bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Fish Drive Recreational Fishing License Sales?
Authors: Hunt Len M. , Bannister Allison E. , Drake D. Andrew R. , Fera Shannon A. , Johnson Timothy B.
Published: January 2017

Management agencies need to understand the factors that influence fishing license purchases. While traits such as gender can influence the decisions of recreational fishers, a gap remains in understanding the influence of catch-related fishing quality on these decisions. We evaluated the use of fish biomass density as a proxy for catch-related fishing quality along with non-catch-related factors (population density, gender, and ethnicity) to explain variation in 2014 resident fishing license rates across 510 origins in Ontario. License rates were higher in areas with lower population density (i.e., rural areas), in areas with higher fish biomass density, and among populations with stronger representation by ethnic majorities. From simulated scenarios, we predicted that resident license sales could increase between 14% and 25% if fish biomass density increased by 30% and 54% in northeastern and southern Ontario, respectively. However, license sales could decrease between 5% and 10% with a 30% redistribution of rural residents to a major urban area. The relationship between license rates and non-catch-related factors confirms the role of urbanization on recreational fishing participation, while catch-related factors provide support for a functional response by fishers to fish.

Received April 28, 2016; accepted October 3, 2016Published online January 3, 2017
Isotopic Structure of Lake Whitefish in Lake Huron: Evidence for Regional and Local Populations Based on Resource Use
Authors: Eberts Rebecca L. , Wissel Björn , Simpson Gavin L. , Crawford Stephen S. , Stott Wendylee , Hanner Robert H. , Manzon Richard G. , Wilson Joanna Y. , Boreham Douglas R. , Somers Christopher M.
Published: January 2017

Lake Whitefish Coregonus clupeaformis is the most commercially valuable species in Lake Huron. The fishery for this species has historically been managed based on 25 management units (17 in Canada, 8 in the USA). However, congruence between the contemporary population structure of Lake Whitefish and management units is poorly understood. We used stable isotopes of carbon (δ13C) and nitrogen (δ15N), food web markers that reflect patterns in resource use (i.e., prey, location, habitat), to assess the population structure of spawning-phase Lake Whitefish collected from 32 sites (1,474 fish) across Lake Huron. We found large isotopic variation among fish from different sites (ranges: δ13C = 10.2‰, δ15N = 5.5‰) and variable niche size and levels of overlap (standard ellipse area = 1.0–4.3‰2). Lake Huron contained spawning-phase fish from four major isotopic clusters largely defined by extensive variation in δ13C, and the isotopic composition of fish sampled was spatially structured both within and between lake basins. Based on cluster compositions, we identified six putative regional groups, some of which represented sites of high diversity (three to four clusters) and others with less (one to two clusters). Analysis of isotopic values from Lake Whitefish collected from summer feeding locations and baseline prey items showed similar isotopic variation and established spatial linkage between spawning-phase and summer fish. Our results show that summer feeding location contributes strongly to the isotopic structure we observed in spawning-phase fish. One of the regional groups we identified in northern Georgian Bay is highly distinct based on isotopic composition and possibly ecologically unique within Lake Huron. Our findings are congruent with several previous studies using different markers (genetics, mark–recapture), and we conclude that current management units are generally too small and numerous to reflect the population structure of Lake Whitefish in Lake Huron.

Received June 2, 2016; accepted October 3, 2016Published online January 3, 2017
Hypertensive Urgencies: The Epidemic, Causes, and Consequences
Authors: Krakoff Lawrence R.
Published: January 2017

There has been a recent in increase visits to emergency rooms (ERs) or unscheduled/urgent visits to clinics for very high blood pressure, defined as ≥180/110 mm Hg without clinical sign of serious cardiovascular disease. The term “hypertensive urgency” defines these visits. Parallel with the increase of hypertensive urgencies has been a reduction in availability of primary care practices. Options for management of hypertensive urgencies are: (i) admit to in-patient services, (ii) briefly observe then discharge without specific treatment, and (iii) treat with rapid acting antihypertensive drugs and discharge. Optimal decisions should be based on evidence-based observations, but such information has not been available. A recent survey of hypertensive urgencies observed in a large health care system summarizing outcomes from nearly 1.3 million visits has recently been published. The results for the small fraction referred from practices to either ER evaluation or admission were compared to a group matched by propensity scoring. Cardiovascular event rates were <1% for a 30-day follow-up period. However, at the 1 month mark, >80% of both groups had uncontrolled hypertension, that remained >60% 5 months later. Occurrence of an a hypertensive urgency should be seen as a signal event or trigger that requires effective measures to assure sustained management of hypertension to achieve the long-term control needed for effective prevention of cardiovascular and renal disease. Development of system wide strategies to track and enroll those with hypertensive urgencies into appropriate medical surveillance and treatment programs is crucial.
AFRESh: an adaptive framework for compression of reads and assembled sequences with random access functionality
Authors: Paridaens Tom , Van Wallendael Glenn , De Neve Wesley , Lambert Peter
Published: January 2017

