Disruptive innovation in the nonprofit arts and cultural sector

The research conducted in this thesis was undertaken in order to investigate evidence of disruptive innovation in the arts and cultural nonprofit sector of the Greater Philadelphia Region. A survey was sent to 120 individuals involved in the arts and cultural nonprofits sector in the Greater Philadelphia area to identify disruptive innovators. Out of the 120 individuals the survey was sent to, 35 people completed the survey. From their feedback, five disruptors were identified and interviewed. Four met the criteria of this thesis. The findings revealed that there are many nonprofit arts and cultural organizations in the Greater Philadelphia Region that are being very innovative however none that were disruptive. Many of the organizations interviewed are instituting innovative programming to set themselves apart from their competitors. More in-depth research conducted over a longer period of time is required to track the organizations that have been identified to see how they progress. Looking back years from now we may realize that they were already being disruptive compared to the rest of the sector, but only time will tell.M.S., Arts Administration -- Drexel University, 201

Prevalence of Pituitary Hormone Dysfunction, Metabolic Syndrome, and Impaired Quality of Life in Retired Professional Football Players: A Prospective Study

Hypopituitarism is common after moderate and severe traumatic brain injury (TBI). Herein, we address the association between mild TBI (mTBI) and pituitary and metabolic function in retired football players. Retirees 30–65 years of age, with one or more years of National Football League (NFL) play and poor quality of life (QoL) based on Short Form 36 (SF-36) Mental Component Score (MCS) were prospectively enrolled. Pituitary hormonal and metabolic syndrome (MetS) testing was performed. Using a glucagon stimulation test, growth hormone deficiency (GHD) was defined with a standard cut point of 3 ng/mL and with a more stringent body mass index (BMI)-adjusted cut point. Subjects with and without hormonal deficiency (HD) were compared in terms of QoL, International Index of Erectile Function (IIEF) scores, metabolic parameters, and football career data. Of 74 subjects, 6 were excluded because of significant non-football-related TBIs. Of the remaining 68 subjects (mean age, 47.3±10.2 years; median NFL years, 5; median NFL concussions, 3; mean BMI, 33.8±6.0), 28 (41.2%) were GHD using a peak GH cutoff of <3 ng/mL. However, with a BMI-adjusted definition of GHD, 13 of 68 (19.1%) were GHD. Using this BMI-adjusted definition, overall HD was found in 16 (23.5%) subjects: 10 (14.7%) with isolated GHD; 3 (4.4%) with isolated hypogonadism; and 3 (4.4%) with both GHD and hypogonadism. Subjects with HD had lower mean scores on the IIEF survey (p=0.016) and trended toward lower scores on the SF-36 MCS (p=0.113). MetS was present in 50% of subjects, including 5 of 6 (83%) with hypogonadism, and 29 of 62 (46.8%) without hypogonadism (p=0.087). Age, BMI, median years in NFL, games played, number of concussions, and acknowledged use of performance-enhancing steroids were similar between HD and non-HD groups. In summary, in this cohort of retired NFL players with poor QoL, 23.5% had HD, including 19% with GHD (using a BMI-adjusted definition), 9% with hypogonadism, and 50% had MetS. Although the cause of HD is unclear, these results suggest that GHD and hypogonadism may contribute to poor QoL, erectile dysfunction, and MetS in this population. Further study of pituitary function is warranted in athletes sustaining repetitive mTBI

Excellent leukemia control after second hematopoietic cell transplants with unrelated cord blood grafts for post-transplant relapse in pediatric patients

BackgroundPatients with leukemia relapse after allogeneic hematopoietic cell transplant (HCT) have poor survival due to toxicity and disease progression. A second HCT often offers the only curative treatment.MethodsWe retrospectively reviewed our bi-institutional experience (MSKCC-USA; Utrecht-NL) with unrelated cord blood transplantation (CBT) for treatment of post-transplant relapse. Overall survival (OS) and event-free survival (EFS) were evaluated using the Kaplan-Meier method, treatment-related mortality (TRM) and relapse were evaluated using the competing risk method by Fine-Gray.ResultsTwenty-six patients age &lt; 21 years received a second (n=24) or third (n=2) HCT with CB grafts during the period 2009-2021. Median age at first HCT (HCT1) was 11.5 (range: 0.9-17.7) years and all patients received myeloablative cytoreduction. Median time from HCT1 to relapse was 12.8 (range 5.5-189) months. At CBT, median patient age was 13.5 (range 1.4-19.1) years. Diagnoses were AML: 13; ALL: 4, MDS: 5, JMML: 2; CML: 1; mixed phenotype acute leukemia: 1. Sixteen patients (62%) were in advanced stage, either CR&gt;2 or with active disease. Median time from HCT1 to CBT was 22.2 (range 7-63.2) months. All patients engrafted after CBT. Thirteen patients developed acute GvHD; 7 had grade III or IV. With a median survivor follow-up of 46.6 (range 17.4-155) months, 3-year OS was 69.2% (95% CI 53.6-89.5%) and 3-year EFS was 64.9% (95% CI 48.8-86.4%). Eight patients died, 3 of AML relapse and 5 due to toxicity (respiratory failure [n=4], GvHD [n=1]) at a median time of 7.7 (range 5.9-14.4) months after CBT. Cumulative incidence of TRM at 3 years was 19.2% (95% CI 4.1-34.4%). Notably, all TRM events occurred in patients transplanted up to 2015; no toxicity-related deaths were seen in the 16 patients who received CBT after 2015. Cumulative incidence of relapse was 15.9% (95% CI 1.6-30.2%) at 3 years, remarkably low for these very high-risk patients.ConclusionsSurvival was very encouraging following CB transplants in pediatric patients with recurrent leukemia after first HCT, and TRM has been low over the last decade. CBT needs to be strongly considered as a relatively safe salvage therapy option for post-transplant relapse

Diel surface temperature range scales with lake size

Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at Diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of Diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface Diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km2, increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer Diel ranges in their near-surface temperatures of between 4 and 7°C. Large Diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored

Diel surface temperature range scales with lake size

Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km2, increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer diel ranges in their near-surface temperatures of between 4 and 7°C. Large diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Dual Commitments to Organizations and Professions: Different Motivational Pathways to Productivity

Commitments to organizations and professions have important implications for behavior in the workplace, but little is known about how these dual commitments combine to affect organizational outcomes. We present a model proposing that commitment to professions influences productivity through a positive effect on intrinsic motivation and a negative effect on extrinsic motivation. Commitment to organizations, conversely, is hypothesized to have a negative effect on intrinsic motivation and a positive effect on extrinsic motivation. We tested the model with a sample of 237 tenured management professors and, overall, the model fit the data well and better than less parsimonious models or ones positing reverse causality. Commitment to the profession was positively related to intrinsic motivation to engage in research and, through this effect, resulted in more challenging research goals, increased commitment to those goals, more hours spent on research, and greater research productivity. Commitment to the organization (university) was positively related to extrinsic motivation and negatively related to intrinsic motivation and was unrelated to goal level, goal commitment, hours spent on research, and research productivity. Our model makes a unique theoretical contribution by revealing the differing paths by which commitments to organizations and professions affect work outcomes, and our results support and extend commitment theory and offer unique insights into posttenure productivity