bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of squamous cell and basal cell carcinomas of the head and neck with perineural invasion
Authors: Gupta Aakriti , Veness Michael , De'Ambrosis Brian , Selva Dinesh , Huilgol Shyamala C
Published: March 2015

Perineural invasion (PNI) occurring in non‐melanoma skin cancers (NMSC) is associated with an increased risk of locoregional recurrence and reduced disease‐free survival. This necessitates early and accurate diagnosis, appropriate risk‐stratification and a clear management strategy. The diagnosis of PNI is based on careful clinical assessment, imaging and histopathology. Surgery, preferably with margin control, and definitive or adjuvant radiotherapy (ART) are established treatment strategies for PNI. Clinical uncertainty remains over the role of ART in incidental PNI. This review synthesises current literature to ascertain which clinicopathological features impart a higher risk to individuals with PNI in NMSC, in order to provide treatment algorithms, including the identification of patient subsets that are most likely to benefit from ART. This includes those with extratumoural PNI, involvement of larger‐calibre nerves, tumour invasion beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with clinical PNI may be optimally managed by a multidisciplinary head and neck cancer service that is best placed to offer skull base surgery and intensity‐modulated radiation therapy (IMRT). The management options presented are stratified by histological subtype and a new classification of PNI into low‐risk, medium‐risk and high‐risk groups.
Modified big‐bubble technique compared to manual dissection deep anterior lamellar keratoplasty in the treatment of keratoconus
Authors: Knutsson Karl Anders , Rama Paolo , Paganoni Giorgio
Published: March 2015

Purpose

To evaluate the clinical findings and results of manual dissection deep anterior lamellar keratoplasty (DALK) compared to a modified big‐bubble DALK technique in eyes affected by keratoconus.

Methods

Sixty eyes of 60 patients with keratoconus were treated with one of the two surgical techniques manual DALK (n = 30); big‐bubble DALK (n = 30). The main outcomes measured were visual acuity, corneal topographic parameters, thickness of residual stroma and endothelial cell density (ECD). Patients were examined postoperatively at 1 month, 6 months, 1 year and 1 month after suture removal.

Results

Final best spectacle‐corrected visual acuity (BSCVA) measured 1 month after suture removal was 0.11 ± 0.08 LogMAR in the big‐bubble group compared to 0.13 ± 0.08 in the manual DALK group (p = 0.227). In patients treated with the big‐bubble technique without complications (Descemet's membrane completely bared), the stromal residue was not measureable. Mean stromal residual thickness in the manual DALK group was 30.50 ± 27.60 μm. Data analysis of the manual DALK group demonstrated a significant correlation between BSCVA and residual stromal thickness; lower residual stromal thickness correlated with better BSCVA values (Spearman ρ = 0.509, p = 0.018). Postoperative ECD was similar in both groups at all intervals, with no statistically significant differences. In both groups, ECD loss was only significant during the 1‐ to 6‐month interval (p = 0.001 and p < 0.001 in the big‐bubble DALK and manual DALK groups, respectively).

Conclusion

Manual DALK provides comparable results to big‐bubble DALK. Big‐bubble DALK permits faster visual recovery and is a surgical technique, which can be easily converted to manual DALK in cases of unsuccessful ‘big‐bubble’ formation.
Myeloperoxidase evokes substantial vasomotor responses in isolated skeletal muscle arterioles of the rat
Authors: Csató V. , Pető A. , Fülöp G. Á. , Rutkai I. , Pásztor E. T. , Fagyas M. , Kalász J. , Édes I. , Tóth A. , Papp Z.
Published: March 2015

Aims

Myeloperoxidase (MPO) catalyses the formation of a wide variety of oxidants, including hypochlorous acid (HOCl), and contributes to cardiovascular disease progression. We hypothesized that during its action MPO evokes substantial vasomotor responses.

Methods

Following exposure to MPO (1.92 mU mL−1) in the presence of increasing concentrations of hydrogen peroxide (H2O2), changes in arteriolar diameter of isolated gracilis skeletal muscle arterioles (SMAs) and coronary arterioles (CAs) and in the isometric force in basilar arteries (BAs) of the rat were monitored.

Results

Myeloperoxidase increased vascular tone to different degrees in CAs, SMAs and BAs. The mechanism of increased vasoconstriction was studied in detail in SMAs. MPO‐evoked vasoconstrictions were prevented by the MPO inhibitor 4‐aminobenzhydrazide (50 μm), by endothelium removal in the SMAs. Surprisingly, the HOCl scavenger L‐methionine (100 μm), the thromboxane A2 (TXA2) antagonist SQ‐29548 (1 μm) or the non‐specific cyclooxygenase (COX) antagonist indomethacin (1 μm) converted the MPO‐evoked vasoconstrictions to pronounced vasodilations in SMAs, not seen in the presence of H2O2. In contrast to noradrenaline‐induced vasoconstrictions, the MPO‐evoked vasoconstrictions were not accompanied by significant increases in arteriolar [Ca2+] levels in SMAs.

