bluuebunny/crossref_metadata_2025 huggingface dataset:
PatternMarkers & GWCoGAPS for novel data-driven biomarkers via whole transcriptome NMF
Authors: Stein-O’Brien Genevieve L , Carey Jacob L , Lee Wai Shing , Considine Michael , Favorov Alexander V , Flam Emily , Guo Theresa , Li Sijia , Marchionni Luigi , Sherman Thomas , Sivy Shawn , Gaykalova Daria A , McKay Ronald D , Ochs Michael F , Colantuoni Carlo , Fertig Elana J
Published: January 2017

Non-negative Matrix Factorization (NMF) algorithms associate gene expression with biological processes (e.g. time-course dynamics or disease subtypes). Compared with univariate associations, the relative weights of NMF solutions can obscure biomarkers. Therefore, we developed a novel patternMarkers statistic to extract genes for biological validation and enhanced visualization of NMF results. Finding novel and unbiased gene markers with patternMarkers requires whole-genome data. Therefore, we also developed Genome-Wide CoGAPS Analysis in Parallel Sets (GWCoGAPS), the first robust whole genome Bayesian NMF using the sparse, MCMC algorithm, CoGAPS. Additionally, a manual version of the GWCoGAPS algorithm contains analytic and visualization tools including patternMatcher, a Shiny web application. The decomposition in the manual pipeline can be replaced with any NMF algorithm, for further generalization of the software. Using these tools, we find granular brain-region and cell-type specific signatures with corresponding biomarkers in GTEx data, illustrating GWCoGAPS and patternMarkers ascertainment of data-driven biomarkers from whole-genome data.

Availability and Implementation

PatternMarkers & GWCoGAPS are in the CoGAPS Bioconductor package (3.5) under the GPL license.

Supplementary information

Supplementary data are available at Bioinformatics online.
qPCR-based characterization of DNA fragmentation efficiency of Tn5 transposomes
Authors: Rykalina Vera , Shadrin Alexey , Lehrach Hans , Borodina Tatiana
Published: January 2017

Here, we describe an electrophoresis free assay for characterizing Tn5 transposomes fragmentation efficiency in a tagmentation reaction, in which double-stranded DNA is fragmented and tagged with adapter sequences. The assay uses plasmid DNA as a reference tagmentation substrate. Fragmentation efficiency is analyzed by comparative qPCR which measures the difference (ΔCt) in amplification of a specific plasmid region before and after tagmentation: more efficient fragmentation is characterized by a larger number of cleavage events within the amplified region, a delayed increase in the amplification curve and as a result, a larger ΔCt. Tagmentation reactions characterized with the same ΔCt exhibit the same fragment size distribution on an agarose gel. The ΔCt values measured can be used to quantitatively determine the relative performance of Tn5 transposome assemblies in optimization experiments and to standardize between batch variations in transposomes for use in next-generation sequencing library preparation. Moreover, the use of a reference tagmentation template added during next-generation sequencing library preparation enabled monitoring of the input DNA fragmentation. The presented qPCR-based assay is quick, contamination-safe, high-throughput and cost-efficient.
Osteopontin RNA aptamer can prevent and reverse pressure overload-induced heart failure
Authors: Li Jihe , Yousefi Keyvan , Ding Wen , Singh Jayanti , Shehadeh Lina A.
Published: January 2017

Aims

Cardiac myocyte hypertrophy, the main compensatory response to chronic stress in the heart often progresses to a state of decompensation that can lead to heart failure. Osteopontin (OPN) is an effector for extracellular signalling that induces myocyte growth and fibrosis. Although increased OPN activity has been observed in stressed myocytes and fibroblasts, the detailed and long term effects of blocking OPN signalling on the heart remain poorly defined. Targeting cardiac OPN protein by an RNA aptamer may be beneficial for tuning down OPN pathologic signalling. We aimed to demonstrate the therapeutic effects of an OPN RNA aptamer on cardiac dysfunction.

Methods and results

In vivo, we show that in a mouse model of pressure overload, treating at the time of surgeries with an OPN aptamer prevented cardiomyocyte hypertrophy and cardiac fibrosis, blocked OPN downstream signalling (PI3K and Akt phosphorylation), reduced expression of extracellular matrix (Lum, Col3a1, Fn1) and hypertrophy (Nppa, Nppb) genes, and prevented cardiac dysfunction. Treating at two months post-surgeries with the OPN aptamer reversed cardiac dysfunction and fibrosis and myocyte hypertrophy. While genetic homozygous deletion of OPN reduced myocardial wall thickness, surprisingly cardiac function and myocardial fibrosis, specifically collagen deposition and myofibroblast infiltration, were worse compared with wild type mice at three months of pressure overload.

