Fetal MRI : an essential step in interpreting complex ultrasound findings

Background: Fetal magnetic resonance imaging (MRI) allows for the interpretation of complex fetal anomalies detected on ultrasound (US). Locally it has been available since 2013 but has remained underused. Method: In this paper we report the US and MRI findings of all cases of fetal MRI that were taken to date locally and how MRI can contribute to the clarification of malformations, management, counseling, evaluation of prognosis and ruling out of other possible malformations. Results: The cases reported were: two cases of hydroureter; gastroschisis; ventriculomegaly; intracranial haemorrhage; splenic cyst; Arnold Chiari II malformation. In all seven cases MRI was able to add to or change the diagnosis. Conclusion: Fetal MRI acts as an adjunct to US in interpreting abnormal fetal development. It is a safe non-invasive method of imaging that allows the clinician to take more informed decisions and better parental counselling.peer-reviewe

Eigenvalue spectral properties of sparse random matrices obeying Dale's law

Understanding the dynamics of large networks of neurons with heterogeneous connectivity architectures is a complex physics problem that demands novel mathematical techniques. Biological neural networks are inherently spatially heterogeneous, making them difficult to mathematically model. Random recurrent neural networks capture complex network connectivity structures and enable mathematically tractability. Our paper generalises previous classical results to sparse connectivity matrices which have distinct excitatory (E) or inhibitory (I) neural populations. By investigating sparse networks we construct our analysis to examine the impacts of all levels of network sparseness, and discover a novel nonlinear interaction between the connectivity matrix and resulting network dynamics, in both the balanced and unbalanced cases. Specifically, we deduce new mathematical dependencies describing the influence of sparsity and distinct E/I distributions on the distribution of eigenvalues (eigenspectrum) of the networked Jacobian. Furthermore, we illustrate that the previous classical results are special cases of the more general results we have described here. Understanding the impacts of sparse connectivities on network dynamics is of particular importance for both theoretical neuroscience and mathematical physics as it pertains to the structure-function relationship of networked systems and their dynamics. Our results are an important step towards developing analysis techniques that are essential to studying the impacts of larger scale network connectivity on network function, and furthering our understanding of brain function and dysfunction.Comment: 18 pages, 6 figure

Report on the excavation of a Punic tomb

On 19th November 2001, while two of us (DB, NJC) were preparing a drawn record of the Punic tomb that is situated on Bajda Ridge, Xemxija, a small ceramic bowl (100211) was uncovered from below a few centimetres of soil that covered the inner part of the threshold to the rock-cut chamber (Fig. 1). An official from the Museums Department was informed of the discovery on the same day and a site inspection was carried out. It was realised that more artefacts could lie undisturbed within the chamber and a decision was taken to excavate the deposit. Authorisation for the Department of Classics and Archaeology, University of Malta, to undertake the excavation was received from the Director, Museums Department, and the excavation was completed on the 22nd November. The tomb is located on the ridge, near a path that diverges eastwards from the track that links Pwales valley to the Mistra valley. It is cut in the Upper Coralline limestone that outcrops in the area on a North-South axis and consists of a sub-rectangular chamber that is reached through a low entrance at the bottom of a rectangular shaft (Fig. 1). The tomb appears in an inventory for the first time in 1996 when it was listed in the survey of archaeological sites prepared by Malta University Services for the Planning Authority by Anthony Bonanno in connection with the preparation of the North-West local plan for Malta. The tomb had been examined and photographed by one of us (NCV) in 1992. At the time, it was littered with debris and it was only with difficulty that a view of the chamber could be achieved through the entrance that was partly concealed by an irregular blocking stone. Late in 2000, members of the St Paul's Bay Heritage Group lifted the debris from the trench and cleared the area around the site.peer-reviewe

Effect of porogen solvent on the synthesis of nickel ion imprinted polymer materials prepared by inverse suspension polymerization

Ion-imprinted polymers (IIPs) for nickel were synthesized by inverse suspension copoly-merization of vinylbenzyl iminodiacetic acid (VbIDA) with ethyleneglycol dimethacrylate (EDMA) in the presence of nickel(II) ions with various porogen solvents to study their impact on the IIPs properties. They were prepared with mixtures of acetonitrile and dimethylsulfoxide (DMSO), 50/50%v/v, for IIP-A/D and 2-methoxyethanol and DMSO, 50/50%v/v, for IIP-M/D. The structure and properties of these polymers were compared with those of IIP-D previously prepared with pure DMSO as porogen solvent. Although IIP-A/D and IIP-M/D were less porous than IIP-D, they presented better nickel adsorption properties and selectivity towards Zn2+, Co2+ and Pb2+. This is assumed to be the result of the stabilization of the ligand-metal complex during the polymerization process. Moreover, the nickel binding capacities of the prepared IIPs in competitive conditions are remarkably high (184 mu mol/g for IIP-D, 170 mu mol/g for IIP-A/D and 174 mu mol/g for IIP-M/D). The impact of the VbIDA chelating monomer was highlighted by comparing the adsorption properties of a copolymer of methyl methacrylate (MMA) and EDMA with NIP-D. It was proved that the methacrylic polymer matrix has low binding properties. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Climatically-Active Gases in the Eastern Boundary Upwelling and Oxygen Minimum Zone (OMZ) Systems

