Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and ...efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.
The number of cases of type 2 diabetes (T2D) is increasing worldwide. This disease can be characterized by insulin resistance and pancreatic β cell dysfunction, which lead to macro- and microvascular ...complications. Anthocyanins are flavonoids that occur naturally in plants and are responsible for their color. Studies with cell lines and animal models and clinical trials in humans suggest that anthocyanins exhibit antidiabetic properties. However, variation in the structure of anthocyanins makes it difficult to determine their effects on T2D. Understanding the absorption and metabolism of anthocyanins is important for understanding their role in the improvement of this disease. Published data suggest that anthocyanins may lower blood glucose by improving insulin resistance, protecting β cells, increasing secretion of insulin and reducing digestion of sugars in the small intestine. The mechanisms of action are primarily related to their antioxidant properties, but enzymatic inhibition and other pathways may also be relevant.
► Diabetes mellitus is a global health problem with an increasing number of cases. ► Anthocyanins are naturally occurring flavonoids with antidiabetic properties. ► The mechanisms of action are primarily related to their antioxidant activities. ► Studying their metabolism is essential for assessing the potential therapeutic role.
Peatlands of the central Congo Basin have accumulated carbon over millennia. They currently store some 29 billion tonnes of carbon in peat. However, our understanding of the controls on peat carbon ...accumulation and loss and the vulnerability of this stored carbon to climate change is in its infancy. Here we present a new model of tropical peatland development, DigiBog_Congo, that we use to simulate peat carbon accumulation and loss in a rain‐fed interfluvial peatland that began forming ~20,000 calendar years Before Present (cal. yr BP, where ‘present’ is 1950 CE). Overall, the simulated age‐depth curve is in good agreement with palaeoenvironmental reconstructions derived from a peat core at the same location as our model simulation. We find two key controls on long‐term peat accumulation: water at the peat surface (surface wetness) and the very slow anoxic decay of recalcitrant material. Our main simulation shows that between the Late Glacial and early Holocene there were several multidecadal periods where net peat and carbon gain alternated with net loss. Later, a climatic dry phase beginning ~5200 cal. yr BP caused the peatland to become a long‐term carbon source from ~3975 to 900 cal. yr BP. Peat as old as ~7000 cal. yr BP was decomposed before the peatland's surface became wetter again, suggesting that changes in rainfall alone were sufficient to cause a catastrophic loss of peat carbon lasting thousands of years. During this time, 6.4 m of the column of peat was lost, resulting in 57% of the simulated carbon stock being released. Our study provides an approach to understanding the future impact of climate change and potential land‐use change on this vulnerable store of carbon.
Peatlands of the central Congo Basin currently store some 29 billion tonnes of carbon. We use a tropical peatland model to explore the vulnerability of this carbon to past climate change. We show that a dry phase beginning ~5200 cal. yr BP caused the peatland to become a long‐term carbon source from ~3975 to 900 cal. yr BP. Peat as old as ~7000 cal. yr BP was decomposed before the peatland's surface became wetter again, suggesting that changes in rainfall alone caused 57% of the simulated carbon stock to be released.
Background and purpose
Stroke assistance is facing changes and new challenges since COVID‐19 became pandemic. A variation on the patient influx might be one of the greater concerns, due to fewer ...people coming to emergency departments or coming too late. However, no data quantifying this have been published until now. The aim was to analyse the impact of the COVID‐19 epidemic outbreak on hospital stroke admissions and their characteristics in our region.
Methods
The data of every patient admitted to any hospital of our healthcare system with a diagnosis of ischaemic stroke between 30 December 2019 and 19 April 2020 were reviewed. Demographic and clinical data were recorded and compared between periods before and after the setting of the state of emergency secondary to the COVID‐19 outbreak.
