Venture creation in the aftermath of COVID-19: The impact of US governor party affiliation and discretion.

In the USA, governors became central figures in the fight against the novel coronavirus. In many cases, state leaders were forced to choose between preserving life and protecting economic livelihood. While prior research has underscored the important role that US governors played in implementing healthcare policies at the onset of the COVID-19 pandemic, we know little about how characteristics of state leaders impacted self-employment. In this paper, we draw from upper echelons theory to examine how governor party and discretion impacted venture creation in the food and restaurant industry. Interestingly, we find no significant relationship between governor party and venture creation. However, we find that when the governor and legislature were unified in their political party - irrespective of party line - there were a higher number of new food and restaurant ventures created. We also found this effect to be strengthened when small business unemployment levels were higher. We explore the implications of these results for how unity of command may be beneficial during times of crisis.

Induction Therapy with Bortezomib and Dexamethasone and Conditioning with High-Dose Melphalan and Bortezomib Followed by Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis: Long-Term Follow-Up Analysis.

In immunoglobulin light-chain (AL) amyloidosis, the depth of hematologic response to treatment is associated with improved survival and organ responses. We conducted a clinical trial using bortezomib in induction and in conditioning with melphalan before stem cell transplantation (SCT) for AL amyloidosis. The results of this clinical trial with a median follow-up of 36 months have been reported previously. Here we report the long-term results of this clinical trial with a median follow-up of 77 months. We describe survival, durability of hematologic and organ responses, and relapse rates. Thirty-five patients were enrolled between 2010 and 2013. Hematologic complete response and very good partial response (VGPR) were noted in 100% (27 of 27) of the evaluable patients at 6 months post-SCT. Four patients (15%) had hematologic relapse at a median of 42 months, and 1 patient (3.7%) had organ progression despite maintaining a VGPR at 37 months. The median overall survival and progression-free survival have not yet been reached at the time of this report. Renal and cardiac responses occurred in 65% and 88%, respectively, at 5 years post-SCT. The median time to renal and cardiac response was 12 months and 6 months, respectively. In conclusion, incorporating bortezomib into induction and conditioning yielded durable hematologic responses of AL amyloidosis, with corresponding organ responses and prolonged survival.

3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.

The mortality caused by tuberculosis (TB) infections is a global concern, and there is a need to improve understanding of the disease. Current in vitro infection models to study the disease have limitations such as short investigation durations and divergent transcriptional signatures. This study aims to overcome these limitations by developing a 3D collagen culture system that mimics the biomechanical and extracellular matrix (ECM) of lung microenvironment (collagen fibers, stiffness comparable to in vivo conditions) as the infection primarily manifests in the lungs. The system incorporates Mycobacterium tuberculosis (Mtb) infected human THP-1 or primary monocytes/macrophages. Dual RNA sequencing reveals higher mammalian gene expression similarity with patient samples than 2D macrophage infections. Similarly, bacterial gene expression more accurately recapitulates in vivo gene expression patterns compared to bacteria in 2D infection models. Key phenotypes observed in humans, such as foamy macrophages and mycobacterial cords, are reproduced in the model. This biomaterial system overcomes challenges associated with traditional platforms by modulating immune cells and closely mimicking in vivo infection conditions, including showing efficacy with clinically relevant concentrations of anti-TB drug pyrazinamide, not seen in any other in vitro infection model, making it reliable and readily adoptable for tuberculosis studies and drug screening.

Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages.

Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5-2 µm) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and led to enhanced anti-bacterial function when compared to non-modified rifampicin-loaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells.

Impact of Human T Cell Lymphotropic Virus Type 1 and 2 Infection on Survival Following Stem Cell Transplantation.

