bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining EMI and GPR for non‐invasive soil sensing at the Stonehenge World Heritage Site: the reconstruction of a WW1 practice trench
Authors: Saey T. , Van Meirvenne M. , De Smedt P. , Stichelbaut B. , Delefortrie S. , Baldwin E. , Gaffney V.
Published: December 2014

Increasingly, conventional soil sampling procedures face restrictions because of their destructive character. Hence there is a growing interest in non‐invasive techniques, on which proximal soil sensors are based. There is great interest in applying proximal soil sensing to improve the characterization of the buried heritage embedded in the soil landscape at sites such as the Stonehenge World Heritage Site, UK. Because calibration and validation procedures based on invasive practices are unconventional, we turned to the investigation of a well‐documented practice trench dug during the First World War (WW1) close to the prehistoric Stonehenge monument. A methodology was tested that would simultaneously invert frequency‐domain ground‐penetrating radar (GPR) and multi‐receiver electromagnetic induction (EMI) data, with the aim of reconstructing the trench network. This trench network could not be distinguished on the EMI apparent electrical conductivity (σa) measurements, but appeared on the apparent magnetic susceptibility (κa) data. The GPR measurements showed the trench infilling as strong reflections contrasting with the surrounding soil. However, converting the two‐way travel times to absolute depths requires knowledge of the relative permittivity (εr). Because of the preference for non‐invasive observation in this protected landscape, we developed a procedure integrating the GPR measurements with κa measurements obtained with EMI. A fitting procedure, assuming a constant susceptibility and permittivity of the sub‐surface layers, allowed us to estimate both the susceptibility of the trench fill and the surrounding soil material, and the εr value of the material above and within the trench. This provided absolute depth values for the GPR reflection data, improving the lateral and vertical reconstruction of the trench system. Moreover, these results allowed depth slices to be determined from EMI κa data. So, integrating both GPR and EMI measurements enabled the detailed reconstruction of the buried trench network at Stonehenge, offering new perspectives on the investigation of features buried within the soil of protected sites.
Asserting Existence: Agentive Narratives Arising From the Restraints of Seeking Asylum in East Anglia, Britain
Authors: Rainbird Sophia
Published: December 2014

This article is based on fieldwork (2002–2003) in Great Yarmouth and Norwich in Britain with asylum seekers from Iraq, Iran, Kenya, Kosovo, Congo, and Montenegro as they await the outcome to their application for refugee status. During this period of liminality, their narratives were both urgent and repetitive expressions of their current immigration status and, to a lesser extent, their past experiences. In this article, I consider how such narratives are elicited by asylum seekers to craft an agentive capacity during this liminal period to overcome an existential crisis and assert their existence within society. Stories that recount traumatic experiences work as a way of reconciling a past that can no longer exist and a current state of liminality with a new sense of being in the world.
Family and Consumer Sciences Graduate Research Productivity in 2013
Authors: Kabaci M. J.
Published: December 2014

Requests were sent in April 2014 to representatives of 151 universities and colleges with family and consumer science programs. The purpose was to collect the titles and authors of theses and dissertations completed in 2013. Thirty‐nine universities responded and they reported a total of 480 theses and dissertations. Of the 480 titles, 307 titles were for theses and 173 titles were for dissertations. The largest number of titles reported for master's theses was in Nutrition and Dietetics. The largest number of titles reported for dissertations was in Family Relations. In addition, 21 of the 39 universities stated that 282 master's students completed nonthesis options in 2013.
The Family and Consumer Sciences Research Center: Guiding and Advancing Research
Authors: Myers Lori A.
Published: December 2014

The Family and Consumer Sciences Research Center was established in 2011 to guide and advance research in family and consumer sciences. The purpose of this article is to provide an introduction to the Research Center and to outline the virtual resources available to FCS researchers and students.
Theses and Dissertations Completed in Family and Consumer Sciences: 2013
Authors: Kabaci M. J.
Published: December 2014

The annual survey of graduate programs at US universities and colleges was conducted in the spring of 2014 to compile a list of theses and dissertations completed in 2013 in family and consumer sciences areas of interest. For the survey, requests for the titles and authors were sent via e‐mail to institutions three times within a 6‐week period. Thirty‐nine colleges and universities responded to the survey. A total of 307 theses and 173 dissertations were reported. A report of those submissions, by subject category, author, and title, is provided.
White Matter Hyperintensities of Presumed Vascular Origin: A Population-Based Study in Rural Ecuador (The Atahualpa Project)
Authors: Del Brutto Oscar H. , Mera Robertino M. , Del Brutto Victor J. , Zambrano Mauricio , Lama Julio
Published: December 2014

Background

Cerebral small vessel disease is probably one of the most common pathogenetic mechanisms underlying stroke in Latin America. However, the importance of silent markers of small vessel disease, including white matter hyperintensities of presumed vascular origin, has not been assessed so far.

