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This report describes two cases of disseminated cutaneous Mycobacterium chelonae after hematopoietic stem cell transplantation (HSCT).

In this study, we use a synergy of in situ and remote sensing measurements collected during the SOuthwest FOGs 3D experiment for processes study (SOFOG3D) field campaign in autumn and winter 2019–2020 to analyse the thermodynamic and turbulent processes related to fog formation, evolution, and dissipation across southwestern France. Based on a unique measurement dataset (synergy of cloud radar, microwave radiometer, wind lidar, and weather station data) combined with a fog conceptual model, an analysis of the four deepest fog episodes (two radiation fogs and two advection–radiation fogs) is conducted. The results show that radiation and advection–radiation fogs form under deep and thin temperature inversions, respectively. For both fog categories, the transition period from stable to adiabatic fog and the fog adiabatic phase are driven by vertical mixing associated with an increase in turbulence in the fog layer due to mechanical production (turbulence kinetic energy (TKE) up to 0.4 m2 s−2 and vertical velocity variance (σw2) up to 0.04 m2 s−2) generated by increasing wind and wind shear. Our study reveals that fog liquid water path, fog top height, temperature, radar reflectivity profiles, and fog adiabaticity derived from the conceptual model evolve in a consistent manner to clearly characterise this transition. The dissipation time is observed at night for the advection–radiation fog case studies and after sunrise for the radiation fog case studies. Night-time dissipation is driven by horizontal advection generating mechanical turbulence (TKE at least 0.3 m2 s−2 and σw2 larger than 0.04 m2 s−2). Daytime dissipation is linked to the combination of thermal and mechanical turbulence related to solar heating (near-surface sensible heat flux larger than 10 W m−2) and wind shear, respectively. This study demonstrates the added value of monitoring fog liquid water content and depth (combined with wind, turbulence, and temperature profiles) and diagnostics such as fog liquid water reservoir and adiabaticity to better explain the drivers of the fog life cycle.

The dominant hydrometeor types associated with Brazilian tropical precipitation systems are identified via research X-band dual-polarization radar deployed in the vicinity of the Manaus region (Amazonas) during both the GoAmazon2014/5 and ACRIDICON-CHUVA field experiments. The present study is based on an agglomerative hierarchical clustering (AHC) approach that makes use of dual polarimetric radar observables (reflectivity at horizontal polarization ZH, differential reflectivity ZDR, specific differential-phase KDP, and correlation coefficient ρHV) and temperature data inferred from sounding balloons. The sensitivity of the agglomerative clustering scheme for measuring the intercluster dissimilarities (linkage criterion) is evaluated through the wet-season dataset. Both the weighted and Ward linkages exhibit better abilities to retrieve cloud microphysical species, whereas clustering outputs associated with the centroid linkage are poorly defined. The AHC method is then applied to investigate the microphysical structure of both the wet and dry seasons. The stratiform regions are composed of five hydrometeor classes: drizzle, rain, wet snow, aggregates, and ice crystals, whereas convective echoes are generally associated with light rain, moderate rain, heavy rain, graupel, aggregates, and ice crystals. The main discrepancy between the wet and dry seasons is the presence of both low- and high-density graupel within convective regions, whereas the rainy period exhibits only one type of graupel. Finally, aggregate and ice crystal hydrometeors in the tropics are found to exhibit higher polarimetric values compared to those at midlatitudes.

Discrepancies in population structures, decision making, health systems and numerous other factors result in various COVID-19-mortality dynamics at country scale, and make the forecast of deaths in a country under focus challenging. However, mortality dynamics of countries that are ahead of time implicitly include these factors and can be used as real-life competing predicting models. We precisely propose such a data-driven approach implemented in a publicly available web app timely providing mortality curves comparisons and real-time short-term forecasts for about 100 countries. Here, the approach is applied to compare the mortality trajectories of second-line and front-line European countries facing the COVID-19 epidemic wave. Using data up to mid-April, we show that the second-line countries generally followed relatively mild mortality curves rather than fast and severe ones. Thus, the continuation, after mid-April, of the COVID-19 wave across Europe was likely to be mitigated and not as strong as it was in most of the front-line countries first impacted by the wave (this prediction is corroborated by posterior data).