Results
In total, 354 patients with ischaemic stroke were admitted in our study period. There was a weekly average of 27.5 cases before the setting of the state of emergency against 12 afterwards (P < 0.001). This drop in stroke cases occurred progressively from week 11, persisting in time despite the decrease in confirmed cases of COVID‐19. No differences in the proportion of intravenous thrombolysis (21.1% vs. 21.5%, P = 0.935) or endovascular therapy (12.4% vs. 15.2%, P = 0.510) were found, nor in other demographic or clinical characteristics except for median onset‐to‐door time (102 vs. 183 min, P = 0.015).
Conclusions
This observational study offers the perspective of a whole region in one of the countries more heavily stricken by the SARS‐CoV‐2 epidemic and shows that the decrease of stroke events, since the beginning of the COVID‐19 outbreak, happened globally and without any specific patient distribution.
The findings from geotechnical laboratory testing has shown that, in addition to the well understood influence of void ratio and effective confining stress, the particle fabric has a significant ...effect on the monotonic and cyclic shear behaviour of silts. There is a need to advance our understanding of these effects through systematic quantification of the particle fabric in a given silt matrix in terms of individual particle parameters (e.g., dimensional sizes, volumes, shapes, orientations) as well as inter-particle contact arrangements. In addressing this need, new methodologies were developed for X-ray micro-computed tomography (μ-CT) imaging of silts with specific attention paid to: sampling and preparing of silt specimens, scanning parameters to obtain the needed image resolutions, and digital processing of images to capture individual particle data. The ability of μ-CT imaging to effectively image and capture individual particle parameters and three-dimensional fabric of silt is demonstrated. The particle fabric in terms of orientation in reconstituted silt specimens is illustrated using the μ-CT images produced using standard-size silica particles. The fabric(s) quantified from the imaging of a natural low plastic silt is also presented, and the findings are in accord with those inferred from the mechanical laboratory element testing of the same silt. The work contributes to systematic accounting for fabric in understanding the macroscopic shear behaviour of natural silts.
Meat derived from pasture feeding, is associated with a high level of antioxidants. Antioxidants are incorporated within cell membranes and protect tissues against oxidation from reactive oxygen ...species. This maintains the overall quality of meat and secondary products. This paper reviews the implications of incorporating natural antioxidants into fresh beef, focusing on the benefits of feeding cattle good quality pasture. Pasture samples typically have higher levels of α-tocopherol, β-carotene, ascorbic acid and glutathione than feedlot samples. These compounds retard lipid and protein oxidation in fresh and stored meat, and preserve the color and odor quality of beef. The significance of antioxidant enzymes is variable, because their behavior depends on individual redox status before slaughter. Understanding total antioxidant activity requires information on antioxidant and pro-oxidant status. With an abundance of pasture, Argentina has a natural advantage in producing meat with a high antioxidant value.
•Proposed methodology for the modelling of the energy use of small appliances in households, categorised in four groups: audio-visual, computing, kitchen and other appliances.•Predictions of time ...varying fractional power demands of aggregations of appliance.•Comparison of seven different modelling approaches, based on two types of stochastic process: discrete time random (Markov) process (combined with clustering algorithms for matrix reduction) and continuous time random (Survival analysis) process.•Models are validated using three types of evaluation measure: time series analysis, model accuracy and aggregated energy use.•These validation measures suggest that the modelling of survival in discrete states performs well and is straightforward to integrate with energy simulation programs.
Accurate forecasting of residential energy loads is highly influenced by the use of electrical appliances, which not only affect electrical energy use but also internal heat gains, which in turn affects thermal energy use. It is therefore important to accurately understand the characteristics of appliance use and to embed this understanding into predictive models to support load forecast and building design decisions. Bottom-up techniques that account for the variability in socio-demographic characteristics of the occupants and their behaviour patterns constitute a powerful tool to this end, and are potentially able to inform the design of Demand Side Management strategies in homes.
