COPD: Optimizing Treatment

A guideline update and an expanded armamentarium have many physicians wondering how best to treat patients with COPD. Chronic obstructive pulmonary disease (COPD) carries a high disease burden. In 2012, it was the 4th leading cause of death worldwide.1,2 In 2015, the World Health Organization updated its Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, classifying patients with COPD based on disease burden as determined by symptoms, airflow obstruction, and exacerbation history.3 These revisions, coupled with expanded therapeutic options within established classes of medications and new combination drugs to treat COPD (TABLE 1),3-6 have led to questions about interclass differences and the best treatment regimen for particular patients

Morphogenesis along the animal-vegetal axis: fates of primary quartet micromere daughters in the gastropod Crepidula fornicata.

BackgroundThe Spiralia are a large, morphologically diverse group of protostomes (e.g. molluscs, annelids, nemerteans) that share a homologous mode of early development called spiral cleavage. One of the most highly-conserved features of spiralian development is the contribution of the primary quartet cells, 1a-1d, to the anterior region of the embryo (including the brain, eyes, and the anterior ciliary band, called the prototroch). Yet, very few studies have analyzed the ultimate fates of primary quartet sub-lineages, or examined the morphogenetic events that take place in the anterior region of the embryo.ResultsThis study focuses on the caenogastropod slipper snail, Crepidula fornicata, a model for molluscan developmental biology. Through direct lineage tracing of primary quartet daughter cells, and examination of these cells during gastrulation and organogenesis stages, we uncovered behaviors never described before in a spiralian. For the first time, we show that the 1a2-1d2 cells do not contribute to the prototroch (as they do in other species) and are ultimately lost before hatching. During gastrulation and anterior-posterior axial elongation stages, these cells cleavage-arrest and spread dramatically, contributing to a thin provisional epidermis on the dorsal side of the embryo. This spreading is coupled with the displacement of the animal pole, and other pretrochal cells, closer to the ventrally-positioned mouth, and the vegetal pole.ConclusionsThis is the first study to document the behavior and fate of primary quartet sub-lineages among molluscs. We speculate that the function of 1a2-1d2 cells (in addition to two cells derived from 1d12, and the 2b lineage) is to serve as a provisional epithelium that allows for anterior displacement of the other progeny of the primary quartet towards the anterior-ventral side of the embryo. These data support a new and novel mechanism for axial bending, distinct from canonical models in which axial bending is suggested to be driven primarily by differential proliferation of posterior dorsal cells. These data suggest also that examining sub-lineages in other spiralians will reveal greater variation than previously assumed

Editorial Board, About this Issue, Table of Contents

Editorial Board, About this Issue, Table of Content

Genome-wide association study for calving performance using high-density genotypes in dairy and beef cattle

peer-reviewedBackground Calving difficulty and perinatal mortality are prevalent in modern-day cattle production systems. It is well-established that there is a genetic component to both traits, yet little is known about their underlying genomic architecture, particularly in beef breeds. Therefore, we performed a genome-wide association study using high-density genotypes to elucidate the genomic architecture of these traits and to identify regions of the bovine genome associated with them. Results Genomic regions associated with calving difficulty (direct and maternal) and perinatal mortality were detected using two statistical approaches: (1) single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian approach. Data included high-density genotypes on 770 Holstein-Friesian, 927 Charolais and 963 Limousin bulls. Several novel or previously identified genomic regions were detected but associations differed by breed. For example, two genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13 % of the genetic variance in direct calving difficulty in the Holstein-Friesian and Charolais populations, respectively. Imputed Holstein-Friesian sequence data was used to refine the genomic regions responsible for significant associations. Several candidate genes on chromosome 18 were identified and four highly significant missense variants were detected within three of these genes (SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense variant with a putative impact on direct calving difficulty based on SIFT (0.06) and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic region on chromosome 4 associated with maternal calving difficulty in the Holstein-Friesian population and found the strongest association with an intronic variant in the PCLO gene. A meta-analysis was performed across the three breeds for each calving performance trait to identify common variants associated with these traits in the three breeds. Our results suggest that a portion of the genetic variation in calving performance is common to all three breeds. Conclusion The genomic architecture of calving performance is complex and mainly influenced by many polymorphisms of small effect. We identified several associations of moderate effect size but the majority were breed-specific, indicating that breed-specific alleles exist for calving performance or that the linkage phase between genotyped allele and causal mutation varies between breeds

What Individual and Organizational Competencies Facilitate Effective Collaboration? Findings from a Collaborative Governance Simulation

