Taxane-containing induction chemotherapy followed by definitive chemoradiotherapy. Outcome in patients with locally advanced head and neck cancer

BACKGROUND Induction chemotherapy followed by definitive chemoradiotherapy is an intensified treatment approach for locally advanced squamous cell carcinoma of the head and neck (HNSCC) that might be associated with high rates of toxicity. MATERIALS AND METHODS The data of 40 consecutive patients who underwent induction chemotherapy with docetaxel-containing regimens followed by intensity-modulated radiotherapy (IMRT) and concomitant systemic therapy for unresectable locally advanced HNSCC were retrospectively analyzed. Primary objectives were RT-related acute and late toxicity. Secondary objectives were response to induction chemotherapy, locoregional recurrence-free survival (LRRFS), overall survival (OS), and influencing factors for LRRFS and OS. RESULTS The median follow-up for surviving patients was 21 months (range, 2-53 months). Patients received a median of three cycles of induction chemotherapy followed by IMRT to 72 Gy. Three patients died during induction chemotherapy and one during chemoradiotherapy. Acute RT-related toxicity was of grade 3 and 4 in 72 and 3 % of patients, respectively, mainly dysphagia and dermatitis. Late RT-related toxicity was mainly xerostomia and bone/cartilage necrosis and was of grade 3 and 4 in 15 % of patients. One- and 2-year LRRFS and OS were 72 and 49 % and 77 and 71 %, respectively. CONCLUSION Induction chemotherapy followed by chemoradiotherapy using IMRT was associated with a high rate of severe acute and late RT-related toxicities in this selected patient cohort. Four patients were lost because of fatal complications. Induction chemotherapy did not compromise the delivery of full-dose RT; however, the use of three cycles of concomitant cisplatin was impaired.

Identification and detection of Actinobacillus pleuropneumoniae by PCR based on the gene apxIVA

The apxIVA gene, a recently discovered RTX determinant of Actinobacillus pleuropneumoniae, was shown to be species-specific. DNA hybridization experiments using probes for various regions of apxIVA revealed that the 3'-terminus of this gene was present in all 14 serotypes of A. pleuropneumoniae but absent from phylogenetically related species. A primer pair spanning this region specifically amplified a 422bp fragment in PCR experiments with DNA from the reference strains of the 14 serotypes and 194 field strains isolated from various geographic locations worldwide. DNA sequence analysis of PCR products derived from all serotypes were identical except in serotypes 3, 8, and 10, which showed minor differences. The PCR did not amplify any product when DNA from 17 different bacterial species closely related to A. pleuropneumoniae was used as template. In addition, the PCR was negative with DNA of several Actinobacillus sp. which were initially characterized as A. pleuropneumoniae using routine phenotypic and serological analyses but which were subsequently shown by 16S rRNA sequence analysis to belong to yet undefined Actinobacillus species. The sensitivity of the PCR was determined to be 10pg of A. pleuropneumoniae DNA. A set of nested primers amplified a 377bp fragment specifically with A. pleuropneumoniae DNA. DNA titration experiments using the flanking and nested primer pairs showed an improved level of sensitivity to approximately 10fg of genomic DNA. The nested PCR was used to monitor the spread of A. pleuropneumoniae in pigs experimentally infected with a virulent serotype 1 strain and housed in a controlled environment facility. A. pleuropneumoniae DNA could be detected by nested PCR in nasal swab samples of infected pigs receiving either a high dose (5x10(5)) or a low dose (1x10(4)) challenge and in unchallenged cohorts that were contact-infected by the inoculated animals. Furthermore, PCR confirmed the presence of A. pleuropneumoniae in 16/17 homogenates from necrotic lung lesions, while the bacterium was successfully recovered from 13 of these lesions by culture.

Effect of lateral meniscectomy and osteochondral grafting of a lateral femoral condylar defect on contact mechanics: a cadaveric study in dogs

BACKGROUND Osteochondral autograft transfer (OAT) aims at restoring normal articular cartilage surface geometry and articular contact mechanics. To date, no studies have evaluated the contact mechanics of the canine stifle following OAT. Additionally, there are no studies that evaluated the role of the meniscus in contact mechanics following OAT in human or canine femorotibial joints. The objective of this study was to measure the changes in femorotibial contact areas (CA), mean contact pressure (MCP) and peak contact pressure (PCP) before and after osteochondral autograft transplantation (OAT) of a simulated lateral femoral condylar cartilage defect with an intact lateral meniscus and following lateral meniscectomy. RESULTS With an intact lateral meniscus, creation of an osteochondral defect caused a decrease in MCP and PCP by 11% and 30%, respectively, compared to the intact stifle (p < 0.01). With an intact meniscus, implanting an osteochondral graft restored MCP and PCP to 96% (p = 0.56) and 92% (p = 0.41) of the control values. Lateral meniscectomy with grafting decreased CA by 54% and increased PCP by 79% compared to the intact stifle (p < 0.01). CONCLUSIONS OAT restored contact pressures in stifles with a simulated lateral condylar defect when the meniscus was intact. The lateral meniscus has a significant role in maintaining normal contact pressures in both stifles with a defect or following OAT. Meniscectomy should be avoided when a femoral condylar defect is present and when performing OAT.

Evaluation of pet contact as a risk factor for carriage of multidrug-resistant staphylococci in nursing home residents

BACKGROUND Pets, often used as companionship and for psychological support in the therapy of nursing home residents, have been implicated as reservoirs for antibiotic-resistant bacteria. We investigated the importance of pets as reservoirs of multidrug-resistant (MDR) staphylococci in nursing homes. METHODS We assessed the carriage of MDR staphylococci in pets and in 2 groups of residents, those living in nursing homes with pets and those living without pet contacts. We collected demographic, health status, and human-pet contact data by means of questionnaires. We assessed potential bacteria transmission pathways by investigating physical resident-to-pet contact. RESULTS The observed prevalence of MDR staphylococci carriage was 84/229 (37%) in residents living with pets and 99/216 (46%) in those not living with pets (adjusted odds ratio [aOR], 0.6; 95% confidence interval [CI], 0.4-0.9). Active pet contact was associated with lower carriage of MDR staphylococci (aOR, 0.5; 95% CI, 0.4-0.8). Antibiotic treatment during the previous 3 months was associated with significantly increased risk for MDR carriage in residents (aOR, 3.1; 95% CI, 1.8-5.7). CONCLUSIONS We found no evidence that the previously reported benefits of pet contact are compromised by the increased risk of carriage of MDR staphylococci in residents associated with interaction with these animals in nursing homes. Thus, contact with pets, always under good hygiene standards, should be encouraged in these settings.

Countering the urbanist agenda in variationist sociolinguistics: dialect contact, demographic change and the rural-urban dichotomy

In variational linguistics, the concept of space has always been a central issue. However, different research traditions considering space coexisted for a long time separately. Traditional dialectology focused primarily on the diatopic dimension of linguistic variation, whereas in sociolinguistic studies diastratic and diaphasic dimensions were considered. For a long time only very few linguistic investigations tried to combine both research traditions in a two-dimensional design – a desideratum which is meant to be compensated by the contributions of this volume. The articles present findings from empirical studies which take on these different concepts and examine how they relate to one another. Besides dialectological and sociolinguistic concepts also a lay perspective of linguistic space is considered, a paradigm that is often referred to as “folk dialectology”. Many of the studies in this volume make use of new computational possibilities of processing and cartographically representing large corpora of linguistic data. The empirical studies incorporate findings from different linguistic communities in Europe and pursue the objective to shed light on the inter-relationship between the different concepts of space and their relevance to variational linguistics.

The role of mundane mobility and contact in dialect death and dialect birth

Urry begins his 2007 book, Mobilities, by throwing some quite stunning statistics at his readers: in 2010, there were one billion legal international arrivals at ports and airports; in 1800 people in the US travelled on average 50 metres per day, today it is 50 kilometres per day; 8.7% of world employment is in tourism; and, at any one time, there are 360,000 passengers in flight above the United States (2007: 3-4). But very many of these mobilities for the individuals concerned are or have become rather unexceptional – a flight to a holiday in Majorca or Florida, a journey on a crowded commuter train into Madrid or Tokyo, a cross-Channel ferry to Calais in France to pick up some cheap wine and a camembert. Whilst much of the theoretically influential dialectological literature on mobility reports on long-distance, often permanent, often dangerous migrations, I turn our attention here to the dialectological consequences of this unexceptional everyday movement. I will argue here that, just as more dramatic and long-distance mobilities can trigger linguistic change, so too can the much more mundane movements we engage in in everyday life. I demonstrate that the linguistic consequences of that contact are similar if not the same – perhaps less dramatic, perhaps involving the convergence of an initially less divergent array of variants – but typologically of the same ilk. And I demonstrate that because these mobilities have been long-term, intensive and ongoing, their consequences on the dialect landscape have been highly significant. Important to remember, however, is that these mobilities are socially stratified and unevenly distributed. As Wolff put it: “the suggestion of free and equal mobility is … a deception, since we don’t all have the same access to the road” (1993: 253).

