A growth type pathway for improving the folding of BPTI.

The in vitro oxidative folding of the protein bovine pancreatic trypsin inhibitor (BPTI) with oxidized dithiothreitol or glutathione has served as a paradigm for protein folding but could take weeks at physiological pH because of the need to escape from kinetic traps via a rearrangement type pathway. The two major kinetic traps are called N' and N* and contain two of the three native disulfide bonds, which occur between residues 5 and 55, 30 and 51, and 14 and 38. N' is missing the disulfide bond between residues 5 and 55 while N* is missing the disulfide bond between residues 30 and 51. By determining rate constant for the reactions of the kinetic traps N* and N' and their mixed disulfides with glutathione and glutathione disulfide, many for the first time, we demonstrate that growth type pathways are feasible and could even be more efficient than rearrangement type pathways. Thus, formally unproductive pathways became productive. Interestingly, under physiological redox conditions both rearrangement and growth type pathways are important highlighting the redundancy of oxidative protein folding. With the new set of rate constants, modeling indicated that in vitro oxidative protein folding of BPTI via a growth type pathway using an oxidation, reduction and oxidation cycle would significantly improve protein folding efficiency, albeit under non-physiological redox conditions. With these changing conditions 91 ± 2% of native BPTI was achieved in 12 h compared to 83% native protein in 24 h using our previous best conditions of 5 mM GSSG and 5 mM GSH. Therefore, changing redox conditions via an oxidation, reduction and oxidation cycle may become an additional methodology for enhancing in vitro protein folding in aqueous solution.

Impact of viral testing on duration of antibiotic treatment and hospitalisation of febrile infants.

AIM: To assess the duration of antimicrobial treatment; hospital length of stay; and invasive bacterial infections rates in hospitalised infants following the adoption of a management guideline. METHODS: Faculty agreed to a standard of 24 h of antibiotic treatment for well-appearing febrile infants with proven viral infection and no growth on bacterial cultures. The outcomes were the duration of hospitalisation and antibiotic treatment of febrile infants less than 8 weeks of age who have enterovirus, parechovirus, respiratory viruses detected. We monitored re-admissions and missed invasive infections. RESULTS: Of the total 1696 infants studied, the median antibiotic treatment duration decreased from 31.5 to 24.8 h in virus-infected infants ≤21 days of age (p = 0.02) and from 26 to 19.7 h in infants 22-56 days of age (p < 0.001). The decrease was less in infants not infected with a virus. No patient had an invasive infection identified after discharge. CONCLUSION: The implementation of our care standard resulted in reduction in antibiotic treatment duration without known delayed diagnosis of bacterial infections. Infants without a proven viral aetiology may need further study to inform management decisions.

Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis.

BACKGROUND: The TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival. METHODS: Tumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH). RESULTS: Levels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis. CONCLUSIONS: Tumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.

Exploring views of members of the public and policymakers on the acceptability of population level dietary and active-travel policies: a qualitative study.

BACKGROUND: There is limited evidence on what shapes the acceptability of population level dietary and active-travel policies in England. This information would be useful in the decision-making process about which policies should be implemented and how to increase their effectiveness and sustainability. To fill this gap, we explored public and policymakers' views about factors that influence public acceptability of dietary and active-travel policies and how to increase public acceptability for these policies. METHODS: We conducted online, semi-structured interviews with 20 members of the public and 20 policymakers in England. A purposive sampling frame was used to recruit members of the public via a recruitment agency, based on age, sex, socioeconomic status and ethnicity. Policymakers were recruited from existing contacts within our research collaborations and via snowball sampling. We explored different dietary and active-travel policies that varied in their scope and focus. Interviews were transcribed verbatim and analysed using thematic reflexive analysis with both inductive and deductive coding. RESULTS: We identified four themes that informed public acceptability of dietary and active-travel policies: (1) perceived policy effectiveness, i.e., policies that included believable mechanisms of action, addressed valued co-benefits and barriers to engage in the behaviour; (2) perceived policy fairness, i.e., policies that provided everyone with an opportunity to benefit (mentioned only by the public), equally considered the needs of various population subgroups and rewarded 'healthy' behaviours rather than only penalising 'unhealthy' behaviours; (3) communication of policies, i.e., policies that were visible and had consistent and positive messages from the media (mentioned only by policymakers) and (4) how to improve policy support, with the main suggestion being an integrated strategy addressing multiple aspects of these behaviours, inclusive policies that consider everyone's needs and use of appropriate channels and messages in policy communication. CONCLUSIONS: Our findings highlight that members' of the public and policymakers' support for dietary and active-travel policies can be shaped by the perceived effectiveness, fairness and communication of policies and provide suggestions on how to improve policy support. This information can inform the design of acceptable policies but can also be used to help communicate existing and future policies to maximise their adoption and sustainability.

