Biobanking in the Year 2007

Biobanking is an emerging specialty in which competencies in cellular and molecular biology, medicine, genetics, cryobiology, bioengineering, information technology and ethics merge into a servic

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

Objectives: The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization. Methods: Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir Cmin range was set at 1-3 mg/L, and average ganciclovir trough concentrations (Cmin ) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average Cmin below or above 1 or 3 mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir Cmin cut-off predictive for clinical efficacy or toxicity. Results: Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13 159.75-151 340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average Cmin below or above 1 mg/L (100.0% vs. 53.8%; p = .25) and/or 3 mg/L (65.2% vs. 33.3%; p = .20). ROC analysis did not allow to identify an average Cmin cut-off predictive of clinical efficacy or toxicity. Conclusions: No clear relationship between ganciclovir Cmin and neither CMV eradication nor safety issues was identified

Developing a policy for paediatric biobanks: Principles for good practice

The participation of minors in biobank research can offer great benefits for science and health care. However, as minors are a vulnerable population they are also in need of adequate protective measures when they are enrolled in research. Research using biobanked biological samples from children poses additional ethical issues to those raised by research using adult biobanks. For example, small children have only limited capacity, if any, to understand the meaning and implications of the research and to give a documented agreement to it. Older minors are gradually acquiring this capacity. We describe principles for good practice related to the inclusion of minors in biobank research, focusing on issues related to benefits and subsidiarity, consent, proportionality and return of results. Some of these issues are currently heavily debated, and we conclude by providing principles for good practice for policy makers of biobanks, researchers and anyone involved in dealing with stored tissue samples from children. Actual implementation of the principles will vary according to different jurisdictions

Relationship between immune response to SARS-CoV2 vaccines and development of breakthrough infection in solid organ transplant recipients: the CONTRAST cohort

Background: SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions: SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI

The Highly Energetic Expansion of SN2010bh Associated with GRB 100316D

We present the spectroscopic and photometric evolution of the nearby (z = 0.059) spectroscopically confirmed type Ic supernova, SN 2010bh, associated with the soft, long-duration gamma-ray burst (X-ray flash) GRB 100316D. Intensive follow-up observations of SN 2010bh were performed at the ESO Very Large Telescope (VLT) using the X-shooter and FORS2 instruments. Owing to the detailed temporal coverage and the extended wavelength range (3000--24800 A), we obtained an unprecedentedly rich spectral sequence among the hypernovae, making SN 2010bh one of the best studied representatives of this SN class. We find that SN 2010bh has a more rapid rise to maximum brightness (8.0 +/- 1.0 rest-frame days) and a fainter absolute peak luminosity (L_bol~3e42 erg/s) than previously observed SN events associated with GRBs. Our estimate of the ejected (56)Ni mass is 0.12 +/- 0.02 Msun. From the broad spectral features we measure expansion velocities up to 47,000 km/s, higher than those of SNe 1998bw (GRB 980425) and 2006aj (GRB 060218). Helium absorption lines He I lambda5876 and He I 1.083 microm, blueshifted by ~20,000--30,000 km/s and ~28,000--38,000 km/s, respectively, may be present in the optical spectra. However, the lack of coverage of the He I 2.058 microm line prevents us from confirming such identifications. The nebular spectrum, taken at ~186 days after the explosion, shows a broad but faint [O I] emission at 6340 A. The light-curve shape and photospheric expansion velocities of SN 2010bh suggest that we witnessed a highly energetic explosion with a small ejected mass (E_k ~ 1e52 erg and M_ej ~ 3 Msun). The observed properties of SN 2010bh further extend the heterogeneity of the class of GRB supernovae.Comment: 37 pages and 12 figures (one-column pre-print format), accepted for publication in Ap

GRIPS - Gamma-Ray Imaging, Polarimetry and Spectroscopy

We propose to perform a continuously scanning all-sky survey from 200 keV to 80 MeV achieving a sensitivity which is better by a factor of 40 or more compared to the previous missions in this energy range. The Gamma-Ray Imaging, Polarimetry and Spectroscopy (GRIPS) mission addresses fundamental questions in ESA's Cosmic Vision plan. Among the major themes of the strategic plan, GRIPS has its focus on the evolving, violent Universe, exploring a unique energy window. We propose to investigate $\gamma$-ray bursts and blazars, the mechanisms behind supernova explosions, nucleosynthesis and spallation, the enigmatic origin of positrons in our Galaxy, and the nature of radiation processes and particle acceleration in extreme cosmic sources including pulsars and magnetars. The natural energy scale for these non-thermal processes is of the order of MeV. Although they can be partially and indirectly studied using other methods, only the proposed GRIPS measurements will provide direct access to their primary photons. GRIPS will be a driver for the study of transient sources in the era of neutrino and gravitational wave observatories such as IceCUBE and LISA, establishing a new type of diagnostics in relativistic and nuclear astrophysics. This will support extrapolations to investigate star formation, galaxy evolution, and black hole formation at high redshifts.Comment: to appear in Exp. Astron., special vol. on M3-Call of ESA's Cosmic Vision 2010; 25 p., 25 figs; see also www.grips-mission.e

