68 research outputs found

    A comparison of retirement saving using discretionary investment and Regulation 28

    Get PDF
    Background: There is growing uncertainty in global society with regard to how retirement savings should be approached. The primary reason for this is that most societies do not save enough and their citizens run out of money during retirement.   Aim: This study investigates whether the limitations imposed by Regulation 28 of the Pension Funds Act of South Africa encourage optimal asset allocation and reduce investment risk for retirement savings when contrasted with discretionary investment.   Setting: The study looks at hypothetical individuals who are subject to tax and retirement consequences as administered by South African legislation.   Methods: A quantitative risk and return analysis was performed while considering two hypothetical investors who are identical in all aspects other than their choice of investments.   Results: The findings indicate that Regulation 28 is effective in reducing the investment risk of retirement savings; however, it may also force the investor to sacrifice wealth.   Conclusion: Depending on the tax bracket in which the investor sits, discretionary investment may be preferential to investing in a retirement fund under the mandate of Regulation 28

    Comparative Risk Assessment to Inform Adaptation Priorities for the Natural Environment: Observations from the First UK Climate Change Risk Assessment

    Get PDF
    Risk assessment can potentially provide an objective framework to synthesise and prioritise climate change risks to inform adaptation policy. However, there are significant challenges in the application of comparative risk assessment procedures to climate change, particularly for the natural environment. These challenges are evaluated with particular reference to the first statutory Climate Change Risk Assessment (CCRA) and evidence review procedures used to guide policy for the UK government. More progress was achieved on risk identification, screening and prioritisation compared to risk quantification. This was due to the inherent complexity and interdependence of ecological risks and their interaction with socio-economic drivers as well as a climate change. Robust strategies to manage risk were identified as those that coordinate organisational resources to enhance ecosystem resilience, and to accommodate inevitable change, rather than to meet specific species or habitats targets. The assessment also highlighted subjective and contextual components of risk appraisal including ethical issues regarding the level of human intervention in the natural environment and the proposed outcomes of any intervention. This suggests that goals for risk assessment need to be more clearly explicated and assumptions on tolerable risk declared as a primer for further dialogue on expectations for managed outcomes. Ecosystem-based adaptation may mean that traditional habitats and species conservation goals and existing regulatory frameworks no longer provide the best guide for long-term risk management thereby challenging the viability of some existing practices

    DJ-1 Mutations are Rare in a Swedish Parkinson Cohort

    Get PDF
    Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide

    Genetic Screening of the Mitochondrial Rho GTPases MIRO1 and MIRO2 in Parkinson’s Disease

    Get PDF
    MIRO1 and MIRO2 (mitochondrial Ras homolog gene family, member T1 and T2) also referred to as RHOT1 and RHOT2, belong to the mitochondrial Rho GTPase family and are involved in axonal transport of mitochondria in neurons. Because mitochondrial dysfunction is strongly implicated in Parkinson’s disease (PD), MIRO1 and MIRO2 can be considered as new candidate genes for PD. We analyzed two non-synonymous polymorphisms and one synonymous polymorphism in MIRO1 and two non-synonymous polymorphisms in MIRO2, in a Swedish Parkinson case-control material consisting of 241 patients and 307 neurologically healthy controls. None of the analyzed polymorphisms in MIRO1 and MIRO2 were significantly associated with PD. Although we did not find a significant association with PD in our Swedish case-control material, we cannot exclude these Rho GTPases as candidate genes for PD or other neurodegenerative disorders

    Structure of the Mg-Chelatase Cofactor GUN4 Reveals a Novel Hand-Shaped Fold for Porphyrin Binding