Human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) are delta retroviruses. HTLV-1 may lead to complications, including adult T cell leukemia-lymphoma (ATLL) and HTLV-1-associated myelopathy. Immunosuppression may result in progression from an asymptomatic carrier state to ATLL. Data on the safety of stem cell transplantation (SCT) in patients with HTLV-1/2 infection are lacking. The Center for International Blood and Marrow Transplant Research database was queried for patients who tested positive for HTLV infection in the pretransplantation workup and underwent either autologous SCT (autoSCT) or allogeneic SCT (alloSCT). Patients were excluded if they underwent SCT for ATLL. The primary outcome was overall survival (OS) at 3 years and 4 years post-SCT. In those who underwent autoSCT, 54 patients were HTLV-positive and 9836 were HTLV-negative. In those who underwent alloSCT, 105 patients were HTLV-positive and 18,077 were HTLV-negative. No difference in OS was noted between the HTLV-positive and HTLV-negative patients at 3 years post-autoSCT (76% versus 77%; P = .916). Inferior OS (32% versus 46%; P = .017) and nonrelapse mortality (35% versus 27%; P = .030) were observed in HTLV-positive patients at 4 years post-alloSCT. Future work should examine the mechanism by which HTLV-1/2 impact survival in alloSCT recipients.

Identifying Actionable Causes of Potentially Avoidable Readmissions to an Oncology Service at a Safety Net Hospital.

PURPOSE: Hospital readmissions occur commonly in those receiving cancer care and result in impaired quality of life and increased costs. Causes of readmission in safety net hospitals that serve vulnerable populations are not well understood. The primary goal of this project was to identify potentially avoidable and intervenable causes of readmissions to an urban safety net hospital. METHODS: A retrospective chart review was performed on patients who were readmitted within 30 days of discharge from the hematology and oncology service at Boston Medical Center over the 6-month period between October 2018 and March 2019. Charts were reviewed by three internal medicine residents and discussed under the supervision of an attending oncologist. RESULTS: Two hundred ninety-one patient encounters involving 203 unique patients were identified in the 6-month study period. Of these 291 encounters, 80 encounters (27.5%) were followed by a readmission within 30 days and occurred in 61 (30.0%) unique patients. Nineteen (31.1%) of these 61 patients experienced two readmissions within 30 days of discharge. Twenty-five readmissions (31.3%) were classified as potentially avoidable, with the most common cause of potentially avoidable readmissions attributed to ascitic or pleural fluid reaccumulation (8, 32%). The majority of presumed nonpreventable readmissions were due to expected complications of cancer progression and treatment-related side effects. DISCUSSION: In conclusion, readmissions were common, and a modifiable reason for 30-day readmissions was identified. Addressing recurrent ascitic and pleural fluid reaccumulation in the outpatient setting could help to reduce inpatient hospital readmission on an inpatient oncology service.

Rapamycin-PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints.

Osteoarthritis (OA) is a joint disease characterized by progressive damage of articular cartilage and the adjoining subchondral bone. Chondrocytes, the primary cells of the cartilage, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Rapamycin, a potent immunomodulator, has shown promise in OA treatment. It activates autophagy and is known to prevent senescence. However, its clinical translation for OA is hampered due to systemic toxicity as high and frequent doses are required. Here, we have fabricated rapamycin encapsulated poly(lactic-co-glycolic acid) (PLGA) based carriers that induced autophagy and prevented cellular senescence in human chondrocytes. The microparticle (MP) delivery system showed sustained release of the drug for several weeks. Rapamycin microparticles protected in vitro cartilage mimics (micromass cultures) from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect under oxidative and genomic stress conditions. These microparticles also exhibited a residence time of ∼30 days after intra-articular injections in murine knee joints. Such particulate systems are promising candidates for intra-articular delivery of rapamycin for the treatment of osteoarthritis.

The effect of gender stereotype activation on entrepreneurial intentions.

In this study, the impact of implicit and explicit activation of gender stereotypes on men's and women's intentions to pursue a traditionally masculine career, such as entrepreneurship, was examined. On the basis of stereotype activation theory, it was hypothesized that men and women would confirm the gender stereotype about entrepreneurship when it was presented implicitly but disconfirm it when it was presented explicitly. Hypotheses were tested by randomly assigning 469 business students to one of 6 experimental conditions and then measuring their entrepreneurial intentions. Results supported the hypothesis when entrepreneurship was associated with stereotypically masculine characteristics but not when it was associated with traditionally feminine characteristics. Men also had higher entrepreneurial intention scores compared with women when no stereotypical information about entrepreneurship was presented, suggesting that underlying societal stereotypes associating entrepreneurship with masculine characteristics may influence people's intentions. However, men and women reported similar intentions when entrepreneurship was presented as gender neutral, suggesting that widely held gender stereotypes can be nullified. Practical implications and directions for future research are discussed.

