Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, ...high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future.
The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field.
Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues.
We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
The Whistler Aerosol and Cloud Study (WACS 2010), included intensive measurements of trace gases and particles at two sites on Whistler Mountain. Between 6–11 July 2010 there was a sustained ...high-pressure system over the region with cloud-free conditions and the highest temperatures of the study. During this period, the organic aerosol concentrations rose from <1 μg m−3 to ∼6 μg m−3. Precursor gas and aerosol composition measurements show that these organics were almost entirely of secondary biogenic nature. Throughout 6–11 July, the anthropogenic influence was minimal with sulfate concentrations <0.2 μg m−3 and SO2 mixing ratios 0.05–0.1 ppbv. Thus, this case provides excellent conditions to probe the role of biogenic secondary organic aerosol in aerosol microphysics. Although SO2 mixing ratios were relatively low, box-model simulations show that nucleation and growth may be modeled accurately if Jnuc = 3 × 10−7H2SO4 and the organics are treated as effectively non-volatile. Due to the low condensation sink and the fast condensation rate of organics, the nucleated particles grew rapidly (2–5 nm h−1) with a 10–25% probability of growing to CCN sizes (100 nm) in the first two days as opposed to being scavenged by coagulation with larger particles. The nucleated particles were observed to grow to ∼200 nm after three days. Comparisons of size-distribution with CCN data show that particle hygroscopicity (κ) was ∼0.1 for particles larger 150 nm, but for smaller particles near 100 nm the κ value decreased near midway through the period from 0.17 to less than 0.06. In this environment of little anthropogenic influence and low SO2, the rapid growth rates of the regionally nucleated particles – due to condensation of biogenic SOA – results in an unusually high efficiency of conversion of the nucleated particles to CCN. Consequently, despite the low SO2, nucleation/growth appear to be the dominant source of particle number.
Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are ...well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a 'pouch and wick' HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR.
Climate change and the intensification of land use practices are causing widespread eutrophication of subarctic lakes. The implications of this rapid change for lake ecosystem function remain poorly ...understood. To assess how freshwater communities respond to such profound changes in their habitat and resource availability, we conducted a space‐for‐time analysis of food‐web structure in 30 lakes situated across a temperature‐productivity gradient equivalent to the predicted future climate of subarctic Europe (temperature +3°C, precipitation +30% and nutrient +45 μg L−1 total phosphorus). Along this gradient, we observed an increase in the assimilation of pelagic‐derived carbon from 25 to 75% throughout primary, secondary and tertiary consumers. This shift was overwhelmingly driven by the consumption of pelagic detritus by benthic primary consumers and was not accompanied by increased pelagic foraging by higher trophic level consumers. Our data also revealed a convergence of the carbon isotope ratios of pelagic and benthic food web endmembers in the warmest, most productive lakes indicating that the incorporation of terrestrial derived carbon into aquatic food webs increases as land use intensifies. These results, reflecting changes along a gradient characteristic of the predicted future environment throughout the subarctic, indicate that climate and land use driven eutrophication and browning are radically altering the function and fuelling of aquatic food webs in this biome.
In hexaploid bread wheat ( Triticum aestivum L. em. Thell), ten members of the IWMMN ( International Wheat Microsatellites Mapping Network) collaborated in extending the microsatellite (SSR = simple ...sequence repeat) genetic map. Among a much larger number of microsatellite primer pairs developed as a part of the WMC ( Wheat Microsatellite Consortium), 58 out of 176 primer pairs tested were found to be polymorphic between the parents of the ITMI ( International Triticeae Mapping Initiative) mapping population W7984 x Opata 85 (ITMI pop). This population was used earlier for the construction of RFLP ( Restriction Fragment Length Polymorphism) maps in bread wheat (ITMI map). Using the ITMI pop and a framework map (having 266 anchor markers) prepared for this purpose, a total of 66 microsatellite loci were mapped, which were distributed on 20 of the 21 chromosomes (no marker on chromosome 6D). These 66 mapped microsatellite (SSR) loci add to the existing 384 microsatellite loci earlier mapped in bread wheat.
Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation ...in the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study was to replicate association of the rs4149056 variant in SLCO1B1 with severe statin-associated myopathy in a cohort of patients using a variety of statin medications and to investigate the association with specific statin types. We identified 25 cases of severe statin-associated myopathy and 84 controls matched for age, gender, statin type and dose. The rs4149056 variant in SLCO1B1 was not significantly associated with myopathy in this group as a whole. However, when subjects were stratified by statin type, the SLCO1B1 rs4149056 genotype was significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin.
Mineral nutrient uptake and utilisation by plants are controlled by many traits relating to root morphology, ion transport, sequestration and translocation. The aims of this study were to determine ...the phenotypic diversity in root morphology and leaf and seed mineral composition of a polyploid crop species, Brassica napus L., and how these traits relate to crop habit. Traits were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127 spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were measured in a 'pouch and wick' system (n = ~24 replicates per genotype). The mineral composition of 3-6 rosette-stage leaves, and mature seeds, was determined on compost-grown plants from a designed experiment (n = 5) by inductively coupled plasma-mass spectrometry (ICP-MS).
Seed size explained a large proportion of the variation in root length. Winter OSR and fodder habits had longer primary and lateral roots than spring OSR habits, with generally lower mineral concentrations. A comparison of the ratios of elements in leaf and seed parts revealed differences in translocation processes between crop habits, including those likely to be associated with crop-selection for OSR seeds with lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in a discriminant analysis provided the most accurate characterisation of crop habit, illustrating the interdependence of plant tissues.
High-throughput morphological and composition phenotyping reveals complex interrelationships between mineral acquisition and accumulation linked to genetic control within and between crop types (habits) in B. napus. Despite its recent genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits could potentially be used in crop improvement, if suitable markers can be identified and if these correspond with suitable agronomy and quality traits.
Daptomycin is a new lipopeptide antibiotic that is rapidly bactericidal against Staphylococcus aureus. We report daptomycin resistance and treatment failure in 2 patients with osteomyelitis due to ...methicillin-resistant S. aureus. Disk diffusion susceptibility testing failed to detect resistance. Daptomycin at high concentration retained bactericidal activity against resistant isolates.
Summary
Multiple myeloma (MM) accounts for 10% of haematological malignancies. Overall survival (OS) has improved in recent years due to increased use of autologous stem cell transplantation (ASCT) ...in the treatment of newly diagnosed MM and the advent of novel agents, including proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies. To assess trends in ASCT including patient selection, choice of induction regimen, depth of response and survival, we performed a retrospective analysis of all patients undergoing first ASCT for MM in European Society for Blood and Marrow Transplantation centres between 1995 and 2019. A total of 117 711 patients across 575 centres were included. The number of transplants performed increased sevenfold across the study period. The median age increased from 55 to 61 years, and the percentage of patients aged >65 years rose from 7% to 30%. Use of chemotherapy‐based induction fell significantly, being largely replaced by bortezomib‐based regimens. The two‐year complete response rate increased from 22% to 42%. The five‐year progression‐free survival and OS rates increased from 28% to 31% and from 52% to 69%, respectively. Transplant mortality fell from 5.9% to 1.5%. Ongoing advances in MM treatment may challenge the future role of ASCT. However, at the current time, ASCT remains central to the MM treatment paradigm.
The increase in the prevalence and impact of infections caused by carbapenemase-producing
is a global health concern. Therefore, rapid and accurate methods to detect these organisms in any clinical ...microbiology laboratory, including those in resource-limited settings, are essential to prevent and contain their spread. It is also important to differentiate between serine- and metal-dependent carbapenemases elaborated by carbapenemase-producing isolates for epidemiologic, infection control and prevention, and therapeutic purposes. Here, we describe the development and evaluation of the EDTA-modified carbapenem inactivation method (eCIM), an assay for discriminating between serine- and metal-dependent (i.e., metallo-β-lactamases MBLs) carbapenemases when used in conjunction with the modified carbapenem inactivation method (mCIM). The eCIM had an overall sensitivity and specificity of 100% and was adopted by the Clinical and Laboratory Standards Institute as a method to use in combination with the mCIM to identify MBL-producing
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