAHs were found, several of which have carcinogenic activity, such as benzofluoranthene, an agent also found in overhaul air samples. Although the concentration for naphthalene, and all other individual PAHs, was very low, the potential simultaneous exposure to multiple chemicals even in small quantities in combination with high ultrafine particle exposure deserves further study. It is recommended that personal respiratory and skin protection be worn throughout the overhaul process.


Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study.
To assess the mental health of children born after fertility treatment by comparing their risk of mental disorders with that of spontaneously conceived children. Prospective register based cohort study. Nationwide register based information from Danish National Health Registers cross linked by a unique personal identification number assigned to all citizens in Denmark. All children born in Denmark in 1995-2003 with follow-up in 2012 when the children were aged 8-17; 33,139 children were conceived after fertility treatment and 555,828 children were born after spontaneous conception. Absolute risks and hazard ratios for overall and specific mental disorders estimated with adjustment for potential confounding variables. Estimated association between the risk of mental disorders and subtypes of procedures, hormone treatments, gamete types, and cause of infertility. The risk of mental disorders in children born after in vitro fertilisation or intracytoplasmic sperm injection was low, and was no higher than in spontaneously conceived children, except for a borderline significant increased risk of tic disorders (hazard ratio 1.40, 95% confidence interval 1.01 to 1.95; absolute risk 0.3%). In contrast, children born after ovulation induction with or without insemination had low but significantly increased risks of any mental disorder (1.20, 1.11 to 1.31; absolute risk 4.1%), autism spectrum disorders (1.20, 1.05 to 1.37; 1.5%), hyperkinetic disorders (1.23, 1.08 to 1.40; 1.7%), conduct, emotional, or social disorder (1.21, 1.02 to 1.45; 0.8%), and tic disorders (1.51, 1.16 to 1.96; 0.4%). There was no risk systematically related to any specific type of hormone drug treatment. There was a small increase in the incidence of mental disorders in children born after ovulation induction/intrauterine insemination. Children born after in vitro fertilisation/intracytoplasmic sperm injection were found to have overall risk comparable with children conceived spontaneously.


More than a meal… integrating non-feeding interactions into food webs.
Organisms eating each other are only one of many types of well documented and important interactions among species. Other such types include habitat modification, predator interference and facilitation. However, ecological network research has been typically limited to either pure food webs or to networks of only a few (<3) interaction types. The great diversity of non-trophic interactions observed in nature has been poorly addressed by ecologists and largely excluded from network theory. Herein, we propose a conceptual framework that organises this diversity into three main functional classes defined by how they modify specific parameters in a dynamic food web model. This approach provides a path forward for incorporating non-trophic interactions in traditional food web models and offers a new perspective on tackling ecological complexity that should stimulate both theoretical and empirical approaches to understanding the patterns and dynamics of diverse species interactions in nature.


Experimental implementation of the multifunctional compact two-photon state analyzer.
We report on experimental implementation of a multifunctional two-photon state analyzer. The device aims to be compact and able to provide several important characteristics about any two-photon quantum state. It operates in two modes: first mode is the two-photon interference analysis giving the information about spectral properties of the photons and the degree of mutual indistinguishability. The second mode provides polarization analysis and complete two-photon state tomography. Density matrix estimated from the tomography data reveals namely the quantum state purity or negativity. This device was tested on the photon pairs generated by the Kwiat source.


Effect of Attitudinal, Situational and Demographic Factors on Annoyance Due to Environmental Vibration and Noise from Construction of a Light Rapid Transit System.
The aim of this paper is to determine what non-exposure factors influence the relationship between vibration and noise exposure from the construction of a Light Rapid Transit (LRT) system and the annoyance of nearby residents. Noise and vibration from construction sites are known to annoy residents, with annoyance increasing as a function of the magnitude of the vibration and noise. There is not a strong correlation between exposure and levels of annoyance suggesting that factors not directly related to the exposure may have an influence. A range of attitudinal, situational and demographic factors are investigated with the aim of understanding the wide variation in annoyance for a given vibration exposure. A face-to-face survey of residents (n = 350) near three sites of LRT construction was conducted, and responses were compared to semi-empirical estimates of the internal vibration within the buildings. It was found that annoyance responses due to vibration were strongly influenced by two attitudinal variables, concern about property damage and sensitivity to vibration. Age, ownership of the property and the visibility of the construction site were also important factors. Gender, time at home and expectation of future levels of vibration had much less influence. Due to the measurement methods used, it was not possible to separate out the effects of noise and vibration on annoyance; as such, this paper focusses on annoyance due to vibration exposure. This work concludes that for the most cost-effective reduction of the impact of construction vibration and noise on the annoyance felt by a community, policies should consider attitudinal factors.