Genome-wide analysis in German shepherd dogs reveals association of a locus on CFA 27 with atopic dermatitis

Humans and dogs are both affected by the allergic skin disease atopic dermatitis (AD), caused by an interaction between genetic and environmental factors. The German shepherd dog (GSD) is a high-risk breed for canine AD (CAD). In this study, we used a Swedish cohort of GSDs as a model for human AD. Serum IgA levels are known to be lower in GSDs compared to other breeds. We detected significantly lower IgA levels in the CAD cases compared to controls (p = 1.1 × 10(-5)) in our study population. We also detected a separation within the GSD cohort, where dogs could be grouped into two different subpopulations. Disease prevalence differed significantly between the subpopulations contributing to population stratification (λ = 1.3), which was successfully corrected for using a mixed model approach. A genome-wide association analysis of CAD was performed (n cases = 91, n controls = 88). IgA levels were included in the model, due to the high correlation between CAD and low IgA levels. In addition, we detected a correlation between IgA levels and the age at the time of sampling (corr = 0.42, p = 3.0 × 10(-9)), thus age was included in the model. A genome-wide significant association was detected on chromosome 27 (praw = 3.1 × 10(-7), pgenome = 0.03). The total associated region was defined as a ~1.5-Mb-long haplotype including eight genes. Through targeted re-sequencing and additional genotyping of a subset of identified SNPs, we defined 11 smaller haplotype blocks within the associated region. Two blocks showed the strongest association to CAD. The ~209-kb region, defined by the two blocks, harbors only the PKP2 gene, encoding Plakophilin 2 expressed in the desmosomes and important for skin structure. Our results may yield further insight into the genetics behind both canine and human AD.

Expression of thymic stromal lymphopoietin in canine atopic dermatitis

BACKGROUND In humans, thymic stromal lymphopoietin (TSLP) plays a central role in the development of allergic inflammation, such as atopic dermatitis (AD), but it is unknown whether it is involved in the pathogenesis of canine AD (CAD). HYPOTHESIS/OBJECTIVES Our aim was to characterize canine TSLP and to assess its expression in CAD. METHODS Canine TSLP was identified based on sequence homology with human TSLP and the complementary DNA (cDNA) cloned by RT-PCR. Real-time quantitative RT-PCR was established to assess the expression of canine TSLP in cultured canine keratinocytes and in skin biopsy specimens from lesional and nonlesional skin of 12 dogs with CAD and eight healthy control dogs. RESULTS Partial canine TSLP cDNA was cloned and characterized. It contained four exons that shared 70 and 73% nucleotide identity with human and equine TSLP, respectively, encoding the signal peptide and full-length secreted protein. We found significantly increased TSLP expression in lesional and nonlesional skin of dogs with CAD compared with healthy control dogs (P < 0.05), whereas no difference was measured between lesional and nonlesional samples. In cultured primary canine keratinocytes, we found increased TSLP expression after stimulation with house dust mite allergen extract or Toll-like receptor ligands lipopolysaccharide and poly I:C. CONCLUSIONS AND CLINICAL IMPORTANCE Increased TSLP expression in the skin of dogs with CAD supports an involvement of TSLP in the pathogenesis of CAD similar to that in humans. Further studies should elucidate the function and therapeutic potential of TSLP in CAD.

A field trial of infrared thermography as a non-invasive diagnostic tool for early detection of digital dermatitis in dairy cows