Conclusion

These data showed that H2O2‐derived HOCl to be a potent vasoconstrictor upon MPO application. HOCl activated the COX pathway, causing the synthesis and release of a TXA2‐like substance to increase the Ca2+ sensitivity of the contractile apparatus in vascular smooth muscle cells and thereby to augment H2O2‐evoked vasoconstrictions. Nevertheless, inhibition of the HOCl–COX–TXA2 pathway unmasked the effects of additional MPO‐derived radicals with a marked vasodilatory potential in SMAs.
Testing for independence in contingency tables with complex sample survey data
Authors: Lipsitz Stuart R. , Fitzmaurice Garrett M. , Sinha Debajyoti , Hevelone Nathanael , Giovannucci Edward , Hu Jim C.
Published: March 2015

The test of independence of row and column variables in a contingency table is a widely used statistical test in many areas of application. For complex survey samples, use of the standard Pearson chi‐squared test is inappropriate due to correlation among units within the same cluster. Rao and Scott (1981, Journal of the American Statistical Association 76, 221–230) proposed an approach in which the standard Pearson chi‐squared statistic is multiplied by a design effect to adjust for the complex survey design. Unfortunately, this test fails to exist when one of the observed cell counts equals zero. Even with the large samples typical of many complex surveys, zero cell counts can occur for rare events, small domains, or contingency tables with a large number of cells. Here, we propose Wald and score test statistics for independence based on weighted least squares estimating equations. In contrast to the Rao–Scott test statistic, the proposed Wald and score test statistics always exist. In simulations, the score test is found to perform best with respect to type I error. The proposed method is motivated by, and applied to, post surgical complications data from the United States’ Nationwide Inpatient Sample (NIS) complex survey of hospitals in 2008.
Heat Shock Protein 47 Promotes Glioma Angiogenesis
Authors: Wu Zhe Bao , Cai Lin , Lin Shao Jian , Leng Zhi Gen , Guo Yu Hang , Yang Wen Lei , Chu Yi Wei , Yang Shao‐Hua , Zhao Wei Guo
Published: March 2015

Heat shock protein 47 (HSP47) is a collagen‐binding protein, which has been recently found to express in glioma vessels. However, the expression profile of HSP47 in glioma patients and the underlying mechanisms of HSP47 on glioma angiogenesis are not fully explored. In the current study, we found that expression of HSP47 in glioma vessels was correlated with the grades of gliomas. HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31 immunohistochemistry in vivo. HSP47 knockdown significantly inhibited tube formation, invasion and proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, conditional medium derived from HSP47 knockdown cells significantly inhibited HUVECs tube formation and migration, while it increased chemosensitivity of HUVECs cells to Avastin. Silencing of HSP47 decreased VEGF expression in glioma cells consistently, and reduced glioma vasculature. Furthermore, HSP47 promoted glioma angiogenesis through HIF1α‐VEGFR2 signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis and highlights the importance of HSP47 as an attractive therapeutic target of GBM.
Measurement Issues: Is standardised diagnostic assessment feasible as an adjunct to clinical practice? A systematic review
Authors: Reeves Katie , Charter Ella , Ford Tamsin
Published: March 2015

Background

A standardised diagnostic assessment (SDA) is a comprehensive assessment of psychiatric disorder that provides a label according to established diagnostic criteria. While standardised assessments are considered essential in child and adolescent mental health research, they are rarely applied systematically in routine clinical practice.

Method

A systematic review of studies that assessed the utility, feasibility and acceptability of SDAs in the assessment of psychopathology among children and young people in routine clinical practice.

Results

Eight papers were identified that applied mixed research methods. Overall, attitudes towards SDAs were positive, with lack of training in administration and interpretation of SDAs and a concern for the validity of diagnostic categories being key barriers. Two randomised control trials and a case series suggest that SDAs might aid the detection of emotional disorders in particular.

Conclusion

The current evidence is not yet sufficient to recommend that SDAs should be universally adopted as an adjunct to clinical practice, but our findings suggest that can they be used if applied cautiously and mindfully pending further evaluation.
Attention and normalization circuits in macaque V1
Authors: Sanayei M. , Herrero J. L. , Distler C. , Thiele A.
Published: March 2015