To this end, this paper presents a comparison of alternative strategies to stochastically model the temporal energy use of low-load appliances (meaning those whose annual energy share is individually small but significant when considered as a group). In particular, discrete-time Markov processes and survival analysis have been explored. Rigorous mathematical procedures, including cluster analysis, have been employed to identify a parsimonious strategy for the modelling of variations in energy demand over time of the four principle categories of small appliances: audio-visual, computing, kitchen and other small appliances. From this it is concluded that a model of the duration for which appliances survive in discrete states expressed as bins in fraction of maximum power demand performs best. This general solution may be integrated with relative ease with dynamic simulation programs, to complement existing models of relatively large load appliances for the comprehensive simulation of household appliance use.
This study presents the use of a low-temperature hydrothermal method for extracting calcium sources from green mussel shell (P. Viridis) wastes and converting them into synthetic nanosized ...hydroxyapatite (HA). In this study, raw mussel shells were washed, pulverised, and sieved to start producing a fine calcium carbonate-rich powder. XRD quantitative analysis confirmed that the powder contains 97.6 wt. % aragonite. This powder was then calcined for 5 h at 900 °C to remove water, salt, and mud, yielding a calcium-rich feedstock with major minerals of calcite (68.7 wt.%), portlandite (24.7 wt.%), and minor aragonite (6.5 wt.%). The calcined powders were dissolved in aqueous stock solutions of HNO
3
and NH
4
OH before hydrothermally reacting with phosphoric acid (NH
4
)
2
HPO
4
, yielding pure, nanoscale (16-18 nm) carbonated HA crystals, according to XRD, FT-IR, and SEM analyses. The use of a low-temperature hydrothermal method for a feedstock powder produced by the calcination of low-cost mussel shell wastes would be a valuable processing approach for the industry's development of large-scale hydroxyapatite nanoparticle production.
The advent of the quantum gas microscope allowed for the in situ probing of ultracold gaseous matter on an unprecedented level of spatial resolution. However, the study of phenomena on ever smaller ...length scales, as well as the probing of three-dimensional systems, is fundamentally limited by the wavelength of the imaging light for all techniques based on linear optics. Here, we report on a high-resolution ion microscope as a versatile and powerful experimental tool to investigate quantum gases. The instrument clearly resolves atoms in an optical lattice with a spacing of 532 nm over a field of view of 50 sites and offers an extremely large depth of field on the order of at least70μm. With a simple model, we extract an upper limit for the achievable resolution of approximately 200 nm from our data. We demonstrate a pulsed operation mode enabling 3D imaging and allowing for the study of ionic impurities and Rydberg physics.
Heat treatment, or thermal disinfection, is one of the simplest disinfection methods, and is widely used in the water, sanitation, and food sectors, especially in low resource settings. Pathogen ...reductions achieved during heat treatment are influenced by a combination of temperature and exposure time. The objective of this paper was to construct updated time-temperature pathogen inactivation curves to define “safety zones” for the reduction of four pathogen groups (bacteria, viruses, protozoan (oo)cysts, and helminth eggs) during heat treatment in a variety of matrices. A systematic review and meta-analysis were conducted to determine the times needed to achieve specified levels of pathogen reduction at different temperatures. Web of Science was searched using a Boolean string to target studies of heat treatment and pasteurization systems that exposed pathogens in water, wastewater, biosolids, soil, or food matrices to temperatures between 20 °C and 95 °C. Data were extracted from tables or figures and regression was used to assess the relationship between time and temperature. Our findings indicate that the temperatures and times needed to achieve a 1-log10 reduction of all pathogen groups are likely higher and longer, respectively, than previously reported. The type of microorganism and the matrix significantly impact T90 values reported at different temperatures. At high temperatures, the time-temperature curves are controlled by thermally stable viruses such as hepatitis A virus. Data gaps include the lack of data on protozoa, and the lack of data on all pathogen groups at low temperatures, for long exposure times, and with high log10 reductions. The findings from this study can be used by engineers, food safety specialists for the planning and design of engineered water, sanitation, and food pasteurization and treatment systems.
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