Identification Of Environmental Variables For Use In Monitoring For The Evaluation Of The Rural Environment Protection Scheme

Teagasc wishes to acknowledge the support of the Environmental RTDI Programme 2000–2006 in financing this research project.End of project reportThe aim of this study was to identify and select quantitative environmental attributes for a monitoring programme that may be integrated into an environmental evaluation of Ireland’s agri-environmental scheme. This was achieved primarily by reviewing a range of agri-environmental indicators and suggesting indicators that would be appropriate for monitoring the REPS. The study conducted a desk review to collate information on current best practice in monitoring for environmental quality. A Project Group (comprising representatives from the Environmental Protection Agency [EPA], Department of Agriculture and Food [DAF], Teagasc, and the project supervisors) advised on the ongoing development of the project. There was a consultation process with national experts, and with a selection of stakeholder organisations with an interest in monitoring the environmental impact of the REPS.Environmental Protection Agenc

Tuberculosis, human rights, and law reform: Addressing the lack of progress in the global tuberculosis response

In 2018, the United Nations General Assembly convened the first-ever high-level meeting (HLM) on tuberculosis (TB). Since that time news on the world’s most lethal infectious disease is not good—the 2019 WHO TB report shows 1.2 million people died from TB, a number that has fallen just 11% since 2015, less than one-third of the way towards the End TB Strategy milestone of a 35% reduction (to about 850 million deaths) by 2020. The same number of people, 10.0 million, are estimated to have fallen ill with TB in 2018 as in 2017. The stubborn persistence of TB is attributable to glaring gaps in case detection and treatment. While case detection has increased in recent years, there is still a significant gap between the 7 million new cases reported and the 10 million incident cases estimated in the most recent WHO data—and treatment success continues to hover at only 85%. There has long been a call for a shift toward a “human rights-based approach” in TB—building policies and programs explicitly on the norms and values set out in international human rights law, treating people with TB as rights holders in their interaction with the state and the health system, and working to overcome stigma and discrimination. Yet laws in high TB-burden countries (HBCs) have not been reformed to include basic rights protections. This helps explain the lack of progress, as individuals who fear discrimination and coercion may avoid diagnosis and treatment. Thus, TB stands in stark contrast to HIV/AIDS, for which the international community has moved far more decisively to recognize and protect key rights, even as more progress is needed. At the UN, heads of state committed to removing discriminatory laws and policies against people with TB, protecting and promoting their human rights and dignity, as a key part of a strategy to improve the TB response and end the epidemic. Here, we analyze key areas of law with particular importance for TB, focusing on five aspects of compulsory public health powers in law and on laws related to migration. We identify significant gaps between core human rights norms and existing legal environments

New roles for the major human 3'-5' exonuclease TREX1 in human disease

Aicardi-Goutières syndrome (AGS), Systemic Lupus Erythematosus (SLE), Familial Chilblain Lupus (FCL) and Retinal Vasculopathy and Cerebral Leukodystrophy (RVCL) {a new term encompassing three independently described conditions with a common etiology—Cerebroretinal Vasculopathy (CRV), Hereditary Vascular Retinopathy (HVR) and Hereditary Endotheliopathy, Retinopathy and Nephropathy (HERNS)}—have previously been regarded as distinct entities. However, recent genetic analysis has demonstrated that each of these diseases maps to chromosome 3p21 and can be caused by mutations in TREX1, the major human 3'–5' exonuclease. In this review, we discuss the putative functions of TREX1 in relationship to the clinical, genetic and functional characteristics of each of these conditions

The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus

Gliotoxin, a redox-active metabolite, is produced by the opportunistic fungal pathogen Aspergillus fumigatus, and its biosynthesis is directed by the gli gene cluster. Knowledge of the biosynthetic pathway to gliotoxin, which contains a disulfide bridge of unknown origin, is limited, although L-Phe and L-Ser are known biosynthetic precursors. Deletion of gliG from the gli cluster, herein functionally confirmed as a glutathione S-transferase, results in abrogation of gliotoxin biosynthesis and accumulation of 6-benzyl-6-hydroxy-1-methoxy-3-methylenepiperazine- 2,5-dione. This putative shunt metabolite from the gliotoxin biosynthetic pathway contains an intriguing hydroxyl group at C-6, consistent with a gliotoxin biosynthetic pathway involving thiolation via addition of the glutathione thiol group to a reactive acyl imine intermediate. Complementation of gliG restored gliotoxin production and, unlike gliT, gliG was found not to be involved in fungal self-protection against gliotoxin

