Dose Finding Study To Assess Safety, Pk And Efficacy Of Fimepinostat (Cudc‐907) With Venetoclax Or Rituximab Plus Bendamustine In Patients With Relapsed/Refractory Lymphoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149554/1/hon9_2632.pd

Outgoing Near‐Infrared Radiation From Vegetation Scales With Canopy Photosynthesis Across a Spectrum of Function, Structure, Physiological Capacity, and Weather

We test the relationship between canopy photosynthesis and reflected near-infrared radiation from vegetation across a range of functional (photosynthetic pathway and capacity) and structural conditions (leaf area index, fraction of green and dead leaves, canopy height, reproductive stage, and leaf angle inclination), weather conditions, and years using a network of field sites from across central California. We based our analysis on direct measurements of canopy photosynthesis, with eddy covariance, and measurements of reflected near-infrared and red radiation from vegetation, with light-emitting diode sensors. And we interpreted the observed relationships between photosynthesis and reflected near-infrared radiation using simulations based on the multilayer, biophysical model, CanVeg. Measurements of reflected near-infrared radiation were highly correlated with measurements of canopy photosynthesis on half-hourly, daily, seasonal, annual, and decadal time scales across the wide range of function and structure and weather conditions. Slopes of the regression between canopy photosynthesis and reflected near-infrared radiation were greatest for the fertilized and irrigated C4 corn crop, intermediate for the C3 tules on nutrient-rich organic soil and nitrogen fixing alfalfa, and least for the native annual grasslands and oak savanna on nutrient-poor, mineral soils. Reflected near-infrared radiation from vegetation has several advantages over other remotely sensed vegetation indices that are used to infer canopy photosynthesis; it does not saturate at high leaf area indices, it is insensitive to the presence of dead legacy vegetation, the sensors are inexpensive, and the reflectance signal is strong. Hence, information on reflected near-infrared radiation from vegetation may have utility in monitoring carbon assimilation in carbon sequestration projects or on microsatellites orbiting Earth for precision agriculture applications

Variation in antibiotic treatment for diabetic patients with serious foot infections: A retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Diabetic foot infections are common, serious, and diverse. There is uncertainty about optimal antibiotic treatment, and probably substantial variation in practice. Our aim was to document whether this is the case: A finding that would raise questions about the comparative cost-effectiveness of different regimens and also open the possibility of examining costs and outcomes to determine which should be preferred.</p> <p>Methods</p> <p>We used the Veterans Health Administration (VA) Diabetes Epidemiology Cohorts (DEpiC) database to conduct a retrospective observational study of hospitalized patients with diabetic foot infections. DEpiC contains computerized VA and Medicare patient-level data for VA patients with diabetes since 1998, including demographics, ICD-9-CM diagnostic codes, antibiotics prescribed, and VA facility. We identified all patients with ICD-9-CM codes for cellulitis/abscess of the foot and then sub-grouped them according to whether they had cellulitis/abscess plus codes for gangrene, osteomyelitis, skin ulcer, or none of these. For each facility, we determined: 1) The proportion of patients treated with an antibiotic and the initial route of administration; 2) The first antibiotic regimen prescribed for each patient, defined as treatment with the same antibiotic, or combination of antibiotics, for at least 5 continuous days; and 3) The antibacterial spectrum of the first regimen.</p> <p>Results</p> <p>We identified 3,792 patients with cellulitis/abscess of the foot either alone (16.4%), or with ulcer (32.6%), osteomyelitis (19.0%) or gangrene (32.0%). Antibiotics were prescribed for 98.9%. At least 5 continuous days of treatment with an unchanged regimen of one or more antibiotics was prescribed for 59.3%. The means and (ranges) across facilities of the three most common regimens were: 16.4%, (22.8%); 15.7%, (36.1%); and 10.8%, (50.5%). The range of variation across facilities proved substantially greater than that across the different categories of foot infection. We found similar variation in the spectrum of the antibiotic regimen.</p> <p>Conclusions</p> <p>The large variations in regimen appear to reflect differences in facility practice styles rather than case mix. It is unlikely that all regimens are equally cost-effective. Our methods make possible evaluation of many regimens across many facilities, and can be applied in further studies to determine which antibiotic regimens should be preferred.</p

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Influence of oxygen levels on chondrogenesis of porcine mesenchymal stem cells cultured in polycaprolactone scaffolds