The associations between phthalate exposure and insulin resistance, β-cell function and blood glucose control in a population-based sample.
In developed countries, phthalate exposure is ubiquitous. Previous studies have shown an association between phthalate levels and health effects. To test associations between phthalate exposures, estimated from urinary phthalate metabolites, and insulin resistance, β-cell function and glucose control. Data were obtained from a cross-sectional, nationally representative study; the Canadian Health Measures Survey (CHMS, 2009-2011). Participants under the age of 12, those with diabetes, who were pregnant or who had not fasted overnight were excluded. Fasting blood glucose, insulin, and glycosylated hemoglobin (HbA1C) levels were measured in a subset of participants, and urine was collected for creatinine and phthalate metabolites. We tested associations between these variables using linear regression analysis. Of 4437 participants (12-79years old), 2119 had fasting glucose measurements and at least one phthalate metabolite above detection limits. MBzP, MCPP, MEHP, MEHHP, MiBP, and the sum of DEHP metabolites were positively associated with increased HbA1C (p<0.05). DEHP metabolites were positively associated with increased fasting glucose, insulin, HOMA-IR and HOMA-β. An interquartile increase in the sum of log transformed DEHP metabolites was associated with increases in HOMA-IR and HOMA-β of 0.15 (95% CI 0.04, 0.26) and 10.24 (95% CI 3.71, 16.77) respectively. Increased concentrations of all measured phthalate metabolites were associated with reduced blood glucose control. DEHP metabolites were also associated with increased glucose concentrations, and indicators of β-cell function and insulin resistance. Our results suggest that exposure to phthalates may possibly impair control of blood glucose and thereby predispose to pre-diabetes.


Introducing Hybrid Problem-Based Learning Modules in Ayurveda Education: Results of an Exploratory Study.
Objectives: Problem-based learning (PBL) is a well-known student-centered instructional approach that is known to enhance problem-solving skills among the learners. Because teaching/learning methods in most of the Ayurveda colleges in India are still didactic and teacher centric, the effects of introducing PBL have not yet been evaluated. The primary objective of this study was to develop PBL modules for Kriya Sharira (Ayurveda Physiology) and their implementation in a hybrid format. In this method, PBL is used as an add-on component along with didactic lectures. The secondary objective of the study was to compare the learning outcomes achieved through hybrid problem-based learning (HPBL) with those achieved through conventional teaching. Design: This is a prospectively planned post-test-only, controlled interventional design with nonequivalent groups. However, the results have been analyzed in a retrospective manner. Subjects: Students enrolled in the first professional Bachelor of Ayurvedic Medicine and Surgery program during two consecutive academic sessions 2016-2017 and 2017-2018 at the Banaras Hindu University were included in the study. While the cohort from 2016 to 2017 session served as the control group, the one from 2017 to 2018 session served as the experimental group. Interventions: The instructional method commonly known as HPBL was introduced to the experimental group. Outcome measures: Five test papers containing mostly Multiple Choice Questions for five different topics were used as the tools for evaluating the learning outcomes in both the groups. Feedback forms regarding the experiences of undergoing HPBL were obtained from experimental group. Results: While the test results for three topics showed that the outcomes of HPBL were comparable with conventional teaching, the results on other two topics suggested that HPBL was slightly better. Feedback obtained showed that there is a considerable acceptance for HPBL over conventional method. Conclusions: The study shows that it is possible to implement HPBL method in a large classroom in the context of Ayurveda education. The findings also indicate that students find HPBL as an acceptable teaching method.


