XMM-Newton observations of the low-luminosity cataclysmic variable V405 Pegasi

V405 Peg is a low-luminosity cataclysmic variable (CV) that was identified as the optical counterpart of the bright, high-latitude ROSAT all-sky survey source RBS1955. The system was suspected to belong to a largely undiscovered population of hibernating CVs. Despite intensive optical follow-up its subclass however remained undetermined. We want to further classify V405 Peg and understand its role in the CV zoo via its long-term behaviour, spectral properties, energy distribution and accretion luminosity. We perform a spectral and timing analysis of \textit{XMM-Newton} X-ray and ultra-violet data. Archival WISE, HST, and Swift observations are used to determine the spectral energy distribution and characterize the long-term variability. The X-ray spectrum is characterized by emission from a multi-temperature plasma. No evidence for a luminous soft X-ray component was found. Orbital phase-dependent X-ray photometric variability by $\sim50\%$ occurred without significant spectral changes. No further periodicity was significant in our X-ray data. The average X-ray luminosity during the XMM-Newton observations was L_X, bol simeq 5e30 erg/s but, based on the Swift observations, the corresponding luminosity varied between 5e29 erg/s and 2e31 erg/son timescales of years. The CV subclass of this object remains elusive. The spectral and timing properties show commonalities with both classes of magnetic and non-magnetic CVs. The accretion luminosity is far below than that expected for a standard accreting CV at the given orbital period. Objects like V405 Peg might represent the tip of an iceberg and thus may be important contributors to the Galactic Ridge X-ray Emission. If so they will be uncovered by future X-ray surveys, e.g. with eROSITA.Comment: A&A, in pres

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

BackgroundNovel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use.MethodsOur mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30.ResultsUnique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context.ConclusionSupplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning

Are we ready for scaling up restoration actions? An insight from Mediterranean macroalgal canopies

Extensive loss of macroalgal forests advocates for large-scale restoration interventions, to compensate habitat degradation and recover the associated ecological functions and services. Yet, restoration attempts have generally been limited to small spatial extensions, with the principal aim of developing efficient restoration techniques. Here, the success of outplanting Cystoseira amentacea v. stricta germlings cultured in aquaria was experimentally explored at a scale of tens of kms, by means of a multifactorial experimental design. In the intertidal rocky shores of SE Italy, locations with a continuous distribution for hundreds of meters or with few thalli forming patches of few centimeters of C. amentacea canopy were selected. In each location, the effects of adult conspecifics and the exclusion of macrograzers (salema fish and sea urchins) on the survival of germlings were tested. We evaluated the most critical determinants of mortality for germlings, including the overlooked pressure of mesograzers (e.g. amphipods, small mollusks, polychaetes). Despite the high mortality observed during outplanting and early settlement stages, survival of C. amentacea germlings was consistently favored by the exclusion of macrograzers, while the presence of adult conspecifics had no effects. In addition, the cost analysis of the interventions showed the feasibility of the ex-situ method, representing an essential tool for preserving Cystoseira forests. Large scale restoration is possible but requires baseline information with an in-depth knowledge of the species ecology and of the areas to be restored, together with the development of specific cultivation protocols to make consistently efficient restoration interventions

Double Heterozygous Mutations Involving Both HNF1A/MODY3 and HNF4A/MODY1 Genes: A case report

none9Abstract We describe the first MODY case with mutations involving both HNF4A and HNF1A genes. History and Examination. A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both parents (father at age 50, mother at age 54) and the sister (age 32 during pregnancy). Investigations. The genetic screening showed a double heterozygosity for the mutation p.E508K in HNF1A/MODY3 gene and the novel variant p.R80Q in HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister and her two children carried the MODY1 mutation. Conclusions. MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation, early need of insulin therapy to control hyperglycemia).mixedG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. MantovaniG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. Mantovan

Miconazole-like scaffold is a promising lead for Naegleria fowleri-specific CYP51 inhibitors

Developing drugs for brain infection by Naegleria fowleri is an unmet medical need. We used a combination of cheminformatics, target-, and phenotypic-based drug discovery methods to identify inhibitors that target an essential N. fowleri enzyme, sterol 14-demethylase (NfCYP51). A total of 124 compounds preselected in silico were tested against N. fowleri. Nine primary hits with EC50 ≤ 10 μM were phenotypically identified. Cocrystallization with NfCYP51 focused attention on one primary hit, miconazole-like compound 2a. The S-enantiomer of 2a produced a 1.74 Å cocrystal structure. A set of analogues was then synthesized and evaluated to confirm the superiority of the S-configuration over the R-configuration and the advantage of an ether linkage over an ester linkage. The two compounds, S-8b and S-9b, had an improved EC50 and KD compared to 2a. Importantly, both were readily taken up into the brain. The brain-to-plasma distribution coefficient of S-9b was 1.02 ± 0.12, suggesting further evaluation as a lead for primary amoebic meningoencephalitis

Spatiotemporal variation of the epifaunal assemblages associated to Sargassum muticum on the NW Atlantic coast of Morocco

Epifaunal assemblages inhabiting the non-indigenous macroalga Sargassum muticum (Yendo) Fensholt were investigated on two physically distinct intertidal rocky (S1) and sandy (S2) sites along the Atlantic coast of Morocco. The objective of this study was to test whether the habitat-forming marine alga S. muticum invasive in these sites supported different epifaunal assemblages under different environmental conditions and through time. The gastropods Steromphala umbilicalis, S. pennanti, and Rissoa parva and the isopod Dynamene bidentata were the most contributive species to the dissimilarity of epifaunal assemblage structure between both sites throughout seasons. SIMPER analysis showed a dissimilarity of 58.3-78.5% in the associated species composition of S. muticum between study sites with respect to sampling season. Species diversity and total abundance were significantly higher at the rocky site compared to the sandy site. PERMANOVA analyses showed significant differences of associated epifaunal assemblage structure for the season and site interaction. Accordingly, site and season were determinant factors conditioning the role of habitat in structuring epifaunal assemblages.info:eu-repo/semantics/publishedVersio