•Real-world performance comparison between compressed natural gas and diesel buses.•Higher THC emissions for the compressed natural gas bus compared to the diesel bus.•Increase of 6–55% of fuel ...consumption with variations in the operating conditions.•Less NOx emissions for the natural gas bus at high congestion and road grade levels.•Vehicle specific power predicts CO2 and NOx emissions with good accuracy.
This study investigated the effects of passenger load, road grade, and congestion level on the fuel consumption and emissions from a Euro VI compressed natural gas (CNG) urban bus and a Euro V diesel urban bus. Testing was performed under real-traffic conditions in Madrid, Spain, using a portable emission measurement system (PEMS). The PEMS data also were combined with the vehicle specific power (VSP) methodology to analyse the differences between the performance of the two types of buses and develop an energy-based emission model. Between the empty and 4000 kg passenger load cases, the fuel consumption and CO2 emissions for the diesel bus showed a significant increase by approximately 25%. With an increase in the road grade, and congestion level, the fuel consumption and CO2 emissions of both types of buses increased, by 6–55%. Unlike in the case of the diesel bus, the NOx emissions of the CNG bus decreased by 40–50% as the level of road grade and congestion increased. At intervals of VSP ≥ 2 kW/t, NOx emission rates for the CNG bus were approximately 60% lower than those of the diesel bus. Finally, the proposed VSP-based model estimated the fuel consumption and the CO2 and NOx emission factors with relative total errors of less than 13%.
EndoG, a member of the DNA/RNA non-specific ββα-metal family of nucleases, has been demonstrated to be present in many organisms, including Trypanosomatids. This nuclease participates in the ...apoptotic program in these parasites by migrating from the mitochondrion to the nucleus, where it takes part in the degradation of genomic DNA that characterizes this process. We now demonstrate that Leishmania infantum EndoG (LiEndoG) is an endo-exonuclease that has a preferential 5' exonuclease activity on linear DNA. Regardless of its role during apoptotic cell death, this enzyme seems to be necessary during normal development of the parasites as indicated by the reduced growth rates observed in LiEndoG hemi-knockouts and their poor infectivity in differentiated THP-1 cells. The pro-life role of this protein is also corroborated by the higher survival rates of parasites that over-express this protein after treatment with the LiEndoG inhibitor Lei49. Taken together, our results demonstrate that this enzyme plays essential roles in both survival and death of Leishmania parasites.
•Blends up to 20% v/v of n-butanol with commercial diesel (EN-590) were evaluated.•Impact of n-butanol in each mode of the WHSC and on the full test was studied.•N-butanol improved engine performance ...regardless of load or speed conditions.•Butanol blends up to 10% showed favourable engine performance and large PM reduction.•N-butanol was most beneficial under high load and low speed conditions.
In recent years, n-butanol produced from waste or lignocellulosic materials has become an attractive and sustainable green energy source for diesel engines because has a clear potential for the partial substitution of fossil-based diesel fuel. This study aims to analyse the effects of different n-butanol/diesel fuel blends on the performance and exhaust emissions of a Euro V heavy-duty diesel engine following the World Harmonised Steady-State Cycle (WHSC), as well as the effect of each mode on the test averaged results. The blends evaluated here were blends of conventional diesel fuel with 5%, 10% and 20% (by volume) n-butanol. Conventional diesel fuel was used as a reference fuel to compare the performance and emission characteristics of the different n-butanol blends. The main findings show that 10% butanol could be considered as a suitable proportion for blending n-butanol/conventional diesel owing to its favourable performance and reduction in particulate emissions, without significant changes in the gaseous emissions of NOX. Mode-by-mode comparative analysis results show improved engine performance with the use of n-butanol in most modes, regardless of speed or load conditions. CO emissions in general increase, despite the incorporation of n-butanol reduces CO emissions under high-load and low-speed conditions. THC emissions increase with n-butanol, being more critical under cold start conditions. The influence of n-butanol on NOX emissions does not have a clear trend, but it is observed that NO2 emissions decrease in all modes with the use of n-butanol blends, mainly in low load modes.
Today, evidence-based nursing practice strives to improve health care, ensure adherence to treatment, improve health outcomes, and guarantee patient safety. The main scientific documents that nurses ...should consult, to obtain the best possible evidence, are systematic reviews and meta-analyses. However, this type of scientific document has a major issue if it uses retracted articles that could directly affect the consistency of the results shown in the reviews. The aim of this commentary is to present the current issue represented by the use of retracted articles in meta-analyses of systematic reviews and how researchers could detect them, through the use of different instruments, avoiding them, and providing a reliable SR or meta-analysis that could be useful for day-to-day clinical and research activities.
MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in ...experimental settings of infection. We describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The MyD88-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.
Background
Community‐acquired pneumonia (CAP) is a lung infection that can be acquired during day‐to‐day activities in the community (not while receiving care in a hospital). Community‐acquired ...pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain.
Objectives
To evaluate the efficacy and safety of short‐course versus longer‐course treatment with the same antibiotic at the same daily dosage for CAP in non‐hospitalised adolescents and adults (outpatients). We planned to investigate non‐inferiority of short‐course versus longer‐term course treatment for efficacy outcomes, and superiority of short‐course treatment for safety outcomes.
