The role of national and international veterinary laboratories.

In the field of diagnostic test validation, World Organisation for Animal Health (OIE) Reference Laboratories (RLs) have a pivotal role and provide the international community with impartial advice and support in the selection, development and validation of diagnostic tests, which can be applied to the specialist diseases for which they are designated. National RLs provide an invaluable function in supporting the introduction, ongoing validation and application of validated diagnostic tests in line with international standards. Experienced staff with extensive knowledge of such systems and access to specialist facilities for conducting work are available to monitor changes or advancements in technology. They consider their relevance and value to evolving diagnostic test requirements. Reference Laboratories often have a broad mandate of activity linking research or development programmes and surveillance activities to benefit the continual assessment and, if necessary, improvement of diagnostic tools. Reference Laboratories maintain or have access to unique biological archives (known positive and negative sample populations) and produce international reference standards, both of which are vital in establishing the necessary and detailed validation of any diagnostic test. Reference Laboratories act either singularly or in collaborative partnerships with other RLs or science institutes, but also, when required, and with impartiality, with the commercial sector, to ensure new tests are validated according to OIE standards. They promote and apply formal programmes of quality assurance (including proficiency testing programmes) for newly validated tests, ensuring ongoing monitoring and compliance with standards, or as required set out any limitations or uncertainties. Reference Laboratories publish information on test validation in the scientific literature and on relevant websites, as well as disseminating information at workshops and international conferences. Furthermore, they can offer training in the processes and systems underpinning test validation.

Dans le domaine de la validation des tests de diagnostic, les Laboratoires de référence de l'Organisation mondiale de la santé animale (OIE) jouent un rôle central et fournissent à la communauté internationale des conseils impartiaux ainsi qu'un soutien pour la sélection, la mise au point et la validation des tests de diagnostic utilisés pour la détection des maladies correspondant à leur domaine de spécialisation. Les Laboratoires de référence nationaux remplissent une fonction inestimable en facilitant l'introduction, la validation continue et l'application de tests de diagnostic validés conformément aux normes internationales. Ces laboratoires sont dotés de personnels expérimentés possédant une connaissance approfondie de ces systèmes et qui ont accès à des installations spécialisées pour mener à bien leurs opérations et suivre de près les changements ou les avancées technologiques. Ils peuvent ainsi examiner leur pertinence et intérêt au regard de l'évolution des exigences relatives aux tests de diagnostic. Le mandat des Laboratoires de référence recouvre souvent un large éventail d'activités reliant les programmes de recherche ou développement et les activités de surveillance, ce qui permet de réaliser une évaluation continue des outils diagnostiques et, si besoin, de procéder à leur amélioration. Les Laboratoires de référence entretiennent ou ont accès à des banques de matériels biologiques uniques (panels d'échantillons positifs et négatifs connus) et produisent des réactifs de référence internationale, deux catégories de matériels essentielles pour procéder à la validation point par point d'un test diagnostique suivant les critères requis. Les Laboratoires de référence interviennent individuellement ou en partenariat avec d'autres Laboratoires de référence ou instituts scientifiques, mais aussi, lorsque c'est nécessaire et dans le respect des règles d'impartialité, avec le secteur privé, afin de s'assurer que les nouveaux tests sont validés conformément aux normes de l'OIE. Ils soutiennent et appliquent des programmes officiels d'assurance de la qualité (y compris en participant à des programmes d'essais d'aptitude inter-laboratoires) pour les tests nouvellement validés et garantissent leur suivi continu ainsi que leur conformité avec les normes, ou, suivant les cas, définissent les limites ou le niveau d'incertitude à prendre en considération. Les Laboratoires de référence publient les données relatives à la validation des tests dans des journaux scientifique et sur les sites Web pertinents et diffusent également des informations sur le sujet lors d'ateliers et de conférences internationales. En outre, ils peuvent proposer des formations sur les procédures et les systèmes qui sous-tendent la validation des tests.