Motivation

The past decade has seen the introduction of new technologies that lowered the cost of genomic sequencing increasingly. We can even observe that the cost of sequencing is dropping significantly faster than the cost of storage and transmission. The latter motivates a need for continuous improvements in the area of genomic data compression, not only at the level of effectiveness (compression rate), but also at the level of functionality (e.g. random access), configurability (effectiveness versus complexity, coding tool set …) and versatility (support for both sequenced reads and assembled sequences). In that regard, we can point out that current approaches mostly do not support random access, requiring full files to be transmitted, and that current approaches are restricted to either read or sequence compression.

Results

We propose AFRESh, an adaptive framework for no-reference compression of genomic data with random access functionality, targeting the effective representation of the raw genomic symbol streams of both reads and assembled sequences. AFRESh makes use of a configurable set of prediction and encoding tools, extended by a Context-Adaptive Binary Arithmetic Coding scheme (CABAC), to compress raw genetic codes. To the best of our knowledge, our paper is the first to describe an effective implementation CABAC outside of its’ original application. By applying CABAC, the compression effectiveness improves by up to 19% for assembled sequences and up to 62% for reads. By applying AFRESh to the genomic symbols of the MPEG genomic compression test set for reads, a compression gain is achieved of up to 51% compared to SCALCE, 42% compared to LFQC and 44% compared to ORCOM. When comparing to generic compression approaches, a compression gain is achieved of up to 41% compared to GNU Gzip and 22% compared to 7-Zip at the Ultra setting. Additionaly, when compressing assembled sequences of the Human Genome, a compression gain is achieved up to 34% compared to GNU Gzip and 16% compared to 7-Zip at the Ultra setting.

Availability and Implementation

A Windows executable version can be downloaded at https://github.com/tparidae/AFresh.
The Concept of the Three Orders of Society and Social Mobility in Eleventh-Century England
Authors: Moilanen Inka
Published: January 2017

This article examines the concept of the three orders of society (oratores, bellatores, laboratores) in the works of Ælfric of Eynsham (d. c.1010) and Wulfstan of York (d. 1023). Paying attention to the immediate contexts in which Ælfric and Wulfstan formulated their views on social order, the article contrasts the varying uses of the metaphor with the discussion on social change and social mobility current around the turn of the first millennium. The reiteration of these categories seems to have surfaced in situations of particular political turbulence, as a means of convincing audiences that contemporary society was in a state of disorder which had to be remedied. The article incorporates analysis of a text previously excluded from discussions of the concept, Napier 50, and reviews some interpretations according to which the three orders functioned as part of criticism of extensive upward social mobility at the beginning of the eleventh century.
Genetic and morphological diversity of the cosmopolitan chaetognath Pseudosagitta maxima (Conant, 1896) in the Atlantic Ocean and its relationship with the congeneric species
Authors: Kulagin Dmitry N. , Neretina Tatiana V.
Published: January 2017

Until recently many oceanic zooplankton species have been considered as cosmopolitan organisms. At present it became evident that some of them comprise many distinct molecular operational taxonomic units (MOTUs) that often are regarded as cryptic species. As they can significantly change our perceptions of large-scale biogeographic patterns, it is important to characterize the true diversity within common and ecologically important groups. We have analysed the molecular and morphological diversity of the cosmopolitan mesopelagic chaetognath Pseudosagitta maxima throughout the Atlantic Ocean from 60° S to 85° N and its position within the genus Pseudosagitta. Three distinct mitochondrial clades within P. maxima were revealed with phylogenetic analyses (Maximum Likelihood, Bayesian Inference) and were geographically separated. The subsequent analyses of nuclear markers (H3, ITS1) have shown that P. maxima most likely comprises two distinct MOTUs, tropical and bipolar, that also have some morphological differences. The latter MOTU consists of two genetically slightly divergent populations: southern and northern. The morphological examination allowed the determination of a character (type of hook coloration) that accurately distinguishes juveniles of the P. maxima complex from the other congeneric species. Molecular data have shown that evolutionary P. lyra and P. gazellae are more closely related to each other than to P. maxima. Number of hooks, number of anterior and posterior teeth and the arrangement of ova in the ovary were proposed to be the most useful morphological characters to distinguish between tropical and bipolar MOTUs within the P. maxima complex. The first three characters should be determined for each maturity stage separately.
Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells
Authors: Yim Ji-Hye , Yun Jung Mi , Kim Ji Young , Lee In Kyung , Nam Seon Young , Kim Cha Soon
Published: January 2017

Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.
Second Generation Electronic Nicotine Delivery System Vape Pen Exposure Generalizes as a Smoking Cue
Authors: King Andrea C , Smith Lia J , McNamara Patrick J , Cao Dingcai
Published: January 2017

Introduction

Second generation electronic nicotine delivery systems (ENDS; also known as e-cigarettes, vaporizers or vape pens) are designed for a customized nicotine delivery experience and have less resemblance to regular cigarettes than first generation “cigalikes.” The present study examined whether they generalize as a conditioned cue and evoke smoking urges or behavior in persons exposed to their use.