Aim

The study aims to evaluate prevalence and correlates of white matter hyperintensities in community-dwelling elders living in Atahualpa (rural Ecuador).

Methods

Atahualpa residents aged ≥60 years were identified during a door-to-door survey and invited to undergo brain magnetic resonance imaging for identification and grading white matter hyperintensities and other markers of small vessel disease. Using multivariate logistic regression models, we evaluated whether white matter hyperintensities is associated with demographics, cardiovascular health status, stroke, cerebral microbleeds, and cortical atrophy, after adjusting for the other variables.

Results

Out of 258 enrolled persons (mean age, 70 ± 8 years; 59% women), 172 (67%) had white matter hyperintensities, which were moderate to severe in 63. Analyses showed significant associations of white matter hyperintensities presence and severity with age and cardiovascular health status, as well as with overt and silent strokes, and a trend for association with cerebral microbleeds and cortical atrophy.

Conclusions

Prevalence and correlates of white matter hyperintensities in elders living in rural Ecuador is almost comparable with that reported from industrialized nations, reinforcing the concept that the burden of small vessel disease is on the rise in underserved Latin American populations.
Nurses' perceptions of patient safety culture in Jordanian hospitals
Authors: Khater W.A. , Akhu‐Zaheya L.M. , AL‐Mahasneh S.I. , Khater R.
Published: December 2014

Background

Patients' safety culture is a key aspect in determining healthcare organizations' ability to address and reduce risks of patients. Nurses play a major role in patients' safety because they are accountable for direct and continuous patient care. There is little known information about patients' safety culture in Jordanian hospitals, particularly from the perspective of healthcare providers.

Aim

The study aimed to assess patient safety culture in Jordanian hospitals from nurses' perspective.

Methods

A cross‐sectional, descriptive design was utilized. A total number of 658 nurses participated in the current study. Data were collected using an Arabic version of the hospital survey of patients' safety culture.

Findings

Teamwork within unit dimensions had a high positive response, and was perceived by nurses to be the only strong suit in Jordanian hospitals. Areas that required improvement, as perceived by nurses, are as follows: communication openness, staffing, handoff and transition, non‐punitive responses to errors, and teamwork across units. Regression analysis revealed factors, from nurses' perspectives, that influenced patients' safety culture in Jordanian hospital. Factors included age, total years of experience, working in university hospitals, utilizing evidence‐based practice and working in hospitals that consider patient safety to be a priority.

Limitations

Participants in this study were limited to nurses. Therefore, there is a need to assess patient safety culture from other healthcare providers' perspectives. Moreover, the use of a self‐reported questionnaire introduced the social desirability biases.

Conclusion

The current study provides insight into how nurses perceive patient safety culture. Results of this study have revealed that there is a need to replace the traditional culture of shame/blame with a non‐punitive culture.

Implications for nursing and health policy

Study results implied that improving patient safety culture requires a fundamental transformation of nurses' work environment. New policies to improve collaboration between units of hospitals would improve patients' safety.
Regulatory fit theory at work: prevention focus' primacy in safe food production
Authors: Park Ernest S. , Hinsz Verlin B , Nickell Gary S.
Published: December 2014

The food‐processing industry emphasizes employee compliance to food‐safety standards to prevent distribution of contaminated foods. Regulatory fit theory was tested to examine the applicability of self‐regulation constructs as potential components of person‐job fit. In contexts emphasizing safety, workers higher in prevention should experience greater person‐job fit, thus prevention focus should relate to desirable outcomes. Poultry‐processing workers (n = 180) completed a work‐related regulatory focus scale as part of a survey including a set of outcome measures. Consistent with theory, prevention focus scores related to self‐reported positive work outcomes (job effectiveness, satisfaction, efficacy, enjoyment, involvement), and relationships were statistically mediated by perceived regulatory fit. Results have implications for selection practices and suggest ways work can be structured to enhance job performance.
A continent‐wide study reveals clear relationships between regional abiotic conditions and post‐dispersal seed predation
Authors: Orrock John L. , Borer Elizabeth T. , Brudvig Lars A. , Firn Jennifer , MacDougall Andrew S. , Melbourne Brett A. , Yang Louie H. , Baker Dirk V. , Bar‐Massada Avi , Crawley Michael J. , Damschen Ellen I. , Davies Kendi F. , Gruner Daniel S. , Kay Adam D. , Lind Eric , McCulley Rebecca L. , Seabloom Eric W.
Published: December 2014

Aim

Large‐scale patterns linking energy availability, biological productivity and diversity form a central focus of ecology. Despite evidence that the activity and abundance of animals may be limited by climatic variables associated with regional biological productivity (e.g. mean annual precipitation and annual actual evapotranspiration), it is unclear whether plant–granivore interactions are themselves influenced by these climatic factors across broad spatial extents. We evaluated whether climatic conditions that are known to alter the abundance and activity of granivorous animals also affect rates of seed removal.

