Population density is a fundamental parameter needed to assess wildlife populations but is difficult to obtain given species are often wide-ranging and elusive. Photographic capture-recapture ...techniques do not require direct observations and thus, have become a common approach for estimating wildlife densities. To date, however, these studies have typically focused on single species. Our research explores study design- and analytical-based approaches for expanding photographic capture-recapture studies to assess multiple species simultaneously. We developed a hybrid-sampling scheme that varied inter-camera distances and used simulations to test the efficacy of this design versus a systematically spaced grid in estimating densities of species with varied space use. Through simulations we found the hybrid design facilitated density estimates for a wider range of species with little or no cost in accuracy for most species. We implemented a hybrid camera design across a 1154-km2 area in northern Botswana to estimate densities of lions, spotted hyenas, leopards, wild dogs, servals, civets, and aardwolves. We estimated densities of these small- to wide-ranging carnivores, where all or some portion of the population was individually identifiable, using spatially explicit capture-recapture and mark-resight models. Mean estimates ranged from 1.2 (95% CI = 0.72–1.99) lions to 10.1 (95% CI = 8.69–11.63) spotted hyenas/100 km2 and provided empirical information needed for the conservation of these species in Botswana. Our research demonstrates how photographic capture-recapture studies can be expanded to estimate the densities of multiple species versus just a single species within a community, thus increasing the conservation value of this globally implemented approach.
•Sample design and analytical choices can maximize efficiency of camera trap surveys.•Spacing cameras at a range of distances facilitates multispecies density estimation.•We used one camera grid to estimate densities of 7 carnivore species in Botswana.•Density estimates ranged from 1.2 lions to 10.1 spotted hyenas per 100 km2.•Knowledge of multiple species' densities will facilitate informed conservation plans.
Recombinant immunotoxins (RITs) are chimeric proteins that are being developed for cancer treatment. We have produced RITs that contain PE38, a portion of the bacterial protein Pseudomonas exotoxin ...A. Because the toxin is bacterial, it often induces neutralizing antibodies, which limit the number of treatment cycles and the effectiveness of the therapy. Because T cells are essential for antibody responses to proteins, we adopted an assay to map the CD4 ⁺ T-cell epitopes in PE38. We incubated peripheral blood mononuclear cells with an immunotoxin to stimulate T-cell expansion, followed by exposure to overlapping peptide fragments of PE38 and an IL-2 ELISpot assay to measure responses. Our observation of T-cell responses in 50 of 50 individuals correlates with the frequency of antibody formation in patients with normal immune systems. We found a single, highly immunodominant epitope in 46% (23/50) of the donors. The immunodominant epitope is DRB1-restricted and was observed in subjects with different HLA alleles, indicating promiscuity. We identified two amino acids that, when deleted or mutated to alanine, eliminated the immunodominant epitope, and we used this information to construct mutant RITs that are highly cytotoxic and do not stimulate T-cell responses in many donors.
New perspectives on propofol allergy Johnson, Jessica L; Hawthorne, Ashley; Bounds, Michael ...
American journal of health-system pharmacy,
12/2021, Letnik:
78, Številka:
24
Journal Article
Recenzirano
Propofol is an intravenous sedative used in many patient populations and care settings. Although generally considered safe and effective, the drug has historically been avoided in patients with ...reported allergies to egg, soy, and/or peanut on the basis of the manufacturer's prescribing information. Concerns exist for potential adverse events, increased medication costs, reduced efficacy, and risk of medication errors when using alternative agents. Here we present a critical examination of the literature concerning cross-reactivity of food allergies with propofol to provide evidence-based recommendations for the evaluation and management of potential allergic reactions.
Literature regarding the history of propofol allergy warnings and clinical trial data were assessed to provide an alternative perspective on avoidance of propofol in patients with food allergies. Suspected trigger molecules are discussed, with evaluation of the antigenic potential of excipient ingredients used in the manufacture of multiple propofol formulations. Evidence-based recommendations are provided for pharmacist-led screening of adult patients with reported food allergies to support selection of propofol or alternative therapy.
