Convalescent troponin and cardiovascular death following acute coronary syndrome

Objectives: High-sensitivity cardiac troponin testing is used in the diagnosis of acute coronary syndromes but its role during convalescence is unknown. We investigated the long-term prognostic significance of serial convalescent high-sensitivity cardiac troponin concentrations following acute coronary syndrome. Methods: In a prospective multicentre observational cohort study of 2140 patients with acute coronary syndrome, cardiac troponin I concentrations were measured in 1776 patients at 4 and 12 months following the index event. Patients were stratified into three groups according to the troponin concentration at 4 months using the 99th centile (women>16 ng/L, men>34 ng/L) and median concentration of those within the reference range. The primary outcome was cardiovascular death. Results: Troponin concentrations at 4 months were measurable in 99.0% (1759/1776) of patients (67±12 years, 72% male), and were ≤5 ng/L (median) and >99th centile in 44.8% (795) and 9.3% (166), respectively. There were 202 (11.4%) cardiovascular deaths after a median of 4.8 years. After adjusting for the Global Registry of Acute Coronary Events score, troponin remained an independent predictor of cardiovascular death (HR 1.4, 95% CI 1.3 to 1.5 per doubling) with the highest risk observed in those with increasing concentrations at 12 months. Patients with 4-month troponin concentrations >99th centile were at increased risk of cardiovascular death compared with those ≤5 ng/L (29.5% (49/166) vs 4.3% (34/795); adjusted HR 4.9, 95% CI 3.8 to 23.7). Conclusions: Convalescent cardiac troponin concentrations predict long-term cardiovascular death following acute coronary syndrome. Recognising this risk by monitoring troponin may improve targeting of therapeutic interventions

The Last Glacial Maximum in the central North Island, New Zealand: palaeoclimate inferences from glacier modelling

Abstract. Quantitative palaeoclimate reconstructions provide data for evaluating the mechanisms of past, natural climate variability. Geometries of former mountain glaciers constrained by moraine mapping afford the opportunity to reconstruct palaeoclimate, due to the close relationship between ice extent and local climate. In this study, we present results from a series of experiments using a 2D coupled energy-balance/ice-flow model that investigate the palaeoclimate significance of Last Glacial Maximum moraines within nine catchments in central North Island, New Zealand. We find that the former ice limits can be simulated when present day temperatures are reduced by between 4 °C and 7 °C, when precipitation remains unchanged from present. The spread in the results between the nine catchments is likely to represent the combination of chronological and model uncertainties. The temperature decrease required to simulate the former glaciers falls in the range of 5.1 °C and 6.3 °C for the majority of catchments targeted, which represents our best estimate of the peak temperature anomaly in central North Island, New Zealand during the Last Glacial Maximum. A decrease in precipitation, as suggested by proxy evidence and climate models, of up to 25 % from present, increases the magnitude of the required temperature changes by up to 0.8 °C. Glacier model experiments using reconstructed topographies that exclude the volume of post-glacial (&lt;15 ka) volcanism, generally increased the magnitude of cooling required to simulate the former ice limits by up to 0.5 °C. Our palaeotemperature estimates expand the spatial coverage of proxy-based quantitative palaeoclimate reconstructions in New Zealand, and are consistent with independent, proximal temperature reconstructions from fossil pollen assemblages, as well as similar glacier modelling reconstructions from central Southern Alps. </jats:p

The Grizzly, October 2, 1990

Books Stolen From Students and Professors: Suspect Arrested, 81 Books Confiscated • New Era of Recycling to Change Actions and Minds • Utilities Tunnel Nears Completion • Hardman\u27s Biography of Finney Turns Paperback • Gender Stereotypes by Dr. Englund • Speech Exemption Exam • Stolen Book List • Foreign Spotlight • Ghost Search Continues • AC/DC High Voltage Rock N\u27 Roll • Cop Rock Off-Key • Prince Premier • WVOU Schedule • Medieval Melodies Fill Forum • Homecoming Candidates • Vital Signs of the Trauma Center • Summer Science at Ursinus • Facelift for LSB • Bear Pack Wins Mets • Come Sailing! • Bears Lose 12-7 • Flag Football Kicks Off • Wagner Takes First in Mets Meet • US Must Aid Soviet Economic Woes • Temple Strike: Avoiding The Real Issue • Letters: Doughty Appreciates Grizzly; Wall Destruction Coincidental? • Soccer Working Hard • Hockey Splitshttps://digitalcommons.ursinus.edu/grizzlynews/1259/thumbnail.jp

Anti-oestrogens but not oestrogen deprivation promote cellular invasion in intercellular adhesion-deficient breast cancer cells