Location

Eleven sites across temperate North America.

Methods

We used a common protocol to assess the removal of the same seed species (Avena sativa) over a 2‐day period. Model selection via the Akaike information criterion was used to determine a set of candidate binomial generalized linear mixed models that evaluated the relationship between local climatic data and post‐dispersal seed predation.

Results

Annual actual evapotranspiration was the single best predictor of the proportion of seeds removed. Annual actual evapotranspiration and mean annual precipitation were both positively related to mean seed removal and were included in four and three of the top five models, respectively. Annual temperature range was also positively related to seed removal and was an explanatory variable in three of the top four models.

Main conclusions

Our work provides the first evidence that energy and precipitation, which are known to affect consumer abundance and activity, also translate to strong, predictable patterns of seed predation across a continent. More generally, these findings suggest that future changes in temperature and precipitation could have widespread consequences for plant species composition in grasslands, through impacts on plant recruitment.
Dermatopathology in sub‐Saharan Africa: a systematic 5‐year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania
Authors: Beltraminelli H. , Kiprono S. , Zuriel D. , Swai B. , Giabbani E. , Grossmann H. , Masenga J.E.
Published: December 2014

Background

Proper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub‐Saharan Africa, where little is known about the spectrum of histopathological features observed.

Objectives

To investigate the spectrum of dermatopathological diagnoses made in a sub‐Saharan African reference centre of a large, mainly rural area.

Patients/Methods

To retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.

Results

There were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC.

Conclusions

In this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.
Within‐population genetic effects of mtDNA on metabolic rate in Drosophila subobscura
Authors: Kurbalija Novičić Z. , Immonen E. , Jelić M. , AnÐelković M. , Stamenković‐Radak M. , Arnqvist G.
Published: December 2014

A growing body of research supports the view that within‐species sequence variation in the mitochondrial genome (mtDNA) is functional, in the sense that it has important phenotypic effects. However, most of this empirical foundation is based on comparisons across populations, and few studies have addressed the functional significance of mtDNA polymorphism within populations. Here, using mitonuclear introgression lines, we assess differences in whole‐organism metabolic rate of adult Drosophila subobscura fruit flies carrying either of three different sympatric mtDNA haplotypes. We document sizeable, up to 20%, differences in metabolic rate across these mtDNA haplotypes. Further, these mtDNA effects are to some extent sex specific. We found no significant nuclear or mitonuclear genetic effects on metabolic rate, consistent with a low degree of linkage disequilibrium between mitochondrial and nuclear genes within populations. The fact that mtDNA haplotype variation within a natural population affects metabolic rate, which is a key physiological trait with important effects on life‐history traits, adds weight to the emergent view that mtDNA haplotype variation is under natural selection and it revitalizes the question as to what processes act to maintain functional mtDNA polymorphism within populations.
Relaxant and Antioxidant Capacity of the Red Wine Polyphenols, Resveratrol and Quercetin, on Isolated Mice Corpora Cavernosa
Authors: Boydens Charlotte , Pauwels Bart , Decaluwé Kelly , Brouckaert Peter , Van de Voorde Johan
Published: December 2014

Introduction

The red wine polyphenols resveratrol and quercetin are known for their vasorelaxant and antioxidant capacity, which is assumed to rely on the activation of the nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway. Vasodilators as well as antioxidants can regulate penile erection and be beneficial for the treatment of erectile dysfunction (ED).

Aims

The goal of this study was to evaluate the NO/sGC dependency of the relaxant effect of resveratrol and quercetin on mice aorta and corpora cavernosa (CC), as well as to explore their influence on oxidative stress-induced ED.

Methods

Isolated mice aorta and CC were mounted for isometric tension recordings into organ baths. Cumulative concentration-response curves were constructed for resveratrol and quercetin in the absence/presence of inhibitors of the NO/sGC pathway. In addition, in CC the effect of resveratrol and quercetin was studied on NO-mediated relaxations using acetylcholine (Ach), sodium nitroprusside (SNP), and electrical field stimulation (EFS). In certain experiments, corporal tissues were exposed to oxidative stress using palmitic acid (PA, 0.5 mM).