En el terreno de la validación de pruebas de diagnóstico, los Laboratorios de Referencia de la Organización Mundial de Sanidad Animal (OIE) cumplen una función central y proporcionan a la comunidad internacional servicios de apoyo y asesoramiento imparcial para la selección, el desarrollo y la validación de pruebas de diagnóstico, que pueden aplicarse a la enfermedad para la que cada laboratorio esté designado. Los laboratorios de referencia nacionales cumplen una inestimable función de apoyo a la implantación, la continua validación y la utilización de pruebas de diagnóstico validadas con arreglo a las normas internacionales. Disponen de personal experimentado y muy buen conocedor de estos sistemas y de acceso a instalaciones especializadas de trabajo, lo que les permite seguir de cerca los cambios o adelantos tecnológicos y estudiar su utilidad o interés en relación con la evolución de los requisitos de las pruebas de diagnóstico. Los Laboratorios de Referencia suelen tener un mandato amplio, que a los programas de investigación y desarrollo aúna actividades de vigilancia, en aras de la continua evaluación y, en caso necesario, mejora de las herramientas de diagnóstico. Estos laboratorios poseen (o tienen acceso a) archivos biológicos únicos (conjuntos de muestras probadamente positivas y negativas) y elaboran patrones de referencia internacional, elementos ambos indispensables para llevar a buen fin la necesaria validación detallada de toda prueba de diagnóstico. Los Laboratorios de Referencia pueden trabajar en solitario o en colaboración con otros Laboratorios de Referencia, con institutos científicos e incluso, cuando hace falta, y procediendo con imparcialidad, con entidades del sector privado, a fin de garantizar que toda nueva prueba sea validada con arreglo a las normas de la OIE. También promueven y llevan adelante programas oficiales de garantía de la calidad de pruebas recién validadas (incluidos programas de pruebas de competencia), lo que asegura un seguimiento continuo y el cumplimiento de la normativa en todo momento, o fijan, cuando es necesario, limitaciones o niveles de incertidumbre. Asimismo, estos laboratorios publican datos sobre la validación de pruebas en revistas científicas y sitios web conexos y difunden información al respecto en talleres y conferencias internacionales. Además, pueden impartir formación sobre los procesos y sistemas que fundamentan la validación de pruebas de diagnóstico.

International validation of a risk prediction algorithm for patients with malignant colorectal polyps.

AIM: The optimal management strategy for patients with endoscopically resected malignant colorectal polyps (MCP) has yet to be defined. The aim of this study was to validate a published decision-making tool, termed the Scottish Polyp Cancer Study (SPOCS) algorithm, on a large international population. METHODS: The SPOCS algorithm allocates patients to risk groups based on just two variables: the polyp resection margin and the presence of lymphovascular invasion (LVI). The risk groups are termed low (clear margin, LVI absent), medium (clear margin, LVI present) or high (involved/non-assessable margin). The International Polyp Cancer Collaborative was formed to validate the algorithm on data from Australia, Denmark, UK and New Zealand. RESULTS: In total, 1423 patients were included in the final dataset. 680/1423 (47.8%) underwent surgical resection and 108/680 (15.9%) had residual disease (luminal disease 8.8%, lymph node metastases 8.8%). The SPOCS algorithm classified 602 patients as low risk (in which 1.5% had residual disease), 198 patients as medium risk (in which 7.1% had residual disease) and 484 as high risk (in which 14.5% had residual disease) (P < 0.001, χ2 test). Receiver operating characteristic curve analysis demonstrated good accuracy of the algorithm in predicting residual disease (area under the curve 0.732, 95% CI 0.687-0.778, P < 0.001). When patients were designated as low risk, the negative predictive value was 98.5%. CONCLUSION: The SPOCS algorithm can be used to predict the risk of residual disease in patients with endoscopically resected MCPs. Surgery can be safely avoided in patients who have a clear margin of excision and no evidence of LVI.

Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease originating from the pilosebaceous unit, in which patients develop painful abscesses, sinus tracts, nodules and scarring, typically in intertriginous areas. Major gaps in our understanding of HS exist, and these may be partially due to the lack of an animal model for experimental studies. We developed an HS xenograft mouse model using human HS lesions grafted onto immunocompromised mice. Although the model had its limitations, several informative lessons were learned, which may contribute to future attempts at an HS animal model.

A qualitative risk assessment of cleansing and disinfection requirements after an avian influenza outbreak in commercial poultry.

