bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of AA amyloidosis patients in San Francisco
Authors: Lejmi Hiba , Jen Kuang‐Yu , Olson Jean L. , James Sam H. , Sam Ramin
Published: September 2015

Background

AA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco.

Design

Here, we describe 24 patients who had kidney biopsy‐proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy‐proven AA amyloidosis were analysed further.

Results

All patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable.

Conclusion

AA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high.
Is it time to think about the sodium glucose co‐transporter 2 sympathetically?
Authors: Elliott Rosemary H , Matthews Vance B , Rudnicka Caroline , Schlaich Markus P
Published: September 2015

Disturbances in glucose homeostasis are a key feature of the metabolic syndrome and type 2 diabetes. Renal glucose reabsorption is an important factor in glycaemic control. Glucose reabsorption in the proximal tubules is mediated by the sodium glucose co‐transporter 2. The capacity for glucose reabsorption is increased in type 2 diabetes and contributes significantly to hyperglycaemia and impaired glucose control. Understanding the mechanisms underpinning the regulation of the sodium glucose co‐transporter 2 is therefore of high clinical relevance. However, despite recent advances in the field and the availability of pharmacological inhibitors of this glucose transporter for the treatment of type 2 diabetes, the mechanisms that regulate sodium glucose co‐transporter 2 expression are not fully understood. The sympathetic nervous system is an important modulator of glucose homeostasis, and sympathetic hyperactivity is a characteristic feature of obesity, the metabolic syndrome and type 2 diabetes. Sympathetic inhibition either achieved pharmacologically or by renal sympathetic denervation has been associated with improved glucose control. Importantly, sympathetic nerves innervate the proximal tubules of the kidney where they have been shown to regulate the expression of other transporters such as the sodium hydrogen exchanger 3. This review aims to explore the evidence for the regulation of sodium glucose co‐transporter 2‐mediated glucose reabsorption by the sympathetic nervous system.
Hydration status measured by BCM: A potential modifiable risk factor for peritonitis in patients on peritoneal dialysis
Authors: Santhakumaran Territa , Samad Nasreen , Fan Stanley L
Published: September 2015

Aim

Peritoneal dialysis peritonitis and fluid overhydration (OH) are frequent problems in peritoneal dialysis. The latter can cause gut wall oedema or be associated with malnutrition. Both may lead to increased peritonitis risk. We wished to determine if OH is an independent risk factor for peritonitis (caused by enteric organisms).

Methods

Retrospectively study of patients with >2 bioimpedance assessments (Body Composition Monitor). We compared peritonitis rates of patients with above or below the median time‐averaged hydration parameter (OH/extracellular water, OH/ECW). Multivariate analysis was performed to determine independent risk factors for peritonitis by enteric organism.

Results

We studied 580 patients. Peritonitis was experienced by 28% patients (followed up for an average of 17 months). The overall peritonitis rate was 1:34 patient months. Patients with low OH/ECW values had significantly lower rates of peritonitis from enteric organisms than overhydrated patients (incident rate ratio 1.53, 95% confidence interval 1.38–1.70, P < 0.001). Hydration remained an independent predictor of peritonitis from enteric organisms when multivariate model included demographic parameters (odds ratio for a 1% increment of OH/ECW was 1.05; 95% confidence interval 1.01–1.10, P < 0.02). However, including biochemical parameters of malnutrition reduced the predictive power of overhydration.

Conclusion

We found an association between overhydration and increased rates of peritonitis. While this may partly be due to the high co‐morbidity of patients (advanced age and diabetes), on multivariate analysis, only inclusion of nutritional parameters reduced this association. It remains to be determined if overhydration will prove to be a modifiable risk factor for peritonitis or whether malnutrition will prove to be more important.
An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake
Authors: He Zhenyan , Yan Huili , Chen Yanshan , Shen Hongling , Xu Wenxiu , Zhang Haiyan , Shi Lei , Zhu Yong‐Guan , Ma Mi
Published: September 2015

The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake.

PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1–GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real‐time PCR. Site‐directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied.

Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4‐64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site‐directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site.

PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake.
Evidence for extensive parallelism but divergent genomic architecture of adaptation along altitudinal and latitudinal gradients in Populus trichocarpa
Authors: Holliday Jason A. , Zhou Lecong , Bawa Rajesh , Zhang Man , Oubida Regis W.
Published: September 2015

Adaptation to climate across latitude and altitude reflects shared climatic constraints, which may lead to parallel adaptation. However, theory predicts that higher gene flow should favor more concentrated genomic architectures, which would lead to fewer locally maladapted recombinants.

We used exome capture to resequence the gene space along a latitudinal and two altitudinal transects in the model tree Populus trichocapra. Adaptive trait phenotyping was coupled with FST outlier tests and sliding window analysis to assess the degree of parallel adaptation as well as the genomic distribution of outlier loci.