Main Outcome Measures

Corporal responses to resveratrol and quercetin were measured in the presence/absence of inhibitors of different molecular pathways. The effect of resveratrol and quercetin incubation on Ach-, SNP-, or EFS-mediated responses was explored in the presence/absence of PA.

Results

While both polyphenols are potent vasodilators of mice aorta, only resveratrol relaxes mice CC. The relaxation response to resveratrol on aorta was diminished in sGCα1−/− mice, but not on CC. The polyphenols did not influence Ach-, SNP-, or EFS-mediated relaxations as such. Resveratrol, but not quercetin, was able to significantly reverse PA-induced decrease of EFS relaxations.

Conclusion

The red wine compound resveratrol, but not quercetin, relaxes isolated mice CC concentration-dependently through mechanisms independent of the NO/sGC pathway. Resveratrol is a more potent antioxidant than quercetin, being able to restore decreased neuronal NO responses in mice CC.
A new point mutation in the iron–sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorum
Authors: Wang Yong , Duan Yabing , Wang Jianxin , Zhou Mingguo
Published: December 2014

Research has established that mutations in highly conserved amino acids of the succinate dehydrogenase (SDH) complex in various fungi confer SDH inhibitor (SDHI) resistance. For Sclerotinia sclerotiorum (Lib.) de Bary, a necrotrophic fungus with a broad host range and a worldwide distribution, boscalid resistance has been attributed to the mutation H132R in the highly conserved SdhD subunit protein of the SDH complex. In our previous study, however, only one point mutation, A11V in SdhB (GCA to GTA change in SdhB), was detected in S. sclerotiorum boscalid‐resistant (BR) mutants. In the current study, replacement of the SdhB gene in a boscalid‐sensitive (BS) S. sclerotiorum strain with the mutant SdhB gene conferred resistance. Compared with wild‐type strains, BR and GSM (SdhB gene in the wild‐type strain replaced by the mutant SdhB gene) mutants were more sensitive to osmotic stress, lacked the ability to produce sclerotia and exhibited lower expression of the pac1 gene. Importantly, the point mutation was not located in the highly conserved sequence of the iron–sulfur subunit of SDH. These results suggest that resistance based on non‐conserved vs. conserved protein domains differs in mechanism. In addition to increasing our understanding of boscalid resistance in S. sclerotiorum, the new information will be useful for the development of alternative antifungal drugs.
Native and denatured egg white protein IgE tests discriminate hen's egg allergic from egg‐tolerant children
Authors: Benhamou Senouf Avigael H. , Borres Magnus P. , Eigenmann Philippe A.
Published: December 2014

Background

Accurate diagnosis of egg allergy by IgE testing is challenged by a large number of atopic subjects sensitized, but clinically tolerant to eggs. In addition, discrimination between allergy to raw only, or raw and cooked egg allergy is important. In this study, we investigate the diagnostic performance of IgE tests to native and denatured egg proteins.

Methods

According to food challenges and clinical tolerance, study subjects were randomized to the following groups: (Group A) sensitized but clinically tolerant to egg, (Group B) allergic to raw egg only, or (Group C) allergic to raw and cooked egg. Serum‐specific IgE to native or reduced and oxidized egg white, ovomucoid, and ovalbumin were measured.

Results

Increasing titers of specific IgE to the various proteins were found according to the degree of the egg allergy. Cut‐off values for IgE testing to native egg could be determined to distinguish between raw egg allergic and egg‐tolerant subjects (1.6 kU/l), as well as raw and cooked egg allergic and egg‐tolerant subjects (4.1 kU/l). ROC curves analysis showed that native ovalbumin was the best test for the diagnosis of allergy to raw and cooked egg, and native ovomucoid was best to distinguish between allergy to raw only, and allergy to raw and cooked egg. Sequential testing improved the diagnosis, when in addition to IgE to native egg white, IgE to native ovalbumin was tested for the diagnosis of raw and cooked egg allergy, and IgE to native ovomucoid for the discrimination between allergy to raw only, or to raw and cooked eggs.

Conclusion

The diagnosis of egg allergy can be significantly improved using a panel of IgE tests to egg proteins in the native or denatured form. The accuracy can be improved using combined IgE testing.
Lichen Nitidus Presenting with Nail Changes—Case Report and Review of the Literature
Authors: Tay Evelyn Yuxin , Ho Madeline Sheun Ling , Chandran Nisha Suyien , Lee Joyce Siong‐See , Heng Yee Kiat
Published: December 2014

Lichen nitidus of the nail is rare and can precede the onset of skin lesions. Delayed diagnosis is common. We present an unusual case of lichen nitidus–associated nail changes that preceded the onset of skin lesions in a 4‐year‐old Indian girl. We also conduct a review of six other cases of lichen nitidus with nail involvement from the English‐language literature. Clues to the diagnosis of lichen nitidus include violaceous or pigmentary changes of the nail fold and subtle lichenoid papules on the affected digits. Lichen nitidus of the nails appears to be less severe than nail changes of lichen planus and is generally self‐limiting. Understanding the natural history of lichen nitidus of the nails will help physicians better counsel patients and their families.
Ulcerated Spitz Nevus Masquerading as a Juvenile Xanthogranuloma
Authors: Ghahramani Grant K. , Swick Brian L. , Ciliberto Heather
Published: December 2014

We report a case of ulcerated atypical Spitz nevi that demonstrated a yellow to light orange background under dermoscopy, which can be seen in juvenile xanthogranuloma (JXG) and is referred to as the “setting sun” appearance. This yellow to orange appearance was due to serous crusting and not histiocytic infiltration, which is seen in JXG. This case highlights overlapping dermatoscopic features between the two skin lesions and polymorphous vascular structures, which are unique to atypical Spitz nevi.
Tallgrass prairie restoration: implications of increased atmospheric nitrogen deposition when site preparation minimizes adventive grasses
Authors: McPhee Jennifer , Borden Laura , Bowles Jane , Henry Hugh A. L.
Published: December 2014

Site preparation designed to exhaust the soil seedbank of adventive species can improve the success of tallgrass prairie restoration. Despite these efforts, increased rates of atmospheric nitrogen (N) deposition over the next century could potentially promote the growth of nitrophilic, adventive species in tallgrass restoration projects. We used a field experiment to examine how N addition affected species composition and plant productivity over the first 3 years of a tallgrass prairie restoration that was preceded by the planting of glyphosate‐resistant crops and multiple applications of glyphosate to exhaust the pre‐existing seedbank. We predicted that N addition would increase the percent cover of adventive plant species not included in the original seeding. Contrary to our prediction, only the cover of native species increased with N addition; native non‐leguminous forbs increased substantially, with Conyza canadensis (a weedy native species not part of the restoration seed mix) exploiting the combination of high N and bare ground in the first year, and non‐leguminous forbs (in particular Monarda fistulosa) and native C3 grasses, all of which were seeded, increasing with N addition by the third year. Native legumes was the only functional group that exhibited lower cover in N addition plots than in control plots. There was no significant response by native C4 grasses to N addition, and adventive grasses remained mostly absent from the plots. Overall, our results suggest that site pre‐treatment with herbicide may continue to be effective in minimizing adventive grasses in restored tallgrass prairie, despite future increases in atmospheric N deposition.
Clinical use of microRNAs as potential non‐invasive biomarkers for detecting non‐small cell lung cancer: A meta‐analysis
Authors: Wang Huoqiang , Wu Songnian , Zhao Long , Zhao Juan , Liu Jinjun , Wang Zhihao
Published: December 2014

Emerging studies have revealed that microRNA(miRNA) in body fluid may serve as a potential biomarker to detect non‐small cell lung cancer (NSCLC). However, the diagnostic accuracy of miRNAforNSCLCdetection is still under debate because there is inconsistency in previous studies. Hence, we conducted this meta‐analysis to comprehensively evaluate the diagnostic performance of miRNA. A systematic literature search was performed to retrieve relevant articles inPubMed and other databases, andSTATA12.0 (StataCorp, College Station, TX, USA) was used to calculate the pooled parameters. A total of 28 articles involving 2121NSCLCpatients and 1582 healthy controls were included in this meta‐analysis. The overall pooled sensitivity and specificity of miRNAwere 0.75 and 0.79, respectively. The pooled positive likelihood ratio was 3.6, negative likelihood ratio was 0.32 and diagnostic odds ratio was 12. The area under the curve (AUC) was 0.84. Subgroup and meta‐regression analyses established that miRNAassays were more accurate inCaucasian populations (AUCof 0.86, sensitivity of 0.79 and specificity of 0.82, respectively) than inAsian populations (AUC, sensitivity and specificity of 0.83, 0.72 and 0.80, respectively). In addition, the multiple miRNAassays (AUCof 0.89, sensitivity of 0.83 and specificity of 0.82, respectively) showed a higher accuracy than single miRNAassays (AUC, sensitivity and specificity of 0.81, 0.77 and 0.71, respectively) inNSCLCdetection. Subgroup analyses based on specimen types suggested that blood‐based miRNA(AUCof 0.86, sensitivity of 0.78 and specificity of 0.80, respectively) may have a higher diagnostic accuracy as biomarkers than sputum‐based miRNA(AUCof 0.81, sensitivity of 0.69 and specificity of 0.80, respectively). In conclusion, miRNAmay serve as a potential biomarker inNSCLSdetection, especially the multiple miRNAfrom blood, with a relatively high diagnostic accuracy.
Adding strength to endurance training does not enhance aerobic capacity in cyclists
Authors: Psilander N. , Frank P. , Flockhart M. , Sahlin K.
Published: December 2014

The molecular signaling of mitochondrial biogenesis is enhanced when resistance exercise is added to a bout of endurance exercise. The purpose of the present study was to examine if this mode of concurrent training translates into increased mitochondrial content and improved endurance performance. Moderately trained cyclists performed 8 weeks (two sessions per week) of endurance training only (E, n = 10; 60‐min cycling) or endurance training followed by strength training (ES, n = 9; 60‐min cycling + leg press). Muscle biopsies were obtained before and after the training period and analyzed for enzyme activities and protein content. Only the ES group increased in leg strength (+19%, P < 0.01), sprint peak power (+5%, P < 0.05), and short‐term endurance (+9%, P < 0.01). In contrast, only the E group increased in muscle citrate synthase activity (+11%, P = 0.06), lactate threshold intensity (+3%, P < 0.05), and long‐term endurance performance (+4%, P < 0.05). Content of mitochondrial proteins and cycling economy was not affected by training. Contrary to our hypothesis, the results demonstrate that concurrent training does not enhance muscle aerobic capacity and endurance performance in cyclists.
10‐20‐30 training increases performance and lowers blood pressure and VEGF in runners
Authors: Gliemann Lasse , Gunnarsson Thomas P. , Hellsten Ylva , Bangsbo Jens
Published: December 2014

The present study examined the effect of training by the 10‐20‐30 concept on performance, blood pressure (BP), and skeletal muscle angiogenesis as well as the feasibility of completing high‐intensity interval training in local running communities. One hundred sixty recreational runners were divided into either a control group (CON; n = 28), or a 10‐20‐30 training group (10‐20‐30; n = 132) replacing two of three weekly training sessions with 10‐20‐30 training for 8 weeks and performance of a 5‐km run (5‐K) and BP was measured. VO2max was measured and resting muscle biopsies were taken in a subgroup of runners (n = 18). 10‐20‐30 improved 5‐K time (38 s) and lowered systolic BP (2 ± 1 mmHg). For hypertensive subjects in 10‐20‐30 (n = 30), systolic and diastolic BP was lowered by 5 ± 4 and 3 ± 2 mmHg, respectively, which was a greater reduction than in the non‐hypertensive subjects (n = 102). 10‐20‐30 increased VO2max but did not influence muscle fiber area, distribution or capillarization, whereas the expression of the pro‐angiogenic vascular endothelial growth factor (VEGF) was lowered by 22%. No changes were observed in CON. These results suggest that 10‐20‐30 training is an effective and easily implemented training intervention improving endurance performance, VO2max and lowering BP in recreational runners, but does not affect muscle morphology and reduces muscle VEGF.
Crosstalk Between Mitochondria and Mitosis
Authors: Hurtley Stella M.
Published: December 2014

Cell division and mitochondrial protein import are directly linked by cyclin-dependent phosphorylation of a mitochondrial assembly factor.
Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch Regimens in Immunocompromised Japanese Pediatric Patients
Authors: Mori Masaaki , Kobayashi Ryoji , Kato Koji , Maeda Naoko , Fukushima Keitaro , Goto Hiroaki , Inoue Masami , Muto Chieko , Okayama Akifumi , Watanabe Kenichi , Liu Ping
Published: December 2014

The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of voriconazole following intravenous-to-oral switch regimens used with immunocompromised Japanese pediatric subjects (age 2 to <15 years) at high risk for systemic fungal infection. Twenty-one patients received intravenous-to-oral switch regimens based on a recent population pharmacokinetic modeling; they were given 9 mg/kg of body weight followed by 8 mg/kg of intravenous (i.v.) voriconazole every 12 h (q12h), and 9 mg/kg (maximum, 350 mg) of oral voriconazole q12h (for patients age 2 to <12 or 12 to <15 years and <50 kg) or 6 mg/kg followed by 4 mg/kg of i.v. voriconazole q12h and 200 mg of oral voriconazole q12h (for patients age 12 to <15 years and ≥50 kg). The steady-state area under the curve over the 12-h dosing interval (AUC
0–12,ss
) was calculated using the noncompartmental method and compared with the predicted exposures in Western pediatric subjects based on the abovementioned modeling. The geometric mean (coefficient of variation) AUC
0–12,ss
values for the intravenous and oral regimens were 51.1 μg · h/ml (68%) and 45.8 μg · h/ml (90%), respectively; there was a high correlation between AUC
0–12,ss
and trough concentration. Although the average exposures were higher in the Japanese patients than those in the Western pediatric subjects, the overall voriconazole exposures were comparable between these two groups due to large interindividual variability. The exposures in the 2 cytochrome P450 2C19 poor metabolizers were among the highest. Voriconazole was well tolerated. The most common treatment-related adverse events were photophobia and abnormal hepatic function. These recommended doses derived from the modeling appear to be appropriate for Japanese pediatric patients, showing no additional safety risks compared to those with adult patients. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01383993.)
In Vitro
and
In Vivo
Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450
Authors: Pilot-Matias Tami , Tripathi Rakesh , Cohen Daniel , Gaultier Isabelle , Dekhtyar Tatyana , Lu Liangjun , Reisch Thomas , Irvin Michelle , Hopkins Todd , Pithawalla Ron , Middleton Timothy , Ng Teresa , McDaniel Keith , Or Yat Sun , Menon Rajeev , Kempf Dale , Molla Akhteruzzaman , Collins Christine
Published: December 2014

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively.
In vitro
, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log
10
was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. NCT01074008.)
The Novel Arylamidine T-2307 Maintains
In Vitro
and
In Vivo
Activity against Echinocandin-Resistant Candida albicans
Authors: Wiederhold Nathan P. , Najvar Laura K. , Fothergill Annette W. , Bocanegra Rosie , Olivo Marcos , McCarthy Dora I. , Kirkpatrick William R. , Fukuda Yoshiko , Mitsuyama Junichi , Patterson Thomas F.
Published: December 2014

We evaluated the
in vitro
and
in vivo
activities of the investigational arylamidine T-2307 against echinocandin-resistant
Candida albicans
. T-2307 demonstrated potent
in vitro
activity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistant
C. albicans
infections.
Mechanism of Reduced Vancomycin Susceptibility Conferred by
walK
Mutation in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain MW2
Authors: Hu Jinfeng , Zhang Xu , Liu Xiaoyu , Chen Chuan , Sun Baolin
Published: December 2014

Point mutations with unclear molecular mechanisms are often associated with vancomycin resistance in
Staphylococcus aureus
. Here, we observed that the
walK
(G223D) mutation caused decreased expression of genes associated with cell wall metabolism, decreased autolytic activity, thickened cell walls, and reduced vancomycin susceptibility. A phosphorylation assay showed that WalK (G223D) exhibited reduced autophosphorylation, which led to reduced phosphorylation of WalR. An electrophoretic mobility shift assay indicated that WalK (G223D)-phosphorylated WalR had a reduced capacity to bind to the
atlA
promoter.
Analysis of Neisseria gonorrhoeae Azithromycin Susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013
Authors: Kirkcaldy Robert D. , Soge Olusegun , Papp John R. , Hook Edward W. , del Rio Carlos , Kubin Grace , Weinstock Hillard S.
Published: December 2014

Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which
Neisseria gonorrhoeae
can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144
N. gonorrhoeae
isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC
50
was 0.25 μg/ml, and the MIC
90
was 0.5 μg/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 μg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States, and the prevalence of reduced azithromycin susceptibility remains low. These findings support the continued use of azithromycin in a combination therapy regimen for gonorrhea.
Hydroxylated Tropolones Inhibit Hepatitis B Virus Replication by Blocking Viral Ribonuclease H Activity
Authors: Lu Gaofeng , Lomonosova Elena , Cheng Xiaohong , Moran Eileen A. , Meyers Marvin J. , Le Grice Stuart F. J. , Thomas Craig J. , Jiang Jian-kang , Meck Christine , Hirsch Danielle R. , D'Erasmo Michael P. , Suyabatmaz Duygu M. , Murelli Ryan P. , Tavis John E.
Published: December 2014

Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of α-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC
50
) being 2.3 μM. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC
50
) being 0.34 μM. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC
50
] = 25 to 79 μM). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact α-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically α-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection.
The Role of Host Phylogeny Varies in Shaping Microbial Diversity in the Hindguts of Lower Termites
Authors: Tai Vera , James Erick R. , Nalepa Christine A. , Scheffrahn Rudolf H. , Perlman Steve J. , Keeling Patrick J.
Published: December 2014