Conclusion

Taken together, these data demonstrate that tuning down cardiac OPN signalling by an OPN RNA aptamer is a novel and effective approach for preventing cardiac hypertrophy and fibrosis, improving cardiac function, and reversing pressure overload-induced heart failure.
Lipoprotein(a): the revenant
Authors: Gencer Baris , Kronenberg Florian , Stroes Erik S. , Mach François
Published: January 2017

In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a ‘side-effect’. Several drug developments did show a potent Lp(a)-lowering effect but did not make it to endpoint studies, mainly for safety reasons. Currently, three therapeutic approaches are either already in place or look highly promising: (i) lipid apheresis (specific or unspecific for Lp(a)) markedly decreases Lp(a) concentrations as well as cardiovascular endpoints; (ii) PCSK9 inhibitors which, besides lowering LDL cholesterol also decrease Lp(a) by roughly 30%; and (iii) antisense therapy targeting apolipoprotein(a) which has shown to specifically lower Lp(a) concentrations by up to 90% in phase 1 and 2 trials without influencing other lipids. Until the results of phase 3 outcome studies are available for antisense therapy, we will have to exercise patience, but with optimism since never before have we had the tools we have now to prove Koch’s extrapolated postulate that lowering high Lp(a) concentrations might be protective against cardiovascular disease.
Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease
Authors: Reddy Yogesh N. V. , Obokata Masaru , Dean Patrick G. , Melenovsky Vojtech , Nath Karl A. , Borlaug Barry A.
Published: January 2017

Aims

Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis.

Methods and results

A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7–9.2), P = 0.001].

Conclusion

In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF.
Outcome in middle-aged individuals with anomalous origin of the coronary artery from the opposite sinus: a matched cohort study
Authors: Gräni Christoph , Benz Dominik C. , Steffen Dominik A. , Clerc Olivier F. , Schmied Christian , Possner Mathias , Vontobel Jan , Mikulicic Fran , Gebhard Cathérine , Pazhenkottil Aju P. , Gaemperli Oliver , Hurwitz Shelley , Kaufmann Philipp A. , Buechel Ronny R.
Published: January 2017

Aims

Anomalous origin of a coronary artery from the opposite sinus (ACAOS) has been associated with adverse cardiac events in the young. It remains unknown whether this holds true for middle-aged patients with uncorrected ACAOS as well. We assessed the outcome in middle-aged patients with newly diagnosed ACAOS by coronary computed tomography angiography (CCTA) compared with a matched cohort.

Methods and results

We retrospectively identified 68 consecutive patients with ACAOS documented by CCTA. ACAOS with a course of the anomalous vessel between the aorta and pulmonary artery were classified as interarterial course (IAC). Each patient with ACAOS was matched to two controls without ACAOS. Major adverse cardiac events (i.e. myocardial infarction, revascularization and cardiac death) were recorded for all patients and controls. Two (3%) patients were lost to follow-up. Thus, 66 patients with ACAOS were included in the final analysis and matched with 132 controls. Mean age of patients was 56 ± 11 years, 73% were male and the mean follow-up was 49 months. Forty (65%) patients were classified as having ACAOS with IAC. The annual event rate of ACAOS vs. controls was 4.9 and 4.8%, the hazard ratio (HR) 0.94 (0.39–2.28, P = 0.89). The annual event rate of ACAOS with IAC compared with their matched controls was 5.2 and 4.3%, and the HR 1.01 (95% CI 0.39–2.58, P = 0.99).

Conclusions

In middle-aged individuals with newly diagnosed ACAOS mid-term outcome is not statistically different to a matched control cohort without coronary artery anomalies, regardless of whether ACAOS with or without IAC variants are present.
Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis
Authors: Quarta Candida Cristina , Gonzalez-Lopez Esther , Gilbertson Janet A. , Botcher Nichola , Rowczenio Dorota , Petrie Aviva , Rezk Tamer , Youngstein Taryn , Mahmood Shameem , Sachchithanantham Sajitha , Lachmann Helen J. , Fontana Marianna , Whelan Carol J. , Wechalekar Ashutosh D. , Hawkins Philip N. , Gillmore Julian D.
Published: January 2017

Aims

Congo red staining of an endomyocardial biopsy is the diagnostic gold-standard in suspected cardiac amyloidosis (CA), but the procedure is associated with the risk, albeit small, of serious complications, and delay in diagnosis due to the requirement for technical expertise. In contrast, abdominal fat pad fine needle aspiration (FPFNA) is a simple, safe and well-established procedure in systemic amyloidosis, but its diagnostic sensitivity in patients with suspected CA remains unclear.

Methods and results

We assessed the diagnostic sensitivity of FPFNA in 600 consecutive patients diagnosed with CA [216 AL amyloidosis, 113 hereditary transthyretin (ATTRm), and 271 wild-type transthyretin (ATTRwt) amyloidosis] at our Centre. Amyloid was detected on Congo red staining of FPFNAs in 181/216 (84%) patients with cardiac AL amyloidosis, including 100, 97, and 78% of those with a large, moderate, and small whole-body amyloid burden, respectively, as assessed by serum amyloid P (SAP) component scintigraphy (P < 0.001); the deposits were successfully typed as AL by immunohistochemistry in 102/216 (47%) cases. Amyloid was detected in FPFNAs of 51/113 (45%) patients with ATTRm CA, and only 42/271 (15%) cases with ATTRwt CA.

