Biochar produced by pyrolysis of organic residues is increasingly used for soil amendment and many other applications. However, analytical methods for its physical and chemical characterization are ...yet far from being specifically adapted, optimized, and standardized. Therefore, COST Action TD1107 conducted an interlaboratory comparison in which 22 laboratories from 12 countries analyzed three different types of biochar for 38 physical–chemical parameters (macro- and microelements, heavy metals, polycyclic aromatic hydrocarbons, pH, electrical conductivity, and specific surface area) with their preferential methods. The data were evaluated in detail using professional interlaboratory testing software. Whereas intralaboratory repeatability was generally good or at least acceptable, interlaboratory reproducibility was mostly not (20% < mean reproducibility standard deviation < 460%). This paper contributes to better comparability of biochar data published already and provides recommendations to improve and harmonize specific methods for biochar analysis in the future.
In this randomized, controlled, phase 3 trial involving children between the ages of 6 and 11 years with uncontrolled moderate-to-severe asthma, those who received the monoclonal antibody dupilumab ...had fewer asthma exacerbations and better lung function and asthma control than those who received placebo.
Both type 1 and type 2 diabetes (T1D and T2D) result from chronic insulin insufficiency due to progressive dysfunction and loss of beta cells, driven by cellular stress. Beta cell failure in both ...forms of diabetes involves defective stress-response and the onset of premature senescence, an irreversible form of cell-cycle arrest induced by chronic stress. However, the mechanisms by which cellular stress triggers beta cell senescence are not clear. We now show that CTCF, a stress-sensitive epigenetic regulator, controls the beta cell stress-response and senescence programs during beta cell maturation process along with the cohesin Smc3. Chromatin immunoprecipitation data suggest that CTCF and Smc3 differentially occupy genes associated with stress and DNA damage responses, functional maturation, and senescence in neonatal versus adult beta cells. Our data show that CTCF and cohesin Smc3 dependent control protects replicating beta cells from DNA damage, and is especially critical during the neonatal growth phase marked by high rates of replication. Beta cell specific loss of CTCF triggers a p53/p21 dependent senescence program, followed by beta cell dysfunction and eventual beta cell failure with advancing age. We further demonstrate that reduced CTCF levels in beta cells lead to adaptive failure in response to a high fat diet challenge, and recapitulate a neonatal beta cell like epigenetic landscape. Notably, CTCF levels are reduced in beta cells in T1D and T2D in mice and humans, and lead to reduced occupancy of CTCF and Smc3 at genes involved in senescence, DNA damage response, and beta cell function. Our data show that CTCF and cohesin collectively protect against senescence and govern beta cell function and fitness through a program established in the neonatal maturation phase.
Disclosure
S.S.Varghese: None. N.Parveen: None. J.K.Wang: Employee; Pfizer Inc., Johnson & Johnson. A.G.Hernandez-de la pena: None. S.Dhawan: None.
Funding
National Institutes of Health (R01DK120253)
OLIMPO is a balloon-borne experiment aiming at spectroscopic measurements of the Sunyaev-Zel'dovich effect in clusters of galaxies. The instrument operates from the stratosphere, so that it can cover ...a wide frequency range (from ∼ 130 to ∼ 520 GHz in 4 bands), including frequencies which are not observable with ground-based instruments. OLIMPO is composed of a 2.6-m aperture telescope, a differential Fourier transform spectrometer and four arrays of lumped element kinetic inductance detectors operating at the temperature of 0.3 K. The payload was launched from the Longyearbyen airport (Svalbard Islands) on July 14th, 2018, and operated for 5 days, at an altitude of 38 km around the North Pole. We report the in-flight performance of the first lumped element kinetic inductance detector arrays ever flown onboard a stratospheric balloon.
Extreme lateral interbody fusion allows for the insertion of a large‐footprint interbody cage while maintaining the presence of natural stabilizing ligaments and the facets. It is unclear how the ...load‐distribution mechanisms through these structures alter with temporal changes in the bone graft. The aim of this study was to examine the effects of temporal bone graft changes on load distribution among the cage, graft, and surrounding spinal structures using finite element analysis. Thoracolumbosacral spine computed tomography data from an asymptomatic male subject were segmented into anatomical regions of interest and digitally stitched to generate a surface mesh of the lumbar spine (L1‐S1). The interbody cage was inserted into the L4‐L5 region during surface meshing. A volumetric mesh was generated and imported into finite element software for pre‐processing, running nonlinear static solves, and post‐processing. Temporal stiffening was simulated in the graft region with unbonded (Soft Callus, Temporal Stages 1–3, Solid Graft) and bonded (Partial Fusion, Full Fusion) contact. In flexion and extension, cage stress reduced by 20% from the soft callus to solid graft state. Force on the graft was directly related to its stiffness, and load‐share between the cage and graft improved with increasing graft stiffness, regardless of whether contact was fused with the endplates. Fused contact between the cage‐graft complex and the adjacent endplates shifted load‐distribution pathways from the ligaments and facets to the implant, however, these changes did not extend to adjacent levels. These results suggest that once complete fusion is achieved, the existing load paths are seemingly diminished.