Infrared thermography (IRT) was used to detect digital dermatitis (DD) prior to routine claw trimming. A total of 1192 IRT observations were collected from 149 cows on eight farms. All cows were housed in tie-stalls. The maximal surface temperatures of the coronary band (CB) region and skin (S) of the fore and rear feet (mean value of the maximal surface temperatures of both digits for each foot separately, CBmax and Smax) were assessed. Grouping was performed at the foot level (presence of DD, n=99; absence, n=304), or at the cow level (all four feet healthy, n=24) or where there was at least one DD lesion on the rear feet, n=37). For individual cows (n=61), IRT temperature difference was determined by subtracting the mean sum of CBmax and Smax of the rear feet from that of the fore feet. Feet with DD had higher CBmax and Smax (P<0.001) than healthy feet. Smax was significantly higher in feet with infectious DD lesions (M-stage: M2+M4; n=15) than in those with non-infectious M-lesions (M1+M3; n=84) (P=0.03), but this was not the case for CBmax (P=0.12). At the cow level, an optimal cut-off value for detecting DD of 0.99°C (IRT temperature difference between rear and front feet) yielded a sensitivity of 89.1% and a specificity of 66.6%. The results indicate that IRT may be a useful non-invasive diagnostic tool to screen for the presence of DD in dairy cows by measuring CBmax and Smax.

Finite element based estimation of contact areas and pressures of the human scaphoid in various functional positions of the hand

The scaphoid is the most frequently fractured carpal bone. When investigating fixation stability, which may influence healing, knowledge of forces and moments acting on the scaphoid is essential. The aim of this study was to evaluate cartilage contact forces acting on the intact scaphoid in various functional wrist positions using finite element modeling. A novel methodology was utilized as an attempt to overcome some limitations of earlier studies, namely, relatively coarse imaging resolution to assess geometry, assumption of idealized cartilage thicknesses and neglected cartilage pre-stresses in the unloaded joint. Carpal bone positions and articular cartilage geometry were obtained independently by means of high resolution CT imaging and incorporated into finite element (FE) models of the human wrist in eight functional positions. Displacement driven FE analyses were used to resolve inter-penetration of cartilage layers, and provided contact areas, forces and pressure distribution for the scaphoid bone. The results were in the range reported by previous studies. Novel findings of this study were: (i) cartilage thickness was found to be heterogeneous for each bone and vary considerably between carpal bones; (ii) this heterogeneity largely influenced the FE results and (iii) the forces acting on the scaphoid in the unloaded wrist were found to be significant. As major limitations, accuracy of the method was found to be relatively low, and the results could not be compared to independent experiments. The obtained results will be used in a following study to evaluate existing and recently developed screws used to fix scaphoid fractures.

Spatial Distribution of Cryptic Species Diversity in European Freshwater Amphipods (Gammarus fossarum) as Revealed by Pyrosequencing

In order to understand and protect ecosystems, local gene pools need to be evaluated with respect to their uniqueness. Cryptic species present a challenge in this context because their presence, if unrecognized, may lead to serious misjudgement of the distribution of evolutionarily distinct genetic entities. In this study, we describe the current geographical distribution of cryptic species of the ecologically important stream amphipod Gammarus fossarum (types A, B and C). We use a novel pyrosequencing assay for molecular species identification and survey 62 populations in Switzerland, plus several populations in Germany and eastern France. In addition, we compile data from previous publications (mainly Germany). A clear transition is observed from type A in the east (Danube and Po drainages) to types B and, more rarely, C in the west (Meuse, Rhone, and four smaller French river systems). Within the Rhine drainage, the cryptic species meet in a contact zone which spans the entire G. fossarum distribution range from north to south. This large-scale geographical sorting indicates that types A and B persisted in separate refugia during Pleistocene glaciations. Within the contact zone, the species rarely co-occur at the same site, suggesting that ecological processes may preclude long-term coexistence. The clear phylogeographical signal observed in this study implies that, in many parts of Europe, only one of the cryptic species is present.

Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers.

Canine atopic dermatitis (CAD) is an allergic skin disease associated with IgE and IgG antibodies (Ab) to environmental allergens. The aim of this study was to determine which other factors influence serum Ab levels in CAD-affected and non-affected dogs as this has only been poorly investigated in dogs so far. Total and allergen-specific IgE levels and Dermatophagoides farinae (DF)-specific IgG1 and IgG4 were measured by ELISA in sera of 145 CAD-affected and 271 non-affected Labrador- and Golden retrievers. A multivariable logistic regression analysis including the factors age, breed, gender, castration, clinical CAD status and allergen-specific immunotherapy (ASIT) was performed. Golden retrievers had more frequently total (OR=1.87, 95% CI=1.26-2.87, p<0.01) and specific IgE levels above the threshold value than Labrador retrievers, suggesting that genetic factors influence IgE levels in dogs. Castration was generally associated with low Ab levels (OR=0.43-0.65, p<0.05). Surprisingly, dogs with CAD did not have increased odds for high IgE against any of the allergens tested. ASIT with DF was associated with high DF-specific IgG1 (OR=4.32, 95% CI 1.46-12.8, p<0.01) but was not associated with DF-specific IgG4 or decreased IgE levels. Further studies are needed to understand the role of allergen-specific IgE in CAD and of IgG1 in ASIT.

