230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

\u3csup\u3e230\u3c/sup\u3eTh Normalization: New Insights on an Essential Tool for Quantifying Sedimentary Fluxes in the Modern and Quaternary Ocean

230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (\u3e1,000 m water depth)

Identification of a myometrial molecular profile for dystocic labor

<p>Abstract</p> <p>Background</p> <p>The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor.</p> <p>Methods</p> <p>Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR.</p> <p>Results</p> <p>Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3</p> <p>Conclusion</p> <p>These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.</p

Baryon content in a sample of 91 galaxy clusters selected by the South Pole Telescope at 0.2 <z < 1.25

We estimate total mass (M500), intracluster medium (ICM) mass (MICM), and stellar mass (M) in a Sunyaev–Zel’dovich effect (SZE) selected sample of 91 galaxy clusters with masses M500 2.5 × 1014 M and redshift 0.2 < z < 1.25 from the 2500 deg2 South Pole Telescope SPT-SZ survey. The total masses M500 are estimated from the SZE observable, the ICM masses MICM are obtained from the analysis of Chandra X-ray observations, and the stellar masses M are derived by fitting spectral energy distribution templates to Dark Energy Survey griz optical photometry and WISE or Spitzer near-infrared photometry. We study trends in the stellar mass, the ICM mass, the total baryonic mass, and the cold baryonic fraction with cluster halo mass and redshift. We find significant departures from self-similarity in the mass scaling for all quantities, while the redshift trends are all statistically consistent with zero, indicating that the baryon content of clusters at fixed mass has changed remarkably little over the past ≈9 Gyr. We compare our results to the mean baryon fraction (and the stellar mass fraction) in the field, finding that these values lie above (below) those in cluster virial regions in all but the most massive clusters at low redshift. Using a simple model of the matter assembly of clusters from infalling groups with lower masses and from infalling material from the low-density environment or field surrounding the parent haloes, we show that the measured mass trends without strong redshift trends in the stellar mass scaling relation could be explained by a mass and redshift dependent fractional contribution from field material. Similar analyses of the ICM and baryon mass scaling relations provide evidence for the so-called ‘missing baryons’ outside cluster virial regions

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Understanding metastasis: current paradigms and therapeutic challenges in breast cancer progression

Metastasis is the terminal event in carcinogenesis and the principal contributor to mortality in breast cancer patients. However, relatively little is known about the molecular mechanisms of this complex, multi-step process. Consequently, management of metastatic breast cancer (MBC) is far less successful than the treatment of primary disease. Research in the field is very active, resulting in the development of numerous models of metastasis and the identification of key factors implicated in the process. Thus it is hoped that with continued research into the mechanisms driving cancer progression and metastasis, insights will be gained that will facilitate earlier diagnosis and improved treatment of MBC. </p

Evolving Role of Risk Tailored Therapy in Early Stage HER2-Positive Breast Cancer: A Canadian Perspective

The advent of HER2-targeted therapies has led to an important shift in the management of HER2-positive early breast cancer. However, initial treatment approaches apply uniform treatment regimens to all patients, with significant treatment-related and financial toxicities for both the patient and the health care system. Recent data demonstrates that for many patients, the chemotherapy backbone, duration and nature (mono- versus dual-targeted therapy) of the HER2 blockade can be better targeted to an individual patient&rsquo;s risk of recurrence. We will provide a review of current data supporting risk tailored therapy in early stage HER2-positive breast cancer along with key completed and ongoing Canadian and international risk tailored trials. Neoadjuvant systemic therapy should now be considered for patients with clinical stage 2 disease, with greater use of non-anthracycline based chemotherapy regimens. Patients with residual disease following neoadjuvant therapy should be considered for escalated treatment with adjuvant T-DM1. Patients with stage I disease can often be managed with upfront surgery and evidence-based de-escalated adjuvant chemotherapy regimens. The modest benefit of 12- versus 6 months of adjuvant HER2 therapy and/or dual adjuvant HER2 therapy should be carefully weighed against the toxicities. All patients with HER2-positive breast cancer should be enrolled in ongoing risk tailored treatment trials whenever possible. Increasing data supports risk tailored therapy in early stage HER2-positive breast cancer in place of the routine application of aggressive and toxic systemic therapy regimens to all patients. While much progress has been made towards treatment de-escalation in appropriate patients, more is needed, as we highlight in this review. Indeed, Canadian-led clinical trials are helping to lead these efforts