bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a neurophysiological signature for fibromyalgia
Authors: López-Solà Marina , Woo Choong-Wan , Pujol Jesus , Deus Joan , Harrison Ben J. , Monfort Jordi , Wager Tor D.
Published: September 2016

Patients with fibromyalgia (FM) show characteristically enhanced unpleasantness to painful and nonpainful sensations accompanied by altered neural responses. The diagnostic potential of such neural alterations, including their sensitivity and specificity to FM (vs healthy controls) is unknown. We identify a brain signature that characterizes FM central pathophysiology at the neural systems level. We included 37 patients with FM and 35 matched healthy controls, and analyzed functional magnetic resonance imaging responses to (1) painful pressure and (2) nonpainful multisensory (visual–auditory–tactile) stimulation. We used machine-learning techniques to identify a brain-based FM signature. When exposed to the same painful stimuli, patients with FM showed greater neurologic pain signature (NPS; Wager et al., 2013. An fMRI-based neurologic signature of physical pain. N Engl J Med 2013;368:1388–97) responses. In addition, a new pain-related classifier (“FM-pain”) revealed augmented responses in sensory integration (insula/operculum) and self-referential (eg, medial prefrontal) regions in FM and reduced responses in the lateral frontal cortex. A “multisensory” classifier trained on nonpainful sensory stimulation revealed augmented responses in the insula/operculum, posterior cingulate, and medial prefrontal regions and reduced responses in the primary/secondary sensory cortices, basal ganglia, and cerebellum. Combined activity in the NPS, FM pain, and multisensory patterns classified patients vs controls with 92% sensitivity and 94% specificity in out-of-sample individuals. Enhanced NPS responses partly mediated mechanical hypersensitivity and correlated with depression and disability (P
uncorrected < 0.05); FM-pain and multisensory responses correlated with clinical pain (P
uncorrected < 0.05). The study provides initial characterization of individual patients with FM based on pathophysiological, symptom-related brain features. If replicated, these brain features may constitute objective neural targets for therapeutic interventions. The results establish a framework for assessing therapeutic mechanisms and predicting treatment response at the individual level.
High GC Content Causes De Novo Created Proteins to be Intrinsically Disordered
Authors: Basile Walter , Sachenkova Oxana , Light Sara , Elofsson Arne
Published: September 2016

De novocreation of protein coding genes involves formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population.De novocreated proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not cause aggregation. Therefore, although the creation of the short ORFs could be truly random, but the fixation should be of subject to some selective pressure. The selective forces acting onde novocreated proteins have been elusive and contradictory results have been reported. InDrosophilathey are more disordered, i.e. are enriched in polar residues, than ancient proteins, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed.

To solve this riddle we studied structural properties and age of all proteins in 187 eukaryotic species. We find that, on average, there are small differences between proteins of different ages, with the exception that younger proteins are shorter. However, when we take the GC content into account we find that this can explain the opposite trends observed in yeast (low GC) and drosophila (high GC). GC content is correlated with codons coding for disorder-promoting amino acids, and inversely correlated with transmembrane, helix and sheet promoting residues. We find that for the youngest proteins, i.e. the ones that are most likely to bede novocreated, there exists a strong correlation with GC and structural properties. In contrast, this strong relationship is not seen for ancient proteins. This leads us to propose that structural features are not a strong determining factor for fixation ofde novocreated genes. Instead these proteins resemble random proteins given a particular GC level. The dependency on GC content is then gradually weakened during evolution.

Author Summary

We show that the GC content of a genomic area is of great importance for the properties of a protein-codingde novocreated gene. The GC content affects the frequency of the codons and this affects the probability for each amino acid to be included in ade novocreated protein. The codons encoding for Ala, Pro and Glu contain 80% GC, while codons for Lys, Phe, Asn, Tyr and Ile contain 20% or less. Pro and Gly are disorder-promoting, while Phe, Tyr and Ile are order-promoting. Therefore random protein sequences at a high GC will be more disordered than the ones created at a low GC. The structural properties of the youngest (orphan) proteins match to a large degree the properties of random proteins when the GC content is taken into account. In contrast structural properties of ancient proteins only show a weak correlation with GC content. This suggests that even after fixation ofde novocreated proteins largely resemble random proteins given a certain GC content. Thereafter, during evolution the correlation between structural properties and GC weakens.
Paperfuge: An ultra-low cost, hand-powered centrifuge inspired by the mechanics of a whirligig toy
Authors: Bhamla M. Saad , Benson Brandon , Chai Chew , Katsikis Georgios , Johri Aanchal , Prakash Manu
Published: September 2016

