Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 ...Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: ∼25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5′ end of
TNRC9
, a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We carried out a genome-wide association study of breast cancer predisposition with replication and refinement studies involving 6,145 cases and 33,016 controls and identified two SNPs (rs4415084 and ...rs10941679) on 5p12 that confer risk, preferentially for estrogen receptor (ER)-positive tumors (OR = 1.27, P = 2.5 × 10−12 for rs10941679). The nearest gene, MRPS30, was previously implicated in apoptosis, ER-positive tumors and favorable prognosis. A recently reported signal in FGFR2 was also found to associate specifically with ER-positive breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The need for more studies on the dynamics of business models has been recognized, especially when considering how business models need to transform to support the transition toward sustainable ...development and a circular economy. System dynamics business model simulations can explore relationships between business strategy, daily operations, strategy implementation, and stakeholder interactions. This study aims to synthesize and analyze findings from existing literature on system dynamic modeling of business models. Following the PSALSAR systematic literature review framework, the results highlight a noticeable focus shift in the evolution of sustainable business model strategies. Before 2016, scholars focused on resource maximization strategies and sustainable scale-up solutions. Post-2016 emphasis has revolved around strategies delivering functionality, adopting a stewardship role, and closing the resource loop. The findings support that system dynamics is a powerful tool for business model innovation, allowing risk-free testing of scenarios and helping to identify leverage points, such as regulations, policies, and product/service design. System dynamics advance the business model paradigm, especially for implementing sustainability strategies. Consequently, this study has implications for scholars, policymakers, and the business community, given its application to furthering sustainable development and the circular economy.
•The emergence of system dynamic modeling of business models is presented.•Sustainable development and circular economy impact business model simulations.•Nine types of sustainable business model strategies are simulated.•Simulating business models aids in implementing sustainable strategies.•Business model simulations support decision-making, enabling circular disruption.
Synstest må tilpasses førerkortkravene Thora Elisabet Jonsdottir; Ødegaard, Eva Meling; Jørstad, Øystein Kalsnes
Tidsskrift for den Norske Lægeforening,
2020, 2020-00-00, Letnik:
140, Številka:
17
Journal Article
Background
The treatment of recurrent cystoid macular edema associated with acute retinal necrosis is challenging due to the concern that treatment with intravitreal steroids may reactivate the ...retinitis.
Case report
An immunocompetent patient diagnosed with acute retinal necrosis was treated with oral valacyclovir and intravitreal injections of foscarnet. Giant tears in her retina necessitated a vitrectomy with silicone oil. She developed cystoid macular edema after the removal of the silicone oil. The edema responded to high-dose prednisolone but recurred when the dose was tapered to 20 mg daily. Under close surveillance and increased antiviral medication, she was treated with a dexamethasone implant with complete resolution of the edema. Unfortunately, the edema recurred, and the treatment had to be repeated. Over 18 months, she received five dexamethasone implants without recurrence of the viral retinitis.
Conclusions
This case shows successful treatment of recurring cystoid macular edema following acute retinal necrosis with repeated intravitreal dexamethasone implants in a patient receiving valacyclovir maintenance treatment.
AimsTo provide an overview of how the European visual field standards for driving (specified in Commission Directive 2009/113/EC) are applied and determine whether individuals with visual field ...defects are treated equally across Europe.MethodsOne ophthalmic expert from each of 32 European countries was invited to participate in an electronic survey. They were presented with threshold and Esterman perimetry results of 15 cases of visual field defects and asked to classify each case as either passed or failed in reference to their national standards. The results were compared with the European Driving Test Group 1 (EDT1), which is a new perimetry algorithm that adheres to the recommendations by the Eyesight Working Group. Fleiss’ kappa was used to determine the inter-rater agreement.ResultsTwenty-five countries responded. Three of 15 cases were passed by all. Full agreement on a failed case was not reached. Denmark graded most leniently and passed 12 cases. Bulgaria, Romania and Slovakia graded most strictly and passed five cases. The Fleiss’ kappa score was 0.52 (95% CI 0.49 to 0.55). Only Slovenia was in full agreement with the EDT1. Fifteen countries endorsed specific perimetric tests for assessing fitness to drive. Five of these also defined pass/fail criteria.ConclusionThe directive fails to establish a uniform approach to the visual field requirements, as evident by moderate pass/fail agreement between the national experts. Because the visual standards for driving are enforced differently, identical visual field loss can result in either revocation or approval of a driving license.
This article proposes a mixed-blended model adapted for Western Balkan countries, advancing the connections between the Icelandic Model of Health Promotion and the assets models for health ...improvement through the whole school approach and non-formal education methodology. The need to reshape health promotion interventions in Western Balkan countries is urgent, and requires explicit synergies so that a more coherent approach can be taken in their utilization. To this end, we propose a new Albanian Health Promotion Model that integrates key concepts that are associated with the involvement of schoolchildren; parents/caregivers, grandparents, communities, and religious leaders; teachers and school staff; involvement of central and local governments; engagement of the private sector; involvement of non-governmental and civil society organizations; and, importantly, enables the development of supportive environments. The proposed model aims to contribute to a more in-depth theoretical understanding of health and development through integration of the key elements of various models, methods, approaches, and tools employed in health promotion practice. Making the theory of the Icelandic model more feasible for non-Nordic cultures could better contextualize the ideas in public health policy and practice. The Albanian Health Promotion Model may also support interventions to maximize their results in vulnerable communities that have specific requirements and, as a result, could be extrapolated to similar countries in the region and beyond.
Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 ...missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer.
The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio OR = 1.82, 95% confidence interval CI 1.11-3.01, p = 0.014). The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015). Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046) in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors of contemporary carriers lived in a single county in the southeast of Iceland and that all carriers shared a SNP haplotype, which is suggestive of a founder event. Cys557Ser was found on the same SNP haplotype background in the HapMap Project CEPH sample of Utah residents.
Our findings suggest that BARD1 Cys557Ser is an ancient variant that confers risk of single and multiple primary breast cancers, and this risk extends to carriers of the BRCA2 999del5 mutation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
European visual requirements for driving generally follow the standards of the European Union (EU), but the lack of a uniform perimetry algorithm leads to differing practices in enforcing ...visual field regulations. The purpose of this study was to develop a perimetry algorithm for group 1 driving licenses (car and motorcycle) that adheres to the European requirements.
Methods
We determined the features of a traffic perimetry algorithm complying with the EU directive 2009/113/EC and the underlying scientific report by the Eyesight Working Group. The final algorithm was a binocular, supra‐threshold test with 37 central and 86 peripheral test points within 140º x 40º. It was created as a custom test for an Octopus 900 perimeter and tested on participants with known visual field defects. Findings were compared with the Esterman program in reference to British and Norwegian regulations, which both recommend the Esterman program for assessing fitness to drive but differ in definition of negative and positive results.
Results
Twenty‐five participants were examined. In comparison with the traffic perimetry algorithm, sensitivity and specificity of the British regulations were 0.78 (95% confidence interval (CI) 0.40‐0.97) and 1.00 (95% CI 0.79‐1.00). Similarly, sensitivity and specificity of the Norwegian regulations were 0.89 (95% CI 0.52‐1.00) and 0.81 (95% CI 0.54‐0.96).
Conclusion
The lack of a perimetry algorithm that conforms to the scientific recommendations challenges the fundamental right of European drivers for legal equality. This study demonstrates a binocular supra‐threshold test that adheres to the European visual field requirements for group 1 driving licenses.
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