Towards a complex model of disaster behaviour.

This paper outlines why a move towards a complex adaptive systems model of behaviour is required if the goal is to generate better understanding of how individuals and groups interact with their environment in a disaster setting. To accomplish this objective, a bridge must be built between the broader social sciences and behavioural economics to incorporate discipline-specific insights that are needed to move towards complexity. This is only possible through a deeper understanding of behaviour and how the environment in which they occur can influence actions. It is then that one can counteract the poor behavioural predictions, flawed policies based on myth, inefficient design, and suboptimal outcomes that have flourished in the absence of a complex adaptive systems model. This paper provides a conceptual framework that draws on concepts from across the natural and social sciences, such as behavioural economics, endocrinology, psychology, sociobiology, and sociology in order to build an interactive theory of disaster behaviour.

Online sperm donors: the impact of family, friends, personality and risk perception on behaviour.

As informal sperm donation becomes more prevalent worldwide, understanding donor psychology and interactions is critical in providing effective policy, equitable legislative frameworks and frontline health support to an ever-growing number of global participants. We analyse data of informal sperm donors who were members of the connection website PrideAngel to identify the role and effect of several factors, e.g. kinship, social networks, personality, and risk perception, on behaviour. A key strength of the study is the ability to analyse various factors, such as the level and history of informal donation, risk concerns, number of women to whom donations are informally made and the number of offspring. Our results indicate donors who have also been active in formal clinical settings (compared with those who exclusively donate informally), donate to more women in the informal market and realise more offspring. Donor's sexual orientation also affects activity. From a personality perspective, conscientiousness provides comparative advantage. It is possible this characteristic provides positive externalities, as more conscientious men may be more efficient or organised in a market that requires increased cooperation and communication. The importance of kin and social networks seems to affect frequency of donation only, possibly representing a time constraint (or opportunity cost).

A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region.

In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10).

Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFßR1.

Lipoxins, which are endogenously produced lipid mediators, promote the resolution of inflammation, and may inhibit fibrosis, suggesting a possible role in modulating renal disease. Here, lipoxin A4 (LXA4) attenuated TGF-ß1-induced expression of fibronectin, N-cadherin, thrombospondin, and the notch ligand jagged-1 in cultured human proximal tubular epithelial (HK-2) cells through a mechanism involving upregulation of the microRNA let-7c. Conversely, TGF-ß1 suppressed expression of let-7c. In cells pretreated with LXA4, upregulation of let-7c persisted despite subsequent stimulation with TGF-ß1. In the unilateral ureteral obstruction model of renal fibrosis, let-7c upregulation was induced by administering an LXA4 analog. Bioinformatic analysis suggested that targets of let-7c include several members of the TGF-ß1 signaling pathway, including the TGF-ß receptor type 1. Consistent with this, LXA4-induced upregulation of let-7c inhibited both the expression of TGF-ß receptor type 1 and the response to TGF-ß1. Overexpression of let-7c mimicked the antifibrotic effects of LXA4 in renal epithelia; conversely, anti-miR directed against let-7c attenuated the effects of LXA4. Finally, we observed that several let-7c target genes were upregulated in fibrotic human renal biopsies compared with controls. In conclusion, these results suggest that LXA4-mediated upregulation of let-7c suppresses TGF-ß1-induced fibrosis and that expression of let-7c targets is dysregulated in human renal fibrosis.

Residential mobility restrictions and adverse mental health outcomes during the COVID-19 pandemic in the UK.

During the COVID-19 pandemic, several governments tried to contain the spread of SARS-CoV-2, the virus that causes COVID-19, with lockdowns that prohibited leaving one's residence unless carrying out a few essential services. We investigate the relationship between limitations to mobility and mental health in the UK during the first year and a half of the pandemic using a unique combination of high-frequency mobility data from Google and monthly longitudinal data collected through the Understanding Society survey. We find a strong and statistically robust correlation between mobility data and mental health survey data and show that increased residential stationarity is associated with the deterioration of mental wellbeing even when regional COVID-19 prevalence and lockdown stringency are controlled for. The relationship is heterogeneous, as higher levels of distress are seen in young, healthy people living alone; and in women, especially if they have young children.

Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer.

Polycomb group proteins (PCGs) are involved in repression of genes that are required for stem cell differentiation. Recently, it was shown that promoters of PCG target genes (PCGTs) are 12-fold more likely to be methylated in cancer than non-PCGTs. Age is the most important demographic risk factor for cancer, and we hypothesized that its carcinogenic potential may be referred by irreversibly stabilizing stem cell features. To test this, we analyzed the methylation status of over 27,000 CpGs mapping to promoters of approximately 14,000 genes in whole blood samples from 261 postmenopausal women. We demonstrate that stem cell PCGTs are far more likely to become methylated with age than non-targets (odds ratio = 5.3 [3.8-7.4], P < 10(-10)), independently of sex, tissue type, disease state, and methylation platform. We identified a specific subset of 69 PCGT CpGs that undergo hypermethylation with age and validated this methylation signature in seven independent data sets encompassing over 900 samples, including normal and cancer solid tissues and a population of bone marrow mesenchymal stem/stromal cells (P < 10(-5)). We find that the age-PCGT methylation signature is present in preneoplastic conditions and may drive gene expression changes associated with carcinogenesis. These findings shed substantial novel insights into the epigenetic effects of aging and support the view that age may predispose to malignant transformation by irreversibly stabilizing stem cell features.

Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy.

BACKGROUND: Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN. METHODS: Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate. RESULTS: A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs in GSK3B (rs17810235, rs17471, rs334543), two in DAAM1 (rs1253192, rs1252906) and one in NFAT5 (rs17297207) as being significantly (P < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing. CONCLUSIONS: These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.

Interaction of natural survival instincts and internalized social norms exploring the Titanic and Lusitania disasters.

To understand human behavior, it is important to know under what conditions people deviate from selfish rationality. This study explores the interaction of natural survival instincts and internalized social norms using data on the sinking of the Titanic and the Lusitania. We show that time pressure appears to be crucial when explaining behavior under extreme conditions of life and death. Even though the two vessels and the composition of their passengers were quite similar, the behavior of the individuals on board was dramatically different. On the Lusitania, selfish behavior dominated (which corresponds to the classical homo economicus); on the Titanic, social norms and social status (class) dominated, which contradicts standard economics. This difference could be attributed to the fact that the Lusitania sank in 18 min, creating a situation in which the short-run flight impulse dominated behavior. On the slowly sinking Titanic (2 h, 40 min), there was time for socially determined behavioral patterns to reemerge. Maritime disasters are traditionally not analyzed in a comparative manner with advanced statistical (econometric) techniques using individual data of the passengers and crew. Knowing human behavior under extreme conditions provides insight into how widely human behavior can vary, depending on differing external conditions.

A GREM1 gene variant associates with diabetic nephropathy.

Gremlin, a cell growth and differentiation factor, promotes the development of diabetic nephropathy in animal models, but whether GREM1 gene variants associate with diabetic nephropathy is unknown. We comprehensively screened the 5' upstream region (including the predicted promoter), all exons, intron-exon boundaries, complete untranslated regions, and the 3' region downstream of the GREM1 gene. We identified 31 unique variants, including 24 with a minor allele frequency exceeding 5%, and 9 haplotype-tagging single nucleotide polymorphisms (htSNPs). We selected one additional variant that we predicted to alter transcription factor binding. We genotyped 709 individuals with type 1 diabetes of whom 267 had nephropathy (cases) and 442 had no evidence of kidney disease (controls). Three individual SNPs significantly associated with nephropathy at the 5% level, and two remained significant after adjustment for multiple testing. Subsequently, we genotyped a replicate population comprising 597 cases and 502 controls: this population supported an association with one of the SNPs (rs1129456; P = 0.0003). Combined analysis, adjusted for recruitment center (n = 8), suggested that the T allele conferred greater odds of nephropathy (OR 1.69; 95% CI 1.36 to 2.11). In summary, the GREM1 variant rs1129456 associates with diabetic nephropathy, perhaps explaining some of the genetic susceptibility to this condition.

