Cholera as a 'sanitary test' of British cities, 1831-1866.

The malign contribution of northern industrial cities to the stagnation of national life expectancy over the period 1820-1870 forms part of one of the most long-running debates in English economic history, regarding the impact of early industrialisation on living standards. The deteriorating quality of urban water supplies often features in these arguments as the key driver of worsening mortality in this period. Here we use mortality reported from cholera in the epidemic years 1831-1832 and 1848-1849 as an indicator of the extent of sewage contamination of water in English and Welsh towns in this period. Surprisingly, the geography of reported mortality did not indicate that northern manufacturing and industrial towns were especially deficient in this respect. However, logistic regression analyses identified a number of risk factors for high cholera mortality, including location on coal-bearing strata, which was a feature of many industrial towns. Notably, however, textile-manufacturing towns, although often located in coal-rich districts, were associated with low levels of cholera mortality, and high population growth rates did not influence the risk of cholera. Reductions in cholera mortality after 1849 raise the possibility of widespread improvements in water quality after mid-century, rather earlier than is often assumed. However, in contrast to cholera, infant and diarrhoeal mortality remained high especially in northern towns until at least 1900. Several lines of evidence suggest that infants were relatively protected from waterborne diseases such as cholera and typhoid, and therefore did not benefit greatly from improvements in water quality. We conclude (1) that any worsening of water quality in urban areas c.1800-1850 was not confined to new͛ or rapidly growing industrial or manufacturing towns; and (2) infants probably rarely drank untreated water, so high infant or diarrhoeal mortality rates should not be read as indicators of poor water quality, in the English context

The geography of smallpox in England before vaccination: A conundrum resolved.

Smallpox is regarded as an ancient and lethal disease of humans, however very little is known about the prevalence and impact of smallpox before the advent of vaccination (c.1800). Here we use evidence from English burial records covering the period 1650-1799 to confirm a striking geography to smallpox patterns. Smallpox apparently circulated as a childhood disease in northern England and Sweden, even where population densities were low and settlement patterns dispersed. However, smallpox was a relatively rare epidemic disease in southern England outside the largest cities, despite its commercialised economy and the growing spatial interconnectedness of its settlements. We investigated a number of factors hypothesised to influence the regional circulation of smallpox, including exposure to naturally occurring orthopox viruses, settlement patterns, and deliberate preventative measures. We concluded that transmission was controlled in southern England by local practices of avoidance and mass inoculation that arose in the seventeenth and eighteenth centuries. Avoidance measures included isolation of victims in pest houses and private homes, as well as cancellation of markets and other public gatherings, and pre-dated the widespread use of inoculation. The historical pattern of smallpox in England supports phylogenetic evidence for a relatively recent origin of the variola strains that circulated in the twentieth century, and provides evidence for the efficacy of preventative strategies complementary to immunisation

Constructing Parish-level Data and RSD-level Data on Transport Infrastructure in England and Wales 1851-1911

This paper documents the methods used to construct a database at parish and RSD-level of transport infrastructure in England and Wales for each census year 1851-1911: for ports; turnpike roads (1851 only); first class roads (1911 only); railway lines and stations; waterways; and presence of sea coasts

Railways, divergence, and structural change in 19th century England and Wales

Railways transformed inland transport during the nineteenth century. In this paper, we study how railways led to local population change and divergence in England and Wales as it underwent dramatic urbanization. We make use of detailed data on railway stations, population, and occupational structure in more than 9000 spatial units. A network of least cost paths based on major towns and the length of the 1851 rail network is also created to address endogeneity. Our instrumental variable estimates show that having a railway station in a locality by 1851 led to significantly higher population growth from 1851 to 1891 and shifted the male occupational structure out of agriculture. Moreover, we estimate that having stations increased population growth more if localities had greater initial population density and for those 3–15 km from stations, they had less growth compared to localities more distant from stations. Overall, we find that railways reinforced the population hierarchy of the early nineteenth century and contributed to further spatial divergence. Their implications for the geographic distribution of population were large

Industry structure, entrepreneurship, and culture: An empirical analysis using historical coalfields

