bluuebunny/crossref_metadata_2025 huggingface dataset:
Population pharmacodynamic analysis of LDL‐cholesterol lowering effects by statins and co‐medications based on electronic medical records
Authors: Kakara Makoto , Nomura Hiroko , Fukae Masato , Gotanda Keisuke , Hirota Takeshi , Matsubayashi Sunao , Shimomura Hideki , Hirakawa Masaaki , Ieiri Ichiro
Published: April 2014

Aims

HMG‐CoA reductase inhibitors are available for use in low density lipoprotein‐cholesterol (LDL‐C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL‐C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records.

Methods

Patient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records. Patients who received atorvastatin, pitavastatin or rosuvastatin were enrolled. A physiological indirect response model was used to describe the changes observed in LDL‐C concentrations. The PPD analysis was performed using nonmem 7.2.0 with the first order conditional estimation method with interaction (FOCE‐INTER).

Results

An indirect response Imax model, based on the 2863 LDL‐C concentrations of 378 patients, successfully and quantitatively described the time course for the LDL‐C lowering effects of three statins. The combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL synthesis rate (Kin) by 10.9%. A simulation indicated that the combined treatment of ezetimibe with rosuvastatin (2.5 mg day−1) led to superior clinical responses than those with high doses of rosuvastatin (5.0 mg day−1) monotherapy, even in patients with higher baseline LDL‐C concentrations prior to the treatment.

Conclusions

A newly constructed PPD model supported previous evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In addition, the established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice.
Mephedrone, Methylone and 3,4‐Methylenedioxypyrovalerone (MDPV) Induce Conditioned Place Preference in Mice
Authors: Karlsson Louise , Andersson Mikael , Kronstrand Robert , Kugelberg Fredrik C.
Published: April 2014

During the last decade, there has been a worldwide increase in popularity and abuse of synthetic cathinones. Common ingredients of the so‐called bath salts include mephedrone, methylone and 3,4‐methylenedioxypyrovalerone (MDPV). Relatively little information about the pharmacology and addiction potential of these drugs is available. We used the conditioned place preference (CPP) paradigm to explore the reinforcing effects of three different synthetic cathinones. The primary aim of this study was to investigate whether mephedrone, methylone and MDPV induce CPP in mice. The secondary aims were to investigate a possible dose–response CPP and whether the synthetic cathinones induce higher CPP than amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone, methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20 mg/kg (i.p.). During the conditioning, the mice received two training sessions per day for 4 days. All four tested drugs showed a significant place preference compared with controls. Mice conditioned with MDPV (5 and 10 mg/kg) displayed a greater preference score compared to mice conditioned with amphetamine (5 and 10 mg/kg). Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher than amphetamine strongly suggesting addictive properties. Given the public health concern of abuse, future pharmacological studies are necessary to fully understand the effects of these drugs.
Subcutaneous pulsatile glucocorticoid replacement therapy
Authors: Russell Georgina M. , Durant Claire , Ataya Alia , Papastathi Chrysoula , Bhake Ragini , Woltersdorf Wolfram , Lightman Stafford
Published: April 2014

The glucocorticoid hormone cortisol is released in pulses resulting in a complex and dynamic ultradian rhythm of plasma cortisol that underlies the classical circadian rhythm. These oscillating levels are also seen at the level of tissues such as the brain and trigger pulses of gene activation and downstream signalling. Different patterns of glucocorticoid presentation (constant vs pulsatile) result not only in different patterns of gene regulation but also in different neuroendocrine and behavioural responses. Current ‘optimal’ glucocorticoid replacement therapy results in smooth hormone blood levels and does not replicate physiological pulsatile cortisol secretion. Validation of a novel portable pulsatile continuous subcutaneous delivery system in healthy volunteers under dexamethasone and metyrapone suppression. Pulsatile subcutaneous hydrocortisone more closely replicates physiological circadian and ultradian rhythmicity.
Why the body comes first: effects of experimenter touch on infants' word finding
Authors: Seidl Amanda , Tincoff Ruth , Baker Christopher , Cristia Alejandrina
Published: April 2014