Working parents, financial insecurity, and childcare: mental health in the time of COVID-19 in the UK.

The COVID-19 pandemic and the policy measures to control its spread-lockdowns, physical distancing, and social isolation-have coincided with the deterioration of people's mental well-being. We use data from the UK Household Longitudinal Study (UKHLS) to document how this phenomenon is related to the situation of working parents who now have to manage competing time demands across the two life domains of work and home. We show that the deterioration of mental health is worse for working parents, and that it is strongly related to increased financial insecurity and time spent on childcare and home schooling. This burden is not shared equally between men and women, and between richer and poorer households. These inequalities ought to be taken into account when crafting policy responses.

Risk attitudes and human mobility during the COVID-19 pandemic.

Behavioural responses to pandemics are less shaped by actual mortality or hospitalisation risks than they are by risk attitudes. We explore human mobility patterns as a measure of behavioural responses during the COVID-19 pandemic. Our results indicate that risk-taking attitudes are a critical factor in predicting reductions in human mobility and social confinement around the globe. We find that the sharp decline in mobility after the WHO (World Health Organization) declared COVID-19 to be a pandemic can be attributed to risk attitudes. Our results suggest that regions with risk-averse attitudes are more likely to adjust their behavioural activity in response to the declaration of a pandemic even before official government lockdowns. Further understanding of the basis of responses to epidemics, e.g., precautionary behaviour, will help improve the containment of the spread of the virus.

How confidence in health care systems affects mobility and compliance during the COVID-19 pandemic.

Confidence in the health care system implies an expectation that sufficient and appropriate treatments will be provided if needed. The COVID-19 public health crisis is a significant, global, and (mostly) simultaneous test of the behavioral implications arising from this confidence. We explore whether populations reporting low levels of confidence in the health care system exhibit a stronger behavioral reaction to the COVID-19 pandemic. We track the dynamic responses to the COVID-19 pandemic across 38 European countries and 621 regions by employing a large dataset on human mobility generated between February 15 and June 5, 2020 and a broad range of contextual factors (e.g., deaths or policy implementations). Using a time-dynamic framework we find that societies with low levels of health care confidence initially exhibit a faster response with respect to staying home. However, this reaction plateaus sooner, and after the plateau it declines with greater magnitude than does the response from societies with high health care confidence. On the other hand, regions with higher confidence in the health care system are more likely to reduce mobility once the government mandates that its citizens are not to leave home except for essential trips, compared to those with lower health care system confidence. Regions with high trust in the government but low confidence in the health care system dramatically reduce their mobility, suggesting a correlation for trust in the state with respect to behavioral responses during a crisis.

Genetic analysis of coronary artery disease single-nucleotide polymorphisms in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy is a leading cause of end-stage renal disease. Premature mortality is common in patients with nephropathy, largely due to cardiovascular disease. Genetic variants implicated in macrovascular disease are therefore excellent candidates to assess for association with diabetic nephropathy. Recent genome-wide association studies have identified a total of 15 single-nucleotide polymorphisms (SNPs) that are reproducibly associated with cardiovascular disease. METHODS: We initially assessed these SNPs for association in UK type 1 diabetic patients with (cases; n = 597) and without (controls; n = 502) nephropathy using iPLEX(TM) and TaqMan(R) assays. Replication studies were performed with DNA genotyped in a total of 2668 individuals from the British Isles. RESULTS: One SNP (rs4420638) on chromosome 19q13 was found to be significantly associated with diabetic nephropathy before (P = 0.0002) and after correction for multiple testing (P(corrected) = 0.002). We replicated this finding in a phenotypically similar case-control collection comprising 709 individuals with type 1 diabetes (P = 0.002; combined P < 0.00001; OR = 1.54, 95% CI: 1.29-1.84). CONCLUSIONS: Our case-control data suggest that rs4420638, or a functional SNP in linkage disequilibrium with this SNP, may be associated with diabetic nephropathy.

Resequencing of genes for transforming growth factor beta1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy.

