Driven to excess? Linking calling, character and the (mis)behaviour of marketers

We are presently at a point of unique circumstantial convergence where recession, an increased emphasis on business ethics, and marketer’s reluctance to accept shifting social agendas have combined to identify the need for a new approach to marketing. Using concepts from the human resources, marketing and psychology literatures, and especially Erich Fromm’s ideas concerning economic character, this paper posits that marketers – as a professional community – are driven to promote consumerist outcomes; victims of an automaton amalgam of calling and character. The analysis suggests the vulnerability of both marketer and consumer are mutually reinforcing and that we need, somehow, to break this damaging cycle of dependence. We know little, however, about how marketers think and feel about their discipline, so this paper also promotes an agenda for marketer behaviour research, as a countervailing balance to a currently disproportionate focus on the consumer

Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial

Background Children with severe atopic dermatitis (AD) have limited treatment options. Objective We report efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6–11 years with severe AD inadequately controlled with topical therapies. Methods In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300mg dupilumab every 4 weeks (300mg-q4w), a weight-based regimen of dupilumab every 2 weeks (100mg-q2w, baseline weight <30kg; 200mg-q2w, ≥30kg), or placebo; with concomitant medium-potency TCS. Results Both the q4w and q2w dupilumab+TCS regimens resulted in clinically meaningful and statistically significant improvement in signs, symptoms, and quality of life (QoL) versus placebo+TCS in all prespecified endpoints. For q4w/q2w/placebo, 32.8%/29.5%/11.4% of patients achieved Investigator’s Global Assessment scores of 0/1; 69.7%/67.2%/26.8% achieved ≥75% improvement in Eczema Area and Severity Index scores; and 50.8%/58.3%/12.3% achieved ≥4-point reduction in worst itch score. Response to therapy was weight-dependent: optimal dupilumab doses for efficacy and safety were 300mg-q4w in children <30kg and 200mg-q2w in children ≥30kg. Conjunctivitis and injection-site reactions were more common with dupilumab+TCS than placebo+TCS. Limitations Short-term 16-week treatment period; severe AD only. Conclusion Dupilumab+TCS is efficacious and well tolerated in children with severe AD, significantly improving signs, symptoms, and QoL

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A randomized phase II/III study to assess the efficacy of trametinib in patients with recurrent or progressive low-grade serous ovarian or peritoneal cancer

Background: Low-grade serous carcinoma of the ovary/peritoneum (LGSOC) is a rare subtype, accounting for 5-10% of all serous cancers, and is characterized by alterations in the MAPK pathway, relative chemoresistance, and prolonged overall survival (OS) compared to high-grade serous carcinoma. NRG Oncology in the US and the National Cancer Research Network (NCRN) in the UK collaborated on a phase II/III trial to assess the efficacy of a MEK inhibitor trametinib (TRAM) compared to physician’s choice standard of care (SOC) in recurrent LGSOC. Methods: Patients (pts) were randomized 1:1 to receive either TRAM 2 mg daily or 1 of 5 SOC options (weekly paclitaxel, PLD, topotecan, letrozole, or tamoxifen) until disease progression. Pts who progressed on SOC were allowed to crossover to TRAM. The primary objective tested the progression-free survival (PFS) superiority of TRAM vs SOC. Secondary objectives included toxicity, QoL, and objective response rate (ORR) by RECIST 1.1. Exploratory objectives were OS and PFS and ORR after crossover. PFS and OS curves were estimated using the Kaplan-Meier method and compared by a 1-sided, α = 0.025 log-rank test. Results: 260 pts (48.1% had &gt;3 prior lines of therapy) were enrolled between Feb 2014 and Apr 2018. Median follow-up was 31.4 months (mo). PFS was significantly improved for TRAM compared to SOC (median, 13.0 vs 7.2 mo; HR 0.48; 95% CI, 0.36-0.64; P &lt; .0001). ORR was 26.2% for TRAM vs 6.2% for SOC (OR 5.4; 95% CI, 2.39-12.21; P&lt; .0001). Response duration for TRAM was significantly better than for SOC (median, 13.63 mo; 95% CI, 8.08-18.76; vs 5.88 mo; 95% CI, 2.76-12.19). Preliminary analysis of QoL patient reported outcomes shows no significant therapy effects. Main Grade &gt;3 AE in TRAM vs SOC were hematologic toxicity (13.4% vs 9.4%), GI toxicity (27.6% vs 29%), skin toxicity (15% vs 3.9%), and vascular toxicity (18.9% vs 8.6%). Median OS for TRAM vs SOC was 37.0 mo (95% CI, 30.3-NE) vs 29.2 mo (95% CI, 23.5-51.6) (HR 0.75; 95% CI, 0.51-1.11). For 88 pts who crossed over to TRAM, median PFS = 10.8 mo (95% CI, 7.3-12.0), and ORR = 15% (95% CI, 0.07-0.22). Conclusions: Compared to physician’s choice SOC, TRAM was associated with significantly improved PFS and ORR in women with recurrent LGSOC

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial

Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo. Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019). Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9–8.9] and 4.1 [95% CI, 2.2–5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5–8.6] and 3.5 [95% CI, 1.7–5.6] months, respectively) in the HRd and ITT populations. Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure. Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016 Plain language summary: Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients’ quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA. Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses: ● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life. ● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects. Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib – they are known as homologous recombination deficiency (HRd) patients. ● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo. ● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo. Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients’ quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib. © The Author(s), 2022.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Examination of the effects of the relationship marketing orientation on the company performance

Relationship marketing orientation, Company performance, Moderating effect, Turkish beverage industry,