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A future UVR × CO2 × Mix × Nut scenario exerted a more inhibitory effect on Pc as the water column became darker. AZD3514 However, the magnitude of this synergistic effect was 40-60% lower than that exerted by double and triple interactions and by UVR acting independently. These results illustrate that although future global-change conditions could reduce Pc in Mediterranean lakes, multiple interacting drivers can temper the impact of a severely detrimental driver (i.e. UVR), particularly as the water column darkens.Although the cardiotoxic effects of cocaine are universally recognized, the association between cocaine and cardiomyopathy and/or heart failure is poorly understood. To conduct a comprehensive review and meta-analysis on the association between cocaine, heart failure, and cardiomyopathy, we first conducted a broad-term search in PubMed, Embase, Web of Science, and Scopus for human studies containing primary data on the relationship between cocaine and heart failure or cardiomyopathy. We were interested in studies with data beyond acute coronary syndromes. Retrieved studies were grouped into different categories based on possible hypotheses to test by meta-analysis. A second search with specific terms was then conducted. For grouped studies with sufficient clinical and methodological homogeneity, effect sizes were calculated and combined for meta-analysis by the Random Effects model. There is in general a need for more primary data studies that investigate heart failure and/or cardiomyopathy in cocaine users for mechanisms independent of ischemia. There were, however, enough studies to combine by meta-analyses that showed that chronic cocaine use is associated with anatomical and functional changes more consistent with diastolic heart failure instead of the commonly taught dilated cardiomyopathy pathway. In patients without a history of ACS, chronic cocaine use was not associated with significantly reduced EF. The few studies on acute cocaine had conflicting results on whether single-dose intravascular cocaine results in acute heart failure. Studies identified that included beta-blockade therapy in cocaine users with cardiac disease suggest that beta-blockers are not unsafe and that may be effective in the treatment of cocaine-associated heart failure. Chronic cocaine use is associated with anatomical and physiological changes of the heart muscle that are potentially reversible with beta-blockade therapy.Quantum cascade lasers (QCL) have revolutionized the generation of mid-infrared light. Yet, the ultrafast carrier transport in mid-infrared QCLs has so far constituted a seemingly insurmountable obstacle for the formation of ultrashort light pulses. Here, we demonstrate that careful quantum design of the gain medium and control over the intermode beat synchronization enable transform-limited picosecond pulses from QCL frequency combs. Both an interferometric radio-frequency technique and second-order autocorrelation shed light on the pulse dynamics and confirm that mode-locked operation is achieved from threshold to rollover current. Furthermore, we show that both anti-phase and in-phase synchronized states exist in QCLs. Being electrically pumped and compact, mode-locked QCLs pave the way towards monolithically integrated non-linear photonics in the molecular fingerprint region beyond 6 μm wavelength.Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.In order to foster animal welfare as well as high quality of research, many countries regulate by law that the severity of animal experiments must be evaluated and considered when performing biomedical research. It is well accepted that multiple parameters rather than a single readout parameter should be applied to describe animal distress or suffering. However, since the performance of readout parameters for animal distress is rarely defined and methods for multivariate analysis have only in rare cases been used, it is not known which methodology is most appropriate to define animal distress. This study used receiver operating characteristic curve analysis to quantify the performance of burrowing activity, body weight change and a distress score of mice after induction of liver damage by bile duct ligation or carbon tetrachloride. In addition, Support Vector Machine classification was used to compare the distress of these mouse models. This approach demonstrated that bile duct ligation causes much more distress than carbon tetrachloride-induced liver damage. This study, therefore, provides a prototype how to compare two animal models by considering several readout parameters. In the future these or similar methods for multivariate analysis will be necessary, when assessing and comparing the severity of animal models.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Bioinsecticides consisting of different sets of Bacillus thuringiensis (Bt) Cry, Cyt and Vip toxins are broadly used in pest control. Possible interactions (synergistic, additive or antagonistic) between these proteins can not only influence the overall efficacy of certain Bt-based bioinsecticide, but also raise questions regarding environmental safety. Here, we assemble, summarize and analyze the outcomes of experiments published over 30 years, investigating combinatorial effects among Bt Cry, Cyt and Vip toxins. We collected the results on 118 various two-to-five-component combinations that have been bioassayed against 38 invertebrate species. Synergism, additive effect and antagonism was indicated in 54%, 32% and 14% of experiments, respectively. Synergism was noted most frequently for Cry/Cyt combinations, followed by Cyt/Vip and Cry/Cry. In Cry/Vip combinations, antagonism is more frequent and higher in magnitude compared to other categories. Despite a significant number of tested Bt toxin combinations, most of them have been bioassayed only against one pest species.

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