BACKGROUND: Diabetic nephropathy is the leading cause of end stage renal failure in the western world. There is substantial epidemiological evidence supporting a genetic predisposition to diabetic nephropathy, however the exact molecular mechanisms remain unknown. Transforming growth factor (TGFbeta1) is a crucial mediator in the pathogenesis of diabetic nephropathy. METHODS: We investigated the role of five known single nucleotide polymorphisms (SNPs) in the TGFB1 gene for their association with diabetic nephropathy in an Irish, type 1 diabetic case (n = 272) control (n = 367) collection. The activity of TGFbeta1 is facilitated by the action of type 1 and type 2 receptors, with both receptor genes (TGFBR1 and TGFBR2) shown to be upregulated in diabetic kidney disease. We therefore screened TGFBR1 and TGFBR2 genes for genomic variants using WAVEtrade mark (dHPLC) technology and confirmed variants by direct capillary sequencing. Allele frequencies were determined in forty-eight healthy individuals. Data for all SNPs was assessed for Hardy Weinberg equilibrium, with genotypes and allele frequencies compared using the chi2 test for contingency tables. Patterns of linkage disequilibrium were established and common haplotypes estimated. RESULTS: Fifteen variants were identified in these genes, seven of which are novel, and putatively functional SNPs were subsequently genotyped using TaqMantrade mark, Invadertrade mark or Pyrosequencing(R) technology. No significant differences (p > 0.1) were found in genotype or allele distributions between cases and controls for any of the SNPs assessed. CONCLUSION: Our results suggest common variants in TGFB1, TGFBR1 and TGFBR2 genes do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population.

Association of VEGF-1499C-->T polymorphism with diabetic nephropathy in type 1 diabetes mellitus.

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C-->A, VEGF-1499C-->T, and VEGF-635G-->C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type 1 diabetes. Genomic DNA was obtained from Irish type 1 diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C-->A (genotype, P=.58; allele, P=.52) and VEGF-635G-->C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P <.001) and subsequently replicated in a separate population from the Republic of Ireland (P <.001; combined, P <.001). Carriage of the VEGF-1499T allele was associated with a twofold excess risk of developing diabetic nephropathy (OR=2.24, 95% CI=1.50-3.36, P <.0001). No significant differences were found between the healthy control population and the type 1 diabetic population. Our results suggest that the VEGF-1499T allele, or an allele in linkage disequilibrium with this allele, is associated with susceptibility to diabetic nephropathy in the Irish population.

Association between haptoglobin gene variants and diabetic nephropathy: haptoglobin polymorphism in nephropathy susceptibility.

BACKGROUND/AIMS: The Hp(1)/Hp(2) DNA polymorphism has previously been implicated in susceptibility to diabetic nephropathy in some but not all studies. In an attempt to clarify these conflicting findings, we conducted a case-control association study in a Caucasian population. METHODS: We recruited 224 and 285 type 1 diabetic patients with (cases) and without (controls) nephropathy, respectively, from 2 centres based in Northern Ireland and the Republic of Ireland. Hp(1)/Hp(2) genotyping was performed using a combination of long-range and multiplex PCR. Allele and genotype frequencies in cases and controls were compared using the chi(2) test. RESULTS: There was a statistically significant increase in the frequency of the Hp(2) allele in cases compared to controls (65.6 vs. 58.6%, OR = 1.35, 95% CI: 1.04-1.76, p = 0.03). The distributions of genotypes were in Hardy-Weinberg equilibrium for both cases and controls, and the overall frequency of the Hp(1) allele was 38.3%, which is similar to that found in other Western European populations. CONCLUSIONS: The results suggest that the Hp(2) allele may confer susceptibility to nephropathy in patients with type 1 diabetes.

Association between variation in the actin-binding gene caldesmon and diabetic nephropathy in type 1 diabetes.