Methods

Data were analyzed inN = 108 young adult smokers (≥5 cigarettes per week) randomized to either a traditional combustible cigarette smoking cue or a second generation ENDS vaping cue in a controlled laboratory setting. Cigarette and e-cigarette urge and desire were assessed pre- and post-cue exposure. Smoking behavior was also explored in a subsample undergoing a smoking latency phase after cue exposure (N = 26).

Results

The ENDS vape pen cue evoked both urge and desire for a regular cigarette to a similar extent as that produced by the combustible cigarette cue. Both cues produced similar time to initiate smoking during the smoking latency phase. The ENDS vape pen cue elicited smoking urge and desire regardless of ENDS use history, that is, across ENDS naїve, lifetime or current users. Inclusion of past ENDS or cigarette use as covariates did not significantly alter the results.

Conclusions

These findings demonstrate that observation of vape pen ENDS use generalizes as a conditioned cue to produce smoking urge, desire, and behavior in young adult smokers. As the popularity of these devices may eventually overtake those of first generation ENDS cigalikes, exposure effects will be of increasing importance.

Implications

This study shows that passive exposure to a second generation ENDS vape pen cue evoked smoking urge, desire, and behavior across a range of daily and non-daily young adult smokers. Smoking urge and desire increases after vape pen exposure were similar to those produced by exposure to a first generation ENDS cigalike and a combustible cigarette, a known potent cue. Given the increasing popularity of ENDS tank system products, passive exposures to these devices will no doubt increase, and may contribute to tobacco use in young adult smokers.
Dry Matter Loss for Hybrid Rough Rice Stored Under Reduced‐Oxygen Conditions
Authors: Atungulu Griffiths G. , Thote Supriya , Wilson Shantae
Published: January 2017

The objectives of this research were to characterize dry matter loss of hybrid long‐grain rough rice during storage under reduced‐oxygen conditions and develop a new approach to predict the dry matter loss by using storage temperature and relative humidity data as input. Two long‐grain hybrid rice cultivars, CL XL745 and XL760, harvested in the year 2015 were stored in rough‐rice form in sealed glass jars at moisture contents of 12.5, 16, 19, and 21%, (wet basis) and temperatures of 10, 15, 20, 27, and 40°C for a total of 16 weeks, with samples taken at 2, 4, 6, 8, 10, 12, and 16 weeks of storage. Results revealed no differences in dry matter loss connected with the rough‐rice moisture content levels and temperature during the storage duration. However, the dry matter loss was statistically different based on rough‐rice cultivar. Experimental data were fitted to a dry matter loss equation for long‐grain rice found in literature. The dry matter loss equation developed for conditions of grain storage without oxygen limitation did not accurately predict rough‐rice dry matter loss under reduced‐oxygen conditions. Equation constants generated for reduced‐oxygen storage conditions were significantly lower than the typical constants used for long‐grain rice in literature. Hence, integration of rice cultivar and storage conditions such as oxygen supply is crucial for accurate determination of kinetics of dry matter loss during storage of hybrid long‐grain rough rice.
Microbiological Examination of Erwinia amylovora Exopolysaccharide Ooze
Authors: Slack Suzanne M. , Zeng Quan , Outwater Cory A. , Sundin George W.
Published: January 2017

Fire blight, caused by the pathogen Erwinia amylovora, is the most devastating bacterial disease of pome fruit in North America and worldwide. The primary method of dispersal for E. amylovora is through ooze, a mass of exopolysaccharides and bacterial cells that is exuded as droplets from infected host tissue. During the 2013 and 2014 field seasons, 317 ooze droplets were collected from field-inoculated apple trees. Populations of E. amylovora in ooze droplets were 108 CFU/μl on average. Ooze droplets harboring larger (>108 CFU/μl) cell populations were typically smaller in total volume and had darker coloring, such as orange, red, or dark red hues. Examination of apple host tissue at the site of emergence of ooze droplets using scanning electron microscopy revealed that ooze was not exuding through natural openings; instead, it was found on erumpent mounds and small (10-μm) tears in tissue. These observations suggested that E. amylovora-induced wounds in tissue provided the exit holes for ooze extrusion from the host. Analyses of E. amylovora populations in ooze droplets and within the stems from which ooze droplets emerged indicated that approximately 9% of the total bacterial population from infected stems is diverted to ooze. Gene expression analyses indicated that E. amylovora cells in stem sections located above ooze droplets and in ooze droplets were actively expressing critical pathogenicity genes such as hrpL, dspE, and amsK. Thus, our study identified ooze as a source of large, concentrated populations of E. amylovora that emerged from the host by rupturing host tissue. Because the cells in ooze droplets are expressing genes required for pathogenesis, they are already primed for infection should they be dispersed from ooze to new infection courts.
Effect of subchronic exposure to opioids on the effective dose of intravenous and inhalation anaesthetics
Authors: Ou Mengchan , Li Yu , Kang Yi , Zhao Xiaolin , Zhu Tao
Published: January 2017