International audienceThe EBUS (Eastern Boundary Upwelling Systems) and OMZs (Oxygen Minimum Zone) contribute very significantly to the gas exchange between the ocean and the atmosphere, notably with respect to the greenhouse gases (hereafter GHG). From in-situ ocean measurements, the uncertainty of the net global ocean-atmosphere CO2 fluxes is between 20 and 30%, and could be much higher in the EBUS-OMZ. Off Peru, very few in-situ data are available presently, which justifies alternative approaches for assessing these fluxes. GHG air-sea fluxes determination can be inferred from inverse modeling applied to Vertical Column Densities (VCDs) from GOSAT, using state of the art modeling, at low spatial resolution. For accurately linking sources of GHGs to EBUS and OMZs, the resolution of the source regions needs to be increased. This task develops on new non-linear and multiscale processing methods for complex signals to infer a higher spatial resolution mapping of the fluxes and the associated sinks and sources between the atmosphere and the ocean. The use of coupled satellite data (e.g. SST and/or Ocean colour) that carry turbulence information associated to ocean dynamics is taken into account at unprecedented detail level to incorporate turbulence effects in the evaluation of the air-sea fluxes. We will present a framework as described above for determining sources and sinks of GHG from satellite remote sensing with the Peru OMZ as a test bed

A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors

Immunotherapy; Oncolytic herpes virus; Pediatric solid tumorInmunoterapia; Virus del herpes oncolítico; Tumor sólido pediátricoImmunoteràpia; Virus de l'herpes oncolític; Tumor sòlid pediàtricBackground: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non–central nervous system tumors. Methods: T-VEC was delivered by intralesional injection at 106 plaque-forming units (PFU)/ml on the first day, followed by 108 PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST). Results: Fifteen patients were enrolled into two cohorts based on age: cohort A1 (n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 (n = 2) 2 to <12 years old (melanoma, n = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response. Conclusions: T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed.This study received funding from Amgen Inc. The funder was involved in the study design; collection, analysis, and interpretation of data; the writing of this article; and the decision to submit it for publication

Normalized difference vegetation index, temperature and age affect faecal thyroid hormone concentrations in free-ranging African elephants

Conservation biologists can use hormone measurements to assess animals’welfare, reproductive state, susceptibility to stressors, as well as energy expenditure. Quantifying hormone concentrations from faecal samples is particularly advantageous as samples can be collected without disturbing animals’ behaviour. In order for an endocrine marker to be useful for wildlife managers, we need to understand how extrinsic and intrinsic factors affect hormone concentrations in free-ranging animal populations. Thyroid hormones are linked to basal metabolic rate and energy expenditure. Previous research demonstrated that triiodothyronine (T3) can be measured successfully in faecal matter of African elephants, Loxodonta africana. However, to our knowledge, research into factors affecting changes in elephant T3 levels has only been carried out in captive elephants so far. Thus, we present the first study of faecal T3 metabolite (mT3) concentrations of a large population of free-ranging African elephants. Over 15 months, we collected faecal samples from identified (n = 43 samples) and unidentified (n = 145 samples) individuals in Madikwe Game Reserve, South Africa. We investigated whether vegetative productivity [normalized difference vegetation index (NDVI)] in interaction with mean monthly temperature, age and sex affected mT3 concentrations. We found a significant negative interaction effect of NDVI and temperature. Increasing NDVI was related to higher concentrations of mT3, but increasing temperature was related to a decrease in mT3 concentrations in individually identified and unidentified elephants. In unidentified individuals, juvenile elephants had significantly higher mT3 concentrations compared to adult elephants. Faecal T3 can successfully be quantified in samples from free-ranging elephant populations and thus provides insight into energy expenditure in large herbivores.https://academic.oup.com/conphyspm2021Anatomy and PhysiologyMammal Research Institut

HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32).

International audienceThe t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation

selection of the recommended phase 2 dose for bintrafusp alfa a bifunctional fusion protein targeting tgf β and pd l1

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Hematopoietic Stem Cell Transplant for the Treatment of X-MAID

We report outcomes after hematopoietic stem cell transplant for three patients with X-MAID, including 1 patient from the originally described cohort and two brothers with positive TREC newborn screening for SCID who were found to have a T-B-NK+ SCID phenotype attributable to X-linked moesin associated immunodeficiency (X-MAID). A c.511C&gt;T variant in moesin was identified via exome sequencing in the older of these siblings in the setting of low lymphocyte counts and poor proliferative responses consistent with SCID. He received reduced intensity conditioning due to CMV, and was transplanted with a T-depleted haploidentical (maternal) donor. His post-transplant course was complicated by hemolytic anemia, neutropenia, and sepsis. He had poor engraftment, requiring a 2nd transplant. His younger brother presented with the same clinical phenotype and was treated with umbilical cord blood transplant following myeloablative conditioning, has engrafted and is doing well. The third case also presented with severe lymphopenia in infancy, received a matched related bone marrow transplant following myeloablative conditioning, has engrafted and is doing well. These cases represent a novel manifestation of non-radiosensitive X-linked form of T-B-NK+ SCID that is able to be detected by TREC based newborn screening and effectively treated with HCT