Funding New Business Ventures: Differences In Minority And Non-Minority Family-Owned Business Access To Start-Up Capital

Access to start-up capital is important in starting any business venture. In addition, the source of that start-up capital can sometimes affect the prospects for success in the new business venture. This study examines the differences in the source of start-up funds between male minority and male non-minority family business owners. The findings indicate that male minority family business owners more often use credit cards and gifts from family as a source of start-up funds whereas the male non-minority family business owners rely more often on bank loans. The authors propose a more extensive survey of a larger sample of family business owners in order to further identify differences in source of start-up capital between male minority and male non-minority family business owners

The ages of quasar host galaxies

We present the results of fitting deep off-nuclear optical spectroscopy of radio-quiet quasars, radio-loud quasars and radio galaxies at z ~ 0.2 with evolutionary synthesis models of galaxy evolution. Our aim was to determine the age of the dynamically dominant stellar populations in the hos t galaxies of these three classes of powerful AGN. Some of our spectra display residual nuclear contamination at the shortest wavelengths, but the detailed quality of the fits longward of the 4000A break provide unequivocal proof, if further proof were needed, that quasars lie in massive galaxies with (at least at z ~ 0.2) evolved stellar populations. By fitting a two-component model we have separated the very blue (starburst and/or AGN contamination) from the redder underlying spectral energy distribution, and find that the hosts of all three classes of AGN are dominated by old stars of age 8 - 14 Gyr. If the blue component is attributed to young stars, we find that, at most, 1% of the baryonic mass of these galaxies is involved in star-formation activity at the epoch of observation. These results strongly support the conclusion reached by McLure et al. (1999) that the host galaxies of luminous quasars are massive ellipticals which formed prior to the peak epoch of quasar activity at z ~ 2.5.Comment: 24 pages, LaTeX, uses MNRAS style file, incorporates 19 postscript figures, final version, to be published in MNRA

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ? 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics.RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001).CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS

Measurement of Hydrogen Peroxide Influx Into Cells: Preparation For Measurement Using On-Chip Microelectrode Array

Hydrogen peroxide (H2O2) is commonly known as a toxic reactive oxidative species (ROS) for cells. Recent studies have found evidence that H2O2 is also an important cellular signalling molecule. Quantifying cellular influx of H2O2 will contribute to researchers’ understanding of the role H2O2 plays in healthy cells and cells involved in the progression of cancers and degenerative diseases. This work utilizes an assay kit and fluorescence techniques to evaluate cell lines and conditions to create a model biological system for measuring cellular H2O2 consumption. Pancreatic beta cells (MIN6), astrocytes, and glioblastoma cells (GBM43 and GBAM1) were placed in 10 μM and 20 μM H2O2 solutions for up to 5 hours. The consumption of H2O2 was measured using an Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit (Molecular Probes/Invitrogen). GBAM1 cells exposed to 20 μM H2O2 displayed the fastest rate of H2O2 consumption (4.8 ± 1.2 nmol H2O2/min/106 cells), followed by GBM43 cells (1.5±0.46), astrocytes (1.1±0.24), and MIN6 cells (0.29±0.075). Additionally, the rate of consumption increased with increases in H2O2 concentration. In the future, an on-chip micro-electrode array (MEA) will be used for real-time electrochemical experiments to measure influx of H2O2 by astrocytes and GBAM1 cells with spatio-temporal resolution that the current techniques lack. The results from the electrochemical experiments will be compared to results from the assay kit to determine the ability of the MEA to accurately measure H2O2 concentration and flux. The MEA can be extended to a wide variety of cellular environments for analysis of additional real-time biological events

Cellular Model of Hydrogen Peroxide Release: In Preparation for On-Chip Sensor Measurements

