Theodicy and End-of-Life Care

Acknowledgments The section on Islamic perspective is contributed by information provided by Imranali Panjwani, Tutor in Theology & Religious Studies, King's College London.Peer reviewedPublisher PD

Distortion and Signal Loss in Medial Temporal Lobe

Background: The medial temporal lobe (MTL) contains subregions that are subject to severe distortion and signal loss in functional MRI. Air/tissue and bone/tissue interfaces in the vicinity of the MTL distort the local magnetic field due to differences in magnetic susceptibility. Fast image acquisition and thin slices can reduce the amount of distortion and signal loss, but at the cost of image signal-to-noise ratio (SNR). Methodology/Principal Findings: In this paper, we quantify the severity of distortion and signal loss in MTL subregions for three different echo planar imaging (EPI) acquisitions at 3 Tesla: a conventional moderate-resolution EPI (36363 mm), a conventional high-resolution EPI (1.561.562 mm), and a zoomed high-resolution EPI. We also demonstrate the advantage of reversing the phase encode direction to control the direction of distortion and to maximize efficacy of distortion compensation during data post-processing. With the high-resolution zoomed acquisition, distortion is not significant and signal loss is present only in the most anterior regions of the parahippocampal gyrus. Furthermore, we find that the severity of signal loss is variable across subjects, with some subjects showing negligible loss and others showing more dramatic loss. Conclusions/Significance: Although both distortion and signal loss are minimized in a zoomed field of view acquisition with thin slices, this improvement in accuracy comes at the cost of reduced SNR. We quantify this trade-off between distortion and SNR in order to provide a decision tree for design of high-resolution experiments investigating the functio

The European Hematology Association Roadmap for European Hematology Research: a consensus document

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients

The European Hematology Association Roadmap for European Hematology Research. A Consensus Document

Abstract The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Received December 15, 2015. Accepted January 27, 2016. Copyright © 2016, Ferrata Storti Foundatio

Recent developments in genetics and medically assisted reproduction : from research to clinical applications

Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.Peer reviewe

Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years

BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality. PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor—a first-in-class HbS polymerization inhibitor—in patients aged 6 months to 17 years with SCD. Initial findings from a cohort of 45 patients aged 4 to 11 years who received voxelotor treatment for up to 48 weeks are reported. RESULTS: Hemoglobin (Hb) response, defined as a >1.0 g/dl increase from baseline, was achieved at week 24 by 47% (n = 16/34) of patients with Hb measurements at baseline and week 24. At week 24, 35% (n = 12/34) and 21% (n = 7/34) of patients had a >1.5 g/dl increase and a >2.0 g/dl increase from baseline in Hb concentration, respectively. Concurrent improvements in hemolytic markers were observed. Voxelotor was well tolerated in this young cohort, with no newly emerging safety signals. CONCLUSIONS: Based on its mechanism as an HbS polymerization inhibitor, voxelotor improves Hb levels and markers of hemolysis and has the potential to mitigate SCD-related complications; these results support its use in patients aged ≥4 years

Determination of βS haplotypes in patients with sickle-cell anemia in the state of Rio Grande do Norte, Brazil

βS haplotypes were studied in 47 non-related patients with sickle-cell anemia from the state of Rio Grande do Norte, Brazil. Molecular analysis was conducted by PCR/RFLP using restriction endonucleases XmnI, HindIII, HincII and HinfI to analyze six polymorphic sites from the beta cluster. Twenty-seven patients (57.5%) were identified with genotype CAR/CAR, 9 (19.1%) CAR/BEN, 6 (12.8%) CAR/CAM, 1 (2.1%) BEN/BEN, 2 (4.3%) CAR/Atp, 1 (2.1%) BEN/Atp and 1 (2.1%) with genotype Atp/Atp. The greater frequency of Cameroon haplotypes compared to other Brazilian states suggests the existence of a peculiarity of African origin in the state of Rio Grande do Norte

Wide Variability in the Sensitivity and Specificity of Rotavirus Immunoassay Diagnostic Kits in Practice

Introduction: Most hospitals rely on rapid antigen-detection kits for the diagnosis of rotavirus infection. Several small studies reviewed the sensitivity and specificity of some of these kits. These studies showed discrepancy in results obtained for sensitivity and specificity that varied according to the type of kit used, area of study, and type of test used as standard for diagnosis of rotavirus infection. The objective of the study is to determine the sensitivity and specificity of five commonly used rotavirus immunoassay kits in comparison to RT-PCR as standard. Methodology: Stool samples (N=1,414) collected from children under 5 years of age hospitalized with gastroenteritis were tested for rotavirus by immunoassay kits and RT-PCR in a prospective hospital-based surveillance study conducted at 7 centers in Lebanon. Concordance and discrepancy between the two methods was used to calculate sensitivity and specificity, using RT-PCR as the “gold standard”. Results: The sensitivity and specificity were respectively 95.08% and 86.62% for the SD Bioline® (Standard Diagnostics, Inc, South Korea) kit calculated on 645 samples, 65.86% and 45.90% for the VIROTECT® (Trinity Biotech, Ireland) kit calculated on 327 samples, 83.9% and 64.2% for the Rota-Strip (C-1001) (Coris Bioconcept, Belgium) calculated on 95 samples, 52.3% and 10.9% for the Acon® (Acon Laboratories, Inc, California, USA) kit calculated on 122 samples, 68.1% and 20% for the VIKIA® Rota-Adéno (Biomerieux, France) kit calculated on 32 samples. Conclusions: A wide discrepancy was detected between the calculated and advertised sensitivity and specificity for most of the kits. Copyright © 2021 Shaker et al. This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Virtual stimulation of the interictal EEG network localizes the EZ as a measure of cortical excitability

Introduction: For patients with drug-resistant epilepsy, successful localization and surgical treatment of the epileptogenic zone (EZ) can bring seizure freedom. However, surgical success rates vary widely because there are currently no clinically validated biomarkers of the EZ. Highly epileptogenic regions often display increased levels of cortical excitability, which can be probed using single-pulse electrical stimulation (SPES), where brief pulses of electrical current are delivered to brain tissue. It has been shown that high-amplitude responses to SPES can localize EZ regions, indicating a decreased threshold of excitability. However, performing extensive SPES in the epilepsy monitoring unit (EMU) is time-consuming. Thus, we built patient-specific in silico dynamical network models from interictal intracranial EEG (iEEG) to test whether virtual stimulation could reveal information about the underlying network to identify highly excitable brain regions similar to physical stimulation of the brain.Methods: We performed virtual stimulation in 69 patients that were evaluated at five centers and assessed for clinical outcome 1 year post surgery. We further investigated differences in observed SPES iEEG responses of 14 patients stratified by surgical outcome.Results: Clinically-labeled EZ cortical regions exhibited higher excitability from virtual stimulation than non-EZ regions with most significant differences in successful patients and little difference in failure patients. These trends were also observed in responses to extensive SPES performed in the EMU. Finally, when excitability was used to predict whether a channel is in the EZ or not, the classifier achieved an accuracy of 91%.Discussion: This study demonstrates how excitability determined via virtual stimulation can capture valuable information about the EZ from interictal intracranial EEG