53 research outputs found
Networks of inter-organisational coordination during disease outbreaks
Multi-organisational environment is demonstrating more complexities due the ever-increasing tasksâ complications in modern environments. Disease outbreak coordination is one of these complex tasks that require multi-skilled and multi-jurisdictional agencies to coordinate in dynamic environment. This research discusses theoretical foundations and practical approaches to suggest frameworks to study complex inter-organisational networks in dynamic environments, specifically during disease outbreak. We study cooÂŹÂŹrdination as being an interdisciplinary domain, and then uses social network theory to model it. I have surveyed 70 health professionals whom have participated in the swine influenza H1N1 2009 outbreak. I collected both qualitative and quantitative data in order to build a comprehensive understanding of the dynamics of the inter-organisational network that evolved during that outbreak. Then I constructed a performance model by use three main components of the network theory: degree centrality, connectedness and tie strength as the independent variables, and disease outbreak inter-organisational performance as the dependent one. In addition, we study both the formal networks and the informal ones. Formal networks are based on the standard operating structures, and the informal ones emerge based on trust, mutual benefits and relationships. Results suggest that the proposed social network measures have positive effect on coordination performance during the outbreak in both formal and informal networks, except centrality in the formal one. In addition, none of those measures influence performance before the outbreak. Practically, the results suggest that increasing the communication frequency and diversifying the tiers of the inter-organisational links enhance the overall networkâs performance in formal coordination. In the informal one, links are created with the intention to improve performance; hence, all suggested network measures improve performance
Occurrence of Comorbidities before and after Soft Tissue Sarcoma Diagnosis
Background. Data is limited on the burden of common comorbidities, such as cardiovascular disease (CVD), respiratory disease and diabetes, or comorbidities related to cancer and its treatment, such as anemia and depression, in patients with soft tissue sarcoma (STS). Patients and Methods. From the Dutch Pathology Registry linked to the PHARMO database (including data on drug use and hospitalizations), 533 patients with STS were selected during 2000â2007 and matched 1â:â10 to cancer-free controls. The occurrences of comorbidities were assessed in the 12 months before and after STS diagnosis. Results. STS patients were 2â4 times more likely to have comorbidities at diagnosis compared with cancer-free controls. The incidence of CVD, anemia, and depression after STS diagnosis differed significantly from cancer-free controls and decreased during followup from 40â124 per 1,000 person-years (py) during the first six months to 11â38 per 1,000âpy more than 12 months after diagnosis. The incidence of respiratory disease and diabetes among STS patients remained stable during followup (5â21 per 1,000âpy) and did not differ significantly from cancer-free controls. Conclusions. STS patients were more likely to have comorbidities before cancer diagnosis and to develop CVD, anemia, and depression after diagnosis compared to cancer-free controls
Cervical cancer incidence after normal cytological sample in routine screening using SurePath, ThinPrep, and conventional cytology: population based study
#### Objective
To compare the cumulative incidence of cervical cancer
diagnosed within 72 months after a normal screening
sample between conventional cytology and liquid
based cytology tests SurePath and ThinPrep.
#### Design
Retrospective population based cohort study.
#### Setting
Nationwide network and registry of histo- and
cytopathology in the Netherlands (PALGA), January
2000 to March 2013.
#### Population
Women with 5924474 normal screening samples
(23833123 person years).
#### Exposure
Use of SurePath or ThinPrep versus conventional
cytology as screening test.
#### Main outcome measure
72 month cumulative incidence of invasive cervical
cancer after a normal screening sample for each
screening test. Cox regression analyses assessed the
hazard ratios, adjusted for calendar time, age,
screening history, and socioeconomic status and
including laboratories as random effects.
#### Results
The 72 month cumulative cancer incidence was 58.5
(95% confidence interval 54.6 to 62.7) per 100000
normal conventional cytology samples, compared with
66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6)
for SurePath. Compared with conventional cytology,
the hazard of invasive cancer was 19% lower (hazard
ratio 0.81, 95% confidence interval 0.66 to 0.99) for
SurePath, mainly caused by a 27% lower hazard (0.73,
0.57 to 0.93) of a clinically detected cancer. For
ThinPrep, the hazard was on average 15% higher
(hazard ratio 1.15, 0.95 to 1.38), mainly caused by a
56% higher hazard of a screen detected cancer (1.56,
1.17 to 2.08).
#### Conclusions
These findings should provoke reconsideration of the
assumed similarity in sensitivity to detect progressive
cervical intraepithelial neoplasia between different
types of liquid based cy
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 Ă 10-20), ER-negative BC (P=1.1 Ă 10-13), BRCA1-associated BC (P=7.7 Ă 10-16) and triple negative BC (P-diff=2 Ă 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 Ă 10-3) and ABHD8 (P<2 Ă 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3âČ-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk
An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers
Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10â8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers
A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10â8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers
Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe
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