Up to 51% of outlier loci overlapped between transect pairs and up to 15% of these loci overlapped among all three transects. Genomic clustering of adaptive loci was more pronounced for altitudinal than latitudinal transects. In both altitudinal transects, there was a larger number of these ‘islands of divergence’, which were on average longer and included several of exceptional physical length.

Our results suggest that recapitulation of genetic clines over latitude and altitude involves extensive parallelism, but that steep altitudinal clines generate islands of divergence. This suggests that physical proximity of genes in coadapted complexes may buffer against the movement of maladapted alleles from geographically proximal but climatically distinct populations.
The state of UK pediatric anesthesia: a survey of National Health Service activity
Authors: Sury Michael R. J. , Arumainathan Renuka , Belhaj Alla M. , MacG Palmer James H. , Cook Tim M. , Pandit Jaideep J.
Published: September 2015

This secondary analysis of the 2013 United Kingdom National Health Service (NHS) Anaesthesia Activity Survey of the Fifth National Audit Project (of the Royal College of Anaesthetists and Association of Anaesthetists of Great Britain and Ireland) shows pediatric anesthesia activity in detail. A local coordinator (LC) in every NHS hospital collected data on patients undergoing any procedure managed by an anesthetist. Questionnaires had 30 question categories. Each LC was randomized to a 2‐day period. The pediatric age groups were infants, (<1 year), preschool age (1–5 year), and school age children (6–15 year). The median questionnaire return rate was 98%. The annual caseload was estimated to be 486 900 children: 36 500 infants, 184 700 preschool age, and 265 800 school age children. Almost 90% of children (1–15 year) were ASA 1 or 2 and the substantial majority underwent routine nonurgent ear nose and throat, dental, orthopaedics, or general surgery procedures; 65% were ‘day cases’. One in six children were managed outside operating theater sites compared with one in 12 adults. Forty one per cent was in district general hospitals. Almost all ASA 4 and 5 children (89%) and infants (92%) were managed in specialist hospitals. ‘Awake’ cases and sedation accounted for only 2% of cases. There were notable differences in demography and anesthetic care compared with adults and between different age groups of children. These data enable analysis of the current state of UK pediatric anesthetic practice and highlight differences between pediatric and adult services.
The development and status of Bt rice in China
Authors: Li Yunhe , Hallerman Eric M. , Liu Qingsong , Wu Kongming , Peng Yufa
Published: September 2015

Multiple lines of transgenic rice expressing insecticidal genes from the bacterium Bacillus thuringiensis (Bt) have been developed in China, posing the prospect of increases in production with decreased application of pesticides. We explore the issues facing adoption of Bt rice for commercial production in China. A body of safety assessment work on Bt rice has shown that Bt rice poses a negligible risk to the environment and that Bt rice products are as safe as non‐Bt control rice products as food. China has a relatively well‐developed regulatory system for risk assessment and management of genetically modified (GM) plants; however, decision‐making regarding approval of commercial production has become politicized, and two Bt rice lines that otherwise were ready have not been allowed to enter the Chinese agricultural system. We predict that Chinese farmers would value the prospect of increased yield with decreased use of pesticide and would readily adopt production of Bt rice. That Bt rice lines may not be commercialized in the near future we attribute to social pressures, largely due to the low level of understanding and acceptance of GM crops by Chinese consumers. Hence, enhancing communication of GM crop science‐related issues to the public is an important, unmet need. While the dynamics of each issue are particular to China, they typify those in many countries where adoption of GM crops has been not been rapid; hence, the assessment of these dynamics might inform resolution of these issues in other countries.
Plant artificial chromosome technology and its potential application in genetic engineering
Authors: Yu Weichang , Yau Yuan‐Yeu , Birchler James A.
Published: September 2015

Genetic engineering with just a few genes has changed agriculture in the last 20 years. The most frequently used transgenes are the herbicide resistance genes for efficient weed control and the Bt toxin genes for insect resistance. The adoption of the first‐generation genetically engineered crops has been very successful in improving farming practices, reducing the application of pesticides that are harmful to both human health and the environment, and producing more profit for farmers. However, there is more potential for genetic engineering to be realized by technical advances. The recent development of plant artificial chromosome technology provides a super vector platform, which allows the management of a large number of genes for the next generation of genetic engineering. With the development of other tools such as gene assembly, genome editing, gene targeting and chromosome delivery systems, it should become possible to engineer crops with multiple genes to produce more agricultural products with less input of natural resources to meet future demands.
The impact of the Tekay chromoviral elements on genome organisation and evolution of Anemone s.l. (Ranunculaceae)
Authors: Mlinarec J. , Franjević D. , Harapin J. , Besendorfer V.
Published: September 2015