This study aimed to investigate the effect of subchronic exposure to morphine on the 50% effective dose (EC50) (median effective concentration/EC50) values of intravenous (propofol and ketamine) and inhalation (sevoflurane) anaesthetics in mice. Eight to 12-week-old male mice were administered morphine subcutaneously for 5 days to create a subchronic morphine exposure model. Control mice were injected with saline. The EC50 for righting reflex loss and tail clip reflex of general anaesthetics on the first (D1), third (D3) and seventh days (D7), after establishing a subchronic morphine exposure model, were determined. Sevoflurane: No change in the minimum alveolar concentration for righting reflex loss or tail clip reflex loss was observed between the treated and the control values (P>0.05). Propofol: the EC50 for righting reflex loss of D7 was significantly lower than the control and D1 (P<0.05). The EC50 for tail clip reflex loss of D3 and D7 decreased compared with the control (P<0.05). Ketamine: the EC50 for righting reflex loss of D3 and D7 was significantly higher than that of the controls. The EC50 for tail clip reflex loss at D1, D3 and D7 increased compared with the control (P<0.05). In summary, after subchronic exposure to morphine, the minimum alveolar concentration value of sevoflurane did not change significantly; the EC50 of propofol decreased, whereas the EC50 of ketamine increased. The changes induced by subchronic exposure to morphine can alter the response to anaesthetics, and the effects vary with the modes of action of anaesthetics.
The association of nonalcoholic fatty liver disease with genetic polymorphisms: a multicenter study
Authors: Uygun Ahmet , Ozturk Kadir , Demirci Hakan , Oztuna Ali , Eren Fatih , Kozan Salih , Yilmaz Yusuf , Kurt Omer , Turker Turker , Vatansever Sezgin , Alper Emrah , Unsal Belkis
Published: January 2017

Introduction

Growing evidence suggests that multiple factors, such as insulin resistance, nutritional factors, gut microbiota, and hormones released from the adipose tissue, act together on genetically predisposed individuals. We aimed to investigate whether various single-nucleotide polymorphisms (SNPs) play a role in the development of nonalcoholic fatty liver disease (NAFLD) and severity of liver damage in the Anatolian population.

Methods

Two hundred and sixteen patients with biopsy-proven NAFLD and 150 control participants, aged 18–70 years, were consecutively enrolled in this multicenter study. Blood samples were genotyped for the PNPLA3 (rs738409), IL28B (rs12979860, rs12980275, rs8099917), PPAR-α 227 ALA, PPAR-γ pro 12 ALA, SOD2 C47T, and LOX-1 IVS4–14 polymorphisms using the custom-made LightSNiP assays on a LightCycler 480 II instrument.

Results

Genotypic distributions of PNPLA3 rs738409 SNPs were different between NAFLD and control participants, but not for other SNPs. The PNPLA3 rs738409 GG polymorphism was associated with a 27-fold increased risk of development of NAFLD (odds ratio=27.8, 95% confidence interval: 3.5–218.4; P=0.002). Patients with the PNPLA3 GG genotype had higher nonalcoholic fatty liver disease activity score levels compared with patients with the PNPLA3 CC genotype (P<0.005). NAFLD patients without fibrosis had a higher frequency of IL28B rs12979860 TT and rs12980275 GG genotypes compared with NAFLD patients with fibrosis (P<0.005).

Conclusion

The present study proposes that polymorphisms in the PNPLA3 gene have highly predictive value in the development of NAFLD and are independently associated with the severity of liver histology in patients with NAFLD. The results of this study suggest that IL28B rs12979860 TT or rs12980275 GG may play an important protective role against the development of advanced fibrosis and even cirrhosis.
Short article: Risk of small intestinal bacterial overgrowth with chronic use of proton pump inhibitors in children
Authors: Cares Kristen , Al-Ansari Namir , Macha Suhasini , Zoubi Najeeb , Zaghloul Hazim , Thomas Ron , Lalinsky Patricia , El-Baba Mohammad
Published: January 2017

Background

Some theorize that prolonged use of proton pump inhibitors (PPIs) may increase the risk of small intestinal bacterial overgrowth (SIBO). Chronic acid suppression and resultant hypochlorhydria may lead to an altered intraluminal environment, which, in turn, may promote the growth of bacteria in the small intestine. A handful of studies measured the risk of SIBO in adults taking PPIs and obtained mixed results; however, this risk has not been exclusively measured in children.

