Rapid increase in simulated North Atlantic dust deposition due to fast change of northwest African landscape during the Holocene

Marine sediment records from a series of core sites along the northwest African margin show a sudden increase in North Atlantic dust deposition at about 5&thinsp;ka&thinsp;BP that has been associated with an abrupt end of the African Humid Period (AHP). To assess the causes of the abrupt shift in North Atlantic dust deposition, we explore changes in the Holocene dust cycle and in North African climate and landscape by performing several time slice simulations from 8&thinsp;ka&thinsp;BP until the preindustrial era. To do this, we use the coupled aerosol–climate model ECHAM6–HAM2 including dynamic vegetation and interactive dust, wherein ocean conditions and lake surface area are prescribed for each time slice.We find a rapid increase in simulated dust deposition between 6 and 4&thinsp;ka&thinsp;BP that is fairly consistent with the abrupt change in marine sediment records at around 20°&thinsp;N close to the northwest African margin. At more northern and more remote cores, a significant change in dust deposition is noticeable roughly between 6 and 2&thinsp;ka&thinsp;BP in the simulations as well as in the records, but the change is less sharp compared to the near-margin core sites. The rapid change in simulated dust deposition is caused by a rapid increase in simulated dust emissions in the western Sahara, where the main dust sources for dust transport towards the North Atlantic are located. The sudden increase in dust emissions in the western Sahara is according to our simulations a consequence of a fast decline of vegetation cover from 22 to 18°&thinsp;N that might occur due to vegetation–climate feedbacks or due to the existence of a precipitation threshold on vegetation growth. Additionally, the prescribed gradual reduction of lake area enforces accelerated dust release as highly productive dust sources are uncovered. Concurrently with the continental drying, surface winds in the western Sahara are accelerated. Changes in the Saharan landscape and dust emissions south of 18°&thinsp;N and in the eastern Sahara play a minor role in driving the dynamics of North Atlantic dust deposition at the core sites. Our study identifies spatial and temporal heterogeneity in the transition of the North African landscape. As a consequence, implications from local data records on large-scale climate have to be treated with caution.</p

Tree insect pests and pathogens: a global systematic review of their impacts in urban areas

Trees contribute greatly to urban environments and human well-being, yet relatively little is known about the extent to which a rising incidence of tree insect pests and pathogens may be affecting these contributions. To address this issue, we undertook a systematic review and synthesis of the diverse global empirical evidence on the impacts of urban tree insect pests and pathogens, using bibliographic databases. Following screening and appraisal of over 3000 articles from a wide range of fields, 100 studies from 28 countries, spanning 1979–2021, were conceptually sorted into a three-part framework: (1) environmental impacts, representing 95 of the studies, including those reporting on tree damage, mortality, reduced growth, and changes in tree function; (2) social impacts were reported by 35 of studies, including on aesthetics, human health, and safety hazards; and (3) economic impacts, reported in 24 of studies, including on costs of pest management, and economic losses. There has been a considerable increase in urban impact studies since 2011. Evidence gaps exist on impacts on climate-regulating capacity, including temperature regulation, water retention, soil erosion, and wind protection, but also on specific hazards, nuisances, human well-being, property damages, and hazard liabilities. As a knowledge synthesis, this article presents the best available evidence of urban tree insect / pathogen impacts to guide policy, management and further research. It will enable us to better forecast how growing threats will affect the urban forest and plan for these eventualities

Complementarity of experimental and lattice QCD data on pion parton distributions

We extract pion parton distribution functions (PDFs) in a Monte Carlo global QCD analysis of experimental data together with reduced Ioffe time pseudo-distributions and matrix elements of current-current correlators generated from lattice QCD. By including both experimental and lattice QCD data, our analysis rigorously quantifies both the uncertainties of the pion PDFs and systematic effects intrinsic to the lattice QCD observables. The reduced Ioffe time pseudo-distributions significantly decrease the uncertainties on the PDFs, while the current-current correlators are limited by the systematic effects associated with the lattice. Consistent with recent phenomenological determinations, the behavior of the valence quark distribution of the pion at large momentum fraction is found to be $\sim (1-x)^{ \beta_{\rm eff}}$ with $\beta_{\rm eff} \approx 1.0-1.2$.Comment: 46 pages, 15 figure

Caspofungin Use in Daily Clinical Practice for Treatment of Invasive Aspergillosis: Results of a Prospective Observational Registry

<p>Abstract</p> <p>Background</p> <p>A prospective observational registry assessed real world experience with caspofungin monotherapy or combination therapy for the initial or salvage treatment of proven or probable invasive aspergillosis (IA).</p> <p>Methods</p> <p>Data were collected from April 2006 to September 2007 for patients treated with caspofungin for a single episode of IA. Clinical effectiveness was categorized as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT).</p> <p>Results</p> <p>Consecutive patients (n = 103) with proven or probable IA (per EORTC/MSG criteria) were identified from 11 countries. Malignancy (76.7%), neutropenia (64.1%), allogeneic hematopoietic stem cell transplantation (HSCT, 22.3%), solid organ transplantation (8.7%), autologous HSCT (4.9%), and HIV/AIDS (2.9%) were the most common underlying conditions. Most patients (84.5%) had pulmonary IA. <it>Aspergillus fumigatus </it>was the most frequently isolated species. The majority of patients received caspofungin monotherapy (82.5%) primarily as salvage therapy (82.4%). The main reason for switching to salvage therapy was clinical failure of the first-line therapy (69%). A favorable response at EOCT was seen in 56.4% (57/101) of patients overall, including 56.5% (48/85) and 56.3% (9/16) of patients receiving caspofungin monotherapy and combination therapy, respectively. Favorable response rates in clinically relevant subgroups were: malignancy, 51.9% (41/79); allogeneic HSCT, 56.5% (13/23); and neutropenia at time of hospitalization, 53.0% (35/66). There was a 72.3% (73/101) survival at 7 days after EOCT. Serious adverse events related to caspofungin were reported in 4 cases (3.9%); 3 patients (2.9%) discontinued treatment due to an adverse event related to caspofungin.</p> <p>Conclusions</p> <p>Caspofungin was both effective and well tolerated among high-risk patient groups such as those with neutropenia and active malignancies.</p

Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation

Background Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient's kidney, liver and coagulation functions. Results In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation

Inositol Hexakisphosphate-Induced Autoprocessing of Large Bacterial Protein Toxins

Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms for effector translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is activated for autoprocessing by binding inositol hexakisphosphate (InsP6), a molecule found exclusively in eukaryotic cells. Thus, InsP6-induced autoprocessing represents a unique mechanism for toxin effector delivery specifically within the target cell. This review summarizes recent studies of the structural and molecular events for activation of autoprocessing for both CGT and MARTX toxins, demonstrating both similar and potentially distinct aspects of autoprocessing among the toxins that utilize this method of activation and effector delivery

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m−2) and epirubicin (120 mg m−2) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12 000 mg m−2), carboplatin (900 mg m−2) and epirubicin (180 mg m−2). Patients were autografted with a median number of 3.7 × 106 CD34+ cells kg−1 (range, 1.9–26.5 × 106) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours. © 1999 Cancer Research Campaig