We studied the highly abundant chromoviral Tekay clade in species from three sister genera – Anemone, Pulsatilla and Hepatica (Ranunculaceae). With this clade, we performed a concomitant survey of its phylogenetic diversity, chromosomal organisation and transcriptional activity in Anemone s.l. in order to investigate dynamics of the Tekay elements at a finer scale than previously achieved in this or any other flowering clade. The phylogenetic tree built from Tekay sequences conformed to expected evolutionary relationships of the species; exceptions being A. nemorosa and A. sylvestris, which appeared more closely related that expected, and we invoke hybridisation events to explain the observed topology. The separation of elements into six clusters could be explained by episodic bursts of activity since divergence from a common ancestor at different points in their respective evolutionary histories. In Anemone s.l. the Tekay elements do not have a preferential position on chromosomes, i.e. they can have a: (i) centromeric/pericentromeric position; (ii) interstitial position in DAPI‐positive AT‐rich heterochromatic regions; can be (iii) dispersed throughout chromosomes; or even (iv) be absent from large heterochromatic blocks. Widespread transcriptional activity of the Tekay elements in Anemone s.l. taxa indicate that some copies of Tekay elements could still be active in this plant group, contributing to genome evolution and speciation within Anemone s.l. Identification of Tekay elements in Anemone s.l. provides valuable information for understanding how different localisation patterns might help to facilitate plant genome organisation in a structural and functional manner.
From Stigmatized Immigrants to Radical Right Voting: A Multilevel Study on the Role of Threat and Contact
Authors: Green Eva G. T. , Sarrasin Oriane , Baur Robert , Fasel Nicole
Published: September 2015

This study examines the interplay between presence of stigmatized immigrants, threat, and intergroup contact that underlies radical right voting (voting propensity and actual district‐level vote results). On the one hand, low‐status immigrants are often stigmatized and depicted as threats. Thus, presence of stigmatized immigrants should heighten threat perceptions, thereby increasing radical right voting. On the other hand, as positive contact with stigmatized immigrants is known to reduce anti‐immigrant prejudice, it should also attenuate radical right voting. As predicted, multilevel path analyses with the Swiss Election Studies 2011 data (N = 1,736 respondents in 136 districts) revealed that the proportion of stigmatized immigrants (from former Yugoslavia and Albania) in districts heightened perceived threat. Threat perceptions, in turn, increased propensity to vote for the Swiss People's Party, the major radical right party. In contrast, experiencing positive, everyday contact with former Yugoslav and Albanian immigrants reduced voting propensity through attenuated threat perceptions. Contact and threat perceptions were also related to the actual vote through voting propensity.
A patient with Alzheimer's disease complicated by elderly‐onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone‐independent macronodular adrenal hyperplasia
Authors: Haraguchi Yoshinori , Mizoguchi Yoshito , Noguchi Tomoyuki , Arai Takeo , Fukuyama Junko , Kato Takahiro A. , Kawashima Toshiro , Monji Akira
Published: September 2015

Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly‐onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful.
Communication About Micropollutants in Drinking Water: Effects of the Presentation and Psychological Processes
Authors: Tobias Robert
Published: September 2015

This study investigates how people change their risk perception, trust, and behavior as a consequence of being informed about the occurrence of micropollutants in drinking water. Micropollutants are substances present in extremely low concentrations that might be dangerous in higher concentrations. Data were gathered in the city of Zurich, Switzerland in 2013 using a questionnaire in which the information on micropollutants was presented differently to 12 experimental groups. Data of the key constructs were gathered before and after this information, so that causal effects could be quantified by regression analyses. Affective reactions to the information turned out to be the critical mediator of changes in risk perception (operationalized as the perceived change of quality due to pollution), which is an important determinant of changes in behavior and trust. Also, direct effects of affective reactions on behavior and trust were observed. Trust before appraising risks reduces negative affective reactions; however, it also reduces perceived quality (i.e., increases risk perception) and trust after risks are appraised. The different forms of information mainly influenced the participants’ affective reactions, but they also influenced perceived quality. The presentation with the least negative effects was a comparison of the intake of the substance by water with intake by food. The experimental design with repeated measurement that considers trust as a determinant and consequence of risk perception uncovered positive and negative effects of trust before appraising risks on changes of risk perception and trust due to appraising risks.
Consequences of Measurement Error for Inference in Cross-Lagged Panel Design—The Example of the Reciprocal Causal Relationship Between Subjective Health and Socio-Economic Status
Authors: Kröger Hannes , Hoffmann Rasmus , Pakpahan Eduwin
Published: September 2015

We discuss the problem of random measurement error in two variables when using a cross-lagged panel design. We apply the problem to the question of the causal direction between socio-economic status and subjective health, known also as health selection versus social causation. We plot the bias of the ratio between the social causation and the health selection coefficient as a function of the degree of measurement error in subjective health and socio-economic status for different scenarios which might occur in practice. Using simulated data we give an example of a Bayesian model for the treatment of measurement error that relies on external information about the degree of measurement error.
Determining the Effect of Strategic Voting on Election Results
Authors: Herrmann Michael , Munzert Simon , Selb Peter
Published: September 2015