Do women CEOs face greater threat of shareholder activism compared to male CEOs? A role congruity perspective.

We examine the glass cliff proposition that female CEOs receive more scrutiny than male CEOs, by investigating whether CEO gender is related to threats from activist investors in public firms. Activist investors are extraorganizational stakeholders who, when dissatisfied with some aspect of the way the firm is being managed, seek to change the strategy or operations of the firm. Although some have argued that women will be viewed more favorably than men in top leadership positions (so-called "female leadership" advantage logic), we build on role congruity theory to hypothesize that female CEOs are significantly more likely than male CEOs to come under threat from activist investors. Results support our predictions, suggesting that female CEOs may face additional challenges not faced by male CEOs. Practical implications and directions for future research are discussed. (PsycINFO Database Record

Merging Outpatient Addiction and Opioid-Maintenance Programs During A Disaster: Lessons From Hurricane Sandy.

OBJECTIVE: After Hurricane Sandy flooded Bellevue Hospital in New York City, its opiate maintenance patients were displaced and Bellevue's outpatient program was temporarily merged with the program at Metropolitan Hospital for continuation of care. The merger forced Metropolitan to accommodate a program twice as large as its own and required special staff coordination and adjustments in clinical care. METHODS: Physicians, clinicians, and administrators from both institutions participated in interviews regarding the merger. RESULTS: Issues that emerged in the interviews fell into 4 major themes: (1) organization and meshing of professional cultures, (2) regulation, (3) communication, and (4) accommodations. CONCLUSIONS: Despite these barriers, data collected after the merger showed high retention rates and low rates of positive urine toxicology results. (Disaster Med Public Health Preparedness. 2017;11:531-537).

Disparities in Age-Associated Cognitive Decline Between African-American and Caucasian Populations: The Roles of Health Literacy and Education.

OBJECTIVES: To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults. DESIGN: Prospective cohort study. SETTING: Secondary analysis of ElderWalk trial in Boston, Massachusetts. PARTICIPANTS: English-speaking African-American and Caucasian individuals in a walking intervention for community-dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12-month evaluations (N = 198). MEASUREMENTS: Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail-Making Test Part B minus Part B (TMT B-A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12-month cognitive decline were modeled using multivariate linear regression. RESULTS: Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B-A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African-American participants (n = 135) on TMT B-A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B-A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences. CONCLUSION: Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population.

Effect of formulation composition on the properties of controlled release tablets prepared by roller compaction.

This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled-release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t70 values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t70 data and gave an adjusted r-square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and develop more robust processes.

Investigation of potential ionic interactions between anionic and cationic polymethacrylates of multiple coatings of novel colonic delivery system.

The objective of this work was to investigate potential interactions between anionic (Eudragit FS) and cationic (Eudragit RL) polymethacrylates of multiple coatings of a novel colonic drug delivery system. Aqueous films of pure polymers Eudragit FS (FS) and Eudragit RL (RL) and their superimposedfilm (FS-RL) were cast on glass slabs. The potential ionic interactions were studied by analysing the dried films using differential scanning calorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). The glass transition temperatures (Tg) of pure RL and FS were 60 degrees C and 22 degrees C, respectively; FS-RL showed two distinct glass transitions at 59 degrees C and 24 degrees C in the second heating cycle. In the 13C-MAS spectra of the samples in the solid state, no shifts of the resonance could be detected in the superimposed film compared with the pure polymers. The FT-IR spectra of the superimposed film did not show any significant shift of the bands of the -NMe3+ group of RL and the -COO- function of FS compared with the spectra of the pure polymers. No ionic interactions between anionic and cationic polymethacrylates were revealed by DSC, FT-IR, and NMR.