Search methods
We searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies.
Selection criteria
Randomised controlled trials (RCTs) comparing short‐ and long‐courses of the same antibiotic for CAP in adolescent and adult outpatients.
Data collection and analysis
We planned to use standard Cochrane methods.
Main results
Our searches identified 5260 records. We did not identify any RCTs that compared short‐ and longer‐courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.
We excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild‐to‐moderate CAP due to its questionable risk‐benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.
We found one ongoing study that we will assess for inclusion in future updates of the review.
Authors' conclusions
We found no eligible RCTs that studied a short‐course of antibiotic compared to a longer‐course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.
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Continuous treatment with lenalidomide (R) and dexamethasone (d) is a standard of care for multiple myeloma (MM) patients (pts) not candidates for autologous stem cell transplantation (ASCT). As ...previously reported, the addition of Clarithromycin (C) to Rd has proven to be safe and effective, and case-control analyses suggested a significant additive value with the combination. C optimizes the therapeutic effect of glucocorticoids by increasing the area under the curve, has immunomodulatory effects and may have direct antineoplastic properties. However, there are not randomized phase III trials confirming these results.
GEM-Claridex in an open, randomized, phase III trial for untreated newly diagnosed MM pts ineligible for ASCT. Enrolled pts were randomly assigned 1:1 to receive 28-day cycles of R (25mg po qd days 1-21), d (40mg po 20mg in pts >75 years, days 1, 8, 15 and 22) plus or minus C (500mg po bid) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and minimal residual disease (MRD) negativity rate and safety. MRD was evaluated in 99 pts using Euroflow NGF (limit of detection, 2x10-6). As expected, most pts in CR were tested for MRD whereas the majority of pts with missing MRD data achieved VGPR or less and were thus considered as MRD-positive for intent to treat analyses.
Two hundred and eighty-eight pts were included (144 to C-Rd and 144 to Rd). Median age was 76 (range: 65-93), 36.8% of pts had ISS 3 and 15.6% presented with high-risk cytogenetic abnormalities. Key baseline characteristics were well balanced between the two arms.
The addition of C to Rd resulted in deeper responses with a ≥ complete response (CR) rate of 20.1% in the C-Rd arm compared to 11.2% in the Rd arm (p = 0.037). Also, the ≥ very good partial response (VGPR) rate was 52.8% in the C-Rd arm as compared to the 37.1% in the Rd arm (p = 0.007). MRD analysis was performed at suspected CR and yearly afterwards. On intent-to-treat, 5/144 (3,5%) and 9/143 (6,2%) of pts achieved undetectable MRD with C-Rd and Rd, respectively (p = 0,7).
With a median follow-up of 16 months (range, 1-47), no significant differences were observed in PFS: in the C-Rd arm the median was 23 months and has not been reached in the Rd arm (p = 0.09); furthermore, although disease progression and/or death rate was comparable in both arms (C-Rd: 57/144 39.6% vs Rd: 45/144 31.2%), a trend towards shorter PFS was observed in the C-Rd group (Figure 1). This effect was less evident in younger (<75) pts (median PFS, C-Rd: 24 months vs Rd NR, p = 0,588) but, in older pts (≥ 75), the addition of C to Rd resulted into a significant deleterious effect on PFS (median PFS, C-Rd: 19 vs Rd 28 months, p = 0.03) (Figure 2a and 2b). Irrespectively of treatment arm, pts with MRD negative had significantly longer PFS (NR vs 26 months, p = 0,03). Concerning OS, no differences have been identified (p = 0.41), although median has not been reached yet in any arm. Out of the 33 and 28 deaths documented in the C-Rd and Rd arms respectively, the percentage of pts dying w/o documented PD was significantly higher in the C-Rd group (27/33 82% vs 13/27 48%, p = 0.004). Furthermore, in the C-Rd arm, the most frequent causes of death were severe infections (14/27 52% and cardiovascular events 6/27 22%) the majority of them occurring in older (≥75) pts (20/27, 74%).
The most common G3-4 adverse events (AE) in the C-Rd and Rd arms were hematologic (neutropenia: 10,4% vs 16,7% p = ns and anemia: 2,1% vs 6,9% p = 0,04, respectively). G3-4 infections occurred in 16% of cases in both arms and were the most frequent non-hematological AE. 7% of pts in both arms developed G3-4 GI toxicity and there were no differences between the two arms in G3-4 skin-related AEs (2,8% vs 3,5%). Only one case of invasive SPM (colon cancer) in the C-Rd arm was reported.
In conclusion, the addition of C to Rd in transplant ineligible newly diagnosed MM pts significantly increases the rate and depth of responses but it is not associated with an improved PFS and OS due to a higher proportion of deaths in the C-Rd arm, mostly infectious, in pts > 75 years and being early deaths. Overexposure to steroids due to the delayed clearance induced by C in this elderly population could explain our results.