Sample preparation, including separation of plasma from whole blood or isolation of parasites, is an unmet challenge in many point of care (POC) diagnostics and requires centrifugation as the first key step. From the context of global health applications, commercial centrifuges are expensive, bulky and electricity-powered, leading to a critical bottle-neck in the development of decentralized, electricity-free POC diagnostic devices. By uncovering the fundamental mechanics of an ancient whirligig toy (3300 B.C.E), we design an ultra-low cost (20 cents), light-weight (2 g), human-powered centrifuge that is made out of paper (“paperfuge”). To push the operating limits of this unconventional centrifuge, we present an experimentally-validated theoretical model that describes the paperfuge as a non-linear, non-conservative oscillator system. We use this model to inform our design process, achieving speeds of 125,000 rpm and equivalent centrifugal forces of 30,000 g, with theoretical limits predicting one million rpm. We harness these speeds to separate pure plasma in less than 1.5 minutes and isolate malaria parasites in 15 minutes from whole human blood. By expanding the materials used, we implement centrifugal microfluidics using PDMS, plastic and 3D-printed devices, ultimately opening up new opportunities for electricity-free POC diagnostics, especially in resource-poor settings.
Biophysical models of protein evolution: Understanding the patterns of evolutionary sequence divergence
Authors: Echave Julian , Wilke Claus O.
Published: September 2016

For decades, rates of protein evolution have been interpreted in terms of the vague concept of “functional importance”. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic mis-folding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in proteins are not directly involved in function, but mutating them has large impacts on protein structure and stability. Here, we review the studies of the emergent field of biophysical protein evolution that have shaped our current understanding of sequence divergence patterns. We also propose future research directions to develop this nascent field.
Detecting High-Order Epistasis in Nonlinear Genotype-Phenotype Maps
Authors: Sailer Zachary R , Harms Michael J
Published: September 2016

High-order epistasis has been observed in many genotype-phenotype maps. These multi-way interactions between mutations may be useful for dissecting complex traits and could have profound implications for evolution. Alternatively, they could be a statistical artifact. High-order epistasis models assume the effects of mutations should add, when they could in fact multiply or combine in some other nonlinear way. A mismatch in the "scale" of the epistasis model and the scale of the underlying map would lead to spurious epistasis. In this paper, we develop an approach to estimate the nonlinear scales of arbitrary genotype-phenotype maps. We can then linearize these maps and extract high-order epistasis. We investigated seven experimental genotype-phenotype maps for which high-order epistasis had been reported previously. We find that five of the seven maps exhibited nonlinear scales. Interestingly, even after accounting for nonlinearity, we found statistically significant high-order epistasis in all seven maps. The contributions of high-order epistasis to the total variation ranged from 2.2% to 31.0%, with an average across maps of 12.7%. Our results provide strong evidence for extensive high-order epistasis, even after nonlinear scale is taken into account. Further, we describe a simple method to estimate and account for nonlinearity in genotype-phenotype maps.
Genetic Prediction of Male Pattern Baldness
Authors: Hagenaars Saskia P , Hill W David , Harris Sarah E , Ritchie Stuart J , Davies Gail , Liewald David C , Gale Catharine R , Porteous David J , Deary Ian J , Marioni Riccardo E
Published: September 2016

Male pattern baldness can have substantial psychosocial effects, and it has been phenotypically linked to adverse health outcomes such as prostate cancer and cardiovascular disease. We explored the genetic architecture of the trait using data from over 52,000 male participants of UK Biobank, aged 40-69 years. We identified over 250 independent novel genetic loci associated with severe hair loss. By developing a prediction algorithm based entirely on common genetic variants, and applying it to an independent sample, we could discriminate accurately (AUC = 0.82) between those with no hair loss from those with severe hair loss. The results of this study might help identify those at the greatest risk of hair loss and also potential genetic targets for intervention.
mtDNA diversity in human populations highlights the merit of haplotype matching in gene therapies
Authors: Røyrvik E.C. , Burgstaller J.P. , Johnston I.G.
Published: September 2016

Modern gene therapies aim to prevent the inheritance of mutant mitochondrial DNA (mtDNA) from mother to offspring by using a third-party mtDNA background. Technological limitations mean that these therapies may result in a small amount of maternal mtDNA admixed with a majority of third-party mtDNA. This situation is unstable if the mother’s mtDNA experiences a proliferative advantage over the third-party mtDNA, in which case the efficacy of the therapy may be undermined. Animal models suggest that the likelihood of such a proliferative advantage increases with increasing genetic distance between mother and third-party mtDNA, but in real therapeutic contexts the genetic distance, and so the importance of this effect, remains unclear. Here we harness a large volume of available human mtDNA data to model random sampling of mother and third-party mtDNAs from real human populations. We show that even within the same haplogroup, genetic differences around 20-80 SNPs are common between mtDNAs. These values are sufficient to lead to substantial segregation in murine models, over an organismal lifetime, even given low starting heteroplasmy, inducing increases from 5% to 35% over one year. Randomly pairing mothers and third-party women in clinical contexts thus runs the risk that substantial mtDNA segregation will compromise the beneficial effects of the therapy. We suggest that choices of ‘mtDNA donors’ be based on recent shared maternal ancestry, or, preferentially, explicit haplotype matching, in order to reduce the potential for problems in the implementation of these therapies.
Panpulmonate transcriptomes reveal candidate genes involved in the adaptation to freshwater and terrestrial habitats in gastropods
Authors: Romero Pedro E. , Feldmeyer Barbara , Pfenninger Markus
Published: September 2016

Background

The conquest of the land from aquatic habitats is a fascinating evolutionary event that happened multiple times in different phyla. Mollusks are among the organisms that successfully invaded the non-marine realm, resulting in the radiation of terrestrial panpulmonate gastropods. We compared transcriptomes from panpulmonates to study the selective pressures that modeled the transitions from marine into freshwater and terrestrial realms in this molluscan lineage.