Speculations about whether strategic voting made a difference to the outcome of an election regularly whip up the passions of pundits, party strategists, electoral reformers and scholars alike. Yet, research on strategic voting's political effect has been hampered by the scarcity of data on district level party preferences. We propose the use of Bayesian small area estimation to predict district level preferences from just a handful of survey responses per district and comparing these predictions against election results to estimate how many voters switched sides in each district. We apply the approach to estimate how many seats changed hands as a result of strategic voting at the 1997 and 2001 UK general elections. Despite similar rates of strategic voting in both elections, the number of seats that were affected was markedly greater in 1997. Interestingly, the Liberal Democrats turn out to win the most seats because of strategic voting. We also estimate how many votes went in the ‘wrong’ direction—away from otherwise viable candidates. We validate our results by using journalistic sources and compare them with previous published estimates.
Growth mechanisms and geochemistry of carbonate concretions from the Cambrian Wheeler Formation (Utah, USA)
Authors: Gaines Robert R. , Vorhies John S.
Published: September 2015

Carbonate concretions provide unique records of ancient biogeochemical processes in marine sediments. Typically, they form in organic‐rich mudstones, where a significant fraction of the bicarbonate required for carbonate precipitation is supplied from the decomposition of organic matter in the sediments. As a result, carbonates that comprise concretions are usually characterized by broad ranges in δ13C and include values that are significantly depleted relative to seawater. This article reports results from a physical, petrographic and geochemical analysis of 238 concretions from the Wheeler Formation (Cambrian Series 3), Utah, USA, which are unusual in several respects. Most prominently, they formed in organic‐poor mudstones (total organic carbon = 0·1 to 0·5%) and are characterized by a narrow range of δ13C that onlaps the range of contemporaneous seawater values. Subtle centre to edge trends in δ13C demonstrate that concretion precipitation was initiated by local chemical gradients set up by microbial activity in the sediments, but was sustained during growth by a large pool of inorganic bicarbonate probably derived from alkaline bottom waters. The large inorganic pool appears to have been important in facilitating rapid precipitation of the concretion matrix, which occurred via both displacive and replacive carbonate precipitation during early diagenesis. Stable isotope data from cogenetic pyrite (δ34S) and silica (δ18O) phases provide insight into the evolution of biogeochemical processes during concretion growth, and suggest that concretions were formed almost entirely during sulphate reduction, with only minor modification thereafter. Concretions of the Wheeler Formation appear to represent an end‐member system of concretion formation in which rapid growth was promoted by ions supplied from sea‐water. As such, they offer insight into the spectrum of processes that may influence the growth of carbonate concretions in marine sediments.
Efficacy of once‐weekly dapsone dosing for Pneumocystis jirovecii pneumonia prophylaxis post transplantation
Authors: Evans R.A. , Clifford T.M. , Tang S. , Au T. , Fugit A.M.
Published: September 2015

Background

Pneumocystis jirovecii pneumonia (PCP) remains a concern after organ transplantation. In 2005, the University of Kentucky (UK) Transplant Center implemented a novel dosing regimen of weekly dapsone as an alternative for patients with contraindications or intolerability to trimethoprim‐sulfamethoxazole (TMP‐SMZ), which remains the drug of choice. The purpose of this study was to compare the efficacy of weekly dapsone with TMP‐SMZ in preventing PCP post transplantation.

Methods

A single‐center, cohort, retrospective review of kidney and liver transplant patients from January 2005 to December 2012 was conducted. Patients who were identified as dapsone cases were matched in a 1:1 ratio with TMP‐SMZ controls based on type of transplant, age, primary diagnosis, and gender. The primary endpoint assessed was the diagnosis of PCP at 6 and 12 months post transplant.

Results

A total of 158 patients were included in the study. No documented cases of PCP occurred in either study group at 6 or 12 months (P = 1.0). In dapsone patients 35 (44%) cases of breakthrough infection occurred, compared to 24 (30%) in the TMP‐SMZ group (P = 0.07) within 12 months post transplant. In the dapsone group, 52 (65%) patients were hospitalized within 6 months post transplant compared to 36 (46%) patients in the TMP‐SMZ group (P = 0.01). Similar results were seen in patients hospitalized within 12 months post transplant; 49% of patients were switched from TMP‐SMZ to dapsone owing to renal dysfunction.

