Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase

In vivo studies suggest that replication forks are arrested due to encounters with head-on transcription complexes. Yet, the fate of the replisome and RNA polymerase (RNAP) following a head-on collision is unknown. Here, we find that the E. coli replisome stalls upon collision with a head-on transcription complex, but instead of collapsing, the replication fork remains highly stable and eventually resumes elongation after displacing the RNAP from DNA. We also find that the transcription-repair coupling factor, Mfd, promotes direct restart of the fork following the collision by facilitating displacement of the RNAP. These findings demonstrate the intrinsic stability of the replication apparatus and a novel role for the transcription-coupled repair pathway in promoting replication past a RNAP block

A “Novel” Approach to the Design of an IS Management Course

We report on the design and implementation of an unusual course in Information Systems (IS) management built around an extended case series: a fictitious but reality-based story about the trials and tribulations of a newly appointed but not-technically-trained Chief Information Officer (CIO) in his first year on the job. Together the cases constitute a true-to-life “novel” about IS management (published, in fact, as a novel, as well as individual cases). Four principles guided development of the series and its associated pedagogy: 1) Emphasis on integrative, soft-skill, and business-oriented aspects of IS, independent of underlying technologies; 2) Student derivation and ongoing refinement of cumulative theoretical frameworks arrived at via in-class discussion; 3) Identification of a set of core issues vital to practice that collectively approximate IS management as a business discipline; and 4) Design for student engagement, in particular by basing the case “story” on the monomyth, a literary pattern common to important narratives around the world. A supporting website facilitates sharing of teaching materials and experiences by faculty using the case series. We report results from using this curriculum with undergraduate and graduate students in two universities in different countries, and with executives at a multinational corporation and in an executive program at Harvard Business School. Our results suggest that a “novel-based” approach holds considerable promise for use at undergraduate, graduate, and executive levels, and that it might have advantages in addressing the so-called “enrollment crisis” in IS education, especially with the generation of “digital natives” who have come of age in an environment crowded with engaging approaches to communication and entertainment that compete for their attention

Dyspnea affective response: comparing COPD patients with healthy volunteers and laboratory model with activities of daily living

Background: Laboratory-induced dyspnea (breathing discomfort) in healthy subjects is widely used to study perceptual mechanisms, yet the relationship between laboratory-induced dyspnea in healthy volunteers and spontaneous dyspnea in patients with chronic lung disease is not well established. We compared affective responses to dyspnea 1) in COPD patients vs. healthy volunteers (HV) undergoing the same laboratory stimulus; 2) in COPD during laboratory dyspnea vs. during activities of daily living (ADL). Methods: We induced moderate and high dyspnea levels in 13 COPD patients and 12 HV by increasing end-tidal CO2 (PETCO2) during restricted ventilation, evoking air hunger. We used the multidimensional dyspnea profile (MDP) to measure intensity of sensory qualities (e.g., air hunger (AH) and work/effort (W/E)) as well as immediate discomfort (A1) and secondary emotions (A2). Ten of the COPD subjects also completed the MDP outside the laboratory following dyspnea evoked by ADL. Results: COPD patients and HV reported similar levels of immediate discomfort relative to sensory intensity. COPD patients and HV reported anxiety and frustration during laboratory-induced dyspnea; variation among individuals far outweighed the small differences between subject groups. COPD patients reported similar intensities of sensory qualities, discomfort, and emotions during ADL vs. during moderate laboratory dyspnea. Patients with COPD described limiting ADL to avoid greater dyspnea. Conclusions: In this pilot study, we found no evidence that a history of COPD alters the affective response to laboratory-induced dyspnea, and no difference in affective response between dyspnea evoked by this laboratory model and dyspnea evoked by ADL

Leadership in the British civil service: an interpretation

This article is essentially a polemic. The argument is that when politicians and officials now talk of ‘leadership’ in the British civil service they do not use that word in the way in which it was previously used. In the past leading civil servants, acting in partnership with ministers and within constitutional constraints, exercised leadership in the sense of setting example, inspiring confidence and encouraging loyalty. The loosening of traditional constitutional patterns, the marginalization of senior officials in the policy process and the emergence of business methods as the preferred model for public ­administration have led to a political and administrative environment in which leadership in the British civil service is now about encouraging patterns of behaviour which fit in with these changes. Leadership skills are now about ‘delivery’; they are not about motivation. It is time for politicians, officials and scholars to be open about this

Chronic locked anterior shoulder dislocation with impaction of the humeral head onto the coracoid: a case report

The glenohumeral joint is one of the most commonly dislocated joints. When dislocated, the humeral head typically moves anteriorly and medially within the soft tissues adjacent to the glenoid. We present a case of a 64-year-old female who presented with a locked anterior shoulder dislocation with impaction of the humeral head onto the coracoid. To our knowledge, this is the first reported instance of humeral head impaction onto the coracoid causing the shoulder dislocation to be irreducible by closed means. Complications of this dislocation can include humeral head deformity, pseudoparalysis, brachial plexus injury, and significant pain. Level of evidence V