Results

De novoassembly of six panpulmonate transcriptomes resulted in 55,000 - 97,000 predicted open reading frames, of which 9 - 14% were functionally annotated. Adding published transcriptomes, we predicted 791 ortholog clusters shared among fifteen panpulmonate species, resulting in 702 amino acid and 736 codon-wise alignments. The branch-site test of positive selection applied to the codon-wise alignments showed twenty-eight genes under positive selection in the freshwater lineages and seven in the terrestrial lineages. Gene ontology categories of these candidate genes include actin assembly, transport of glucose, and the tyrosine metabolism in the terrestrial lineages; and, DNA repair, metabolism of xenobiotics, mitochondrial electron transport, and ribosome biogenesis in the freshwater lineages.

Conclusions

We identified candidate genes representing processes that may have played a key role during the water-to-land transition in Panpulmonata. These genes were involved in energy metabolism and gas-exchange surface development in the terrestrial lineages and in the response to the abiotic stress factors (UV radiation, osmotic pressure, xenobiotics) in the freshwater lineages. Our study expands the knowledge of possible adaptive signatures in genes and metabolic pathways related to the invasion of non-marine habitats in invertebrates.
A High-Throughput Yeast Halo Assay for Bioactive Compounds
Authors: Bray Walter , Lokey R. Scott
Published: September 2016

When a disk of filter paper is impregnated with a cytotoxic or cytostatic drug and added to solid medium seeded with yeast, a visible clear zone forms around the disk whose size depends on the concentration and potency of the drug. This is the traditional “halo” assay and provides a convenient, if low-throughput, read-out of biological activity that has been the mainstay of antifungal and antibiotic testing for decades. Here, we describe a protocol for a high-throughput version of the halo assay, which uses an array of 384 pins to deliver ∼200 nL of stock solutions from compound plates onto single-well plates seeded with yeast. Using a plate reader in the absorbance mode, the resulting halos can be quantified and the data archived in the form of flat files that can be connected to compound databases with standard software. This assay has the convenience associated with the visual readout of the traditional halo assay but uses far less material and can be automated to screen thousands of compounds per day.
Detection of Indel Mutations in Drosophila by High-Resolution Melt Analysis (HRMA)
Authors: Housden Benjamin E. , Perrimon Norbert
Published: September 2016

Although CRISPR technology allows specific genome alterations to be created with relative ease, detection of these events can be problematic. For example, CRISPR-induced double-strand breaks are often repaired imprecisely to generate unpredictable short indel mutations. Detection of these events requires the use of molecular screening techniques such as endonuclease assays, restriction profiling, or high-resolution melt analysis (HRMA). Here, we provide detailed protocols for HRMA-based mutation screening in Drosophila and analysis of the resulting data using the online tool HRMAnalyzer.
Synchronization of S Phase in Schizosaccharomyces pombe Cells by Transient Exposure to M-Factor Pheromone
Authors: Nielsen Olaf
Published: September 2016

A well-characterized S phase, a unicellular lifestyle, and a plethora of mutations in key components of DNA metabolism make fission yeast a particularly attractive system in which to study DNA replication. However, synchronization of passage through a normal S phase has proved challenging. This protocol describes how combining nitrogen starvation with M-factor mating pheromone treatment presents a highly effective method for synchronizing passage through an ostensibly normal S phase.
Cas9-Mediated Genome Engineering in Drosophila melanogaster
Authors: Housden Benjamin E. , Perrimon Norbert
Published: September 2016

The recent development of the CRISPR–Cas9 system for genome engineering has revolutionized our ability to modify the endogenous DNA sequence of many organisms, including Drosophila. This system allows alteration of DNA sequences in situ with single base-pair precision and is now being used for a wide variety of applications. To use the CRISPR system effectively, various design parameters must be considered, including single guide RNA target site selection and identification of successful editing events. Here, we review recent advances in CRISPR methodology in Drosophila and introduce protocols for some of the more difficult aspects of CRISPR implementation: designing and generating CRISPR reagents and detecting indel mutations by high-resolution melt analysis.
Rapid measurement scheme for texture in cubic metallic materials using time-of-flight neutron diffraction at iMATERIA
Authors: Onuki Yusuke , Hoshikawa Akinori , Sato Shigeo , Xu Pingguang , Ishigaki Toru , Saito Yoichi , Todoroki Hidekazu , Hayashi Makoto
Published: September 2016