Attention affects neuronal processing and improves behavioural performance. In extrastriate visual cortex these effects have been explained by normalization models, which assume that attention influences the circuit that mediates surround suppression. While normalization models have been able to explain attentional effects, their validity has rarely been tested against alternative models. Here we investigate how attention and surround/mask stimuli affect neuronal firing rates and orientation tuning in macaque V1. Surround/mask stimuli provide an estimate to what extent V1 neurons are affected by normalization, which was compared against effects of spatial top down attention. For some attention/surround effect comparisons, the strength of attentional modulation was correlated with the strength of surround modulation, suggesting that attention and surround/mask stimulation (i.e. normalization) might use a common mechanism. To explore this in detail, we fitted multiplicative and additive models of attention to our data. In one class of models, attention contributed to normalization mechanisms, whereas in a different class of models it did not. Model selection based on Akaike's and on Bayesian information criteria demonstrated that in most cells the effects of attention were best described by models where attention did not contribute to normalization mechanisms. This demonstrates that attentional influences on neuronal responses in primary visual cortex often bypass normalization mechanisms.
Expression of freezing and fear‐potentiated startle during sustained fear in mice
Authors: Daldrup T. , Remmes J. , Lesting J. , Gaburro S. , Fendt M. , Meuth P. , Kloke V. , Pape H.‐C. , Seidenbecher T.
Published: March 2015

Fear‐potentiated acoustic startle paradigms have been used to investigate phasic and sustained components of conditioned fear in rats and humans. This study describes a novel training protocol to assess phasic and sustained fear in freely behaving C57BL/6J mice, using freezing and/or fear‐potentiated startle as measures of fear, thereby, if needed, allowing in vivo application of various techniques, such as optogenetics, electrophysiology and pharmacological intervention, in freely behaving animals. An auditory Pavlovian fear conditioning paradigm, with pseudo‐randomized conditioned–unconditioned stimulus presentations at various durations, is combined with repetitive brief auditory white noise burst presentations during fear memory retrieval 24 h after fear conditioning. Major findings are that (1) a motion sensitive platform built on mechano‐electrical transducers enables measurement of startle responses in freely behaving mice, (2) absence or presence of startle stimuli during retrieval as well as unpredictability of a given threat determine phasic and sustained fear response profiles and (3) both freezing and startle responses indicate phasic and sustained components of behavioral fear, with sustained freezing reflecting unpredictability of conditioned stimulus (CS)/unconditioned stimulus (US) pairings. This paradigm and available genetically modified mouse lines will pave the way for investigation of the molecular and neural mechanisms relating to the transition from phasic to sustained fear.
Externalities or Experience? Localization Economies and Start‐up Business Survival
Authors: Renski Henry
Published: March 2015

This study examines whether spatial variations in the human capital of business owners help explain why the failure rates of new businesses tend to be lower in areas where similar businesses are concentrated. More specifically,Itest whether the prior industry experience of the firm's owner/founder has a mediating influence on the relationship between industrial localization and new business failure for six industry sectors. Localization is found to have either a beneficial or a damaging relationship to new firm survival, depending on the industry in question. Localization reduces the likelihood of failure in two sectors, while competition effects prevail in two others. When industry experience is added to the models, the benefits of localization diminish, but only for entrants in the business, professional, and information services sector and only by a small amount. This suggests that at least some of the observed benefits of localization are due to regional differences in embodied human capital, but localization economies remain significant. Further study is needed to see if such mediating effects are common among a wider array of more narrowly defined industries and for other forms of entrepreneurial human capital.
How Effects of Local Labor Demand Shocks Vary with the Initial Local Unemployment Rate
Authors: Bartik Timothy J.
Published: March 2015

This article estimates how effects of local labor demand shocks on labor market outcomes vary with the initial local unemployment rate, which has not been previously studied. The data are on 23 large U.S. metro areas from 1979 to 2011. The article finds that demand shocks to local job growth have greater effects in increasing real wages if the local economy initially has low unemployment. However, demand shocks have greater effects in reducing unemployment, and increasing labor force participation, if the local economy initially has high unemployment, although these differences are only of modest statistical significance. The estimates are based on a new econometric approach to determining the correct dynamic structure for how local labor markets respond to demand shocks. This new approach finds that demand shocks have persistent effects on labor force participation and real wages, but not on unemployment, which contradicts some previous research.
The Qualitative Problem of Major Quotation Errors, as Illustrated by 10 Different Examples in the Headache Literature
Authors: Tfelt‐Hansen Peer
Published: March 2015

There are two types of errors when references are used in the scientific literature: citation errors and quotation errors, and these errors have in reviews mainly been evaluated quantitatively. Quotation errors are the major problem, and 1 review reported 6% major quotation errors. The objective of this listing of quotation errors is to illustrate by qualitative analysis of different types of 10 major quotation errors how and possibly why authors misquote references.

The author selected for review the first 10 different consecutive major quotation errors encountered from his reading of the headache literature.

The characteristics of the 10 quotation errors ranged considerably. Thus, in a review of migraine therapy in a very prestigious medical journal, the superiority of a new treatment (sumatriptan) vs an old treatment (aspirin plus metoclopramide) was claimed despite no significant difference for the primary efficacy measure in the trial. One author, in a scientific debate, referred to the lack of dilation of the middle meningeal artery in spontaneous migraine despite the fact that only 1 migraine attack was studied.

