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Purpose To review the use of different valve types in infants with hydrocephalus, in doing so, determining whether an optimal valve choice exists for this patient cohort. Methods We conducted (1) a literature review for all studies describing valve types used (programmable vs. non-programmable, valve size, pressure) in infants (≤ 2 years) with hydrocephalus, (2) a review of data from the pivotal BASICS trial for infant patients and (3) a separate, institutional cohort study from Alder Hey Children’s Hospital NHS Foundation Trust. The primary outcome was any revision not due to infection. Results The search identified 19 studies that were included in the review. Most did not identify a superior valve choice between programmable and non-programmable, small compared to ultra-small, and differential pressure compared to flow-regulating valves. Five studies investigated a single-valve type without a comparator group. The BASICS data identified 391 infants, with no statistically significant difference between gravitational and programmable subgroups. The institutional data from our tertiary referral centre did not reveal any significant difference in failure rate between valve subtypes. Conclusion Our review highlights the challenges of valve selection in infant hydrocephalus, reiterating that the concept of an optimal valve choice in this group remains a controversial one. While the infant-hydrocephalic population is at high risk of valve failure, heterogeneity and a lack of direct comparison between valves in the literature limit our ability to draw meaningful conclusions. Data that does exist suggests at present that there is no difference in non-infective failure rate are increasing in number, with the British valve subtypes in infant hydrocephalus, supported by both the randomised trial and institutional data in this study.

Introduction: Systematic reviews (SR) and systematic reviews with meta-analysis (SRMA) can constitute the highest level of research evidence. Such evidence syntheses are relied upon heavily to inform the clinical knowledge base and to guide clinical practice for meningioma. This review evaluates the reporting and methodological quality of published meningioma evidence syntheses to date. Methods: Eight electronic databases/registries were searched to identify eligible meningioma SRs with and without meta-analysis published between January 1990 and December 2020. Articles concerning spinal meningioma were excluded. Reporting and methodological quality were assessed against the following tools: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2), and Risk Of Bias in Systematic reviews (ROBIS). Results: 116 SRs were identified, of which 57 were SRMAs (49.1%). The mean PRISMA score for SRMA was 20.9 out of 27 (SD 3.9, 77.0% PRISMA adherence) and for SR without meta-analysis was 13.8 out of 22 (SD 3.4, 63% PRISMA adherence). Thirty-eight studies (32.8%) achieved greater than 80% adherence to PRISMA. Methodological quality assessment against AMSTAR 2 revealed that 110 (94.8%) studies were of critically low quality. Only 21 studies (18.1%) were judged to have a low risk of bias against ROBIS. Conclusion: The reporting and methodological quality of meningioma evidence syntheses was poor. Established guidelines and critical appraisal tools may be used as an adjunct to aid methodological conduct and reporting of such reviews, in order to improve the validity and transparency of research which may influence clinical practice.

Monte Carlo simulations are widely used in nuclear physics to model experimental systems. In cases where there are significant unknown quantities, such as energies of states, an iterative process of simulating and fitting is often required to describe experimental data. We describe a Bayesian approach to fitting experimental data, designed for data from a $^{12}$Be(d,p) reaction measurement, using simulations made with GEANT4. Q-values from the $^{12}$C(d,p) reaction to well-known states in $^{13}$C are compared with simulations using BayesOpt. The energies of the states were not included in the simulation to reproduce the situation for $^{13}$Be where the states are poorly known. Both cases had low statistics and significant resolution broadening owing to large proton energy losses in the solid deuterium target. Excitation energies of the lowest three excited states in $^{13}$C were extracted to better than 90 keV, paving a way for extracting information on $^{13}$Be., 8 pages, 6 figures