Conclusions

FPFNA has reasonable diagnostic sensitivity in cardiac AL amyloidosis, particularly in patients with a large whole-body amyloid burden. Although the diagnostic sensitivity of FPFNA is substantially lower in transthyretin CA, particularly ATTRwt, it may nevertheless sometimes obviate the need for endomyocardial biopsy.
Intensive forestry filters understory plant traits over time and space in boreal forests
Authors: Patry Cynthia , Kneeshaw Daniel , Aubin Isabelle , Messier Christian
Published: January 2017

Because of their scarcity, protected areas alone cannot maintain biodiversity. Therefore, it is necessary to create conditions appropriate for plants and wildlife in managed landscapes. We compared the effects of different intensities of forest management on functional responses of vascular understory plants using the fourth-corner method. We analysed functional community composition along a management gradient that spanned semi-natural forests to extensively managed forests (naturally regenerated cuts) to intensively managed forests (planted forests) in Canada. Results showed trait filtering along the gradient of forest management intensity. In natural and extensively managed forests, where forest retention was high in time and space, persistence traits (e.g. perennial geophytes or chamaephytes, non-leafy stem foliage structure) were maintained. At the opposite end of the gradient, in intensively managed plantations where forest retention elements (e.g. amount of dead wood) were reduced, trait filtering led to species associated with colonization, such as tall species with limited lateral extension. These results suggest that intensive forestry conducted over a large extent may change the functional composition of understory plants.
Turning Train Travel to Account: Locomotion, Femininity, and Diary-Writing in the
Journal
of Marie Bashkirtseff
Authors: Wilson Sonia
Published: January 2017

This essay draws on the enduring nature of Maurice Barrès’s canonization of Marie Bashkirtseff as ‘Notre-Dame du sleeping-car’ in 1890 as the basis for an investigation into the configuration of genre, gender, and train travel in Marie Bashkirtseff’s
Journal
. It argues that by following through the allusions to scandal that were deleted from the 1887 edition of the
Journal
, a link emerges between Bashkirtseff’s precarious social status and her constant geographical mobility. Bashkirtseff’s exclusion from those social sites that were constitutive of feminine gentility resulted in a pattern of train travel and diary-writing that unravelled both the logic of return underpinning the
journal de voyage
, and the protocols of femininity that propelled Bashkirtseff into diary-writing in the first place. It is argued that Bashkirtseff’s simultaneous locomotive travel and assiduous diarizing makes her diary not just a source of data on train travel, but rather the point of intersection of two nineteenth-century technologies: the
journal de jeune fille
as the means by which young girls in the late nineteenth century whiled away the long years before marriage, and locomotion, as a means of shifting the subject through the landscape, more directly and far faster than before. Bashkirtseff draws on each in order to ‘fill in’ the other — diarizing as a means of whiling away the time she spends in the train, and train travel as the stuff of her diary entries.
Presque un livre: l’édition photolithographiée des
Poésies
de Mallarmé
Authors: Valazza Nicolas
Published: January 2017

Parue en 1887, la première édition des
Poésies
date de l’époque où Mallarmé méditait une nouvelle conception du ‘Livre’ rompant avec les conventions du volume imprimé. Si l’aspect fragmentaire et inabouti de cet ouvrage le prive de sa qualité de livre, la rareté de l’édition, son grand format in-quarto et ses attributs plastiques (le frontispice de Félicien Rops et les autographes photolithographiés du poète) le désignent pourtant comme œuvre. En examinant cette édition à la lumière des écrits de Mallarmé sur ‘le Livre’ (correspondance, notes, ‘divagations’), cet article envisage les
Poésies
de 1887 comme une forme de médiation entre les contraintes de l’imprimé et certains principes théoriques que Mallarmé associe au projet du ‘Livre’: la mise en scène de l’écriture, l’exclusivité du lecteur, assimilé à un spectateur, la transformation de l’auteur en ‘opérateur’, etc. Aussi cette édition s’apparente-t-elle à un compromis entre l’idéal mallarméen du ‘Livre’, dont la réalisation se révèle de plus en plus impossible, et l’exigence de recueillir l’œuvre accomplie. En endossant le rôle d’artisan de son œuvre jusque dans la matérialité du volume, le poète en vient dès lors à redéfinir le livre de poésie ainsi que la poétique du livre à la fin du dix-neuvième siècle, tout en contribuant à la genèse du livre d’artiste.
Neighborhood Disadvantage and Biological Aging: Using Marginal Structural Models to Assess the Link Between Neighborhood Census Variables and Epigenetic Aging
Authors: Lei Man-Kit , Simons Ronald L , Beach Steven R H , Philibert Robert A
Published: January 2017

Objectives

Past research has reported an association between neighborhood disadvantage and healthy aging, but most of these studies utilize self-report measures of health or physical functioning and do not properly account for neighborhood selection effects, creating concerns regarding inflated associations. To overcome these limitations and provide a more stringent estimate of effects, the current study investigated the effect of neighborhood disadvantage on aging using newly developed epigenetic methods to assess rate of biological aging and marginal structural modeling (MSM) to account for potential confounds due to neighborhood selection.