The possibility for creative major quotation errors in the medical literature is most likely infinite. Qualitative evaluations, as the present, of major quotation errors will hopefully result in more general awareness of quotation problems in the medical literature.

Even if the final responsibility for correct use of quotations is with the authors, the referees, the experts with the knowledge needed to spot quotation errors, should be more involved in ensuring correct and fair use of references. Finally, this paper suggests that major misleading quotations, if pointed out by readers of the journal, should, as a rule, be corrected by way of an erratum statement.
Strengths and capabilities of Chinese patients with severe ocular injuries: A qualitative study
Authors: Guo Xiaodong , Saito Shinobu , Yamamoto Toshie
Published: March 2015

The purpose of this qualitative study is to illustrate health‐centred nursing by assessing the capabilities of patients with acute and severe ocular injuries. This study draws upon analyzing 17 nursing encounters with four adult male patients admitted to the ophthalmological ward of a university hospital in a rural Chinese city. The analysis identified that patients demonstrated the following strengths: (i) comprehension; (ii) self‐reflection and examination; (iii) cooperation; (iv) patience and self‐control; (v) self‐efficacy; (vi) proactive acceptance; (vii) independence and a positive attitude towards challenges; (viii) support from family members; (ix) volition; and (x) flexibility. The results of this study highlight the importance of observing patients, assessing their abilities and helping them mobilize these strengths for recovery.
Salt Stress Delayed Flowering and Reduced Reproductive Success of Chickpea (Cicer arietinum L.), A Response Associated with Na+ Accumulation in Leaves
Authors: Pushpavalli R. , Quealy J. , Colmer T. D. , Turner N. C. , Siddique K. H. M. , Rao M. V. , Vadez V.
Published: March 2015

Salinity is known to reduce chickpea yields in several regions of the world. Although ion toxicity associated with salinity leads to yield reductions in a number of other crops, its role in reducing yields in chickpea growing in saline soils is unclear. The purpose of this study was to (i) identify the phenological and yield parameters associated with salt stress tolerance and sensitivity in chickpea and (ii) identify any pattern of tissue ion accumulation that could relate to salt tolerance of chickpea exposed to saline soil in an outdoor pot experiment. Fourteen genotypes of chickpea (Cicer arietinum L.) were used to study yield parameters, of which eight were selected for ion analysis after being grown in soil treated with 0 and 80 mm NaCl. Salinity delayed flowering and the delay was greater in sensitive than tolerant genotypes under salt stress. Filled pod and seed numbers, but not seed size, were associated with seed yield in saline conditions, suggesting that salinity impaired reproductive success more in sensitive than tolerant lines. Of the various tissues measured for concentrations of Cl−, Na+ and K+, higher seed yields in saline conditions were positively correlated with higher K+ concentration in seeds at the mid‐filling stage (R2 = 0.55), a higher K+/Na+ ratio in the laminae of fully expanded young leaves (R2 = 0.50), a lower Na+ concentration in old green leaves (R2 = 0.50) and a higher Cl− concentration in mature seeds. The delay in flowering was associated with higher concentrations of Na+ in the laminae of fully expanded young leaves (R2 = 0.61) and old green leaves (R2 = 0.51). We conclude that although none of the ions appeared to have any toxic effect, Na+ accumulation in leaves was associated with delayed flowering that in turn could have played a role in the lower reproductive success in the sensitive lines.
Exploring the Effect of Arrest Across a Domestic Batterer Typology
Authors: Johnson Richard R. , Goodlin‐Fahncke Wendi
Published: March 2015

While arrest is a common intervention utilized in intimate partner violence, it is not known if this strategy affects all types of offenders equally. The present study used data from three of the Spousal Assault Replication Program (SARP) studies to examine the deterrent effect of arrest on four different batterer subtypes (those identified by Holtzworth‐Munroe and Stuart, 1994) among a sample of 2,412 heterosexual male batterers. The results indicated that arrest increased the recidivism of IPV for two of the batterer subtypes (generally violent/antisocial and low‐level antisocial subtypes), suggesting the need for pre‐trial protection of victims.
Effects of Grape Seed Powder and Whey Protein on Quality Characteristics of Chicken Nuggets
Authors: Kumcuoglu Seher , Cagdas Ece
Published: March 2015

In this study, two different treatments and their effects on quality characteristics of chicken nuggets after three different cooking procedures were evaluated. Batters containing grape seed powder (GSP) dipped into whey protein solution (WPS) were compared with control (without any treatment) using deep fat frying, conventional oven and microwave oven. Batters contained equal amounts of wheat and corn flours with 5 and 10% GSP. All batters exhibited thixotropic behavior, and the GSP enhanced batters had lower viscosities. The lowest pickup values and highest total color change (ΔE) values were observed in deep fat fried samples. The microwaved samples had higher crispness levels and pickup values but achieved lighter colors that were identical to those of the pre‐fried samples. Samples dipped into WPS provided reduced oil absorption consistent with their moisture contents. The scores for overall acceptability tended to decrease with the increase in GSP amount.