Mutations in Complement Regulatory Proteins Predispose to Preeclampsia: A Genetic Analysis of the PROMISSE Cohort

Jane Salmon and colleagues studied 250 pregnant patients with SLE and/or antiphospholipid antibodies and found an association of risk variants in complement regulatory proteins in patients who developed preeclampsia, as well as in preeclampsia patients lacking autoimmune disease

Dietary Cholesterol Promotes Adipocyte Hypertrophy and Adipose Tissue Inflammation in Visceral, But Not Subcutaneous, Fat in Monkeys

Objective—Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates. Approach and Results—Age-matched, male African Green monkeys (n=5 per group) were assigned to one of three diets containing 0.002 (Lo), 0.2 (Med) or 0.4 (Hi) mg cholesterol/Kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a step-wise manner in visceral, but not subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r2=0.298; n=15; p=0.035). In visceral fat, dietary cholesterol intake was associated with: 1) increased pro-inflammatory gene expression and macrophage recruitment, 2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and 3) increased expression of proteins involved in FC efflux. Conclusions—Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates

Determination of a suitable low-dose abdominopelvic CT protocol using model-based iterative reconstruction through cadaveric study.

Introduction: Cadaveric studies provide a means of safely assessing new technologies and optimizing scanning prior to clinical validation. Reducing radiation exposure in a clinical setting can entail incremental dose reductions to avoid missing important clinical findings. The use of cadavers allows assessment of the impact of more substantial dose reductions on image quality. Our aim was to identify a suitable low‐dose abdominopelvic CT protocol for subsequent clinical validation. Methods: Five human cadavers were scanned at one conventional dose and three low‐dose settings. All scans were reconstructed using three different reconstruction algorithms: filtered back projection (FBP), hybrid iterative reconstruction (60% FBP and 40% adaptive statistical iterative reconstruction (ASIR40)), and model‐based iterative reconstruction (MBIR). Two readers rated the image quality both quantitatively and qualitatively. Results: Model‐based iterative reconstruction images had significantly better objective image noise and higher qualitative scores compared with both FBP and ASIR40 images at all dose levels. The greatest absolute noise reduction, between MBIR and FBP, of 34.3 HU (equating to a 68% reduction) was at the lowest dose level. MBIR reduced image noise and improved image quality even in CT images acquired with a mean radiation dose reduction of 62% compared with conventional dose studies reconstructed with ASIR40, with lower levels of objective image noise, superior diagnostic acceptability and contrast resolution, and comparable subjective image noise and streak artefact scores. Conclusion: This cadaveric study demonstrates that MBIR reduces image noise and improves image quality in abdominopelvic CT images acquired with dose reductions of up to 62%

Review of the role of abdominal imaging in irritable bowel syndrome.

The role of radiologic imaging in the investigation of irritable bowel syndrome (IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on associated costs and radiation exposure, that imaging is being used relatively widely in these patients. This review aims to assess current best evidence to accurately define the role of radiologic imaging in IBS patients. Primary and secondary literature searches were performed. Evidence suggests that the lack of "red flag" or alarm features in IBS patients should reassure the clinician that the diagnosis of IBS is correct and United States and United Kingdom guidelines recommend no radiologic imaging for IBS patients if alarm features are not present. In patients presenting with IBS symptoms and alarm features, radiologic testing may be used to exclude an alternative diagnosis and the imaging modality should be chosen based on the most likely alternative diagnosis

Study of the 7Be(p,γ)8B^7Be(p,\gamma)^8B and 7Li(n,γ)8Li^7Li(n,\gamma)^8Li capture reactions using the shell model embedded in the continuum

We apply the realistic shell model which includes the coupling between many-particle (quasi-)bound states and the continuum of one-particle scattering states to the spectroscopy of mirror nuclei: $^8$B and $^8$Li, as well as to the description of low energy cross sections (the astrophysical S factors) in the capture reactions:$^7Be(p,\gamma)^8B$ and $^7Li(n,\gamma)^8Li$.Comment: 36 pages, 10 figure