Aim

This study aimed to measure the risk of SIBO in children taking PPI versus those not taking PPI.

Patients and methods

This was a prospective cohort study. Evaluation of SIBO was performed using the glucose hydrogen breath test. Patients younger than 18 years of age taking a PPI longer than 6 months were compared with healthy control participants. After ingestion of glucose substrate, breath samples were obtained every 15 min for 2 h. An increase in breath hydrogen or methane above 12 ppm was considered diagnostic of SIBO.

Results

Overall, 83 participants were tested, of whom 56 were taking PPIs. SIBO was detected in five (8.9%) of the 56 participants taking PPI versus one (3.7%) of the 27 participants in the control group (P=0.359), with a relative risk of 2.4 (95% confidence interval: 0.29–19.6).

Conclusion

To our knowledge, this is the first study in the English literature measuring the risk of SIBO in children taking PPIs. Our results indicate a potential risk of SIBO in chronic PPI users; however, this is not statistically significant. This is an important finding as PPIs are readily prescribed for children and are often taken longer than 6 months’ duration.
Nonalcoholic steatohepatitis recurrence and rate of fibrosis progression following liver transplantation
Authors: Sourianarayanane Achuthan , Arikapudi Sowminya , McCullough Arthur J. , Humar Abhinav
Published: January 2017

Background

Nonalcoholic steatohepatitis (NASH) is known to recur following liver transplantation (LT). Metabolic risk factors increase with immunosuppression. However, the rate of fibrosis progression following LT for NASH while on immunosuppression is less clear.

Aim

The incidences of steatosis, NASH, and fibrosis following LT for NASH were quantified and compared with those transplanted for alcoholic liver disease (ALD).

Patients and methods

Records of all NASH patients and 1 : 2 match with ALD transplant recipients between 2001 and 2006 were reviewed retrospectively. Patients without liver biopsies beyond 2 months following LT were excluded.

Results

NASH patients (n=77) were older (P=0.0006) and less likely male (P<0.001) than ALD patients (n=108). The incidence of steatosis, NASH, and fibrosis stage increased at 1, 3, and 5 years in both groups. Although steatosis and nonalcoholic fatty liver disease activity scores were higher, fibrosis was lower in NASH compared with ALD (0.43 vs. 1.0 stage/year; P=0.0045). The incremental increase in the rate of fibrosis was faster in the first year compared with 4–5 years (0.8 vs. 0.04 stage/year) following LT. The rate of fibrosis progression during 4–5 years was decreased in NASH compared with ALD recipients (0.04 vs. 0.33 stage/year; P=0.015). NASH etiology was associated with reduced rate of fibrosis progression (odds ratio=0.67) on multivariate analysis.

Conclusion

Despite having more steatosis and inflammation, progression of fibrosis was slower in NASH compared with ALD recipients. Fibrosis progression slows with time following LT on immunosuppression and approximates the pretransplant progression rate by year 5.
Short article: Aspiration of capsule endoscopes: a comprehensive review of the existing literature
Authors: Yung Diana E. , Plevris John N. , Koulaouzidis Anastasios
Published: January 2017

Introduction

Capsule endoscopy (CE) has an excellent safety profile. Although retention is the most cited complication, capsule aspiration is less frequent and is often reported only as isolated cases. This study represents a systematic effort to compile and scrutinize the available data on capsule aspiration to provide comprehensive and conclusive information on this CE complication.

Materials and methods

A systematic literature search was performed in PubMed, Embase and Chinese National Knowledge Infrastructure. The search terms used were ‘capsule endoscopy’ AND ‘aspiration’ (both terms searched as keyword and MeSH). We included case reports and/or series on capsule aspiration, as well as observational cohort studies that reported capsule aspiration among their complications/outcomes.

Results

Thirty-four case reports with 37 cases of capsule aspiration were identified. A further four observational studies reported aspiration as part of a cohort of patients undergoing CE. 94.6% of aspirations occurred in elderly men. 87.1% had significant comorbidities. 59.5% had symptoms on aspiration, with cough reported most frequently. The most common location of aspiration was the right main bronchus. Half of the patients required intervention for capsule retrieval; bronchoscopy was the most common management, with good effect. There was a single fatality following capsule aspiration, not directly related to the procedure, and one case of aspiration pneumonia. Outcomes were good for all other patients. The estimated overall aspiration rate is 0.1%.

Conclusion

Although very rare and generally safely managed, capsule aspiration should be anticipated in certain patient groups and capsule administration should be approached with necessary precautions.
Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine – Part 2: Immunohistochemistry Test Performance Characteristics
Authors: Torlakovic Emina E. , Cheung Carol C. , D’Arrigo Corrado , Dietel Manfred , Francis Glenn D. , Gilks C. Blake , Hall Jacqueline A. , Hornick Jason L. , Ibrahim Merdol , Marchetti Antonio , Miller Keith , van Krieken J. Han , Nielsen Soren , Swanson Paul E. , Vyberg Mogens , Zhou Xiaoge , Taylor Clive R.
Published: January 2017

All laboratory tests have test performance characteristics (TPCs), whether or not they are explicitly known to the laboratorian or the pathologist. TPCs are thus also an integral characteristic of immunohistochemistry (IHC) tests and other in situ, cell-based molecular assays such as DNA or RNA in situ hybridization or aptamer-based testing. Because of their descriptive, in situ, cell-based nature, IHC tests have a limited repertoire of appropriate TPCs. Although only a few TPCs are relevant to IHC, proper selection of informative TPCs is nonetheless essential for the development of and adherence to appropriate quality assurance measures in the IHC laboratory. This paper describes the TPCs that are relevant to IHC testing and emphasizes the role of TPCs in the validation of IHC tests. This is part 2 of the 4-part series “Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine.”
RAS-expanded Mutations and HER2 Expression in Metastatic Colorectal Cancer: A New Step of Precision Medicine
Authors: Valentini Anna M. , Cavalcanti Elisabetta , Di Maggio Marianna , Caruso Maria L.
Published: January 2017

Cetuximab and panitumumab monoclonal antibodies are a milestone in the history of treatment of metastatic colorectal cancer (mCRC) and point toward future directions for personalized treatment. Recent studies have shown that broader RAS testing is needed to select patients for targeted therapy. The objectives of our study were to identify the prevalence of RAS mutations and evaluate human epidermal growth factor receptor 2 (HER2) expression in KRAS exon 2 wild-type (WT) mCRC patients, correlating the findings with objective response rate, progression-free survival, and overall survival. In total, 29 mCRC patients undergoing treatment with cetuximab therapy were enrolled in this study. By pyrosequencing, mutations were found in 17% of nonresponder patients, in KRAS codon 146 and NRAS codon 12. HER2 positivity was limited to only 1 responder carcinoma specimen. There was no correlation between RAS mutation, HER2/neu expression, and clinicopathologic findings. We highlighted significantly the differences between objective response rate and RAS gene status. The overall survival and progression-free survival of RAS WT patients were higher compared with those with RAS-mutated disease. Clinical response to cetuximab therapy is impaired in the presence of RAS-expanded mutations. In fact, our finding of 5 mutations in RAS-expanded genes allowed us to understand the resistance to cetuximab in 33% of KRAS WT exon 2 nonresponder patients. HER2 does not seem to be a potential biomarker for cetuximab-targeted therapy. These analyses suggest that the assessment of other biomarkers is needed to determine the best treatment for patients with mCRC, to maximize benefit and minimize harm.
Imaging of the Lungs in Organ Donors and its Clinical Relevance
Authors: Bozovic Gracijela , Adlercreutz Catharina , Höglund Peter , Björkman-Burtscher Isabella , Reinstrup Peter , Ingemansson Richard , Schaefer-Prokop Cornelia , Siemund Roger , Geijer Mats
Published: January 2017

Purpose:

The aim of the study was to retrospectively evaluate the diagnostic imaging that potential lung donors undergo, the reader variability of image interpretation and its relevance for donation, and the potential information gained from imaging studies not primarily intended for lung evaluation but partially including them.

Materials and Methods:

Bedside chest radiography and computed tomography (CT), completely or incompletely including the lungs, of 110 brain-dead potential organ donors in a single institution during 2007 to 2014 were reviewed from a donation perspective. Two chest radiologists in consensus analyzed catheters and cardiovascular, parenchymal, and pleural findings. Clinical reports and study review were compared for substantial differences in findings that could have led to a treatment change, triggered additional examinations such as bronchoscopy, or were considered important for donation.

Results:

Among 136 bedside chest radiographs, no differences between clinical reports and study reviews were found in 37 (27%), minor differences were found in 28 (21%), and substantial differences were found in 71 (52%) examinations (P<0.0001). In 31 of 42 (74%) complete or incomplete CT examinations, 50 of 74 findings with relevance for lung donation were not primarily reported (P<0.0001).

