JWST/NIRSpec Prospects on Transneptunian Objects

The transneptunian region has proven to be a valuable probe to test models of the formation and evolution of the solar system. To further advance our current knowledge of these early stages requires an increased knowledge of the physical properties of Transneptunian Objects (TNOs). Colors and albedos have been the best way so far to classify and study the surface properties of a large number TNOs. However, they only provide a limited fraction of the compositional information, required for understanding the physical and chemical processes to which these objects have been exposed since their formation. This can be better achieved by near-infrared (NIR) spectroscopy, since water ice, hydrocarbons, and nitrile compounds display diagnostic absorption bands in this wavelength range. Visible and NIR spectra taken from ground-based facilities have been observed for ~80 objects so far, covering the full range of spectral types: from neutral to extremely red with respect to the Sun, featureless to volatile-bearing and volatile-dominated (Barkume et al., 2008; Guilbert et al., 2009; Barucci et al., 2011; Brown, 2012). The largest TNOs are bright and thus allow for detailed and reliable spectroscopy: they exhibit complex surface compositions, including water ice, methane, ammonia, and nitrogen. Smaller objects are more difficult to observe even from the largest telescopes in the world. In order to further constrain the inventory of volatiles and organics in the solar system, and understand the physical and chemical evolution of these bodies, high-quality NIR spectra of a larger sample of TNOs need to be observed. JWST/NIRSpec is expected to provide a substantial improvement in this regard, by increasing both the quality of observed spectra and the number of observed objects. In this paper, we review the current knowledge of TNO properties and provide diagnostics for using NIRSpec to constrain TNO surface compositions

Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis

Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64% (60-68%) and overall survival was 74% (71-78%) at ten years; results were better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients aged = 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.Peer reviewe

Tree ring record from a Redwood

The permanent exhibition of the Staatliches Museum für Naturkunde Stuttgart, Schloss Rosenstein, contains the cross section of a California coast redwood tree (Sequoia sempervirens) from Humboldt County, California, felled in 1966 reveals 1285 annual tree-rings. The measured thicknesses of tree-rings comprise a time series with distinct thickness variations, which are the expression of changing environmental conditions such as precipitation and fog. These factors are controlled by nearby coastal upwelling, which is again influenced by El Nino-Southern Oscillation (ENSO), and which in turn can be influenced by variations of solar radiance. In fact, the tree-ring time series comprises evidence for three orders of solar cycles that may have indirectly controlled tree growth: Hale cycle (21.9 yr), Gleissberg cycle (88.6 yr) and De Vries cycle (209.8 yr). These interpretations should, however, be treated with caution, because it is the only cross section known and the acquirement of reliable data requires cross dating of several sections. (was: The cross section of a California coast redwood tree (Sequoia sempervirens) felled in 1966 reveals 1285 annual tree-rings. The measured thicknesses of tree-rings comprise a time series with distinct thickness variations, which are the expression of changing environmental conditions such as precipitation and fog. These factors are controlled by nearby coastal upwelling, which is again influenced by El Nino-Southern Oscillation (ENSO), and which in turn can be influenced by variations of solar radiance. In fact, the tree-ring time series comprises evidence for three orders of solar cycles that may have indirectly controlled tree growth: Hale cycle (21.9 yr), Gleissberg cycle (88.6 yr) and De Vries cycle (209.8 yr)

Bridging Integrator 1 (BIN1) Protein Expression Increases in the Alzheimer's Disease Brain and Correlates with Neurofibrillary Tangle Pathology

