Impact of Timing of Lung resection on Survival for Clinical Stage I and II Lung Cancer

Background: Lung cancer has the highest mortality among the leading cancers in the U.S. Surgical resection is considered as the most effective treatment for lung cancer in early stages, providing greater long-term survival. Clinical guidelines on delays in resection of early-stage lung cancer do not exist. This work aims to assess whether increasing time between diagnosis/first doctor visit and surgery for early stage non-small cell lung cancer (NSCLC) is associated with poorer survival. Methods: We identified a retrospective cohort of incident lung cancer cases who had surgical treatment for lung cancer at our institution between January 2009 and December 2017, and no prior radiation or chemotherapy. We assessed overall survival (OS) and predictors included a) time from first contact to surgery; and b) time from diagnosis to surgery. The association between time from diagnosis and time from first contact to surgery, and survival for patients with early stage NSCLC was assessed using multivariable Cox proportional hazard. We investigated four cut-off points: surgery within 15 days, 30 days, 60 days and 90 days. We controlled for sociodemographic characteristics as well as clinical outcomes. Results: Our cohort comprised 491 patients. The age average was 66.9 years, 61% female, 94.7% white, and 9% never smoked. Clinical Stage 1A and 1B corresponded to 86.5% of patients while in pathological stage it was 76%. The 5-year overall survival was 56.0%. Surgery occurred a median 40 days after the diagnosis and 43 days after the first visit and within 35 days if the first appointment was with a thoracic surgeon. The threshold time associated with statistically significant worse survival was 60 days after diagnosis. Surgery was performed more than 60 days of diagnosis in 115 (25.7%) patients, their OS was significantly worse than patients who had surgery earlier (HR=1.7 [95% CI: 1.1-2.6]). Conclusions: Greater intervals between diagnosis of early-stage NSCLC and surgery are associated with worse survival. Efforts to minimize delays, particularly factors that prolong the period from diagnosis to first contact with a lung cancer provider may improve survival

Hyper-contractility and impaired cGMP signaling in the BKCa channel deletion model of erectile dysfunction

Matthias E. Werner is with the Division of Cardiovascular and Endocrine Science, School of Medicine, University of Manchester, Manchester M13 9NT, UK -- Andrea L. Meredith is with the Department of Physiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA -- Richard W. Aldrich is with the Section of Neurobiology, 1 University Station C7000, The University of Texas at Austin, Austin, TX 78712, USA -- Mark T. Nelson is with the Department of Pharmacology, College of Medicine, University of Vermont, Burlington, VT 05405, USAErectile dysfunction (ED) is frequently elicited by a multiplicity of pathogenic factors, predominantly by impaired formation of and responsiveness to nitric oxide (NO) and the downstream effectors soluble guanylate cyclase (sGC) and cGMP-dependent protein kinase I (PKGI). In smooth muscle, one important target of PKGI is the large conductance, calcium-sensitive potassium (BKCa) channel, which upon activation hyperpolarizes the smooth muscle cell membrane, causing relaxation. In our earlier report [1], we demonstrated that ablation of the gene, encoding for the pore-forming α subunit of the BKCa channel in mice (Slo-/-) induced an increase of corpus cavernosum smooth muscle (CCSM) force oscillations, led to reduced nerve-evoked relaxations and ED. In our current work, we used this ED model to explore the role of the BKCa channel in the NO/cGMP pathway. Electrical field stimulation (EFS)-induced contractions of CCSM strips from Slo-/- mice demonstrated a 53% increase that could be reduced by sildenafil similar to levels observed in strips from wild-type (Slo+/+) mice. In Slo-/- strips precontracted with phenylephrine (PE), SNP and sildenafil induced relaxations, which were diminished by 10% and 7% over Slo+/+, respectively. Neither SNP nor sildenafil was able to reduce the enhanced force oscillations, which were induced by the loss of BKCa channel function. Yet, these oscillations could be completely eliminated by blocking L-type voltage-dependent calcium channels (VDCCs). The latter results indicate that loss of BKCa channel leads to ED and hyper-contractility likely due to instability of membrane potential which activates VDCCs. Moreover, since the relaxing effects of SNP and sildenafil were reduced in Slo-/-, the ED phenotype in our BKCa channel deletion model could also be the consequence of an impaired NO/cGMP signaling [email protected]

Organizational Mortality of Small Firms: The Effects of Entrepreneurial Age and Human Capital

This paper addresses the issue of internal determination of organizational outcomes. It is argued that in small and simply structured organizations a considerable proportion of the variance in organizational activities and outcomes is associated with individuals. In particular, the paper uses human capital theory to derive hypotheses about individual determinants of organizational mortality. These hypotheses are tested with event-history data of firm registrations and de-registrations in a West German region. The hypotheses are corroborated by the data, but the effects may nonetheless be due to processes linking individual characteristics with organizational performance other than those suggested by the human capital approach

Reprint: Learning With a Strategic Management Simulation Q2 Game: A Case Study

The use of simulation games as a pedagogic method is well established though its effective use is context-driven. This study adds to the increasing growing body of empirical evidence of the effectiveness of simulation games but more importantly emphasises why by explaining the instructional design implemented reflecting best practices. This multimethod study finds evidence that student learning was enhanced through the use of simulation games, reflected in the two key themes; simulation games as a catalyst for learning and simulation games as a vehicle for learning. In so doing the research provides one of the few empirically based studies that support simulation games in enhancing learning and, more importantly, contextualizes the enhancement in terms of the instructional design of the curriculum. This research should prove valuable for those with an academic interest in the use of simulation games and management educators who use, or are considering its use. Further, the findings contribute to the academic debate concerning the effective implementation of simulation game-based training in business and management education

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Through a Glass, Darkly:The CIA and Oral History

This article broaches the thorny issue of how we may study the history of the CIA by utilizing oral history interviews. This article argues that while oral history interviews impose particular demands upon the researcher, they are particularly pronounced in relation to studying the history of intelligence services. This article, nevertheless, also argues that while intelligence history and oral history each harbour their own epistemological perils and biases, pitfalls which may in fact be pronounced when they are conjoined, the relationship between them may nevertheless be a productive one. Indeed, each field may enrich the other provided we have thought carefully about the linkages between them: this article's point of departure. The first part of this article outlines some of the problems encountered in studying the CIA by relating them to the author's own work. This involved researching the CIA's role in US foreign policy towards Afghanistan since a landmark year in the history of the late Cold War, 1979 (i.e. the year the Soviet Union invaded that country). The second part of this article then considers some of the issues historians must confront when applying oral history to the study of the CIA. To bring this within the sphere of cognition of the reader the author recounts some of his own experiences interviewing CIA officers in and around Washington DC. The third part then looks at some of the contributions oral history in particular can make towards a better understanding of the history of intelligence services and the CIA

A Role for Adenosine Deaminase in Drosophila Larval Development

Adenosine deaminase (ADA) is an enzyme present in all organisms that catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine. Both adenosine and deoxyadenosine are biologically active purines that can have a deep impact on cellular physiology; notably, ADA deficiency in humans causes severe combined immunodeficiency. We have established a Drosophila model to study the effects of altered adenosine levels in vivo by genetic elimination of adenosine deaminase-related growth factor-A (ADGF-A), which has ADA activity and is expressed in the gut and hematopoietic organ. Here we show that the hemocytes (blood cells) are the main regulator of adenosine in the Drosophila larva, as was speculated previously for mammals. The elevated level of adenosine in the hemolymph due to lack of ADGF-A leads to apparently inconsistent phenotypic effects: precocious metamorphic changes including differentiation of macrophage-like cells and fat body disintegration on one hand, and delay of development with block of pupariation on the other. The block of pupariation appears to involve signaling through the adenosine receptor (AdoR), but fat body disintegration, which is promoted by action of the hemocytes, seems to be independent of the AdoR. The existence of such an independent mechanism has also been suggested in mammals

The Presentation of Temperature Information in Television Broadcasts: What is Normal?

In a typical weather broadcast, observed daily temperature information such as maximum and minimum temperatures are shown and compared to the daily average or “normal”. Such information, however, does not accurately describe whether or not that particular day is fairly typical for that time of year or truly an unusual occurrence. Thus it is suggested that the presentation of temperature information can be augmented with elementary statistical information in order to give a more meaningful presentation of temperature information without the need to explain the basis of such statistical information. A study of the climatological maximum and minimum temperatures over a 30-year period for Columbia, Missouri is performed in order to provide the rationale for displaying a "typical" temperature range. This information was incorporated into television weather broadcasts at KOMU TV-8, which is the campus television station and local NBC affiliate