Conclusion

No documented cases of PCP occurred in either study group. Future studies are warranted to show the efficacy of weekly dapsone dosing compared to other PCP prophylaxis regimens.
Genotypic relatedness and antimicrobial resistance of Staphylococcus schleiferi in clinical samples from dogs in different geographic regions of the United States
Authors: Kunder Darcie A. , Cain Christine L. , O'Shea Kathleen , Cole Stephen D. , Rankin Shelley C.
Published: September 2015

Background

Staphylococcus schleiferi is a known pathogen that can cause canine skin and ear infections. The aim of this study was to determine the molecular epidemiology and antimicrobial susceptibility of clinical veterinary isolates from different geographic regions in the United States.

Hypothesis

It was hypothesized that S. schleiferi would maintain genotypic homogeneity across the different geographic regions and that meticillin‐resistant (MR) isolates of S. schleiferi would predominate.

Methods

Isolates were identified as S. schleiferi by a commercial microbiology identification system and confirmed by nuc gene PCR. Antibiotic susceptibility data were collected and PBP2a latex agglutination testing was performed on MR isolates. Pulsed‐field gel electrophoresis (PFGE) was performed and clonal clusters were identified with a Dice coefficient similarity of >80%.

Results

There were 116 isolates from the Mid‐Atlantic region and 101 from across the United States. Of these 217 isolates, 209 (96%) were obtained from cutaneous sites. Of the Mid‐Atlantic isolates, 62% (72 of 116) were MR and 16% (18 of 116) were multidrug‐resistant (MDR). Of the isolates from the other geographic regions, 73% (74 of 101) were MR and 24% (24 of 101) were MDR. All MR isolates were positive by PBP2a latex agglutination. PFGE identified 155 individual pulsed‐field profiles and three major pulsed‐field types (PFT) that contained 61% (133 of 217) of the isolates. These pulsed‐field types were geographically heterogeneous.

Conclusions

This study demonstrates the dissemination of successful MR pulsed‐field types of S. schleiferi across the United States.
Canine epidermolysis bullosa acquisita: a retrospective study of 20 cases
Authors: Bizikova Petra , Linder Keith E. , Wofford Jessica A. , Mamo Lisa B. , Dunston Stanley M. , Olivry Thierry
Published: September 2015

Background

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune subepidermal blistering disease of dogs and humans.

Objectives

Our objectives were to describe clinical phenotypes, histopathology and treatment outcomes of canine EBA.

Animals

Twenty dogs diagnosed with EBA based on a subepidermal blister formation and collagen VII autoreactivity.

Results

Most dogs were young (median: 1.2‐year‐old) with a male‐to‐female ratio of 2.3:1. Nine of 20 dogs (45%) developed lesions before one year of age and 11 of 20 dogs (55%) were great danes. Tense vesicles and bullae (18 of 20; 90%) and deep erosions and ulcers (20 of 20; 100%) were the most common lesions and these affected predominantly the oral cavity (19 of 20; 95%), pinnae (16 of 20; 80%), axillae (15 of 20; 75%) and footpads (14 of 20; 70%). Histopathology identified neutrophilic perivascular dermatitis (17 of 17; 100%) without or with (12 of 17; 71%) eosinophils, which occasionally equalled (four cases) or outnumbered neutrophils (two cases). Subepidermal vesicles were either devoid of inflammation or contained neutrophils with or without eosinophils, fibrin and/or haemorrhage. A complete remission of skin lesions was obtained in 14 dogs with a median time of 58 days. Glucocorticoids were used in these dogs either as a monotherapy (3 of 14; 21%) or in combination with other immunomodulating drugs (11 of 14; 79%). The median dose of prednisone was 3 mg/kg/day. The remaining six dogs were euthanized.

Conclusions and clinical importance

Canine EBA is a rare subepidermal blistering disease with an inflammatory phenotype and a predilection for young great danes and male dogs. The outcome of treatment appears more favourable than assumed previously.
Contours for Planar Cracks Growing in Three Dimensions: Influence of Kinetic Energy
Authors: Brock L. M.
Published: September 2015

Dynamic steady-state growth in 3D of a semi-infinite plane brittle crack in isotropic elastic solids is considered. Loads cause growth by translating on the crack surfaces at constant, subcritical speed. An analytical solution is obtained and subjected to a criterion for brittle crack growth based on dynamic energy release rate, with kinetic energy included. The result is a nonlinear differential equation for the crack contour, i.e., the curve formed by the crack edge in the crack plane. The equation is studied for the case of compression loading by translating point forces. At large distances from the forces, the crack edge asymptotically approaches the rectilinear and kinetic energy effects can be negligible. A bulge forms around the forces, however, the effect of kinetic energy on its size can be pronounced.
Assembly Based Methods to Support Product Innovation in Design for Additive Manufacturing: An Exploratory Case Study
Authors: Laverne Floriane , Segonds Frédéric , Anwer Nabil , Le Coq Marc
Published: September 2015