Practical Applications

This study shows the effects of grape seed and whey protein solution treatments on batter quality as well as their interaction with cooking procedures. Although negative impressions toward battered and fried food products have been increased, consumers are becoming aware of health and nutritional food concepts. Therefore, new strategies are necessary in order to obtain healthier battered and fried foods without compromising the sensory quality. Grape seed powder is a promising ingredient as well as whey protein solution treatment as a post dip for improving the major components of frying batter in terms of textural properties, flow behavior, oil uptake and batter pickup. The results of this study could be helpful in the development of novel fried nuggets that include natural antioxidants having similar characteristics with grape seed powder.
A Randomised trial to investigate the erosive effect of hot drinks
Authors: Hooper S. M. , Macdonald E. L. , Addy M. , Antognozzi M. , Davies M. , West N. X.
Published: March 2015

Research on dental erosion has largely been undertaken at room temperature despite fruit juice drinks often being consumed at elevated temperatures in the United Kingdom, notably during periods of convalesce. The aim of the study was to evaluate the erosive potential of two fruit juices containing acidic non‐alcoholic drinks at elevated temperatures in situ on human enamel after 5, 10 and 15 days. A commercially available conventional apple and blackcurrant fruit juice drink was compared to a blackcurrant juice drink modified to have low erosive potential, and mineral water consumed at approximately 59 °C. Twenty‐one healthy volunteers aged 18 or over participated in a single‐centre, single‐blind (blinded to the investigator), three‐treatment crossover study. Subjects were randomised to a treatment sequence using a Latin square design. Subjects wore upper removable appliances containing one human enamel specimen from 9 am to 5 pm for 15 days for each beverage. Measurements of enamel loss were recorded after 5, 10 and 15 days by contact surface profilometry. The low erosive blackcurrant drink caused significantly less enamel loss (P < 0·05) than the commercially available conventional apple and blackcurrant fruit juice drink and was not statistically significantly different to mineral water at any of the time points in the study. Consuming the modified low erosive blackcurrant drink at an elevated temperature resulted in negligible enamel loss in situ, consistent with room temperature findings.
Nature and psychological management of anxiety disorders in youth
Authors: Rapee Ronald M
Published: March 2015

Anxiety disorders affect around 5% of the paediatric population at any given time and are associated with high social and personal impact. These disorders typically begin early in life, and children with anxiety disorders are at increased risk for a variety of later difficulties across the life‐span. Although causes of anxiety in childhood are not fully understood, there is a strong heritable component. Additional risk factors include temperament, parent psychopathology, parent handling and peer interactions. Psychological treatments have demonstrated good efficacy with around 60% of anxious youth being in diagnostic remission immediately following treatment and a further 10% remitting over the following months. Because young people with anxiety disorders are among the least likely to seek appropriate help, paediatricians are in a unique position to identify anxious young people, educate families and recommend appropriate intervention.
Genetic divergence of weedy rice populations associated with their geographic location and coexisting conspecific crop: Implications on adaptive evolution of agricultural weeds
Authors: Song Zhuo‐Jun , Wang Zhe , Feng Yang , Yao Nan , Yang Ji , Lu Bao‐Rong
Published: March 2015

Weedy rice, the same biological species of cultivated rice, is a noxious weed that infests rice fields worldwide. To determine the genetic diversity, structure, and relationships of weedy rice in China, we applied insertion/deletion (InDel) molecular fingerprints to analyze weedy rice populations from northeastern to southern rice planting regions, using japonica and indica rice cultivars as references. The InDel fingerprints indicated relatively high overall genetic diversity (He = 0.42) for the 240 samples from 14 weedy rice populations. However, much lower within‐population diversity was detected, particularly for populations from northeastern and southern China, with the He value ranging from 0.006 to 0.06. Jiangsu populations showed much higher within‐population genetic diversity (He = 0.12–0.31) than those from other regions. Analysis of molecular variance and Fst showed ∼88% genetic variation among weedy rice populations. Principal component and structure analyses indicated substantial japonica–indica genetic differentiation of weedy rice populations. Weedy rice from Jiangsu province was undergoing indica–japonica differentiation even within populations, which was likely due to the replacement of indica by japonica rice varieties in this region. In conclusion, significant genetic divergence has taken place among weedy rice populations in China, which is associated with their geographic locations and coexisting rice varieties. Introgression from cultivated rice has a critical role in shaping the genetic diversity and structure of weedy rice populations in agro‐ecosystems influenced by humans.
Antiviral therapy in chronic hepatitis E: a systematic review
Authors: Peters van Ton A. M. , Gevers T. J. G. , Drenth J. P. H.
Published: March 2015

Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon‐α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords ‘“Hepatitis E” or HEV’ AND ‘ribavirin or Rebetol or Copegus’ OR ‘pegylated interferon OR peginterferon′ were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty‐four studies matched our criteria, representing a total of 105 ribavirin‐treated and 8 pegylated interferon‐treated patients. The majority of patients had a solid organ transplant. Sixty‐four per cent of ribavirin‐treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon‐treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.
The effect of sex‐biased dispersal on opposite‐sexed spatial genetic structure and inbreeding risk
Authors: Blyton Michaela D. J. , Banks Sam C. , Peakall Rod
Published: March 2015

Natal sex‐biased dispersal has long been thought to reduce the risk of inbreeding by spatially separating opposite‐sexed kin. Yet, comprehensive and quantitative evaluations of this hypothesis are lacking. In this study, we quantified the effectiveness of sex‐biased dispersal as an inbreeding avoidance strategy by combining spatially explicit simulations and empirical data. We quantified the extent of kin clustering by measuring the degree of spatial autocorrelation among opposite‐sexed individuals (FMstructure). This allowed us to systematically explore how the extent of sex‐biased dispersal, generational overlap, and mate searching distance, influenced both kin clustering, and the resulting inbreeding in the absence of complementary inbreeding avoidance strategies. Simulations revealed that when sex‐biased dispersal was limited, positiveFMgenetic structure developed quickly and increased as the mate searching distance decreased or as generational overlap increased. Interestingly, complete long‐range sex‐biased dispersal did not prevent the development ofFMgenetic structure when generations overlapped. We found a very strong correlation betweenFMgenetic structure and bothFISunder random mating, and pedigree‐based measures of inbreeding. Thus, we show that the detection ofFMgenetic structure can be a strong indicator of inbreeding risk. Empirical data for two species with different life history strategies yielded patterns congruent with our simulations. Our study illustrates a new application of spatial genetic autocorrelation analysis that offers a framework for quantifying the risk of inbreeding that is easily extendable to other species. Furthermore, our findings provide other researchers with a context for interpreting observed patterns of opposite‐sexed spatial genetic structure.
Were Fertile Crescent crop progenitors higher yielding than other wild species that were never domesticated?
Authors: Preece Catherine , Livarda Alexandra , Wallace Michael , Martin Gemma , Charles Michael , Christin Pascal‐Antoine , Jones Glynis , Rees Mark , Osborne Colin P.
Published: March 2015

During the origin of agriculture in the Fertile Crescent, the broad spectrum of wild plant species exploited by hunter‐gatherers narrowed dramatically. The mechanisms responsible for this specialization and the associated domestication of plants are intensely debated. We investigated why some species were domesticated rather than others, and which traits they shared.

We tested whether the progenitors of cereal and pulse crops, grown individually, produced a higher yield and less chaff than other wild grasses and legumes, thereby maximizing the return per seed planted and minimizing processing time. We compared harvest traits of species originating from the Fertile Crescent, including those for which there is archaeological evidence of deliberate collection.

Unexpectedly, wild crop progenitors in both families had neither higher grain yield nor, in grasses, less chaff, although they did have larger seeds. Moreover, small‐seeded grasses actually returned a higher yield relative to the mass of seeds sown. However, cereal progenitors had threefold fewer seeds per plant, representing a major difference in how seeds are packaged on plants.

These data suggest that there was no intrinsic yield advantage to adopting large‐seeded progenitor species as crops. Explaining why Neolithic agriculture was founded on these species, therefore, remains an important unresolved challenge.
Arabidopsis EF‐Tu receptor enhances bacterial disease resistance in transgenic wheat
Authors: Schoonbeek Henk‐jan , Wang Hsi‐Hua , Stefanato Francesca L. , Craze Melanie , Bowden Sarah , Wallington Emma , Zipfel Cyril , Ridout Christopher J.
Published: March 2015

Perception of pathogen (or microbe)‐associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF‐Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF‐Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad‐spectrum bacterial disease resistance.

In this study, we developed a set of bioassays to study the activation of PAMP‐triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18.

We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication.

These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops.
Oral mucosal lesions in older people: relation to salivary secretion, systemic diseases and medications
Authors: Lynge Pedersen AM , Nauntofte B , Smidt D , Torpet LA
Published: March 2015

Objectives

To determine the prevalence of oral mucosal lesions in a sample of older Danish people and to investigate their associations with age, gender, systemic diseases, medications, xerostomia and salivary secretion.

Methods

A total of 668 community‐dwelling individuals aged 65–95 years underwent a clinical examination, measurements of unstimulated and stimulated whole and labial salivary flow rates and an interview regarding xerostomia, general health, medication, tobacco and alcohol habits.