There is a lack of definitive evidence that propofol must be routinely avoided in patients with reported allergies to egg, soy, and/or peanut products. Data from clinical trials suggest that propofol is safe for patients with nonanaphylactic food allergies. Patients who do experience allergic reactions following administration of propofol should undergo further testing to definitively identify the specific trigger and prevent future unnecessary avoidance of preferred medication regimens. Pharmacists can play an important role in interviewing patients with reported food allergies to better determine the risk vs benefit of propofol avoidance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Thymic stromal lymphopoietin (TSLP) and IL‐7 are cytokines that signal via the IL‐7 receptor alpha (IL‐7Rα) to exert both overlapping and unique functions during early stages of mouse B‐cell ...development. In human B lymphopoiesis, the requirement for IL‐7Rα signaling is controversial and the roles of IL‐7 and TSLP are less clear. Here, we evaluated human B‐cell production using novel in vitro and xenograft models of human B‐cell development that provide selective IL‐7 and human TSLP (hTSLP) stimulation. We show that in vitro human B‐cell production is almost completely blocked in the absence of IL‐7Rα stimulation, and that either TSLP or IL‐7 can provide a signal critical for the production and proliferation of human CD19+ PAX5+ pro‐B cells. Analysis of primary human bone marrow stromal cells shows that they express both IL‐7 and TSLP, providing an in vivo source of these cytokines. We further show that the in vivo production of human pro‐B cells under the influence of mouse IL‐7 in a xenograft scenario is reduced by anti‐IL‐7 neutralizing antibodies, and that this loss can be restored by hTSLP at physiological levels. These data establish the importance of IL‐7Rα mediated signals for normal human B‐cell production.
The production of human B‐cell precursors was studied using novel in vitro and xenograft models that provide selective cytokine stimulation. Data show that the production of human B‐cell precursors, in vitro and in xenograft, is dependent on an IL‐7Rα signal that can be induced by either TSLP or IL‐7.
Thymic stromal lymphopoietin (TSLP) and IL-7 are cytokines that signal via the IL-7 receptor alpha (IL-7Ralpha) to exert both overlapping and unique functions during early stages of mouse B-cell ...development. In human B lymphopoiesis, the requirement for IL-7Ralpha signaling is controversial and the roles of IL-7 and TSLP are less clear. Here, we evaluated human B-cell production using novel in vitro and xenograft models of human B-cell development that provide selective IL-7 and human TSLP (hTSLP) stimulation. We show that in vitro human B-cell production is almost completely blocked in the absence of IL-7Ralpha stimulation, and that either TSLP or IL-7 can provide a signal critical for the production and proliferation of human CD19+ PAX5+ pro-B cells. Analysis of primary human bone marrow stromal cells shows that they express both IL-7 and TSLP, providing an in vivo source of these cytokines. We further show that the in vivo production of human pro-B cells under the influence of mouse IL-7 in a xenograft scenario is reduced by anti-IL-7 neutralizing antibodies, and that this loss can be restored by hTSLP at physiological levels. These data establish the importance of IL-7Ralpha mediated signals for normal human B-cell production.
Immunotoxins based on Pseudomonas exotoxin A (PE) are promising anticancer agents that combine a variable fragment (Fv) from an antibody to a tumor-associated antigen with a 38-kDa fragment of PE ...(PE38). The intoxication pathway of PE immunotoxins involves receptor-mediated internalization and trafficking through endosomes/lysosomes, during which the immunotoxin undergoes important proteolytic processing steps but must otherwise remain intact for eventual transport to the cytosol. We have investigated the proteolytic susceptibility of PE38 immunotoxins to lysosomal proteases and found that cleavage clusters within a limited segment of PE38. We subsequently generated mutants containing deletions in this region using HA22, an anti-CD22 Fv-PE38 immunotoxin currently undergoing clinical trials for B-cell malignancies. One mutant, HA22-LR, lacks all identified cleavage sites, is resistant to lysosomal degradation, and retains excellent biologic activity. HA22-LR killed chronic lymphocytic leukemia cells more potently and uniformly than HA22, suggesting that lysosomal protease digestion may limit immunotoxin efficacy unless the susceptible domain is eliminated. Remarkably, mice tolerated doses of HA22-LR at least 10-fold higher than lethal doses of HA22, and these higher doses exhibited markedly enhanced antitumor activity. We conclude that HA22-LR advances the therapeutic efficacy of HA22 by using an approach that may be applicable to other PE-based immunotoxins.