A rapid texture measurement system has been developed on the time-of-flight neutron diffractometer iMATERIA (beamline BL20, MLF/J-PARC, Japan). Quantitative Rietveld texture analysis with a neutron beam exposure of several minutes without sample rotation was investigated using a duplex stainless steel, and the minimum number of diffraction spectra required for the analysis was determined experimentally. The rapid measurement scheme employs 132 spectra, and by this scheme the quantitative determination of volume fractions of texture components in ferrite and austenite cubic phases in a duplex stainless steel can be made in a short time. This quantitative and rapid measurement scheme is based on the salient features of iMATERIA as a powder diffractometer, i.e. a fairly high resolution in d spacing and numerous detectors covering a wide range of scattering angle.
Crystallographic insights into Ni–Co–Mn–In metamagnetic shape memory alloys
Authors: Yan Haile , Zhang Chunyang , Zhang Yudong , Wang Xinli , Esling Claude , Zhao Xiang , Zuo Liang
Published: September 2016

In the present work, the morphological and crystallographic features of the 6M modulated martensite in the Ni45Co5Mn37In13alloy were investigated by electron backscatter diffraction and high-resolution transmission electron microscopy (HRTEM) at room temperature. The 6M modulated martensite is in plate form and organized in colonies within which the plates stretch roughly in the same direction. Each colony has four types of orientation variants that are related to three kinds of twin relations,i.e.\{ 1 \bar 2\bar 3\} _{\rm M} type I, \langle \bar 3\bar 3{{1}} \rangle _{\rm M} type II and {{\{ 103\} }}_{\rm M} compound twins. The twinning shears of type I and type II twins are the same and equal to 0.2681, being about one order of magnitude higher than that of the compound twin (0.0330). Variant interfaces are microscopically defined by their corresponding twinning planeK1. The HRTEM investigations show that the interfaces of the type I twin are straight and coherent at atomic scale, whereas those of the type II and compound twins are `stepped'. The step height of the compound twin interfaces is much larger than that of the type II twin interfaces. In view of variant organization, there is only one oriented type I interface and one compound twin interface, but there are two oriented type II interfaces which have an angular deviation of ±5.32° with respect to the type I twin interface. The results of the present work provide comprehensive information on morphological and crystallographic features of Ni–Co–Mn–In metamagnetic shape memory alloys.
MoRad6‐mediated ubiquitination pathways are essential for development and pathogenicity inMagnaporthe oryzae
Authors: Shi Huan‐Bin , Chen Guo‐Qing , Chen Ya‐Ping , Dong Bo , Lu Jian‐Ping , Liu Xiao‐Hong , Lin Fu‐Cheng
Published: September 2016

The ubiquitin system modulates protein functions through targeting substrates for ubiquitination. Here, E2 conjugating enzyme MoRad6‐related ubiquitination pathways are identified and analyzed inMagnaporthe oryzae, the causal agent of rice blast disease. Disruption of MoRad6 leads to severe defects in growth, sporulation, conidial germination, appressorium formation, and plant infection. To depict the functions of MoRad6, three putative ubiquitin ligases, MoRad18, MoBre1 and MoUbr1, are also characterized. Deletion of MoRad18 causes minor phenotypic changes, while MoBre1 is required for growth, conidiation and pathogenicity inM. oryzae. Defectsin ΔMobre1likely resulted from the reduction in di‐ and tri‐methylation level of Histone 3 lysine 4 (H3K4). Notably, MoUbr1 is crucial for conidial adhesion and germination, possibly by degrading components of cAMP/PKA and mitogen‐activated protein kinase (MAPK) Pmk1 signaling pathways via the N‐end rule pathway. Germination failure ofΔMoubr1conidia could be rescued by elevation of cAMP level or enhanced Pmk1 phosphorylation resulting from further deletion of MoIra1, theM. oryzaehomolog of yeast Ira1/2. These reveal vital effects of cAMP/PKA and MAPK Pmk1 signaling on conidial germination inM. oryzae. Altogether, our results suggest that MoRad6‐mediated ubiquitination pathways are essential for the infection‐related development and pathogenicity ofM. oryzae.
Oligotrophic lagoons of the South Pacific Ocean are home to a surprising number of novel eukaryotic microorganisms
Authors: Kim Eunsoo , Sprung Ben , Duhamel Solange , Filardi Christopher , Kyoon Shin Mann
Published: September 2016

The diversity of microbial eukaryotes was surveyed by environmental sequencing from tropical lagoon sites of the South Pacific, collected through the American Museum of Natural History (AMNH)'s Explore21 expedition to the Solomon Islands in September 2013. The sampled lagoons presented low nutrient concentrations typical of oligotrophic waters, but contained levels of chlorophyll a, a proxy for phytoplankton biomass, characteristic of meso‐ to eutrophic waters. Two 18S rDNA hypervariable sites, the V4 and V8–V9 regions, were amplified from the total of eight lagoon samples and sequenced on the MiSeq system. After assembly, clustering at 97% similarity, and removal of singletons and chimeras, a total of 2741 (V4) and 2606 (V8–V9) operational taxonomic units (OTUs) were identified. Taxonomic annotation of these reads, including phylogeny, was based on a combination of automated pipeline and manual inspection. About 18.4% (V4) and 13.8% (V8–V9) of the OTUs could not be assigned to any of the known eukaryotic groups. Of these, we focused on OTUs that were not divergent and possessed multiple sources of evidence for their existence. Phylogenetic analyses of these sequences revealed more than ten branches that might represent new deeply‐branching lineages of microbial eukaryotes, currently without any cultured representatives or morphological information.
Why Does Australia Have an Affordable Housing Problem and What Can Be Done About It?
Authors: Yates Judith
Published: September 2016