An in-field evaluation of rapid DNA instruments for disaster victim identification.

In 2019 and 2020, disaster victim identification (DVI) simulations were conducted at the Australian Facility for Taphonomic Experimental Research. Whole and fragmented cadavers were positioned to replicate a building collapse scenario and left to decompose for up to 4 weeks. This study evaluated the utility of the ANDE™ 6C Rapid DNA System and the RapidHITTM ID System for DVI in the field and mortuary. Applying post-mortem nail and tissue biopsy samples showed promise, with the added benefit of minimally invasive collection procedures and limited preparation requirements. The preferred platform will depend on a number of factors, including its intended use and operating environment.

Augmentation of Fracture Repair: Is Anything Ready for Prime Time?

There continues to be a significant burden of disease associated with the delayed healing of common fractures. Despite a number of trials focused on the augmentation of fracture repair, management remains controversial and evidence regarding cost-effectiveness is lacking. The recent evidence that has challenged traditional thinking regarding management of fracture healing problems will be evaluated.

Development of a Formative Assessment Rubric for Peer Evaluation of Teaching (FARPET) and Pilot Use in Veterinary Online Teaching.

Peer evaluation of teaching (PET) serves an important role as a component of faculty development in the medical education field. With the emergence of COVID-19, the authors recognized the need for a flexible tool that could be used for a variety of lecture formats, including virtual instruction, and that could provide a framework for consistent and meaningful PET feedback. This teaching tip describes the creation and pilot use of a PET rubric, which includes six fixed core items (lesson structure, content organization, audiovisual facilitation, concept development, enthusiasm, and relevance) and items to be assessed separately for asynchronous lectures (cognitive engagement-asynchronous) and synchronous lectures (cognitive engagement-synchronous, discourse quality, collaborative learning, and check for understanding). The instrument packet comprises the rubric, instructions for use, definitions, and examples of each item, plus three training videos for users to compare with authors' consensus training scores; these serve as frame-of-reference training. The instrument was piloted among veterinary educators, and feedback was sought in a focus group setting. The instrument was well received, and training and use required a minimum time commitment. Inter-rater reliability within 1 Likert scale point (adjacent agreement) was assessed for each of the training videos, and consistency of scoring was demonstrated between focus group members using percent agreement (0.82, 0.85, 0.88) and between focus members and the authors' consensus training scores (all videos: 0.91). This instrument may serve as a helpful resource for institutions looking for a framework for PET. We intend to continually adjust the instrument in response to feedback from wider use.

The value of virtual biobanks for transparency purposes with respect to reagents and samples used during test development and validation.

Biobanks represent a valuable resource in many areas of biomedical research and development. They function as repositories for well-documented and well-characterised biological material that can be used as the basis for this work. Virtual biobanks amplify the availability of this resource by linking multiple biobanks via a single interface. Test development and validation is an essential process that helps to provide confidence in diagnostic test results and, by extension, the disease and health status of animal populations demonstrated by such results. The quality of the development and validation pathway can be enhanced by the use of well-characterised material for standards and validation panels. Virtual biobanks represent a powerful mechanism for enhancing access to such material, and allow other parties to both have greater confidence in the work done, and to be able to repeat it themselves, as required.