Dysfunction of the actin cytoskeleton is a key event in the pathogenesis of diabetic nephropathy. We previously reported that certain cytoskeletal genes are upregulated in mesangial cells exposed to a high extracellular glucose concentration. One such gene, caldesmon, lies on chromosome 7q35, a region linked to nephropathy in family studies, making it a candidate susceptibility gene for diabetic nephropathy. We screened all exons, untranslated regions, and a 5-kb region upstream of the gene for variation using denaturing high-performance liquid chromatography technology. An A>G single nucleotide polymorphism (SNP) at position -579 in the promoter region was associated with nephropathy in a case-control study using 393 type 1 diabetic patients from Northern Ireland (odds ratio [OR] 1.38, 95% CI 1.02-1.86, P = 0.03). A similar trend was found in an independent sample from a second center. When the sample groups were combined (n = 606), the association between the -579G allele and nephropathy remained significant (OR 1.35, 1.07-1.70, P = 0.01). The haplotype structure in the surrounding 7-kb region was determined. No single haplotype was more strongly associated with nephropathy than the -579A>G SNP. These results suggest a role for the caldesmon gene in susceptibility to diabetic nephropathy in type 1 diabetes.

Lack of association of the Ala(45)Thr polymorphism and other common variants of the NeuroD gene with type 1 diabetes.

Variation in genes necessary for normal functioning and development of beta-cells, e.g., NEUROD1, which encodes a transcription factor for the insulin gene and is important in beta-cell development, causes maturity-onset diabetes of the young. Some studies have reported an association between a nonsynonymous Ala(45)Thr (+182G-->A) single nucleotide polymorphism (SNP) in NEUROD1 and type 1 diabetes, but this result has not been consistently found. To clarify this, we genotyped Ala(45)Thr in 2,434 type 1 diabetic families of European descent and Caucasian ethnicity from five different countries. Taking the allele frequency of 36% for Thr(45) and an odds ratio (OR) of 1.2, this sample provided >99% power to detect an association (P < 0.05). We could not confirm the association (P = 0.77). No evidence of population heterogeneity in the lack of association of Thr(45) with type 1 diabetes was observed. To evaluate the possibility that another NEUROD1 variant was associated with type 1 diabetes, we resequenced the gene in 32 U.K. affected individuals and identified and genotyped all common SNPs (minor allele frequency >10%; n = 5) in 786 families. We report no evidence of association of these common variants in NEUROD1 and type 1 diabetes in these samples.

Analysis of the type 2 diabetes-associated single nucleotide polymorphisms in the genes IRS1, KCNJ11, and PPARG2 in type 1 diabetes.

It has been proposed that type 1 and 2 diabetes might share common pathophysiological pathways and, to some extent, genetic background. However, to date there has been no convincing data to establish a molecular genetic link between them. We have genotyped three single nucleotide polymorphisms associated with type 2 diabetes in a large type 1 diabetic family collection of European descent: Gly972Arg in the insulin receptor substrate 1 (IRS1) gene, Glu23Lys in the potassium inwardly-rectifying channel gene (KCNJ11), and Pro12Ala in the peroxisome proliferative-activated receptor gamma2 gene (PPARG2). We were unable to confirm a recently published association of the IRS1 Gly972Arg variant with type 1 diabetes. Moreover, KCNJ11 Glu23Lys showed no association with type 1 diabetes (P > 0.05). However, the PPARG2 Pro12Ala variant showed evidence of association (RR 1.15, 95% CI 1.04-1.28, P = 0.008). Additional studies need to be conducted to confirm this result.

Association analysis of the lymphocyte-specific protein tyrosine kinase (LCK) gene in type 1 diabetes.

Prior data associating the expression of lymphocyte-specific protein tyrosine kinase (LCK) with type 1 diabetes, its critical function in lymphocytes, and the linkage of the region to diabetes in the nonobese diabetic (NOD) mouse model make LCK a premier candidate for a susceptibility gene. Resequencing of LCK in 32 individuals detected seven single nucleotide polymorphisms (SNPs) with allele frequencies >3%, including four common SNPs previously reported. These and six other SNPs from dbSNP were genotyped in a two-stage strategy using 2,430 families and were all shown not to be significantly associated with type 1 diabetes. We conclude that a major role for the common LCK polymorphisms in type 1 diabetes is unlikely. However, we cannot rule out the possibility of there being a causal variant outside the exonic, intronic, and untranslated regions studied.