Five new species of Acanthobothrium (Cestoda: Tetraphyllidea) from an unusual species of Himantura (Rajiformes: Dasyatidae) from northern Australia.
Five new species of Acanthobothrium van Beneden, 1850 from the spiral intestine of a specimen of an unusual species of Himantura from the Arafura Sea off northern Australia are described. Acanthobothrium oceanharvestae sp. n. is one of 26 category 1 species (sensu Ghoshroy and Caira 2001) lacking post-ovarian testes; it differs from these in total length, number of proglottids, number of testes, cirrus sac size and details of the terminal genitalia. Acanthobothrium popi sp. n. is unique among category 2 species in its possession of post-ovarian testes. Acanthobothrium rodmani sp. n. is a category 6 species distinct from all congeners in the dense blade-like spinitriches on the distal surfaces of its anterior-most bothridial loculi and conspicuously tapered posterior bothridial margins, which are reflexed anteriorly. Acanthobothrium romanowi sp. n. differs from most other category 1 species in that its genital pore is distinctly posterior. It differs from the remaining category 1 species in size, testis number, cephalic peduncle microthrix form, proglottid shape, and bothridial loculus dimensions. Acanthobothrium zimmeri sp. n. is among the six category 1 species with post-ovarian testes. It differs from these species in total length, ovary shape, number of proglottids and testes and vas deferens extent. This brings the number of Acanthobothrium species with post-ovarian testes to 10, all of which are Indo-Pacific in distribution, and 7 of which parasitize Himantura species. A key to the five new species parasitizing Himantura sp. is provided. Sequence data for the D1-D3 region of 28S rDNA for the five new species and two congeners parasitizing other Himantura species shows no intraspecific variation. Analysis of these and comparable data for two species available in GenBank (Acanthobothrium parviuncinatum and Acanthobothrium sp. 1) showed an interspecific variation of 0.7-11.3% among species pairs. Bayesian, Likelihood and Parsimony phylogenetic analyses of these data for these nine species indicate that the five new species parasitizing Himantura sp. are generally not each others' closest relatives.


Primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst: a case report and literature review.
Primary intraosseous squamous cell carcinoma (PIOSCC) derived from an odontogenic keratocyst (OKC) is a rare malignant neoplasm of the jaws, which is locally aggressive with quite poor prognosis. The incidence of carcinomas arising in odontogenic cysts was reported to be approximately 1-2/1000. The number of well-documented cases of PIOSCC ex OKC is extremely small; hence, no sufficient incidence data are available in the literature. Overall, the survival rate of an individual, which is a period of two years, is very poor, and this can be attributed to the delayed diagnosis. But knowledge of the histopathological and immunohistological features of PIOSCC allows accurate and early diagnosis of the lesion so that an early and appropriate treatment can be instituted for better prognosis. The following report describes an extremely rare case of PIOSCC of the mandible derived from an OKC in a 20-year-old female patient.


Balloon Pumps Inserted via the Subclavian Artery: Bridging the Way to Heart Transplant.
Intra-aortic balloon pumps have traditionally been inserted via the femoral artery, limiting patients' activity and exposing patients to complications of immobility. For patients awaiting cardiac transplant, these complications may threaten a successful outcome, or at the least, complicate recuperation after transplant. A novel approach to insertion of balloon pumps via the subclavian artery is presented here, including routine nursing care, complications and related nursing actions, and experience with and advantages of this method. A team approach to care of these patients, including rehabilitation and exercise protocols, is recommended.


Rapid interferometric imaging of printed drug laden multilayer structures.
The developments in printing technologies allow fabrication of micron-size nano-layered delivery systems to personal specifications. In this study we fabricated layered polymer structures for drug-delivery into a microfluidic channel and aimed to interferometrically assure their topography and adherence to each other. We present a scanning white light interferometer (SWLI) method for quantitative assurance of the topography of the embedded structure. We determined rapidly in non-destructive manner the thickness and roughness of the structures and whether the printed layers containing polymers or/and active pharmaceutical ingredients (API) adhere to each other. This is crucial in order to have predetermined drug release profiles. We also demonstrate non-invasive measurement of a polymer structure in a microfluidic channel. It shown that traceable interferometric 3D microscopy is a viable technique for detailed structural quality assurance of layered drug-delivery systems. The approach can have impact and find use in a much broader setting within and outside life sciences.


