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Additional file 5: Table S4. Antibiotic use according to class of antibiotic during study period and annual hospital use 2017-2018.

Additional file 10: Table S9. Multivariate regression analysis of clinical variables and resistance genes.

Additional file 2: Table S1. Patient co-location categories that were assigned to determine spatial relation between patients.

Additional file 6: Table S5. Significant correlations between detected AMR genes and bacterial taxa (n=24 patients)

Additional file 1: Supplementary methods and materials

Additional file 9: Table S8. Univariate analysis of clinical variables and resistance genes.

Additional file 3: Table S2. Primer sequences of antibiotic resistance and positive control (16S rRNA) genes for quantitative PCR.

Additional file 11: Table S10. Correlation between relative abundance of specific taxa and absolute abundance of associated AMR genes.

Additional file 4: Table S3. Antimicrobial resistance genes identified through shotgun metagenomics.

Additional file 8: Table S7. Distribution of resistance genes according to patient location on the ward.

Additional file 7: Table S6. Proportion of genes detected in shotgun metagenomic sequencing and qPCR analysis.

This presentation is an introduction to the open-source Cumulus tool for getting your data into the cloud and providing free and open access to that data. This presentation was given in July 2019 at the Earth Science Information Partners (ESIP) Summer Meeting held in Tacoma, Washington.

N7 has a desire for an enterprise model of the US Navy, a model that can be utilized to perform what-if studies in an interactive fashion similar to that found with simulation games like SimCity. Inspiration for this project comes from the NRC study “Modeling and Simulation: Linking Entertainment and Defense,” wherein it is suggested that the Department of Defense can benefit from partnering with entertainment companies in order to accomplish its requirements for modeling and simulation [Zyda,1997].

We present 2817 new southern proper motion systems with 0.40 "/yr > mu > 0.18 "/yr and declination between -47 degrees and 00 degrees. This is a continuation of the SuperCOSMOS-RECONS (SCR) proper motion searches of the southern sky. We use the same photometric relations as previous searches to provide distance estimates based on the assumption that the objects are single main sequence stars. We find 79 new red dwarf systems predicted to be within 25 pc, including a few new components of previously known systems. Two systems - SCR 1731-2452 at 9.5 pc and SCR 1746-3214 at 9.9 pc - are anticipated to be within 10 pc. We also find 23 new white dwarf candidates with distance estimates of 15-66 pc, as well as 360 new red subdwarf candidates. With this search, we complete the SCR sweep of the southern sky for stars with mu > 0.18 "/yr and R_59F < 16.5, resulting in a total of 5042 objects in 4724 previously unreported proper motion systems. Here we provide selected comprehensive lists from our SCR proper motion search to date, including 152 red dwarf systems estimated to be within 25 pc (nine within 10 pc), 46 white dwarfs (ten within 25 pc), and 598 subdwarf candidates. The results of this search suggest that there are more nearby systems to be found at fainter magnitudes and lower proper motion limits than those probed so far., 47 pages, 16 of text. 7 figures

Here we present 1584 new southern proper motion systems with mu > 0.18 "/yr and 16.5 > R_59F > 18.0. This search complements the six previous SuperCOSMOS-RECONS (SCR) proper motion searches of the southern sky for stars within the same proper motion range, but with R_59F < 16.5. As in previous papers, we present distance estimates for these systems and find that three systems are estimated to be within 25 pc, including one, SCR 1546-5534, possibly within the RECONS 10 pc horizon at 6.7 pc, making it the second nearest discovery of the searches. We find 97 white dwarf candidates with distance estimates between 10 and 120 pc, as well as 557 cool subdwarf candidates. The subdwarfs found in this paper make up nearly half of the subdwarf systems reported from our SCR searches, and are significantly redder than those discovered thus far. The SCR searches have now found 155 red dwarfs estimated to be within 25 pc, including 10 within 10 pc. In addition, 143 white dwarf candidates and 1155 cool subdwarf candidates have been discovered. The 1584 systems reported here augment the sample of 4724 systems previously discovered in our SCR searches, and imply that additional systems fainter than R_59F = 18.0 are yet to be discovered., 11 pages of text, seven figures