Simple Summary This study investigated patients who underwent more than one operation for a meningioma, a type of brain tumor. Currently, there is little evidence available for this specific patient group. The purpose of this study was to determine if patients had an improvement or deterioration following a second operation for a recurrent meningioma, and to identify any factors that may influence this change. The results demonstrated that following a second operation for meningioma, patients have poorer outcomes. The findings of this study provide supporting information for surgeons and patients, thereby informing decisions related to patient care and re-operation. Abstract The outcomes following re-operation for meningioma are poorly described. The aim of this study was to identify risk factors for a performance status outcome following a second operation for a recurrent meningioma. A retrospective, comparative cohort study was conducted. The primary outcome measure was World Health Organization performance. Secondary outcomes were complications, and overall and progression free survival (OS and PFS respectively). Baseline clinical characteristics, tumor details, and operation details were collected. Multivariable binary logistic regression was used to identify risk factors for performance status outcome following a second operation. Between 1988 and 2018, 712 patients had surgery for intracranial meningiomas, 56 (7.9%) of which underwent a second operation for recurrence. Fifteen patients (26.8%) had worsened performance status after the second operation compared to three (5.4%) after the primary procedure (p = 0.002). An increased number of post-operative complications following the second operation was associated with a poorer performance status following that procedure (odds ratio 2.2 [95% CI 1.1–4.6]). The second operation complication rates were higher than after the first surgery (46.4%, n = 26 versus 32.1%, n = 18, p = 0.069). The median OS was 312.0 months (95% CI 257.8–366.2). The median PFS following the first operation was 35.0 months (95% CI 28.9–41.1). Following the second operation, the median PFS was 68.0 months (95% CI 49.1–86.9). The patients undergoing a second operation for meningioma had higher rates of post-operative complications, which is associated with poorer clinical outcomes. The decisions surrounding second operations must be balanced against the surgical risks and should take patient goals into consideration.

BACKGROUND Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma. MATERIAL AND METHODS Retrospective cohort study (1998–2018). Eligible patients had reoperation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each reoperation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS). RESULTS Fifty-eight patients were eligible (37 female, mean age at 1st re-operation 56.1 years (SD=11.6)). Eleven patients (19.6%) had 2 re-operations and 3 patients (5.4%) had 3 re-operations. Median follow up was 128.5 months (IQR=73–194.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR=24.3–81.0) and 43.8 months (IQR=20.3–103.4), respectively. Fifteen patients (26.8%) had worse performance status after 1st reoperation, compared to 5.4% (n=3) after the primary operation. Complication rate was 32.1% (n=18) after the primary operation compared to 48.2% (n=27) after 1st reoperation. At primary operation, there were 29 (51.8%) grade 1, 24 (42.9%) grade 2, and 1 (1.8%) grade 3 tumours. Median RFS after first re-operation was 36.5 months (95% CI 29.3–43.9). Median OS was 312 months (95 % CI 257.8–366.2). Increased number of post-operative complications were a risk factor for worsened performance status following reoperation (OR 2.2 [95% CI 1.1–4.6], P=0.029). CONCLUSION Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.

BACKGROUND Systematic reviews and meta-analyses constitute the highest level of research evidence and for a disease with limited clinical trial activity, are often relied upon to help inform clinical practice. This review of reviews evaluates both the reporting & methodological quality of meningioma evidence syntheses. MATERIAL AND METHODS Potentially eligible meningioma reviews published between 1st January 1990 and 31st December 2020 were identified from eight electronic databases. Inclusion required the study to meet the Cochrane guideline definition of a systematic review or meta-analysis. Reviews concerning neurofibromatosis type 2, spinal and pediatric meningiomas were excluded. The reporting and methodological quality of articles were assessed against the following modified guidelines: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), A MeaSurement Tool to Assess Systematic Reviews (AMSTAR2) and the Risk of Bias in Systematic Reviews (ROBIS) guidelines. RESULTS 117 systematic reviews were identified, 57 of which included meta-analysis (48.7%). The number of meningioma systematic reviews published each year has increased with 63 studies (53.9%) published between 01/2018 and 12/2020. A median of 17 studies (IQR 9–29) were included per review. Impact factor of journals publishing a systematic review with or without a meta-analysis was similar (median 2.3 vs 1.8, P=0.397). The mean PRISMA scores for systematic reviews with a meta-analysis was 21.11 (SD 4.1, 78% adherence) and without was 13.89 (SD 3.4, 63% adherence). Twenty-nine systematic reviews with meta-analysis (51%) and 11 without meta-analysis (18%) achieved greater than 80% adherence to PRISMA recommendations. Methodological quality assessment using AMSTAR2 revealed one study (0.9%) as high quality whilst 111 (94.8%) studies were graded as critically low. One hundred and two articles (87.2%) did not utilize a comprehensive search strategy as defined by the AMSTAR2 tool. Ninety-nine studies (84.6%) obtained a high level of concern for potential bias as per the ROBIS assessment. One hundred and eight articles (92.3%) failed to present information that a protocol had been established prior to study commencement and 76 articles (65.0%) did not conduct a risk of bias assessment. Across the three tools, domains relating to the establishment of a protocol prior to review commencement and conducting appropriate risk of bias assessments were frequently low scoring. CONCLUSION Overall reporting and methodological quality of meningioma systematic reviews was sub-optimal. Established critical appraisal tools and reporting guidelines should be utilized a priori to assist in producing high-quality systematic reviews.

