Metformin-associated lactic acidosis in an intensive care unit

International audienceIntroduction Metformin-associated lactic acidosis (MALA) is aclassic side effect of metformin and is known to be a severedisease with a high mortality rate. The treatment of MALA withdialysis is controversial and is the subject of many case reportsin the literature. We aimed to assess the prevalence of MALA ina 16-bed, university-affiliated, intensive care unit (ICU), and theeffect of dialysis on patient outcome.Methods Over a five-year period, we retrospectively identifiedall patients who were either admitted to the ICU with metforminas a usual medication, or who attempted suicide by metforminingestion. Within this population, we selected patientspresenting with lactic acidosis, thus defining MALA, anddescribed their clinical and biological features.Results MALA accounted for 0.84% of all admissions duringthe study period (30 MALA admissions over five years) and wasassociated with a 30% mortality rate. The only factorsassociated with a fatal outcome were the reason for admissionin the ICU and the initial prothrombin time. Although patientswho went on to haemodialysis had higher illness severity scores,as compared with those who were not dialysed, the mortalityrates were similar between the two groups (31.3% versus28.6%).Conclusions MALA can be encountered in the ICU severaltimes a year and still remains a life-threatening condition.Treatment is restricted mostly to supportive measures, althoughhaemodialysis may possess a protective effect

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases

Investigations on the vulnerability of advanced CMOS technologies to MGy dose environments

This paper investigates the TID sensitivity of silicon-based technologies at several MGy irradiation doses to evaluate their potential for high TID-hardened circuits. Such circuits will be used in several specific applications suc as safety systems of current or future nuclear power plants considering various radiation environments including normal and accidental operating conditions, high energy physics instruments, fusion experiments or deep space missions. Various device designs implemented in well established bulk silicon and Partially Depleted SOI technologies are studied here up to 3 MGy. Furthermore, new insights are given on the vulnerability of more advanced technologies including planar Fully Depleted SOI and multiple-gate SOI transistors at such high dose. Potential of tested technologies are compared and discussed for stand-alone integrated circuits

Transparent Electrodes in Silicon Heterojunction Solar Cells: Influence on Contact Passivation

Charge carrier collection in silicon heterojunction solar cells occurs via intrinsic/doped hydrogenated amorphous silicon layer stacks deposited on the crystalline silicon wafer surfaces. Usually, both the electron and hole collecting stacks are externally capped by an n-type transparent conductive oxide, which is primarily needed for carrier extraction. Earlier, it has been demonstrated that the mere presence of such oxides can affect the carrier recombination in the crystalline silicon absorber. Here, we present a detailed investigation of the impact of this phenomenon on both the electron and hole collecting sides, including its consequences for the operating voltages of silicon heterojunction solar cells. Based on our findings, we define guiding principles for improved passivating contact design for high-efficiency silicon solar cells

Pseudomonas aeruginosa PAO1 Preferentially Grows as Aggregates in Liquid Batch Cultures and Disperses upon Starvation

In both natural and artificial environments, bacteria predominantly grow in biofilms, and bacteria often disperse from biofilms as freely suspended single-cells. In the present study, the formation and dispersal of planktonic cellular aggregates, or ‘suspended biofilms’, by Pseudomonas aeruginosa in liquid batch cultures were closely examined, and compared to biofilm formation on a matrix of polyester (PE) fibers as solid surface in batch cultures. Plankton samples were analyzed by laser-diffraction particle-size scanning (LDA) and microscopy of aggregates. Interestingly, LDA indicated that up to 90% of the total planktonic biomass consisted of cellular aggregates in the size range of 10–400 µm in diameter during the growth phase, as opposed to individual cells. In cultures with PE surfaces, P. aeruginosa preferred to grow in biofilms, as opposed to planktonicly. However, upon carbon, nitrogen or oxygen limitation, the planktonic aggregates and PE-attached biofilms dispersed into single cells, resulting in an increase in optical density (OD) independent of cellular growth. During growth, planktonic aggregates and PE-attached biofilms contained densely packed viable cells and extracellular DNA (eDNA), and starvation resulted in a loss of viable cells, and an increase in dead cells and eDNA. Furthermore, a release of metabolites and infective bacteriophage into the culture supernatant, and a marked decrease in intracellular concentration of the second messenger cyclic di-GMP, was observed in dispersing cultures. Thus, what traditionally has been described as planktonic, individual cell cultures of P. aeruginosa, are in fact suspended biofilms, and such aggregates have behaviors and responses (e.g. dispersal) similar to surface associated biofilms. In addition, we suggest that this planktonic biofilm model system can provide the basis for a detailed analysis of the synchronized biofilm life cycle of P. aeruginosa