    Get PDF
    In plants, the accumulation of the chlorophyll precursor Mg-protoporphyrin IX (Mg-Proto) in the plastid regulates the expression of a number of nuclear genes with functions related to photosynthesis. Analysis of the plastid-to-nucleus signaling activity of Mg-Proto in Arabidopsis thaliana led to the discovery of GUN4, a novel porphyrin-binding protein that also dramatically enhances the activity of Mg-chelatase, the enzyme that synthesizes Mg-Proto. GUN4 may also play a role in both photoprotection and the cellular shuttling of tetrapyrroles. Here we report a 1.78-Å resolution crystal structure of Synechocystis GUN4, in which the porphyrin-binding domain adopts a unique three dimensional fold with a “cupped hand” shape. Biophysical and biochemical analyses revealed the specific site of interaction between GUN4 and Mg-Proto and the energetic determinants for the GUN4 • Mg-Proto interaction. Our data support a novel protective function for GUN4 in tetrapyrrole trafficking. The combined structural and energetic analyses presented herein form the physical-chemical basis for understanding GUN4 biological activity, including its role in the stimulation of Mg-chelatase activity, as well as in Mg-Proto retrograde signaling

    Разработка и оптимизация дистанционного режима управления станцией механической очистки СУ-МОК4310V

    Get PDF
    The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson’s disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on Unified PD Rating Scale (UPDRS) and 39-item PD Questionnaire (PDQ-39) scales. In LCIG-naïve patients, mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non-naïve patients, there were no significant changes in mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS respectively. The trends of the test scores were similar to the trends of clinical rating scores but dropout rate was high. Correlations between OTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS.FLOAT - Flexibel levodopa-optimerings och individanpassningstekni

    The Potential Role of Magnetic Resonance Spectroscopy in Image-Guided Radiotherapy

    Get PDF
    Magnetic resonance spectroscopy (MRS) is a non-invasive technique to detect metabolites within the normal and tumoral tissues. The ability of MRS to diagnose areas of high metabolic activity linked to tumor cell proliferation is particularly useful for radiotherapy treatment planning because of better gross tumor volume (GTV) delineation. The GTV may be targeted with higher radiation dose, potentially improving local control without excessive irradiation to the normal adjacent tissues. Prostate cancer and glioblastoma multiforme (GBM) are two tumor models that are associated with a heterogeneous tumor distribution. Preliminary studies suggest that the integration of MRS into radiotherapy planning for these tumors is feasible and safe. Image-guided radiotherapy (IGRT) by virtue of daily tumor imaging and steep dose gradient may allow for tumor dose escalation with the simultaneous integrated boost technique (SIB) and potentially decrease the complications rates in patients with GBM and prostate cancers

    Embracing heterogeneity: coalescing the Tree of Life and the future of phylogenomics

    Get PDF
    Building the Tree of Life (ToL) is a major challenge of modern biology, requiring advances in cyberinfrastructure, data collection, theory, and more. Here, we argue that phylogenomics stands to benefit by embracing the many heterogeneous genomic signals emerging from the first decade of large-scale phylogenetic analysis spawned by high-throughput sequencing (HTS). Such signals include those most commonly encountered in phylogenomic datasets, such as incomplete lineage sorting, but also those reticulate processes emerging with greater frequency, such as recombination and introgression. Here we focus specifically on how phylogenetic methods can accommodate the heterogeneity incurred by such population genetic processes; we do not discuss phylogenetic methods that ignore such processes, such as concatenation or supermatrix approaches or supertrees. We suggest that methods of data acquisition and the types of markers used in phylogenomics will remain restricted until a posteriori methods of marker choice are made possible with routine whole-genome sequencing of taxa of interest. We discuss limitations and potential extensions of a model supporting innovation in phylogenomics today, the multispecies coalescent model (MSC). Macroevolutionary models that use phylogenies, such as character mapping, often ignore the heterogeneity on which building phylogenies increasingly rely and suggest that assimilating such heterogeneity is an important goal moving forward. Finally, we argue that an integrative cyberinfrastructure linking all steps of the process of building the ToL, from specimen acquisition in the field to publication and tracking of phylogenomic data, as well as a culture that values contributors at each step, are essential for progress
    corecore