Chronic pain and restricted knee motion is a significant problem following the total knee arthroplasty (TKA). The molecular pathogenesis of pain post‐TKA is not known and no targeted therapeutic intervention is available. The aim of this study was to investigate whether pro‐inflammatory mediators are elevated in revision knee patients, indicating an active, ongoing inflammatory process that may contribute to pain. Twelve key markers (pro‐inflammatory cytokines granulocyte‐macrophage colony‐stimulating factor [GM‐CSF], interleukin 5 [IL‐5], IL‐8 and IL‐10, chemokines CCL2, CCL3, CCL4, and CCL13, mediators of angiogenesis Flt‐1, vascular endothelial growth factor, and cell migration vascular cell adhesion molecule 1 and intercellular adhesion molecule 1) were measured in knee tissue and synovial fluid (SF) from primary TKA (n = 29) and revision patients (n = 32). Indications for surgery were osteoarthritis (OA) for primary TKA, and component loosening (n = 11), stiffness (n = 11), laxity pattern (n = 8), or progression of OA in patella resurfacing (n = 3) for revision surgery. Pain levels (WOMAC score) were higher in revision than primary patients (p ≤ 0.05). Time from primary to revision ranged from 8 months to 30 years (median 10 years). All markers were elevated in revision TKA; there was no trend toward decreasing levels with greater time from primary surgery for any marker studied in SF. Similar results were seen in knee tissue. We found no differences comparing indications for revision surgery (p ≥ 0.05). The elevation of inflammatory mediators in painful post‐TKA knees requiring revision suggests active, chronic inflammation. Characterization of upregulated markers provides rationale for targeted therapy, even many years from the primary surgery. © 2019 The Authors. Journal of Orthopaedic Research ® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2316–2324, 2019

International audience; This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world

The flagellar systems of Escherichia coli and Salmonella enterica exhibit a significant level of genetic and functional synteny. Both systems are controlled by the flagellar specific master regulator FlhD4C2. Since the early days of genetic analyses of flagellar systems it has been known that E. coli flhDC can complement a ∆flhDC mutant in S. enterica. The genomic revolution has identified how genetic changes to transcription factors and/or DNA binding sites can impact the phenotypic outcome across related species. We were therefore interested in asking: using modern tools to interrogate flagellar gene expression and assembly, what would the impact be of replacing the flhDC coding sequences in S. enterica for the E. coli genes at the flhDC S. entercia chromosomal locus? We show that even though all strains created are motile, flagellar gene expression is measurably lower when flhDCEC are present. These changes can be attributed to the impact of FlhD4C2 DNA recognition and the protein-protein interactions required to generate a stable FlhD4C2 complex. Furthermore, our data suggests that in E. coli the internal flagellar FliT regulatory feedback loop has a marked difference with respect to output of the flagellar systems. We argue due diligence is required in making assumptions based on heterologous expression of regulators and that even systems showing significant synteny may not behave in exactly the same manner.

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction‐based models and packages that extend the core with features suited to other model types including constraint‐based models, reaction‐diffusion models, logical network models, and rule‐based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single‐cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., Over the past two decades, scientists from different fields have been developing SBML, a standard format for encoding computational models in biology and medicine. This article summarizes recent progress and gives perspectives on emerging challenges.

Background With the increased rate of childhood cancer survivors, a marked rise in the incidence of secondary intracranial meningiomas has been established. Objective Determine the outcomes of patients diagnosed with radiation-induced meningiomas (RIM). Methods Single-centre retrospective cohort study of patients with new or recurrent RIM (2007–2018). Results 47 patients were identified (21 females). Mean age at radiation was 15 years (SD=14) and the most common indications were leukaemia (n=8) and childhood brain tumours (n=35; medulloblastoma and pilocytic astrocytoma (n=7 each)). 93 de-novo meningiomas were identified. The median latency period between radiation and diagnosis was 28.5 years (IQR 22–37). 61% were asymptomatic whilst the remainder manifested headache (20%), focal neurological deficit (12%) and epilepsy (5%). 32 operated de-novo RIM revealed WHO grade I (n=19; 59%), WHO grade II (n=11; 34%) and 2 intraosseous meningiomas (n=2; 6%). After a median of 5 years (IQR 3–10), 9 (28%) operated RIM recurred/progressed. At recurrence, 5 were operated (3 WHO grade I, 2 WHO grade II and 1 WHO grade III), 2 patients were palliated and 2 remain under active observation. By the end of the study period, 20 patients were harbouring multiple meningiomas and 8 patients were deceased. Conclusion Radiation-induced meningioma should be monitored until symptomatic. Operated RIMs have a high recurrence rate. Further radiotherapy is not effective. Further clinical and genetic analyses as part of an international multi-centre collaboration are planned.

