73 research outputs found
Economic Crisis and Investor Behaviour
This study investigates the effects of crises on domestic and foreign investors’ behaviours by utilizing a nonlinear approach. Considering the nonlinearity inherent in many financial variables, this study proposes an appropriate econometric modelling for analysing the investors’ behaviour, particularly during turbulent times. Specifically, STAR-STGARCH family models and generalized impulse response function analysis (GIRF) are employed to understand the different reactions of foreign and domestic investors at the Malaysian Stock Exchange market during the 1997 Asian crisis. The results of the model and the GIRF analysis have shown that foreign investors exhibited a herding behavior during the crisis and responded the shock more quickly than the domestic investors. When the same analysis is applied to understand the effects of the 2008 Subprime Mortgage Crisis in the Malaysian market, the behaviors of foreign and domestic investors are found to be very similar
Contribution of Somatic Ras/Raf/Mitogen-Activated Protein Kinase Variants in the Hippocampus in Drug-Resistant Mesial Temporal Lobe Epilepsy
Importance: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. Objective: To test the association between pathogenic somatic variants in the hippocampus and MTLE. Design, Setting, and Participants: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy-associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. Exposures: Drug-resistant MTLE. Main Outcomes and Measures: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. Results: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P =.01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. Conclusions and Relevance: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery
Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas
RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features
Advances, gaps and way forward in provision of climate services over the Greater Horn of Africa
The Greater Horn of Africa is prone to extreme climatic conditions, thus, making climate services increasingly important in supporting decision-making processes across a range of climate sensitive sectors. This study aims to provide a comprehensive review of the recent advances, gaps and challenges in the provision of climate services over the region, for each of the components of the Global Framework for Climate Services. The study explores various milestones that have been achieved toward climate service delivery. The achievements include improvement of station network coverage, and enhancing the capacity of member states to utilize various tools in data analysis and generate routine climate products. The advancement in science, and availability of High-Performance Computing has made it possible for forecast information to be provided from nowcasting to seasonal timescales. Moreover, operationalizing of the objective forecasting method for monthly and seasonal forecasts has made it possible to translate tercile forecasts for applications models. Additionally, innovative approaches to user engagement through co-production, communication channels, user-friendly interfaces, and dissemination of climate information have also been developed. Despite the significant progress that has been made in the provision of climate services, there are still many challenges and gaps that need to be overcome in order to ensure that these services are effectively meeting the needs of users. The research of the science underpinning climate variability, capacity building and stakeholder engagement, as well as improved data management and quality control processes are some of the gaps that exist over the region. Additionally, communication and dissemination of climate information, including timely warnings and risk communication, require improvement to reach diverse user groups effectively. Addressing these challenges will require strengthened partnerships, increased investment in capacity building, enhanced collaboration between the climate information producers and stakeholders, and the development of user-friendly climate products. Bridging these gaps will foster greater resilience to climate-related hazards and disasters in the Greater Horn of Africa and support sustainable development in the region
Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need
The current status of 5-ALA fluorescence-guided resection of intracranial meningiomas—a critical review
On fractional filtering versus conventional filtering in economics
In this study, we compare the Hodrick-Prescott Filter technique with the Fractional filtering technique that has recently started to be used in various applied sciences like physics, engineering, and biology. We apply these filtering techniques to quarterly GDP data from Turkey for the period 1988:1-2003:2. The filtered series are analyzed using Minimum Square Error (MSE) and real life evidence. In the second part of the study, we use simulated data to analyze the statistical properties of the aforementioned filtering techniques. © 2009 Elsevier B.V. All rights reserved
On fractional filtering versus conventional filtering in economics
In this study, we compare the Hodrick-Prescott Filter technique with the Fractional filtering technique that has recently started to be used in various applied sciences like physics, engineering, and biology. We apply these filtering techniques to quarterly GDP data from Turkey for the period 1988:1-2003:2. The filtered series are analyzed using Minimum Square Error (MSE) and real life evidence. In the second part of the study, we use simulated data to analyze the statistical properties of the aforementioned filtering techniques. © 2009 Elsevier B.V. All rights reserved
Vena cava superior syndrome due to sternal plasmacytoma in the course of systemic myeloma
WOS: 000183326800025PubMed ID: 12803129Here we present a patient with multiple myeloma course. The first clinical manifestation was superior vena cava syndrome due to a huge sternal plasmocytoma. The patient was treated with a combination of high dose radiotherapy and autologous peripheral blood stem cell transplantation. We suggest careful evaluation of these patients with respect to aggressive therapy
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