Hydrogen peroxide is traditionally associated with cellular damage; however, recent studies show that low levels of H2O2 are released by cells as part of normal intercellular communication. The mechanisms of hydrogen peroxide transport, uptake and release, and biological effects are not yet well known but have important implications for cancer, stem cells, and aging. Standard H2O2 assays cannot make spatially or temporally resolved quantitative measurements at a cellular scale. Previously we developed a microelectrode array (MEA) and calibration methods for quantifying H2O2 gradients in space and time. The sensor was validated using artificial H2O2 gradients at subsecond and micrometer scale resolutions. The present study begins cellular work on H2O2 release to identify a cellular model system for MEA sensor testing. The morphology and H2O2 release from U937 human monocytes were analyzed after stimulation with ionomycin (1.2 ug/mL) and/or phorbol 12-myristate 13-acetate (PMA). Monocytes were stimulated with PMA (10 ng/mL to 150 ng/mL) for six hours. Hydrogen peroxide release was quantified over time using a traditional amplex red flurometric assay method. Mouse pancreatic beta (MIN6) cells were also tested as a negative control. Monocytes stimulated with PMA alone produced, on average, three times more H2O2 than those stimulated with ionomycin or a combination. Monocytes without ionomycin released H2O2 at 18.34 pmol/min/106 cells at 25 ng/mL of PMA. Ten, 25, and 100 ng/mL of PMA produced H2O2 significantly faster than the non-stimulated control. No significant difference was seen between PMA concentrations when ionomycin was added. These results indicate that PMA stimulated human monocytes may serve as a good model system for cellular validation of the H2O2 MEAs. In the future, biofunctionalization of the electrodes for additional molecular specificity will allow for the expansion of the method to other analytes, giving the sensor potential use in non-traditional lab environments with the ability to perform multiple assays autonomously

Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort

Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients’ health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60−75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Results: Overall health care costs ranged from $26,889 (A1) to$42,139 (A3), and from $28,627 (G2) to$42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3]). Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers

Pseudomonas aeruginosa is capable of natural transformation in biofilms

Natural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation. P. aeruginosa has a remarkable level of genome plasticity and diversity that suggests a high degree of horizontal gene transfer and recombination but is thought to be incapable of natural transformation. Here we show that P. aeruginosa possesses homologues of all proteins known to be involved in natural transformation in other bacterial species. We found that P. aeruginosa in biofilms is competent for natural transformation of both genomic and plasmid DNA. Furthermore, we demonstrate that type-IV pili (T4P) facilitate but are not absolutely essential for natural transformation in P. aeruginosa

Evidence of Molecular Evolution Driven by Recombination Events Influencing Tropism in a Novel Human Adenovirus that Causes Epidemic Keratoconjunctivitis

In 2005, a human adenovirus strain (formerly known as HAdV-D22/H8 but renamed here HAdV-D53) was isolated from an outbreak of epidemic keratoconjunctititis (EKC), a disease that is usually caused by HAdV-D8, -D19, or -D37, not HAdV-D22. To date, a complete change of tropism compared to the prototype has never been observed, although apparent recombinant strains of other viruses from species Human adenovirus D (HAdV-D) have been described. The complete genome of HAdV-D53 was sequenced to elucidate recombination events that lead to the emergence of a viable and highly virulent virus with a modified tropism. Bioinformatic and phylogenetic analyses of this genome demonstrate that this adenovirus is a recombinant of HAdV-D8 (including the fiber gene encoding the primary cellular receptor binding site), HAdV-D22, (the ε determinant of the hexon gene), HAdV-D37 (including the penton base gene encoding the secondary cellular receptor binding site), and at least one unknown or unsequenced HAdV-D strain. Bootscanning analysis of the complete genomic sequence of this novel adenovirus, which we have re-named HAdV-D53, indicated at least five recombination events between the aforementioned adenoviruses. Intrahexon recombination sites perfectly framed the ε neutralization determinant that was almost identical to the HAdV-D22 prototype. Additional bootscan analysis of all HAdV-D hexon genes revealed recombinations in identical locations in several other adenoviruses. In addition, HAdV-D53 but not HAdV-D22 induced corneal inflammation in a mouse model. Serological analysis confirmed previous results and demonstrated that HAdV-D53 has a neutralization profile representative of the ε determinant of its hexon (HAdV-D22) and the fiber (HAdV-D8) proteins. Our recombinant hexon sequence is almost identical to the hexon sequences of the HAdV-D strain causing EKC outbreaks in Japan, suggesting that HAdV-D53 is pandemic as an emerging EKC agent. This documents the first genomic, bioinformatic, and biological descriptions of the molecular evolution events engendering an emerging pathogenic adenovirus