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Puig:The Binding Site: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding. Rosinol Dachs:Janssen, Celgene, Amgen and Takeda: Honoraria. De Arriba:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Honoraria. Oriol:Celgene Corporation: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Janssen: Consultancy; Amgen: Consultancy, Speakers Bureau. De La Rubia:AbbVie: Consultancy; AMGEN: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy. Amor:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Martín Sánchez:GILEAD SCIENCES: Research Funding. Rossi:BMS: Research Funding; Janssen, Celgene, Amgen: Consultancy. Coleman:Merck: Research Funding; Pharmacyclics: Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Paiva:Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. San-Miguel:Amgen, Bristol-Myers Squibb, Celgene, Janssen, MSD, Novartis, Roche, Sanofi, and Takeda: Consultancy, Honoraria. Bladé:Jansen, Celgene, Takeda, Amgen and Oncopeptides: Honoraria. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Mateos:EDO: Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria.
•PEMS and OBD systems were used to obtain data for engine maps.•A Euro V diesel engine operates with a brake thermal efficiency of 41%•The real-world NOx energy-emission factor was higher than Euro V ...Standard.•The passenger load does not produce difference in engine performance.•The grid engine maps model predicts CO2 emissions with good accuracy.
Until recently, heavy-duty vehicle (HDV) engines were subjected to pollutant emissions type-approval tests, which were developed on engine test benches under standardised driving cycles. However, these results do not reflect engine behaviour under real-world driving conditions. In this context, experimental measurements were conducted on a diesel Euro V bus under urban off-cycle conditions in Madrid (Spain). The main objective was to create efficiency and emissions engine maps by combining transient-state engine data obtained directly from portable emission measurement system (PEMS) and on-board diagnostic (OBD) data acquisition systems. The engine maps were used to evaluate engine performance in real-world conditions, and to create a model that allows for second-by-second prediction of the engine fuel consumption and emissions. Owing to the variability of transient-state engine data, this work proposed an engine map development method, consisting of grouping the measured data into grids by engine speed and torque ranges, and then averaging them to obtain a single value per grid.
The results showed that the Euro V diesel bus engine operates in urban off-cycle conditions with a brake thermal efficiency (BTE) of 41%, a brake-specific fuel consumption (BSFC) of 205 g/kWh, and a carbon dioxide (CO2) energy-emission factor of 637 g/kWh. The NOx energy-emission factor was 80% higher than the levels in the Euro V Standard.
This work demonstrated that the grid engine maps model has the potential to predict second-by-second fuel consumption and CO2 emissions, with a relative total error of less than 5%. Therefore, this approach could be useful for accurately simulating engine or vehicle performance for any operation scenarios at a microscopic level, provided engine torque and engine speed data from the bus are available.
Exhaust aftertreatment systems are crucial to ensuring real-world NOx emission limits for motor vehicles. Operating conditions constrain the NOx reduction performance of aftertreatment devices. This ...study analysed real-world NOx emissions, tailpipe exhaust gas temperatures, and air-fuel ratios during cold start in a closed-loop urban route, followed by hot-start real driving emissions (RDE) tests. Five Euro-6b sport utility vehicles (SUV) were tested: two gasoline vehicles with three-way catalyst (TWC), namely, one gasoline direct injection (G-DI) and one hybrid electric vehicle (HEV); three diesel vehicles with different NOx control systems, namely, only exhaust gas recirculation (EGR), lean-burn NOx trap (LNT), and selective catalytic reduction (SCR).
The only-EGR- and LNT-equipped diesel vehicles and the G-DI vehicle surpassed the NOx Euro 6 limits in all tested sections. For the same vehicles, the total RDE emission factors were 9.0, 7.4, and 5.0 times the Euro 6 limits, respectively. In contrast, the diesel vehicle with SCR had an RDE emission factor 1.0 times the limit, and the HEV exhibited very low emissions at approximately 2 mg NOx km−1. However, during the cold start phase (first 5 min), the emission levels of the SCR and HEV vehicles surpassed the Euro 6 limits by 2.7 and 1.1 times, respectively. Based on the measurements at the tailpipe, the results indicate that cold start, urban driving, and cooling conditions of aftertreatment devices can lead to a decrease in the NOx conversion efficiency of TWC and SCR systems. The air-fuel ratio was key for the NOx conversion in TWC aftertreatment. The large differences between G-DI and HEV vehicles were primarily attributed to the lean and rich operations of the G-DI and HEV engines, respectively. To comply with stringent future regulations, lean-burn engines would require diesel-like aftertreatment. SCR and hybrid vehicles would require a careful aftertreatment thermal management or heating to further exploit their potential for reducing emissions in urban areas.
•Cold start strongly affected NOx reduction of SCR and TWC aftertreatments.•Post-Euro-6b diesel vehicles will require SCR devices and optimal thermal management.•Air-fuel ratio control is key for the performance of TWCs in gasoline vehicles.•Lean-burn-DI gasoline vehicles require diesel-like aftertreatments for NOx mitigation.•The HEV had very low NOx emissions using an enriched air-fuel ratio strategy.
The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced
...GATA2
and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence
GATA2
. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.
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