OBJECTIVES: Availability of donor lungs suitable for transplant falls short of current demand and contributes to waiting list mortality.\ud Ex vivo lung perfusion (EVLP) offers the opportunity to objectively assess and recondition organs unsuitable for immediate transplant.\ud Identifying robust biomarkers that can stratify donor lungs during EVLP to use or non-use or for specific interventions could further improve its clinical impact.\ud METHODS: In this pilot study, 16 consecutive donor lungs unsuitable for immediate transplant were assessed by EVLP. Key inflammatory mediators and tissue injury markers were measured in serial perfusate samples collected hourly and in bronchoalveolar lavage fluid (BALF) collected before and after EVLP. Levels were compared between donor lungs that met criteria for transplant and those that did not.\ud RESULTS: Seven of the 16 donor lungs (44%) improved during EVLP and were transplanted with uniformly good outcomes. Tissue and vascular injury markers lactate dehydrogenase, HMGB-1 and Syndecan-1 were significantly lower in perfusate from transplanted lungs. A model combining IL-1b and IL-8 concentrations in perfusate could predict final EVLP outcome after 2 h assessment. In addition, perfusate IL-1b concentrations showed an inverse correlation to recipient oxygenation 24 h post-transplant.\ud CONCLUSIONS: This study confirms the feasibility of using inflammation and tissue injury markers in perfusate and BALF to identify donor lungs most likely to improve for successful transplant during clinical EVLP. These results support examining this issue in a larger study.

The American Indian war lasted over one hundred years, and is a major event in the history of North America. As expected, since the war commenced in late eighteenth century, casualty records surrounding this conflict contain numerous sources of error, such as rounding and counting. Additionally, while major battles such as the Battle of the Little Bighorn were recorded, many smaller skirmishes were completely omitted from the records. Over the last few decades, it has been observed that the number of casualties in major conflicts follows a power law distribution. This paper places this observation within the Bayesian paradigm, enabling modelling of different error sources, allowing inferences to be made about the overall casualty numbers in the American Indian war.

Social Networking is a powerful medium to advertise good things about people and places. Therefore, it is now being used to promote the tourism industry through networking sites where people mostly communicate and meet new ventures. This study aimed to assess the effects of social media in tourism industry of Batangas province. Descriptive type of research was utilized in the study. Results showed that Facebook, Twitter, YouTube, Blogs and Websites were the social networking site frequently used by individuals and hospitality industry. Social media applications served as an avenue to disseminate the information faster especially for the tourism establishments with lesser cost. The main problem encountered in using social media is that, customers’ opinions, thoughts and expressions are not well presented that leads to bad impressions and unfair criticism. Action plan was proposed to address the problem encountered in using Social Media.

The flagellum is a rotary motor that enables bacteria to swim in liquids and swarm over surfaces. Numerous global regulators control flagellar assembly in response to cellular and environmental factors. Previous studies have also shown that flagellar assembly is affected by the growth-rate of the cell. However, a systematic study has not yet been described under controlled growth conditions. Here, we investigated the effect of growth rate on flagellar assembly in Escherichia coli using steady-state chemostat cultures where we could precisely control the cell growth-rate. Our results demonstrate that flagellar abundance correlates with growth rate, where faster growing cells produce more flagella. They also demonstrate that this growth-rate dependent control occurs through the expression of the flagellar master regulator, FlhD4C2. Collectively, our results demonstrate that motility is intimately coupled to the growth-rate of the cell.