As a result of economic trends in Australia over the past 25 years, a growing proportion of households have faced high housing costs in relation to their income because of a shortage of affordable housing, particularly in areas where there is ready access to well‐paid employment. Problems have been particularly severe for lower income renters. This article provides a proposal to address this shortage, based on encouraging institutional financing of affordable rental housing, suggests more controversial policies that might be needed to address underlying causes and identifies a number of reasons why so little progress has been made.
Ireland—A Remarkable Economic Recovery?
Authors: Ruane Frances
Published: September 2016

The collapse of the Irish economy during the Global Financial Crisis brought a substantial decline in gross domestic product, a trebling of the unemployment rate and a sharp increase in public debt. Key to the scale of Ireland's crisis was the scale of a domestic property bubble. In the Corden Lecture, I explored how Ireland's notable turnaround since 2013 contrasts with the experiences of Spain, Portugal and Greece. This was primarily due to Ireland's large, foreign‐owned, modern, export‐oriented, multinational sector and its early and sustained action to deal with the fiscal deficit that emerged in 2008.
The Reasonable Expectation of Privacy and the Criminal Suspect
Authors: Purshouse Joe
Published: September 2016

In In re JR38, the Supreme Court unanimously dismissed an appeal from a 14 year‐old boy who argued that the dissemination of his image, taken whilst he was participating in sectarian rioting, to local newspapers, violated his rights under Article 8 of the European Convention on Human Rights (ECHR). However, the Court was divided on whether or not the measures taken by the police engaged the applicant's Article 8(1) rights at all. This case raises fundamental questions as to the scope of private life in the context of criminal investigations, and the place of the European Court of Human Rights’ ‘reasonable expectation of privacy’ test in determining whether Article 8(1) of the ECHR is engaged. This case comment subjects the majority's interpretation of Article 8(1) to critical scrutiny, concluding that this interpretation may unduly restrict the scope of Article 8 protection for those subject to criminal investigations.
Pregnancy at very advanced maternal age: a UK population‐based cohort study
Authors: Fitzpatrick KE , Tuffnell D , Kurinczuk JJ , Knight M
Published: September 2016

Objectives

To describe the characteristics, management and outcomes of women giving birth at advanced maternal age (≥48 years).

Design

Population‐based cohort study using the UK Obstetric Surveillance System (UKOSS).

Setting

All UK hospitals with obstetrician‐led maternity units.

Population

Women delivering at advanced maternal age (≥48 years) in the UK between July 2013 and June 2014 (n = 233) and 454 comparison women.

Methods

Cohort and comparison group identification through the UKOSS monthly mailing.

Main outcome measures

Pregnancy complications.

Results

Older women were more likely than comparison women to be overweight (33% versus 23%, P = 0.0011) or obese (23% versus 19%, P = 0.0318), nulliparous (53% versus 44%, P = 0.0299), have pre‐existing medical conditions (44% versus 28%, P < 0.0001), a multiple pregnancy (18% versus 2%, P < 0.0001), and conceived following assisted conception (78% versus 4%, P < 0.0001). Older women appeared more likely than comparison women to have pregnancy complications including gestational hypertensive disorders, gestational diabetes, postpartum haemorrhage, caesarean delivery, iatrogenic and spontaneous preterm delivery on univariable analysis and after adjustment for demographic and medical factors. However, adjustment for multiple pregnancy or use of assisted conception attenuated most effects, with significant associations remaining only with gestational diabetes (adjusted odds ratio [aOR] 4.81, 95% CI 1.93–12.00), caesarean delivery (aOR 2.78, 95% CI 1.44–5.37) and admission to an intensive care unit (aOR 33.53, 95% CI 2.73–412.24).

Conclusions

Women giving birth at advanced maternal age have higher risks of a range of pregnancy complications. Many of the increased risks appear to be explained by multiple pregnancy or use of assisted conception.

Tweetable abstract

The pregnancy complications in women giving birth aged 48 or over are mostly explained by multiple pregnancy.
How Does Medicaid Reimbursement Impact Nursing Home Quality? The Effects of Small Anticipatory Changes
Authors: Bowblis John R. , Applebaum Robert
Published: September 2016

Objective

In 2006, Ohio changed its Medicaid reimbursement methodology for nursing homes (NHs) to promote more efficient staffing levels. This study examines the impacts of this policy change on quality.

Research Design and Subjects

Ohio NHs were categorized based on their anticipated change in reimbursement under a new reimbursement system initiated in 2006. Linear regressions were utilized to determine how quality changed from 2006 to 2010 relative to a group of NHs that were not anticipated to experience any significant change in reimbursement. We examine resident outcomes constructed from the Minimum Data Set, deficiency citations, staffing levels, and satisfaction scores for residents and families as measures of quality.

Principal Findings

Nursing homes in the group receiving increased reimbursement showed an increase in nursing and nursing aide staffing levels. NHs in the group receiving a reduction in reimbursement did lower staffing levels. None of the nonstaffing quality outcomes were impacted by changes in Medicaid reimbursement.