The lexicon of 6‐month‐olds is comprised of names and body part words. Unlike names, body part words do not often occur in isolation in the input. This presents a puzzle: How have infants been able to pull out these words from the continuous stream of speech at such a young age? We hypothesize that caregivers' interactions directed at and on the infant's body may be at the root of their early acquisition of body part words. An artificial language segmentation study shows that experimenter‐provided synchronous tactile cues help 4‐month‐olds to find words in continuous speech. A follow‐up study suggests that this facilitation cannot be reduced to the highly social situation in which the directed interaction occurs. Taken together, these studies suggest that direct caregiver–infant interaction, exemplified in this study by touch cues, may play a key role in infants' ability to find word boundaries, and suggests that early vocabulary items may consist of words often linked with caregiver touches.

A video abstract of this article can be viewed athttp://youtu.be/NfCj5ipatyE
Altered plasma fibrin clot properties and fibrinolysis in patients with multiple myeloma
Authors: Undas Anetta , Zubkiewicz‐Usnarska Lidia , Helbig Grzegorz , Woszczyk Dariusz , Kozińska Justyna , Dmoszyńska Anna , Podolak‐Dawidziak Maria , Kuliczkowski Kazimierz
Published: April 2014

Background

Multiple myeloma (MM) is associated with increased risk of venous and arterial thromboembolism. Formation of denser and poorly lysable fibrin clots is observed in patients with arterial and venous thromboembolism. We investigated fibrin clot properties and their determinants in MM patients.

Materials and Methods

Ex vivo plasma fibrin clot permeability, turbidity and susceptibility to lysis were evaluated in 106 MM patients at the time of diagnosis vs. 100 age‐ and sex‐matched controls. MM patients had lower clot permeability (Ks), compaction, indicating denser fibrin clots, impaired fibrin polymerization with longer lag phase and lower final turbidity (D−Dmax), combined with hypofibrinolysis reflected by longer lysis time and slower rate of D‐dimer release from fibrin clots (D−Drate) compared with controls (all P < 0·001).

Results

Patients with IgG MM had lower Ks compared with IgA MM [5·9 (5·1–6·4) vs. 6·3 (5·9–7·2) 10−9 cm2; P = 0·007] and longer lysis time compared with light‐chain‐disease patients [11·4 (10·9–12·3) vs. 10·7 (9·8–11·9) min; P = 0·022]. Of the fibrin variables, only Ks was significantly lower in patients with International Staging System (ISS) grade III than in those with ISS grade I and II [5·9 (4·9–6·6) vs. 6·2 (5·7–6·8) 10−9 cm2; P = 0·015]. Multivariate analysis adjusted for age and fibrinogen showed that in MM patients elevated peak thrombin levels determine Ks and D−Dmax, while thrombin‐activatable fibrinolysis inhibitor (TAFI) activity predicts Ks, t50%, D−Drate and lag phase.

Conclusions

Our study demonstrates prothrombotic fibrin clot phenotype in patients with MM, with a significant impact of increased thrombin formation and TAFI activity.
Horizontal transfer of the msp130 gene supported the evolution of metazoan biomineralization
Authors: Ettensohn Charles A.
Published: April 2014

It is widely accepted that biomineralized structures appeared independently in many metazoan clades during the Cambrian. How this occurred, and whether it involved the parallel co‐option of a common set of biochemical and developmental pathways (i.e., a shared biomineralization “toolkit”), are questions that remain unanswered. Here, I provide evidence that horizontal gene transfer supported the evolution of biomineralization in some metazoans. I show that Msp130 proteins, first described as proteins expressed selectively by the biomineral‐forming primary mesenchyme cells of the sea urchin embryo, have a much wider taxonomic distribution than was previously appreciated. Msp130 proteins are present in several invertebrate deuterostomes and in one protostome clade (molluscs). Surprisingly, closely related proteins are also present in many bacteria and several algae, and I propose that msp130 genes were introduced into metazoan lineages via multiple, independent horizontal gene transfer events. Phylogenetic analysis shows that the introduction of an ancestral msp130 gene occurred in the sea urchin lineage more than 250 million years ago and that msp130 genes underwent independent, parallel duplications in each of the metazoan phyla in which these genes are found.
Traumatic dental injuries among 8‐ to 12‐year‐old schoolchildren in Pinggu District, Beijing, China, during 2012
Authors: Chen Zhuo , Si Yan , Gong Yi , Wang Jian‐Guo , Liu Jing‐Xin , He Yang , He Wen‐Peng , Nan Zhe , Zhang Yi
Published: April 2014

Background

Although traumatic dental injuries are most common during childhood and can cause significant health problems, the literature contains few reports of the prevalence of traumatic dental injuries in children in China.

