On Objective Measures of Rule Surprisingness

Most of the literature argues that surprisingness is an inherently subjective aspect of the discovered knowledge, which cannot be measured in objective terms. This paper departs from this view, and it has a twofold goal: (1) showing that it is indeed possible to define objective (rather than subjective) measures of discovered rule surprisingness; (2) proposing new ideas and methods for defining objective rule surprisingness measures

Unwinding of a DNA replication fork by a hexameric viral helicase

Hexameric helicases are motor proteins that unwind double-stranded DNA (dsDNA) during DNA replication but how they are optimised for strand separation is unclear. Here we present the cryo-EM structure of the full-length E1 helicase from papillomavirus, revealing all arms of a bound DNA replication fork and their interactions with the helicase. The replication fork junction is located at the entrance to the helicase collar ring, that sits above the AAA + motor assembly. dsDNA is escorted to and the 5´ single-stranded DNA (ssDNA) away from the unwinding point by the E1 dsDNA origin binding domains. The 3´ ssDNA interacts with six spirally-arranged β-hairpins and their cyclical top-to-bottom movement pulls the ssDNA through the helicase. Pulling of the RF against the collar ring separates the base-pairs, while modelling of the conformational cycle suggest an accompanying movement of the collar ring has an auxiliary role, helping to make efficient use of ATP in duplex unwinding

TITAN's Digital RFQ Ion Beam Cooler and Buncher, Operation and Performance

We present a description of the Radio Frequency Quadrupole (RFQ) ion trap built as part of the TITAN facility. It consists of a gas-filled, segmented, linear Paul trap and is the first stage of the TITAN setup with the purpose of cooling and bunching radioactive ion beams delivered from ISAC-TRIUMF. This is the first such device to be driven digitally, i.e., using a high voltage ($V_{pp} = \rm{400 \, V}$), wide bandwidth ($0.2 < f < 1.2 \, \rm{MHz}$) square-wave as compared to the typical sinusoidal wave form. Results from the commissioning of the device as well as systematic studies with stable and radioactive ions are presented including efficiency measurements with stable $^{133}$Cs and radioactive $^{124, 126}$Cs. A novel and unique mode of operation of this device is also demonstrated where the cooled ion bunches are extracted in reverse mode, i.e., in the same direction as previously injected.Comment: 34 pages, 17 figure

Canadian paediatric neurology workforce survey and consensus statement

Background: Little knowledge exists on the availability of academic and community paediatric neurology positions. This knowledge is crucial for making workforce decisions. Our study aimed to: 1) obtain information regarding the availability of positions for paediatric neurologists in academic centres; 2) survey paediatric neurology trainees regarding their perceptions of employment issues and career plans; 3) survey practicing community paediatric neurologists 4) convene a group of paediatric neurologists to develop consensus regarding how to address these workforce issues. Methods: Surveys addressing workforce issues regarding paediatric neurology in Canada were sent to: 1) all paediatric neurology program directors in Canada (n=9) who then solicited information from division heads and from paediatric neurologists in surrounding areas; 2) paediatric neurology trainees in Canada (n=57) and; 3) community paediatric neurologists (n=27). A meeting was held with relevant stakeholders to develop a consensus on how to approach employment issues. Results: The response rate was 100% from program directors, 57.9% from residents and 44% from community paediatric neurologists. We found that the number of projected positions in academic paediatric neurology is fewer than the number of paediatric neurologists that are being trained over the next five to ten years, despite a clinical need for paediatric neurologists. Paediatric neurology residents are concerned about job availability and desire more career counselling. Conclusions: There is a current and projected clinical demand for paediatric neurologists despite a lack of academic positions. Training programs should focus on community neurology as a viable career option

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

Fatigue Crack Growth Mechanisms At the Microstructure Scale in Al-Si-Mg Cast Alloys: Mechanisms in Regions II and III

The fatigue crack growth behavior in Regions 11 and III of crack growth was investigated for hypoeutectic and eutectic Al-Si-Mg cast alloys. To isolate and establish the mechanistic contributions of characteristic microstructural features (dendritic α-Al matrix, eutectic phases, Mg-Si strengthening precipitates), alloys with various Si content/morphology, grain size level, and matrix strength were studied; the effect of secondary dendrite arm spacing (SDAS) was also assessed. In Regions 11 and III of crack growth, the observed changes in the fracture surface appearance were associated with changes in crack growth mechanisms at the microstructural scale (from a linear advance predominantly through primary α-Al to a tortuous advance exclusively through AI-Si eutectic Regions). The extent of the plastic zone ahead of the crack tip was successfully used to explain the changes in growth mechanisms. The fatigue crack growth tests were conducted on compact tension specimens under constant stress ratio, R = 0.1, in ambient conditions

Walking with light and the discontinuous experience of urban change

The information, practices and views in this article are those of the author and do not necessarily reflect the opinion of the Royal Geographical Society (with IBG). © 2020 The Authors. Transactions of the Institute of British Geographers published by John Wiley & Sons Ltd on behalf of Royal Geographical Society (with The Institute of British Geographers). This paper is concerned with the affective power of light, darkness, and illumination and their role in exposing and obscuring processes of rapid urban change. Little academic attention has focused on how lighting informs multiple, overlapping, and intersecting urban temporalities and mediates our experience of an ever-changing city. This paper foregrounds a walk through the illuminated city at night as an epistemic opportunity to develop an embodied account of material and temporal change in ways that disrupt the aesthetic organisation of the sensible world at night. By detailing the discontinuous experience of walking through differently lit spaces, the paper develops novel ways of conceptualising the experience of urban change that unsettle common understandings of subjectivity, temporality, and the city. The paper draws on a single night's walk from Canning Town to Canary Wharf in east London – an area that has recently undergone rapid change, including the erection of enclaves of high-rise development. By accentuating the shared experiences of walking with light, we reveal the affective capacities of light and dark to conceal and expose wider material, embodied, and temporal urban changes but also how we might challenge the organisation of the nocturnal field of the sensible

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation