Raising Capital: On pricing, liquidity, and incentives

This thesis aims to foster a greater understanding of primary market functioning. It aims to be of use as an input in the continuous debate on how we can best shape our financial markets to provide greater affluence for society. It contains three essays, included as separate chapters, that each focus on a separate question related to raising capital via primary markets. Chapter 2 deals with the market for initial public stock offerings. It shows that stereotypes about industry performance are related to the opening performance of newly issued stocks. Chapter 3 deals with the general market for new equity. It shows that firms issue more new stocks when markets become more liquid; i.e., when it becomes easier to buy or sell large quantities of stocks without having to make adjus

From Project to Strategic Vision: Taking the Lead in Research Data Management Support at the University of Sydney Library

This paper explores three stories, each occurring a year apart, illustrating an evolution toward a strategic vision for Library leadership in supporting research data management at the University of Sydney. The three stories describe activities undertaken throughout the Seeding the Commons project and beyond, as the establishment of ongoing roles and responsibilities transition the Library from project partner to strategic leader in the delivery of research data management support. Each story exposes key ingredients that characterise research data management support: researcher engagement; partnerships; and the complementary roles of policy and practice

Higher incidence of clear cell adenocarcinoma of the cervix and vagina among women born between 1947 and 1971 in the United States

Although the association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma of the cervix and vagina (CCA) was first reported among young women, subsequent case reports and cohort studies suggest that an elevated risk for CCA may persist with age. Data from the National Program of Cancer Registries (NPCR) and the Surveillance, Epidemiology and End Results (SEER) Program were used to construct indirect standardized incidence ratios (SIR) comparing CCA risk among women born during the exposure period 1947 through 1971, when DES was prescribed to pregnant women, to the relevant time period for nonexposed women born before or after DES exposure period. CCA incidence among the women born before the DES exposure period (ages 30–54 at diagnosis of CAA) or after the DES exposure period (ages 15–29 at diagnosis) were used to calculate the expected rates for women born during the DES exposure period. Among women aged 15–29 years, CCA risk increased with age and peaked in the 25–29 year age group, but the risk estimates were unstable (SIR = 6.06; 95% CI: 0.97, −251.07, SEER data). Among women aged 40–54 years, CCA risk was greatest in the 40–44 year age group (SIR = 4.55; 95% CI: 1.11, 40.19, SEER data and SIR = 3.94; 95% CI: 1.06, 33.01, NPCR/SEER data) and remained significantly elevated throughout this age group in the combined data set. Risk was not elevated among women aged 30–39 years. The observed risk of CCA, if causally related to DES exposure, reflects a persistent health impact from in utero exposure that is widespread in the general population. When assessing a woman’s cancer risks, whether her mother took DES while pregnant may still be a relevant aspect of the medical history for women born during the period of DES use in pregnancy

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19∗

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort (n = 214 patients) was 53% and 60% in ward and ICU starters, respectively (p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p &lt; 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pao2:Fio2ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values &gt; 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.</p

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

Surrogate endpoint biomarkers for cervical cancer chemoprevention trials

Cervical intraepithelia neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve as both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention of progression. In planning chemopreventive trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38459/1/240590915_ftp.pd