[EN] Chondrogenesis of mesenchymal stem cells (MSCs) is known to be regulated by a number of environmental factors, including local oxygen levels. The hypothesis of this study is that the response of MSCs to hypoxia is dependent on the physical and chemical characteristics of the substrate used. The objective of this study was to explore how different modifications to polycaprolactone (PCL) scaffolds influenced the response of MSCs to hypoxia. PCL, PCL-hyaluronic acid (HA), and PCL-Bioglass (R) (BG) scaffolds were seeded with MSCs derived from bone marrow and cultured for 35 days under normoxic or low oxygen conditions, and the resulting biochemical properties of the MSC laden construct were assessed. Low oxygen tension has a positive effect over cell proliferation and macromolecules biosynthesis. Furthermore, hypoxia enhanced the distribution of collagen and glycosaminoglycans (GAGs) deposition through the scaffold. On the other hand, MSCs displayed certain material dependent responses to hypoxia. Low oxygen tension had a positive effect on cell proliferation in BG and HA scaffolds, but only a positive effect on GAGs synthesis in PCL and HA scaffolds. In conclusion, hypoxia increased cell viability and expression of chondrogenic markers but the cell response was modulated by the type of scaffold used.Contract grant sponsors: VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, Instituto de Salud Carlos III, and European Regional Development FundRódenas Rochina, J.; Kelly, DJ.; Gómez Ribelles, JL.; Lebourg, MM. (2017). Influence of oxygen levels on chondrogenesis of porcine mesenchymal stem cells cultured in polycaprolactone scaffolds. Journal of Biomedical Materials Research Part A. 105(6):1684-1691. https://doi.org/10.1002/jbm.a.36043S16841691105

Early Release - Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia - Volume 29, Number 11—November 2023 - Emerging Infectious Diseases journal - CDC

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future

Systemic in vivo delivery of siRNA to tumours using combination of polyethyleneimine and transferrin–polyethyleneimine conjugates

Materials for delivery of oligonucleotides need to be simple to produce yet effective in vivo to be considered for clinical applications. Formulations of biomaterials based on combinations of existing demonstrated polymeric gene carriers with targeted derivatives are potential candidates for rapid translation but have not been fully explored for siRNA applications. Here we investigated formulations based on derivatised PEI for delivery of siRNA to gastrointestinal cancer cells. siRNA was complexed with linear PEI alone or with a mixture of linear PEI and transferrin-conjugated branched PEI (TfPEI), and knockdown of reporter genes was investigated. Overall, the in vitro use of complexes containing TfPEI resulted in up to 93% knockdown at 72 h post-transfection. Sustained knockdown was also achieved in a bioluminescent xenograft model. When complexes were delivered intratumorally, a 43% reduction in luminescence was achieved in the treated group compared with the control group 48 h after treatment. For systemic administration, only the intraperitoneal route, and not the intravenous route was effective, with 49% knockdown achieved at 72 h and sustained up to 144 h (44%) after a single administration of TfPEI-complexed siRNA. No toxicity or induction of the interferon response was observed. These findings demonstrate that simple formulations of transferrin-conjugated PEI with a ‘parent’ polymer such as linear PEI have potential as a method for therapeutic delivery of siRNA when administered either intratumorally or systemically

Singular Fermi Liquids

An introductory survey of the theoretical ideas and calculations and the experimental results which depart from Landau Fermi-liquids is presented. Common themes and possible routes to the singularities leading to the breakdown of Landau Fermi liquids are categorized following an elementary discussion of the theory. Soluble examples of Singular Fermi liquids (often called Non-Fermi liquids) include models of impurities in metals with special symmetries and one-dimensional interacting fermions. A review of these is followed by a discussion of Singular Fermi liquids in a wide variety of experimental situations and theoretical models. These include the effects of low-energy collective fluctuations, gauge fields due either to symmetries in the hamiltonian or possible dynamically generated symmetries, fluctuations around quantum critical points, the normal state of high temperature superconductors and the two-dimensional metallic state. For the last three systems, the principal experimental results are summarized and the outstanding theoretical issues highlighted.Comment: 170 pages; submitted to Physics Reports; a single pdf file with high quality figures is available from http://www.lorentz.leidenuniv.nl/~saarloo

Epigenetic management of major psychosis

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders

A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells

Epstein-Barr virus (EBV) replication contributes to multiple human diseases, including infectious mononucleosis, nasopharyngeal carcinoma, B cell lymphomas, and oral hairy leukoplakia. We performed systematic quantitative analyses of temporal changes in host and EBV proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. We quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. Our approach revealed EBV-induced remodeling of cell cycle, innate and adaptive immune pathways, including upregulation of the complement cascade and proteasomal degradation of the B cell receptor complex, conserved between EBV types I and II. Cross-comparison with proteomic analyses of human cytomegalovirus infection and of a Kaposi-sarcoma-associated herpesvirus immunoevasin identified host factors targeted by multiple herpesviruses. Our results provide an important resource for studies of EBV replication