Aim

To study the prevalence of and factors related to traumatic dental injuries among 8‐ to 12‐year‐old schoolchildren in Pinggu District, Beijing during 2012.

Material and Methods

An epidemiological survey of traumatic dental injuries was performed in all nine primary schools of Pinggu District, Beijing, China. Andreasen criteria as the diagnostic criteria were used in the study. A sample of 5165 students aged from 8 to 12 years old were examined, consisting of 2711 boys and 2454 girls.

Results

A total of 367 students (7.1%), 251 boys and 116 girls, were found to have traumatic dental injuries, and 442 permanent teeth were involved. Maxillary central incisors were the most affected by dental injuries (378, 85.5%). Among the 52 traumatized teeth (11.8%) that were treated, endodontic treatment (55.8%) was the most common method.

Conclusions

The study showed a relatively low prevalence of dental injuries in Pinggu District. The treatment rate of traumatized teeth was relatively low. Schoolchildren need more medical assistance when they face accidents. Policymakers should develop a strategy for the prevention of traumatic dental injuries. Educational programs to increase the knowledge of traumatic dental injuries and prevent them should be initiated for teachers and schoolchildren.
Effect of local spatial plant distribution and conspecific density on bumble bee foraging behaviour
Authors: GESLIN BENOÎT , BAUDE MATHILDE , MALLARD FRANCOIS , DAJOZ ISABELLE
Published: April 2014

1. Size variations in pollinator populations may modify competitive interactions among foragers. Competition among pollinators has been shown to lead to one of two contrasting behaviours: either specialisation to the most profitable plant species or generalisation to several species. When foraging, pollinators are also confronted with heterogeneity in the spatial distribution of plant resources. Because variations in both the forager density and plant spatial distribution can affect pollinator behaviour, focus was on the interactive effect of these two factors.

2. Bumble bee (Bombus terrestris
L.) individuals were trained on a focal species (Lotus corniculatus L.) and experimentally tested whether variations in the forager density (two or six bumble bees foraging together), plant community spatial distribution (two plant species: L. corniculatus and Medicago sativa, which were either patchily or randomly distributed), and their interaction modified bumble bee foraging behaviour.

3. It was shown that when confronted with a high forager density, bumble bees focused their visits towards the most familiar species, especially when foraging under a random plant distribution. These modifications affected the fruiting of the focal plant species, with a significantly lower reproductive success under low density/patchy conditions.

4. This study demonstrates that the foraging decisions of bumble bees are influenced by variations in both the conspecific density and plant spatial distribution. Given the increasing impact of human activities on plant‐pollinator communities, this raises the question of the potential implications of these results for plant communities in natural conditions when confronted with variations in the pollinator density and spatial distribution of plants.
How context dependent are species interactions?
Authors: Chamberlain Scott A. , Bronstein Judith L. , Rudgers Jennifer A.
Published: April 2014

The net effects of interspecific species interactions on individuals and populations vary in both sign (−, 0, +) and magnitude (strong to weak). Interaction outcomes are context‐dependent when the sign and/or magnitude change as a function of the biotic or abiotic context. While context dependency appears to be common, its distribution in nature is poorly described. Here, we used meta‐analysis to quantify variation in species interaction outcomes (competition, mutualism, or predation) for 247 published articles. Contrary to our expectations, variation in the magnitude of effect sizes did not differ among species interactions, and while mutualism was most likely to change sign across contexts (and predation least likely), mutualism did not strongly differ from competition. Both the magnitude and sign of species interactions varied the most along spatial and abiotic gradients, and least as a function of the presence/absence of a third species. However, the degree of context dependency across these context types was not consistent among mutualism, competition and predation studies. Surprisingly, study location and ecosystem type varied in the degree of context dependency, with laboratory studies showing the highest variation in outcomes. We urge that studying context dependency per se, rather than focusing only on mean outcomes, can provide a general method for describing patterns of variation in nature.
Unusual 4p16.3 deletions suggest an additional chromosome region for the Wolf‐Hirschhorn syndrome–associated seizures disorder
Authors: Zollino Marcella , Orteschi Daniela , Ruiter Mariken , Pfundt Rolph , Steindl Katharina , Cafiero Concetta , Ricciardi Stefania , Contaldo Ilaria , Chieffo Daniela , Ranalli Domiziana , Acquafondata Celeste , Murdolo Marina , Marangi Giuseppe , Asaro Alessia , Battaglia Domenica
Published: April 2014

