PurposeThe purpose of this study is to investigate mentorship practices during the COVID-19 pandemic and to consider how mentorship could be improved to support students of educational leadership ...(EDLE) during crises.Design/methodology/approachParticipants in this collective self-study were four faculty members (i.e. the authors) within an EDLE program in one public, research-intensive university in the southern USA. Data sources were memos, email correspondence, reflective dialogue, course evaluations and meeting notes. Analysis involved dialogic engagement among the research team to identify emergent themes.FindingsAnalysis revealed five themes that reflect our collective experiences as mentors during the pandemic. These themes were challenges created by dismantled systems; meeting students' needs for understanding, flexibility and meaningful learning experiences; evolving personal–professional boundaries; grappling with our own sense-making and well-beingness; and clarifying values and priorities.Practical implicationsThe pandemic exemplifies the need for a deeper conceptualization of mentorship that stimulates more intimate, compassionate relationships between mentors and mentees. When mentorship is grounded in compassion, intimacy and mutual vulnerability, it demonstrates a genuine ethic of care and concern for others that is supportive of well-being and serves as a model for mentees entering the profession.Originality/valueThis paper extends disciplinary knowledge by focusing on the mentorship of EDLE students during crises and provides insights on how mentorship could be enacted to mutually support mentor–mentee well-being.
A simple method to produce record concentrations (up to 10 mg mL–1) of high-quality aqueous graphene suspensions by using an ordinary benchtop magnetic stirrer is reported. The shear rates employed ...here are almost 10 times less than those in previous reports, and graphene is efficiently separated from unexfoliated graphite during the synthesis. Systematic optimization of synthesis parameters, such as pH, protein concentration, temperature, stirrer speed, and volume of solution, afforded efficient conversion (100%) of graphite to graphene–aqueous suspensions. The synthesis is readily scaled-up with a continuous flow reactor where the graphene is produced and separated 24/7, with little or no human intervention. Raman spectroscopy confirmed little to no sp3 or oxidative defects, and that the graphene nanosheets consisted of three to five layers. The graphene suspensions were coated on aluminum and tested for thermal conductivity applications. The thermal conductivity of our graphene sample was calculated to be 684 W m–1 K–1, a value greater than that of a commercial sample. The activation energy measured for shear exfoliation by stirring was found to be over 45 billion times smaller than the corresponding thermal activation energy, affording physical insight into the process. We hypothesize that stirring selectively populates translational states that are necessary for exfoliation and thus requires far less energy than conventional exfoliation methods, where the energy is uniformly distributed among all available modes. Therefore, an efficient, convenient, and inexpensive method for graphene production in limited-resource settings is reported here.
Receptors show promise for the transport of monoclonal antibodies (mAbs) across the blood-brain barrier. However, safety liabilities associated with peripheral receptor binding and Fc effector ...function have been reported. We present the Brain Shuttle-mAb (BS-mAb) technology, and we investigate the role of Fc effector function in vitro and in an Fcγ receptor (FcγR)-humanized mouse model. Strong first infusion reactions (FIRs) were observed for a conventional mAb against transferrin receptor (TfR) with a wild-type immunoglobulin G1 (IgG1) Fc. Fc effector-dead constructs completely eliminated all FIRs. Remarkably, no FIR was observed for the BS-mAb construct with a native IgG1 Fc function. Using various BS-mAb constructs, we show that TfR binding through the C-terminal BS module attenuates Fc-FcγR interactions, primarily because of steric hindrance. Nevertheless, BS-mAbs maintain effector function activity when binding their brain target. Thus, mAbs with full effector function can be transported in a stealth mode in the periphery while fully active when engaged with their brain target.
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•Antibody against transferrin receptor induces Fc-mediated first infusion reaction•Brain Shuttle antibody against β-amyloid prevents plaque formation•Effector function hidden in the periphery leads to attenuated first infusion reaction•Results can be explained by the unique binding mode of the Brain Shuttle antibody
Weber et al. show that a Brain Shuttle antibody against amyloid-β prevents plaque formation mediated by the effector function. Their study reveals that the effector function is hidden in the periphery, due to the unique binding mode of the Brain Shuttle, but becomes fully active in the brain.
Distance education as a primary means of instruction is expanding significantly at the college and university level. Simultaneously, the growth of social networking sites (SNS) including Facebook, ...LinkedIn, and MySpace is also rising among today's college students. An increasing number of higher education instructors are beginning to combine distance education delivery with SNSs. However, there is currently little research detailing the educational benefits associated with the use of SNSs. Non-commercial, education-based SNSs, such as Ning in Education, have been recently shown to build communities of practice and facilitate social presence for students enrolled in distance education courses. In order to evaluate the largely unexplored educational benefits of SNSs, we surveyed graduate students enrolled in distance education courses using Ning in Education, an education-based SNS, based on their attitudes toward SNSs as productive online tools for teaching and learning. The results of our study suggest that education-based SNSs can be used most effectively in distance education courses as a technological tool for improved online communications among students in higher distance education courses. (Contains 2 tables.)