Conclusion

Increased Medicaid reimbursement was found to increase staffing levels, but it had a limited effect, at least in the short run, on an array of nonstaffing quality outcomes.
Is the acute surgical unit model feasible for Australian regional centres?
Authors: Shilton Hamish , Tanveer Amin , Poh Benjamin Ruimin , Croagh Daniel , Jayasuriya Neil , Chan David
Published: September 2016

Background

A significant proportion of general surgery emergency procedures are conducted after‐hours in regional centres. The acute surgical unit (ASU) model reduces the number of after‐hours operations performed. We review the burden of emergency surgery in a regional centre and assess what components of the ASU model would benefit regional hospitals.

Methods

Retrospective analysis was performed on data for all emergency cases performed at Latrobe Regional Hospital (LRH) over a 1‐year period. Time into and out of theatre was used to determine total theatre usage and if the operation occurred after‐hours. ED triage time to theatre and start time for appendicectomy was compared to data from our metropolitan referral hospital, Monash Medical Centre (MMC), which has employed an ASU.

Results

General surgery emergency cases in regional areas are regular and predictable with a median of two emergency cases performed, and a mean theatre time of 156 min per day at LRH. On weekdays, 43.1% (n = 503) of emergency cases were done in the evening (18.00–24.00 hours), compared to 20.3% (n = 217) on weekends when an emergency theatre is available during the day. LRH performed more appendicectomies after‐hours than MMC over a 1‐year period.

Conclusion

Regional centres have a significant burden of general surgery emergency procedures; of which the number performed after‐hours is comparable to metropolitan centres. The number of procedures and theatre time required by these cases justify a dedicated emergency theatre in‐hours similar to metropolitan ASU models and this would reduce emergency operating after‐hours.
Is immediate reconstruction after mastectomy in breast cancer patients beneficial to shoulder function?
Authors: Lee Bong Gun , Kim Joon Kuk , Choi Sung Hyouk , Ahn Hee Chang , Chung Min Sung
Published: September 2016

Background

To compare shoulder morbidity between patients who received transverse rectus abdominis myocutaneous (TRAM) flaps after mastectomy (MX + TRAM) and patients who underwent mastectomy only (MX).

Methods

Thirty patients in each group were followed for a minimum of 2 postoperative years. Visual analog scale (VAS) score, restricted range of motion (ROM), rotator cuff disease, muscle strength, shoulder function scores (American Shoulder and Elbow Score and Shoulder Pain and Disability Index), measurement of scapular tilt on chest radiography and standing position in each group were compared.

Results

There were no significant differences in VAS, restricted ROM, rotator cuff disease, muscle strength, shoulder function scores or scapula tilt on physical examination. However, lower angles of the scapula on chest radiography (4.0 ± 13.2 versus −3.4 ± 12.4 mm; P = 0.029) and pectoralis minor index (0.4 ± 7.7 mm versus 7.8 ± 9.1 mm; P = 0.001) were significantly different between the two groups.

Conclusions

Immediate breast reconstruction after a MX had advantages for preserving scapular resting alignment but did not provide benefits for shoulder morbidity on short‐term follow‐up.
Is resection of pancreatic adenocarcinoma with synchronous hepatic metastasis justified? A review of current literature
Authors: Antoniou Efstathios , Margonis Georgios A. , Sasaki Kazunari , Andreatos Nikolaos , Polychronidis Georgios , Pawlik Timothy M. , Pikoulis Emmanouil
Published: September 2016

Background

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal neoplastic process, largely due to the presence of disseminated disease at presentation. As such, evidence‐based management of metastatic disease is integral to patient care in such circumstances. This review aimed to summarize the current state of knowledge regarding the potential effectiveness of liver metastasectomy in the setting of PDAC.

Methods

A structured review of the literature was performed from April to May 2016, using the PubMed database. Relevant original research articles and systematic reviews/meta‐analyses published between 1990 and 2015 were considered eligible. The primary endpoint was overall survival in patients undergoing resection for PDAC and liver metastasectomy. Studies reporting on fewer than 10 patients were excluded.

Results

Ultimately, eight studies met our inclusion criteria. Their results suggest that hepatic metastasectomy for PDAC is a safe procedure, with a potential survival benefit for carefully selected patients, particularly those with metachronous metastases. Nonetheless, small sample sizes and inconsistent use of appropriate controls preclude generalization of these findings.

Conclusion

Multi‐institutional prospective studies are required to fully delineate the potential therapeutic utility and operative indications of liver metastasectomy in the setting of modern interdisciplinary management of PDAC.
Altered pharmacodynamics and pharmacokinetics of cisatracurium in patients with severe mitral valve regurgitation during anaesthetic induction period
Authors: Liu Jiayi , Lu Chunying , Zou Qirong , Wang Sheng , Peng Xuemei
Published: September 2016

Aim

The aim of the current study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in patients with severe mitral valve regurgitation (MR) during the anaesthetic induction period.