Search for contact interactions and large extra dimensions in dilepton events from pp collisions at sqrts=7 TeV with the ATLAS detector

A search for nonresonant new phenomena, originating from either contact interactions or large extra spatial dimensions, has been carried out using events with two isolated electrons or muons. These events, produced at the LHC in proton-proton collisions at root s = 7 TeV, were recorded by the ATLAS detector. The data sample, collected throughout 2011, corresponds to an integrated luminosity of 4.9 and 5.0 fb(-1) in the e(+)e(-) and mu(+)mu(-) channels, respectively. No significant deviations from the Standard Model expectation are observed. Using a Bayesian approach, 95% confidence level lower limits ranging from 9.0 to 13.9 TeV are placed on the energy scale of llqq contact interactions in the left-left isoscalar model. Lower limits ranging from 2.4 to 3.9 TeV are also set on the string scale in large extra dimension models. After combining these limits with results from a similar search in the diphoton channel, slightly more stringent limits are obtained.

Contact, Mobility and Authenticity: Language Ideologies in Koineisation

New Zealand English first emerged at the beginning of the 19th century as a result of the dialect contact of British (51%), Scottish (27.3%) and Irish (22%) migrants (Hay and Gordon 2008:6). This variety has subsequently developed into an autonomous and legitimised national variety and enjoys a distinct socio-political status, recognition and codification. In fact, a number of dictionaries of New Zealand English have been published1 and the variety is routinely used as the official medium on TV, radio and other media. This however, has not always been the case, as for long only British standard norms were deemed suitable for media broadcasting. While there is some work already on lay commentary about New Zealand English (see for example Gordon 1983, 1994; Hundt 1998), there is much more to be done especially concerning more recent periods of the history of this variety and the ideologies underlying its development and legitimisation. Consequently, the current project aims at investigating the metalinguistic discourses during the period of transition from a British norm to a New Zealand norm in the media context, this will be done by focusing on debates about language in light of the advent of radio and television. The main purpose of this investigation is thus to examine the (language) ideologies that have shaped and underlain these discourses (e.g. discussions about the appropriateness of New Zealand English vis à vis external, British models of language) and their related practices in these media (e.g. broadcasting norms). The sociolinguistic and pragmatic effects of these ideologies will also be taken into account. Furthermore, a comparison will be carried out, at a later stage in the project, between New Zealand English and a more problematic and less legitimised variety: Estuary English. Despite plenty of evidence of media and other public discourses on Estuary English, in fact, there has been very little metalinguistic analysis of this evidence, nor examinations of the underlying ideologies in these discourses. The comparison will seek to discover whether similar themes emerge in the ideologies played out in publish discourses about these varieties, themes which serve to legitimise one variety, whilst denying such legitimacy to the other.

Gamma-linolenic acid levels correlate with clinical efficacy of evening primrose oil in patients with atopic dermatitis.

INTRODUCTION Atopic dermatitis (AD) has been related to a deficiency of delta-6-desaturase, an enzyme responsible for the conversion of linoleic acid to gamma-linolenic acid (GLA). Evening primrose oil (EPO) contains high amounts of GLA. Therefore, this study investigated whether EPO supplementation results in an increase in plasma GLA and its metabolite dihomo-gamma-linolenic acid (DGLA) correlating with clinical improvement of AD, assessed by the SCORing Atopic Dermatitis (SCORAD) index. METHODS The open study included 21 patients with AD. EPO (4-6 g) was administered daily for 12 weeks. Before treatment, and 4 and 12 weeks after initiation of EPO supplementation, objective SCORAD was assessed and plasma concentrations of GLA and DGLA were determined by gas chromatography. RESULTS A significant increase in plasma GLA and DGLA levels and a decrease in the objective SCORAD were observed 4 and 12 weeks after initiation of EPO treatment. In the per-protocol population (n = 14), a significant inverse correlation between the changes in plasma GLA levels and SCORAD was found (P = 0.008). CONCLUSION The clinical disease activity under EPO treatment correlates with the individual increase in plasma GLA levels. Thus, the results of this pilot study indicate that an increase in plasma GLA might be used as predictive parameter for responsiveness of AD to EPO therapy.