No difference in radiologic outcomes for natalizumab patients treated with extended interval dosing compared with standard interval dosing: Real-world evidence from MS PATHS

BACKGROUND: Extended interval dosing (EID; average dosing interval approximately every 6 weeks) of natalizumab is associated with significantly lower risk of progressive multifocal leukoencephalopathy than standard interval dosing (SID; every 4 weeks) in patients with relapsing-remitting multiple sclerosis (MS). Real-world studies, though limited, suggest that natalizumab effectiveness is generally maintained in patients who switch to EID after initiation of stable treatment with SID. MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions) is a collaborative, multicenter learning health system that generates real-world clinical and MRI data using highly standardized acquisition protocols. We compared MRI outcomes in MS PATHS patients treated with natalizumab EID versus SID. We also compared MRI outcomes in patients treated with natalizumab (EID and/or SID) versus injectable MS platform therapy. METHODS: Natalizumab infusion data from the TOUCH Prescribing Program database and MS PATHS MRI assessment data from seven US sites as of July 23, 2020, were used to identify patients with relapsing-remitting MS who had received natalizumab EID or SID in the interval between two MRI scans (an MRI segment). Patients who received injectable platform MS therapy between two MRI scans were also identified. MRI data were used to determine the incidence rate and odds of developing new or enlarging T2 lesions, annualized percentage change in T2 lesion volume (T2LV), and annualized percentage change in brain parenchymal fraction (BPF). MRI outcomes were compared for 1) natalizumab EID treatment versus natalizumab SID treatment, 2) natalizumab treatment (EID + SID) versus platform therapy, and 3) natalizumab EID versus platform therapy. Propensity score-based weighting or matching were used to balance covariates at the start of MRI segments for all comparisons. RESULTS: The MRI outcomes observed with natalizumab EID treatment did not differ significantly from those observed with natalizumab SID treatment. The odds ratio for any new or enlarging T2 lesion was 1.07 (95% confidence interval [CI]: 0.93, 1.24; p = 0.355), and the rate ratio (95% CI) for new or enlarging T2 lesions was 1.62 (0.93, 2.82; p = 0.090). Differences (95% CI) between EID and SID patients in mean annualized percentage change in T2LV and BPF were 1.56% (-3.77%, 6.90%; p = 0.566) and -0.11% (-0.25%, -0.10%; p = 0.096), respectively. Conversely, when MRI outcomes in natalizumab and platform therapy patients were compared, there were significant differences favoring natalizumab in all assessments: the odds of any new or enlarging T2 lesion (odds ratio: 0.69 [95% CI: 0.64, 0.75]; p\u3c0.001), the incidence rate of new or enlarging T2 lesions (rate ratio: 0.47 [95% CI: 0.37, 0.61]; p\u3c0.001), annualized percentage change (decrease) in T2LV (difference: -3.68% [95% CI: -7.06%, -0.30%]; p = 0.033), and annualized percentage change (increase) in BPF (difference: 0.22% [95% CI: 0.16%, 0.29%]; p\u3c0.001). Results of the subgroup comparison of natalizumab EID patients with platform therapy patients were similar to those of the overall-natalizumab-group-versus-platform-therapy comparison. CONCLUSIONS: The results indicate that natalizumab EID and SID provide comparable real-world effectiveness on quantitative MRI metrics. These data further demonstrate that natalizumab EID can provide superior real-world effectiveness to injectable platform therapy on quantitative MRI metrics