Objectives This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS).\ud \ud Methods Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels.\ud \ud Results 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy.\ud \ud Conclusions Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

Cajal bands are cytoplasmic channels flanked by appositions where the abaxonal surface of Schwann cell myelin apposes and adheres to the overlying plasma membrane. These appositions contain a dystroglycan complex that includes periaxin and dystrophin-related protein 2 (Drp2). Loss of periaxin disrupts appositions and Cajal bands in Schwann cells and causes a severe demyelinating neuropathy in mouse and human. Here, we investigated the role of mouse Drp2 in apposition assembly and Cajal band function and compared it with periaxin. We show that periaxin and Drp2 are not only both required to form appositions, but they must also interact. Periaxin-Drp2 interaction is also required for Drp2 phosphorylation, but phosphorylation is not required for the assembly of appositions. Drp2 loss causes corresponding increases in Dystrophin family members, utrophin and dystrophin Dp116, although dystroglycan remains unchanged. We also show that all dystroglycan complexes in Schwann cells use the uncleaved form of beta-dystroglycan. Drp2-null Schwann cells have disrupted appositions and Cajal bands, and they undergo focal hypermyelination and concomitant demyelination. Nevertheless, they do not have the short internodal lengths and associated reduced nerve conduction velocity seen in the absence of periaxin, showing that periaxin regulates Schwann cell elongation independent of its role in the dystroglycan complex. We conclude that the primary role of the dystroglycan complex in appositions is to stabilize and limit the radial growth of myelin.

Increases in cellular Reactive Oxygen Species (ROS) concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells. One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage). However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS). We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

The increasing complexity of research requires scientists to work at the intersection of multiple fields and to face problems for which their formal education has not prepared them. For example, biologists with no or little background in programming are now often using complex scripts to handle the results from their experiments; vice versa, programmers wishing to enter the world of bioinformatics must know about biochemistry, genetics, and other fields. In this context, communication tools such as mailing lists, web forums, and online communities acquire increasing importance. These tools permit scientists to quickly contact people skilled in a specialized field. A question posed properly to the right online scientific community can help in solving difficult problems, often faster than screening literature or writing to publication authors. The growth of active online scientific communities, such as those listed in Table S1, demonstrates how these tools are becoming an important source of support for an increasing number of researchers. Nevertheless, making proper use of these resources is not easy. Adhering to the social norms of World Wide Web communication—loosely termed “netiquette”—is both important and non-trivial. In this article, we take inspiration from our experience on Internet-shared scientific knowledge, and from similar documents such as “Asking the Questions the Smart Way” and “Getting Answers”, to provide guidelines and suggestions on how to use online communities to solve scientific problems.

Background The aim of this study was to assess the content validity of a questionnaire to measure melanoma risk, knowledge and protective behaviour in a convenience sample of Scots and Australians. Australia has the highest melanoma incidence worldwide but has developed a culture of skin cancer avoidance with a long history of skin cancer primary prevention campaigns of proven effectiveness. Scotland has lower incidence, but has shown a greater rate of increase between 1985 and 2007. There is an urgent need in Scotland, therefore, to identify those groups at greatest risk and provide them with effective preventative advice. Method A self-administered postal survey was completed by four groups formed from convenience samples in two geographical locations (Northeast Scotland and Western Australia). In univariate analysis scores on personal risk, level of concern, protective behaviour, and knowledge were compared by nationality, previous skin cancer diagnosis and personally knowing someone with melanoma. Multivariate linear regression analysis modelled the influence of potential predictor variables upon each of the scores. Results 540 people completed the questionnaire, 273 Scots (50.6%). 133 (24.6%) Scots and 83 (15.4%) Australians previously had melanoma or non-melanoma skin cancer, whilst 120 (22.2%) Scots and 190 (35.2%) Australians personally knew someone with melanoma. Australians had higher knowledge (p < 0.001), level of concern (p < 0.001) and protective behaviour (p < 0.001) scores than the Scottish. Australian nationality was the strongest independent predictor of a higher knowledge score (p < 0.001), followed by a previous skin cancer diagnosis (p = 0.003), personal knowledge of someone with melanoma (p = 0.011), female gender (p = 0.005) and higher education status (p < 0.001) (R 2 = 0.163). Conclusion The questionnaire detected higher levels of knowledge and skin cancer protective behaviours in Australians than in Scottish people. This was expected and supports the content validity of the questionnaire and its value as a future research tool in the Scottish population.

