162 research outputs found
Evaluation of low cost, high sensitivity GNSS receivers based on the ISO RTK standards
ABSTRACT The emergence of single-frequency, navigation-type receivers capable to provide carrier phase data (the so-called high sensitivity carrier phase positioning) has been steadily growing over the recent years. The level of positioning accuracy obtained with navigation-type receivers has raised interest to various communities that use positioning information. Over the last years, various researchers have investigated the potential of high-sensitivity navigation-type receivers and antennas with analysis on their positioning performance in post-processing and RTK modes. Although the above efforts express valuable guidelines for the practical use of navigation-type receivers, they lack standardized test procedures. In addition, these procedures are not always easily tractable and the time and effort required to perform these are not insignificant. The main purpose of this study is evaluate the positioning performance of high-sensitivity carrier phase-based navigation receivers based on the official International Standards Organisation (ISO) specifications for real-time kinematic (RTK) GNSS geodetic receivers. A number of standardised experiments are described using as rover receiver the u-blox NEO-7P XXL bundle package that contains the NEO-7P module and the low-cost antenna Tallysman TW2410. Based on the ISO 17123 part 8 GNSS RTK standards, the experiments include a number of simplified and full test procedures in different observation periods and under varying satellite geometry. The results demonstrate the suitability of the u-blox NEO-7P XXL bundle package with the NEO-7P module for different accuracy levels of RTK positioning applications
Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis
Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis
Two Pathways Recruit Telomerase to Saccharomyces cerevisiae Telomeres
The catalytic subunit of yeast telomerase, Est2p, is a telomere associated throughout most of the cell cycle, while the Est1p subunit binds only in late S/G2 phase, the time of telomerase action. Est2p binding in G1/early S phase requires a specific interaction between telomerase RNA (TLC1) and Ku80p. Here, we show that in four telomerase-deficient strains (cdc13-2, est1Ä, tlc1-SD, and tlc1-BD), Est2p telomere binding was normal in G1/early S phase but reduced to about 40–50% of wild type levels in late S/G2 phase. Est1p telomere association was low in all four strains. Wild type levels of Est2p telomere binding in late S/G2 phase was Est1p-dependent and required that Est1p be both telomere-bound and associated with a stem-bulge region in TLC1 RNA. In three telomerase-deficient strains in which Est1p is not Est2p-associated (tlc1-SD, tlc1-BD, and est2Ä), Est1p was present at normal levels but its telomere binding was very low. When the G1/early S phase and the late S/G2 phase telomerase recruitment pathways were both disrupted, neither Est2p nor Est1p was telomere-associated. We conclude that reduced levels of Est2p and low Est1p telomere binding in late S/G2 phase correlated with an est phenotype, while a WT level of Est2p binding in G1 was not sufficient to maintain telomeres. In addition, even though Cdc13p and Est1p interact by two hybrid, biochemical and genetic criteria, this interaction did not occur unless Est1p was Est2p-associated, suggesting that Est1p comes to the telomere only as part of the holoenzyme. Finally, the G1 and late S/G2 phase pathways for telomerase recruitment are distinct and are likely the only ones that bring telomerase to telomeres in wild-type cells
Lung transplantation for pulmonary fibrosis in dyskeratosis congenita: Case Report and systematic literature review
<p>Abstract</p> <p>Background</p> <p>Dyskeratosis congenita (DC) is a progressive, multi-system, inherited disorder of telomere biology with high risks of morbidity and mortality from bone marrow failure, hematologic malignancy, solid tumors and pulmonary fibrosis. Hematopoietic stem cell transplantation (HSCT) can cure the bone marrow failure, but it does not eliminate the risks of other complications, for which life-long surveillance is required. Pulmonary fibrosis is a progressive and lethal complication of DC.</p> <p>Case presentation</p> <p>In this report, we describe a patient with DC who developed pulmonary fibrosis seven years after HSCT for severe aplastic anemia, and was successfully treated with bilateral lung transplantation. We also performed a systematic literature review to understand the burden of pulmonary disease in patients with DC who did or did not receive an HSCT. Including our patient, we identified 49 DC patients with pulmonary disease (12 after HSCT and 37 without HSCT), and 509 with no reported pulmonary complications.</p> <p>Conclusion</p> <p>Our current case and literature review indicate that pulmonary morbidity is one of the major contributors to poor quality of life and reduced long-term survival in DC. We suggest that lung transplantation be considered for patients with DC who develop pulmonary fibrosis with no concurrent evidence of multi-organ failure.</p
A stakeholder co-design approach for developing a community pharmacy service to enhance screening and management of atrial fibrillation
The authors would like to thank all participants in this research for their
valuable input into the co-design process.Background: Community pharmacies provide a suitable setting to promote self-screening programs aimed at
enhancing the early detection of atrial fibrillation (AF). Developing and implementing novel community pharmacy
services (CPSs) is a complex and acknowledged challenge, which requires comprehensive planning and the
participation of relevant stakeholders. Co-design processes are participatory research approaches that can enhance
the development, evaluation and implementation of health services. The aim of this study was to co-design a
pharmacist-led CPS aimed at enhancing self-monitoring/screening of AF.
