Adam Smith’s Green Thumb and Malthus’ Three Horsemen: Cautionary tales from classical political economy

This essay identifies a contradiction between the flourishing interest in the environmental economics of the classical period and a lack of critical parsing of the works of its leading representatives. Its focus is the work of Adam Smith and Thomas Malthus. It offers a critical analysis of their contribution to environmental thought and surveys the work of their contemporary devotees. It scrutinizes Smith's contribution to what Karl Polanyi termed the "economistic fallacy," as well as his defenses of class hierarchy, the "growth imperative" and consumerism. It subjects to critical appraisal Malthus's enthusiasm for private property and the market system, and his opposition to market regulation. While Malthus's principal attraction to ecological economists lies in his having allegedly broadened the scope of economics, and in his narrative of scarcity, this article shows that he, in fact, narrowed the scope of the discipline and conceptualized scarcity in a reified and pseudo-scientific way

Informed Conditioning on Clinical Covariates Increases Power in Case-Control Association Studies

Genetic case-control association studies often include data on clinical covariates, such as body mass index (BMI), smoking status, or age, that may modify the underlying genetic risk of case or control samples. For example, in type 2 diabetes, odds ratios for established variants estimated from low–BMI cases are larger than those estimated from high–BMI cases. An unanswered question is how to use this information to maximize statistical power in case-control studies that ascertain individuals on the basis of phenotype (case-control ascertainment) or phenotype and clinical covariates (case-control-covariate ascertainment). While current approaches improve power in studies with random ascertainment, they often lose power under case-control ascertainment and fail to capture available power increases under case-control-covariate ascertainment. We show that an informed conditioning approach, based on the liability threshold model with parameters informed by external epidemiological information, fully accounts for disease prevalence and non-random ascertainment of phenotype as well as covariates and provides a substantial increase in power while maintaining a properly controlled false-positive rate. Our method outperforms standard case-control association tests with or without covariates, tests of gene x covariate interaction, and previously proposed tests for dealing with covariates in ascertained data, with especially large improvements in the case of case-control-covariate ascertainment. We investigate empirical case-control studies of type 2 diabetes, prostate cancer, lung cancer, breast cancer, rheumatoid arthritis, age-related macular degeneration, and end-stage kidney disease over a total of 89,726 samples. In these datasets, informed conditioning outperforms logistic regression for 115 of the 157 known associated variants investigated (P-value = 1×10−9). The improvement varied across diseases with a 16% median increase in χ2 test statistics and a commensurate increase in power. This suggests that applying our method to existing and future association studies of these diseases may identify novel disease loci

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Regulation of GTP-binding Protein (Galpha s) Expression in Human Myometrial Cells A ROLE FOR TUMOR NECROSIS FACTOR IN MODULATING G s PROMOTER ACETYLATION BY TRANSCRIPTIONAL COMPLEXES

The onset of parturition is associated with a number of proinflammatory mediators that are themselves regulated by the nuclear factor κB (NF-κB) family of transcription factors. In this context, we previously reported that the RelA NF-κB subunit represses transcription and mRNA expression of the proquiescent Gαs gene in human myometrial cells following stimulation with the proinflammatory cytokine TNF. In the present study, we initially defined the functional consequence of this on myometrial contractility. Here we show that, contrary to our initial expectations, TNF did not induce myometrial contractility but did inhibit the relaxation produced by the histone deacetylase inhibitor trichostatin A, an effect that in turn was abolished by the NF-κB inhibitor N4-[2-(4-phenoxyphenyl)ethyl]-4,6-quinazolinediamine. This result suggested a role for TNF in regulating Gαs expression via activating NF-κB and modifying histone acetylation associated with the promoter region of the gene. In this context, we show that the −837 to −618 region of the endogenous Gαs promoter is occupied by cAMP-response element-binding protein (CREB), Egr-1, and Sp1 transcription factors and that CREB-binding protein (CBP) transcriptional complexes form within this region where they induce histone acetylation, resulting in increased Gαs expression. TNF, acting via NF-κB, did not change the levels of CREB, Sp1, or Egr-1 binding to the Gαs promoter, but it induced a significant reduction in the level of CBP. This was associated with increased levels of histone deacetylase-1 and surprisingly an increase in H4K8 acetylation. The latter is discussed herein

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Ambient ionisation mass spectrometry for the trace detection of explosives using a portable mass spectrometer

Five different classes of explosives were analysed by ambient ionisation mass spectrometry testing selectivity, sensitivity, and repeatability. We compare the effectiveness of two techniques (ASAP and SESI) for the trace detection of five explosives representative of the most common classes of high explosive: HMTD, RDX, PETN, Tetryl and TNT. Experiments also compared the effectiveness of sample loading via a glass fibre swab or glass rod. All analyses were carried out with a Waters Acquity QDa mass spectrometer, a small format mass spectrometer which can be operated in a transportable mode (using ambient air and a small diaphragm pump).Both ambient ionisation techniques, ASAP and SESI, successfully detected the five different explosives which could make them suitable for a screening method. By directly comparing a calibration range of 0.8–10 ng on both swabs and rods for each explosive, it appears that SESI produces less variability per repeat, particularly at the higher end of the range when compared to ASAP which typically has a lower limit of detection and better linearity

Short-Term Psychodynamic Psychotherapy for Functional Somatic Disorders: A Meta-Analysis of Randomized Controlled Trials

Introduction: Functionalsomatic disorders (FSD) are common and costly, thereby driving the need for the development of effective brief treatment options. Short-term psychodynamic psychotherapy (STPP) is one candidate treatment method. Objective: To review and meta-analyze, where possible, randomized controlled trials (RCTs) of STPP for FSD. Methods: Following a systematic search of the literature, we performed a meta-analysis of available RCT groups to determine the effects of STPP on a range of outcomes after treatment, and medium- and long-term follow-ups. Results: In meta-analyses of 17 RCTs, STPP significantly outperformed minimal treatment, treatment as usual, or waiting list controls on somatic symptom measures at all time frames, with small to large magnitude effect sizes. Descriptive reviews of 5 RCTs suggest that STPP performed at least as well as other bona fide psychological therapies. Limitations of this meta-analysis include small samples of studies and possible publication bias. Conclusions: STPP is a valid treatment option for diverse FSD conditions resulting in somatic symptom reductions that persist over time. STPP should be included in FSD treatment guidelines.status: Published onlin

Short-Term Psychodynamic Psychotherapy for Functional Somatic Disorders: A Meta-Analysis of Randomized Controlled Trials

Introduction: Functionalsomatic disorders (FSD) are common and costly, thereby driving the need for the development of effective brief treatment options. Short-term psychodynamic psychotherapy (STPP) is one candidate treatment method. Objective: To review and meta-analyze, where possible, randomized controlled trials (RCTs) of STPP for FSD. Methods: Following a systematic search of the literature, we performed a meta-analysis of available RCT groups to determine the effects of STPP on a range of outcomes after treatment, and medium- and long-term follow-ups. Results: In meta-analyses of 17 RCTs, STPP significantly outperformed minimal treatment, treatment as usual, or waiting list controls on somatic symptom measures at all time frames, with small to large magnitude effect sizes. Descriptive reviews of 5 RCTs suggest that STPP performed at least as well as other bona fide psychological therapies. Limitations of this meta-analysis include small samples of studies and possible publication bias. Conclusions: STPP is a valid treatment option for diverse FSD conditions resulting in somatic symptom reductions that persist over time. STPP should be included in FSD treatment guidelines