Additive manufacturing (AM) is emerging as an important manufacturing process and a key technology for enabling innovative product development. Design for additive manufacturing (DFAM) is nowadays a major challenge to exploit properly the potential of AM in product innovation and product manufacturing. However, in recent years, several DFAM methods have been developed with various design purposes. In this paper, we first present a state-of-the-art overview of the existing DFAM methods, then we introduce a classification of DFAM methods based on intermediate representations (IRs) and product's systemic level, and we make a comparison focused on the prospects for product innovation. Furthermore, we present an assembly based DFAM method using AM knowledge during the idea generation process in order to develop innovative architectures. A case study demonstrates the relevance of such approach. The main contribution of this paper is an early DFAM method consisting of four stages as follows: choice and development of (1) concepts, (2) working principles, (3) working structures, and (4) synthesis and conversion of the data in design features. This method will help designers to improve their design features, by taking into account the constraints of AM in the early stages.
Experimental and Numerical Study of Pressure in a Shock Tube
Authors: Khawaja Hassan A. , Messahel Ramzi , Ewan Bruce , Mhamed Souli , Moatamedi Mojtaba
Published: September 2015

This paper presents the behavior of pressure in an air–water shock tube. In this work, high-pressure air (at 100 bar) interacts with water (at 1 atm ∼ 1 bar) through an orifice in a 100 mm constant diameter tube. The experiments are repeated with three different orifice plate diameters of 4, 8, and 15 mm. The variation of pressure during the transient stage is recorded in these experiments and it is found that with increasing orifice diameter, the amplitude of the pressure increases linearly with time when all other conditions are unchanged. The same phenomenon is simulated using the ls-dyna® software using an arbitrary Lagrangian Eulerian (ALE) method to solve the problem numerically. Simulations are made with a range of orifice diameters. The experimental results confirm the validity of the simulations algorithm. The simulations also demonstrated that the pressure behaves linearly with orifice diameter only when orifice diameter is less than 15% of the tube diameter.
Multidimensional dosimetry of 106Ru eye plaques using EBT3 films and its impact on treatment planning
Authors: Heilemann G. , Nesvacil N. , Blaickner M. , Kostiukhina N. , Georg D.
Published: September 2015

Purpose:

The purpose of this study was to establish a method to perform multidimensional radiochromic film measurements of 106Ru plaques and to benchmark the resulting dose distributions against Monte Carlo simulations (MC), microdiamond, and diode measurements.

Methods:

Absolute dose rates and relative dose distributions in multiple planes were determined for three different plaque models (CCB, CCA, and COB), and three different plaques per model, using EBT3 films in an in‐house developed polystyrene phantom and the mcnp6 MC code. Dose difference maps were generated to analyze interplaque variations for a specific type, and for comparing measurements against MC simulations. Furthermore, dose distributions were validated against values specified by the manufacturer (BEBIG) and microdiamond and diode measurements in a water scanning phantom. Radial profiles were assessed and used to estimate dosimetric margins for a given combination of representative tumor geometry and plaque size.

Results:

Absolute dose rates at a reference depth of 2 mm on the central axis of the plaque show an agreement better than 5% (10%) when comparing film measurements (mcnp6) to the manufacturer's data. The reproducibility of depth‐dose profile measurements was <7% (2 SD) for all investigated detectors and plaque types. Dose difference maps revealed minor interplaque deviations for a specific plaque type due to inhomogeneities of the active layer. The evaluation of dosimetric margins showed that for a majority of the investigated cases, the tumor was not completely covered by the 100% isodose prescribed to the tumor apex if the difference between geometrical plaque size and tumor base ≤4 mm.

Conclusions:

EBT3 film dosimetry in an in‐house developed phantom was successfully used to characterize the dosimetric properties of different 106Ru plaque models. The film measurements were validated against MC calculations and other experimental methods and showed a good agreement with data from BEBIG well within published tolerances. The dosimetric information as well as interplaque comparison can be used for comprehensive quality assurance and for considerations in the treatment planning of ophthalmic brachytherapy.
B cell antigen receptors of the IgM and IgD classes are clustered in different protein islands that are altered during B cell activation
Authors: Maity Palash Chandra , Blount Amy , Jumaa Hassan , Ronneberger Olaf , Lillemeier Björn F. , Reth Michael
Published: September 2015

Antigen stimulates the dispersion and remodeling of preformed distinct clusters of B cell receptors on the cell surface.
Systematic profiling of the bacterial phosphoproteome reveals bacterium-specific features of phosphorylation
Authors: Lin Miao-Hsia , Sugiyama Naoyuki , Ishihama Yasushi
Published: September 2015

Improved enrichment of phosphorylated proteins from bacteria enables the identification of phosphorylation motifs not found in eukaryotes.
Neutrophils mediate surgery-induced cancer formation
Authors: VanHook Annalisa M.
Published: September 2015