Conclusions:

The majority of donor patients undergo only chest radiography. A targeted imaging review of abnormalities affecting the decision to use donor lungs may be useful in the preoperative stage. With a targeted list, substantial changes were made from initial clinical interpretations. CT can provide valuable information on donor lung pathology, even if the lungs are only partially imaged.
Imaging in Chronic Thromboembolic Pulmonary Hypertension
Authors: Renapurkar Rahul D. , Shrikanthan Sankaran , Heresi Gustavo A. , Lau Charles T. , Gopalan Deepa
Published: January 2017

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the potentially curable causes of pulmonary hypertension and is definitively treated with pulmonary thromboendartectomy. CTEPH can be overlooked, as its symptoms are nonspecific and can be mimicked by a wide range of diseases that can cause pulmonary hypertension. Early diagnosis of CTEPH and prompt evaluation for surgical candidacy are paramount factors in determining future outcomes. Imaging plays a central role in the diagnosis of CTEPH and patient selection for pulmonary thromboendartectomy and balloon pulmonary angioplasty. Currently, various imaging tools are used in concert, with techniques such as computed tomography (CT) and conventional pulmonary angiography providing detailed structural information, tests such as ventilation-perfusion (V/Q) scanning providing functional data, and magnetic resonance imaging providing a combination of morphologic and functional information. Emerging techniques such as dual-energy CT and single photon emission computed tomography-CT V/Q scanning promise to provide both anatomic and functional information in a single test and may change the way we image these patients in the near future. In this review, we discuss the roles of various imaging techniques and discuss their merits, limitations, and relative strengths in depicting the structural and functional changes of CTEPH. We also explore newer imaging techniques and the potential value they may offer.
Contributions of low- and high-level properties to neural processing of visual scenes in the human brain
Authors: Groen Iris I. A. , Silson Edward H. , Baker Chris I.
Published: January 2017

Visual scene analysis in humans has been characterized by the presence of regions in extrastriate cortex that are selectively responsive to scenes compared with objects or faces. While these regions have often been interpreted as representing high-level properties of scenes (e.g. category), they also exhibit substantial sensitivity to low-level (e.g. spatial frequency) and mid-level (e.g. spatial layout) properties, and it is unclear how these disparate findings can be united in a single framework. In this opinion piece, we suggest that this problem can be resolved by questioning the utility of the classical low- to high-level framework of visual perception for scene processing, and discuss why low- and mid-level properties may be particularly diagnostic for the behavioural goals specific to scene perception as compared to object recognition. In particular, we highlight the contributions of low-level vision to scene representation by reviewing (i) retinotopic biases and receptive field properties of scene-selective regions and (ii) the temporal dynamics of scene perception that demonstrate overlap of low- and mid-level feature representations with those of scene category. We discuss the relevance of these findings for scene perception and suggest a more expansive framework for visual scene analysis.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Contextual modulation of primary visual cortex by auditory signals
Authors: Petro L. S. , Paton A. T. , Muckli L.
Published: January 2017

Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013
Curr. Opin. Neurobiol.
23
, 195–201. (
doi:10.1016/j.conb.2013.01.020
)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter
et al.
2014
Curr. Biol.
24
, 1256–1262. (
doi:10.1016/j.cub.2014.04.020
)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
Auditory multistability and neurotransmitter concentrations in the human brain
Authors: Kondo Hirohito M. , Farkas Dávid , Denham Susan L. , Asai Tomohisa , Winkler István
Published: January 2017

Multistability in perception is a powerful tool for investigating sensory–perceptual transformations, because it produces dissociations between sensory inputs and subjective experience. Spontaneous switching between different perceptual objects occurs during prolonged listening to a sound sequence of tone triplets or repeated words (termed auditory streaming and verbal transformations, respectively). We used these examples of auditory multistability to examine to what extent neurochemical and cognitive factors influence the observed idiosyncratic patterns of switching between perceptual objects. The concentrations of glutamate–glutamine (Glx) and γ-aminobutyric acid (GABA) in brain regions were measured by magnetic resonance spectroscopy, while personality traits and executive functions were assessed using questionnaires and response inhibition tasks. Idiosyncratic patterns of perceptual switching in the two multistable stimulus configurations were identified using a multidimensional scaling (MDS) analysis. Intriguingly, although switching patterns within each individual differed between auditory streaming and verbal transformations, similar MDS dimensions were extracted separately from the two datasets. Individual switching patterns were significantly correlated with Glx and GABA concentrations in auditory cortex and inferior frontal cortex but not with the personality traits and executive functions. Our results suggest that auditory perceptual organization depends on the balance between neural excitation and inhibition in different brain regions.