Results

Seventy‐five per cent of all participants and 70% of the non‐medicated ones had one or more oral mucosal lesions. The most prevalent lesions were lingual varicosities (28.3%), denture stomatitis (12.7%), candidiasis (11.8%), fissured tongue (9.1%) and frictional keratosis (8.4%). Lesions were generally associated with smoking and xerostomia. Varicosities were more common in participants with systemic diseases and medication intake, particularly with cardiovascular diseases and agents. Fissured tongue and atrophic tongue were associated with female gender, xerostomia and low unstimulated whole and labial salivary secretion. Oral candidiasis was associated with older age; being male; current smoker; having >3 diseases, intake of medications and low salivary flow rates; and identified in relation to denture stomatitis, fissured tongue and atrophic tongue and median rhomboid glossitis.

Conclusions

Oral mucosal lesions are prevalent in older Danish people and generally associated with changes in both local and systemic factors. Tongue lesions in particular appeared as indicators that may identify patients with specific need of oral intervention.
Candida–streptococcal mucosal biofilms display distinct structural and virulence characteristics depending on growth conditions and hyphal morphotypes
Authors: Bertolini M.M. , Xu H. , Sobue T. , Nobile C.J. , Del Bel Cury A. A. , Dongari‐Bagtzoglou A.
Published: March 2015

Candida albicans and streptococci of the mitis group form communities in multiple oral sites, where moisture and nutrient availability can change spatially or temporally. This study evaluated structural and virulence characteristics of Candida–streptococcal biofilms formed on moist or semidry mucosal surfaces, and tested the effects of nutrient availability and hyphal morphotype on dual‐species biofilms. Three‐dimensional models of the oral mucosa formed by immortalized keratinocytes on a fibroblast‐embedded collagenous matrix were used. Infections were carried out using Streptococcus oralis strain 34, in combination with a C. albicans wild‐type strain, or pseudohyphal‐forming mutant strains. Increased moisture promoted a homogeneous surface biofilm by C. albicans. Dual biofilms had a stratified structure, with streptococci growing in close contact with the mucosa and fungi growing on the bacterial surface. Under semidry conditions, Candida formed localized foci of dense growth, which promoted focal growth of streptococci in mixed biofilms. Candida biofilm biovolume was greater under moist conditions, albeit with minimal tissue invasion, compared with semidry conditions. Supplementing the infection medium with nutrients under semidry conditions intensified growth, biofilm biovolume and tissue invasion/damage, without changing biofilm structure. Under these conditions, the pseudohyphal mutants and S. oralis formed defective superficial biofilms, with most bacteria in contact with the epithelial surface, below a pseudohyphal mass, resembling biofilms growing in a moist environment. The presence of S. oralis promoted fungal invasion and tissue damage under all conditions. We conclude that moisture, nutrient availability, hyphal morphotype and the presence of commensal bacteria influence the architecture and virulence characteristics of mucosal fungal biofilms.
Refractory cardiogenic shock in a patient with β‐thalassemia major requiring mechanical circulatory support: Case report and literature review
Authors: Horne David , Conway Jennifer , Kantor Paul F. , AlAklabi Mohammed M. , Anand Vijay , Bruce Aisha , Garcia Guerra Gonzalo , Rebeyka Ivan M. , Ross David B. , Buchholz Holger
Published: March 2015

Iron overload cardiomyopathy secondary to β‐thalassemia major is a potentially reversible condition managed with chelation and medical hemodynamic support, as bridge‐to‐recovery or transplant. We describe our experience, and challenges faced, in a pediatric patient with iron overload cardiomyopathy secondary to β‐thalassemia major, requiring biventricular MCS.
Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report
Authors: Hida Tomoyuki , Hamasaki Makoto , Matsumoto Shinji , Abe Sosei , Takakura Koji , Hiroshima Kenzo , Nabeshima Kazuki
Published: March 2015

A 67‐year‐old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round‐to‐oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2‐40, and CK5/6, focally positive for Ber‐EP4, but negative for WT‐1, TTF‐1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.
Coincidence of virulence shifts and population genetic changes of Pseudoperonospora cubensis in the Czech Republic
Authors: Kitner M. , Lebeda A. , Sharma R. , Runge F. , Dvořák P. , Tahir A. , Choi Y.‐J. , Sedláková B. , Thines M.
Published: March 2015