1. During an avian influenza (AI) outbreak in the United Kingdom, the joint aim of the poultry industry and the Government is to eliminate and prevent the spread of infection, through control measures based on the current European Union (EU) Council Directive (2005/94/EC). An essential part of these measures is the cleansing and disinfection (C&D) of infected premises.2. This risk assessment assessed the differences in re-infection in a repopulated flock if the EU Directive is interpreted to permit secondary C&D to be undertaken either with or without dismantling complex equipment. The assessment estimated the probability of virus survival on different types of equipment in a depopulated contaminated poultry house before and after preliminary and secondary C&D procedures. A risk matrix spreadsheet tool was used to carry out the assessment and concluded that, provided secondary C&D is carried out with due diligence (i.e. carried out to a defined code of practice as agreed by both industry and policymakers), the risk of re-infection from equipment is negligible, both with and without dismantling complex equipment in all farm types considered.3. By considering the equipment types individually, the assessment identified those areas of the house which may still contain viable virus post-preliminary C&D and on which attention should be focussed during secondary C&D. The generic risk pathway and matrix spreadsheet tool have the potential to be used for other pathogens and species, given appropriate data.

Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks.

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any 'gold standard'. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.

The Amazon basin in transition.

Agricultural expansion and climate variability have become important agents of disturbance in the Amazon basin. Recent studies have demonstrated considerable resilience of Amazonian forests to moderate annual drought, but they also show that interactions between deforestation, fire and drought potentially lead to losses of carbon storage and changes in regional precipitation patterns and river discharge. Although the basin-wide impacts of land use and drought may not yet surpass the magnitude of natural variability of hydrologic and biogeochemical cycles, there are some signs of a transition to a disturbance-dominated regime. These signs include changing energy and water cycles in the southern and eastern portions of the Amazon basin.

MRI in adult patients with aortic coarctation: diagnosis and follow-up.

Aortic coarctation is a disease that usually presents in infancy; however, a proportion of patients present for the first time in adulthood. These lesions generally require repair with either surgery or interventional techniques. The success of these techniques means that increasing numbers of patients are presenting for follow-up imaging in adulthood, whether their coarctation was initially repaired in infancy or as adults. Thus, the adult presenting to the radiologist for assessment of possible coarctation or follow-up of coarctation repair is not an uncommon scenario. In this review, we present details of the MRI protocols and MRI findings in these patients so that a confident and accurate assessment can be made.

Operationalisation of quality of life for adults with severe disabilities.

BACKGROUND: The operationalisation of quality of life for people with more severe disabilities has been acknowledged in the published research for more than two decades. This study aims to contribute to our knowledge and understanding of the quality of life of adults with severe disabilities by developing a set of quality of life indicators appropriate to this population using a Delphi method and the eight-domain conceptual model proposed by Schalock & Verdugo (2002). METHOD: The participating panel in the Delphi method included 12 experts who evaluated each proposed item according to four criteria: suitability, importance, observability and sensitivity. Descriptive analyses were used to select the best items in each of the four rounds of this Delphi study, as well as examining the coefficients of concordance that were calculated for the final pool of items. RESULTS: The four rounds of the Delphi study resulted in a final pool of 118 items (91 that were considered valid in the first round plus 27 items proposed, reformulated or discussed in the following rounds). Importance and sensitivity were the criteria that received the highest and lowest ratings, respectively, but also the ones that had the highest and lowest mean coefficients of concordance. Experts showed the strongest agreement for items related to material well-being, while the weakest was found for items related to personal development. CONCLUSIONS: This study further contributes to our understanding of how to operationalise and measure quality of life in adults with severe disabilities. The item pool generated may prove helpful in the development of instruments for the measurement of quality of life-related outcomes in this population.

Kinetic study of the thermal denaturation of a hyperthermostable extracellular α-amylase from Pyrococcus furiosus.

Hyperthermophilic enzymes are of industrial importance and interest, especially due to their denaturation kinetics at commercial sterilisation temperatures inside safety indicating time-temperature integrators (TTIs). The thermal stability and irreversible thermal inactivation of native extracellular Pyrococcus furiosus α-amylase were investigated using differential scanning calorimetry, circular dichroism and Fourier transform infrared spectroscopy. Denaturation of the amylase was irreversible above a Tm of approximately 106°C and could be described by a one-step irreversible model. The activation energy at 121°C was found to be 316kJ/mol. Using CD and FT-IR spectroscopy it was shown that folding and stability greatly increase with temperature. Under an isothermal holding temperature of 121°C, the structure of the PFA changes during denaturation from an α-helical structure, through a ß-sheet structure to an aggregated protein. Such data reinforces the use of P. furiosus α-amylase as a labile species in TTIs.

Comparing introduction to Europe of highly pathogenic avian influenza viruses A(H5N8) in 2014 and A(H5N1) in 2005.

Since the beginning of November 2014, nine outbreaks of highly pathogenic avian influenza virus (HPAIV) A(H5N8) in poultry have been detected in four European countries. In this report, similarities and differences between the modes of introduction of HPAIV A(H5N1) and A(H5N8) into Europe are described. Experiences from outbreaks of A(H5N1) in Europe demonstrated that early detection to control HPAIV in poultry has proven pivotal to minimise the risk of zoonotic transmission and prevention of human cases.

Antigenic and genetic analyses of isolate APMV/wigeon/Italy/3920-1/2005 indicate that it represents a new avian paramyxovirus (APMV-12).

Isolate wigeon/Italy/3920-1/2005 (3920-1) was obtained during surveillance of wild birds in November 2005 in the Rovigo province of Northern Italy and shown to be a paramyxovirus. Analysis of cross-haemagglutination-inhibition tests between 3920-1 and representative avian paramyxoviruses showed only a low-level relationship to APMV-1. Phylogenetic analysis of the whole genome and each of the six genes indicated that while 3920-1 grouped with APMV-1 and APMV-9 viruses, it was quite distinct from these two. In the whole-genome analysis, 3920-1 had 52.1 % nucleotide sequence identity to the closest APMV-1 virus, 50.1 % identity to the APMV-9 genome, and less than 42 % identity to representatives of the other avian paramyxovirus groups. We propose isolate wigeon/Italy/3920-1/2005 as the prototype strain of a further APMV group, APMV-12.

Evaluation of the pooling of swabs for real-time PCR detection of low titre shedding of low pathogenicity avian influenza in turkeys.

The purpose of this study was to determine whether pooling avian influenza (AI)-positive swabs with negative swabs has a detrimental effect on the sensitivity of AI real-time reverse transcription-polymerase chain reactions (rRT-PCRs). Cloacal and buccal swabs were sampled daily from 12 turkeys infected with A/goose/England/07(H2N2). For half the turkeys, each swab was mixed with four swabs from known AI-negative turkeys, and for the other half the swabs were tested individually. Bayesian modelling was used to (i) determine whether pooling the positive swabs compromised the cycle threshold (C(t)) value obtained from the rRT-PCRs, and (ii) estimate the likelihood of detection of an H2N2 infected turkey flock via rRT-PCR for pooled and individually tested swabs (cloacal and buccal) vs. the number of days post-infection of the flock. Results indicated that there was no significant effect of compromising AI rRT-PCR sensitivity by pooling a weak positive swab with negative swabs on the Ct values which were obtained. Pooled sampling was able to widen the detection window compared to individual sampling, for the same number of rRT-PCR tests. This indicates that pooled sampling would be an effective method of reducing the number of tests to be performed to determine flock status during an AI outbreak and for surveillance.

Happiness and health behaviour in Iranian adolescent girls.

This study was conducted to examine the association of happiness in adolescent females with leisure time and health related behaviours namely diet, physical activity and first or second hand smoking. Using a self-administered questionnaire, data were collected from 8159 female high school students ages 11-19 years. Multivariate linear regression analysis revealed statistically significant associations between happiness and weight, regular exercise, exposure to second-hand tobacco smoke, daily fruit or vegetable consumption and the way participants spent their leisure time. Happiness was associated with lower BMI, regular physical activity, absence of exposure to second-hand smoke, higher consumption of fruits and vegetables, and spending leisure time with family (all P < 0.005). These exploratory findings suggest that encouraging children and adolescents to adopt healthy behaviours, providing family time and a smoke-free environment may make them not only healthier but also happier.

Evaluating a novel patient pathway to manage symptomatic breast referrals (the blue flag clinic): a longitudinal observational study.

