Since 2009, the U.S. National Science Foundation Directorate for Biological Sciences has funded Research Coordination Networks (RCN) aimed at collaborative efforts to improve participation, learning, ...and assessment in undergraduate biology education (UBE). RCN-UBE projects focus on coordination and communication among scientists and educators who are fostering improved and innovative approaches to biology education. When faculty members collaborate with the overarching goal of advancing undergraduate biology education, there is a need to optimize collaboration between participants in order to deeply integrate the knowledge across disciplinary boundaries. In this essay we propose a novel guiding framework for bringing colleagues together to advance knowledge and its integration across disciplines, the "Five 'C's' of Collaboration: Commitment, Collegiality, Communication, Consensus, and Continuity." This guiding framework for professional network practice is informed by both relevant literature and empirical evidence from community-building experience within the RCN-UBE Advancing Competencies in Experimentation-Biology (ACE-Bio) Network. The framework is presented with practical examples to illustrate how it might be used to enhance collaboration between new and existing participants in the ACE-Bio Network as well as within other interdisciplinary networks.
Background
We previously described experiences of clinicians who published adverse drug reaction reports. We now report on threats and intimidations leveled against clinicians and scientists who ...received publicly documented threats after communicating safety, efficacy, or data integrity findings contrary to corporate interests.
Methods
Data on threats and intimidations were obtained from transcripts of governmental hearings or agencies, university-affiliated reports, media interviews, and investigative journalism articles. Content and timing of threats and intimidation, subsequent harms, numbers of persons seriously injured or who died from individual toxicities, financial payments from sponsors related to safety, efficacy, or data integrity concerns, and civil settlements and criminal findings were evaluated.
Findings
Twenty-six individuals who communicated safety, efficacy, or data integrity concerns were targets of threats and intimidation from corporate employees (twenty-three individuals) or regulatory personnel (three). Seventeen individuals identified instances where pharmaceutical sponsors submitted fraudulent data in support of regulatory approval of a drug or device. Scientist and clinician communications were followed by drug/device withdrawals (fourteen drugs/devices), black box warnings (six drugs), withdrawal of a sponsor’s application for regulatory approval (one device), and delay of approval of a sponsor’s application for regulatory approval (one drug). Actions mainly occurred after persons communicated with pharmaceutical employees (fourteen). Intimidation efforts by corporate personnel included threats of lawsuits (eighteen individuals), hiring private investigators (nine), and public disparagement at conferences (eleven). Related intimidation efforts carried out by academia or regulatory agency superiors included threats of: loss of positions (six), loss of grant funding (two), delays in decisions regarding tenure (two); or reassignment to a low-level position (one). Academic harms included lost: hospital or university appointments (nine and six, respectively), grant funding (two), chairperson title of an international clinical trial group (one), and journal editorial board position (one). Corporate harms included payment of $1 million to defense attorneys in three cases filed against clinicians.
Interpretation
Threats and intimidation carried out by corporate employees and/or academic supervisors followed public communication of concerns regarding patient safety, drug efficacy, or data integrity, including instances where sponsors were identified as having submitted fraudulent data to regulatory or government agencies. Consideration should be given to filing criminal charges against pharmaceutical executives who are discovered by scientists or clinicians to have knowingly submitted fraudulent data to regulatory or governmental agencies, rather than causing the scientists and clinicians who submit such reports to risk losing their reputations and occupations.
Over 400 variants in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) are CF-causing. CFTR modulators target variants to improve lung function, but marked variability in response ...exists and current therapies do not address all CF-causing variants highlighting unmet needs. Alternative epithelial ion channel/transporters such as SLC26A9 could compensate for CFTR dysfunction, providing therapeutic targets that may benefit all individuals with CF. We investigate the relationship between rs7512462, a marker of SLC26A9 activity, and lung function pre- and post-treatment with CFTR modulators in Canadian and US CF cohorts, in the general population, and in those with chronic obstructive pulmonary disease (COPD). Rs7512462 CC genotype is associated with greater lung function in CF individuals with minimal function variants (for which there are currently no approved therapies; p = 0.008); and for gating (p = 0.033) and p.Phe508del/ p.Phe508del (p = 0.006) genotypes upon treatment with CFTR modulators. In parallel, human nasal epithelia with CC and p.Phe508del/p.Phe508del after Ussing chamber analysis of a combination of approved and experimental modulator treatments show greater CFTR function (p = 0.0022). Beyond CF, rs7512462 is associated with peak expiratory flow in a meta-analysis of the UK Biobank and Spirometa Consortium (p = 2.74 × 10
) and provides p = 0.0891 in an analysis of COPD case-control status in the UK Biobank defined by spirometry. These findings support SLC26A9 as a therapeutic target to improve lung function for all people with CF and in individuals with other obstructive lung diseases.
Posttransplant lymphoproliferative disorders (PTLD) remain an uncommon complication of solid organ transplantation with a high mortality rate reported after conventional therapies. Alternative ...treatments such as rituximab have been explored.
