METHODS: Data related to awards to UK institutions for pneumonia research from 1997 to 2013 were systematically sourced and categorised by disease area and type of science. Investment was compared to mortality figures in 2010 and 2013 for pneumonia, tuberculosis and influenza. Investment was also compared to publication data.
RESULTS: Of all infectious disease research between 2011 and 2013 (£917.0 million), £28.8 million (3.1%) was for pneumonia. This was an absolute and proportionate increase from previous time periods. Translational pneumonia research (33.3%) received increased funding compared with 1997-2010 where funding was almost entirely preclinical (87.5%, here 30.9%), but high-burden areas such as paediatrics, elderly care and antimicrobial resistance received little investment. Annual investment remains volatile; publication temporal trends show a consistent increase. When comparing investment to global burden with a novel 'investment by mortality observed' metric, tuberculosis (£48.36) and influenza (£484.21) receive relatively more funding than pneumonia (£43.08), despite investment for pneumonia greatly increasing in 2013 compared to 2010 (£7.39). Limitations include a lack of private sector data and the need for careful interpretation of the comparisons with burden, plus categorisation is subjective.
CONCLUSIONS: There has been a welcome increase for pneumonia funding awarded to UK institutions in 2011-2013 compared with 1997-2010, along with increases for more translational research. Published outputs relating to pneumonia rose steadily from 1997 to 2013. Investment relative to mortality for pneumonia has increased, but it remains low compared to other respiratory infections and clear inequities remain. Analyses that measure investments in pneumonia can provide an insight into funding trends and research gaps.
RESEARCH IN CONTEXT: Pneumonia continues to be a high-burden illness around the globe. This paper shows that although research funding is increasing in the UK (between 1997 and 2013), it remains poorly funded compared to other important respiratory infectious diseases such as tuberculosis and influenza. Publications about pneumonia have been steadily increasing over time, indicating continuing academic and clinical interest in the topic. Though global mortality of pneumonia is declining, it should still be an area of high priority for funders, policymakers and researchers.
METHODS: fNIRS signals during a verbal fluency task designed for clinical assessment was recorded for all participants. Demographics, clinical history and symptom severity were also noted.
FINDINGS: Compared to HCs (n = 31), both patient groups (MDD, n = 31; BPD, n = 31) displayed diminished haemodynamic response in the frontal, temporal and parietal cortices. Moreover, haemodynamic response in the right frontal cortex is markedly lower in patients with MDD compared to patients with BPD.
INTERPRETATION: Normal cortical function in patients with BPD is disrupted, but not as extensively as in patients with MDD. These results provide further neurophysiological evidence for the distinction of patients with MDD from patients with BPD.
METHODS: A subcohort of 201 children with behavioural outcome measures was identified within a longitudinal, Australian birth-cohort study. The faecal microbiota were analysed at 1, 6, and 12 months of age. Behavioural outcomes were measured at 2 years of age.
FINDINGS: In an unselected birth cohort, we found a clear association between decreased normalised abundance of Prevotella in faecal samples collected at 12 months of age and increased behavioural problems at 2 years, in particular Internalizing Problem scores. This association appeared independent of multiple potentially confounding variables, including maternal mental health. Recent exposure to antibiotics was the best predictor of decreased Prevotella.
INTERPRETATION: Our findings demonstrate a strong association between the composition of the gut microbiota in infancy and subsequent behavioural outcomes; and support the importance of responsible use of antibiotics during early life.
FUNDING: This study was funded by the National Health and Medical Research Council of Australia (1082307, 1147980, 1129813), The Murdoch Children's Research Institute, Barwon Health, Deakin University, Perpetual Trustees, and The Shepherd Foundation. The funders had no involvement in the data collection, analysis or interpretation, trial design, recruitment or any other aspect pertinent to the study.
METHODS: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.
FINDINGS: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC
METHODS: The study was designed as a randomized controlled trial. After receiving a pre-test, participants were randomly allocated to either an e-learning or non-e-learning group. Only those in the e-learning group gained access to the e-learning system. Two months after the pre-test, both groups received a post-test. The primary endpoint was the difference between the two groups regarding the rate of improvement of their test results.
FINDINGS: 515 endoscopists from 35 countries were assessed for eligibility, and 332 were enrolled in the study, with 166 allocated to each group. Of these, 151 participants in the e-learning group and 144 in the non-e-learning group were included in the analysis. The mean improvement rate (standard deviation) in the e-learning and non-e-learning groups was 1·24 (0·26) and 1·00 (0·16), respectively (P<0·001).
INTERPRETATION: This global study clearly demonstrated the efficacy of an e-learning system to expand knowledge and provide invaluable experience regarding the endoscopic detection of early gastric cancer (R000012039).
METHODS: Rosetting rates of clinical isolates pre- and post- brief (one hour) exposure to artesunate (AS, an ART derivative) were evaluated. The effects of AS-mediated rosetting on the post-AS-exposed parasite's replication and survival, as well as the extent of protection by AS-mediated rosetting on different parasite stages were investigated. The rosetting ligands, mechanisms, and gene mutations involved were studied.
FINDINGS: Brief AS exposure stimulated rosetting, with AS-resistant isolates forming more rosettes in a more rapid manner. AS-mediated rosetting enabled infected erythrocytes (IRBC) to withstand AS exposure for several hours and protected the IRBC from phagocytosis. When their rosetting ability was blocked experimentally, the post-AS exposure survival advantage by the AS-resistant parasites was abrogated. Deletions in two genes coding for PfEMP1 exon 2 (PF3D7_0200300 and PF3D7_0223300) were found to be associated with AS-mediated rosetting, and these mutations were significantly selected through time in the parasite population under study, along with the K13 mutations, a molecular marker of ART-resistance.
INTERPRETATION: Rapid ART parasite clearance is driven by the direct oxidative damages on IRBC by ART and the phagocytic destruction of the damaged IRBC. Rosetting serves as a rapid 'buying time' strategy that allows more parasites to complete schizont maturation, reinvasion and subsequent development into the intrinsically less ART-susceptible ring stage.
FUNDING: A*STAR, NMRC-OF-YIRG, HRC e-ASIA, Wellcome.
METHODS: We produced two NiV vaccine candidates using the licensed VSV-EBOV vaccine as a backbone and tested its efficacy against lethal homologous and heterologous NiV challenge with Nipah virus Bangladesh and Nipah virus Malaysia, respectively, in the African green monkey model.
FINDINGS: The VSV-EBOV vaccine expressing NiV glycoprotein G (VSV-NiVG) induced high neutralising antibody titers and afforded complete protection from homologous and heterologous challenge. The VSV-EBOV vaccine expressing NiV fusion protein F (VSV-NiVF) induced a lower humoral response and afforded complete homologous protection, but only partial heterologous protection. Both vaccines reduced virus shedding from the upper respiratory tract, and virus replication in the lungs and central nervous system. None of the protected animals vaccinated with VSV-NiVG or VSV-NiVF showed histological lesions in the CNS, but one VSV-NiVF-vaccinated animal that was not protected developed severe meningoencephalitis.
INTERPRETATION: The VSV-NiVG vaccine offers broad protection against NiV disease.
FUNDING: This study was supported by the Intramural Research Program, NIAID, NIH.
METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.
FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P
METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years.
FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI.
INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments.
FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.