INTRODUCTION: A novel referral pathway for exhibited breast symptom (EBS) referrals to manage increasing referrals of urgent suspected cancer (USC) was implemented in our trust. We report on the safety and effect on compliance with the 2-week-wait rule (2WW). METHODS: A single-centre longitudinal observational study included all patients referred to a UK breast unit during 13 May 2019 to 27 March 2020 (period 1) and 8 February 2021 to 31 January 2022 (period 2). USC referrals were assessed in a one-stop clinic (red flag clinic [RFC]); EBS referrals were assessed in a new clinic in which clinical evaluation was performed and imaging occurred subsequently (blue flag clinic [BFC]). Patients were followed up to determine the symptomatic interval cancer rate. RESULTS: There were 9,695 referrals; 1,655 referrals (17%) were assessed in the BFC after 63 exclusions. Some 95.9% of patients had a benign clinical examination (P1/P2), 80.1% had imaging (mammogram or ultrasound) and 4% had a tissue biopsy. In total, 16/1,655 (0.97%) BFC patients and 510/7,977 (8.2%) RFC patients were diagnosed with breast cancer (breast cancer detection rate). Some 1,631 patients (with 1,639 referrals) were discharged and followed up for a median of 17 months (interquartile range 12-32) with one subsequent cancer diagnosis (symptomatic interval cancer rate, 0.06%). Implementation of the BFC pathway increased 3-month average trust performance of USC referrals with 2WW standard from 8.5% to 98.7% (period 1) and from 30% to 66% (period 2). CONCLUSIONS: The BFC pathway for EBS patients is safe and implementation led to improvement against the 2WW target for USC referrals, ensuring resources are prioritised to patients with the highest likelihood of breast cancer.

H9N2 avian influenza virus dispersal along Bangladeshi poultry trading networks.

Avian influenza virus subtype H9N2 is endemic in Bangladesh's poultry population. The subtype affects poultry production and poses a potential zoonotic risk. Insufficient understanding of how the poultry trading network shapes the dissemination of avian influenza viruses has hindered the design of targeted interventions to reduce their spread. Here, we use phylodynamic analyses of haemagglutinin sequences to investigate the spatial spread and dispersal patterns of H9N2 viruses in Bangladesh's poultry population, focusing on its two largest cities (Dhaka and Chattogram) and their poultry production and distribution networks. Our analyses suggest that H9N2 subtype avian influenza virus lineage movement occurs relatively less frequently between Bangladesh's two largest cities than within each city. H9N2 viruses detected in single markets are often more closely related to viruses from other markets in the same city than to each other, consistent with close epidemiological connectivity between markets. Our analyses also suggest that H9N2 viruses may spread more frequently between chickens of the three most commonly sold types (sunali-a cross-bred of Fayoumi hen and Rhode Island Red cock, deshi-local indigenous, and exotic broiler) in Dhaka than in Chattogram. Overall, this study improves our understanding of how Bangladesh's poultry trading system impacts avian influenza virus spread and should contribute to the design of tailored surveillance that accommodates local heterogeneity in virus dispersal patterns.

Estimating reassortment rates in co-circulating Eurasian swine influenza viruses.

Swine have often been considered as a mixing vessel for different influenza strains. In order to assess their role in more detail, we undertook a retrospective sequencing study to detect and characterize the reassortants present in European swine and to estimate the rate of reassortment between H1N1, H1N2 and H3N2 subtypes with Eurasian (avian-like) internal protein-coding segments. We analysed 69 newly obtained whole genome sequences of subtypes H1N1-H3N2 from swine influenza viruses sampled between 1982 and 2008, using Illumina and 454 platforms. Analyses of these genomes, together with previously published genomes, revealed a large monophyletic clade of Eurasian swine-lineage polymerase segments containing H1N1, H1N2 and H3N2 subtypes. We subsequently examined reassortments between the haemagglutinin and neuraminidase segments and estimated the reassortment rates between lineages using a recently developed evolutionary analysis method. High rates of reassortment between H1N2 and H1N1 Eurasian swine lineages were detected in European strains, with an average of one reassortment every 2-3 years. This rapid reassortment results from co-circulating lineages in swine, and in consequence we should expect further reassortments between currently circulating swine strains and the recent swine-origin H1N1v pandemic strain.

miRNA-34a is associated with docetaxel resistance in human breast cancer cells.

Docetaxel is a chemotherapy drug to treat breast cancer, however as with many chemotherapeutic drugs resistance to docetaxel occurs in 50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through microRNAs (miRNA) has been shown to play an important role in cancer drug resistance. By directly targeting mRNA, miRNAs are able to inhibit genes that are necessary for signalling pathways or drug induced apoptosis rendering cells drug resistant. This study investigated the role of differential miRNA expression in two in vitro breast cancer cell line models (MCF-7, MDA-MB-231) of acquired docetaxel resistance. MiRNA microarray analysis identified 299 and 226 miRNAs altered in MCF-7 and MDA-MB-231 docetaxel-resistant cells, respectively. Docetaxel resistance was associated with increased expression of miR-34a and miR-141 and decreased expression of miR-7, miR-16, miR-30a, miR-125a-5p, miR-126. Computational target prediction revealed eight candidate genes targeted by these miRNAs. Quantitative PCR and western analysis confirmed decreased expression of two genes, BCL-2 and CCND1, in docetaxel-resistant cells, which are both targeted by miR-34a. Modulation of miR-34a expression was correlated with BCL-2 and cyclin D1 protein expression changes and a direct interaction of miR-34a with BCL-2 was shown by luciferase assay. Inhibition of miR-34a enhanced response to docetaxel in MCF-7 docetaxel-resistant cells, whereas overexpression of miR-34a conferred resistance in MCF-7 docetaxel-sensitive cells. This study is the first to show differences in miRNA expression, in particular, increased expression of miR-34a in an acquired model of docetaxel resistance in breast cancer. This serves as a mechanism of acquired docetaxel resistance in these cells, possibly through direct interactions with BCL-2 and CCND1, therefore presenting a potential therapeutic target for the treatment of docetaxel-resistant breast cancer.

Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. METHODS: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.

The ecology and age structure of a highly pathogenic avian influenza virus outbreak in wild mute swans.

The first UK epizootic of highly pathogenic (HP) H5N1 influenza in wild birds occurred in 2008, in a population of mute swans that had been the subject of ornithological study for decades. Here we use an innovative combination of ornithological, phylogenetic and immunological approaches to investigate the ecology and age structure of HP H5N1 in nature. We screened samples from swans and waterbirds using PCR and sequenced HP H5N1-positive samples. The outbreak's origin was investigated by linking bird count data with a molecular clock analysis of sampled virus sequences. We used ringing records to reconstruct the age-structure of outbreak mortality, and we estimated the age distribution of prior exposure to avian influenza. Outbreak mortality was low and all HP H5N1-positive mute swans in the affected population were <3 years old. Only the youngest age classes contained an appreciable number of individuals with no detectable antibody responses to viral nucleoprotein. Phylogenetic analysis indicated that the outbreak strain circulated locally for ~1 month before detection and arrived when the immigration rate of migrant waterbirds was highest. Our data are consistent with the hypothesis that HP H5N1 epizootics in wild swans exhibit limited mortality due to immune protection arising from previous exposure. Our study population may represent a valuable resource for investigating the natural ecology and epidemiology of avian influenza.

Prospective randomised trial of endobronchial ultrasound-guide sheath versus computed tomography-guided percutaneous core biopsies for peripheral lung lesions.

AIM: To determine diagnostic rate, complications and patient tolerability of endobronchial ultrasound-guide sheath (EBUS-GS) and computed tomography (CT)-guided percutaneous core biopsy for peripheral lung lesions. METHODS: Lesions >1 cm diameter on CT were randomised to either EBUS-GS or CT-guided biopsy. Excluded were patients with severe chronic obstructive airway disease, lesions touching visceral pleura or hilum, and patients with symptoms needing bronchoscopic evaluation. Patients completed preprocedure and postprocedure questionnaires on tolerability. RESULTS: Of 64 participants (mean lesion size 29 ± 16 mm), 57 completed the study. Diagnostic sensitivity was 67% for EBUS-GS and 78% for CT-guided biopsy (P = not significant). In those with negative results, in the EBUS group, nine had a CT-guided biopsy as a cross-over, seven of which were positive. In the CT group, four had cross-over EBUS-GS of which three were diagnostic. Sensitivity for malignancy was 17/23 for EBUS-GS (74%) and 23/26 (88%, P = not significant). For lesions <2 cm, CT-guided biopsy had a significantly better diagnostic yield (80% vs 50%, P = 0.05). In EBUS-GS cases, for lesions with an air bronchogram, sensitivity was 89%. Pneumothorax and intercostal catheter insertion occurred in three and two cases, respectively, for EBUS, and 10 and 3 cases for CT-guided biopsy (P = 0.02 for pneumothorax). Nine unexpected admissions occurred after CT-guided biopsy compared with three after EBUS-GS. Overall, tolerability was high for both groups; however three patients had moderate-to-severe pain after CT-guided biopsy. CONCLUSIONS: In lesions <2 cm, CT-guided biopsy had higher yields; however, EBUS-GS had better tolerability and fewer complications.