Thermal Characterization of Next-Generation Workloads on Heterogeneous MPSoCs

Next-generation High-Performance Computing (HPC) applications need to tackle outstanding computational complexity while meeting latency and Quality-of-Service constraints. Heterogeneous Multi-Processor Systems-on-Chip (MPSoCs), equipped with a mix of general-purpose cores and reconfigurable fabric for custom acceleration of computational blocks, are key in providing the flexibility to meet the requirements of next-generation HPC. However, heterogeneity brings new challenges to efficient chip thermal management. In this context, accurate and fast thermal simulators are becoming crucial to understand and exploit the trade-offs brought by heterogeneous MPSoCs. In this paper, we first thermally characterize a next-generation HPC workload, the online video transcoding application, using a highly-accurate Infra-Red (IR) microscope. Second, we extend the 3D-ICE thermal simulation tool with a new generic heat spreader model capable of accurately reproducing package surface temperature, with an average error of 6.8% for the hot spots of the chip. Our model is used to characterize the thermal behaviour of the online transcoding application when running on a heterogeneous MPSoC. Moreover, by using our detailed thermal system characterization we are able to explore different application mappings as well as the thermal limits of such heterogeneous platforms

Endogenous cyclin D1 promotes the rate of onset and magnitude of mitogenic signaling via Akt1 Ser473 phosphorylation

Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates RB and functions as a collaborative nuclear oncogene. The serine threonine kinase Akt plays a pivotal role in the control of cellular metabolism, survival, and mitogenic signaling. Herein, Akt1-mediated phosphorylation of downstream substrates in the mammary gland is reduced by cyclin D1 genetic deletion and is induced by mammary-gland-targeted cyclin D1 overexpression. Cyclin D1 is associated with Akt1 and augments the rate of onset and maximal cellular Akt1 activity induced by mitogens. Cyclin D1 is identified in a cytoplasmic-membrane-associated pool, and cytoplasmic-membrane-localized cyclin D1-but not nuclear-localized cyclin D1-recapitulates Akt1 transcriptional function. These studies identify a novel extranuclear function of cyclin D1 to enhance proliferative functions via augmenting Akt1 phosphorylation at Ser473

Bridging fluorescence microscopy and electron microscopy

Development of new fluorescent probes and fluorescence microscopes has led to new ways to study cell biology. With the emergence of specialized microscopy units at most universities and research centers, the use of these techniques is well within reach for a broad research community. A major breakthrough in fluorescence microscopy in biology is the ability to follow specific targets on or in living cells, revealing dynamic localization and/or function of target molecules. One of the inherent limitations of fluorescence microscopy is the resolution. Several efforts are undertaken to overcome this limit. The traditional and most well-known way to achieve higher resolution imaging is by electron microscopy. Moreover, electron microscopy reveals organelles, membranes, macromolecules, and thus aids in the understanding of cellular complexity and localization of molecules of interest in relation to other structures. With the new probe development, a solid bridge between fluorescence microscopy and electron microscopy is being built, even leading to correlative imaging. This connection provides several benefits, both scientifically as well as practically. Here, I summarize recent developments in bridging microscopy

Excess resource use and cost of drug-resistant infections for six key pathogens in Europe: a systematic review and Bayesian meta-analysis

© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Quantifying the resource use and cost of antimicrobial resistance establishes the magnitude of the problem and drives action.[Objectives] Assessment of resource use and cost associated with infections with six key drug-resistant pathogens in Europe.[Methods] A systematic review and Bayesian meta-analysis.[Data sources] MEDLINE (Ovid), Embase (Ovid), Econlit databases, and grey literature for the period 1 January 1990, to 21 June 2022.[Study eligibility criteria] Resource use and cost outcomes (including excess length of stay, overall costs, and other excess in or outpatient costs) were compared between patients with defined antibiotic-resistant infections caused by carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, CR or third-generation cephalosporin Escherichia coli (3GCREC) and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus faecium, and patients with drug-susceptible or no infection.[Participants] All patients diagnosed with drug-resistant bloodstream infections (BSIs).[Interventions] NA.[Assessment of risk of bias] An adapted version of the Joanna Briggs Institute assessment tool, incorporating case-control, cohort, and economic assessment frameworks.[Methods of data synthesis] Hierarchical Bayesian meta-analyses were used to assess pathogen-specific resource use estimates.[Results] Of 5969 screened publications, 37 were included in the review. Data were sparse and heterogeneous. Most studies estimated the attributable burden by, comparing resistant and susceptible pathogens (32/37). Four studies analysed the excess cost of hospitalization attributable to 3GCREC BSIs, ranging from -€ 2465.50 to € 6402.81. Eight studies presented adjusted excess length of hospital stay estimates for methicillin-resistant S. aureus and 3GCREC BSIs (4 each) allowing for Bayesian hierarchical analysis, estimating means of 1.26 (95% credible interval [CrI], −0.72 to 4.17) and 1.78 (95% CrI, −0.02 to 3.38) days, respectively.[Conclusions] Evidence on most cost and resource use outcomes and across most pathogen-resistance combinations was severely lacking. Given the importance of this evidence for rational policymaking, further research is urgently needed.This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 101034420 (Predicting the Impact of Monoclonal Antibodies & Vaccines on Antimicrobial Resistance [PrIMAVeRa]) on the November 1, 2021. This joint undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and EFPIA. The funder has not been involved in the protocol drafting or methods selection of this study.Peer reviewe

A systematic review on the excess health risk of antibiotic-resistant bloodstream infections for six key pathogens in Europe

© 2023 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined.[Objectives] We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe.[Methods] A systematic review and meta-analysis.[Data sources] MEDLINE, Embase, and grey literature for the period January 1990 to May 2022.[Study eligibility criteria] Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries.[Participants] Paediatric and adult patients diagnosed with drug-resistant BSI.[Interventions] Not applicable.[Assessment of risk of bias] An adapted version of the Joanna-Briggs Institute assessment tool.[Methods of data synthesis] Random-effect models were used to pool pathogen-specific burden estimates.[Results] We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03–1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62–7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92–18.09] and OR 6.18 [95% CI 2.10–18.17], respectively).[Conclusions] Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions.Peer reviewe

A systematic review on the excess health risk of antibiotic-resistant bloodstream infections for six key pathogens in Europe

Background: Antimicrobial resistance is a global threat, which requires novel intervention strategies, for which priority pathogens and settings need to be determined. Objectives: We evaluated pathogen-specific excess health burden of drug-resistant bloodstream infections (BSIs) in Europe. Methods: A systematic review and meta-analysis. Data sources: MEDLINE, Embase, and grey literature for the period January 1990 to May 2022. Study eligibility criteria: Studies that reported burden data for six key drug-resistant pathogens: carbapenem-resistant (CR) Pseudomonas aeruginosa and Acinetobacter baumannii, third-generation cephalosporin or CR Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Excess health outcomes compared with drug-susceptible BSIs or uninfected patients. For MRSA and third-generation cephalosporin E. coli and K. pneumoniae BSIs, five or more European studies were identified. For all others, the search was extended to high-income countries. Participants: Paediatric and adult patients diagnosed with drug-resistant BSI. Interventions: Not applicable. Assessment of risk of bias: An adapted version of the Joanna-Briggs Institute assessment tool. Methods of data synthesis: Random-effect models were used to pool pathogen-specific burden estimates. Results: We screened 7154 titles, 1078 full-texts and found 56 studies on BSIs. Most studies compared outcomes of drug-resistant to drug-susceptible BSIs (46/56, 82.1%), and reported mortality (55/56 studies, 98.6%). The pooled crude estimate for excess all-cause mortality of drug-resistant versus drug-susceptible BSIs ranged from OR 1.31 (95% CI 1.03–1.68) for CR P. aeruginosa to OR 3.44 (95% CI 1.62–7.32) for CR K. pneumoniae. Pooled crude estimates comparing mortality to uninfected patients were available for vancomycin-resistant Enterococcus and MRSA BSIs (OR of 11.19 [95% CI 6.92–18.09] and OR 6.18 [95% CI 2.10–18.17], respectively). Conclusions: Drug-resistant BSIs are associated with increased mortality, with the magnitude of the effect influenced by pathogen type and comparator. Future research should address crucial knowledge gaps in pathogen- and infection-specific burdens to guide development of novel interventions

Colorful calcium sensors

(R)evolution of protein-based calcium sensors: Expanding the toolbox of genetically encoded calcium sensors with new colors and traits is important for understanding calcium signaling and its relation to other intracellular pathways. Campbell and co-workers have used a new directed-evolution strategy to develop a rich palette of new sensors, including the first red-shifted

Predictors of High-grade Vesicoureteral Reflux in Children with Febrile Urinary Tract Infections

Purpose This study aimed to investigate clinical and radiological factors that may predict high-grade vesicoureteral reflux (VUR) in patients with febrile urinary tract infection (UTI). Methods We retrospectively analyzed medical records of 446 patients diagnosed with febrile UTI from March 2008 to February 2017. All patients underwent renal-bladder ultrasonography (RBUS), 99mTc dimercaptosuccinic acid (DMSA) renal scan, and voiding cystourethrography (VCUG), and were divided in to 3 groups: a high-grade VUR group (n=53), a low-grade VUR group (n=28), and a group without VUR (n=365). Results The recurrence and non-Escherichia coli infection rates in febrile UTI were significantly higher in the high-grade VUR group than in the other two groups (P<0.05). RBUS showed that hydronephrosis and ureter dilatation were more frequent in the high-grade VUR group than in the other groups (P<0.05). In the high-grade VUR group, a renal cortical defect was more likely to appear as multiple defects, and the difference in bilateral renal scan uptake between both kidneys was larger than in the other two groups (P<0.001). Conclusion Recurrent UTI, non-E. coli UTI, abnormal findings on RBUS such as hydronephrosis and ureter dilatation, and abnormal findings in the DMSA renal scan such as multiple renal cortical defects and greater uptake difference were associated with high-grade VUR. VCUG should be selectively performed when RBUS and/or DMSA renal scan reveal significant abnormalities