Osbornejustice2867
Many global changes take the form of resource enhancements that have potential to transform multiple aspects of ecosystems from slower to faster cycling, including a suite of both above- and belowground variables. We developed a novel analytic approach to measure integrated ecosystem responses to resource-enhancing global changes, and how such whole ecosystem slow-to-fast transitions are linked to diversity and exotic invasions in real-world ecosystems. We asked how 5-yr experimental rainfall and nutrient enhancements in a natural grassland system affected 16 ecosystem functions, pools, and stoichiometry variables considered to indicate slow vs. fast cycling. We combined these metrics into a novel index we termed "slow-fast multifunctionality" and assessed its relationship to plant community diversity and exotic plant dominance. Nutrient and rainfall addition interacted to affect average slow-fast multifunctionality. selleck products Nutrient addition alone pushed the system toward faster cycling, but this effect weakened with the joint addition of rainfall and nutrients. Variables associated with soil nutrient pools and cycling most strongly contributed to this antagonistic interaction. link2 Nutrient and water addition together, respectively, had additive or synergistic effects on plant trait composition and productivity, demonstrating divergence of above- and belowground ecosystem responses. Our novel metric of faster cycling was strongly associated with decreased plant species richness and increased exotic species dominance. These results demonstrate the breadth of interacting community and ecosystem changes that ensue when resource limitation is relaxed.
LMB-100 is an antibody-toxin conjugate with an antimesothelin Fab linked to a 24-kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first-in-human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin.
Cohorts of 1 to 7 patients received intravenous LMB-100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1, 3, and 5 of a 21-day cycle.
Of the 25 patients accrued, 17 had mesothelioma, 3 each had ovarian or pancreatic cancer, and 2 patients had gastric cancer. Dose-limiting toxicities occurred in 2 of 4 patients treated at a dose of 250 µg/kg (capillary leak syndrome) and in 3 of 7 patients treated at a dose of 170 µg/kg (creatinine increase). The MTD of LMB-100 was 140 µg/kg. Of the 10 patients with mesothelioma who were treated at doses of 170 µg/kg or 140 µg/kg, 8 had stable disease and 2 developed progressive disease. Peak LMB-100 plasma. In the current study, the authors determined the safety, maximum tolerated dose, and pharmacokinetics of LMB-100, as well as the generation of antidrug antibodies. Ongoing phase 2 clinical trials are evaluating the combination of LMB-100 plus pembrolizumab in patients with treatment-refractory mesothelioma and non-small cell lung cancer.
Mesothelin, a cell surface antigen, is an attractive target for cancer therapy given its limited expression in normal human tissues and high expression in many human cancers. link3 LMB-100 is a recombinant antimesothelin immunotoxin consisting of a humanized antimesothelin antibody fragment fused to a truncated Pseudomonas exotoxin A. In the current study, the authors determined the safety, maximum tolerated dose, and pharmacokinetics of LMB-100, as well as the generation of antidrug antibodies. Ongoing phase 2 clinical trials are evaluating the combination of LMB-100 plus pembrolizumab in patients with treatment-refractory mesothelioma and non-small cell lung cancer.
Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates.
Relevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included.
Sixty-three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non-neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4-related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias.
Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation.
Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation.
To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial).
Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m
, and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA
<48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m
) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss.
Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better qualityet.The diagnosis of ovarian torsion is challenging and relies mostly on morphologic findings. Occasionally, women or children with acute pelvic pain who have undergone an initial ultrasound (US) evaluation with results interpreted as negative for ovarian torsion will return with recurrent or increasing pain, prompting an US reevaluation. The flipped ovary sign refers to a demonstrable change in the orientation of the ovary on follow-up US examinations, recognized by changing positions of ovarian landmarks established by follicles, cysts, or masses. This sign is valuable for identifying ovarian torsion in these patients, even in the absence of classic morphologic or Doppler features of ovarian torsion.Previously, we introduced DFT-D3(BJ)ωB97X-V and ωB97M-V functionals and assessed them for the GMTKN55 database [Najibi and Goerigk, J Chem. Theory Comput. 2018, 14, 5725]. In this study, we present DFT-D4 damping parameters to build the DFT-D4 counterparts of these functionals and assess these in comparison. We extend our analysis beyond GMTKN55 and especially turn our attention to enzymatically catalyzed and metal-organic reactions. We find that B97M-D4 is now the second-best performing meta-generalized-gradient approximation functional for the GMTKN55 database and it can provide noticeably better organometallic reaction energies compared to B97M-D3(BJ). Moreover, the aforementioned DFT-D3(BJ)-based functionals have not been thoroughly assessed for geometries and herein we close this gap by analyzing geometries of noncovalently bound dimers and trimers, peptide conformers, water hexamers and transition-metal complexes. We find that several of the B97(M)-based methods-particularly the DFT-D4 versions-surpass the accuracy of previously studied methods for peptide conformer, water hexamer, and transition-metal complex geometries, making them safe-to-use, cost-efficient alternatives to the original methods. The DFT-D4 variants can be easily used with ORCA4.1 and above.The COVID-19 pandemic has demonstrated the fragility of clinic-based care for Parkinson's disease and other movement disorders. In response to the virus, many clinics across the world abruptly closed their doors to persons with Parkinson's disease. Fortunately, a niche care model, telemedicine-first described in this journal a generation ago-emerged as the dominant means of providing care. As we adjust to a new normal, we should focus future care not on clinics but on patients. Their needs, guided by clinicians, should determine how care is delivered, whether in the clinic, at home, remotely, or by some combination. Within this patient-centered approach, telemedicine is an attractive care option but not a complete replacement for in-person consultations, which are valuable for specific problems and for those who have access. Now that many clinicians and patients have gained exposure to telemedicine, we can better appreciate its advantages (eg, convenience) and disadvantages (eg, restricted examination). We can also create a new future that utilizes the Internet, video conferencing, smartphones, and sensors. This future will bring many clinicians to one patient, connect individual experts to countless patients, use widely available devices to facilitate diagnosis, and apply novel technologies to measure the disease in new ways. These approaches, which extend to education and research, enable a future where we can care for anyone anywhere and will help us stem the tide of Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.
The COVID-19 pandemic has resulted in massive disruptions to society, to the economy, and to daily life. Some people may turn to alcohol to cope with stress during the pandemic, which may put them at risk for heavy drinking and alcohol-related harms. Research is needed to identify factors that are relevant for coping-motivated drinking during these extraordinary circumstances to inform interventions. This study provides an empirical examination of coping motive pathways to alcohol problems during the early stages of the COVID-19 pandemic.
Participants (N=320; 54.7% male; mean age of 32years) were Canadian adult drinkers who completed an online survey assessing work- and home-related factors, psychological factors, and alcohol-related outcomes over the past 30days, covering a time period beginning within 1month of the initiation of the COVID-19 emergency response.
The results of a theory-informed path model showed that having at least 1 child under the age of 18, greater depression, and lower social connandemic and highlight the need for longitudinal research to establish longer term outcomes of drinking to cope during the pandemic.