Objective

Seizure disorder is one of the most relevant clinical manifestations in Wolf‐Hirschhorn syndrome (WHS) and it acts as independent prognostic factor for the severity of intellectual disability (ID). LETM1, encoding a mitochondrial protein playing a role in K+/H+ exchange and in Ca2+ homeostasis, is currently considered the major candidate gene. However, whether haploinsufficiency limited to LETM1 is enough to cause epilepsy is still unclear. The main purpose of the present research is to define the 4p chromosome regions where genes for seizures reside.

Methods

Comparison of our three unusual 4p16.3 deletions with 13 literature reports. Array‐comparative genomic hybridization (a‐CGH). Real‐time polymerase chain reaction (RT‐PCR) on messanger RNA (mRNA) of LETM1 and CPLX1. Direct sequencing of LETM1.

Results

Three unusual 4p16.3 deletions were detected by array‐CGH in absence of a obvious clinical diagnosis of WHS. Two of these, encompassing LETM1, were found in subjects who never had seizures. The deletions were interstitial, spanning 1.1 Mb with preservation of the terminal 1.77 Mb region in one case and 0.84 Mb with preservation of the terminal 1.07 Mb region in the other. The other deletion was terminal, affecting a 0.564 Mb segment, with preservation of LETM1, and it was associated with seizures and learning difficulties. Upon evaluating our patients along with literature reports, we noted that six of eight subjects with terminal 4p deletions preserving LETM1 had seizures, whereas seven of seven with interstitial deletions including LETM1 and preserving the terminal 1 Mb region on 4p did not. An additional chromosome region for seizures is suggested, falling within the terminal 1.5 Mb on 4p, not including LETM1.

Significance

We consider that haploinsufficiency not limited to LETM1 but including other genes acts as a risk factor for the WHS‐associated seizure disorder, according to a comorbidity model of pathogenesis. Additional candidate genes reside in the terminal 1.5 Mb region on 4p, most likely distal to LETM1.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Prevalence of and risk factors for equine obesity in Great Britain based on owner‐reported body condition scores
Authors: Robin C. A. , Ireland J. L. , Wylie C. E. , Collins S. N. , Verheyen K. L. P. , Newton J. R.
Published: April 2014

Reasons for performing the study

Few data are available on the prevalence of obesity in the general equine population of Great Britain (GB), and its associated risk factors.

Objectives

To estimate the prevalence of owner‐reported obesity in veterinary‐registered horses and ponies in GB, and identify factors associated with obesity.

Study design

A cross‐sectional survey of horse/pony owners in GB was undertaken using a postal questionnaire.

Methods

Thirty veterinary practices randomly selected horse/pony owners to complete a self‐administered postal questionnaire. Owners estimated body condition score using a modified Carroll and Huntington method (1–6 scale), and animals were classified as obese if they were scored as either 5 (fat) or 6 (very fat). Factors associated with obesity were assessed using logistic regression analysis.

Results

Prevalence of obesity was 31.2% (n = 247/792; 95% confidence interval [CI] 27.9–34.2%). Factors associated with increased odds of obesity were breed (P<0.001), ease of maintaining weight (P<0.001) and primary use (P = 0.002). Compared to Thoroughbreds, draught‐type (odds ratio [OR] 7.3; 95% CI 3.1–17.1), cob‐type (OR 5.6; 95% CI 2.5–12.5), native (OR 3.2; 95% CI 1.8–5.78) and Welsh breeds (OR 3.5; 95% CI 1.9–6.2) were more likely to be obese. Animals described as ‘good doers’ were more likely to be obese than those described as readily maintaining normal weight (OR 3.7; 95% CI 2.6–5.3). Compared to competition animals, animals used for pleasure riding (OR 2.5; 95% CI 1.4–4.4) and nonridden animals (OR 2.9; 95% CI 1.5–5.5) were more likely to be obese.

