A Dynamic Process Model of Private Politics: Activist Targeting and Corporate Receptivity to Social Challenges

This project explores whether and how corporations become more receptive to social activist challenges over time. Drawing from social movement theory, we suggest a dynamic process through which contentious interactions lead to increased receptivity. We argue that when firms are chronically targeted by social activists, they respond defensively by adopting strategic management devices that help them better manage social issues and demonstrate their normative appropriateness. These defensive devices have the incidental effect of empowering independent monitors and increasing corporate accountability, which in turn increase a firm’s receptivity to future activist challenges. We test our theory using a unique longitudinal dataset that tracks contentious attacks and the adoption of social management devices among a population of 300 large firms from 1993 to 2009

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

NMR studies of the structure and dynamics of filamentous bacteriophage fd coat proteins

The structure and dynamics of the coat proteins from the bacteriophage fd were determined using multidimensional high resolution solution NMR spectroscopy. The coat protein is a 50 amino acid protein which resides in the E. coli bacterial inner membrane during its lifecycle. The coat protein is synthesized in the cytoplasm of its host as a precursor procoat protein which has a 23 residue signal sequence. The characterization of the structure and dynamics of both coat and procoat proteins is essential to gain an understanding of the molecular events associated with phage assembly, protein translocation across a membrane and the role of the signal sequence. Multidimensional heteronuclear (\sp{15}N) solution NMR was used to determine the structure and dynamics of coat protein/micelle complexes. The correlation times of the coat protein/micelle complexes are approximately 10 nanoseconds, making the spectroscopic studies much more difficult than would be expected for 50 and 73 amino acid proteins. The incorporation of \sp{15}N into the proteins, the use of inverse detected experiments and the use of three dimensional NMR experiments allowed for the characterization of the secondary structure of fd coat protein in micelles. The structure of fd coat protein is almost entirely $\alpha$ helical, except for loosely structured, mobile termini. The backbone dynamics of both coat and procoat proteins indicate residues that are mobile on the nanosecond timescale, when compared to the overall correlation time of the proteins. Mobile termini are present in both procoat and coat protein and procoat protein has additional mobility in residues near the cleavage protein is almost entirely $\alpha$ helical, except for loosely structured, mobile termini. The backbone dynamics of both coat and procoat proteins indicate residues that are mobile on the nanosecond timescale, when compared to the overall correlation time of the proteins. Mobile termini are present in both procoat and coat protein and procoat protein has additional mobility in residues near the cleavage site ($-$1/+1). The structure and dynamics of fd coat protein are similar to to other membrane proteins because they are composed $\alpha$ helices and have mobile termini and loops

NMR studies of the structure and dynamics of filamentous bacteriophage fd coat proteins

The structure and dynamics of the coat proteins from the bacteriophage fd were determined using multidimensional high resolution solution NMR spectroscopy. The coat protein is a 50 amino acid protein which resides in the E. coli bacterial inner membrane during its lifecycle. The coat protein is synthesized in the cytoplasm of its host as a precursor procoat protein which has a 23 residue signal sequence. The characterization of the structure and dynamics of both coat and procoat proteins is essential to gain an understanding of the molecular events associated with phage assembly, protein translocation across a membrane and the role of the signal sequence. Multidimensional heteronuclear (\sp{15}N) solution NMR was used to determine the structure and dynamics of coat protein/micelle complexes. The correlation times of the coat protein/micelle complexes are approximately 10 nanoseconds, making the spectroscopic studies much more difficult than would be expected for 50 and 73 amino acid proteins. The incorporation of \sp{15}N into the proteins, the use of inverse detected experiments and the use of three dimensional NMR experiments allowed for the characterization of the secondary structure of fd coat protein in micelles. The structure of fd coat protein is almost entirely $\alpha$ helical, except for loosely structured, mobile termini. The backbone dynamics of both coat and procoat proteins indicate residues that are mobile on the nanosecond timescale, when compared to the overall correlation time of the proteins. Mobile termini are present in both procoat and coat protein and procoat protein has additional mobility in residues near the cleavage protein is almost entirely $\alpha$ helical, except for loosely structured, mobile termini. The backbone dynamics of both coat and procoat proteins indicate residues that are mobile on the nanosecond timescale, when compared to the overall correlation time of the proteins. Mobile termini are present in both procoat and coat protein and procoat protein has additional mobility in residues near the cleavage site ($-$1/+1). The structure and dynamics of fd coat protein are similar to to other membrane proteins because they are composed $\alpha$ helices and have mobile termini and loops

Women’s Perceptions of Their Community’s Social Norms Towards Assisting Women Who Have Experienced Intimate Partner Violence

The role of social norms has played an often unrecognized role in the perception of and action to assist low-income urban women who are in violent relationships. Two forms of social norms will be assessed, including descriptive norms—what people typically do to assist women in a violent relationship—and injunctive norms—defined as what people should do to assist women. This study will present our initial findings into the development of measures to assess women’s perception of their community’s social norms toward assisting women who have experienced intimate partner violence (IPV) and how these norms are related to women’s perception of the community, reasons for community assistance toward women experiencing IPV, and women’s own experience of IPV. Systematic measurement development processes were applied to reliably and validly develop the social norms measures. A three-phase approach was used to develop eight paired items measuring descriptive and injunctive norms. A total of 176 low-income urban women were interviewed and the scale responses were compared to length of time at the residence, perceptions of their neighborhood, perceived reasons for community involvement and non-involvement in assisting women experiencing IPV, and IPV experienced as an adult. The two developed social norms scales were found to have high internal consistency alpha coefficients of 0.84 for descriptive norms and 0.93 for injunctive norms. Paired t tests were statistically significant, denoting higher injunctive than descriptive social norms. Lowered descriptive norms were found among younger women, women who reported that they did not think their neighborhood was a good place to live, women who had ever experienced intimate partner violence as an adult, and perceived lower reasons for neighbor involvement and higher reasons for neighbor non-involvement toward assisting women experiencing IPV. Higher levels of injunctive social norms were statistically associated with living in a good place and increased perceived reasons for neighbor involvement toward assisting women experiencing IPV. Significant differences between descriptive and injunctive norms suggest that women, especially those who are currently experiencing IPV, would prefer greater support from community neighbors than they are currently providing. The descriptive and injunctive social norms scales demonstrated a high level of internal reliability and significantly associated with other influencing factors thought to be associated with social norms. Overall, the performance of the injunctive and descriptive norms scales support their use as a tool to investigate social norms toward neighbors taking action to assist women experiencing IPV