There is mounting evidence demonstrating that entrepreneurship is spatially clustered and that these spatial differences are quite persistent over long periods of time. However, especially the sources of that persistence are not yet well-understood, and it is largely unclear whether persistent differences in entrepreneurship are reflected in differences in entrepreneurship culture across space as it is often argued in the literature. We approach the cluster phenomenon by theorizing that a historically high regional presence of large-scale firms negatively affects entrepreneurship, due to low levels of human capital and entrepreneurial skills, fewer opportunities for entry and entrepreneurship inhibiting formal and informal institutions. These effects can become self-perpetuating over time, ultimately resulting in persistent low levels of entrepreneurship activity and entrepreneurship culture. Using data from Great Britain, we analyze this long-term imprinting effect by using the distance to coalfields as an exogenous instrument for the regional presence of large-scale industries. IV regressions show that British regions with high employment shares of large-scale industries in the 19th century, due to spatial proximity to coalfields, have lower entrepreneurship rates and weaker entrepreneurship culture today. We control for an array of competing hypotheses like agglomeration forces, the regional knowledge stock, climate, and soil quality. Our main results are robust with respect to inclusion of these control variables and various other modifications which demonstrates the credibility of our empirical identification strategy. A mediation analysis reveals that a substantial part of the impact of large-scale industries on entrepreneurship is through human capital

In the shadow of coal: How large-scale industries contributed to present-day regional differences in personality and well-being

Recent research has identified regional variation of personality traits within countries but we know little about the underlying drivers of this variation. We propose that the Industrial Revolution, as a key era in the history of industrialized nations, has led to a persistent clustering of well-being outcomes and personality traits associated with psychological adversity via processes of selective migration and socialization. Analyzing data from England and Wales, we examine relationships between the historical employment share in large-scale coal-based industries (coal mining and steam-powered manufacturing industries that used this coal as fuel for their steam engines) and today’s regional variation in personality and well-being. Even after controlling for possible historical confounds (historical energy supply, education, wealth, geology, climate, population density), we find that the historical local dominance of large-scale coal-based industries predicts today’s markers of psychological adversity (lower Conscientiousness [and order facet scores], higher Neuroticism [and anxiety and depression facet scores], lower activity [an Extraversion facet], and lower life satisfaction and life expectancy). An instrumental variable analysis, using the historical location of coalfields, supports the causal assumption behind these effects (with the exception of life satisfaction). Further analyses focusing on mechanisms hint at the roles of selective migration and persisting economic hardship. Finally, a robustness check in the U.S. replicates the effect of the historical concentration of large-scale industries on today’s levels of psychological adversity. Taken together, the results show how today’s regional patterns of personality and well-being may have their roots in major societal changes underway decades or centuries earlier

Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset

Background: Age at symptom onset (ASO) is a prognostic factor that could affect the accrual of disability in multiple sclerosis (MS) patients. Some factors are known to influence the risk of multiple sclerosis (MS), but their influence on the ASO is less well-investigated. Objective: Examine the associations between known or emerging MS risk factors and ASO. Methods: This was a multicenter study, incident cases (n = 279) with first clinical diagnosis of demyelinating event aged 18-59 years recruited at four Australian centres (latitudes 27°-43°S), from 1 November 2003 to 31 December 2006. Environmental/behavioral variables and initial symptoms were recorded at baseline interview. Linear regression was used to assess the association between risk factors and ASO. Results: Five factors were significantly associated with ASO: a history of tobacco smoking was associated with 3.05-years later ASO (p = 0.002); a history of marijuana use was associated with 6.03-years earlier ASO (p < 0.001); progressive-onset cases had 5.61-years later ASO (p = 0.001); an initial presentation of bowel & bladder and cerebral dysfunctional were associated with 3.39 (p = 0.017) and 4.37-years (p = 0.006) later ASO, respectively. Other factors, including sex, offspring number, latitude of study site, history of infectious mononucleosis, HLA-DR15 & HLA-A2 genotype, 25(OH)D levels, and ultraviolet radiation exposure were not associated with ASO. Including all five significant variables into one model explained 12% of the total variance in ASO. Conclusion: We found a novel association between a history of tobacco smoking and later onset, whereas marijuana use was associated with earlier onset. Behavioral factors seem important drivers of MS onset timing although much of the variance remains unexplained