High Total Ionizing Dose and Temperature Effects on Micro- and Nano-Electronic Devices

This paper investigates the vulnerability of several micro- and nano-electronic technologies to a mixed harsh environment involving high total ionizing dose at MGy levels and high temperature. Such operating conditions emerge today for several applications like new security systems in existing or future nuclear power plants, fusion experiments, or deep space missions. In this work, the competing effects of ionizing radiations and temperature are characterized in elementary devices made of MOS transistors from several technologies. First, devices are irradiated using a radiation laboratory X-ray source up to MGy dose levels at room temperature. Devices are either grounded or biased during irradiation to simulate two major circuit cases: a circuit which waits for a wake up signal, representing most of the lifetime of an integrated circuit operating in a harsh environment, and a nominal circuit function. Devices are then annealed at several temperatures to discuss the post-irradiation behavior and to determine whether an elevated temperature is an issue or not for circuit function in mixed harsh environments

Efficient Near-Infrared-Transparent Perovskite Solar Cells Enabling Direct Comparison of 4-Terminal and Monolithic Perovskite/Silicon Tandem Cells

Combining market-proven silicon solar cell technology with an efficient wide band gap top cell into a tandem device is an attractive approach to reduce the cost of photovoltaic systems. For this, perovskite solar cells are promising high-efficiency top cell candidates, but their typical device size (<0.2 cm2), is still far from standard industrial sizes. We present a1cm2 near-infrared transparent perovskite solar cell with 14.5% steady- state efficiency, as compared to 16.4% on 0.25 cm2. By mechanically stacking these cells with silicon heterojunction cells, we experimentally demonstrate a 4-terminal tandem measurement with a steady-state efficiency of 25.2%, with a 0.25 cm2 top cell. The developed top cell processing methods enable the fabrication of a 20.5% efficient and 1.43 cm2 large monolithic perovskite/silicon heterojunction tandem solar cell, featuring a rear-side textured bottom cell to increase its near-infrared spectral response. Finally, we compare both tandem configurations to identify efficiency-limiting factors and discuss the potential for further performance improvement

Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and investigation of the presumed underlying mechanism of action

International audienc

Rationale for BepiColombo Studies of Mercury's Surface and Composition

BepiColombo has a larger and in many ways more capable suite of instruments relevant for determination of the topographic, physical, chemical and mineralogical properties of Mercury's surface than the suite carried by NASA's MESSENGER spacecraft. Moreover, BepiColombo's data rate is substantially higher. This equips it to confirm, elaborate upon, and go beyond many of MESSENGER's remarkable achievements. Furthermore, the geometry of BepiColombo's orbital science campaign, beginning in 2026, will enable it to make uniformly resolved observations of both northern and southern hemispheres. This will offer more detailed and complete imaging and topographic mapping, element mapping with better sensitivity and improved spatial resolution, and totally new mineralogical mapping. We discuss MESSENGER data in the context of preparing for BepiColombo, and describe the contributions that we expect BepiColombo to make towards increased knowledge and understanding of Mercury's surface and its composition. Much current work, including analysis of analogue materials, is directed towards better preparing ourselves to understand what BepiColombo might reveal. Some of MESSENGER's more remarkable observations were obtained under unique or extreme conditions. BepiColombo should be able to confirm the validity of these observations and reveal the extent to which they are representative of the planet as a whole. It will also make new observations to clarify geological processes governing and reflecting crustal origin and evolution. We anticipate that the insights gained into Mercury's geological history and its current space weathering environment will enable us to better understand the relationships of surface chemistry, morphologies and structures with the composition of crustal types, including the nature and mobility of volatile species. This will enable estimation of the composition of the mantle from which the crust was derived, and lead to tighter constraints on models for Mercury's origin including the nature and original heliocentric distance of the material from which it formed.Peer reviewe