Exploring natural resource management tradeoffs in an agricultural landscape - an application of the MOSAIC model.

We describe a landscape scale non-linear discrete choice spatial optimisation model for identifying cost-effective strategies for achieving environmental goals. Spatial heterogeneity and configuration issues such as fencing costs, patch sizes and network linkages are explicitly accounted for and quasi-optimal allocations are determined using simulated annealing. Applications of the model being developed with New South Wales Catchment Management Authorities are discussed. These focus on targeting investments in revegetation to control dryland salinity and erosion and provide biodiversity benefits whilst minimising direct and opportunity costs. We compare our approach with alternate investment approaches.natural resource management, cost effectiveness, land use change, multicriteria, spatial optimisation, Resource /Energy Economics and Policy,

Phytocannabinoids as novel therapeutic agents in CNS disorders

The Cannabis sativa herb contains over 100 phytocannabinoid (pCB) compounds and has been used for thousands of years for both recreational and medicinal purposes. In the past two decades, characterisation of the body's endogenous cannabinoid (CB) (endocannabinoid, eCB) system (ECS) has highlighted activation of central CB1 receptors by the major pCB, Δ9-tetrahydrocannabinol (Δ9-THC) as the primary mediator of the psychoactive, hyperphagic and some of the potentially therapeutic properties of ingested cannabis. Whilst Δ9-THC is the most prevalent and widely studied pCB, it is also the predominant psychotropic component of cannabis, a property that likely limits its widespread therapeutic use as an isolated agent. In this regard, research focus has recently widened to include other pCBs including cannabidiol (CBD), cannabigerol (CBG), Δ9tetrahydrocannabivarin (Δ9-THCV) and cannabidivarin (CBDV), some of which show potential as therapeutic agents in preclinical models of CNS disease. Moreover, it is becoming evident that these non-Δ9-THC pCBs act at a wide range of pharmacological targets, not solely limited to CB receptors. Disorders that could be targeted include epilepsy, neurodegenerative diseases, affective disorders and the central modulation of feeding behaviour. Here, we review pCB effects in preclinical models of CNS disease and, where available, clinical trial data that support therapeutic effects. Such developments may soon yield the first non-Δ9-THC pCB-based medicines

Using Search Queries to Understand Health Information Needs in Africa

The lack of comprehensive, high-quality health data in developing nations creates a roadblock for combating the impacts of disease. One key challenge is understanding the health information needs of people in these nations. Without understanding people's everyday needs, concerns, and misconceptions, health organizations and policymakers lack the ability to effectively target education and programming efforts. In this paper, we propose a bottom-up approach that uses search data from individuals to uncover and gain insight into health information needs in Africa. We analyze Bing searches related to HIV/AIDS, malaria, and tuberculosis from all 54 African nations. For each disease, we automatically derive a set of common search themes or topics, revealing a wide-spread interest in various types of information, including disease symptoms, drugs, concerns about breastfeeding, as well as stigma, beliefs in natural cures, and other topics that may be hard to uncover through traditional surveys. We expose the different patterns that emerge in health information needs by demographic groups (age and sex) and country. We also uncover discrepancies in the quality of content returned by search engines to users by topic. Combined, our results suggest that search data can help illuminate health information needs in Africa and inform discussions on health policy and targeted education efforts both on- and offline.Comment: Extended version of an ICWSM 2019 pape

The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo

Maternal and zygotic activities of the homeodomain protein PAL-1 specify the identity and maintain the development of the multipotent C blastomere lineage in the C. elegans embryo. To identify PAL-1 regulatory target genes, we used microarrays to compare transcript abundance in wild-type embryos with mutant embryos lacking a C blastomere and to mutant embryos with extra C blastomeres. pal-1-dependent C-lineage expression was verified for select candidate target genes by reporter gene analysis, though many of the target genes are expressed in additional lineages as well. The set of validated target genes includes 12 transcription factors, an uncharacterized wingless ligand and five uncharacterized genes. Phenotypic analysis demonstrates that the identified PAL-1 target genes affect specification, differentiation and morphogenesis of C-lineage cells. In particular, we show that cell fate-specific genes (or tissue identity genes) and a posterior HOX gene are activated in lineage-specific fashion. Transcription of targets is initiated in four temporal phases, which together with their spatial expression patterns leads to a model of the regulatory network specified by PAL-1

Alpha1 -adrenergic stimulation selectively enhances endothelium-mediated vasodilation in rat cremaster arteries.

We have systematically investigated how vascular smooth muscle α1 -adrenoceptor activation impacts endothelium-mediated vasodilation in isolated, myogenically active, rat cremaster muscle 1A arteries. Cannulated cremaster arteries were pressurized intraluminally to 70 mmHg to induce myogenic tone, and exposed to vasoactive agents via bath superfusion at 34°C. Smooth muscle membrane potential was measured via sharp microelectrode recordings in pressurized, myogenic arteries. The α1 -adrenergic agonist phenylephrine (25-100 nmol/L) produced further constriction of myogenic arteries, but did not alter the vasorelaxant responses to acetylcholine (0.3 μmol/L), SKA-31 (an activator of endothelial Ca2+ -dependent K+ channels) (3 μmol/L) or sodium nitroprusside (10 μmol/L). Exposure to 0.25-1 μmol/L phenylephrine or 1 μmol/L norepinephrine generated more robust constrictions, and also enhanced the vasodilations evoked by acetylcholine and SKA-31, but not by sodium nitroprusside. In contrast, the thromboxane receptor agonist U46619 (250 nmol/L) dampened responses to all three vasodilators. Phenylephrine exposure depolarized myogenic arteries, and mimicking this effect with 4-aminopyridine (1 mmol/L) was sufficient to augment the SKA-31-evoked vasodilation. Inhibition of L-type Ca2+ channels by 1 μmol/L nifedipine decreased myogenic tone, phenylephrine-induced constriction and prevented α1 -adrenergic enhancement of endothelium-evoked vasodilation; these latter deficits were overcome by exposure to 3 and 10 μmol/L phenylephrine. Mechanistically, augmentation of ACh-evoked dilation by phenylephrine was dampened by eNOS inhibition and abolished by blockade of endothelial KCa channels. Collectively, these data suggest that increasing α1 -adrenoceptor activation beyond a threshold level augments endothelium-evoked vasodilation, likely by triggering transcellular signaling between smooth muscle and the endothelium. Physiologically, this negative feedback process may serve as a "brake" to limit the extent of vasoconstriction in the skeletal microcirculation evoked by the elevated sympathetic tone

Does evidence influence policy? Resource allocation and the Indigenous Burden of Disease study

Objective The Indigenous Burden of Disease (IBoD) report is the most comprehensive assessment of Indigenous disease burden in Australia. The aim of the present study was to investigate the potential effect of the IBoD report on Australian Indigenous health policy, service expenditure and research funding. Findings have significance for understanding factors that may influence Indigenous health policy. Methods The potential effect of the IBoD report was considered by: (1) conducting a text search of pertinent documents published by the federal government, Council of Australian Governments and the National Health and Medical Research Council of Australia (NHMRC) and observing the quantity and quality of references to IBoD; (2) examining data on government Indigenous healthcare expenditure for trends consistent with the findings and policy implications of the IBoD report; and (3) examining NHMRC Indigenous grant allocation trends consistent with the findings and policy implications of the IBoD report. Results Of 110 government and NHMRC documents found, IBoD was cited in 27. Immediately after publication of the IBoD report, federal and state governments increased Indigenous health spending (relative to non-Indigenous), notably for community health and public health at the state level. Expenditure on Indigenous hospital separations for chronic diseases also increased. These changes are broadly consistent with the findings of the IBoD report on the significance of chronic disease and the need to address certain risk factors. However, there is no evidence that such changes had a causal connection with the IBoD study. After publication of the IBoD report, changes in NHMRC Indigenous research funding showed little consistency with the findings of the IBoD report. Conclusions The present study found only indirect and inconsistent correlational evidence of the potential influence of the IBoD report on Indigenous health expenditure and research funding. Further assessment of the potential influence of the IBoD report on Indigenous health policy will require more targeted research, including interviews with key informants involved in developing health policy. What is known about the topic? There are currently no publications that consider the potential effed of the IBoD study on Indigenous health expenditure and research funding. What does this paper add? This paper offers the first consideration of the potential effect of the IBoD report. It contains analyses of data from readily available sources, examining national expenditures on Indigenous health and NHMRC Indigenous research, before and after the publication of the IBoD report. What are the implications for practitioners? The paper is relevant to analysts interested in drivers of Indigenous health policy. Although it finds correlations between the release of the IBoD report and some subsequent health spending decisions, other factors should be investigated to better understand the complexity of processes that drive government efforts to improve Indigenous health

Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RationaleAs part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).ObjectivesTo estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.MethodsWe created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.Measurements and main resultsIn the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to$48 billion. These had an incremental cost per QALY of $657,000 to$3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.ConclusionsSubstantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks

Survival After Endovascular Aneurysm Sealing Compared With Endovascular Aneurysm Repair

Introduction Endovascular aneurysm sealing (EVAS) is a sac-filling device with a blunted systemic inflammatory response compared to conventional endovascular aneurysm repair (EVAR), with a suggested impact on all-cause mortality. This study compares mortality after both EVAS and EVAR. Materials and Methods This is a retrospective observational study including data from 2 centres, with ethical approval. Elective procedures on asymptomatic infrarenal aneurysms performed between January 2011 until April 2018 were enrolled. Laboratory values (serum creatinine, haemoglobin, white blood cell count, platelet count) were measured pre- and postoperatively and at 1 and 2 years, respectively. Mortality and cause of death were recorded during follow-up. Results A total of 564 patients were included (225 EVAS, 369 EVAR), after propensity score matching there were 207 patients in both groups. Baseline characteristics were similar, except for larger neck angulation and more pulmonary disease in the EVAR group. The median follow-up time was 49 (EVAS) and 44 (EVAR) months. No significant differences regarding creatinine and haemoglobin were observed. Preoperative white blood cell count was higher in the EVAR group (p=0.011), without significant differences during follow-up. Median platelet count was lower in the EVAR group preoperatively (p=0.001), but was significantly higher at 1 year follow-up (p=0.003). There were 43 deaths within the EVAS group (20.8%) and 52 within the EVAR group (25.1%) (p=0.293). Of these, 4 were aneurysm related (EVAS n=3, EVAR n=1; p=0.222) and 14 cardiovascular (EVAS n=6, EVAR n=8, p=0.845). For the EVAS cohort, survival was 95.5% at 1 year and 74.9% at 5 years. For the EVAR cohort, this was 93.3% at 1 year and 75.5% at 5 years. No significant differences were observed in causes of death. Conclusion This study showed comparable survival rates through 5 years between EVAS and EVAR with a tendency toward higher inflammatory response in the EVAR patients through the first 2 years

Update on Electricity Customer Choice In Ohio: Competition Continues to Outperform Traditional Monopoly Regulation (Executive Summary)

Key Findings at a Glance: Deregulated Markets Save Ohio Electricity Consumers Billions Since 2011, deregulation has saved Ohio consumers $23.9 billion. The Study Team anticipates that savings will continue for the near term to be around$3 billion per year. However, these savings may be lost, in whole or in part, if deregulated energy markets continue to be undermined by cross subsidies. Competition Outperforms Monopoly Regulation Competition has driven down average electricity prices in deregulated Midwestern states while their regulated peers have seen a steady increase in price of generated electricity