This study provides an overview of precipitation processes and their sensitivities to environmental conditions in the Central Amazon Basin near Manaus during the GoAmazon2014/5 and ACRIDICON-CHUVA experiments. This study takes advantage of the numerous measurement platforms and instrument systems operating during both campaigns to sample cloud structure and environmental conditions during 2014 and 2015; the rainfall variability among seasons, aerosol loading, land surface type, and topography has been carefully characterized using these data. Differences between the wet and dry seasons were examined from a variety of perspectives. The rainfall rates distribution, total amount of rainfall, and raindrop size distribution (the mass-weighted mean diameter) were quantified over both seasons. The dry season generally exhibited higher rainfall rates than the wet season and included more intense rainfall periods. However, the cumulative rainfall during the wet season was 4 times greater than that during the total dry season rainfall, as shown in the total rainfall accumulation data. The typical size and life cycle of Amazon cloud clusters (observed by satellite) and rain cells (observed by radar) were examined, as were differences in these systems between the seasons. Moreover, monthly mean thermodynamic and dynamic variables were analysed using radiosondes to elucidate the differences in rainfall characteristics during the wet and dry seasons. The sensitivity of rainfall to atmospheric aerosol loading was discussed with regard to mass-weighted mean diameter and rain rate. This topic was evaluated only during the wet season due to the insignificant statistics of rainfall events for different aerosol loading ranges and the low frequency of precipitation events during the dry season. The impacts of aerosols on cloud droplet diameter varied based on droplet size. For the wet season, we observed no dependence between land surface type and rain rate. However, during the dry season, urban areas exhibited the largest rainfall rate tail distribution, and deforested regions exhibited the lowest mean rainfall rate. Airplane measurements were taken to characterize and contrast cloud microphysical properties and processes over forested and deforested regions. Vertical motion was not correlated with cloud droplet sizes, but cloud droplet concentration correlated linearly with vertical motion. Clouds over forested areas contained larger droplets than clouds over pastures at all altitudes. Finally, the connections between topography and rain rate were evaluated, with higher rainfall rates identified at higher elevations during the dry season.

The PEACH project (Projet en Electricité Atmosphérique pour la Campagne HyMeX – the Atmospheric Electricity Project of the HyMeX Program) is the atmospheric electricity component of the Hydrology cycle in the Mediterranean Experiment (HyMeX) experiment and is dedicated to the observation of both lightning activity and electrical state of continental and maritime thunderstorms in the area of the Mediterranean Sea. During the HyMeX SOP1 (Special Observation Period) from 5 September to 6 November 2012, four European operational lightning locating systems (ATDnet, EUCLID, LINET, ZEUS) and the HyMeX lightning mapping array network (HyLMA) were used to locate and characterize the lightning activity over the northwestern Mediterranean at flash, storm and regional scales. Additional research instruments like slow antennas, video cameras, microbarometer and microphone arrays were also operated. All these observations in conjunction with operational/research ground-based and airborne radars, rain gauges and in situ microphysical records are aimed at characterizing and understanding electrically active and highly precipitating events over southeastern France that often lead to severe flash floods. Simulations performed with cloud resolving models like Meso-NH and Weather Research and Forecasting are used to interpret the results and to investigate further the links between dynamics, microphysics, electrification and lightning occurrence. Herein we present an overview of the PEACH project and its different instruments. Examples are discussed to illustrate the comprehensive and unique lightning data set, from radio frequency to acoustics, collected during the SOP1 for lightning phenomenology understanding, instrumentation validation, storm characterization and modeling.

Usually self-limited, hepatitis E virus (HEV) infection may evolve to chronicity and cirrhosis in immunosuppressed patients. HEV infection has been described in solid-organ transplantation and hematology patients, but for allogeneic hematopoietic stem cell transplant (alloHSCT) recipients, only small cohorts are available. This retrospective nationwide multi-center series aimed to describe HEV diagnostic practices in alloHSCT French centers, and the course of infection in the context of alloHSCT. Twenty-nine out of 37 centers participated. HEV search in case of liver function tests (LFT) abnormalities was never performed in 24% of centers, occasionally in 55%, and systematically in 21%. Twenty-five cases of active HEV infection were diagnosed in seven centers, all because of LFT abnormalities, by blood nucleic acid testing. HEV infection was diagnosed in three patients before alloHSCT; HEV infection did not influence transplantation planning, and resolved spontaneously before or after alloHSCT. Twenty-two patients were diagnosed a median of 283 days after alloHSCT. Nine patients (41%) had spontaneous viral clearance, mostly after immunosuppressive treatment decrease. Thirteen patients (59%) received ribavirin, with sustained viral clearance in 11/12 evaluable patients. We observed three HEV recurrences but no HEV-related death or liver failure, nor evolution to cirrhosis.

This study is a multi-technique investigation of the Paris carbonaceous chondrite directly applied on two selected 500 × 500 µm² areas of a millimetric fragment, without any chemical extraction. By mapping the partial hydration of the amorphous silicate phase dominating the meteorite sample matrix, infrared spectroscopy gave an interesting glimpse into the way the fluid may have circulated into the sample and partially altered it. The TOF-SIMS in-situ analysis allowed the studying and mapping of the wide diversity of chemical moieties composing the meteorite organic content. The results of the combined techniques show that at the micron scale, the organic matter was always spatially associated with the fine-grained and partially-hydrated amorphous silicates and to the presence of iron in different chemical states. These systematic associations, illustrated in previous studies of other carbonaceous chondrites, were further supported by the identification by TOF-SIMS of cyanide and/or cyanate salts that could be direct remnants of precursor ices that accreted with dust during the parent body formation, and by the detection of different metal-containing large organic ions. Finally, the results obtained emphasized the importance of studying the specific interactions taking place between organic and mineral phases in the chondrite matrix, in order to investigate their role in the evolution story of primitive organic matter in meteorite parent bodies.