Graduating student pharmacists who are practice-ready is an essential responsibility of pharmacy programs and heavily emphasized by Accreditation Council of Pharmacy Education (ACPE), pharmacy ...education's accrediting body. Although several studies have examined students' readiness to engage in advanced pharmacy practice experiences (APPE), few studies examine graduating students' readiness to practice. The objective of this study was to examine national trends in graduating pharmacy students' and preceptors' perceptions of students' pharmacy practice preparedness across a six-year time frame (2016–2021) and trends in graduating students' overall impressions of their program and the pharmacy profession across the same time period. A longitudinal descriptive study to examine trends in graduating student and preceptor perception was conducted utilizing data from the 2016–2021 American Association of Colleges of Pharmacy (AACP) Graduating Student Surveys (GSS) (n = 65,461) and Preceptor Surveys (PS) (n = 41,951). Over six years of survey data analyzed, a large percentage of students at both public and private institutions reported they felt prepared for practice (96.5% vs 95.5% respectively, p < 0.001). There was overall agreement (>90%) among preceptors that graduating students were prepared to enter pharmacy practice based on responses, although preceptors had lower levels of agreement compared to students on most statements. Based on the findings, both graduating pharmacy students and preceptors feel that graduates are prepared to practice pharmacy, with consistent trends in perceptions over the last six years. However, results also indicate that a consistent downward trend in students' willingness to pursue pharmacy again, indicating decreased optimism of graduating students for the profession.
We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.
...Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.
Five U.S. medical centers.
Adults inpatients with severe COVID-19 disease and hyperinflammation.
Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo.
The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival, frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio OR = 3.84; p OR > 1 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p OR > 1 86.5% and OR = 2.53; p OR > 1 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p OR < 1; 99.9%) and ICU admission (OR = 0.26; p OR < 1 99.6%); shorter durations of ventilation and ICU stay (risk ratio RR < 0.75; p RR < 1 > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p OR > 1 98.1%; OR = 3.36, p OR > 1 99.6%; and OR = 3.52, p OR > 1 99.8%, respectively).
Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.
Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions ...become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.
To assess how department chairs/administrators define, measure, and evaluate faculty workload to better understand practices within the Academy.
An 18-item survey was distributed to department ...chairs/administrators via American Association of Colleges of Pharmacy Connect. Participants identified if they are a primary decision maker for faculty workload, whether their program has a workload policy, how workload is calculated, and how faculty satisfaction with workload equity is measured.
Of 71 participants initiating the survey, data from 64 participants from 52 colleges/schools were eligible for analysis. Leaders of practice departments reported that their faculty spend an average of 38% of their time on teaching (compared to 46% for non-practice departments), 13% on research (vs 37%), 12% on service (vs 16%), and 36% on clinical practice (vs 0%). Most survey participants (n = 57, 89%) are at schools/colleges with a tenure system, and about 24 participants reported that faculty workload metrics differ across departments/divisions. Teaching assignments and service are reportedly negotiable between faculty and supervisors, and workload expectations are widely variable. The majority indicated they do not analyze faculty satisfaction with workload fairness (n = 35) and faculty do not provide evaluative feedback on how supervisors assign faculty workload (n = 34). Of 6 priorities considered when determining workload, ‘support college/school strategies and priorities’ ranked highest (1.92) and ‘trust between the chair and faculty’ ranked lowest (4.87).
Overall, only half of the participants reported having a clear, written process of quantifying faculty workload. The use of workload metrics may be needed for evidence-based decision-making for personnel management and resource allocation.
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