Les biobanques constituent une ressource précieuse dans un grand nombre de domaines de la recherche et du développement biomédicaux. Elles servent d'archives destinées au stockage de matériels biologiques suffisamment documentés et caractérisés pour être utilisés comme éléments de base dans ces domaines. Les biobanques virtuelles opèrent comme multiplicateurs des ressources disponibles en reliant plusieurs biobanques sur une même interface. La mise au point et la validation des tests constituent un processus essentiel qui contribue à asseoir la confiance dans les résultats d'un test et, par voie de conséquence, dans le statut sanitaire d'une population animale tel qu'il ressort de ces résultats. La qualité du processus de développement et de validation peut être améliorée en faisant appel à des matériels bien caractérisés en tant que panels de référence et de validation. Les biobanques virtuelles sont un mécanisme puissant pour améliorer l'accès à ce type de matériels et permettent à d'autres intervenants d'avoir une plus grande confiance dans les travaux réalisés, et de pouvoir eux-mêmes les répéter, si besoin.

Los biobancos constituyen un recurso muy útil en numerosas vertientes de la labor de investigación y desarrollo (I+D) en biomedicina. Estos bancos funcionan como repositorios de material biológico bien descrito y caracterizado que cabe utilizar como base de dicha labor. Los biobancos virtuales, al vincular entre sí múltiples biobancos por medio de una única interfaz, ponen este recurso al alcance de muchos más usuarios. La creación y validación de pruebas analíticas es un proceso esencial, que ayuda a ofrecer confianza en los resultados de una prueba de diagnóstico y, por extensión, en la condición sanitaria de las poblaciones animales que dichos resultados indican. Es posible conferir mayor calidad al procedimiento de creación y validación utilizando muestras biológicas bien caracterizadas como material de referencia y para establecer paneles de validación. Los biobancos virtuales, amén de constituir un potente mecanismo para mejorar el acceso a material biológico, infunden a terceras partes mayor confianza en la labor realizada y permiten a estas partes replicar por sí mismas el proceso de ser necesario.

Anomalous Nematic States in High Half-Filled Landau Levels.

It is well established that the ground states of a two-dimensional electron gas with half-filled high (N≥2) Landau levels are compressible charge-ordered states, known as quantum Hall stripe (QHS) phases. The generic features of QHSs are a maximum (minimum) in a longitudinal resistance R_{xx} (R_{yy}) and a nonquantized Hall resistance R_{H}. Here, we report on emergent minima (maxima) in R_{xx} (R_{yy}) and plateaulike features in R_{H} in half-filled N≥3 Landau levels. Remarkably, these unexpected features develop at temperatures considerably lower than the onset temperature of QHSs, suggestive of a new ground state.

Predicting population responses to environmental change from individual-level mechanisms: towards a standardized mechanistic approach.

Animal populations will mediate the response of global biodiversity to environmental changes. Population models are thus important tools for both understanding and predicting animal responses to uncertain future conditions. Most approaches, however, are correlative and ignore the individual-level mechanisms that give rise to population dynamics. Here, we assess several existing population modelling approaches and find limitations to both 'correlative' and 'mechanistic' models. We advocate the need for a standardized mechanistic approach for linking individual mechanisms (physiology, behaviour, and evolution) to population dynamics in spatially explicit landscapes. Such an approach is potentially more flexible and informative than current population models. Key to realizing this goal, however, is overcoming current data limitations, the development and testing of eco-evolutionary theory to represent interactions between individual mechanisms, and standardized multi-dimensional environmental change scenarios which incorporate multiple stressors. Such progress is essential in supporting environmental decisions in uncertain future conditions.