Fusarium species cause rare and severe infections. Their incidence is increasing in immunocompromised patients but they are also observed in healthy hosts. Because of the rapid dissemination of infection and the frequent resistance of Fusarium species to antifungal drugs, histopathologic evidence of hyphae is very helpful to obtain the diagnosis rapidly. We report the clinical and pathological features of two patients with initial cutaneous lesions. Cutaneous early biopsies showed microvessel involvement with hyphae and thrombosis. Fusarium infection was confirmed by skin culture. Hyphae within a microvessel thrombus in the skin were highly suggestive of disseminated fungal infection. These pathological features enabled to establish an early diagnosis and to start efficient antifungal treatment. In early cutaneous biopsies of immunocompromised patients, the presence of cutaneous vessel thrombosis can suggest a fungal infection and may help to start specific therapy without delay for these life-threatening infections.

Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of graft-versus-host disease, and profiles of cytomegalovirus reactivation. In multivariate analysis we found that the absolute numbers of CD56bright natural killer cells at month 3 were significantly higher after myeloablative conditioning than after reduced intensity conditioning. Acute graft-versus-host disease impaired reconstitution of total and CD56dim natural killer cells at month 3. In contrast, high natural killer cell count at month 3 was associated with a lower incidence of chronic graft-versus-host disease, independently of a previous episode of acute graft-versus-host disease and stem cell source. NKG2C+CD56dim and total natural killer cell counts at month 3 were lower in patients with reactivation of cytomegalovirus between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced later cytomegalovirus reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus, and contributing to their translation and degradation in the cytoplasm. Here we show by yeast two hybrid and co-immunoprecipitation experiments, followed by ribosome fractionation and fluorescent microscopy, that a subunit of the Ccr4-Not complex, Not5, is essential in the nucleus for the cytoplasmic functions of Rpb4. Not5 interacts with Rpb4; it is required for the presence of Rpb4 in polysomes, for interaction of Rpb4 with the translation initiation factor eIF3 and for association of Rpb4 with mRNAs. We find that Rpb7 presence in the cytoplasm and polysomes is much less significant than that of Rpb4, and that it does not depend upon Not5. Hence Not5-dependence unlinks the cytoplasmic functions of Rpb4 and Rpb7. We additionally determine with RNA immunoprecipitation and native gel analysis that Not5 is needed in the cytoplasm for the co-translational assembly of RNA polymerase II. This stems from the importance of Not5 for the association of the R2TP Hsp90 co-chaperone with polysomes translating RPB1 mRNA to protect newly synthesized Rpb1 from aggregation. Hence taken together our results show that Not5 interconnects translation and transcription.

Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged

Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01).

Background Voriconazole treatment increases early survival of allogeneic hematopoietic stem cell transplant recipients with invasive aspergillosis. We investigated whether this survival advantage translates into an increased long-term survival.Design and Methods This retrospective study involved all patients with an invasive aspergillosis diagnosis transplanted between September 1997 and December 2008, at the Saint-Louis Hospital, Paris, France. The primary end point was survival up to 36 months. Survival analysis before and after 12 weeks, as well as cumulative incidence analysis in a competing risk framework, were used to assess the effect of voriconazole treatment and other factors on mortality.Results Among 87 patients, 42 received first-line voriconazole and 45 received another antifungal agent. Median survival time was 2.6 months and survival rate at 36 months was 18%. Overall, there was a significant difference in the survival rates of the two groups. Specifically, there was a dramatic difference in survival rates up to ten months post-aspergillosis diagnosis but no significant difference after this time. Over the first 36 months as a whole, no significant difference in survival rate was observed between the two groups. First-line voriconazole significantly reduced aspergillosis-attributable mortality. However, first-line voriconazole patients experienced a significantly higher probability of death from a non-aspergillosis-attributable cause.Conclusions Although the prognosis for invasive aspergillosis after stem cell transplantation has dramatically improved with the use of voriconazole, this major advance in care does not translate into increased long-term survival for these severely immunocompromised patients.

Background Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen.Design and Methods We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days).Results Median age was 21 years (range 4–43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II–IV graft-versus-host disease was 23% (95%CI 13–34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20–46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P=0.017). With a median follow up of 73 months (range 8–233), the estimated 6-year overall survival was 87% (95% CI 78–97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin’s lymphoma) during follow up.Conclusions Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.

Immune reconstitution was analyzed in 140 consecutive patients who were 2-year disease-free and who underwent myeloablative allogeneic transplantation. A CD4 and CD8 defect was observed involving naive, terminally differentiated, memory and competent cells and above limits values for activated subsets. Natural killer cells normalize at six months while we observed expansion of CD19+/CD5+ B cells after three months and a persisting defect of memory B cells. Chronic graft-versus-host disease did not influence significantly those parameters for CD8 subsets while the naïve and competent CD4 subsets were strongly affected. But the most profound impact of chronic graft-versus-host disease was on B-cell subsets, especially on the memory B population. The cumulative incidence of late severe infections was low (14% at four years). Using Cox’s models, only low B-cell counts at 12 (P=0.02) and 24 (P=0.001) months were associated with the hazard of developing late infection, in particular if patients did not develop chronic graft-versus-host disease.