Segmentation of Non-viable Myocardium in Delayed Enhancement Magnetic Resonance Images

Purpose: To evaluate six algorithms for segmenting non-viable left ventricular (LV) myocardium in delayed enhancement (DE) magnetic resonance imaging (MRI). Methods: Twenty-three patients with known chronic ischemic heart disease underwent DE-MRI. DE images were first manually thresholded using an interactive region-filling tool to isolate non-viable myocardium. Then, six thresholding algorithms, based on the image intensity characteristics of either LV blood pool (BP), viable LV myocardium, or both, were applied to each image. For the Mean−2SDBP algorithm, thresholds were equal to the mean BP intensity minus twice its standard deviation. For the Mean+2SDSemi, Mean+3SDSemi, Mean+2SDAuto, and Mean+3SDAuto algorithms, thresholds equaled the mean intensity of viable myocardium plus twice (or thrice, as denoted by the name) the standard deviation of intensity (subscripts denote how these values were determined: automatic or semi-automatic). For the Minimum Intensity algorithm, the threshold equaled the minimum intensity between the BP and LV myocardium mean intensities. Percent Scar was defined as the ratio of non-viable to total myocardial pixels in each image. Agreement between each algorithm and manual thresholding was assessed using Bland–Altman analysis. Results: Mean Percent Scar was 25 ± 16% by manual thresholding. Five of the six algorithms demonstrated mean bias within ±3% (all except Mean+2SDAuto); however, limits of agreement (LoA) were large in general (range 12–36%). The best overall agreement was demonstrated by the Mean+2SDSemi (bias, 0%; LoA, 12%) and Mean+3SDSemi(bias, −3%; LoA, 14%) algorithms. Conclusion: On average, five of the six algorithms proved satisfactory for clinical implementation; however, in some images, manual correction of automatic results was necessary

Challenges associated with e-cigarette use by people in custody in Scottish prisons: a qualitative interview study with prison staff

Objectives: Little is known about the perspectives of staff working in prisons where e-cigarettes are permitted. Scotland now permits people in custody (PiC), but not staff/visitors to use e-cigarettes, following implementation of smoke-free prisons policy in 2018. Previous studies, conducted before and immediately after the introduction of e-cigarettes in Scottish prisons, have evidenced stakeholder support for their use by PiC. This study focuses on key challenges associated with e-cigarette use in prisons, using data collected from prison staff once ecigarettes had been allowed in a smoke-free environment for 6–9 months. Setting: Five prisons in Scotland. Participants: Sixteen qualitative interviews were conducted with prison staff from five prisons varying by population (sex, age and sentence length). Data were managed and analysed using the framework approach. Results: While these staff confirmed strong support for the smoke-free prison policy and reported some benefits of replacing tobacco with e-cigarettes, they also spoke of the challenges e-cigarettes pose. These included: workplace e-cigarette vapour exposures; perceptions that e-cigarettes provide a new, effective way for some PiC to take illegal drugs, particularly new psychoactive substances; organisational challenges relating to the value attached to e-cigarettes in prisons; and implications for long-term nicotine use and tobacco cessation. Staff anticipated difficulties in tightening restrictions on ecigarette use by PiC given its scale and significance among this population. Conclusions: Maximising the benefits of e-cigarette use by PiC is likely to require multiple measures to support effective and safe use and e-cigarette reduction/cessation where desired. This includes monitoring any misuse of e-cigarettes, and provision of guidance and support on appropriate e-cigarette use and how to limit or quit use if desired. Findings are relevant to jurisdictions considering or planning changes in prison smoking or vaping policies

Do the poor cost much more? The relationship between small area income deprivation and length of stay for elective hip replacement in the English NHS from 2001 to 2008

The Blair/Brown reforms of the English NHS in the early to mid 2000s gave hospitals strong new incentives to reduce waiting times and length of stay for elective surgery. One concern was that these efficiency-oriented reforms might harm equity, by giving hospitals new incentives to select against socio-economically disadvantaged patients who stay longer and cost more to treat. This paper aims to assess the magnitude of these new selection incentives in the test case of hip replacement. Anonymous hospital records are extracted on 274,679 patients admitted to English NHS Hospital Trusts for elective total hip replacement from 2001/2 through 2007/8. The relationship between length of stay and small area income deprivation is modelled allowing for other patient characteristics (age, sex, number and type of diagnoses, procedure type) and hospital effects. After adjusting for these factors, we find that patients from the most deprived tenth of areas stayed just 6% longer than others in 2001/2, falling to 2% by 2007/8. By comparison, patients aged 85 or over stayed 57% longer than others in 2001/2, rising to 71% by 2007/8, and patients with seven or more diagnoses stayed 58% longer than others in 2001/2, rising to 73% by 2007/8. We conclude that the Blair/Brown reforms did not give NHS hospitals strong new incentives to select against socio-economically deprived hip replacement patients