In 1990, Congress passed the Breast and Cervical Cancer Mortality Prevention Act because of increases in the number of low‐income and uninsured women being diagnosed with breast cancer. This act ...authorized the Centers for Disease Control and Prevention (CDC) to establish the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to provide high‐quality and timely breast and cervical cancer screening and diagnostic services to low‐income, uninsured women. The program started in 1991, and, in 1993, Congress amended the act to allow the CDC to fund American Indian and Alaska Native tribes and tribal organizations. By 1996, the program was providing cancer screening across the United States. To ensure appropriate delivery and monitoring of services, the program adopted detailed policies on program management, evidence‐based guidelines for clinical services, a systematized clinical data system to track service quality, and key partnerships that expand the program's reach. The NBCCEDP currently funds 67 programs, including all 50 states, the District of Columbia, 5 US territories, and 11 tribes or tribal organizations. Cancer 2014;120(16 suppl):2540‐8. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
The Breast and Cervical Cancer Mortality Prevention Act of 1990 authorized the Centers for Disease Control and Prevention to establish the National Breast and Cervical Cancer Early Detection Program to provide quality breast and cervical cancer screening and diagnostic services to low‐income, uninsured women. The program began in 1991 and has grown to be the only nationwide cancer screening program serving all 50 states, the District of Columbia, 5 US territories, and 11 tribes or tribal organizations.
There are few treatments that slow neurodegeneration in Alzheimer's disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the ...central nervous system is restricted by the blood-brain barrier. This study investigates a bispecific modular fusion protein composed of gantenerumab, a fully human monoclonal anti- amyloid-beta (Aβ) antibody under investigation for AD treatment, with a human transferrin receptor 1-directed Brainshuttle™ module (trontinemab; RG6102, INN trontinemab). In vitro, trontinemab showed a similar binding affinity to fibrillar Aβ40 and Aβ plaques in human AD brain sections to gantenerumab. A single intravenous administration of trontinemab (10 mg/kg) or gantenerumab (20 mg/kg) to non-human primates (NHPs, Macaca fascicularis), was well tolerated in both groups. Immunohistochemistry indicated increased trontinemab uptake into the brain endothelial cell layer and parenchyma, and more homogeneous distribution, compared with gantenerumab. Brain and plasma pharmacokinetic (PK) parameters for trontinemab were estimated by nonlinear mixed-effects modeling with correction for tissue residual blood, indicating a 4-18-fold increase in brain exposure. A previously developed clinical PK/pharmacodynamic model of gantenerumab was adapted to include a brain compartment as a driver of plaque removal and linked to the allometrically scaled above model from NHP. The new brain exposure-based model was used to predict trontinemab dosing regimens for effective amyloid reduction. Simulations from these models were used to inform dosing of trontinemab in the first-in-human clinical trial.
Cysteine-rich knob domains can be isolated from the ultralong heavy-chain complementarity-determining region (CDR) 3, which are unique to a subset of bovine antibodies, to create antibody fragments ...of ~4 kDa. Advantageously, the N- and C- termini of these small binding domains are in close proximity, and we propose that this may offer a practical route to engineer extrinsic binding specificity into proteins. To test this, we transplanted knob domains into various loops of rat serum albumin, targeting sites that were distal to the interface with the neonatal Fc receptor. Using knob domains raised against the clinically validated drug target complement component C5, we produced potent inhibitors, which exhibit an extended plasma half-life
via attenuated renal clearance and neonatal Fc receptor-mediated avoidance of lysosomal catabolism. The same approach was also used to modify a
V
, targeting a framework loop situated at the opposing end of the domain to the CDRs, to produce a small, single-chain bispecific antibody and a dual inhibitor of Complement C3 and C5. This study presents new protein inhibitors of the complement cascade and demonstrates a broadly applicable method to engineer target specificity within polypeptide chains, using bovine knob domains.
A prospective, multi-center study (RECON) was conducted to evaluate the clinical outcomes of pericardial closure using a decellularized extracellular matrix (ECM) graft derived from porcine small ...intestinal submucosa.
Patients indicated for open cardiac surgery with pericardial closure using ECM were eligible for the RECON study cohort. Postoperative complications and readmission of the RECON patients were compared to the patient cohort in the Nationwide Readmissions Database (NRD). Inverse probability of treatment weighting was used to control the differences in patient demographics, comorbidities, and risk factors.
A total of 1420 patients at 42 centers were enrolled, including 923 coronary artery bypass grafting (CABG) surgeries and 436 valve surgeries. Significantly fewer valve surgery patients in the RECON cohort experienced pleural effusion (3.1% vs. 13.0%; p < 0.05) and pericardial effusion (1.5% vs. 2.6%; p < 0.05) than in the NRD cohort. CABG patients in the RECON cohort were less likely to suffer bleeding (1.2% vs. 2.9%; p < 0.05) and pericardial effusion (0.2% vs. 2.2%, p < 0.05) than those in the NRD cohort. The 30-day all-cause hospital readmission rate was significantly lower among RECON patients than NRD patients following both valve surgery (HR: 0.34; p < 0.05) and CABG surgery (HR: 0.42; p < 0.05). In the RECON study, 14.4% of CABG patients and 27.0% of valve patients had postoperative atrial fibrillation as compared to previously reported risks, which generally ranges from 20 to 30% after CABG and from 35 to 50% after valve surgery.
Pericardial closure with ECM following cardiac surgery is associated with a reduction in the proportion of patients with pleural effusion, pericardial effusion, and 30-day readmission compared to a nationwide database.
NCT02073331 , Registered on February 27, 2014.
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