Methods

We tested the hypothesis that neighborhood disadvantage accelerates aging using U.S. census data and five waves of interview data from a sample of 100 middle-aged African American women. Using a recently developed epigenetic index of aging, biological age was measured using weighted methylation values at 71 CpG sites. We calculated a measure of accelerated methylomic aging (in years) based upon the residual scores resulting from a regression of methylomic age on chronological age.

Results

Controlling for a variety of individual difference factors that could be confounded with neighborhood effects, including various health behaviors, neighborhood disadvantage was associated with accelerated biological aging. Using MSM to account for selection effects, a standard deviation increase in neighborhood disadvantage accelerated aging an average of 9 months.

Conclusions

Our findings converge with prior work to provide strong evidence that neighborhood context is a significant determinant of healthy aging.
Large and fine scale population structure in European hake (Merluccius merluccius) in the Northeast Atlantic
Authors: Westgaard Jon-Ivar , Staby Arved , Aanestad Godiksen Jane , Geffen Audrey J. , Svensson Anders , Charrier Gregory , Svedäng Henrik , André Carl
Published: January 2017

Recently, there have been reports of increased abundance and landings of European hake in the northern part of the species range. Biological studies are however scarce and information about finer scale population structure important for stock assessments and fishery management is largely lacking. Here, we report on a population genetic study using neutral and outlier SNP loci assessing population structure in hake in the north-eastern parts of its range in the Atlantic. Hake samples from localities along the west coast of Norway, the Kattegat, the northern North Sea, and one locality in the Bay of Biscay were analysed using 53 SNPs, six of which were outliers potentially influenced by natural selection. We detected small-scale structure among northern samples, all of which were also distinct from Bay of Biscay hake, with the exception of a few individuals from the North Sea and the coast of Norway who clustered genetically together with Bay of Biscay hake. Our findings suggest that the present management unit of a single northern stock of hake is not biologically correct, and that there is more detail in the fine-scale population structure indicating that independent population dynamics could be expected in response to fishing patterns or changing environmental conditions.
Experimental potting impacts on common UK reef habitats in areas of high and low fishing pressure
Authors: Stephenson Fabrice , Mill Aileen C. , Scott Catherine L. , Polunin Nicholas V. C. , Fitzsimmons Clare
Published: January 2017

Impacts of mobile fishing gears on habitat and benthos have been well-documented; in contrast, less studied physical impacts of static fishing gear on benthic habitats are still debated. Pot fishing, is a growing sector in the UK and evidence of any impacts is needed to inform management. This study simulated high intensity experimental pot fishing on the epibenthos of two common UK reef habitats in Northumberland, UK. Single tethered pots were fished in intensively and lightly fished areas over the course of 2 months. Within each area, three experimental sites and control sites were surveyed before and after fishing using photoquadrats (n =  240 per 290 m2 site) collected by scuba divers. PERMANOVA analysis indicated no evidence of epibenthic species abundances decreasing due to physical crushing or abrasion from potting on either intensively or lightly fished reefs. A shift in community composition over time was detected but was attributed to natural change as epibenthos in control sites shifted similarly. Experimental pot impacts far exceeded those of the local commercial pot fishery, providing relevant evidence for statutory governing bodies revisiting current fisheries management. Results are applicable across Western Europe due to the selection of habitats with abundant and commonly distributed benthic species.
Spatial growth variability in marine fish: example from Northeast Pacific groundfish
Authors: Gertseva Vladlena , Matson Sean E. , Cope Jason
Published: January 2017

Marine fish populations exist in a complex environment, with oceanographic and fisheries factors affecting their dynamics. It has been shown that life history characteristics of marine fish vary in space and time. We examined spatial variability in growth of eight groundfish species in the Northeast Pacific Ocean to identify shared spatial patterns and hypothesize about common mechanisms behind them. Growth parameters were estimated in different areas over the latitudinal range of the species, and several hypotheses were tested as to how these parameters vary along the US west coast. Clear differences in spatial growth variability emerged among the species examined. Shelf species exhibit the highest growth rate between Cape Blanco and Cape Mendocino, which may, in part, be attributed to area-specific upwelling patterns in the California Current ecosystem, when nutrient-rich deep water is brought to the surface south of Cape Blanco and is uniquely distributed throughout this area, providing favourable conditions for primary productivity. Slope species showed a cline in asymptotic size (L∞), with L∞ increasing from south to north. This cline, previously attributed to fishery removals, also fits a specific case of the widely described Bergmann’s rule, and we explore specific potential ecological mechanisms behind this relationship.
Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer’s disease
Authors: Liew Lee Chuen , Katsuda Takeshi , Gailhouste Luc , Nakagama Hitoshi , Ochiya Takahiro
Published: January 2017

