Intensification of chemotherapy for the treatment of solid tumours: feasibility of a 3-fold increase in dose intensity with peripheral blood progenitor cells and granulocyte colony-stimulating factor.

Dose intensity may be an important determinant of the outcome in cancer chemotherapy, but is often limited by cumulative haematological toxicity. The availability of haematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and of peripheral blood progenitor cell (PBPC) transplantation has allowed the development of a new treatment strategy in which several courses of high-dose combination chemotherapy are administered for the treatment of solid tumours. PBPCs were mobilised before chemotherapy using 12 or 30 micrograms kg-1 day-1 G-CSF (Filgrastim) for 10 days, and were collected by 2-5 leucaphereses. The yields of mononuclear cells, colony-forming units and CD34-positive cells were similar at the two dose levels of Filgrastim, and the numbers of PBPCs were sufficient for rescue following multiple cycles of chemotherapy. High-dose chemotherapy (cyclophosphamide 2.5 g m-2 for 2 days, etoposide 300 mg m-2 for 3 days and cisplatin 50 mg m-2 for 3 days) was administered sequentially for a median of three cycles (range 1-4) to ten patients. Following the 30 evaluable cycles, the median duration of leucopenia < or = 0.5 x 10(9) l-1 and < or = 1.0 x 10(9) l-1 was 7 and 8 days respectively. The median time of thrombopenia < or = 20 x 10(9) l-1 was 6 days. There was no cumulative haematological toxicity. The duration of leucopenia, but not of thrombopenia, was inversely related to the number of reinfused CFU-GM (granulocyte-macrophage colony-forming units). In the majority of patients, neurotoxicity and ototoxicity became dose limiting after three cycles of therapy. However, the average dose intensity delivered was about three times higher than in a standard regimen. The complete response rate in patients with small-cell lung cancers was 66% (95% CI 30-92%) and the median progression-free survival and overall survival were 13 months and 17 months respectively. These results are encouraging and should be compared, in a randomised fashion, with standard dose chemotherapy

Nosocomial nontyphoidal salmonellosis after antineoplastic chemotherapy: reactivation of asymptomatic colonization?

An increased frequency of nontyphoidal salmonellosis is well established in cancer patients, but it is unclear whether this represents increased susceptibility to exogenous infection or opportunistic, endogenous reactivation of asymptomatic carriage. In a retrospective study, a simple case definition was used to identify the probable presence of reactivation salmonellosis in five cancer patients between 1996 and 2002. Reactivation salmonellosis was defined as the development of nosocomial diarrhea >72h after admission and following the administration of antineoplastic chemotherapy in an HIV-seronegative cancer patient who was asymptomatic on admission, in the absence of epidemiological evidence of a nosocomial outbreak. Primary salmonellosis associated with unrecognized nosocomial transmission or community acquisition and an unusually prolonged incubation period could not entirely be ruled out. During the same time period, another opportunistic infection, Pneumocystis pneumonia, was diagnosed in six cancer patients. Presumably, asymptomatic intestinal Salmonella colonization was converted to invasive infection by chemotherapy-associated intestinal mucosal damage and altered innate immune mechanisms. According to published guidelines, stool specimens from patients hospitalized for longer than 72h should be rejected unless the patient is neutropenic or ≧65 years old with significant comorbidity. However, in this study neutropenia was present in only one patient, and four patients were <65 years old. Guidelines should thus be revised in order not to reject stool culture specimens from such patients. In cancer patients, nosocomial salmonellosis can occur as a chemotherapy-triggered opportunistic reactivation infection that may be similar in frequency to Pneumocystis pneumoni

Improving Estimates of Gross Primary Productivity by Assimilating Solar-Induced Fluorescence Satellite Retrievals in a Terrestrial Biosphere Model Using a Process-Based SIF Model

Abstract Over the last few years, solar-induced chlorophyll fluorescence (SIF) observations from space have emerged as a promising resource for evaluating the spatio-temporal distribution of gross primary productivity (GPP) simulated by global terrestrial biosphere models. SIF can be used to improve GPP simulations by optimizing critical model parameters through statistical Bayesian data assimilation techniques. A prerequisite is the availability of a functional link between GPP and SIF in terrestrial biosphere models. Here we present the development of a mechanistic SIF observation operator in the ORCHIDEE (Organizing Carbon and Hydrology In Dynamic Ecosystems) terrestrial biosphere model. It simulates the regulation of photosystem II fluorescence quantum yield at the leaf level thanks to a novel parameterization of non-photochemical quenching as a function of temperature, photosynthetically active radiation, and normalized quantum yield of photochemistry. It emulates the radiative transfer of chlorophyll fluorescence to the top of the canopy using a parametric simplification of the SCOPE (Soil Canopy Observation Photosynthesis Energy) model. We assimilate two years of monthly OCO-2 (Orbiting Carbon Observatory-2) SIF product at 0.5° (2015?2016) to optimize ORCHIDEE photosynthesis and phenological parameters over an ensemble of grid points for all plant functional types. The impact on the simulated GPP is considerable with a large decrease of the global scale budget by 28 GtC/year over the period 1990?2009. The optimized GPP budget (134/136 GtC/year over 1990?2009/2001?2009) remarkably agrees with independent GPP estimates, FLUXSAT (137 GtC/year over 2001?2009) in particular and FLUXCOM (121 GtC/year over 1990?2009). Our results also suggest a biome dependency of the SIF-GPP relationship that needs to be improved for some plant functional types.Peer reviewe