Conclusions

Identification of at‐risk breeds and other horse‐ and management‐level risk factors for obesity will enable optimal targeting of owner education regarding management strategies to reduce the frequency of equine obesity.
Management and horse‐level risk factors for recurrent colic in theUKgeneral equine practice population
Authors: Scantlebury C. E. , Archer D. C. , Proudman C. J. , Pinchbeck G. L.
Published: April 2014

Reasons for performing study

Recurrent colic occurs frequently in the general horse population but little evidence exists about what factors place horses at greater risk of recurrent colic.

Objectives

To quantify time‐varying and non time‐varying risk factors for recurrent colic among horses attended by first‐opinion veterinary surgeons in northwest England.

Study design

Nested case‐control study.

Methods

A nested case‐control study was conducted on data from a prospective longitudinal cohort study of 127 horses recruited subsequent to an episode of medical colic. Data were collected on management and recurrent colic episodes at 4‐monthly intervals by telephone questionnaires. All recurrent colic episodes were selected as cases; controls were unmatched and randomly selected from all horse‐time at risk. Data relating to the 30 days prior to the date of colic or control selection were used to determine exposure status. Multivariable logistic regression analyses were used to determine risk factors for recurrent colic.

Results

In total, 59 cases and 177 controls were included. The final model showed that horses that displayed crib‐biting/windsucking (odds ratio [OR] 10.1, 95% confidence interval [CI] 2.5–41.0) or weaving behaviour (OR3.9, 95%CI1.5–10.1) had an increased risk of recurrence of colic. Increasing time at pasture reduced the risk of recurrence (OR0.99, 95%CI0.99–1.0). A significant interaction was found suggesting that the risk associated with crib‐biting/windsucking may be modified by feeding fruit/vegetables; however, further research is required before recommendations for feeding practices can be made.

Conclusions

This study suggests that sufficient access to pasture may be an important means of reducing recurrent colic risk. The behavioural risk factors highlight individuals who may be at increased risk of recurrent colic and whose colic prevention strategies should be carefully managed.
Surgical stress influences cytokine content in autologous conditioned serum
Authors: Fjordbakk C. T. , Johansen G. M. , Løvås A. C. , Oppegård K. L. , Storset A. K.
Published: April 2014

Reasons for performing study

No recommendations have been made regarding the relative timing of blood collection for autologous conditioned serum (ACS) preparation and surgical procedures.

Objectives

1) To identify effects of surgical stress on cytokine levels inACS, 2) identify haematological markers for prediction of cytokine production inACSand 3) investigate the necessity for specialisedACScontainers when preparing a cytokine‐rich serum.

Study design

Experimentalin vitrostudy.

Methods

Blood was drawn from 15 stallions admitted for elective castration preoperatively and 22–24 h post operatively and incubated inACScontainers and plastic vacutainer tubes containingZSerum Clot Activator. Concentrations of interleukin (IL)‐1 receptor agonist (IL‐1Ra),IL‐10,IL‐1β, tumour necrosis factor (TNF)‐α, insulin‐like growth factor (IGF)‐1 and transforming growth factor (TGF)‐β were determined in all serum samples and compared between preparation methods and sampling time byANOVA. Changes in cytokine levels induced by incubation, defined as delta cytokine, were calculated by subtracting the baseline levels from the levels in incubated samples. Based on post operative serum amyloidA(SAA), horses were grouped into ‘mild‘, moderate’ and ‘marked’ surgical stress; delta cytokine levels in post operative samples were compared between these groups byANOVA.

Results

DeltaIGF‐1 was significantly lower in post operative samples compared with preoperative. Horses in the ‘marked’ surgical stress group had significantly lower deltaIL‐1Ra and deltaTGF‐β than the ‘moderate’ group and significantly lower deltaIGF‐1 than the ‘mild’ group. No association between cytokine levels and haematology variables were identified. Cytokine levels were comparable between serum prepared in blood tubes and in specialisedACScontainers.

