HECKERT, J. BROOKS. The Analysis and Control of Distribution Costs for Sales Executives and Accountants. Pp. xvii, 420. New York: Ronald Press Co., 1940. $5.00

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66973/2/10.1177_000271624020900143.pd

Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection

Happy Protest Voters: The Case of Rotterdam 1997–2009

Protest parties are on the rise in several European countries. This development is commonly attributed to a growing dissatisfaction with life and associated with declining quality of life in modern society of the lowest social strata. This explanation is tested in a cross-sectional analysis of voting and life-satisfaction in 63 districts of the city of Rotterdam in the Netherlands, where the share of protest voters increased from 10 % in 1994 to 31 % in 2009. Contrary to this explanation protest voting appeared not to be the most frequent in the least happy districts of Rotterdam, but in the medium happy segment. Also divergent from this explanation was that average happiness in city districts is largely independent of local living conditions, but is rather a matter of personal vulnerability in terms of education, income and health. These results fit alternative explanations in terms of mid

Human Cysteine Cathepsins Are Not Reliable Markers of Infection by Pseudomonas aeruginosa in Cystic Fibrosis

Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF. We have characterized the cathepsins in CF expectorations and evaluated their use as markers of colonization by Pseudomonas aeruginosa. The concentrations of active cathepsins B, H, K, L and S were the same in P. aeruginosa-positive (19 Ps+) and P. aeruginosa-negative (6 Ps−) samples, unlike those of human neutrophil elastase. Also the cathepsin inhibitory potential and the cathepsins/cathepsin inhibitors imbalance remained unchanged and similar (∼2-fold) in the Ps+ and Ps− groups (p<0.001), which correlated with the breakdown of their circulating cystatin-like inhibitors (kininogens). Procathepsins, which may be activated autocatalytically, are a potential proteolytic reservoir. Immunoblotting and active-site labeling identified the double-chain cathepsin B, the major cathepsin in CF sputum, as the main molecular form in both Ps+ and Ps− samples, despite the possible release of the ∼31 kDa single-chain form from procathepsin B by sputum elastase. Thus, the hydrolytic activity of cysteine cathepsins was not correlated with bacterial colonization, indicating that cathepsins, unlike human neutrophil elastase, are not suitable markers of P. aeruginosa infection

Attitudes, norms and controls influencing lifestyle risk factor management in general practice

<p>Abstract</p> <p>Background</p> <p>With increasing rates of chronic disease associated with lifestyle behavioural risk factors, there is urgent need for intervention strategies in primary health care. Currently there is a gap in the knowledge of factors that influence the delivery of preventive strategies by General Practitioners (GPs) around interventions for smoking, nutrition, alcohol consumption and physical activity (SNAP). This qualitative study explores the delivery of lifestyle behavioural risk factor screening and management by GPs within a 45–49 year old health check consultation. The aims of this research are to identify the influences affecting GPs' choosing to screen and choosing to manage SNAP lifestyle risk factors, as well as identify influences on screening and management when multiple SNAP factors exist.</p> <p>Methods</p> <p>A total of 29 audio-taped interviews were conducted with 15 GPs and one practice nurse over two stages. Transcripts from the interviews were thematically analysed, and a model of influencing factors on preventive care behaviour was developed using the Theory of Planned Behaviour as a structural framework.</p> <p>Results</p> <p>GPs felt that assessing smoking status was straightforward, however some found assessing alcohol intake only possible during a formal health check. Diet and physical activity were often inferred from appearance, only being assessed if the patient was overweight. The frequency and thoroughness of assessment were influenced by the GPs' personal interests and perceived congruence with their role, the level of risk to the patient, the capacity of the practice and availability of time. All GPs considered advising and educating patients part of their professional responsibility. However their attempts to motivate patients were influenced by perceptions of their own effectiveness, with smoking causing the most frustration. Active follow-up and referral of patients appeared to depend on the GPs' orientation to preventive care, the patient's motivation, and cost and accessibility of services to patients.</p> <p>Conclusion</p> <p>General practitioner attitudes, normative influences from both patients and the profession, and perceived external control factors (time, cost, availability and practice capacity) all influence management of behavioural risk factors. Provider education, community awareness raising, support and capacity building may improve the uptake of lifestyle modification interventions.</p

ESC core curriculum for the general cardiologist (2013)

[No abstract available

The Hydrogen-Poor Superluminous Supernovae from the Zwicky Transient Facility Phase-I Survey: II. Light Curve Modeling and Characterization of Undulations

We present analysis of the light curves (LCs) of 77 hydrogen-poor superluminous supernovae (SLSNe-I) discovered during the Zwicky Transient Facility Phase-I operation. We find that the majority (67\%) of the sample can be fit equally well by both magnetar and ejecta-circumstellar medium (CSM) interaction plus $^{56}$Ni decay models. This implies that LCs alone can not unambiguously constrain the physical power sources for a SLSN-I. However, 23\% of the sample show inverted V-shape, steep declining LCs or features of long rise and fast post-peak decay, which are better described by the CSM+Ni model. The remaining 10\% of the sample favor the magnetar model. Moreover, our analysis shows that the LC undulations are quite common, with a fraction of $18-44\%$ in our gold sample. Among those strongly undulating events, about 62\% of them are found to be CSM-favored, implying that the undulations tend to occur in the CSM-favored events. Undulations show a wide range in energy and duration, with median values (and 1$\sigma$ errors) being as $1.7\%^{+1.5\%}_{-0.7\%}\,\rm E_{\rm rad,total}$ and $28.8^{+14.4}_{-9.1}$\,days, respectively. Our analysis of the undulation time scales suggests that intrinsic temporal variations of the central engine can explain half of the undulating events, while CSM interaction can account for the majority of the sample. Finally, all of the well-observed He-rich SLSNe-Ib have either strongly undulating LCs or the LCs are much better fit by the CSM+Ni model. These observations imply that their progenitor stars have not had enough time to lose all of the He-envelopes before supernova explosions, and H-poor CSM are likely to present in these events.Comment: 30 pages, 20 figures, Accepted by AP