Population and Economics in Ireland in the Recent Past and in the Near Future. ESRI Memorandum Series No. 148 1981

There is far more to population than economics. The existence of any person now is the result of one chance in countless billions of possibilities down the ages so, by this test, the value of a person is immeasurably great whatever her or his social status, though this may not appear about ourselves or to us about our fellow humans, there are so many of us. The existence of a person will usually create love and ether social relations of incomparable significance. We are aware that in law and in less worthy connections (including kidnapping) the question of valuation of a person can arise; figures are mentioned but they cannot be regarded seriously as statistics. At one time in Ireland* long ago the argument was rife in respectable circles that because it cost 1,000 to rear an emigrant the country lost 20 million a year if emigration amounted to 20,000 persons. R. C. Geary's (1941) refutation of this thesis is nowadays as likely to amuse as to instruct. You may hold that human existence is always better than non-existence, a philosophical question which shall not concern us. Our approach is almost exclusively statistical. We bear in mind, however, the peroration of Sean Lemass at the Centenary Banquet in 1947 of the SSISI. "The best things in life are not measurable by statistics and we pray that they will remain so". We mention non-statistical values lest they be forgotten. Population policy may be determined by such values, despite any statistical showing; this is for the people to determine. There may be no such conflict

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Economic Impact of Withdrawing Specific Agricultural Pesticides in the Lower Rio Grande Valley

The Air, Pesticides, and Toxics Division of the Environmental Protection Agency (EPA) has encouraged all states to develop a plan to manage the use of pesticides to prevent application that would result in unreasonable risks to human health and the environment from contamination of ground water. In February, 1988, EPA proposed a strategy where by they would regulate certain pesticides by prohibiting their use in areas vulnerable to leaching unless a state develops and implements a management plan acceptable to EPA. However, banning the use of a pesticide in a region is the worst case scenario available to the TWC for managing water quality. The Texas Water Commission (TWC) assessed the State for areas vulnerable to leaching and found the Lower Rio Grande Valley (LRGV) to be a highly vulnerable area. This study examines three pesticides (atrazine, dicrotophos, and aldicarb) currently used in the LRGV that were identified by the TWC as potential contaminants of ground water. Alternative methods of controlling pests in this region were identified, and the economic impacts of withdrawing one or all three of these pesticides from the study area were estimated. Regional impacts on gross receipts (sales), variable costs, and net returns were determined. If atrazine use were banned in the LRGV, corn and sorghum sales would decrease by approximately $1 million, variable costs to produce corn, sorghum, and sugarcane would increase by almost$2 million dollars, leaving farmers in the region with a $3 million dollar 1088 in net income per year. If dicrotophos use were prohibited in the LRGV, variable cost to produce cotton would increase by over$600,000 for the region as a whole. Banning aldicarb use in the study area would reduce citrus sales by almost $3 million, increase variable costs to produce citrus by over$200,000, and reduce farmer net income by over $3 million annually

Acute administration of dopaminergic drugs has differential effects on locomotion in larval zebrafish

Altered dopaminergic signaling causes behavioral changes in mammals. In general, dopaminergic receptor agonists increase locomotor activity, while antagonists decrease locomotor activity. In order to determine if zebrafish (a model organism becoming popular in pharmacology and toxicology) respond similarly, the acute effects of drugs known to target dopaminergic receptors in mammals were assessed in zebrafish larvae. Larvae were maintained in 96-well microtiter plates (1 larva/well). Non-lethal concentrations (0.2–50 µM) of dopaminergic agonists (apomorphine, SKF-38393, and quinpirole) and antagonists (butaclamol, SCH-23390, and haloperidol) were administered at 6 days post-fertilization (dpf). An initial experiment identified the time of peak effect of each drug (20–260 minutes post-dosing, depending on the drug). Locomotor activity was then assessed for 70 minutes in alternating light and dark at the time of peak effect for each drug to delineate dose-dependent effects. All drugs altered larval locomotion in a dose-dependent manner. Both the D1- and D2-like selective agonists (SKF-38393 and quinpirole, respectively) increased activity, while the selective antagonists (SCH-23390 and haloperidol, respectively) decreased activity. Both selective antagonists also blunted the response of the larvae to changes in lighting conditions at higher doses. The nonselective drugs had biphasic effects on locomotor activity: apomorphine increased activity at the low dose and at high doses, while butaclamol increased activity at low to intermediate doses, and decreased activity at high doses. This study demonstrates that (1) larval zebrafish locomotion can be altered by dopamine receptor agonists and antagonists, (2) receptor agonists and antagonists generally have opposite effects, and (3) drugs that target dopaminergic receptors in mammals appear, in general, to elicit similar locomotor responses in zebrafish larvae

The long‐term effectiveness and cost‐effectiveness of public health interventions; how can we model behavior? A review

The effectiveness and cost of a public health intervention is dependent on complex human behaviors, yet health economic models typically make simplified assumptions about behavior, based on little theory or evidence. This paper reviews existing methods across disciplines for incorporating behavior within simulation models, to explore what methods could be used within health economic models and to highlight areas for further research. This may lead to better-informed model predictions. The most promising methods identified which could be used to improve modeling of the causal pathways of behavior-change interventions include econometric analyses, structural equation models, data mining and agent-based modeling; the latter of which has the advantage of being able to incorporate the non-linear, dynamic influences on behavior, including social and spatial networks. Twenty-two studies were identified which quantify behavioral theories within simulation models. These studies highlight the importance of combining individual decision making and interactions with the environment and demonstrate the importance of social norms in determining behavior. However, there are many theoretical and practical limitations of quantifying behavioral theory. Further research is needed about the use of agent-based models for health economic modeling, and the potential use of behavior maintenance theories and data mining

Hard-Loop Effective Action for Anisotropic Plasmas

We generalize the hard-thermal-loop effective action of the equilibrium quark-gluon plasma to a non-equilibrium system which is space-time homogeneous but for which the parton momentum distribution is anisotropic. We show that the manifestly gauge-invariant Braaten-Pisarski form of the effective action can be straightforwardly generalized and we verify that it then generates all n-point functions following from collisionless gauge-covariant transport theory for a homogeneous anisotropic plasma. On the other hand, the Taylor-Wong form of the hard-thermal-loop effective action has a more complicated generalization to the anisotropic case. Already in the simplest case of anisotropic distribution functions, it involves an additional term that is gauge invariant by itself, but nontrivial also in the static limit.Comment: 12 pages. Version 3: typo in (15) corrected, note added discussing metric conventions use

Comparison of the Oxidation State of Fe in Comet 81P/Wild 2 and Chondritic-Porous Interplanetary Dust Particles

The fragile structure of chondritic-porous interplanetary dust particles (CP- IDPs) and their minimal parent-body alteration have led researchers to believe these particles originate in comets rather than asteroids where aqueous and thermal alteration have occurred. The solar elemental abundances and atmospheric entry speed of CP-IDPs also suggest a cometary origin. With the return of the Stardust samples from Jupiter-family comet 81P/Wild 2, this hypothesis can be tested. We have measured the Fe oxidation state of 15 CP-IDPs and 194 Stardust fragments using a synchrotron-based x-ray microprobe. We analyzed ~300 nanograms of Wild 2 material - three orders of magnitude more material than other analyses comparing Wild 2 and CP-IDPs. The Fe oxidation state of these two samples of material are >2{\sigma} different: the CP-IDPs are more oxidized than the Wild 2 grains. We conclude that comet Wild 2 contains material that formed at a lower oxygen fugacity than the parent body, or parent bodies, of CP-IDPs. If all Jupiter-family comets are similar, they do not appear to be consistent with the origin of CP-IDPs. However, comets that formed from a different mix of nebular material and are more oxidized than Wild 2 could be the source of CP-IDPs.Comment: Earth and Planetary Science Letters, in pres

Regulation of the androgen receptor by SET9-mediated methylation

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9. Methylation of the AR on lysine 632 is necessary for enhancing transcriptional activity of the receptor by facilitating both inter-domain communication between the N- and C-termini and recruitment to androgen-target genes. We also show that SET9 is pro-proliferative and anti-apoptotic in prostate cancer cells and demonstrates up-regulated nuclear expression in prostate cancer tissue. In all, our date indicate a new mechanism of AR regulation that may be therapeutically exploitable for prostate cancer treatment

The structural basis for high‐affinity uptake of lignin‐derived aromatic compounds by proteobacterial TRAP transporters

The organic polymer lignin is a component of plant cell walls, which like (hemi)-cellulose is highly abundant in nature and relatively resistant to degradation. However, extracellular enzymes released by natural microbial consortia can cleave the β-aryl ether linkages in lignin, releasing monoaromatic phenylpropanoids that can be further catabolised by diverse species of bacteria. Biodegradation of lignin is therefore important in global carbon cycling, and its natural abundance also makes it an attractive biotechnological feedstock for the industrial production of commodity chemicals. Whilst the pathways for degradation of lignin-derived aromatics have been extensively characterised, much less is understood about how they are recognised and taken up from the environment. The purple phototrophic bacterium Rhodopseudomonas palustris can grow on a range of phenylpropanoid monomers and is a model organism for studying their uptake and breakdown. R. palustris encodes a tripartite ATP-independent periplasmic (TRAP) transporter (TarPQM) linked to genes encoding phenylpropanoid-degrading enzymes. The periplasmic solute-binding protein component of this transporter, TarP, has previously been shown to bind aromatic substrates. Here, we determine the high-resolution crystal structure of TarP from R. palustris as well as the structures of homologous proteins from the salt marsh bacterium Sagittula stellata and the halophile Chromohalobacter salexigens, which also grow on lignin-derived aromatics. In combination with tryptophan fluorescence ligand-binding assays, our ligand-bound co-crystal structures reveal the molecular basis for high-affinity recognition of phenylpropanoids by these TRAP transporters, which have potential for improving uptake of these compounds for biotechnological transformations of lignin