The distributional effects of adaption and anticipation to ill health on subjective wellbeing

Adaption and anticipation to reported illness upon subjective wellbeing is analysed across the wellbeing distribution. Anticipation effects are muted, but substantial adaption effects are apparent that differ markedly over the range of wellbeing, being most evident at the upper quartile

Isothermal and non-isothermal crystallization kinetics of composites of poly(propylene) and MWCNTs

The isothermal and non-isothermal crystallization behaviour of composites of a poly(propylene) (PP) and multi-walled carbon nanotubes (MWCNTs) were investigated using Differential Scanning Calorimetry (DSC). An Avrami analysis was used to study the isothermal crystallization kinetics of unfilled PP and composites of PP with MWCNT loadings up to 2 (w/w). The value of the Avrami exponent (n) was greater than 2 for all samples, confirming the primary stage of crystal growth is a three-dimensional phenomenon. The activation energy (ΔE), determined using an Arrhenius type expression, for the isothermal crystallization of PP increased from 87 kJ for unfilled PP to 228 kJ on incorporation of 2 (w/w) MWCNTs to PP. An attempt was made to model the non-isothermal crystallization kinetics of composites of PP and MWCNTs using a range of mathematical models, including the Jeziorny extended Avrami equation, Ozawa equation, Cazé and Chuah average Avrami exponents, and a combined Avrami/Ozawa approach. The Jeziorny extended Avrami approach confirmed that the non-isothermal crystallization of MWCNT filled PP is clearly a two-stage process. Fitting of the Ozawa model was shown to be not valid and both the Cazé and Chuah average Avrami approaches were ineffective as neither took in to account the effects of secondary crystallization. Only the combined Avrami/Ozawa method successfully modelled the two-stage crystallization of composites of PP and MWCNTs. The activation energy (ΔE) for the non-isothermal crystallization of PP on addition of MWCNTs increased with increasing MWCNT content, up to as high as 726 kJ

On the Microstructural Evolution and Failure Mechanism in Laser Powder Bed Fusioned Ti-6Al-4V during Low Cycle Fatigue at Room and Elevated Temperatures

Microstructural features and their evolution during cyclic deformation directly impact the low cycle fatigue (LCF) life of additively manufactured Laser Powder Bed Fusion (LPBF) Ti-6Al-4V. Tensile and strain controlled LCF tests were performed at room (RT) and elevated temperature (ET, @ 400 °C) to study the cyclic softening behaviour and failure mechanism of LPBF Ti-6Al-4V. The evolution of α’ grains and free dislocation density were studied using Electron Back Scatter Diffraction (EBSD). LPBF Ti-6Al-4V has greater tensile strengths than the conventionally manufactured wrought Ti-6Al-4V due to its microstructure with fine α’ needles which provide small slip lengths. For cyclic loading at ET, the interaction between the dislocations increases which in-turn increase the ability of material to overcome the obstacles to dislocation motion, resulting into higher cyclic softening compared to the RT test. During cyclic deformation, evolution of dislocation substructures takes place to subsequently produce Low Angle Boundaries (LABs) inside the prior α’ grains. The LABs progressively lead to nucleation and coalescence of voids with fatigue cycles, eventually leading to fracture. An increase in strain range (i.e. plasticity levels) causes more significant dislocation pile-up contributing to a greater amount of cyclic softening. The lack of fusion voids or pores, present at or near the surface, and microcracks, present at the rough surface, act as the crack initiation locations which propagate to cause fracture of the LPBF specimens/components under LCF loading, where the primary mode of fatigue fracture observed is intergranular

Effectiveness and effects of attempts to regulate the UK petrol industry

This paper evaluates the impact that investigation and regulation of the UK petrol industry has had on the profitability of the companies. Using a gross margin for petrol, we estimate a series of variable parameter autoregressive processes. The results demonstrate that the 1979 Monopolies and Mergers Commission investigation into the industry, caused a long term decline in profit margins in the industry, despite the fact that no recommendations or undertakings were made. This cannot however be said for subsequent investigations

Inhibiting translation elongation can aid genome duplication in Escherichia coli

Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking. Suppression depends on RelA-directed synthesis of (p)ppGpp, a signalling molecule that reduces replication-transcription conflicts, with RelA activation requiring ribosomal pausing. Levels of (p)ppGpp in these suppressors also correlate inversely with the need for Rho activity, an RNA translocase that can bind to emerging transcripts and displace transcription complexes. These data illustrate the fine balance between different mechanisms in facilitating gene expression and genome duplication and demonstrate that accessory helicases are a major determinant of this balance. This balance is also critical for other aspects of bacterial survival: the mutations identified here increase persistence indicating that similar mutations could arise in naturally occurring bacterial populations facing antibiotic challenge

Mechanisms, predictors, and evolution of severe peri-device leaks with two different left atrial appendage occluders.

AIMS Incomplete left atrial appendage occlusion (LAAO) due to peri-device leak (PDL) is a limitation of the therapy. The Amulet IDE trial is the largest randomized head-to-head trial comparing the Amulet and Watchman 2.5 LAAO devices with fundamentally different designs. The predictors and mechanistic factors impacting differences in PDLs within the Amulet IDE trial are assessed in the current analysis. METHODS AND RESULTS An independent core lab analysed all images for the presence or absence of severe PDL (>5 mm). The incidence, mechanistic factors, predictors using propensity score-matched controls, and evolution of severe PDLs through 18 months were assessed. Of the 1878 patients randomized in the trial, the Amulet occluder had significantly fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, P < 0.001) and 12 months (0.1 vs. 1.1%, P < 0.001). Off-axis deployment or missed lobes were leading mechanistic PDL factors in each device group. Larger left atrial appendage (LAA) dimensions including orifice diameter, landing zone diameter, and depth predicted severe PDL with the Watchman device, with no significant anatomical limitations noted with the Amulet occluder. Procedural and device implant predictors were found with the Amulet occluder attributed to the learning curve with the device. A majority of Watchman device severe PDLs did not resolve over time through 18 months. CONCLUSION The dual-occlusive Amplatzer Amulet LAA occluder provided improved LAA closure compared with the Watchman 2.5 device. Predictors and temporal observations of severe PDLs were identified in the Amulet IDE trial. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov Unique identifier NCT02879448

A monocyte-TNF-endothelial activation axis in sickle transgenic mice: Therapeutic benefit from TNF blockade

Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+SAntilles, and SS‐BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr‐1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL‐1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro‐inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM‐1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent—and possibly dominant—role for an abnormal monocyte‐TNF‐endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal

Addition of the mammalian target of rapamycin inhibitor, Everolimus, to consolidation therapy in acute myeloid leukaemia: experience from the UK NCRI AML17 trial

As part of the UK NCRI AML17 trial, adult patients with acute myeloid leukemia in remission could be randomized to receive the mammalian target of rapamycin inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse-free survival. At 5 years there was no difference in relapse-free survival [29% versus 40%; odds ratio 1.19 (0.9-1.59) P=0.2], cumulative incidence of relapse [60% versus 54%: odds ratio 1.12 (0.82-1.52): P=0.5] or overall survival [45% versus 58%: odds ratio 1.3 (0.94-1.81): P=0.11]. The independent Data Monitoring Committee advised study termination after randomization of 339 of the intended 600 patients because of excess mortality in the everolimus arm without any evidence of beneficial disease control. The delivery of the everolimus dose was variable, but there was no evidence of clinical benefit in patients with adequate dose delivery compared with no treatment. This study suggests that the addition of mammalian target of rapamycin inhibition to chemotherapy provides no benefit