202 research outputs found

    Investigating the Presence of Regional Economic Growth Convergence in the Philippines using Kalman Filter

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    This paper investigates the presence of stochastic and dynamic convergence of the 14 regional economies in the Philippines in terms of per capita Gross Regional Domestic Product (GRDP) using regional panel data from 1988 to 2007. Stochastic convergence, which indicates convergence of regions in the long-run, is tested using Levin, Lin & Chu (LLC) and Im, Pesaran & Shin (IPS) panel unit root tests. The presence of convergence, on one hand, indicates that the economically laggard regions are gaining on the economically better-performing regions with respect to per capita GRDP. On the other hand, the lack of convergence indicates a need to reevaluate existing regional and national economic policies on development. Dynamic convergence reveals several convergence characteristics of individual regions over time. Dynamic convergence is determined by the time-varying parameter (TVP) model derived using the Kalman Filter. The paper proceeds to examine the individual convergence behavior of each region based on the value of the estimate of the parameter of the TVP. The results show that out of the 14 regions studied, seven regions are found to converge towards the average of the national per capita GDP growth rate over 1988 to 2007 while six regions lag behind the average of the national per capita GDP growth rate over the same period. No region converges towards the economic growth rate of National Capital Region, the lead region used in the study.Panel Unit Root Test, Time-varying Parameter (TVP) Model, Kalman Filter, Stochastic Convergence, Dynamic Convergence

    The Human Right to Water and the Responsibilities of Businesses: An Analysis of Legal Issues

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    90% of the world’s fresh water resources are consumed within the industrial and agricultural sectors. Indicating water’s place at the top of the corporate agenda, a recent survey by the Carbon Disclosure Project (CDP) of more than 300 of the 500 largest companies in the world, found that 67% of respondents placed responsibility for water-related issues at the Board or Executive Committee level, 89% have developed specific water policies, and 60% have set water-related performance targets. Significantly, respondents across all sectors identified regulation as one of the key risks in corporate water practices. Part 1 of this paper provides an overview of the international recognition of the human right to water and its current legal scope – the legal framework guiding States’ obligations in fully realising the right to water for all, including State liability for businesses’ operations. Part 2 examines the mechanisms at both national and international level that are increasingly being used to hold water users and providers to account. Lastly, in Part 3, we attempt to answer why the human right to water is important to businesses by considering the implications of trends around the issue of business and human rights and how these trends can be used as an opportunity to operationalise the right to water within business practices

    Investigating the Presence of Regional Economic Growth Convergence in the Philippines using Kalman Filter

    Get PDF
    This paper investigates the presence of stochastic and dynamic convergence of the 14 regional economies in the Philippines in terms of per capita Gross Regional Domestic Product (GRDP) using regional panel data from 1988 to 2007. Stochastic convergence, which indicates convergence of regions in the long-run, is tested using Levin, Lin & Chu (LLC) and Im, Pesaran & Shin (IPS) panel unit root tests. The presence of convergence, on one hand, indicates that the economically laggard regions are gaining on the economically better-performing regions with respect to per capita GRDP. On the other hand, the lack of convergence indicates a need to reevaluate existing regional and national economic policies on development. Dynamic convergence reveals several convergence characteristics of individual regions over time. Dynamic convergence is determined by the time-varying parameter (TVP) model derived using the Kalman Filter. The paper proceeds to examine the individual convergence behavior of each region based on the value of the estimate of the parameter of the TVP. The results show that out of the 14 regions studied, seven regions are found to converge towards the average of the national per capita GDP growth rate over 1988 to 2007 while six regions lag behind the average of the national per capita GDP growth rate over the same period. No region converges towards the economic growth rate of National Capital Region, the lead region used in the study

    Investigating the Presence of Regional Economic Growth Convergence in the Philippines using Kalman Filter