One of the pathological hallmarks of Alzheimer’s disease (AD) is the presence of extracellular plaques resulting from the accumulation of beta-amyloid peptide (Aβ). To date, a definitive cure for this disease is still lacking as the currently approved drugs used are mainly symptomatic treatments. The revolutionary discovery of extracellular vesicles (EVs) has shed new light on the development of disease-modifying treatments for AD, owing to their potential in delivering the therapeutic agents to the brain. The feasibility of harnessing EVs for clinical applications is highly dependent on the donor cell, which determines the intrinsic properties of EVs. The merit of mesenchymal stem cells (MSCs) as therapeutic delivery vehicles, and the proven therapeutic effects of the EVs derived from these cells, make researchers esteem MSCs as ideal producers of EVs. Therefore, MSC-derived EVs (MSC-EVs) emerge to be an appealing therapeutic delivery approach for the treatment of AD. Here, we discuss perspectives on the therapeutic strategies using MSC-EVs to treat AD and the associated challenges in clinical application.
Systematic review of the effectiveness of health-related behavioral interventions using portable activity sensing devices (PASDs)
Authors: Abedtash Hamed , Holden Richard J
Published: January 2017

Background: Portable activity sensing devices (PASDs) have received significant interest as tools for objectively measuring activity-related parameters and promoting health-related outcomes. Studies of PASDs suggest the potential value of integrating them with behavioral interventions to improve intermediate and downstream clinical outcomes.

Objectives: This systematic review describes and evaluates evidence from controlled studies of interventions using PASDs on their effectiveness in health-related outcomes. Study quality was also assessed.

Methods: A systematic literature search was performed of MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, EMBASE, and CINAHL databases. We included English-language papers of controlled trials through 2015 reporting the effectiveness of PASDs in improving health-related outcomes in any population. We extracted and analyzed data on study characteristics including design, target population, interventions, and findings.

Results: Seventeen trials met the inclusion criteria from a total of 9553 unique records. Study objectives varied greatly, but most sought to increase physical activity. Studies with a “passive” intervention arm using a PASD with minimal behavioral support generally did not demonstrate effectiveness in improving health-related outcomes. Interventions integrating PASDs with multiple behavioral change techniques were more likely to be effective, particularly for intermediate outcomes such as physical activity and weight loss. Trials had small sample sizes but were generally free of bias, except for blinding and selection bias.

Conclusion: There is insufficient evidence to draw a conclusion about the general health-related benefits of PASD interventions. PASD interventions may improve intermediate outcomes when coupled with multiple behavioral change techniques. Devices alone or with minimal behavioral change support are insufficient to change health-related outcomes.
Implementing patient-reported outcome surveys as part of routine care: lessons from an academic radiation oncology department
Authors: Rotenstein Lisa S , Agarwal Ankit , O’Neil Kelly , Kelly Andrea , Keaty Maureen , Whitehouse Colleen , Kalinowski Barbara , Orio Peter F , Wagle Neil , Martin Neil E
Published: January 2017

Patient reported outcomes (PROs) are reports of health conditions that come directly from patients. Use of PROs has been associated with improved patient outcomes, enhanced quality of life, and reduced end-of-life spending. Yet there are still outstanding questions regarding the process of implementing PRO collection in routine practice. In this article, we describe the experience of selecting and implementing PROs in a multisite, multidisease academic medical center–based radiation oncology practice and demonstrate that such large-scale rollout is feasible. We establish that PROs can be implemented with minimal to no workflow delays, are generally seen as valuable by clinicians, and can enhance patient-doctor communication. We additionally detail the challenges involved in selecting clinically relevant PRO questionnaires and the centrality of physician buy-in, easy data access, and clear workflows to successful implementation.
The Effect of Nest Box Distribution on Sustainable Propagation of Osmia lignaria (Hymenoptera: Megachilidae) in Commercial Tart Cherry Orchards
Authors: Boyle N. K. , Pitts-Singer T. L.
Published: January 2017

The blue orchard bee, Osmia lignaria (Say), is a solitary bee that is an excellent pollinator of tree fruit orchards. Due to the annual rising costs of honey bee hive rentals, many orchardists are eager to develop management tools and practices to support O. lignaria as an alternative pollinator. Establishing O. lignaria pollination as a sustainable industry requires careful consideration of both bee and orchard management. Here, we test the effect of artificial nest box distribution on in-orchard propagation of O. lignaria in Utah commercial tart cherry orchards. Two nest box distributions were compared across three paired, 1.2-ha plots. One distribution, traditionally employed by O. lignaria consultants, included a centrally located tote for mass-nesting with smaller, surrounding ‘satellite’ nest boxes at orchard margins. The other distribution was composed of smaller, more equally distributed nest boxes throughout the 1.2-ha plots. Significantly higher propagation of O. lignaria was observed in the latter nest box distribution, although all treatments resulted in bee return exceeding the number of bees initially released. These findings provide support for the use of O. lignaria in tart cherry orchards, and demonstrate how simple changes to bee set-up and management can influence propagation efforts.
Being a Refugee University Student: A Collaborative Auto-ethnography
Authors: Student R , Kendall Kathleen , Day Lawrence
Published: January 2017