Pseudoperonospora cubensis is an oomycete pathogen causing downy mildew disease on a variety of Cucurbitaceae, and has recently re‐emerged as a destructive disease on crops in this family, mainly on cucumber and squash. Multilocus sequence analysis (MLSA) of four mitochondrial and two nuclear DNA regions was used to detect changes in the genetic structure of P. cubensis populations occurring in the Czech Republic that might be associated with recently reported shifts in virulence. The analysed sample set contains 67 P. cubensis isolates collected from 1995 to 2012 in the Czech Republic and some other European countries. Sequence analyses revealed differences and changes in the genetic backgrounds of P. cubensis isolates. While all isolates sampled before 2009 exhibited the genotype of the subspecies of Clade II and were collected from cucumber, all samples collected from other hosts belonged to Clade I (P. cubensis sensu stricto) or were sampled from 2009 onwards. In addition, 67·16% of all post‐2009 isolates from Clade II had two heterozygous positions in their nrITS sequence, which suggests sexual reproduction and/or a mutational origin. Thus, the results indicate that, apart from the rise in prevalence of Clade I, the change in the genetic structure of P. cubensis populations may be linked with a hybridization or, less likely, a mutation event that rendered strains able to infect a broader spectrum of host species.
Life Cycle Price Trends and Product Replacement: Implications for the Measurement of Inflation
Authors: Melser Daniel , Syed Iqbal A.
Published: March 2015

The paper explores the extent to which products follow systematic pricing patterns over their life cycle and the impact this has on the measurement of inflation. Using a large U.S. scanner data set on supermarket products and applying flexible regression methods, we find that on average prices decline as items age. This life cycle price change is often attributed to quality difference in the construction of CPI as items are replaced due to disappearance or during sample rotations. This introduces a systematic bias in the measurement of inflation. For our data we find that the life cycle bias leads to the underestimation of inflation by around 0.30 percentage points each year for the products examined.
Economic Growth Evens Out Happiness: Evidence from Six Surveys
Authors: Clark Andrew E. , Flèche Sarah , Senik Claudia
Published: March 2015

In spite of the great U‐turn that saw income inequality rise in Western countries in the 1980s, happiness inequality has fallen in countries that have experienced income growth (but not in those that did not). Modern growth has reduced the share of both the “very unhappy” and the “perfectly happy.” Lower happiness inequality is found both between and within countries, and between and within individuals. Our cross‐country regression results suggest that the extension of various public goods helps to explain this greater happiness homogeneity. This new stylized fact arguably comes as a bonus to the Easterlin paradox, offering a somewhat brighter perspective for developing countries.
Identification of a novel HLA allele, HLA‐B*53:39, in a Guadaloupean individual
Authors: Proust B. , Masson D. , Giraud C. , Bouille C. , Dehaut F. , Assaqa A. , Jollet I.
Published: March 2015

The novel HLA‐B*53:39 allele differs from HLA‐B*53:01 by a single nucleotide substitution at codon 45 (ACG>AAG).
The glucosinolate breakdown product indole‐3‐carbinol acts as an auxin antagonist in roots of Arabidopsis thaliana
Authors: Katz Ella , Nisani Sophia , Yadav Brijesh S. , Woldemariam Melkamu G. , Shai Ben , Obolski Uri , Ehrlich Marcelo , Shani Eilon , Jander Georg , Chamovitz Daniel A.
Published: March 2015

The glucosinolate breakdown product indole‐3‐carbinol functions in cruciferous vegetables as a protective agent against foraging insects. While the toxic and deterrent effects of glucosinolate breakdown on herbivores and pathogens have been studied extensively, the secondary responses that are induced in the plant by indole‐3‐carbinol remain relatively uninvestigated. Here we examined the hypothesis that indole‐3‐carbinol plays a role in influencing plant growth and development by manipulating auxin signaling. We show that indole‐3‐carbinol rapidly and reversibly inhibits root elongation in a dose‐dependent manner, and that this inhibition is accompanied by a loss of auxin activity in the root meristem. A direct interaction between indole‐3‐carbinol and the auxin perception machinery was suggested, as application of indole‐3‐carbinol rescues auxin‐induced root phenotypes. In vitro and yeast‐based protein interaction studies showed that indole‐3‐carbinol perturbs the auxin‐dependent interaction of Transport Inhibitor Response (TIR1) with auxin/3‐indoleacetic acid (Aux/IAAs) proteins, further supporting the possibility that indole‐3‐carbinol acts as an auxin antagonist. The results indicate that chemicals whose production is induced by herbivory, such as indole‐3‐carbinol, function not only to repel herbivores, but also as signaling molecules that directly compete with auxin to fine tune plant growth and development.
Light stress and photoprotection in Chlamydomonas reinhardtii
Authors: Erickson Erika , Wakao Setsuko , Niyogi Krishna K.
Published: March 2015

Plants and algae require light for photosynthesis, but absorption of too much light can lead to photo‐oxidative damage to the photosynthetic apparatus and sustained decreases in the efficiency and rate of photosynthesis (photoinhibition). Light stress can adversely affect growth and viability, necessitating that photosynthetic organisms acclimate to different environmental conditions in order to alleviate the detrimental effects of excess light. The model unicellular green alga, Chlamydomonas reinhardtii, employs diverse strategies of regulation and photoprotection to avoid, minimize, and repair photo‐oxidative damage in stressful light conditions, allowing for acclimation to different and changing environments.