This article is part of the themed issue ‘Auditory and visual scene analysis'.
How is visual salience computed in the brain? Insights from behaviour, neurobiology and modelling
Authors: Veale Richard , Hafed Ziad M. , Yoshida Masatoshi
Published: January 2017

Inherent in visual scene analysis is a bottleneck associated with the need to sequentially sample locations with foveating eye movements. The concept of a ‘saliency map’ topographically encoding stimulus conspicuity over the visual scene has proven to be an efficient predictor of eye movements. Our work reviews insights into the neurobiological implementation of visual salience computation. We start by summarizing the role that different visual brain areas play in salience computation, whether at the level of feature analysis for bottom-up salience or at the level of goal-directed priority maps for output behaviour. We then delve into how a subcortical structure, the superior colliculus (SC), participates in salience computation. The SC represents a visual saliency map via a centre-surround inhibition mechanism in the superficial layers, which feeds into priority selection mechanisms in the deeper layers, thereby affecting saccadic and microsaccadic eye movements. Lateral interactions in the local SC circuit are particularly important for controlling active populations of neurons. This, in turn, might help explain long-range effects, such as those of peripheral cues on tiny microsaccades. Finally, we show how a combination of
in vitro
neurophysiology and large-scale computational modelling is able to clarify how salience computation is implemented in the local circuit of the SC.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
An auditory illusion reveals the role of streaming in the temporal misallocation of perceptual objects
Authors: Mehta Anahita H. , Jacoby Nori , Yasin Ifat , Oxenham Andrew J. , Shamma Shihab A.
Published: January 2017

This study investigates the neural correlates and processes underlying the ambiguous percept produced by a stimulus similar to Deutsch's ‘octave illusion’, in which each ear is presented with a sequence of alternating pure tones of low and high frequencies. The same sequence is presented to each ear, but in opposite phase, such that the left and right ears receive a high–low–high … and a low–high–low … pattern, respectively. Listeners generally report hearing the illusion of an alternating pattern of low and high tones, with all the low tones lateralized to one side and all the high tones lateralized to the other side. The current explanation of the illusion is that it reflects an illusory feature conjunction of pitch and perceived location. Using psychophysics and electroencephalogram measures, we test this and an alternative hypothesis involving synchronous and sequential stream segregation, and investigate potential neural correlates of the illusion. We find that the illusion of alternating tones arises from the synchronous tone pairs across ears rather than sequential tones in one ear, suggesting that the illusion involves a misattribution of time across perceptual streams, rather than a misattribution of location within a stream. The results provide new insights into the mechanisms of binaural streaming and synchronous sound segregation.

This article is part of the themed issue ‘Auditory and visual scene analysis’.
The singular nature of auditory and visual scene analysis in autism
Authors: Lin I.-Fan , Shirama Aya , Kato Nobumasa , Kashino Makio
Published: January 2017

Individuals with autism spectrum disorder often have difficulty acquiring relevant auditory and visual information in daily environments, despite not being diagnosed as hearing impaired or having low vision. Resent psychophysical and neurophysiological studies have shown that autistic individuals have highly specific individual differences at various levels of information processing, including feature extraction, automatic grouping and top-down modulation in auditory and visual scene analysis. Comparison of the characteristics of scene analysis between auditory and visual modalities reveals some essential commonalities, which could provide clues about the underlying neural mechanisms. Further progress in this line of research may suggest effective methods for diagnosing and supporting autistic individuals.

This article is part of the themed issue ‘Auditory and visual scene analysis'.
Composite measurements and molecular compressed sensing for highly efficient transcriptomics
Authors: Cleary Brian , Cong Le , Lander Eric S. , Regev Aviv
Published: January 2017

RNA profiling is an excellent phenotype of cellular responses and tissue states, but can be costly to generate at the massive scale required for studies of regulatory circuits, genetic states or perturbation screens. Here, we draw on a series of advances over the last decade in the field of mathematics to establish a rigorous link between biological structure, data compressibility, and efficient data acquisition. We propose that very few random composite measurements – in which gene abundances are combined in a random linear combination – are needed to approximate the high-dimensional similarity between any pair of gene abundance profiles. We then show how finding latent, sparse representations of gene expression data would enable us to “decompress” a small number of random composite measurements and recover high-dimensional gene expression levels that were not measured (unobserved). We present a new algorithm for finding sparse, modular structure, which improves the ability to interpret samples in terms of small numbers of active modules, and show that the modular structure we find is sufficient to recover gene expression profiles from composite measurements (with ~100-fold fewer composite measurements than genes). Moreover, the knowledge that sparse, modular structures exist allows us to recover expression profiles from composite measurements, even without access to any training data. Finally, we present a proof-of-concept experiment for making composite measurements in the laboratory, involving the measurement of linear combinations of RNA abundances. Altogether, our results suggest new compressive modalities in experimental biology that can form a foundation for massive scaling in high-throughput measurements, while also offering new insights into the interpretation of high-dimensional data.