Recent genome wide association studies (GWAS) have implicated bridging integrator 1 (BIN1) as a late-onset Alzheimer’s disease (AD) susceptibility gene. There are at least 15 different known isoforms of BIN1, with many being expressed in the brain including the longest isoform (iso1), which is brain-specific and localizes to axon initial segments and nodes of Ranvier. It is currently unknown what role BIN1 plays in AD. We analyzed BIN1 protein expression from a large number (N = 71) of AD cases and controls from five different brain regions [hippocampus, inferior parietal (IP) cortex, inferior temporal (IT) cortex, frontal cortex (BA9), and superior and middle temporal gyri (SMTG)]. We found that the amount of the largest isoform of BIN1 was significantly reduced in the AD brain compared to age-matched controls, and smaller BIN1 isoforms were significantly increased. Further, BIN1 was significantly correlated with the amount of neurofibrillary tangle (NFT) pathology but not with either diffuse or neuritic plaques, or with the amount of amyloid-β peptide. BIN1 is known to be abnormally expressed in another human disease, myotonic dystrophy, which also features prominent NFT pathology. These data suggest that BIN1 is likely involved in AD as a modulator of NFT pathology, and that this role may extend to other human diseases that feature tau pathology

Outcome of allogeneic haematopoietic stem cell transplantation in myeloproliferative neoplasm, unclassifiable: a retrospective study by the Chronic Malignancies Working Party of the EBMT

Myeloproliferative Neoplasm (MPN), unclassifiable (MPN-U) is a heterogeneous disease with regards to both clinical phenotype and disease course. Patients may initially be asymptomatic or present with leucocytosis or thrombocytosis, anaemia, progressive splenomegaly, constitutional symptom, thromboses or accelerated/blastic phase disease. Treatment strategies are variable and there are no widely accepted consensus management guidelines for MNU-U. Allogeneic Haematopoietic Cell Transplantation (allo-HCT) remains the only curative strategy yet outcomes, to date, are not well defined. We hereby report on the largest retrospective study of patients with MPN-U undergoing allo-HCT, highlighting the potentially curative role and providing clinicians with robust engraftment, GvHD and outcome data to facilitate patient discussion

Towards multi-order hard X-ray imaging with multilayer zone plates

This article describes holographic imaging experiments using a hard X-ray multilayer zone plate (MZP) with an outermost zone width of 10 nm at a photon energy of 18 keV. An order-sorting aperture (OSA) is omitted and emulated during data analysis by a `software OSA'. Scanning transmission X-ray microscopy usually carried out in the focal plane is generalized to the holographic regime. The MZP focus is characterized by a three-plane phase-retrieval algorithm to an FWHM of 10 nm

Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT.

Allogeneic Haematopoietic Stem Cell Transplant (allo-HSCT) remains the only curative approach for Myelofibrosis (MF). Scarce information exists in the literature on the outcome and, indeed, management of those MF patients who relapse following transplant. We hereby report on the management and outcome of 202 patients who relapsed post allo-HSCT for MF

Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trialResearch in context

Summary: Background: Failure of gastrointestinal acute graft-versus-host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD. Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980). Findings: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (ORR) was 38% in the prospective population, including 5 complete responses (CR), 2 very good partial responses (VGPR) and 2 partial responses (PR). In the EAP, the GI-ORR was 58% (17 CR, 9 VGPR and 4 PR). The 12-month overall survival (OS) was 25% in the prospective study and 38% in the EAP. Regarding safety, five infectious complications, including 3 sepsis, could not be excluded from being related to the study procedure in HERACLES. Shotgun sequencing analyses of the identified strains suggest that none were found in MaaT013. In the EAP, 18 pharmacovigilance cases were reported among 52 treated patients, including 11 bacteraemia/sepsis. In HERACLES, we observed in stools from responding patients at D28 a higher microbiota richness and increased levels of beneficial bacteria, in particular butyrate producers, along with increased levels of short-chain fatty acid and bile acids. In contrast, stools from non-responding (NR) patients displayed increased levels of pathogenic pro-inflammatory bacteria along with increased systemic inflammatory parameters. Interpretation: Overall, MaaT013 was safe in this population of highly immunocompromised patients and was associated with responses in some patients with GI-aGvHD and deserves further investigation. Funding: MaaT Pharma