Eleven patients with PTLD, who were CD20 positive, received an intravenous dose of rituximab, 375 mg/m2, weekly x 4 weeks, repeated every 6 months for 2 years in responding patients. The median age of the patients was 56 years (range, 43-68 yrs), and 9 patients were male. The type of solid organ transplantation that these patients received included lung (five patients), kidney (four patients), heart (one patient), and kidney/pancreas (one patient). The median time from transplantation to a PTLD diagnosis was 9 months (range, 1-122 mos). Diagnostic B-cell histology was diffuse large cell lymphoma or polymorphous process. No patient had bone marrow or central nervous system involvement. Primary extranodal disease was noted in 82% of patients. Immunosuppressive therapy was decreased at the time of diagnosis.
Rituximab was well tolerated, with mild infusional blood pressure alterations noted in two patients. The median follow-up period was 10 months (range, 1-32 mos). The overall response rate was 64%, with 6 complete responses (CR), 1 partial response, 2 cases of progressive disease, and 2 deaths. The median duration of CR was 8 months (range, 2-19+ mos). The median time to treatment failure was 10 months (range, 5-25+ mos). The median survival was 14 months (range, < 1-32+ mos). Four patients were alive at the time of last follow-up.
Single-agent rituximab may offer a response and survival advantage in patients with PTLD. Further evaluation of rituximab in these disorders, potentially in combination with other therapies, is warranted.
Objective
This study prospectively assessed putative promising biomarkers for use in assessing infants with spinal muscular atrophy (SMA).
Methods
This prospective, multi‐center natural history study ...targeted the enrollment of SMA infants and healthy control infants less than 6 months of age. Recruitment occurred at 14 centers within the NINDS National Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) Network. Infant motor function scales and putative electrophysiological, protein and molecular biomarkers were assessed at baseline and subsequent visits.
Results
Enrollment began November, 2012 and ended September, 2014 with 26 SMA infants and 27 healthy infants enrolled. Baseline demographic characteristics of the SMA and control infant cohorts aligned well. Motor function as assessed by the Test for Infant Motor Performance Items (TIMPSI) and the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP‐INTEND) revealed significant differences between the SMA and control infants at baseline. Ulnar compound muscle action potential amplitude (CMAP) in SMA infants (1.4 ± 2.2 mV) was significantly reduced compared to controls (5.5 ± 2.0 mV). Electrical impedance myography (EIM) high‐frequency reactance slope (Ohms/MHz) was significantly higher in SMA infants than controls SMA infants had lower survival motor neuron (SMN) mRNA levels in blood than controls, and several serum protein analytes were altered between cohorts.
Interpretation
By the time infants were recruited and presented for the baseline visit, SMA infants had reduced motor function compared to controls. Ulnar CMAP, EIM, blood SMN mRNA levels, and serum protein analytes were able to distinguish between cohorts at the enrollment visit.
Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse ...Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting.
We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings.
Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p<0.0018). Manufacturers of four drugs paid $1.7 billion total in criminal fines for failing to inform the FDA and physicians about very serious ADRs. Following FDA approval, the median time to ADR reporting was 7.5 years (Interquartile range 3,13 years). Twelve drugs received Box warnings and one drug received a warning (median, 7.5 years following ADR reporting (IQR 5,11 years). Six drugs and 1 device were withdrawn from marketing (median, 5 years after ADR reporting (IQR 4,6 years)).
Because very serious ADRs impacts are so large, policy makers should consider developing independently funded pharmacovigilance centers of excellence to assist with clinician investigations.
This work received support from the National Cancer Institute (1R01 CA102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; and two Pilot Project grants from the American Cancer Society's Institutional Grant Award to the University of South Carolina (IRG-13–043–01) https://www.cancer.org/ (SH; BS).
Abstract The optimal type and timing of specimens to study the immune responses to cold-adapted influenza vaccine (CAIV) and shedding of vaccine virus are not well established. Healthy adults were ...vaccinated with CAIV ( n = 10) or trivalent influenza vaccine (TIV) ( n = 5). Shedding of vaccine strain influenza B was detected by culture in 6 of 10 CAIV recipients; influenza A was also detected in one of these subjects. Viral shedding by quantitative RT-PCR was detected in 9 of 10 subjects. We detected a ≥2-fold increase in influenza-specific IgA in nasal wash in 80–100% of CAIV recipients following vaccination, but specific IgG increased in neither nasal wash nor saliva. Recipients of TIV had significant increases in specific serum IgG antibodies. Recipients of both CAIV and TIV had significant increases in IFNγ-secreting peripheral blood mononuclear cells (PBMCs). PBMCs from subjects receiving CAIV showed a higher proportion of functional, tissue-tropic T-cells (CD4+CD69+CD18+MIP1α+) specific for homotypic and heterosubtypic strains of influenza by flow cytometry.
Frederick L. Whitam (1933–2009) Vasey, Paul L.; Bartlett, Nancy H.
Archives of sexual behavior,
08/2011, Letnik:
40, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Frederick L. Whitam, 76, Professor Emeritus in Sociology at Arizona State University, died in July 2009 in Tempe,Arizona. A profile of Whitam is presented.
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