Carbonyl sulfide : comparing a mechanistic representation of the vegetation uptake in a land surface model and the leaf relative uptake approach

Land surface modellers need measurable proxies to constrain the quantity of carbon dioxide (CO2) assimilated by continental plants through photosynthesis, known as gross primary production (GPP). Carbonyl sulfide (COS), which is taken up by leaves through their stomates and then hydrolysed by photosynthetic enzymes, is a candidate GPP proxy. A former study with the ORCHIDEE land surface model used a fixed ratio of COS uptake to CO2 uptake normalised to respective ambient concentrations for each vegetation type (leaf relative uptake, LRU) to compute vegetation COS fluxes from GPP. The LRU approach is known to have limited accuracy since the LRU ratio changes with variables such as photosynthetically active radiation (PAR): while CO2 uptake slows under low light, COS uptake is not light limited. However, the LRU approach has been popular for COS-GPP proxy studies because of its ease of application and apparent low contribution to uncertainty for regional-scale applications. In this study we refined the COS-GPP relationship and implemented in ORCHIDEE a mechanistic model that describes COS uptake by continental vegetation. We compared the simulated COS fluxes against measured hourly COS fluxes at two sites and studied the model behaviour and links with environmental drivers. We performed simulations at a global scale, and we estimated the global COS uptake by vegetation to be -756 Gg S yr(-1) , in the middle range of former studies (-490 to -1335 Gg S yr(-1)). Based on monthly mean fluxes simulated by the mechanistic approach in ORCHIDEE, we derived new LRU values for the different vegetation types, ranging between 0.92 and 1.72, close to recently published averages for observed values of 1.21 for C-4 and 1.68 for C-3 plants. We transported the COS using the monthly vegetation COS fluxes derived from both the mechanistic and the LRU approaches, and we evaluated the simulated COS concentrations at NOAA sites. Although the mechanistic approach was more appropriate when comparing to high-temporal-resolution COS flux measurements, both approaches gave similar results when transporting with monthly COS fluxes and evaluating COS concentrations at stations. In our study, uncertainties between these two approaches are of secondary importance compared to the uncertainties in the COS global budget, which are currently a limiting factor to the potential of COS concentrations to constrain GPP simulated by land surface models on the global scale.Peer reviewe

Climate-Driven Variability and Trends in Plant Productivity Over Recent Decades Based on Three Global Products

Variability in climate exerts a strong influence on vegetation productivity (gross primary productivity; GPP), and therefore has a large impact on the land carbon sink. However, no direct observations of global GPP exist, and estimates rely on models that are constrained by observations at various spatial and temporal scales. Here, we assess the consistency in GPP from global products which extend for more than three decades; two observation‐based approaches, the upscaling of FLUXNET site observations (FLUXCOM) and a remote sensing derived light use efficiency model (RS‐LUE), and from a suite of terrestrial biosphere models (TRENDYv6). At local scales, we find high correlations in annual GPP among the products, with exceptions in tropical and high northern latitudes. On longer time scales, the products agree on the direction of trends over 58% of the land, with large increases across northern latitudes driven by warming trends. Further, tropical regions exhibit the largest interannual variability in GPP, with both rainforests and savannas contributing substantially. Variability in savanna GPP is likely predominantly driven by water availability, although temperature could play a role via soil moisture‐atmosphere feedbacks. There is, however, no consensus on the magnitude and driver of variability of tropical forests, which suggest uncertainties in process representations and underlying observations remain. These results emphasize the need for more direct long‐term observations of GPP along with an extension of in situ networks in underrepresented regions (e.g., tropical forests). Such capabilities would support efforts to better validate relevant processes in models, to more accurately estimate GPP

Post-acute sequelae after SARS-CoV-2 infection by viral variant and vaccination status: a multicenter cross-sectional study.