In this article, we adopt a collaborative auto-ethnographic approach to explore the experiences of one refugee university student. Our method involved all three authors systematically analysing narratives written by one of us: R Student. These accounts provide deep descriptions of his life while studying at three different United Kingdom universities and our analysis of them demonstrates that higher education was a double-edged sword for R Student. Our research illuminates how R Student’s past as a survivor of genocide and forced migration, his corrosive and supportive relationships, and neo-liberal policies and practices all intersected in complex ways to circumscribe his agency and inform his experience as a refugee student. This understanding runs counter to neo-liberal policies and practices within higher education which often blame individuals for the problems they encounter and obscure social and relational forces. In describing the operable effects of abstract policies and concepts upon R Student, our study provides a counter-narrative to neo-liberal discourse and identifies systemic issues that may affect other students, too.
Historic timeline of obstetric anaesthesia
Authors: McKenzie Alistair G.
Published: January 2017

Foremost in the history of obstetric anaesthesia was the introduction of inhalational analgesia by James Simpson in 1847, first with ether and then chloroform. Nitrous oxide was first used in obstetrics in 1880. Neuraxial anaesthesia in obstetrics began with spinal block by Oskar Kreis in 1900, and within 25 years included pudendal, caudal, and paracervical blocks. From 1902 there was a vogue for ‘twilight sleep’, which remained in use until the 1950s. Spinal anaesthesia only became popular with the advent of procaine in 1905; favour declined in the United Kingdom from 1948 and did not return until 40 years later. In 1930, Aburel described the pain pathways of labour. Continuous caudal analgesia for labour was popularized from 1942; it was superseded by the lumbar epidural approach in the 1960s. The arrival of lidocaine in 1950 was a major advance. Another important event in the 1960s was the elucidation of the supine hypotensive syndrome of late pregnancy. In the 1940s, intravenous barbiturates became popular. Mendelson published on the acid aspiration syndrome in 1946. It took 40 years to establish a reliable system of prevention, including fasting, antacids, and rapid sequence induction. This developed piecemeal, aided by recommendations from the British Confidential Enquiries into Maternal Deaths reports beginning in 1957. Neuraxial anaesthesia advanced: 24-hour epidural services (1960s), bupivacaine (1970s), epidural opioids (1980s), use of low-concentration bupivacaine with fentanyl mixtures, patient-controlled epidural and combined spinal–epidural analgesia (1990s), and pencil-point spinal needles (1990s). From the 1980s obstetric anaesthetists have assumed key roles in management of labour, preeclampsia/eclampsia, major haemorrhage, and perioperative care.
Physiological changes associated with pregnancy
Authors: Toledano Roulhac D.
Published: January 2017

Pregnant patients pose several challenges to anaesthetists and other healthcare providers. Significant systemic and organ-specific changes accompany each stage of pregnancy, culminating during labour and delivery and in the early postpartum period. While healthy parturients tolerate these physiological adaptations to pregnancy well, patients with coexisting disease or pregnancy-related medical conditions may experience acute decompensation, with potential long-term sequelae. Alternatively, symptoms of a disease state may be obscured by pregnancy or mistaken for physiological changes of pregnancy. Anaesthetic management of pregnant patients is further complicated by concerns regarding difficulty with airway management, aspiration of gastric contents, haemodynamic effects of aortocaval compression, maternal obesity, and the effects of volatile agents on uterine tone; reference ranges for laboratory results that differ from those of the non-pregnant population; fears of fetal exposure to antibiotics, analgesics, and anaesthetics; and concerns that more than one patient must be taken into consideration. This chapter reviews the systemic and organ-specific physiological changes that occur during different stages of pregnancy, with a focus on how these adaptations to pregnancy affect anaesthetic management. Familiarity with updated, evidence-based practices and a firm understanding of the physiological changes of pregnancy are essential components of the anaesthetic management of obstetric patients at any gestational age.
Anaesthesia for non-obstetric surgery
Authors: Dahl Vegard , Spreng Ulrich J.
Published: January 2017