Methods

Thirty patients in the clinical trial were divided into two groups: the MR group (n = 15) and the control group (n = 15). Arterial blood samples were obtained before (time 0) and at 1, 2, 4, 6, 8, 10, 15 and 20 min after intravenous injection of 0.15 mg kg−1 cisatracurium. The degree of neuromuscular block was measured by train of four (TOF) testing. The concentration of cisatracurium in the plasma was determined by high‐performance liquid chromatography. A conventional two‐compartment model and integrated PK/PD model were applied to PK and PD data analysis, respectively.

Results

The results of PK model fitting demonstrated that severe MR reduced the distribution rate of cisatracurium from the central to peripheral compartment, resulting in a higher concentration of the drug in the plasma. The time to the maximal neuromuscular blocking effect of cisatracurium was delayed in the MR group (2.08 min in the control group vs. 4.12 min in the MR group). The PK/PD model indicated that the distribution rate of cisatracurium from the blood to the effect compartment was decreased in the MR group.

Conclusions

The present study suggested that the PK and PD of cisatracurium were significantly altered in patients with severe MR. The study has the potential to improve the safety of anaesthetic induction in patients with severe MR through accurate prediction of the PD responses of cisatracurium using the established PK/PD model.
Quality and consistency of outcome reporting in clinical trials of immunosuppression in renal transplantation
Authors: Hussain Samia , Knight Simon R.
Published: September 2016

Interpretation, comparison, and combination of results of clinical trials are reliant on accurate and complete reporting of outcomes. This study aimed to assess the quality and variability in outcome reporting in immunosuppression trials following renal transplantation. All randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published over a 5‐year period were included. Outcomes reported in these studies were extracted, along with data regarding completeness of reporting and whether a clear definition of the method used to measure the outcome was provided. A total of 4760 outcomes were identified from 182 studies. Overall, 90.3% outcomes were completely reported; the remainder had missing data that would preclude use in meta‐analysis; 31.5% manuscripts did not define a primary endpoint. Efficacy outcomes were more likely to be clearly defined than safety outcomes (OR: 0.022, P<.001) or patient‐reported outcome measures (PROMs) (OR: 0.014, P<.001). PROMs were reported in less than half of manuscripts, and only five reported quality‐of‐life data using a validated tool. There was significant variability in the way that common efficacy and safety outcomes were defined. Variability in the way that endpoints are selected and reported in trials in renal transplantation makes interpretation and comparison between studies difficult.
Anticipatory scene representation in preschool children's recall and recognition memory
Authors: Kreindel Erica , Intraub Helene
Published: September 2016

Behavioral and neuroscience research on boundary extension (false memory beyond the edges of a view of a scene) has provided new insights into the constructive nature of scene representation, and motivates questions about development. Early research with children (as young as 6–7 years) was consistent with boundary extension, but relied on an analysis of spatial errors in drawings which are open to alternative explanations (e.g. drawing ability). Experiment 1 replicated and extended prior drawing results with 4–5‐year‐olds and adults. In Experiment 2, a new, forced‐choice immediate recognition memory test was implemented with the same children. On each trial, a card (photograph of a simple scene) was immediately replaced by a test card (identical view and either a closer or more wide‐angle view) and participants indicated which one matched the original view. Error patterns supported boundary extension; identical photographs were more frequently rejected when the closer view was the original view, than vice versa. This asymmetry was not attributable to a selection bias (guessing tasks; Experiments 3–5). In Experiment 4, working memory load was increased by presenting more expansive views of more complex scenes. Again, children exhibited boundary extension, but now adults did not, unless stimulus duration was reduced to 5 s (limiting time to implement strategies; Experiment 5). We propose that like adults, children interpret photographs as views of places in the world; they extrapolate the anticipated continuation of the scene beyond the view and misattribute it to having been seen. Developmental differences in source attribution decision processes provide an explanation for the age‐related differences observed.
Trouble at the top? Restricted distribution and extreme population isolation in an alpine crustacean assemblage with unexpected lineage diversity
Authors: Hatley Jude , Murphy Nicholas P.
Published: September 2016

The fragile alpine freshwater ecosystems of Australia are threatened by historic land use and projected climate change, yet little is known about the fauna of these environments. The aim of this study was to analyse the phylogeography of two important components of this ecosystem, an amphipod (Neoniphargus) and an isopod (Coluboltelson), to determine the potential impacts of environmental change on these crustaceans.

DNA sequences were generated for the mitochondrial cytochrome c oxidase subunit I (COI) and nuclear 28S ribosomal RNA (28S) of 229 amphipods and 153 isopods from 19 sites across seven creeks in the Bogong High Plains, Victoria, Australia. Phylogenetic analyses were undertaken to define evolutionary significant units (ESUs), and population genetic structure was examined.

Analyses of both markers found deep divergences in both taxa, leading to the definition of six amphipod and two isopod ESUs, within both Neoniphargus and Colubotelson. The majority of amphipod ESUs exhibited highly restricted distributions, with essentially no gene flow between sites, even within the same creeks, consistent with the Death Valley Model of population connectivity. By contrast, both isopod ESUs had overlapping distributions across the entire sample area and exhibited some highly limited population connectivity among sites in adjacent headwaters, consistent with the Headwater Model.

