Aims: To gain an understanding of the environmental factors that affect the growth of the bacterium Sporosarcina pasteurii, the metabolism of the bacterium and the calcium carbonate precipitation ...induced by this bacterium to optimally implement the biological treatment process, microbial induced calcium carbonate precipitation (MICP), in situ. Methods and Results: Soil column and batch tests were used to assess the effect of likely subsurface environmental factors on the MICP treatment process. Microbial growth and mineral precipitation were evaluated in freshwater and seawater. Environmental conditions that may influence the ureolytic activity of the bacteria, such as ammonium concentration and oxygen availability, as well as the ureolytic activities of viable and lysed cells were assessed. Treatment formulation and injection rate, as well as soil particle characteristics are other factors that were evaluated for impact on uniform induction of cementation within the soils. Conclusions: The results of the study presented herein indicate that the biological treatment process is equally robust over a wide range of soil types, concentrations of ammonium chloride and salinities ranging from distilled water to full seawater; on the time scale of an hour, it is not diminished by the absence of oxygen or lysis of cells containing the urease enzyme. Significance and Impact of Study: This study advances the biological treatment process MICP towards field implementation by addressing key environmental hurdles faced with during the upscaling process.
In a study involving more than 5.9 million persons in a Danish registry, the presence of a mental disorder (in 11.8% of the population) was associated with subsequent medical conditions encompassing ...31 specific diagnoses, with hazard ratios that ranged from 0.82 to 3.62 and varied greatly over time.
Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative ...impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.
Objective:Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this ...association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods of infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia
Method:Nationwide population-based registers in Denmark were linked, and the data were analyzed in a cohort study using survival analysis. All analyses were adjusted for calendar year, age, and sex. Incidence rate ratios and accompanying 95% confidence intervals (CIs) as measures of relative risk were used.
Results:A prior autoimmune disease increased the risk of schizophrenia by 29% (incidence rate ratio=1.29; 95% CI=1.18–1.41). Any history of hospitalization with infection increased the risk of schizophrenia by 60% (incidence rate ratio=1.60; 95% CI=1.56–1.64). When the two risk factors were combined, the risk of schizophrenia was increased even further (incidence rate ratio=2.25; 95% CI=2.04–2.46). The risk of schizophrenia was increased in a dose-response relationship, where three or more infections and an autoimmune disease were associated with an incidence rate ratio of 3.40 (95% CI=2.91–3.94). The results remained significant after adjusting for substance use disorders and family history of psychiatric disorders. Hospital contact with infection occurred in nearly 24% of individuals prior to a schizophrenia diagnosis.
Conclusions:Autoimmune disease and the number of infections requiring hospitalization are risk factors for schizophrenia. The increased risk is compatible with an immunological hypothesis in subgroups of schizophrenia patients.
Immunological hypotheses have become increasingly prominent when studying the etiology of schizophrenia. Autoimmune diseases, and especially the number of infections requiring hospitalization, have ...been identified as significant risk factors for schizophrenia in a dose–response relationship, which seem compatible with an immunological hypothesis for subgroups of patients with schizophrenia. Inflammation and infections may affect the brain through many different pathways that are not necessarily mutually exclusive and can possibly increase the risk of schizophrenia in vulnerable individuals. However, the findings could also be an epiphenomenon and not causal, due to, for instance, common genetic vulnerability, which could be supported by the observations of an increased prevalence of autoimmune diseases and infections in parents of patients with schizophrenia. Nevertheless, autoimmune diseases and infections should be considered in the treatment of individuals with schizophrenia symptoms, and further research is needed of the immune system's possible contributing pathogenic factors in the etiology of schizophrenia.
ObjectiveResection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in ...resection for PaC in Europe and USA and determinants for its utilisation.DesignData from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003–2016 were analysed. Age-standardised resection rates for overall and stage I–II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models.ResultsA total of 153 698 records were analysed. In population-based registries in 2012–2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I–II tumours, with great international variations. During 2003–2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I–II tumours: 0.05–0.18 and 0.01–0.06 across countries) and increasing age (ORs for patients 70–79 and ≥80 versus those <60 years: 0.37–0.63 and 0.03–0.16 across countries). Patients with advanced-stage tumours (stage III–IV: 63.8%–81.2%) and at older ages (≥70 years: 52.6%–59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application.ConclusionRates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.