This study seeks to elicit insights on the individual and organizational competencies associated with effective collaboration. Specifically, the authors gathered grounded insights on collaborative competencies from undergraduate students enrolled in an introductory public affairs course at a research-intensive, Midwestern university -- following student participation in an interactive and replicable simulation designed according to Ansell and Gash’s (2008) “collaborative governance” framework. Results indicate that respondents associated being open-minded, strategic, respectful, an effective communicator, and patient with individual competencies; whereas compromise, teamwork, and trustworthiness were identified as organizational characteristics. Findings also highlight the educational value of simulations and related experiential- and active-learning techniques in elevating the knowledge, skills, abilities, and confidence of students in relation to practices integral to public service delivery, such as collaboration

Sensory properties of menthol and smoking topography

Although there is a great deal known about menthol as a flavoring agent in foods and confections, less is known about the particular sensory properties of menthol cigarette smoke. Similarly, although smoking topography (the unique way an individual smokes a cigarette) has been well studied using non-menthol cigarettes, there is relatively less known about how menthol affects smoking behavior. The objective of this review is to assess the sensory properties of menthol tobacco smoke, and smoking topography associated with menthol cigarettes. The cooling, analgesic, taste, and respiratory effects of menthol are well established, and studies have indicated that menthol’s sensory attributes can have an influence on the positive, or rewarding, properties associated smoking, including ratings of satisfaction, taste, perceived smoothness, and perceived irritation. Despite these sensory properties, the data regarding menthol’s effect on smoking topography are inconsistent. Many of the topography studies have limitations due to various methodological issues

Mobilisation or dilution? Nitrate response of karst springs to high rainfall events

peer-reviewedNitrate (NO3−) contamination of groundwater associated with agronomic activity is of major concern in many countries. Where agriculture, thin free draining soils and karst aquifers coincide, groundwater is highly vulnerable to nitrate contamination. As residence times and denitrification potential in such systems are typically low, nitrate can discharge to surface waters unabated. However, such systems also react quickest to agricultural management changes that aim to improve water quality. In response to storm events, nitrate concentrations can alter significantly, i.e. rapidly decreasing or increasing concentrations. The current study examines the response of a specific karst spring situated on a grassland farm in South Ireland to rainfall events utilising high-resolution nitrate and discharge data together with on-farm borehole groundwater fluctuation data. Specifically, the objectives of the study are to formulate a scientific hypothesis of possible scenarios relating to nitrate responses during storm events, and to verify this hypothesis using additional case studies from the literature. This elucidates the controlling key factors that lead to mobilisation and/or dilution of nitrate concentrations during storm events. These were land use, hydrological condition and karstification, which in combination can lead to differential responses of mobilised and/or diluted nitrate concentrations. Furthermore, the results indicate that nitrate response in karst is strongly dependent on nutrient source, whether mobilisation and/or dilution occur and on the pathway taken. This will have consequences for the delivery of nitrate to a surface water receptor. The current study improves our understanding of nitrate responses in karst systems and therefore can guide environmental modellers, policy makers and drinking water managers with respect to the regulations of the European Union (EU) Water Framework Directive (WFD). In future, more research should focus on the high-resolution monitoring of karst aquifers to capture the high variability of hydrochemical processes, which occur at time intervals of hours to days.Teagasc Walsh Fellowship Programm

The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds

peer-reviewedDomestication and the subsequent selection of animals for either economic or morphological features can leave a variety of imprints on the genome of a population. Genomic regions subjected to high selective pressures often show reduced genetic diversity and frequent runs of homozygosity (ROH). Therefore, the objective of the present study was to use 42,182 autosomal SNPs to identify genomic regions in 3,191 sheep from six commercial breeds subjected to selection pressure and to quantify the genetic diversity within each breed using ROH. In addition, the historical effective population size of each breed was also estimated and, in conjunction with ROH, was used to elucidate the demographic history of the six breeds. ROH were common in the autosomes of animals in the present study, but the observed breed differences in patterns of ROH length and burden suggested differences in breed effective population size and recent management. ROH provided a sufficient predictor of the pedigree inbreeding coefficient, with an estimated correlation between both measures of 0.62. Genomic regions under putative selection were identified using two complementary algorithms; the fixation index and hapFLK. The identified regions under putative selection included candidate genes associated with skin pigmentation, body size and muscle formation; such characteristics are often sought after in modern-day breeding programs. These regions of selection frequently overlapped with high ROH regions both within and across breeds. Multiple yet uncharacterised genes also resided within putative regions of selection. This further substantiates the need for a more comprehensive annotation of the sheep genome as these uncharacterised genes may contribute to traits of interest in the animal sciences. Despite this, the regions identified as under putative selection in the current study provide an insight into the mechanisms leading to breed differentiation and genetic variation in meat production.This work was supported by MultiGS Research Stimulus Fund (11/S/112) and OviGen project (14/S/849) which are funded by the Department of Agriculture, Food and Marine, Ireland