Methods: A 3-step co-design process was conducted using qualitative methods: (1) interviews and focus group
with potential service users (n = 8) to identify key needs and concerns; (2) focus group with a mixed group of
stakeholders (n = 8) to generate a preliminary model of the service; and (3) focus group with community pharmacy
owners and managers (n = 4) to explore the feasibility and appropriateness of the model. Data were analysed
qualitatively to identify themes and intersections between themes. The JeMa2 model to conceptualize pharmacybased
health programs was used to build a theoretical model of the service.
Results: Stakeholders delineated: a clear target population (i.e., individuals ≥65 years old, with hypertension, with or
without previous AF or stroke); the components of the service (i.e., patient education; self-monitoring at home;
results evaluation, referral and follow-up); and a set of circumstances that may influence the implementation of the
service (e.g., quality of the service, competency of the pharmacist, inter-professional relationships, etc.). A number of
strategies were recommended to enable implementation (e.g.,. endorsement by leading cardiovascular
organizations, appropriate communication methods and channels between the pharmacy and the general medical
practice settings, etc.).
Conclusion: A novel and preliminary model of a CPS aimed at enhancing the management of AF was generated
from this participatory process. This model can be used to inform decision making processes aimed at adopting
and piloting of the service. It is expected the co-designed service has been adapted to suit existing needs of
patients and current care practices, which, in turn, may increase the feasibility and acceptance of the service when
it is implemented into a real setting.This work was funded by Covidien Pty Ltd. (Medtronic Australasia Pty Ltd)
[UTS Project code: PRO16–0688], which is the company that has the rights to distribute the device Microlife BP A200 AFIB in Australia. Also, funding for
this research has been provided by a UTS Chancellor’s postdoctoral
fellowship awarded to the first author of this article (ID number:
2013001605)
Telomere Lengths, Pulmonary Fibrosis and Telomerase (TERT) Mutations
mutations. mutation carriers demonstrate reduced life expectancy, with a mean age of death of 58 and 67 years for males and females, respectively. mutation have shorter telomere lengths than controls, demonstrating epigenetic inheritance of a shortened parental telomere length set-point
Ancestral Mutation in Telomerase Causes Defects in Repeat Addition Processivity and Manifests As Familial Pulmonary Fibrosis
The telomerase reverse transcriptase synthesizes new telomeres onto chromosome ends by copying from a short template within its integral RNA component. During telomere synthesis, telomerase adds multiple short DNA repeats successively, a property known as repeat addition processivity. However, the consequences of defects in processivity on telomere length maintenance are not fully known. Germline mutations in telomerase cause haploinsufficiency in syndromes of telomere shortening, which most commonly manifest in the age-related disease idiopathic pulmonary fibrosis. We identified two pulmonary fibrosis families that share two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene hTERT: V791I and V867M. The two variants fell on the same hTERT allele and were associated with telomere shortening. Genealogy suggested that the pedigrees shared a single ancestor from the nineteenth century, and genetic studies confirmed the two families had a common founder. Functional studies indicated that, although the double mutant did not dramatically affect first repeat addition, hTERT V791I-V867M showed severe defects in telomere repeat addition processivity in vitro. Our data identify an ancestral mutation in telomerase with a novel loss-of-function mechanism. They indicate that telomere repeat addition processivity is a critical determinant of telomere length and telomere-mediated disease
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