Wounding attracts neutrophils to nearby preneoplastic lesions, which promote cell proliferation and tumor progression.
Viruses pack antiviral mediators
Authors: Mueller Kristen L.
Published: September 2015

Viruses package an antiviral second messenger into virions, facilitating an immune response in newly infected cells.
Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates
Authors: Rueda Johana , Realpe Teresa , Mejia Gloria Isabel , Zapata Elsa , Rozo Juan Carlos , Ferro Beatriz Eugenia , Robledo Jaime
Published: September 2015

Ethionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in the
Mycobacterium tuberculosis
population. ETH resistance in
M. tuberculosis
is phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in the
inhA
promoter and in the following genes:
katG
,
ethA
,
ethR
,
mshA
,
ndh
, and
inhA
. We sequenced the above genes in 64
M. tuberculosis
isolates (
n
= 57 ETH-resistant MDR-TB isolates;
n
= 3 ETH-susceptible MDR-TB isolates; and
n
= 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% in
katG
, 72% in
ethA
, 45.6% in
mshA
, 8.7% in
ndh
, and 33.3% in
inhA
or its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations in
katG
; one had a mutation in
ethA
, and another, in
mshA
and
inhA
. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations in
mshA
gene unrelated to the resistance. Mutations not previously reported were found in the
ethA
,
mshA
,
katG
, and
ndh
genes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in the
M. tuberculosis
isolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.
Comparative Effectiveness of Single versus Combination Antibiotic Prophylaxis for Infections after Transrectal Prostate Biopsy
Authors: Marino Kaylee , Parlee Anne , Orlando Ralph , Lerner Lori , Strymish Judith , Gupta Kalpana
Published: September 2015

An increase in fluoroquinolone resistance and transrectal ultrasound-guided prostate (TRUS) biopsy infections has prompted the need for alternative effective antibiotic prophylaxis. We aimed to compare ciprofloxacin and other single-agent therapies to combination therapy for efficacy and adverse effects. Men who underwent a TRUS biopsy within the VA Boston health care system with documented receipt of prophylactic antibiotics periprocedure were eligible for inclusion. Postprocedure infections within 30 days were ascertained by chart review from electronic records, including any inpatient, outpatient, or urgent-care visits. Among 455 evaluable men over a 3-year period, there were 25 infections (5.49%), with sepsis occurring in 2.4%, urinary tract infections (UTI) in 1.54%, and bacteremia in 0.44% of patients.
Escherichia coli
was the most common urine (89%) and blood (92%) pathogen, with fluoroquinolone resistance rates of 88% and 91%, respectively. Ciprofloxacin alone was associated with significantly more infections than ciprofloxacin plus an additional agent (
P
= 0.014). Intramuscular gentamicin alone was also significantly associated with a higher infection rate obtained with all other regimens (
P
= 0.004). Any single-agent regimen, including ciprofloxacin, ceftriaxone, or gentamicin, was associated with significantly higher infection rates than any combination regimen (odds ratio [OR], 4; 95% confidence interval [CI], 1.47, 10.85;
P
= 0.004). Diabetes, immunosuppressive condition or medication, hospitalization within the previous year, and UTI within the previous 6 months were not associated with infection risk.
Clostridium difficile
infections were similar. These findings suggest that ciprofloxacin, ceftriaxone, and gentamicin alone are inferior to a combination regimen. Institutions with high failure rates of prophylaxis for TRUS biopsies should consider combination regimens derived from their local data.
High Prevalence of
vanM
in Vancomycin-Resistant Enterococcus faecium Isolates from Shanghai, China
Authors: Chen Chunhui , Sun Jingyong , Guo Yan , Lin Dongfang , Guo Qinglan , Hu Fupin , Zhu Demei , Xu Xiaogang , Wang Minggui
Published: September 2015

The
vanM
gene was first found in a vancomycin-resistant
Enterococcus faecium
(VREm) isolate in Shanghai in 2006. In this study, we found that, in 70 VREm strains isolated in nine Shanghai hospitals from 2006 to 2014,
vanM
was more prevalent than the
vanA
gene (64.3% [45/70] versus 35.7% [25/70]). The
vanM
-type isolates showed similar antimicrobial susceptibility patterns with the
vanA
types. The
vanM
-type VREm emerged and disseminated in Shanghai.
Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System
Authors: Poole Keith , Lau Calvin Ho-Fung , Gilmour Christie , Hao Youai , Lam Joseph S.
Published: September 2015