This study suggests that there is a high level of undiscovered biodiversity within Australian alpine aquatic invertebrates. The highly limited population structure, and restricted distributions have important consequences for the conservation of the headwaters of Australia's largest river system. These findings indicate that habitat loss and/or fragmentation associated with environmental change will result in biodiversity reductions, with species unlikely to shift their ranges in response to future climate change, or recover rapidly from localised extinction events.
The expansion of short rotation forestry: characterization of determinants with an agent‐based land use model
Authors: Schulze Jule , Gawel Erik , Nolzen Henning , Weise Hanna , Frank Karin
Published: September 2016

Wood is a limited resource which is exposed to a continuously growing global demand not least because of a politically fostered bioenergy use. One approach to master the challenge to sustainably meet this increasing wood demand is short rotation forestry (SRF). However, SRF is only gradually evolving and it is not fully understood which determinants hamper its expansion. This study provides theoretical insights into economic and environmental determinants of an SRF expansion and their interplay. This assessment requires the incorporation of farmers' decision‐making based on an explicit investment appraisal. Therefore, we use an agent‐based model to depict the decision‐making of profit‐maximizing farmers facing the choice between SRF, the cultivation of conventional annual agricultural crops and abstaining from cultivation (fallow land). The land use decisions are influenced by general economic determinants, such as market prices for wood and annual crops, and by site‐dependent determinants, such as the environmental site quality. We found that the willingness to pay for SRF‐based products and for annual crops most strongly influences the coverage of SRF in the landscape. SRF will in most cases be established on sites with low productivity. However, a decrease in the willingness to pay for annual crops will lead to a reallocation of SRF plantations to sites with higher productivity. Furthermore, our model results indicate that the impact of the distance to processing plants on farmers' decisions strongly depends on general economic determinants and the given spatial structure of the underlying natural landscape. Analysing the relative importance of different determinants of an SRF expansion, this study gives insights into the approach of using SRF to sustainably meet the growing wood demand. Moreover, these insights are taken as a starting point for the design of effective government interventions to promote SRF.
Comparison of standard forearm prosthetic loop grafts to composite semiloop forearm grafts (“semi‐grafts”) in hemodialysis patients: A prospective study
Authors: Georgiadis George S. , Antoniou George A. , Kantartzi Konstantia , Georgakarakos Efstratios I. , Argyriou Christos , Passadakis Ploumis , Lazarides Miltos K.
Published: September 2016

Introduction: To prospectively assess the performance of composite semiloop antebrachial grafts (“semi‐grafts,” SGs) in hemodialysis patients.

Methods: Eighty‐five patients who received 67 loop antebrachial grafts (LG‐group) and 25 antebrachial semigrafts (SG‐group) were enrolled. SGs were defined as those originating from the brachial artery and anastomosed with the proximal mature mid‐antebrachial cephalic vein. Cephalic vein length should be at least 10 cm in length and of ≥5 mm in diameter for inclusion in the SG‐group. LG‐group included all possible outflow vein options of minimum diameter 3 mm. Kaplan‐Meier statistics was used for comparison of groups.

Findings: Main indication for a SG was a failing radiocephalic fistula with extensive distal cephalic vein stenosis not amenable to correction or failed after endovascular repair or requiring long interposition grafting. The mean follow‐up period was 20.16 ± 22.6 and 29.6 ± 36.7 months for the LG‐ and SG‐group, respectively (P = 0.14). Forty‐two patients died during the follow‐up. Primary patency (up to first intervention or failure) at 6 and 12 months for LG‐ vs. SG‐group was 93.9% vs. 83.7% and 47% vs. 55.8% (P = 0.08). Secondary patency (up to abandonment) was 58.2% vs. 61.1% and 36% vs. 45.8% at 12 and 24 months (P = 0.18). Mortality at 48 months was 22.4% (LG‐group) and 24% (SG‐group) (P = 0.9).

Discussion: There was a trend toward better primary and secondary patency rates for the SGs especially in the long‐term. This is a valuable option in selected patients that access surgeons and nephrologists should be aware of.
Differential effects of SA and intensive AH courses on teenagers' L2 pronunciation
Authors: Llanes Àngels , Mora Joan C. , Serrano Raquel
Published: September 2016

The present study compares the differential effects of two learning contexts on the L2 pronunciation accuracy of L1‐Spanish/Catalan teenage learners of English. The learners engaged in either a study abroad (SA) course in the UK (n = 14) or in an intensive course at home (AH) in Spain (n = 22) for 3 weeks. Sentence‐sized production samples were elicited before and after the SA and AH courses through a delayed imitation task targeting difficult L2 phonetic and phonological features. L2 pronunciation accuracy was assessed through voice onset time (VOT) and perceived foreign accent (FA) measures. The results indicated that the SA learner group significantly improved their VOT and reduced their FA to a greater extent than the AH learner group did. VOT gains were significantly correlated with amount of FA reduction, suggesting that speakers who had developed a more target‐like production of oral stops were also perceived to have reduced their overall FA to a greater extent. Taken together these results underscore the potential of SA to induce improvement in L2 pronunciation. Several pedagogical implications are discussed.