    Get PDF
    This paper investigates the presence of stochastic and dynamic convergence of the 14 regional economies in the Philippines in terms of per capita Gross Regional Domestic Product (GRDP) using regional panel data from 1988 to 2007. Stochastic convergence, which indicates convergence of regions in the long-run, is tested using Levin, Lin & Chu (LLC) and Im, Pesaran & Shin (IPS) panel unit root tests. The presence of convergence, on one hand, indicates that the economically laggard regions are gaining on the economically better-performing regions with respect to per capita GRDP. On the other hand, the lack of convergence indicates a need to reevaluate existing regional and national economic policies on development. Dynamic convergence reveals several convergence characteristics of individual regions over time. Dynamic convergence is determined by the time-varying parameter (TVP) model derived using the Kalman Filter. The paper proceeds to examine the individual convergence behavior of each region based on the value of the estimate of the parameter of the TVP. The results show that out of the 14 regions studied, seven regions are found to converge towards the average of the national per capita GDP growth rate over 1988 to 2007 while six regions lag behind the average of the national per capita GDP growth rate over the same period. No region converges towards the economic growth rate of National Capital Region, the lead region used in the study

    Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

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    Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

    The genetic basis of apparently idiopathic ventricular fibrillation:A retrospective overview

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    Aims: During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. Methods and results: We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27-51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P &lt; 0.001). Conclusion: Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed.</p

    Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia.

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    Purpose Salvage options for patients who relapse after allogeneic stem-cell transplantation (allo-SCT) for acute myeloid leukemia (AML) and myelodysplasia (MDS) remain limited, and novel treatment strategies are required. Both lenalidomide (LEN) and azacitidine (AZA) possess significant antitumor activity effect in AML. Administration of LEN post-transplantation is associated with excessive rates of graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in murine transplantation models. We therefore examined the tolerability and activity of combined LEN/AZA administration in post-transplantation relapse.Patients and methods Twenty-nine patients who had relapsed after allo-SCT for AML (n = 24) or MDS (n = 5) were treated with sequential AZA (75 mg/m2 for 7 days) followed by escalating doses of LEN on days 10 to 30. Dose allocation and maximum tolerated dose (MTD) estimation were guided by a modified Bayesian continuous reassessment method (CRM).Results Sequential AZA and LEN therapy was well tolerated. The MTD of post-transplantation LEN, in combination with AZA, was determined as 25 mg daily. Three patients developed grade 2 to 4 GVHD. There was no GVHD-related mortality. Seven of 15 (47%) patients achieved a major clinical response after LEN/AZA therapy. CD8+ T cells demonstrated impaired interferon-γ/tumor necrosis factor-α production at relapse, which was not reversed during LEN/AZA administration.Conclusion We conclude LEN can be administered safely post-allograft in conjunction with AZA, and this combination demonstrates clinical activity in relapsed AML/MDS without reversing biologic features of T-cell exhaustion. The use of a CRM model delivered improved efficiency in MTD assessment and provided additional flexibility. Combined LEN/AZA therapy represents a novel and active salvage therapy in patients who had relapsed post-allograft

    Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders

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    OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings

    The best time to acquire new skills: age-related differences in implicit sequence learning across the human lifespan

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    Implicit skill learning underlies obtaining not only motor, but also cognitive and social skills through the life of an individual. Yet, the ontogenetic changes in humans’ implicit learning abilities have not yet been characterized, and, thus, their role in acquiring new knowledge efficiently during development is unknown. We investigated such learning across the life span, between 4-85 years of age with an implicit probabilistic sequence learning task, and we found that the difference in implicitly learning high vs. low probability events - measured by raw reaction time (RT) - exhibited a rapid decrement around age of 12. Accuracy and z-transformed data showed partially different developmental curves suggesting a re-evaluation of analysis methods in developmental research. The decrement in raw RT differences supports an extension of the traditional 2-stage lifespan skill acquisition model: in addition to a decline above the age 60 reported in earlier studies, sensitivity to raw probabilities and, therefore, acquiring new skills is significantly more effective until early adolescence than later in life. These results suggest that due to developmental changes in early adolescence, implicit skill learning processes undergo a marked shift in weighting raw probabilities vs. more complex interpretations of events, which, with appropriate timing, prove to be an optimal strategy for human skill learning

    The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

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    Background: The arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin‑2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. Methods: Clinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C &gt; T (p.Arg79*), c.397C &gt; T (p.Gln133*) and c.2489+1G &gt; A (p.?)). Results: Of the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p &lt; 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia–free survival between 4 PKP2 founder variants, including c.1211dup. Conclusions: The PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.</p
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