The ribosome-targeting antimicrobial, spectinomycin (SPC), strongly induced the
mexXY
genes of the MexXY-OprM multidrug efflux system in
Pseudomonas aeruginosa
and increased susceptibility to the polycationic antimicrobials polymyxin B and polymyxin E, concomitant with a decrease in expression of the polymyxin resistance-promoting lipopolysaccharide (LPS) modification loci,
arnBCADTEF
and PA4773-74. Consistent with the SPC-promoted reduction in
arn
and PA4773-74 expression being linked to
mexXY
, expression of these LPS modification loci was moderated in a mutant constitutively expressing
mexXY
and enhanced in a mutant lacking the efflux genes. Still, the SPC-mediated increase in polymyxin susceptibility was retained in mutants lacking
arnB
and/or PA4773-74, an indication that their reduced expression in SPC-treated cells does not explain the enhanced polymyxin susceptibility. That the polymyxin susceptibility of a mutant strain lacking
mexXY
was unaffected by SPC exposure, however, was an indication that the unknown polymyxin resistance ‘mechanism’ is also influenced by the MexXY status of the cell. In agreement with SPC and MexXY influencing polymyxin susceptibility as a result of changes in the LPS target of these agents, SPC treatment yielded a decline in common polysaccharide antigen (CPA) synthesis in wild-type
P. aeruginosa
but not in the Δ
mexXY
mutant. A mutant lacking CPA still showed the SPC-mediated decline in polymyxin MICs, however, indicating that the loss of CPA did not explain the SPC-mediated MexXY-dependent increase in polymyxin susceptibility. It is possible, therefore, that some additional change in LPS promoted by SPC-induced
mexXY
expression impacted CPA synthesis or its incorporation into LPS and that this was responsible for the observed changes in polymyxin susceptibility.
TheCnes2Locus on Mouse Chromosome 17 Regulates Host Defense against Cryptococcal Infection through Pleiotropic Effects on Host Immunity
Authors: Shourian Mitra , Flaczyk Adam , Angers Isabelle , Mindt Barbara C. , Fritz Jörg H. , Qureshi Salman T.
Published: September 2015

The genetic basis of natural susceptibility to progressiveCryptococcus neoformansinfection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated withC. neoformanssusceptibility (Cnes1,Cnes2, andCnes3). To validate and characterize the role ofCnes2during the host response, we constructed a congenic strain on the C57BL/6 background (B6.CBA-Cnes2). Phenotypic analysis of B6.CBA-Cnes2mice 35 days afterC. neoformansinfection showed a significant reduction of fungal burden in the lungs and spleen with higher pulmonary expression of gamma interferon (IFN-γ) and interleukin-12 (IL-12), lower expression of IL-4, IL-5, and IL-13, and an absence of airway epithelial mucus production compared to that in C57BL/6 mice. Multiparameter flow cytometry of infected lungs also showed a significantly higher number of neutrophils, exudate macrophages, CD11b+dendritic cells, and CD4+cells in B6.CBA-Cnes2than in C57BL/6 mice. The activation state of recruited macrophages and dendritic cells was also significantly increased in B6.CBA-Cnes2mice. Taken together, these findings demonstrate that theCnes2interval is a potent regulator of host defense, immune responsiveness, and differential Th1/Th2 polarization followingC. neoformansinfection.
Interspecies Variations in Bordetella Catecholamine Receptor Gene Regulation and Function
Authors: Brickman Timothy J. , Suhadolc Ryan J. , Armstrong Sandra K.
Published: September 2015

Bordetella bronchiseptica
can use catecholamines to obtain iron from transferrin and lactoferrin via uptake pathways involving the BfrA, BfrD, and BfrE outer membrane receptor proteins, and although
Bordetella pertussis
has the
bfrD
and
bfrE
genes, the role of these genes in iron uptake has not been demonstrated. In this study, the
bfrD
and
bfrE
genes of
B. pertussis
were shown to be functional in
B. bronchiseptica
, but neither
B. bronchiseptica bfrD
nor
bfrE
imparted catecholamine utilization to
B. pertussis
. Gene fusion analyses found that expression of
B. bronchiseptica bfrA
was increased during iron starvation, as is common for iron receptor genes, but that expression of the
bfrD
and
bfrE
genes of both species was decreased during iron limitation. As shown previously for
B. pertussis
,
bfrD
expression in
B. bronchiseptica
was also dependent on the BvgAS virulence regulatory system; however, in contrast to the case in
B. pertussis
, the known modulators nicotinic acid and sulfate, which silence Bvg-activated genes, did not silence expression of
bfrD
in
B. bronchiseptica
. Further studies using a
B. bronchiseptica
bvgAS
mutant expressing the
B. pertussis
bvgAS
genes revealed that the interspecies differences in
bfrD
modulation are partly due to BvgAS differences. Mouse respiratory infection experiments determined that catecholamine utilization contributes to the
in vivo
fitness of
B. bronchiseptica
and
B. pertussis
. Additional evidence of the
in vivo
importance of the
B. pertussis
receptors was obtained from serologic studies demonstrating pertussis patient serum reactivity with the
B. pertussis
BfrD and BfrE proteins.