Smartphone-based pathogen diagnosis in urinary sepsis patients.

BackgroundThere is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome.MethodsA smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time.FindingsA head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18-28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood - potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures.InterpretationThe smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. FUND: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation

ENGOT-ov-6/TRINOVA-2: Randomised, double-blind, phase 3 study of pegylated liposomal doxorubicin plus trebananib or placebo in women with recurrent partially platinum-sensitive or resistant ovarian cancer

Aims: Trebananib, a peptide-Fc fusion protein, inhibits angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. This randomised, double-blind, placebo-controlled phase 3 study evaluated whether trebananib plus pegylated liposomal doxorubicin (PLD) improved progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer. / Methods: Women with recurrent ovarian cancer (platinum-free interval ≤12 months) were randomised to intravenous PLD 50 mg/m2 once every 4 weeks plus weekly intravenous trebananib 15 mg/kg or placebo. PFS was the primary end-point; key secondary end-points were objective response rate (ORR) and duration of response (DOR). Owing to PLD shortages, enrolment was paused for 13 months; the study was subsequently truncated. / Results: Two hundred twenty-three patients were enrolled. Median PFS was 7.6 months (95% CI, 7.2–9.0) in the trebananib arm and 7.2 months (95% CI, 4.8–8.2) in the placebo arm, with a hazard ratio of 0.92 (95% CI, 0.68–1.24). However, because the proportional hazards assumption was not fulfilled, the standard Cox model did not provide a reliable estimate of the hazard ratio. ORR in the trebananib arm was 46% versus 21% in the placebo arm (odds ratio, 3.43; 95% CI, 1.78–6.64). Median DOR was improved (trebananib, 7.4 months [95% CI, 5.7–7.6]; placebo, 3.9 months [95% CI, 2.3–6.5]). Adverse events with a greater incidence in the trebananib arm included localised oedema (61% versus 32%), ascites (29% versus 9%) and vomiting (45% versus 33%). / Conclusions: Trebananib demonstrated anticancer activity in this phase 3 study, indicated by improved ORR and DOR. Median PFS was not improved. No new safety signals were identified. / Trial registration: ClinicalTrials.gov, NCT0128125

Extending reference assembly models

The human genome reference assembly is crucial for aligning and analyzing sequence data, and for genome annotation, among other roles. However, the models and analysis assumptions that underlie the current assembly need revising to fully represent human sequence diversity. Improved analysis tools and updated data reporting formats are also required

Lunar Surface Systems Supportability Technology Development Roadmap

The Lunar Surface Systems Supportability Technology Development Roadmap is a guide for developing the technologies needed to enable the supportable, sustainable, and affordable exploration of the Moon and other destinations beyond Earth. Supportability is defined in terms of space maintenance, repair, and related logistics. This report considers the supportability lessons learned from NASA and the Department of Defense. Lunar Outpost supportability needs are summarized, and a supportability technology strategy is established to make the transition from high logistics dependence to logistics independence. This strategy will enable flight crews to act effectively to respond to problems and exploit opportunities in an environment of extreme resource scarcity and isolation. The supportability roadmap defines the general technology selection criteria. Technologies are organized into three categories: diagnostics, test, and verification; maintenance and repair; and scavenge and recycle. Furthermore, "embedded technologies" and "process technologies" are used to designate distinct technology types with different development cycles. The roadmap examines the current technology readiness level and lays out a four-phase incremental development schedule with selection decision gates. The supportability technology roadmap is intended to develop technologies with the widest possible capability and utility while minimizing the impact on crew time and training and remaining within the time and cost constraints of the program

Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group

Background: Combination chemotherapy yields better response rates which do not always lead to a survival advantage. The aim of this study was to investigate whether the reported differences in the efficacy and toxicity of monotherapy with doxorubicin (DOX) versus combination therapy with cisplatin (CDDP) in endometrial adenocarcinoma lead to significant advantage in favour of the combination. Patients and methods: Eligible patients had histologically-proven advanced and/or recurrent endometrial adenocarcinoma and were chemo-naïve. Treatment consisted of either DOX 60 mg/m2 alone or CDDP 50 mg/m2 added to DOX 60 mg/m2, every 4 weeks. Results: A total of 177 patients were entered and median follow-up is 7.1 years. The combination DOX-CDDP was more toxic than DOX alone. Haematological toxicity consisted mainly of white blood cell toxicity grade 3 and 4 (55% versus 30%). Non-haematological toxicity consisted mainly of grade 3 and 4 alopecia (72% versus 65%) and nausea/vomiting (36 % versus 12%). The combination DOX-CDDP provided a significantly higher response rate than single agent DOX (P <0.001). Thirty-nine patients (43%) responded on DOX-CDDP [13 complete responses (CRs) and 26 partial responses (PRs)], versus 15 patients (17%) on DOX alone (8 CR and 7 PR). The median overall survival (OS) was 9 months in the DOX-CDDP arm versus 7 months in the DOX alone arm (Wilcoxon P = 0.0654). Regression analysis showed that WHO performance status was statistically significant as a prognostic factor for survival, and stratifying for this factor, treatment effect reaches significance (hazard ratio = 1.46, 95% confidence interval 1.05-2.03, P = 0.024). Conclusions: In comparison to single agent DOX, the combination of DOX-CDDP results in higher but acceptable toxicity. The response rate produced is significantly higher, and a modest survival benefit is achieved with this combination regimen, especially in patients with a good performance statu

Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

Existence and multiplicity of positive periodic solutions for a class of higher-dimension functional differential equations with impulses

AbstractThis paper deals with the existence of multiple periodic solutions for n-dimensional functional differential equations with impulses. By employing the Krasnoselskii fixed point theorem, we obtain some easily verifiable sufficient criteria which extend previous results