IMG 305 - PEMBUNGKUSAN MAKANAN NOV.05.

We discuss the use of Agent-based Modelling for the development and testing of theories about emergent social phenomena in marketing and the social sciences in general. We address both theoretical aspects about the types of phenomena that are suitably addressed with this approach and practical guidelines to help plan and structure the development of a theory about the causes of such a phenomenon in conjunction with a matching ABM. We argue that research about complex social phenomena is still largely fundamental research and therefore an iterative and cyclical development process of both theory and model is to be expected. To better anticipate and manage this process, we provide theoretical and practical guidelines. These may help to identify and structure the domain of candidate explanations for a social phenomenon, and furthermore assist the process of model implementation and subsequent development. The main goal of this paper was to make research on complex social systems more accessible and help anticipate and structure the research process

Evolution of microstructure and crystallographic texture during dissimilar friction stir welding of duplex stainless steel to low carbon-manganese structural steel

Electron backscattered diffraction (EBSD) was used to analyze the evolution of microstructure and crystallographic texture during friction stir welding of dissimilar type 2205 duplex stainless steel (DSS) to type S275 low carbon-manganese structural steel. The results of microstructural analyses show that the temperature in the center of stirred zone reached temperatures between Ac 1 and Ac 3 during welding, resulting in a minor ferrite-to-austenite phase transformation in the S275 steel, and no changes in the fractions of ferrite and austenite in the DSS. Temperatures in the thermomechanically affected and shoulder-affected zones of both materials, in particular toward the root of the weld, did not exceed the Ac 1 of S275 steel. The shear generated by the friction between the material and the rotating probe occurred in austenitic/ferritic phase field of the S275 and DSS. In the former, the transformed austenite regions of the microstructure were transformed to acicular ferrite, on cooling, while the dual-phase austenitic/ferritic structure of the latter was retained. Studying the development of crystallographic textures with regard to shear flow lines generated by the probe tool showed the dominance of simple shear components across the whole weld in both materials. The ferrite texture in S275 steel was dominated by D 1, D 2, E, E¯ , and F, where the fraction of acicular ferrite formed on cooling showed a negligible deviation from the texture for the ideal shear texture components of bcc metals. The ferrite texture in DSS was dominated by D 1, D 2, I, I¯ , and F, and that of austenite was dominated by the A, A¯ , B, and B¯ of the ideal shear texture components for bcc and fcc metals, respectively. While D 1, D 2, and F components of the ideal shear texture are common between the ferrite in S275 steel and that of dual-phase DSS, the preferential partitioning of strain into the ferrite phase of DSS led to the development of I and I¯ components in DSS, as opposed to E and E¯ in the S275 steel. The formations of fine and ultrafine equiaxed grains were observed in different regions of both materials that are believed to be due to strain-induced continuous dynamic recrystallization (CDRX) in ferrite of both DSS and S275 steel, and discontinuous dynamic recrystallization (DDRX) in austenite phase of DSS

Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival

Background Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. Aim To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Methods Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. Results There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09–1.56)]. Conclusion Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92–0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88–0.94). Conclusions Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer

Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 11), 10p14 (rs3781093, P=9.49 × 10-13), 13q34 (rs112998813, P=4.58 × 10-8) and 16p13.13 (rs34972832, P=2.12 × 10-8). Additionally, independent loci within the HLA region are observed for NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely