bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Team Cognitive Styles on Performance of Radical and Incremental NPD Projects
Authors: de Visser Matthias , Faems Dries , Visscher Klaasjan , de Weerd‐Nederhof Petra
Published: October 2014

Although prior studies increased our understanding of the performance implications of new product development (NPD) team members' functional backgrounds and demographic variables, they remained relatively silent on the impact of underlying psychological characteristics such as the team members' cognitive styles on project performance. The goal of this study is to explore the effects of NPD teams' cognitive styles on project performance in different kinds of NPD projects. Based on survey data from members of 95 NPD teams gathered in four Dutch manufacturing companies, hypotheses about the relationships between teams' cognitive styles and project performance of radical and incremental NPD projects are tested. Results of linear regression analyses show that the level of teams' analytical information processing positively affects project performance in both incremental and radical NPD projects, whereas the relationship between the level of teams' intuitive information processing and project performance depends on the radicalness of the project. These findings contribute to the academic discussion on team innovation, suggesting that, next to demographic and functional characteristics, cognitive styles in teams also significantly influence project performance.
The life course of women who have experienced abuse – a life chart study in general psychiatric care
Authors: Örmon K. , Torstensson‐Levander M. , Bahtsevani C. , Sunnqvist C.
Published: October 2014

Accessible summary

The life chart offers rich information that provides a broader picture of the lives of women who have experienced abuse.

Life charts could be useful for nurses identifying women in general psychiatric care who have experienced abuse.

Despite experiences of abuse and stressful events during childhood, there were only a few indications of them receiving support in the life charts. Many of the women had as adults been in contact with or received care at numerous healthcare services.

Violence against women is a worldwide problem and has an impact on the lives of women and girls. The study aims to investigate the life course of women within psychiatric care who have experienced abuse. The women's resources, stressful events, experience of abuse, perpetrators, mental ill health, and care and support throughout the life course are also highlighted. Eleven women who had all sought general psychiatric care in an urban area in Sweden participated. A computer software program was used for constructing life charts for each participant, and manifest content analysis was used to analyse the data. The women's social status and resources differed, and some of them spoke of only experiencing few stressful events growing up, while others described a stressful childhood. All of the women had been abused sometime during their life course, and most of the perpetrators were known to the women. Even so, the women had seldom disclosed their childhood abuse. As adults, the women were diagnosed with psychiatric diagnoses, and suicidal behaviour increased. The life chart offers rich information and a broader picture of the life history of women who experienced abuse as well as constituting a tool useful for identifying women with experiences of abuse.
Tests for Volatility Shifts in Garch Against Long‐Range Dependence
Authors: Lee Taewook , Kim Moosup , Baek Changryong
Published: October 2014

Many empirical findings show that volatility in financial time series exhibits high persistence. Some researchers argue that such persistency is due to volatility shifts in the market, while others believe that this is a natural fluctuation explained by stationary long‐range dependence models. These two approaches confuse many practitioners, and forecasts for future volatility are dramatically different depending on which models to use. In this article, therefore, we consider a statistical testing procedure to distinguish volatility shifts in generalized AR conditional heteroscedasticity (GARCH) model against long‐range dependence. Our testing procedure is based on the residual‐based cumulative sum test, which is designed to correct the size distortion observed for GARCH models. We examine the validity of our method by providing asymptotic distributions of test statistic. Also, Monte Carlo simulations study shows that our proposed method achieves a good size while providing a reasonable power against long‐range dependence. It is also observed that our test is robust to the misspecified GARCH models.
Changes in characteristics of hepatitis C patients seen in a liver centre in the United States during the last decade
Authors: Talaat N. , Yapali S. , Fontana R. J. , Conjeevaram H. S. , Lok A. S.
Published: October 2014

With the approval of 2 direct‐acting antivirals (DAAs) in 2011 and anticipation of interferon (IFN)‐free regimens, more hepatitis C virus (HCV) chronically infected patients are now seeking treatment. To describe the characteristics of newly referred HCV patients in 2011–2012 (Era‐2) and compare them to those seen in 1998–1999 (Era‐1). Retrospective data were collected from HCV patients newly referred to our tertiary liver clinics. Advanced liver disease was defined as cirrhosis (based on histology or Aspartate aminotransferase–platelet‐ratio index (APRI) >2), hepatic decompensation or hepatocellular carcinoma (HCC). A total of 1348 patients (538 in Era‐1, 810 in Era‐2) were included. Compared to Era‐1, Era‐2 patients were older (median age 56 vs 45 years), more likely to be black (17.2% vs 11.6%) and had a longer interval between diagnosis and referral (median 4 vs 2 years). Genotype (GT) 1 predominated in both Eras with a significant increase in GT1a from 39.9% in Era‐1 to 53.8% in Era‐2. A higher per cent of patients in Era‐2 were treatment experienced, but 77% had never received treatment. Era‐2 patients were more likely to have advanced disease at referral (61.6% vs 51.5%, P < 0.001), with an eightfold higher prevalence of HCC (21.6% vs 2.6%, P < 0.001). HCV patients newly referred in recent years were older, predominantly infected with GT1a and had more advanced liver disease yet only a quarter had received HCV treatment. Reduction in HCV disease burden will require development of treatment regimens targeted towards patients in the current Era as well as increase in diagnosis and referral of patients for treatment.
To what degree are invaders drivers or passengers of phylogenetic community structure?
Authors: Burns Jean H.
Published: October 2014

Bennett et al. (2014, Journal of Vegetation Science 25: 1315–1326), test the biotic resistance hypothesis and show that the phylogenetic structure of the invaded community responds to an invader, rather than driving invasion patterns. More such field experiments are needed, including those that manipulate the phylogenetic structure of communities at multiple spatial scales, to disentangle phylogenetic biotic resistance from other drivers of invasion patterns.
Comparative functional genomics of adaptation to muscular disuse in hibernating mammals
Authors: Fedorov Vadim B. , Goropashnaya Anna V. , Stewart Nathan C. , Tøien Øivind , Chang Celia , Wang Haifang , Yan Jun , Showe Louise C. , Showe Michael K. , Barnes Brian M.
Published: October 2014

Hibernation is an energy‐saving adaptation that involves a profound suppression of physical activity that can continue for 6–8 months in highly seasonal environments. While immobility and disuse generate muscle loss in most mammalian species, in contrast, hibernating bears and ground squirrels demonstrate limited muscle atrophy over the prolonged periods of physical inactivity during winter, suggesting that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional programmes that underlie molecular mechanisms preventing muscle loss, we conducted a large‐scale gene expression screen in hind limb muscles comparing hibernating and summer‐active black bears and arctic ground squirrels using custom 9600 probe cDNA microarrays. A molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during torpor of hibernation that suggests induction of translation at different hibernation states. The induction of protein biosynthesis probably contributes to attenuation of disuse muscle atrophy through the prolonged periods of immobility of hibernation. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction in multiple genes involved in oxidation–reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation.
Cryptic no more: soil macrofossils uncover Pleistocene forest microrefugia within a periglacial desert
Authors: de Lafontaine Guillaume , Amasifuen Guerra Carlos Alberto , Ducousso Alexis , Petit Rémy J.
Published: October 2014

Despite their critical importance for understanding the local effects of global climate change on biodiversity, glacial microrefugia are not well studied because they are difficult to detect by using classical palaeoecological or population genetics approaches. We used soil macrofossil charcoal analysis to uncover the presence of cryptic glacial refugia for European beech (Fagus sylvatica) and other tree species in theLandes de Gascogne(southwesternFrance).

Using botanical identification and direct radiocarbon dating (14014C‐dates) of macrofossil charcoal extracted from mineral soils, we reconstructed the glacial and postglacial history of all extant beech stands in the region (n = 11).

Soil charcoal macrofossils were found in all sites, allowing the identification of up to at least 14 distinct fire events per site. There was direct evidence of the presence of beech during the last glacial period at three sites. Beech was detected during Heinrich stadial‐1, one of the coldest and driest intervals of the last glacial period in Western Europe.

Together with previous results on the genetic structure of the species in the region, these findings suggest that beech persistedin situin several microrefugia through full glacial and interglacial periods up to the present day.
Autoimmune encephalopathies
Authors: Leypoldt Frank , Armangue Thaís , Dalmau Josep
Published: October 2014

Over the past 10 years, the continual discovery of novel forms of encephalitis associated with antibodies to cell‐surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of 11 autoimmune encephalitic disorders, grouped by syndromes and approached from a clinical perspective. Anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, several subtypes of limbic encephalitis, stiff‐person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell‐surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti‐NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases.
Group size correlates with territory size in European badgers: implications for the resource dispersion hypothesis?
Authors: Robertson Andrew , Palphramand Kate L. , Carter Stephen P. , Delahay Richard J.
Published: October 2014

The resource dispersion hypothesis (RDH) predicts that resource heterogeneity can act as a passive cause of group‐living in social carnivores and potentially many other species. One central prediction of the RDH is that territory size and group size are not related, as they are determined by resource dispersion and quality, respectively. In this study we investigated the relationship between territory size, group size and group composition in the European badger, a non‐cooperative social mustelid whose behavioural ecology was central to the development of the RDH. Using data from a long‐term study in the UK, we found that territory size and group size were positively related, contradicting a core prediction of the RDH. Furthermore, territory size was more strongly correlated with the number of adult males in the group than to the number of females or total group size. This result suggests that male badgers may have a more important role in territoriality and receive greater benefits from territory enlargement. These findings are consistent with the predictions of the anti‐kleptogamy hypothesis, and suggest that badger territorial and social behaviour is not purely driven by resource dispersion, but may also be associated with breeding behaviour, as in other mustelids.
Reducing Radiation Exposure during CRT Implant Procedures: Early Experience with a Sensor‐Based Navigation System
Authors: THIBAULT BERNARD , ANDRADE JASON G. , DUBUC MARC , TALAJIC MARIO , GUERRA PETER G. , DYRDA KATIA , MACLE LAURENT , RIVARD LÉNA , ROY DENIS , MONDÉSERT BLANDINE , KHAIRY PAUL
Published: October 2014

Background

Cardiac resynchronization therapy (CRT) implant procedures are often complex and prolonged, resulting in significant ionizing radiation (IR) exposure to the patient and operator. We report our early experience working with a novel sensor‐based electromagnetic tracking system (MediGuide™, MDG, St. Jude Medical Inc., St. Paul, MN, USA), in terms of procedural IR exposure reduction.

Methods and Results

Information regarding patient demographics, procedural details, procedural duration, and IR exposure were prospectively collected on 130 consecutive CRT procedures performed between January 2013 and January 2014. Sixty procedures were performed with MDG guidance, and 70 were performed without MDG guidance. Despite a nonsignificant trend toward shorter procedure duration with the use of MDG (120 minutes vs 138 minutes with non‐MDG, P = 0.088), a 66% reduction in total IR exposure (median 769 μGray·m2 vs 2,608 μGray·m2, P < 0.001) was found. This reduction was primarily driven by a >90% reduction in IR dose required to cannulate the coronary sinus (median 80 μGray·m2 vs 922 μGray·m2, P < 0.001), and to a lesser extent from a reduction in IR dose required for LV lead placement (median 330 μGray·m2 vs 737 μGray·m2, P = 0.059). In addition, a significant learning curve effect was observed with a significantly shorter procedural duration for the last 15 cases compared to the first 15 cases (median 98 minutes vs 175 minutes, P < 0.001).

Conclusion

The nonfluoroscopic MDG positioning system is associated with a dramatic reduction in exposure to IR during CRT implant procedures, with a 90% decrease in the IR dose required to cannulate the coronary sinus. A steep learning curve was quantified.
Cryoablation of Focal Tachycardia Originating from the Right Atrial Free Wall during Upstream Phrenic Pacing to Avoid Phrenic Nerve Injury
Authors: JOHNSRUDE CHRISTOPHER
Published: October 2014

Background

Recognition of the potential for phrenic nerve injury (PNI) often prompts less aggressive attempts at catheter ablation of multiple forms of tachycardia or abandoning ablation altogether. Some novel techniques to avoid PNI during catheter ablation have been described.

Methods

Five patients (age: 13–57 years, three females) with ectopic atrial tachycardia originating from the right atrial free wall (RAFW) near the phrenic nerve underwent electrophysiology study with three‐dimensional mapping and endocardial cryoablation. Upstream phrenic pacing was performed after cryoadherence was achieved, and cryoablation of ectopic foci was performed during close observation for occurrence of PNI and tachycardia elimination.

Results

Cryoablation acutely eliminated five of six atrial tachycardias originating close to the phrenic nerve. Transient PNI during cryothermy occurred in two patients, and resolved within 3 minutes. Patients were observed overnight on telemetry, with no early recurrences of targeted atrial tachycardias and no evidence of PNI. At last follow‐up of 1–39 months, four patients were arrhythmia free on no medications.

Conclusions

Catheter cryoablation during simultaneous upstream phrenic nerve pacing can lead to safe and effective elimination of focal atrial tachycardias originating from the RAFW close to the phrenic nerve.
OsAUX1 controls lateral root initiation in rice (Oryza sativa L.)
Authors: Zhao Heming , Ma Tengfei , Wang Xin , Deng Yingtian , Ma Haoli , Zhang Rongsheng , Zhao Jie
Published: October 2014

Polar auxin transport, mediated by influx and efflux transporters, controls many aspects of plant growth and development. The auxin influx carriers in Arabidopsis have been shown to control lateral root development and gravitropism, but little is known about these proteins in rice. This paper reports on the functional characterization of OsAUX1. Three OsAUX1 T‐DNA insertion mutants and RNAi knockdown transgenic plants reduced lateral root initiation compared with wild‐type (WT) plants. OsAUX1 overexpression plants exhibited increased lateral root initiation and OsAUX1 was highly expressed in lateral roots and lateral root primordia. Similarly, the auxin reporter, DR5‐GUS, was expressed at lower levels in osaux1 than in the WT plants, which indicated that the auxin levels in the mutant roots had decreased. Exogenous 1‐naphthylacetic acid (NAA) treatment rescued the defective phenotype in osaux1‐1 plants, whereas indole‐3‐acetic acid (IAA) and 2,4‐D could not, which suggested that OsAUX1 was a putative auxin influx carrier. The transcript levels of several auxin signalling genes and cell cycle genes significantly declined in osaux1, hinting that the regulatory role of OsAUX1 may be mediated by auxin signalling and cell cycle genes. Overall, our results indicated that OsAUX1 was involved in polar auxin transport and functioned to control auxin‐mediated lateral root initiation in rice.
Histone modification and signalling cascade of the dormancy‐associated MADS‐box gene, PpMADS13‐1, in Japanese pear (Pyrus pyrifolia) during endodormancy
Authors: SAITO TAKANORI , BAI SONGLING , IMAI TSUYOSHI , ITO AKIKO , NAKAJIMA IKUKO , MORIGUCHI TAKAYA
Published: October 2014

Dormancy‐associated MADS‐box (DAM) genes play an important role in endodormancy phase transition. We investigated histone modification in the DAM homolog (PpMADS13‐1) from Japanese pear, via chromatin immunoprecipitation–quantitative PCR, to understand the mechanism behind the reduced expression of the PpMADS13‐1 gene towards endodormancy release. Our results indicated that the reduction in the active histone mark by trimethylation of the histone H3 tail at lysine 4 contributed to the reduction of PpMADS13‐1 expression towards endodormancy release. In contrast, the inactive histone mark by trimethylation of the histone H3 tail at lysine 27 in PpMADS13‐1 locus was quite low, and these levels were more similar to a negative control [normal mouse immunoglobulin G (IgG)] than to a positive control (AGAMOUS) in endodormancy phase transition. The loss of histone variant H2A.Z also coincided with the down‐regulation of PpMADS13‐1. Subsequently, we investigated the PpMADS13‐1 signalling cascade and found that PpCBF2, a pear C‐repeated binding factor, regulated PpMADS13‐1 expression via interaction of PpCBF2 with the 5′‐upstream region of PpMADS13‐1 by transient reporter assay. Furthermore, transient reporter assay confirmed no interaction between the PpMADS13‐1 protein and the pear FLOWERING LOCUS T genes. Taken together, our results enhance understanding of the molecular mechanisms underlying endodormancy phase transition in Japanese pear.
Ultraviolet‐Bcomponent of sunlight stimulates photosynthesis and flavonoid accumulation in variegatedPlectranthus coleoidesleaves depending on background light
Authors: VIDOVIĆ MARIJA , MORINA FILIS , MILIĆ SONJA , ZECHMANN BERND , ALBERT ANDREAS , WINKLER JANA BARBRO , VELJOVIĆ JOVANOVIĆ SONJA
Published: October 2014

We used variegatedPlectranthus coleoidesas a model plant with the aim of clarifying whether the effects of realistic ultraviolet‐B (UV‐B) doses on phenolic metabolism in leaves are mediated by photosynthesis. Plants were exposed toUV‐Bradiation (0.90 W m−2) combined with two photosynthetically active radiation (PAR) intensities [395 and 1350 μmol m−2 s−1, low light (LL) and high light (HL)] for 9 d in sun simulators. Our study indicates thatUV‐Bcomponent of sunlight stimulatesCO2assimilation and stomatal conductance, depending on background light.UV‐B‐specific induction of apigenin and cyanidin glycosides was observed in both green and white tissues. However, all the other phenolic subclasses were up to four times more abundant in green leaf tissue. Caffeic and rosmarinic acids, catechin and epicatechin, which are endogenous peroxidase substrates, were depleted atHLin green tissue. This was correlated with increased peroxidase and ascorbate peroxidase activities and increased ascorbate content. TheUV‐Bsupplement toHLattenuated antioxidative metabolism and partly recovered the phenolic pool indicating stimulation of the phenylpropanoid pathway. In summary, we propose thatortho‐dihydroxy phenolics are involved in antioxidative defence in chlorophyllous tissue upon light excess, while apigenin and cyanidin in white tissue have preferentiallyUV‐screening function.
Transgenic Arabidopsis thaliana plants expressing a β‐1,3‐glucanase from sweet sorghum (Sorghum bicolor L.) show reduced callose deposition and increased tolerance to aluminium toxicity
Authors: ZHANG HUI , SHI WU LIANG , YOU JIANG FENG , BIAN MING DI , QIN XIAO MEI , YU HUI , LIU QING , RYAN PETER R. , YANG ZHEN MING
Published: October 2014

Seventy‐one cultivars of sweet sorghum (Sorghum bicolor L.) were screened for aluminium (Al) tolerance by measuring relative root growth (RRG). Two contrasting cultivars, ROMA (Al tolerant) and POTCHETSTRM (Al sensitive), were selected to study shorter term responses to Al stress. POTCHETSTRM had higher callose synthase activity, lower β‐1,3‐glucanase activity and more callose deposition in the root apices during Al treatment compared with ROMA. We monitored the expression of 12 genes involved in callose synthesis and degradation and found that one of these, SbGlu1 (Sb03g045630.1), which encodes a β‐1,3‐glucanase enzyme, best explained the contrasting deposition of callose in ROMA and POTCHETSTRM during Al treatment. Full‐length cDNAs of SbGlu1 was prepared from ROMA and POTCHETSTRM and expressed in Arabidopsis thaliana using the constitutive cauliflower mosaic virus (CaMV) 35S promoter. Independent transgenic lines displayed significantly greater Al tolerance than wild‐type plants and vector‐only controls. This phenotype was associated with greater total β‐1,3‐glucanase activity, less Al accumulation and reduced callose deposition in the roots. These results suggest that callose production is not just an early indicator of Al stress in plants but likely to be part of the toxicity pathway that leads to the inhibition of root growth.
DNA Damage Checkpoint Responses in the S Phase of Synchronized Diploid Human Fibroblasts
Authors: Chastain Paul D. , Brylawski Bruna P. , Zhou Yingchun C. , Rao Shangbang , Chu Haitao , Ibrahim Joseph G. , Kaufmann William K. , Cordeiro‐Stone Marila
Published: October 2014

We investigated the hypothesis that the strength of the activation of the intra‐S DNA damage checkpoint varies within the S phase. Synchronized diploid human fibroblasts were exposed to either 0 or 2.5 J m−2 UVC in early, mid‐ and late‐S phase. The endpoints measured were the following: (1) radio‐resistant DNA synthesis (RDS), (2) induction of Chk1 phosphorylation, (3) initiation of new replicons and (4) length of replication tracks synthesized after irradiation. RDS analysis showed that global DNA synthesis was inhibited by approximately the same extent (30 ± 12%), regardless of when during S phase the fibroblasts were exposed to UVC. Western blot analysis revealed that the UVC‐induced phosphorylation of checkpoint kinase 1 (Chk1) on serine 345 was high in early and mid S but 10‐fold lower in late S. DNA fiber immunostaining studies indicated that the replication fork displacement rate decreased in irradiated cells at the three time points examined; however, replicon initiation was inhibited strongly in early and mid S, but this response was attenuated in late S. These results suggest that the intra‐S checkpoint activated by UVC‐induced DNA damage is not as robust toward the end of S phase in its inhibition of the latest firing origins in human fibroblasts.
The production and comparative evaluation of native and recombinant antigens for the fast serodiagnosis of cystic echinococcosis with dot immunogold filtration assay
Authors: Chen X. , Chen X. , Lu X. , Feng X. , Wen H.
Published: October 2014

Clinical diagnosis and post‐surgery assessment of cystic echinococcosis depend on laboratory serodiagnosis and ultrasound examinations. This study aims to produce the recombinant antigen (rAgB) and compare its diagnostic effect with natural antigens (crude fluid antigen, protoscolex antigen). After rAgB, crude fluid antigen, protoscolex antigen were produced, and the diagnostic accuracy was evaluated with dot immunogold filtration assay (DIGFA) by the sera from the following groups: surgically confirmed cystic echinococcosis patients (n = 113), alveolar echinococcosis patients (n = 46), other parasitic diseases (n = 49), nonparasitic hepatic diseases (n = 63) and healthy people (n = 121). In diagnosing cystic echinococcosis, the sensitivity of recombinant AgB was 77·9% and the specificity was 98·3%. The crude fluid antigen B showed a sensitivity of 92·9% and specificity of 81·0%. The protoscolex antigen had sensitivity of 87·6% and specificity of 90·9%. The recombinant AgB indicates the advantage of no cross‐reaction with other parasite diseases or nonparasite hepatic diseases. Recombinant antigen B can improve the specificity but decrease the sensitivity. The combination of native and recombinant antigens will improve the overall performance of serodiagnosis of cystic echinococcosis.
Expression analysis of genes associated with sucrose accumulation in sugarcane (Saccharum spp. hybrids) varieties differing in content and time of peak sucrose storage
Authors: Chandra A. , Verma P. K. , Islam M. N. , Grisham M. P. , Jain R. , Sharma A. , Roopendra K. , Singh K. , Singh P. , Verma I. , Solomon S.
Published: October 2014

Sucrose synthesis/accumulation in sugarcane is a complex process involving many genes and regulatory sequences that control biochemical events in source–sink tissues. Among these, sucrose synthase (SuSy), sucrose phosphate synthase (SPS), soluble acid (SAI) and cell wall (CWI) invertases are important. Expression of these enzymes was compared in an early (CoJ64) and late (BO91) maturing sugarcane variety using end‐point and qRT‐PCR. Quantitative RT‐PCR at four crop stages revealed high CWI expression in upper internodes of CoJ64, which declined significantly in both top and bottom internodes with maturity. In BO91, CWI expression was high in top and bottom internodes and declined significantly only in top internodes as the crop matured. Overall, CWI expression was higher in CoJ64 than in BO91. During crop growth, there was no significant change in SPS expression in bottom internodes in CoJ64, whereas in BO91 it decreased significantly. Apart from a significant decrease in expression of SuSy in mature bottom internodes of BO91, there was no significant change. Similar SAI expression was observed with both end‐point and RT‐PCR, except for significantly increased expression in top internodes of CoJ64 with maturity. SAI, being a major sucrose hydrolysing enzyme, was also monitored with end‐point PCR expression in internode tissues of CoJ64 and BO91, with higher expression of SAI in BO91 at early crop stages. Enzyme inhibitors, e.g. manganese chloride (Mn++), significantly suppressed expression of SAI in both early‐ and late‐maturing varieties. Present findings enhance understanding of critical sucrose metabolic gene expression in sugarcane varieties differing in content and time of peak sucrose storage. Thus, through employing these genes, improvement of sugarcane sucrose content is possible.
Predicting Time to Threshold for Initiating Antiretroviral Treatment to Evaluate Cost of Treatment as Prevention of Human Immunodeficiency Virus
Authors: Lynch Miranda L. , DeGruttola Victor
Published: October 2014

The goal of the paper is to predict the additional amount of antiretroviral treatment that would be required to implement a policy of treating all human immunodeficiency virus (HIV) infected people at the time of detection of infection rather than at the time that their CD4 T-lymphocyte counts are observed to be below a threshold—the current standard of care. We describe a sampling-based inverse prediction method for predicting time from HIV infection to attainment of the CD4 cell threshold and apply it to a set of treatment naive HIV-infected subjects in a village in Botswana who participated in a household survey that collected cross-sectional CD4 cell counts. The inferential target of interest is the population level mean time to reaching the CD4 cell-based treatment threshold in this group of subjects. To address the challenges arising from the fact that these subjects’ dates of HIV infection are unknown, we make use of data from an auxiliary cohort study of subjects enrolled shortly after HIV infection in which CD4 cell counts were measured over time. We use a multiple-imputation framework to combine across the different sources of data, and we discuss how the methods compensate for the length-biased sampling that is inherent in cross-sectional screening procedures, such as household surveys. We comment on how the results bear on analyses of costs of implementation of treatment-for-prevention use of antiretroviral drugs in HIV prevention interventions.
Regression Analysis for Differentially Misclassified Correlated Binary Outcomes
Authors: Tang Li , Lyles Robert H. , King Caroline C. , Hogan Joseph W. , Lo Yungtai
Published: October 2014

In many epidemiological and clinical studies, misclassification may arise in one or several variables, resulting in potentially invalid analytic results (e.g. estimates of odds ratios of interest) when no correction is made. Here we consider the situation in which correlated binary response variables are subject to misclassification. Building on prior work, we provide an approach to adjust for potentially complex differential misclassification via internal validation sampling applied at multiple study time points. We seek to estimate the parameters of a primary generalized linear mixed model that accounts for baseline and/or time-dependent covariates. The misclassification process is modelled via a second generalized linear model that captures variations in sensitivity and specificity parameters according to time and a set of subject-specific covariates that may or may not overlap with those in the primary model. Simulation studies demonstrate the precision and validity of the method proposed. An application is presented based on longitudinal assessments of bacterial vaginosis conducted in the ‘HIV epidemiology research’ study.
Optimal Observation Times for Multistate Markov Models—Applications to Pneumococcal Colonization Studies
Authors: Mehtälä Juha , Auranen Kari , Kulathinal Sangita
Published: October 2014

Applications of finite state Markov transition models are numerous and the problem of estimating transition rates of such processes has been considered in many fields of science. Because these processes cannot always be followed in continuous time, the investigators often confront the question of when to measure the state of the process. The estimation of transition rates then needs to be based on a sequence of discrete time data, and the variance and estimability of the estimators greatly depend on the time spacings between consecutive observations. We study optimal time spacings for a sequence of discrete time observations to estimate the transition rates of a time homogeneous multistate Markov process. For comparative studies, optimal time spacings to estimate rate ratios are considered. Optimality criteria are formulated through the minimization of the variances of the parameter estimators of interest and are investigated assuming a stationary initial distribution. For practical purposes, we propose a simple approximation for the optimal time spacing and study the limits for its applicability. The work is motivated by studies of colonization with Streptococcus pneumoniae.
Dacryocystitis following a nasolacrimal duct obstruction caused by an ectopic intranasal tooth in a dog
Authors: Voelter‐Ratson Katrin , Hagen Regine , Grundmann Stefan , Spiess Bernhard Martin
Published: October 2014

Purpose

To describe a nasolacrimal duct (NLD) obstruction secondary to an ectopic tooth in a 5‐year‐old male Border collie. The dog was presented with a 1‐month history of mucopurulent discharge from the left eye (OS) preceded by a lifelong history of epiphora OS. Treatment with neomycin/polymyxin B/dexamethasone ophthalmic solution had not improved the clinical signs, and the NLD was not patent when irrigated by the referring veterinarian.

Methods

A complete ophthalmologic examination was performed followed by dacryocystorhinography and computed tomography (CT).

Results

The ophthalmologic examination revealed marked mucopurulent discharge, mild conjunctivitis, slightly elevated STT measurements, and a negative Jones test OS. Both nasolacrimal puncta OS could be cannulated without resistance for approximately 1.5 cm. Upon irrigation, copious amounts of mucopurulent discharge were exited through the corresponding punctum, while no fluid could be detected at the nares. Dacryocystorhinography was performed. Radiographs revealed an ectopic left canine tooth within the left nasal cavity. A cystic dilation of the NLD was observed proximal to the ectopic tooth. Computed tomography was performed to determine the exact position of the tooth and possible involvement of adjacent structures; CT confirmed the previous imaging findings. Treatment with systemic antibiotics, NSAIDs, and ofloxacin ophthalmic solution led to resolution of the clinical signs within several days. Surgery was declined by the owner.