GRB 081007 AND GRB 090424: THE SURROUNDING MEDIUM, OUTFLOWS, AND SUPERNOVAE

We discuss the results of the analysis of multi-wavelength data for the afterglows of GRB 081007 and GRB 09042We discuss the results of the analysis of multi-wavelength data for the afterglows of GRB 081007 and GRB 090424, two bursts detected by Swift. One of them, GRB 081007, also shows a spectroscopically confirmed supernova, SN 2008hw, which resembles SN 1998bw in its absorption features, while the maximum magnitude may be fainter, up to 0.7 mag, than observed in SN 1998bw. Bright optical flashes have been detected in both events, which allows us to derive solid constraints on the circumburst-matter density profile. This is particularly interesting in the case of GRB081007, whose afterglow is found to be propagating into a constant-density medium, yielding yet another example of a gamma-ray burst (GRB) clearly associated with a massive star progenitor which did not sculpt the surroundings with its stellar wind. There is no supernova component detected in the afterglow of GRB090424, likely because of the brightness of the host galaxy, comparable to the Milky Way. We show that the afterglow data are consistent with the presence of both forward- and reverse-shock emission powered by relativistic outflows expanding into the interstellar medium. The absence of optical peaks due to the forward shock strongly suggests that the reverse-shock regions should be mildly magnetized. The initial Lorentz factor of outflow of GRB081007 is estimated to be ?? ~ 200, while for GRB090424 a lower limit of ?? > 170 is derived. We also discuss the prompt emission of GRB081007, which consists of just a single pulse. We argue that neither the external forward-shock model nor the shock-breakout model can account for the prompt emission data and suggest that the single-pulse-like prompt emission may be due to magnetic energy dissipation of a Poynting-flux-dominated outflow or to a dissipative photosphere

Coe Genes Are Expressed in Differentiating Neurons in the Central Nervous System of Protostomes

Genes of the coe (collier/olfactory/early B-cell factor) family encode Helix-Loop-Helix transcription factors that are widely conserved in metazoans and involved in many developmental processes, neurogenesis in particular. Whereas their functions during vertebrate neural tube formation have been well documented, very little is known about their expression and role during central nervous system (CNS) development in protostomes. Here we characterized the CNS expression of coe genes in the insect Drosophila melanogaster and the polychaete annelid Platynereis dumerilii, which belong to different subgroups of protostomes and show strikingly different modes of development. In the Drosophila ventral nerve cord, we found that the Collier-expressing cells form a subpopulation of interneurons with diverse molecular identities and neurotransmitter phenotypes. We also demonstrate that collier is required for the proper differentiation of some interneurons belonging to the Eve-Lateral cluster. In Platynereis dumerilii, we cloned a single coe gene, Pdu-coe, and found that it is exclusively expressed in post mitotic neural cells. Using an original technique of in silico 3D registration, we show that Pdu-coe is co-expressed with many different neuronal markers and therefore that, like in Drosophila, its expression defines a heterogeneous population of neurons with diverse molecular identities. Our detailed characterization and comparison of coe gene expression in the CNS of two distantly-related protostomes suggest conserved roles of coe genes in neuronal differentiation in this clade. As similar roles have also been observed in vertebrates, this function was probably already established in the last common ancestor of all bilaterians

Unveiling the enigma of ATLAS17aeu

Aims: The unusual transient ATLAS17aeu was serendipitously detected within the sky localisation of the gravitational wave trigger GW 170104. The importance of a possible association with gravitational waves coming from a binary black hole merger led to an extensive follow-up campaign, with the aim of assessing a possible connection with GW 170104. Methods: With several telescopes, we carried out both photometric and spectroscopic observations of ATLAS17aeu, for several epochs, between ∼3 and ∼230 days after the first detection. Results: We studied in detail the temporal and spectroscopic properties of ATLAS17aeu and its host galaxy. Although at low significance and not conclusive, we found similarities to the spectral features of a broad-line supernova superposed onto an otherwise typical long-GRB afterglow. Based on analysis of the optical light curve, spectrum, and host galaxy spectral energy distribution, we conclude that the redshift of the source is probably z ≃ 0.5 ± 0.2. Conclusions: While the redshift range we have determined is marginally compatible with that of the gravitational wave event, the presence of a supernova component and the consistency of this transient with the Ep-Eiso correlation support the conclusion that ATLAS17aeu was associated with the long gamma-ray burst GRB 170105A. This rules out the association of the GRB 170105A/ATLAS17aeu transient with the gravitational wave event GW 170104, which was due to a binary black hole merger. Based on observations made with the following telescopes: Copernico, TNG (under programme A34TAC_24), GTC (under programmes GTCMULTIPLE2D-16B and GTCMULTIPLE2G-17A), LBT (under programme 2016_2017_19), and HST (under programme GO14270).Spectral data for this source shown on this paper are available on the Weizmann Interactive Supernova Data Repository (WISeREP, http://https://wiserep.weizmann.ac.il/)

GRAWITA: VLT Survey Telescope observations of the gravitational wave sources GW150914 and GW151226

We report the results of deep optical follow-up surveys of the first two gravitational-wave sources, GW150914 and GW151226, done by the GRAvitational Wave Inaf TeAm Collaboration (GRAWITA). The VLT Survey Telescope (VST) responded promptly to the gravitational wave alerts sent by the LIGO and Virgo Collaborations, monitoring a region of 90 and 72 deg2 for GW150914 and GW151226, respectively, and repeated the observations over nearly two months. Both surveys reached an average limiting magnitude of about 21 in the r band. The paper describes the VST observational strategy and two independent procedures developed to search for transient counterpart candidates in multi-epoch VST images. Several transients have been discovered but no candidates are recognized to be related to the gravitational wave events. Interestingly, among many contaminant supernovae, we find a possible correlation between the supernova VSTJ57.77559-59.13990 and GRB 150827A detected by Fermi-GBM. The detection efficiency of VST observations for different types of electromagnetic counterparts of gravitational wave events is evaluated for the present and future follow-up surveys