Anaesthesia for non-obstetric reasons is performed in 1–2% of all pregnant women. Although the chances of complications like miscarriage, preterm labour, and abortion are higher when surgery is performed during gestation, careful evaluation, preparation, and a multidisciplinary approach will minimize these risks. There are no methods of anaesthesia that are preferable to others during pregnancy. The most important preventive measure is to maintain maternal haemodynamic stability and normoventilation in order to ensure fetal well-being. Extensive knowledge of the profound anatomical and physiological changes that a pregnancy induces is mandatory for the team when operating on a pregnant woman. Short time exposure to anaesthetic agents in clinically relevant doses during surgery has never been demonstrated to have teratogenic effects. Lately, focus has been made on the possible behavioural teratogenic properties of anaesthesia, especially on the use of NMDA receptor antagonists and GABA receptor agonists. Emergency diagnostic imaging during pregnancy is considered safe and should be performed if necessary. Electroconvulsive therapy for the treatment of serious psychiatric disorders during pregnancy is a possibility that should be considered if necessary. Electric cardioversion seems safe for the fetus if life-threatening arrhythmias occur during pregnancy. Trauma is one of the leading non-obstetric causes of maternal mortality and morbidity. When treating a traumatized pregnant woman one should initially focus on the mother’s safety and haemodynamic stability.
Drugs in pregnancy and lactation
Authors: Kraemer Oliver , Fraisse Timothée
Published: January 2017

Medical or surgical interventions, requiring anaesthesia and/or analgesia, are frequent during various stages of pregnancy and lactation when the mother, the embryo/fetus, and the breastfeeding infant are vulnerable. Many physiological alterations occur during pregnancy, which might result in modified pharmacokinetic/pharmacodynamic drug profiles. These are often challenging situations for the treating physician who has to rely on scarce clinical or epidemiological data to support their prescriptions. This chapter reviews the underlying principles of pharmacology and related toxicity during pregnancy and lactation. It outlines current recommendations for most commonly used drugs in anaesthesia (i.e. local anaesthetics, hypnotics, opioids, and muscle relaxants) and pain relief (i.e. analgesics and anti-inflammatory drugs). It should not be considered as an exhaustive description of the potential side effects nor should it be used as a prescription guide for specific clinical situations. When administering drugs to pregnant or lactating women, one should always refer to up-to-date best standard of care and review references, which should be clearly documented in the patient’s medical record, especially with respect to newly marketed compounds.
Neuraxial anaesthesia for caesarean delivery
Authors: Armstrong Sarah L. , Walters Michelle , Cheesman Katherine , O’Sullivan Geraldine
Published: January 2017

Neuraxial anaesthesia is the safest and preferred method of anaesthesia for both elective and emergency caesarean delivery. It has significant advantages over general anaesthesia including the avoidance of failed intubation and ventilation, awareness, and aspiration of pulmonary contents. It also allows the partner to be present at delivery and facilitates maternal–newborn bonding. This chapter examines the indications and contraindications to neuraxial blockade for caesarean delivery and discusses preoperative assessment and consent for these patients. Neuraxial techniques for caesarean delivery include single-shot spinal, combined spinal–epidural, epidural anaesthesia, and continuous spinal anaesthesia. These techniques are described and critically evaluated. The choice of local anaesthetic drugs and adjuvants is also discussed along with a troubleshooting section for dealing with unexpected complications of neuraxial blockade for caesarean delivery.
Postoperative analgesia after caesarean delivery
Authors: Armstrong Sarah L. , Stocks Gary M.
Published: January 2017

Caesarean delivery (CD) is one of the most common operations in the world and providing effective pain relief is important not only for humanitarian reasons but also to speed up recovery and reduce postoperative complications. An understanding of the anatomy and physiology of pain transmission after CD has led to a multimodal approach to analgesia. This involves combining analgesics which work by different mechanisms resulting in an additive effect whilst at the same time reducing side effects. In contemporary practice, most CDs are carried out under neuraxial anaesthesia and neuraxial techniques using either intrathecal or epidural opioids have become central to the provision of effective postoperative analgesia. They reduce the need for systemic opioid analgesia and have few side effects, respiratory depression being the most significant but extremely uncommon. In circumstances where it is not possible to use neuraxial analgesia, for example, after general anaesthesia, other techniques such as intravenous patient-controlled analgesia using opioids and the transversus abdominis plane block have been shown to be effective. As part of the multimodal analgesic approach, many patients will require systemic analgesics to further improve pain relief and to limit side effects. Paracetamol and non-steroidal anti-inflammatory drugs are now widely established in the management of postoperative CD pain where they have been shown to potentiate opioid effects, decrease opioid consumption, reduce side effects, and complement the somatic pain relief provided by opioids. As part of a step-down approach after primary management with neuraxial or intravenous opioids, oral opioids are often required as part of a multimodal regimen.
Postdural puncture headache
Authors: Paech Michael J. , Nivatpumin Patchareya
Published: January 2017