Conclusion

This is the first case report describing a blocked NLD due to an ectopic tooth in a dog. Ectopic teeth should be included as a differential diagnosis in cases of dacryocystitis and chronic epiphora in dogs.
Fabrication and characterization of silver- and copper-coated Nylon 6 forcespun nanofibers by thermal evaporation
Authors: Mihut Dorina M. , Lozano Karen , Foltz Heinrich
Published: October 2014

Silver and copper nanoparticles were deposited as thin films onto substrates consisting of Nylon 6 nanofibers manufactured using forcespinning® equipment. Different rotational speeds were used to obtain continuous nanofibers of various diameters arranged as nonwoven mats. The Nylon 6 nanofibers were collected as successive layers on frames, and a high-vacuum thermal evaporation method was used to deposit the silver and copper thin films on the nanofibers. The structures were investigated using scanning electron microscopy–scanning transmission electron microscopy, atomic force microscopy, x-ray diffraction, and electrical resistance measurements. The results indicate that evaporated silver and copper nanoparticles were successfully deposited on Nylon 6 nanofibers as thin films that adhered well to the polymer substrate while the native morphology of the nanofibers were preserved, and electrically conductive nanostructures were achieved.
Anticancer Cocktails
Authors: VanHook Annalisa M.
Published: October 2014

Intravenous delivery of nanoparticles containing combinations of small interfering RNAs that target RAS signaling networks reduces tumor growth in mice.
Inhibition of Salmonella enterica Biofilm Formation Using Small-Molecule Adenosine Mimetics
Authors: Koopman Jacob A. , Marshall Joanna M. , Bhatiya Aditi , Eguale Tadesse , Kwiek Jesse J. , Gunn John S.
Published: October 2014

Biofilms have been widely implicated in chronic infections and environmental persistence of
Salmonella enterica
, facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts.
Salmonella enterica
serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while
Salmonella enterica
serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries.
Salmonella
regulates expression of many virulence- and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by
S
. Typhimurium and
S
. Typhi. The compound was not bactericidal or bacteriostatic toward
S
. Typhimurium or cytotoxic to mammalian cells. An ATP-Sepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of
Acinetobacter baumannii
as well. The identification of a lead compound with biofilm-inhibiting capabilities toward
Salmonella
provides a potential new avenue of therapeutic intervention against
Salmonella
biofilm formation, with applicability to biofilms of other bacterial pathogens.
Seasonal Variation in Penicillin Use in Mexico and Brazil: Analysis of the Impact of Over-the-Counter Restrictions
Authors: Santa-Ana-Tellez Yared , Mantel-Teeuwisse Aukje K. , Leufkens Hubert G. M. , Wirtz Veronika J.
Published: October 2014

During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use.
Antibiotic-Loaded Synthetic Calcium Sulfate Beads for Prevention of Bacterial Colonization and Biofilm Formation in Periprosthetic Infections
Authors: Howlin R. P. , Brayford M. J. , Webb J. S. , Cooper J. J. , Aiken S. S. , Stoodley P.
Published: October 2014

Periprosthetic infection (PI) causes significant morbidity and mortality after fixation and joint arthroplasty and has been extensively linked to the formation of bacterial biofilms. Poly(methyl methacrylate) (PMMA), as a cement or as beads, is commonly used for antibiotic release to the site of infection but displays variable elution kinetics and also represents a potential nidus for infection, therefore requiring surgical removal once antibiotics have eluted. Absorbable cements have shown improved elution of a wider range of antibiotics and, crucially, complete biodegradation, but limited data exist as to their antimicrobial and antibiofilm efficacy. Synthetic calcium sulfate beads loaded with tobramycin, vancomycin, or vancomycin-tobramycin dual treatment (in a 1:0.24 [wt/wt] ratio) were assessed for their abilities to eradicate planktonic methicillin-resistant
Staphylococcus aureus
(MRSA) and
Staphylococcus epidermidis
relative to that of PMMA beads. The ability of the calcium sulfate beads to prevent biofilm formation over multiple days and to eradicate preformed biofilms was studied using a combination of viable cell counts, confocal microscopy, and scanning electron microscopy of the bead surface. Biofilm bacteria displayed a greater tolerance to the antibiotics than their planktonic counterparts. Antibiotic-loaded beads were able to kill planktonic cultures of 10
6
CFU/ml, prevent bacterial colonization, and significantly reduce biofilm formation over multiple days. However, established biofilms were harder to eradicate. These data further demonstrate the difficulty in clearing established biofilms; therefore, early preventive measures are key to reducing the risk of PI. Synthetic calcium sulfate loaded with antibiotics has the potential to reduce or eliminate biofilm formation on adjacent periprosthetic tissue and prosthesis material and, thus, to reduce the rates of periprosthetic infection.
Impact of Nonlinear Interactions of Pharmacokinetics and MICs on Sputum Bacillary Kill Rates as a Marker of Sterilizing Effect in Tuberculosis
Authors: Chigutsa Emmanuel , Pasipanodya Jotam G. , Visser Marianne E. , van Helden Paul D. , Smith Peter J. , Sirgel Frederick A. , Gumbo Tawanda , McIlleron Helen
Published: October 2014

The relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex and nonlinear. In patients on treatment, an analysis of the rate of decline in the sputum bacillary burden reveals two slopes. The first is the α-slope, which is thought to reflect bactericidal effect, followed by a β-slope, which is thought to reflect sterilizing activity. We sought to characterize the effects of standard first-line treatment on sterilizing activity. Fifty-four patients receiving combination therapy for pulmonary tuberculosis in a clinical trial had drug concentrations measured and
Mycobacterium tuberculosis
isolates available for MIC identification. Sputum sample cultures were performed at baseline and weekly for 8 weeks. A time-to-event model based on the days to positivity in the liquid cultures was used to estimate the β-slope. The pharmacokinetic parameters of rifampin, isoniazid, ethambutol, and pyrazinamide were determined for each patient. Multivariate adaptive regression splines analyses, which simultaneously perform linear and nonlinear analyses, were used to identify the relationships between the predictors and the β-slope. The potential predictors examined included HIV status, lung cavitation, 24-h area under the concentration-time curve (AUC), peak drug concentration (
C
max
), AUC/MIC ratio,
C
max
/MIC ratio, and the time that that concentration persisted above MIC. A rifampin
C
max
of >8.2 mg/liter and a pyrazinamide AUC/MIC of >11.3 were key predictors of the β-slope and interacted positively to increase the β-slope. In patients with a rifampin AUC of <35.4 mg · h/liter, an increase in the pyrazinamide AUC/MIC and/or ethambutol
C
max
/MIC increased the β-slope, while increasing isoniazid
C
max
decreased it, suggesting isoniazid antagonism. Antibiotic concentrations and MICs interact in a nonlinear fashion as the main drivers of a sterilizing effect. The results suggest that faster speeds of sterilizing effect might be achieved by omitting isoniazid and by increasing rifampin, pyrazinamide, and ethambutol exposures. However, isoniazid and ethambutol exposures may only be of importance when rifampin exposure is low. These findings need confirmation in larger studies. (This study has been registered at
controlled-trials.com
under registration no. ISRCTN80852505.)
Effect of Rifampin and Rifabutin on Serum Itraconazole Levels in Patients with Chronic Pulmonary Aspergillosis and Coexisting Nontuberculous Mycobacterial Infection
Authors: Moon Seong Mi , Park Hye Yun , Jeong Byeong-Ho , Jeon Kyeongman , Lee Soo-Youn , Koh Won-Jung
Published: October 2014

We investigated the effects of rifampin and rifabutin on serum itraconazole levels in patients with chronic pulmonary aspergillosis. Serum itraconazole concentrations were significantly lower in patients who received itraconazole with rifampin (median, 0.1 μg/ml;
P
< 0.001) or rifabutin (median, 0.34 μg/ml;
P
< 0.001) than those receiving itraconazole alone (median, 5.92 μg/ml). Concomitant use of rifampin or rifabutin and itraconazole should be avoided in patients with chronic pulmonary aspergillosis and coexisting mycobacterial infections.
The Bioactive Lipid 4-Hydroxyphenyl Retinamide Inhibits Flavivirus Replication
Authors: Carocci Margot , Hinshaw Stephen M. , Rodgers Mary A. , Villareal Valerie A. , Burri Dominique J. , Pilankatta Rajendra , Maharaj Natalya P. , Gack Michaela U. , Stavale Eric J. , Warfield Kelly L. , Yang Priscilla L.
Published: October 2014

Dengue virus (DENV), a member of the
Flaviviridae
family, is a mosquito-borne pathogen and the cause of dengue fever. The increasing prevalence of DENV worldwide heightens the need for an effective vaccine and specific antivirals. Due to the dependence of DENV upon the lipid biosynthetic machinery of the host cell, lipid signaling and metabolism present unique opportunities for inhibiting viral replication. We screened a library of bioactive lipids and modulators of lipid metabolism and identified 4-hydroxyphenyl retinamide (4-HPR) (fenretinide) as an inhibitor of DENV in cell culture. 4-HPR inhibits the steady-state accumulation of viral genomic RNA and reduces viremia when orally administered in a murine model of DENV infection. The molecular target responsible for this antiviral activity is distinct from other known inhibitors of DENV but appears to affect other members of the
Flaviviridae
, including the West Nile, Modoc, and hepatitis C viruses. Although long-chain ceramides have been implicated in DENV replication, we demonstrate that DENV is insensitive to the perturbation of long-chain ceramides in mammalian cell culture and that the effect of 4-HPR on dihydroceramide homeostasis is separable from its antiviral activity. Likewise, the induction of reactive oxygen species by 4-HPR is not required for the inhibition of DENV. The inhibition of DENV
in vivo
by 4-HPR, combined with its well-established safety and tolerability in humans, suggests that it may be repurposed as a pan-
Flaviviridae
antiviral agent. This work also illustrates the utility of bioactive lipid screens for identifying critical interactions of DENV and other viral pathogens with host lipid biosynthesis, metabolism, and signal transduction.