A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more ...frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples.
All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression.
Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individual's risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth.
Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.
Previous studies have shown associations between maternal infections during pregnancy and increased risks of schizophrenia and autism spectrum disorder in the offspring. However, large-scale studies ...investigating an association between parental infections both during and outside the pregnancy period and the risk of any mental disorder in the child are lacking.
A nationwide Danish cohort study identified 1,206,600 children born between 1996 and 2015 and followed them to a maximum of 20 years of age. Exposure included all maternal and paternal infections treated with anti-infective agents or hospital contacts before, during, or after pregnancy. The main outcome was a diagnosis of any mental disorder in the child. Hazard ratios (HRs) were calculated using Cox regression analysis.
Maternal infections during pregnancy treated with anti-infective agents (n = 567,016) increased the risk of mental disorders (n = 70,037) in the offspring (HR, 1.09; 95% confidence interval CI, 1.06–1.12), which was more elevated (p < .001) than after paternal infections (n = 350,835; HR, 1.01; 95% CI, 0.98–1.03). Maternal hospital contacts for infections (n = 39,753) conferred an increased HR of 1.21 (95% CI, 1.14–1.28), which was not significantly (p = .08) different from the risk after paternal infections (n = 8559; HR, 1.07; 95% CI, 0.95–1.20). The increased risks observed during pregnancy were not different from the similarly increased risks for maternal and paternal infections before and after pregnancy. The risk of mental disorders increased in a dose-response relationship with the number of maternal infections treated with anti-infective agents, particularly during and after pregnancy (both p < .001).
Maternal infections were associated with an increased risk of mental disorder in the offspring; however, there were similar estimates during and outside the pregnancy period.
Depression is a common psychiatric disorder and a leading cause of disability worldwide. Here we conducted a genome-wide association study meta-analysis of six datasets, including >1.3 million ...individuals (371,184 with depression) and identified 243 risk loci. Overall, 64 loci were new, including genes encoding glutamate and GABA receptors, which are targets for antidepressant drugs. Intersection with functional genomics data prioritized likely causal genes and revealed new enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found depression to be highly polygenic, with ~11,700 variants explaining 90% of the single-nucleotide polymorphism heritability, estimating that >95% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and attention deficit hyperactivity disorder) were influencing depression risk when both concordant and discordant variants were considered, and nearly all depression risk variants influenced educational attainment. Additionally, depression genetic risk was associated with impaired complex cognition domains. We dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across subgroups of depression and demonstrating significantly increased absolute risks for recurrence and psychiatric comorbidity among cases of depression with the highest polygenic burden, with considerable sex differences. The risks were up to 5- and 32-fold higher than cases with the lowest polygenic burden and the background population, respectively. These results deepen the understanding of the biology underlying depression, its disease progression and inform precision medicine approaches to treatment.
Objective
Information on mental disorders over time is critical for documenting changes in population burden, and aiding understanding of potential causal and non‐causal factors. The aim of this ...study was to provide temporal changes in the sex‐ and age‐specific incidence rates (IR) of mental disorders diagnosed in Danish hospitals during five decades and investigate whether such changes may be attributable to changes in administrative reporting practice.
Methods
This population‐based cohort study included all people living in Denmark between 1970 and 2016. Mental disorders diagnoses were obtained from the Danish Psychiatric Central Research Register. We estimated the IR of each mental disorder (all persons, and sex‐ and age‐specific IRs) and examined the impact of two administrative changes.
Results
Our study included 9 107 157 people, followed for 233.0 million person‐years. During follow‐up, 9.5% were diagnosed with at least one mental disorder. The IR for any mental disorder was 39.0 per 10,000 person‐years. Despite fluctuations, this increased between 1970–84 and 2005–2016, from 28.9 to 63.0 per 10,000 person‐years. Increases were most pronounced for younger age groups. Administrative changes did appear to influence incidence rates.
Conclusion
Mental disorder IRs have increased in Denmark since 1970, with age of diagnosis shifting downwards. Both trends were likely impacted by administrative changes, while the latter is likely to be (partly) attributable to earlier detection and increased reporting of child‐onset conditions. Our findings may provide valuable context of the epidemiology of mental disorders across age groups for comparison with other studies and populations.
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