The hindguts of lower termites and
Cryptocercus
cockroaches are home to a distinct community of archaea, bacteria, and protists (primarily parabasalids and some oxymonads). Within a host species, the composition of these hindgut communities appears relatively stable, but the evolutionary and ecological factors structuring community composition and stability are poorly understood, as are differential impacts of these factors on protists, bacteria, and archaea. We analyzed the microbial composition of parabasalids and bacteria in the hindguts of
Cryptocercus punctulatus
and 23 species spanning 4 families of lower termites by pyrosequencing variable regions of the small-subunit rRNA gene. Especially for the parabasalids, these data revealed undiscovered taxa and provided a phylogenetic basis for a more accurate understanding of diversity, diversification, and community composition. The composition of the parabasalid communities was found to be strongly structured by the phylogeny of their hosts, indicating the importance of historical effects, although exceptions were also identified. Particularly, spirotrichonymphids and trichonymphids likely were transferred between host lineages. In contrast, host phylogeny was not sufficient to explain the majority of bacterial community composition, but the compositions of the
Bacteroidetes
,
Elusimicrobia
,
Tenericutes
,
Spirochaetes
, and
Synergistes
were structured by host phylogeny perhaps due to their symbiotic associations with protists. All together, historical effects probably resulting from vertical inheritance have had a prominent role in structuring the hindgut communities, especially of the parabasalids, but dispersal and environmental acquisition have played a larger role in community composition than previously expected.
Development of a Matrix Tool for the Prediction of Vibrio Species in Oysters Harvested from North Carolina
Authors: Froelich B. A. , Ayrapetyan M. , Fowler P. , Oliver J. D. , Noble R. T.
Published: December 2014

The United States has federal regulations in place to reduce the risk of seafood-related infection caused by the estuarine bacteria
Vibrio vulnificus
and
Vibrio parahaemolyticus
. However, data to support the development of regulations have been generated in a very few specific regions of the nation. More regionally specific data are needed to further understand the dynamics of human infection relating to shellfish-harvesting conditions in other areas. In this study, oysters and water were collected from four oyster harvest sites in North Carolina over an 11-month period. Samples were analyzed for the abundances of total
Vibrio
spp.,
V. vulnificus
, and
V. parahaemolyticus
; environmental parameters, including salinity, water temperature, wind velocity, and precipitation, were also measured simultaneously. By utilizing these data, preliminary predictive management tools for estimating the abundance of
V. vulnificus
bacteria in shellfish were developed. This work highlights the need for further research to elucidate the full suite of factors that drive
V. parahaemolyticus
abundance.
Klebsiella pneumoniae Translocates across the Intestinal Epithelium via Rho GTPase- and Phosphatidylinositol 3-Kinase/Akt-Dependent Cell Invasion
Authors: Hsu Chun-Ru , Pan Yi-Jiun , Liu Ju-Yun , Chen Chun-Tang , Lin Tzu-Lung , Wang Jin-Town
Published: December 2014

Klebsiella pneumoniae
is an important pathogen that causes hospital-acquired septicemia and is associated with the recent emergence of community-acquired pyogenic liver abscess (PLA). Clinical typing suggests that
K. pneumoniae
infections originate from the gastrointestinal reservoir. However, the underlying mechanism remains unknown. Here, we have sought to determine how
K. pneumoniae
penetrates the intestinal barrier. We identified that bacteremia and PLA clinical isolates adhered to and invaded intestinal epithelial cells. Internalization of
K. pneumoniae
in three different human colonic cell lines was visualized by confocal microscopy and three-dimensional (3D) imaging. Using a Transwell system, we demonstrated that these
K. pneumoniae
isolates translocated across a polarized Caco-2 monolayer. No disruptions of transepithelial electrical resistance and altered distribution of tight junction protein ZO-1 or occludin were observed. Therefore,
K. pneumoniae
appeared to penetrate the intestinal epithelium via a transcellular pathway. Using specific inhibitors, we characterized the host signaling pathways involved. Inhibition by cytochalasin D and nocodazole suggested that actin and microtubule cytoskeleton were both important for
K. pneumoniae
invasion. A Rho inhibitor, ML141, LY294002, and an Akt1/2 inhibitor diminished
K. pneumoniae
invasion in a dose-dependent manner, indicating that Rho family GTPases and phosphatidylinositol 3-kinase (PI3K)/Akt signaling were required. By a mouse model of gastrointestinal colonization,
in vivo
invasion of
K. pneumoniae
into colonic epithelial cells was demonstrated. Our results present evidence to describe a possible mechanism of gastrointestinal translocation for
K. pneumoniae
. Cell invasion by manipulating host machinery provides a pathway for gut-colonized
K. pneumoniae
cells to penetrate the intestinal barrier and access extraintestinal locations to cause disease.