The efficiency of deep-ocean CO
sequestration is regulated by the relative balance between inorganic and organic carbon export respectively acting through the biological carbon pump (BCP) and the ...carbonate counter pump (CCP). The composition and abundance of calcifying species in the prevailing oceanic plankton community plays a major role in driving the CCP. Here we assess the role of these calcifying organisms in regulating the strength of the CCP in a Southern Ocean region (northern Scotia Sea) known to be a major hotspot for the drawdown of atmospheric CO
. We show that, when shelled pteropods dominate the calcifying community, the total annual reduction of CO
transferred to the deep ocean doubles (17%) compared to when other plankton calcifiers dominate (3-9%). Furthermore, predation enhances their contribution through the removal of organic soft tissue. Pteropods are threatened in polar regions by ocean warming and acidification. We determine that their potential decline would have major implications to the comparative strengths of the BCP and CCP.
Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown.
The ...authors sought to assess the role of hyaluronan (HA) metabolism in ACS.
Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis.
Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively).
HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.
Time-series analyses of satellite images reveal that sea ice extent in the Ross Sea has experienced significant changes over the last 40 years, likely triggered by large-scale atmospheric anomalies. ...However, resolving how sea ice in the Ross Sea has changed over longer timeframes has until now remained more elusive. Here we used a laminated sediment piston core (14.6 m) collected from the Edisto inlet (Western Ross Sea) to reconstruct fast ice dynamics over the last 2.6 ka. Our goal was to first understand the climate expression of selected well-defined sediment laminae and then use these characteristics for reconstructing past sea ice behaviour across the whole sedimentary sequence. We used the recently established sea ice diatom biomarker proxy IPSO25 in combination with diatom census counts and bulk analyses. Analyses performed on a suite of discrete laminae revealed statistically significant differences between dark and light laminae reflecting different depositional conditions. Based on their respective biogeochemical fingerprints, we infer that dark laminae accumulated during sea ice thaws in early summer. Under these conditions, laminae contain relatively high concentrations of IPSO25 and display an enriched δ13C composition for the bulk organic matter (OM). While diatom assemblages in dark laminae are relatively homogenous, as the thaw continues later in the summer, Corethron pennatum becomes the dominant diatom species, resulting in the formation of light laminae characterized by low IPSO25 concentrations. Since C. pennatum can migrate vertically through the water column to uptake nutrients and avoid competition in oligotrophic waters, its high concentration likely reflects stratified and ice-free surface waters typical of late summer.
Down-core trends show that the correlation between sediment brightness and geochemical fingerprint (i.e., IPSO25 and δ13C) holds throughout the record. Based on the knowledge gained at lamina level, our down-core high-resolution reconstruction shows that the summer fast ice coverage changed dramatically during the late Holocene. Specifically, we conclude that the Edisto inlet experienced regular early summer opening between 2.6 ka, and ca. 0.7 ka, after which, coastal fast ice persisted during summer months and ice-free conditions became less frequent. Comparison with previous regional ice core data suggests that the sudden cooling recorded over the Victoria Land Coast region since 0.7 ka might potentially explain our observation of persistent summer fast ice in the Western Ross Sea. Our study has shown that multi-proxy data derived from laminated sediments can provide hitherto unknown detail regarding past summer sea ice dynamics in coastal Antarctic regions.
•Dark and light sediment laminae exhibit different chemical and ecological features.•Dark and light sediment laminae reflect different fast ice coverage during summer.•Enriched δ13C and high IPSO25 (dark laminae) track early thawing of fast ice.•High concentration of C. pennatum (light laminae) identifies protracted ice-free conditions.•Summer ice-free conditions became less frequent since 0.7 ka BP along the north-western Ross Sea.
Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we ...explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
Aims
Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with ...the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression.
Methods and Results
We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (
P
< 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend
P
< 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences.
Conclusions
Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.
Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown.
The ...authors sought to assess the role of hyaluronan (HA) metabolism in ACS.
Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis.
Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively).
HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability.
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Objectives:
Significant variation in emergency department (ED) patient arrival rates necessitates the adjustment of staffing patterns to optimize the timely care of patients. This study evaluated the ...effectiveness of a queueing model in identifying provider staffing patterns to reduce the fraction of patients who leave without being seen.
Methods:
The authors collected detailed ED arrival data from an urban hospital and used a Lag SIPP queueing analysis to gain insights on how to change provider staffing to decrease the proportion of patients who leave without being seen. The authors then compared this proportion for the same 39‐week period before and after the resulting changes.
Results:
Despite an increase in arrival volume of 1,078 patients (6.3%), an average increase in provider hours of 12 hours per week (3.1%) resulted in 258 fewer patients who left without being seen. This represents a decrease in the proportion of patients who left without being seen by 22.9%. Restricting attention to a four‐day subset of the week during which there was no increase in total provider hours, a reallocation of providers based on the queueing model resulted in 161 fewer patients who left without being seen (21.7%), despite an additional 548 patients (5.5%) arriving in the second half of the study.
Conclusions:
Timely access to a provider is a critical dimension of ED quality performance. In an environment in which EDs are often understaffed, analyses of arrival patterns and the use of queueing models can be extremely useful in identifying the most effective allocation of staff.
Atlantification of Arctic ocean is causing a sharp increase in temperature and salinity around Svalbard Islands and in Kongsfjorden. Such phenomenon and the input of sediment-rich glacial meltwater ...influence salinity, water column turbidity, and light penetration with ecological implications on the microbial features. With the aim to address the temporal variability of the microbial assemblage in relation to environmental variables, a 7-day study was carried out in Kongsfjorden, in late summer 2013. Abiotic (temperature, salinity, nutrients, total suspended matter, particulate inorganic, and organic carbon) and biotic (phyto -, picophyto-, bacterio-, and virioplankton abundance and microbial respiration) parameters were investigated at a station in the inner fjord area, ca. 8.5 km away from the glacier front. Phyto-, picophyto-, and virioplankton showed low abundance. Dinoflagellates and coccolithophorids dominated the phytoplankton community while
Synechococcus
sp. the picophytoplankton alone, in relation with Atlantic water. Low virus to bacteria ratios were detected, presumably linked to the high sedimentation rates. Interesting variability for picophytoplankton with depth, virioplankton with both time and depth, and respiratory rates with time were found. Moreover, the organic matter turnover was slower on the first sampling day compared to that of the following days. Planktonic abundance depended on the variability of both hydrology (seawater mass inflow) and freshwater runoff from the glacier (relative turbidity degree). Differently, the metabolic rates of respiration appeared to be linked with the particulate carbon pool. Over 1-week study, the diverse microbial dynamics appeared to be conditioned on complex forcing, emphasizing the importance of high-resolution experiment.
Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may ...rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.
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