Despite widespread use of tunneled hemodialysis (HD) catheters, their utility is limited by the development of thrombotic complications. To address this problem, this study investigated whether the thrombolytic agent tenecteplase can restore blood flow rates (BFRs) in dysfunctional HD catheters.In this randomized, double-blind study, patients with dysfunctional tunneled HD catheters, defined as a BFR300 ml/min at -250 mmHg pressure in the arterial line, received 1-hour intracatheter dwell with tenecteplase (2 mg) or placebo. The primary endpoint was the percentage of patients with BFRor =300 ml/min and an increase ofor =25 ml/min above baseline 30 minutes before and at the end of HD. Safety endpoints included the incidence of hemorrhagic, thrombotic, and infectious complications.Eligible patients (n = 149) were treated with tenecteplase (n = 74) or placebo (n = 75). Mean baseline BFR was similar for the tenecteplase and placebo groups at 151 and 137 ml/min, respectively. After a 1-hour dwell, 22% of patients in the tenecteplase group had functional catheters compared with 5% among placebo controls (P = 0.004). At the end of dialysis, mean change in BFR was 47 ml/min in the tenecteplase group versus 12 ml/min in the placebo group (P = 0.008). Four catheter-related bloodstream infections (one tenecteplase, three placebo) and one thrombosis (tenecteplase) were observed. There were no reports of intracranial hemorrhage, major bleeding, embolic events, or catheter-related complications.Tenecteplase improved HD catheter function and had a favorable safety profile compared with placebo.

Background Large scale microarray experiments are becoming increasingly routine, particularly those which track a number of different cell lines through time. This time-course information provides valuable insight into the dynamic mechanisms underlying the biological processes being observed. However, proper statistical analysis of time-course data requires the use of more sophisticated tools and complex statistical models. Findings Using the open source CRAN and Bioconductor repositories for R, we provide example analysis and protocol which illustrate a variety of methods that can be used to analyse time-course microarray data. In particular, we highlight how to construct appropriate contrasts to detect differentially expressed genes and how to generate plausible pathways from the data. A maintained version of the R commands can be found at http://www.mas.ncl.ac.uk/~ncsg3/microarray/. Conclusions CRAN and Bioconductor are stable repositories that provide a wide variety of appropriate statistical tools to analyse time course microarray data.

Summary Patients with chronic mucocutaneous candidiasis (CMC) have an unknown primary immune defect and are unable to clear infections with the yeast Candida. CMC includes patients with AIRE gene mutations who have autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), and patients without known mutations. CMC patients have dysregulated cytokine production, suggesting that defective expression of pattern recognition receptors (PRRs) may underlie disease pathogenesis. In 29 patients with CMC (13 with APECED) and controls, we assessed dendritic cell (DC) subsets and monocyte Toll-like receptor (TLR) expression in blood. We generated and stimulated monocyte-derived (mo)DCs with Candida albicans, TLR-2/6 ligand and lipopolysaccharide and assessed PRR mRNA expression by polymerase chain reaction [TLR-1–10, Dectin-1 and -2, spleen tyrosine kinase (Syk) and caspase recruitment domain (CARD) 9] in immature and mature moDCs. We demonstrate for the first time that CMC patients, with or without APECED, have normal blood levels of plasmocytoid and myeloid DCs and monocyte TLR-2/TLR-6 expression. We showed that in immature moDCs, expression levels of all PRRs involved in anti-Candida responses (TLR-1, -2, -4, -6, Dectin-1, Syk, CARD9) were comparable to controls, implying that defects in PRR expression are not responsible for the increased susceptibility to Candida infections seen in CMC patients. However, as opposed to healthy controls, both groups of CMC patients failed to down-regulate PRR mRNA expression in response to Candida, consistent with defective DC maturation, as we reported recently. Thus, impaired DC maturation and consequent altered regulation of PRR signalling pathways rather than defects in PRR expression may be responsible for inadequate Candida handling in CMC patients.

Summary There is a growing realisation that complex biological processes cannot be understood through the application of ever more reductionist experimental programs alone. Recognising this, we have a constructed a flexible web-service based modelling system called BASIS (Biology of Ageing e-Science Integration and Simulation), which facilitates model construction and development. In particular it allows users to store, share and simulate their models. The system is accessed through web-services using any language (e.g. Python or Java) or under any operating system (e.g. Linux or Windows).

This paper describes the results of a beam test using the Engineering Model of the GLAST Large Area Telescope, which was installed in a beam of positrons, hadrons and tagged photons at SLAC. The performance of the four subsystems, Anti Coincidence Detector, Silicon Tracker, Calorimeter and Data Acquisition will be described.