The beamlines at CERN's North and East Areas offer secondary beams in a wide range of momenta between 0.5 GeV/c and 400 GeV/c for fixed-target experiments as well as for test beam campaigns with a ...flexible configuration and variable beam composition and intensities. Recently, two new facilities for neutrino detectors tests have been established in an extension of the CERN North Area in context of the CERN Neutrino Platform project. These new tertiary beams extend the current capabilities of the H2 and H4 beamlines towards lower momenta in the range of 0.3 GeV/c to 12 GeV/c, respectively 7 GeV/c, and currently serve the two ProtoDUNE prototype detectors. In addition, a complete overhaul of the CERN East Area is underway, which will provide secondary beams with momenta of up to 15 GeV/c (T9 beam) and 12 GeV/c (T10 beam). New beam optics and an optimised design will allow for electron, hadron and muon beams with high purity. We discuss the layout and performance of both North and East Area beamlines as well as the available infrastructure for the neutrino detector community.
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Blood eosinophils and fractional exhaled nitric oxide (Feno) are prognostic biomarkers for exacerbations and predict lung function responses to dupilumab in adolescents and adults ...with asthma.
We evaluated the relationship between baseline blood eosinophils and Feno and response to dupilumab in children with asthma.
Children aged 6 to 11 years with uncontrolled moderate-to-severe asthma (n = 408) were randomized to receive dupilumab 100/200 mg by body weight or volume-matched placebo every 2 weeks for 52 weeks. Annualized exacerbation rate (AER) reduction and least squares mean change in prebronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) at week 12 were assessed according to cutoff baseline levels for Feno (<20 ppb vs ≥20 ppb) and blood eosinophil count (<150, ≥150 to <300, ≥300 to <500, and ≥500 cells/μL). Quadrant analyses in populations defined by biomarker thresholds and spline models across continuous end points assessed the relationship with Feno and eosinophil count. Interaction testing evaluated the independent roles of Feno and blood eosinophils as predictive markers.
Exacerbation risk and magnitude of AER reduction increased in subgroups with higher baseline biomarker levels. Quadrant analyses revealed that disease of patients with either elevated Feno or eosinophil counts demonstrated a clinical response to dupilumab. Interaction testing indicated blood eosinophil counts or Feno independently added value as predictive biomarkers.
In children with uncontrolled moderate-to-severe asthma, blood eosinophil counts and Feno are clinically relevant biomarkers to identify those at risk for asthma exacerbations, as well as those with disease with clinical response to dupilumab.
Liberty Asthma VOYAGE ClinicalTrials.gov NCT02948959.
A new family of anticancer compounds has been derived from oxaliplatin by inserting a double-bond between carbons 4 and 5 of the 1,2-diaminocyclohexane ring. Testing against a panel of human tumour ...cell lines including cervical (A431), ovarian (2008), and colon carcinomas (HCT-15 and LoVo), and two oxaliplatin-resistant clones (LoVo OXP and LoVo MDR) has shown that the new compounds have, in general, equal if not better cytotoxic activity and are able to overcome the oxaliplatin-resistance. Moreover, the oxalato derivative induced lipid droplets increase in LoVo OXP cells thus suggesting the involvement of metabolism stress in its mechanism of action.
A new family of anticancer compounds has been derived from oxaliplatin by inserting a double-bond between carbons 4 and 5 of the 1,2-diaminocyclohexane ring.
In 2019, the São Paulo State Cancer Institute (ICESP) implemented a novel model integrating Oncology with Palliative Care specialists. We evaluated the impact of this model on healthcare resource ...utilization and costs.
We analyzed data from all patients who passed away in February (1 month prior to implementation) and November (8 months after model implementation group) at ICESP, Brazil. Healthcare utilization data, including emergency department visits, hospital and intensive care unit admissions, chemotherapy, and radiotherapy use, were retrieved from Electronic Medical Records. Unit cost values were obtained from the administrative database.
A total of 198 patients who died in February and 196 in November were included in the analysis. Groups exhibited similarities in sex, age, ECOG, cancer type, previous outpatient palliative care consultations, and place of death (ward: 56.6% pre-intervention, 50% post-intervention). The mean cost per patient was US$13,226.29 pre-intervention and US$11,445.82 post-intervention (
= .007). Statistically significant differences were noted in days hospitalized in the surgical ward (227 vs 115), emergency department visits (233 vs 45), chemotherapy sessions (140 vs 26), and radiotherapy sessions (146 vs 10). Excluding outpatient treatments, the total costs for chemotherapy and radiotherapy in the last 30 days of life were US$16,924.45 pre-intervention and US$7851.65 post-intervention. Reductions were more pronounced in patients with ECOG 3-4 (
= .039).
Our data suggests that the integration model was associated with a reduction in potentially inappropriate treatments during the last month of life, leading to decreased healthcare utilization and costs.
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