BACKGROUND Disentangling the effects of SARS-CoV-2 variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in North-Eastern Switzerland. HCW were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCW without positive swab and with negative serology served as controls. The sum of eighteen self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyse the association of mean symptom number with viral variant and vaccination status. RESULTS Among 2'912 participants (median age 44 years, 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number 1.12, p<0.001; median time since infection 18.3 months), after Alpha/Delta infection (0.67 symptoms, p<0.001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms, p=0.005; 3.1 months) compared to uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals, compared to 0.71 with 1-2 vaccinations (p=0.028) and 0.49 with ≥3 prior vaccinations (p=0.30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCW. Vaccination prior to Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population

The European land and inland water CO2, CO, CH4 and N2O balance between 2001 and 2005

Globally, terrestrial ecosystems have absorbed about 30% of anthropogenic greenhouse gas emissions over the period 2000–2007 and inter-hemispheric gradients indicate that a significant fraction of terrestrial carbon sequestration must be north of the Equator. We present a compilation of the CO2, CO, CH4 and N2O balances of Europe following a dual constraint approach in which (1) a landbased balance derived mainly from ecosystem carbon inventories and (2) a land-based balance derived from flux measurements are compared to (3) the atmospheric data-based balance derived from inversions constrained by measurements of atmospheric GHG (greenhouse gas) concentrations. Good agreement between the GHG balances based on fluxes (1294±545 Tg C in CO2-eq yr−1), inventories (1299±200 Tg C in CO2-eq yr−1) and inversions (1210±405 Tg C in CO2-eq yr−1) increases our confidence that the processes underlying the European GHG budget are well understood and reasonably sampled. However, the uncertainty remains large and largely lacks formal estimates. Given that European net land to atmosphere exchanges are determined by a few dominant fluxes, the uncertainty of these key components needs to be formally estimated before efforts could be made to reduce the overall uncertainty. The net land-to-atmosphere flux is a net source for CO2, CO, CH4 and N2O, because the anthropogenic emissions by far exceed the biogenic sink strength. The dual-constraint approach confirmed that the European biogenic sink removes as much as 205±72 Tg C yr−1 from fossil fuel burning from the atmosphere. However, This C is being sequestered in both terrestrial and inland aquatic ecosystems. If the C-cost for ecosystem management is taken into account, the net uptake of ecosystems is estimated to decrease by 45% but still indicates substantial C-sequestration. However, when the balance is extended from CO2 towards the main GHGs, C-uptake by terrestrial and aquatic ecosystems is offset by emissions of non-CO2 GHGs. As such, the European ecosystems are unlikely to contribute to mitigating the effects of climate change.JRC.H.2-Air and Climat

Impact of baseline SARS-CoV-2 antibody status on syndromic surveillance and the risk of subsequent COVID-19-a prospective multicenter cohort study.

BACKGROUND In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. METHODS Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. RESULTS A total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15-0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39-0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49-0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. CONCLUSIONS Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months

A vertically discretised canopy description for ORCHIDEE (SVN r2290) and the modifications to the energy, water and carbon fluxes

Since 70% of global forests are managed and forests impact the global carbon cycle and the energy exchange with the overlying atmosphere, forest management has the potential to mitigate climate change. Yet, none of the land surface models used in Earth system models, and therefore none of today’s predictions of future climate, account for the interactions between climate and forest management. We addressed this gap in modelling capability by developing and parametrizing a version of the land surface model ORCHIDEE to simulate the biogeochemical and biophysical effects of forest management. The most significant changes between the new branch called ORCHIDEE-CAN (SVN r2290) and the trunk version of ORCHIDEE (SVN r2243) are the allometric-based allocation of carbon to leaf, root, wood, fruit and reserve pools; the transmittance, absorbance and reflectance of radiation within the canopy; and the vertical discretisation of the energy budget calculations. In addition, conceptual changes were introduced towards a better process representation for the interaction of radiation with snow, the hydraulic architecture of plants, the representation of forest management and a numerical solution for the photosynthesis formalism of Farquhar, von Caemmerer and Berry. For consistency reasons, these changes were extensively linked throughout the code. Parametrization was revisited after introducing twelve new parameter sets that represent specific tree species or genera rather than a group of often distantly related or even unrelated species, as is the case in widely used plant functional types. Performance of the new model was compared against the trunk and validated against independent spatially explicit data for basal area, tree height, canopy strucure, GPP, albedo and evapotranspiration over Europe. For all tested variables ORCHIDEE-CAN outperformed the trunk regarding its ability to reproduce large-scale spatial patterns as well as their inter-annual variability over Europe. Depending on the data stream, ORCHIDEE-CAN had a 67% to 92% chance to reproduce the spatial and temporal variability of the validation data.JRC.H.5-Land Resources Managemen