Introduction Anti-oestrogens have been the mainstay of therapy in patients with oestrogen-receptor (ER) positive breast cancer and have provided significant improvements in survival. However, their benefits are limited by tumour recurrence in a significant proportion of initially drug-responsive breast cancer patients because of acquired anti-oestrogen resistance. Relapse on such therapies clinically presents as local and/or regional recurrences, frequently with distant metastases, and the prognosis for these patients is poor. The selective ER modulator, tamoxifen, classically exerts gene inhibitory effects during the drug-responsive phase in ER-positive breast cancer cells. Paradoxically, this drug is also able to induce the expression of genes, which in the appropriate cell context may contribute to an adverse cell phenotype. Here we have investigated the effects of tamoxifen and fulvestrant treatment on invasive signalling and compared this with the direct effects of oestrogen withdrawal to mimic the action of aromatase inhibitors. Methods The effect of oestrogen and 4-hydroxy-tamoxifen on the invasive capacity of endocrine-sensitive MCF-7 cells, in the presence or absence of functional E-cadherin, was determined by Matrigel invasion assays. Studies also monitored the impact of oestrogen withdrawal or treatment with fulvestrant on cell invasion. Western blotting using phospho-specific antibodies was performed to ascertain changes in invasive signalling in response to the two anti-oestrogens versus both oestradiol treatment and withdrawal. Results To the best of our knowledge, we report for the first time that tamoxifen can promote an invasive phenotype in ER-positive breast cancer cells under conditions of poor cell-cell contact and suggest a role for Src kinase and associated pro-invasive genes in this process. Our studies revealed that although this adverse effect is also apparent for further classes of anti-oestrogens, exemplified by the steroidal agent fulvestrant, it is absent during oestrogen withdrawal. Conclusions These data highlight a previously unreported effect of tamoxifen (and potentially further anti-oestrogens), that such agents appear able to induce breast cancer cell invasion in a specific context (absence of good cell-cell contacts), where these findings may have major clinical implications for those patients with tumours that have inherently poor intercellular adhesion. In such patients oestrogen deprivation with aromatase inhibitors may be more appropriate

HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Ecosystem productivity and carbon cycling in intact and annually burnt forest at the dry southern limit of the Amazon rainforest (Mato Grosso, Brazil)

<div><p> <b><i>Background:</i></b> The impact of fire on carbon cycling in tropical forests is potentially large, but remains poorly quantified, particularly in the locality of the transition forests that mark the boundaries between humid forests and savannas.</p> <p> <b><i>Aims:</i></b> To present the first comprehensive description of the impact of repeated low intensity, understorey fire on carbon cycling in a semi-deciduous, seasonally dry tropical forest on infertile soil in south-eastern Amazonia.</p> <p> <b><i>Methods:</i></b> We compared an annually burnt forest plot with a control plot over a three-year period (2009–2011). For each plot we quantified the components of net primary productivity (NPP), autotrophic (<i>R</i>_a) and heterotrophic respiration (<i>R</i>_h), and estimated total plant carbon expenditure (PCE, the sum of NPP and <i>R</i>_a) and carbon-use efficiency (CUE, the quotient of NPP/PCE).</p> <p> <b><i>Results:</i></b> Total NPP and <i>R</i>_a were 15 and 4% lower on the burnt plot than on the control, respectively. Both plots were characterised by a slightly higher CUE of 0.36–0.39, compared to evergreen lowland Amazon forests.</p> <p> <b><i>Conclusions:</i></b> These measurements provide the first evidence of a distinctive pattern of carbon cycling within this transitional forest. Overall, regular understorey fire is shown to have little impact on ecosystem-level carbon fluxes.</p> </div

Implementing commercial information exchange: a construction supply chain case study

This is an Open Access Article. It is published by Taylor and Francis under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/The concept of electronic trading (e-trading) has transformed supply chain interactions in many industries, yet little research explored its implementation by Architecture, Engineering and Construction (AEC) supply chain firms. E-trading relies on commercial information exchange by supply chain partners which is generally adopted through intermediary technology partners (Hub Providers) to facilitate the accurate and timely communication of transactional data between buyers and supplier. A case study was conducted to explore the challenges and barriers to implementation of cross-firm commercial information exchange. The study primarily involved investigation of the interfaces between software development and organizational functions assisting with the electronic exchange of commercial information (eCIX) implementation. Findings from the case study show that implementation of commercial information exchange is not an easy task with several themes of factors to be considered during delivery of such projects, namely technical, coordination, integration and organizational. The study contributes to the knowledge and deployment of e-trading solutions within the context of AEC firms, and should be of interest to the practitioners contemplating similar project

Ecosystem respiration and net primary productivity after 8–10 years of experimental through-fall reduction in an eastern Amazon forest

<div><p> <b><i>Background:</i></b> There is much interest in how the Amazon rainforest may respond to future rainfall reduction. However, there are relatively few ecosystem-scale studies to inform this debate.</p> <p> <b><i>Aims:</i></b> We described the carbon cycle in a 1 ha rainforest plot subjected to 8–10 consecutive years of ca. 50% through-fall reduction (TFR) and compare these results with those from a nearby, unmodified control plot in eastern Amazonia.</p> <p> <b><i>Methods:</i></b> We quantified the components of net primary productivity (<i>NPP</i>), autotrophic (<i>R</i>_a) and heterotrophic respiration, and estimate gross primary productivity (<i>GPP</i>, the sum of <i>NPP</i> and <i>R</i>_a) and carbon-use efficiency (<i>CUE</i>, the ratio of <i>NPP</i>/<i>GPP</i>).</p> <p> <b><i>Results:</i></b> The TFR forest exhibited slightly lower <i>NPP</i> but slightly higher <i>R</i>_a, such that forest <i>CUE</i> was 0.29 ± 0.04 on the control plot but 0.25 ± 0.03 on the TFR plot. Compared with four years earlier, TFR plot leaf area index and small tree growth recovered and soil heterotrophic respiration had risen.</p> <p> <b><i>Conclusions:</i></b> This analysis tested and extended the key findings of a similar analysis 4 years earlier in the TFR treatment. The results indicated that, while the forest recovered from extended drought in some respects, it maintained higher overall <i>R</i>_a relative to the undroughted control, potentially causing the droughted forest to act as a net source of CO₂.</p> </div