Evaluation of a human in vitro skin test for predicting drug hypersensitivity reactions.

The occurrence of drug hypersensitivity reactions (DHRs) following administration of low molecular weight (LMW) drugs is an important health concern. However, in vivo animal models which could be used as tools for the prediction of DHRs are lacking. As a result, research has focused on development of in vitro tools for predicting DHRs. In this study a novel human in vitro pre-clinical skin explant test was used to predict T cell-mediated hypersensitivity responses induced by LMW drugs. Responses in the skin explant test for 12 LMW drugs associated with T cell-mediated hypersensitivity in the clinic (abacavir, amoxicillin, carbamazepine, diclofenac, lamotrigine, lapatinib, lumiracoxib, nevirapine, ofloxacin, phenytoin, propranolol, sulfamethoxazole) were compared with responses for 5 drugs with few/no reports of T cell-mediated hypersensitivity reactions (acetaminophen, cimetidine, flecainide, metformin, verapamil). Changes in skin histology following in vitro exposure to the drugs as well as T cell proliferation and interferon gamma (IFNγ) production were studied. The results of the skin explant assays showed a good positive correlation (r = 0.77, p < .001) between the test outcome (prediction of positive or negative) and the clinical classification of the tested drugs. The T cell proliferation assay showed a correlation of r = 0.60 (p < .01) and the IFNγ assay r = 0.51 (p < .04). The data suggest that the skin explant model could be a useful tool to predict the potential of LMW drugs to induce DHRs.

Metrics of progress in the understanding and management of threats to Australian birds.

Although evidence-based approaches have become commonplace for determining the success of conservation measures for the management of threatened taxa, there are no standard metrics for assessing progress in research or management. We developed 5 metrics to meet this need for threatened taxa and to quantify the need for further action and effective alleviation of threats. These metrics (research need, research achievement, management need, management achievement, and percent threat reduction) can be aggregated to examine trends for an individual taxon or for threats across multiple taxa. We tested the utility of these metrics by applying them to Australian threatened birds, which appears to be the first time that progress in research and management of threats has been assessed for all threatened taxa in a faunal group at a continental scale. Some research has been conducted on nearly three-quarters of known threats to taxa, and there is a clear understanding of how to alleviate nearly half of the threats with the highest impact. Some management has been attempted on nearly half the threats. Management outcomes ranged from successful trials to complete mitigation of the threat, including for one-third of high-impact threats. Progress in both research and management tended to be greater for taxa that were monitored or occurred on oceanic islands. Predation by cats had the highest potential threat score. However, there has been some success reducing the impact of cat predation, so climate change (particularly drought), now poses the greatest threat to Australian threatened birds. Our results demonstrate the potential for the proposed metrics to encapsulate the major trends in research and management of both threats and threatened taxa and provide a basis for international comparisons of evidence-based conservation science.

Medidas de Progreso en el Entendimiento y el Manejo de las Amenazas que Enfrentan las Aves Australianas Resumen Aunque los métodos basados en evidencias se han vuelto muy comunes para la determinación del éxito de las medidas de conservación del manejo de los taxones amenazados, hoy en día no existen medidas estandarizadas para la evaluación del progreso de la investigación o el manejo. Desarrollamos cinco medidas para cumplir con esta necesidad que tienen los taxones amenazados y para cuantificar la necesidad de una mayor acción y un alivio efectivo de las amenazas. Estas medidas (falta de investigación, éxito de la investigación, falta de manejo, éxito del manejo y porcentaje de reducción de amenazas) pueden agregarse para examinar las tendencias de un taxón individual o las tendencias de las amenazas para múltiples taxones. Probamos la utilidad de estas medidas por medio de su aplicación en aves australianas amenazadas, que parece ser la primera vez que se evalúa el progreso en la investigación y en el manejo de amenazas para el caso de varios taxones amenazados dentro de un grupo faunístico a escala continental. Se ha realizado algún tipo de investigación sobre casi tres cuartas partes de las amenazas conocidas para los taxones, y hay un claro entendimiento de cómo aliviar casi la mitad de las amenazas con el impacto más alto. Se ha intentado algún tipo de manejo con casi la mitad de las amenazas. Los resultados del manejo variaron desde ensayos exitosos hasta la mitigación completa de la amenaza, incluso para un tercio de las amenazas de alto impacto. Tanto el progreso en la investigación como en el manejo tendió a ser mayor para los taxones que estaban siendo monitoreados, o que ocurrían en islas oceánicas. La depredación por gatos tuvo el puntaje más como amenaza potencial. Sin embargo, ha habido poco de éxito en la reducción del impacto de la depredación por gatos, así que ahora el cambio climático (particularmente la sequía) es la mayor amenaza para las aves amenazadas en Australia. Nuestros resultados demuestran el potencial que tienen las medidas propuestas de encapsular las tendencias más importantes en la investigación y en el manejo tanto de las amenazas como de los taxones amenazados y de proporcionar una base para comparaciones internacionales de la ciencia de la conservación basada en evidencias.

With widespread adoption of MIS colectomy for colon cancer, does hospital type matter?

BACKGROUND: Recent studies have shown that hospital type impacts patient outcomes, but no studies have examined hospital differences in outcomes for patients undergoing minimally invasive surgery (MIS) for segmental colectomies. METHODS: The 2010-2014 National Cancer Data Base was queried for patients undergoing segmental colectomy for non-metastatic colon adenocarcinoma. Descriptive statistics characterized MIS utilization by hospital type. Multivariable models were used to examine the effect of hospital type on outcomes after MIS. Survival probability was plotted using the Kaplan-Meier method. RESULTS: 80,922 patients underwent MIS segmental colectomy for colon cancer from 2010 to 2014. From 2010 to 2014, the number of MIS segmental colectomies increased by 157% at academic hospitals, 151% at comprehensive hospitals, and 153% at community hospitals. Compared to academic hospitals, community and comprehensive hospitals had greater adjusted odds of positive margins (Community OR 1.525, 95% Confidence Interval 1.233-1.885; Comprehensive OR 1.216, 95% CI 1.041-1.42), incomplete number of lymph nodes analyzed (< 12 LNs) from surgery (Community OR 2.15, 95% CI 1.98-2.32; Comprehensive OR 1.42, 95% CI 1.34-1.51), and greater 30-day mortality (Community OR 1.43, 95% CI 1.14-1.78; Comprehensive OR 1.36, 95% CI 1.17-1.59). Patient survival probability was higher at academic hospitals at 5 years (Academic 69% vs. Comprehensive 66% vs. Community 63%, p < 0.001). Community hospitals and comprehensive hospitals had significantly higher risk of adjusted long-term mortality (Community HR 1.28; 95% CI 1.19-1.37; p < 0.001; Comprehensive HR 1.14; 95% CI 1.09-1.20; p < 0.001). CONCLUSIONS: Despite widespread use of laparoscopic oncologic surgery, short- and long-term outcomes from MIS for segmental colectomy are superior at academic hospitals. This difference may be due to superior perioperative oncologic technique and surgical outcomes at academic hospitals. Our data provide important information for patients, referring physicians, and surgeons about the significance of hospital type in management of colon cancer.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) Not Yet Applicable for Widespread Out-of-Hospital Use: A Case of Nonsurvivable Complication from Prolonged REBOA Inflation.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is being considered for temporizing catastrophic hemorrhage before arriving at a specialty center for definitive surgical management. CASE: We describe the clinical case of a 72-year-old male with a ruptured infrarenal aortic abdominal aneurysm initially stabilized with REBOA at an outside facility and transferred to our care. Transport time was >100 minutes. Despite successful surgical repair of the ruptured aneurysm, the patient expired from multiple-organ failure likely related to ischemia-reperfusion injuries from prolonged balloon occlusion of the aorta. CONCLUSIONS: Ischemia-mitigating techniques and therapies need to improve drastically before the clinical application of REBOA can be effectively extended to outside the vicinity of specialty centers.