Background: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events. Methods and findings: We included all participants with complete risk factor (covariate) data, baseline eGFR > 60 ml/min/1.73 m2, and a confirmed (>3 months apart) eGFR < 60 ml/min/1.73 m2 thereafter to calculate CVD and CKD risk scores. We calculated CVD and CKD event rates by predicted 5-year CVD and CKD risk groups (≤1%, >1%–5%, >5%) and fitted Poisson models to assess whether CVD and CKD risk group effects were multiplicative. A total of 27,215 participants contributed 202,034 person-years of follow-up: 74% male, median (IQR) age 42 (36, 49) years, median (IQR) baseline year of follow-up 2005 (2004, 2008). D:A:D risk equations predicted 3,560 (13.1%) participants at high CVD risk, 4,996 (18.4%) participants at high CKD risk, and 1,585 (5.8%) participants at both high CKD and high CVD risk. CVD and CKD event rates by predicted risk group were multiplicative. Participants at high CVD risk had a 5.63-fold (95% CI 4.47, 7.09, p < 0.001) increase in CKD events compared to those at low risk; participants at high CKD risk had a 1.31-fold (95% CI 1.09, 1.56, p = 0.005) increase in CVD events compared to those at low risk. Participants’ CVD and CKD risk groups had multiplicative predictive effects, with no evidence of an interaction (p = 0.329 and p = 0.291 for CKD and CVD, respectively). The main study limitation is the difference in the ascertainment of the clinically defined CVD endpoints and the laboratory-defined CKD endpoints. Conclusions: We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events. This suggests that CVD and CKD risk in HIV-positive persons should be assessed together. The results further encourage clinicians to prioritise addressing modifiable risks for CVD and CKD in HIV-positive people.

Introduction: Glucose-regulated protein 78-kDa (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone that is essential for correct protein folding and assembly in the ER lumen. Micro-environmental stress and a requirement for increased protein synthesis, typical of solid tumours, leads to a disruption of ER homeostasis, and accumulation of misfolded proteins. The ability of GRP78 to dissociate from several important ER-resident transmembrane proteins under conditions of ER stress leads to a cascade of signal transduction pathways, known as the unfolded protein response (UPR), that modulate cell survival or, if the stress is significantly severe, apoptosis. GRP78 has been found to be overexpressed in a variety of cancers compared with benign tissue and has been associated with poor outcome. In-vitro data indicate that GRP78 expression is often associated with aggressive phenotype and drug resistance. Thus, GRP78 has potential as a biomarker for tumour behaviour and treatment response. For stage III colorectal cancer, there is overwhelming evidence to recommend the use of fluoropyrimidine-based adjuvant chemotherapy. Unfortunately, a large proportion of patients do not benefit from adjuvant chemotherapy, and biomarkers that can determine the likelihood of response to chemotherapy remain elusive. The benefit of chemotherapy in stage II disease is less certain and markers that could reliably predict benefit would be particularly useful in this population. This study explores a potential mechanistic relationship between GRP78 and 5-FU sensitivity using both siRNA transfection and treatment with an engineered fusion protein, epidermal growth factor (EGF)-SubA, which has been demonstrated to cause highly selective cleavage of GRP78 at a single amino acid point. It was then examined whether GRP78 may have prognostic or predictive value in the context of colorectal cancer patients treated with fluoropyrimidine-based chemotherapy. The potential therapeutic value of targeting GRP78 in vitro using EGF-SubA is also examined. Methods: Colon cancer cell lines were used to examine response to 5-FU upon modulation of endogenous GRP78 using siRNA technology and EGF-SubA. Apoptosis and cell cycle progression were assessed using flow cytometry. Immunohistochemistry was used to characterise GRP78 expression in a large cohort of colorectal cancers on tissue microarrays and the results were correlated with clinicopathological parameters and with 5-year survival for the whole cohort and those treated with fluoropyrimidine-based (5-FU) adjuvant chemotherapy. The action of EGF-SubA upon colon cancer cells was examined using western blotting, MTT assay and flow cytometry. Results: GRP78 promotes apoptosis in response to 5-FU. Better overall 5-year survival was associated with high GRP78 expression (P=0.036). Stage III patients with high GRP78 showed significant benefit from adjuvant chemotherapy (P=0.026), whereas patients with low GRP78 failed to benefit (P=0.805). Low GRP78 was an independent poor prognostic indicator of overall 5-year survival (P=0.005; HR=1.536; 95%CI 1.139-2.122). Colon cancer cells expressing EGFR were highly sensitive to EGF-SubA, demonstrating reduced proliferation and cell cycle arrest. However, EGF-SubA did not induce significant apoptosis and reduced the effectiveness of 5-FU in vitro. Conclusion: This study demonstrates a mechanistic relationship between GRP78 expression and response to 5-FU. GRP78 expression may provide a useful additional risk stratification to inform the adjuvant treatment of colorectal cancer. EGF-SubA does not have therapeutic value in colorectal cancer but is a useful tool for studying GRP78 and the UPR.