Isolation of a wide range of minerals from a thermally treated plant: Equisetum arvense, a Mare’s tale

Silica is the second most abundant biomineral being exceeded in nature only by biogenic CaCO3. Many land plants (such as rice, cereals, cucumber, etc.) deposit silica in significant amounts to reinforce their tissues and as a systematic response to pathogen attack. One of the most ancient species of living vascular plants, Equisetum arvense is also able to take up and accumulate silica in all parts of the plant. Numerous methods have been developed for elimination of the organic material and/or metal ions present in plant material to isolate biogenic silica. However, depending on the chemical and/or physical treatment applied to branch or stem from Equisetum arvense; other mineral forms such glass-type materials (i.e. CaSiO3), salts (i.e. KCl) or luminescent materials can also be isolated from the plant material. In the current contribution, we show the chemical and/or thermal routes that lead to the formation of a number of different mineral types in addition to biogenic silica

Meta-analysis of pharmacogenetic interactions in amyotrophic lateral sclerosis clinical trials

OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months. On an exploratory basis, we assessed whether the effect of lithium depended on the genotype. RESULTS: Clinical data were available for 518 of the 606 participants. Overall, treatment with lithium carbonate did not improve 12-month survival (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.7-1.4; p = 0.96). Both the UNC13A and C9orf72 genotype were independent predictors of survival (HR 2.4, 95% CI 1.3-4.3; p = 0.006 and HR 2.5, 95% CI 1.1-5.2; p = 0.032, respectively). The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3). CONCLUSIONS: This study incorporated genetic data into past ALS trials to determine treatment effects in a genetic post hoc analysis. Our results suggest that we should reorient our strategies toward finding treatments for ALS, start focusing on genotype-targeted treatments, and standardize genotyping in order to optimize randomization and analysis for future clinical trials

Onset symptoms, tobacco smoking, and progressive-onset phenotype are associated with a delayed onset of multiple sclerosis, and marijuana use with an earlier onset

Background: Age at symptom onset (ASO) is a prognostic factor that could affect the accrual of disability in multiple sclerosis (MS) patients. Some factors are known to influence the risk of multiple sclerosis (MS), but their influence on the ASO is less well-investigated. Objective: Examine the associations between known or emerging MS risk factors and ASO. Methods: This was a multicenter study, incident cases (n = 279) with first clinical diagnosis of demyelinating event aged 18–59 years recruited at four Australian centres (latitudes 27°-43°S), from 1 November 2003 to 31 December 2006. Environmental/behavioral variables and initial symptoms were recorded at baseline interview. Linear regression was used to assess the association between risk factors and ASO. Results: Five factors were significantly associated with ASO: a history of tobacco smoking was associated with 3.05-years later ASO (p = 0.002); a history of marijuana use was associated with 6.03-years earlier ASO (p < 0.001); progressive-onset cases had 5.61-years later ASO (p = 0.001); an initial presentation of bowel & bladder and cerebral dysfunctional were associated with 3.39 (p = 0.017) and 4.37-years (p = 0.006) later ASO, respectively. Other factors, including sex, offspring number, latitude of study site, history of infectious mononucleosis, HLA-DR15 & HLA-A2 genotype, 25(OH)D levels, and ultraviolet radiation exposure were not associated with ASO. Including all five significant variables into one model explained 12% of the total variance in ASO. Conclusion: We found a novel association between a history of tobacco smoking and later onset, whereas marijuana use was associated with earlier onset. Behavioral factors seem important drivers of MS onset timing although much of the variance remains unexplained.Chunrong Tao, Steve Simpson Jr., Bruce V. Taylor, Leigh Blizzard, Robyn M. Lucas, Anne-Louise Ponsonby, Simon Broadley, Keith Dear, AusLong, Ausimmune Investigators Group and Ingrid van der Me