Postdural puncture headache (PDPH) may follow either deliberate or unintentional (accidental) penetration of the interdigitating meninges, the dura and arachnoid mater. It is one of the most common and clinically important complications of regional anaesthesia and analgesia in the obstetric population. The headache develops as a consequence of cerebrospinal fluid loss, low intracranial pressure and cerebrovascular changes in the upright position and can prove debilitating. The diagnosis is clinical, making thorough assessment and regular review all the more important, to revise treatment plans, exclude rare serious pathology such as subdural haematoma, and avoid misdiagnosis. This chapter reviews the pathophysiology, incidence, risk factors (needle, technical and patient related), features, natural history, diagnosis, and management of PDPH. High level evidence supports prevention by using small gauge, non-cutting spinal needles, but other preventative strategies against either unintentional dural puncture or PDPH are poorly supported. The absent or poor efficacy of measures such as bed rest, hydration, cerebral vasoconstrictor therapy, epidural or intrathecal saline injection, intrathecal catheter placement or prophylactic epidural blood patch, is noted. Validation of better evidence supporting epidural morphine or intravenous cosyntropin is required. Symptomatic treatment of PDPH is also unreliable. Very limited evidence that requires substantiation supports a modest benefit from caffeine, gabapentinoids or intravenous hydrocortisone. The intervention of epidural blood patch is highly likely to relieve post-spinal PDPH, but only completely resolves epidural needle-induced PDPH in 30–50% of cases. Much detail about EBP remains undetermined, but delayed intervention and injection of approximately 20 mL of autologous blood appear appropriate.
Sepsis in obstetrics
Authors: Lucas Nuala , Acosta Colleen D. , Knight Marian
Published: January 2017

Sepsis in pregnancy and the puerperium remains a significant cause of maternal mortality and morbidity worldwide. Major morbidity arising as a result of obstetric sepsis includes fetal demise, organ failure, chronic pelvic inflammatory disease, chronic pelvic pain, bilateral tubal occlusion, and infertility. Sepsis may arise at any time during pregnancy and the puerperium. Prior to the advent of routine prophylactic antibiotics for caesarean delivery, endometritis used to be a major cause of postpartum infection. Diagnosis can be difficult as the physiological changes of pregnancy can overlap significantly with the pathophysiology of sepsis. The clinician must often rely on a high index of clinical suspicion rather than objective criteria. Women at risk of infection should be identified early in pregnancy. Management of the septic pregnant patient must encompass resuscitation, identification, and treatment of the source of sepsis and management of complications such as hypotension and tissue hypoxia. The Royal College of Obstetricians and Gynaecologists recommend that sepsis should be managed in accordance with the Surviving Sepsis Campaign guidelines. Anaesthetists have broad experience in all the elements required to care for a sick parturient and obstetric anaesthetists are key members of the team required to successfully manage these women.
Amniotic fluid embolism (anaphylactoid syndrome of pregnancy)
Authors: Anderson John A. , Laloë Pierre-Antoine , Tuffnell Derek J.
Published: January 2017

Amniotic fluid embolus (AFE) is a rare occurrence but consistently remains one of the leading causes of maternal death in the developed world each year. Incidence in the United Kingdom is approximately 1 in 50,000 maternities and this seems to have stayed roughly stable. Quoted survival rates are improving, which may be a reflection of improved understanding and better care. This chapter aims to give an epidemiological background, outline the principles which are believed to underpin the pathophysiological changes which occur in episodes of AFE, and give readers a guide to treatment immediately following a maternal collapse due to AFE and ongoing supportive care thereafter.
Moderate to complex congenital heart disease
Authors: Dob Daryl P. , Pickering Elspeth E. , Gatzoulis Michael A.
Published: January 2017

Children born with congenital heart disease no longer face the prospect of early death and a poor quality of life. In fact, most neonates with moderate to complex congenital heart disease have a survival rate to adulthood of over 80%. The ratio of adults to children with congenital heart disease is increasing, due to better surgical repairs, and longer survival with a better quality of life. In the Western world, there are more adults than children alive with congenital heart disease. This remarkable medical effort has allowed young women with congenital heart disease to mature to an age where they wish to have babies of their own. Early generations of women, palliated with Mustard or Senning repairs, have shown it is possible to face the cardiovascular challenges of pregnancy and survive. As the number of women with congenital heart disease is predicted to grow by 25% in the next decade and more women with congenital heart disease become pregnant; a better understanding of moderate to complex heart disease, different surgical repair procedures, and residual anomalies is paramount. This chapter examines the management of parturients with transposition complexes (both classical and congenitally corrected), tetralogy of Fallot, the Fontan circulation, Eisenmenger’s syndrome, and congenital aortic stenosis, taking into consideration the effect of pregnancy, labour, delivery, and anaesthesia on each circulation.
Respiratory disease
Authors: Teoh Wendy H. L.
Published: January 2017

Cystic fibrosis and asthma are the two common and challenging respiratory diseases encountered on the delivery suite and these are described in detail in this chapter. Seasonal and pandemic viral influenzas and acute pneumonias are not uncommon either However, there are several other respiratory conditions which arise as part of other diseases, for example, cardiac or neuromuscular disorders and they are dealt with in the relevant chapters. A multidisciplinary approach to the care of women with respiratory disease, including that of the intensive care, is essential for good outcome and anaesthetists are often called upon to lead in this care.