Germline replications and somatic mutation accumulation are independent of vegetative life span in Arabidopsis.

In plants, gametogenesis occurs late in development, and somatic mutations can therefore be transmitted to the next generation. Longer periods of growth are believed to result in an increase in the number of cell divisions before gametogenesis, with a concomitant increase in mutations arising due to replication errors. However, there is little experimental evidence addressing how many cell divisions occur before gametogenesis. Here, we measured loss of telomeric DNA and accumulation of replication errors in Arabidopsis with short and long life spans to determine the number of replications in lineages leading to gametes. Surprisingly, the number of cell divisions within the gamete lineage is nearly independent of both life span and vegetative growth. One consequence of the relatively stable number of replications per generation is that older plants may not pass along more somatically acquired mutations to their offspring. We confirmed this hypothesis by genomic sequencing of progeny from young and old plants. This independence can be achieved by hierarchical arrangement of cell divisions in plant meristems where vegetative growth is primarily accomplished by expansion of cells in rapidly dividing meristematic zones, which are only rarely refreshed by occasional divisions of more quiescent cells. We support this model by 5-ethynyl-2'-deoxyuridine retention experiments in shoot and root apical meristems. These results suggest that stem-cell organization has independently evolved in plants and animals to minimize mutations by limiting DNA replication.

The side of the primary tumor affects overall survival in colon adenocarcinoma: an analysis of the national cancer database.

BACKGROUND: Due to conflicting study results on the effect of laterality on overall survival in primary colon cancers, we sought to examine the impact of left compared to right-sided primary tumors on overall survival for stage I-III colon cancer using the largest dataset to date. METHODS: The 2006-2013 NCDB was queried for patients with single primary, stage I-III colon adenocarcinoma and grouped by stage and tumor location. RESULTS: For stage I-II tumors, 114,839 patients had resection (62% right:38% left). After adjustment, patients with right-sided tumors had superior survival ([HR right as reference]: 1.13, 95% CI 1.09-1.17, p < 0.001). For stage III tumors, 71,024 patients had resection, (59% right:41% left). After adjustment, patients with left-sided tumors had superior survival with chemotherapy (HR 0.85, p < 0.001) and no difference in survival without chemotherapy (HR 0.97, p = 0.18). CONCLUSIONS: The side of the primary tumor impacts overall survival across stages for colon adenocarcinoma. Patients with right-sided tumors have superior survival for stage I-II disease while patients with left-sided stage III disease demonstrate a survival advantage, suggesting an opportunity for investigators to use sidedness as a surrogate for prognosis and chemoresponsiveness.

High-Energy Midfoot Fracture-Dislocations: Staged Treatment With an External Fixator.

The purpose of this study was to analyze the clinical outcomes of patients treated for high-energy midfoot (Lisfranc) injuries with initial temporization of an external fixator before definitive fixation. A retrospective chart review at two level 1 trauma centers was completed. Clinical parameters including demographics and comorbidities were evaluated in addition to hospital and clinical data. Time to full weight bearing took an average of 4.4 months, and with the numbers available no significant difference (p < .05) was found between the open reduction and internal fixation (ORIF) group and the arthrodesis group in regard to length of stay, days from initial reduction with an external fixator to definitive fixation, time to full weight bearing, or return to work. Staged treatment of high-energy Lisfranc injuries with external fixation demonstrated minimal soft tissue complications similar to other series reported in the literature. Definitive stabilization with either ORIF or arthrodesis produced similar results in staged treatment of these injuries. (Journal of Surgical Orthopaedic Advances 28(1):24-30, 2019).

Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Assessing the severity of influenza: a role for longitudinal telephone surveys?

During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.