Suspected sphenoid bone osteomyelitis causing visual impairment in two dogs and one cat.
To present the clinical and magnetic resonance imaging (MRI) characteristics of sphenoid bone osteomyelitis. Two dogs (English Springer Spaniel--ESS, Golden Retriever--GR) and one cat (Domestic Long Haired) were presented with a 2-14-day history of visual deficits and reduced pupillary light reflexes. Investigations included physical, ophthalmologic and neurological examination as well as hematology, serum biochemistry, MRI of the head and cerebrospinal fluid (CSF) analysis. MRI changes included thickening of the sphenoid bone and a loss of normal bone marrow signal on T1W MRI. Enhancement of the sphenoid bones, ventral meninges and ventral surface of the brain was present using paramagnetic contrast medium. CSF analysis was abnormal in the two dogs with increased cellularity, neutrophilic pleocytosis, intracellular bacteria and increased total protein in one, and with lymphocytic pleocytosis in another. CSF analysis was normal in the cat. An underlying cause for the osteomyelitis could not be identified. The use of broad-spectrum antibiotics for 3-6 weeks combined with anti-inflammatory medications proved effective. Full clinical recovery occurred with no relapse during the follow up time of 7 (ESS) and 4 (Domestic Long Haired) years. The GR relapsed 10 months after treatment and recovered following a second 3-week course of broad-spectrum antibiotics with no relapse during the following 3 years. Visual pathway deficits in dogs and cats may be due to sphenoid bone osteomyelitis. MRI and CSF analysis can assist diagnosing this potentially treatable condition. To the authors' knowledge this is the first report of sphenoid bone osteomyelitis in these species.


Upskirting: A Systematic Literature Review.
Upskirting' - the non-consensual taking and/or dissemination of intimate images taken surreptitiously up a skirt - is a relatively new addition to the repertoire of men's violence against women and girls. Recently, it has received considerable media and public attention in many countries and some academic scrutiny. This systematic review explicates how scholars construct upskirting as a matter for academic inquiry and a social problem that requires remedy. Four research sub-questions address how scholarship constructs: the problem of upskirting; perpetrators of upskirting; victims of upskirting, and remedies. Five bibliographical databases were searched, yielding 26 sources that met the inclusion criteria. Most of the studies (16) and most of the earlier work are from the discipline of Law. Other studies come from a combination of Criminology, Media Studies, Cultural Studies, Psychology, Social Work, Sociology, and Computing. The predominance of legal scholarship has created a framing of upskirting which constructs it as an individual sexual act, for purposes of sexual gratification, as gender-neutral, as the act of aberrant individuals, and scrutinises the act of taking the photograph. By contrast, scholarship from other disciplines is more likely to locate upskirting as highly gendered behaviour in the context of gendered relations of power, and of violence against women and girls, and to consider both the act of taking the photograph and its dissemination online. We argue that future research ought to: approach upskirting as a form of violence against women and girls; be empirical and intersectional, and engage with victims and perpetrators.


Extraordinary Genome Instability and Widespread Chromosome Rearrangements During Vegetative Growth.
The haploid genome of the pathogenic fungus Zymoseptoria tritici is contained on "core" and "accessory" chromosomes. While 13 core chromosomes are found in all strains, as many as eight accessory chromosomes show presence/absence variation and rearrangements among field isolates. The factors influencing these presence/absence polymorphisms are so far unknown. We investigated chromosome stability using experimental evolution, karyotyping, and genome sequencing. We report extremely high and variable rates of accessory chromosome loss during mitotic propagation in vitro and in planta Spontaneous chromosome loss was observed in 2 to >50% of cells during 4 weeks of incubation. Similar rates of chromosome loss in the closely related Zymoseptoria ardabiliae suggest that this extreme chromosome dynamic is a conserved phenomenon in the genus. Elevating the incubation temperature greatly increases instability of accessory and even core chromosomes, causing severe rearrangements involving telomere fusion and chromosome breakage. Chromosome losses do not affect the fitness of Zymoseptoria tritici in vitro, but some lead to increased virulence, suggesting an adaptive role of this extraordinary chromosome instability.