Conclusions

Surgical stress influences the cytokine content inACS. Useful predictors of cytokine production inACSwere not identified. SpecialisedACScontainers may not be necessary for preparation of a cytokine‐rich serum.
Douglas‐fir plantations in Europe: a retrospective test of assisted migration to address climate change
Authors: Isaac‐Renton Miriam G. , Roberts David R. , Hamann Andreas , Spiecker Heinrich
Published: April 2014

We evaluate genetic test plantations of North American Douglas‐fir provenances in Europe to quantify how tree populations respond when subjected to climate regime shifts, and we examined whether bioclimate envelope models developed for North America to guide assisted migration under climate change can retrospectively predict the success of these provenance transfers to Europe. The meta‐analysis is based on long‐term growth data of 2800 provenances transferred to 120 European test sites. The model was generally well suited to predict the best performing provenances along north–south gradients in Western Europe, but failed to predict superior performance of coastal North American populations under continental climate conditions in Eastern Europe. However, model projections appear appropriate when considering additional information regarding adaptation of Douglas‐fir provenances to withstand frost and drought, even though the model partially fails in a validation against growth traits alone. We conclude by applying the partially validated model to climate change scenarios for Europe, demonstrating that climate trends observed over the last three decades warrant changes to current use of Douglas‐fir provenances in plantation forestry throughout Western and Central Europe.
A comparison of computational models with and without genotyping for prediction of response to second‐line HIV therapy
Authors: Revell AD , Boyd MA , Wang D , Emery S , Gazzard B , Reiss P , van Sighem AI , Montaner JS , Lane HC , Larder BA
Published: April 2014

Objectives

We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first‐line virological failure.

Methods

Two sets of models predicted virological response for 99 three‐drug regimens for patients on a failing regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and one nonnucleoside reverse transcriptase inhibitor in the Second‐Line study. One set used viral load, CD4 count, genotype, plus treatment history and time to follow‐up to make its predictions; the second set did not include genotype. Genotypic sensitivity scores were derived and the ranking of the alternative regimens compared with those of the models. The accuracy of the models and that of genotyping as predictors of the virological responses to second‐line regimens were compared.

Results

The rankings of alternative regimens by the two sets of models were significantly correlated in 60−69% of cases, and the rankings by the models that use a genotype and genotyping itself were significantly correlated in 60% of cases. The two sets of models identified alternative regimens that were predicted to be effective in 97% and 100% of cases, respectively. The area under the receiver‐operating curve was 0.72 and 0.74 for the two sets of models, respectively, and significantly lower at 0.55 for genotyping.

Conclusions

The two sets of models performed comparably well and significantly outperformed genotyping as predictors of response. The models identified alternative regimens predicted to be effective in almost all cases. It is encouraging that models that do not require a genotype were able to predict responses to common second‐line therapies in settings where genotyping is unavailable.
A EUBOEAN WARRIOR TRADER
Authors: POPHAM MERVYN R. , LEMOS IRENE S.
Published: April 2014

Summary A recently discovered burial in the Toumba Cemetery at Lefkandi, Euboea, differs from others previously found there in the shape of the tomb and the method of burial, which is a cremation contained in a bronze cauldron. The offerings, which include a sword, spearhead and iron arrowheads, make it certain that it is the burial of a warrior, but others, such as a series of stone weights, a N. Syrian cylinder seal and vases from Cyprus and Phoenicia indicate that he was a trader as well. In this preliminary acount, these and other aspects of the burial are considered.
SHIPS ON ROMAN COINS
Authors: ORNA‐ORNSTEIN J.
Published: April 2014

Summary More than 250 Roman coin types bear ships as their principal motif. These depictions cannot be assumed to be literal copies of Roman vessels. Their consistency and accuracy within each type and period must be tested to validate their use as historical documents. This having been done, a comparatively detailed picture of the form and development of Roman ships can be constructed from numismatic evidence. The closely datable nature of the evidence allows a more accurate assessment of the evolution of Roman vessels than is possible using any other data, and suggests that significant alterations need to be made to the accepted chronology of changes in Roman craft. Such alterations also have consequences for our understanding of the changing role of the Roman navy.
THE CELTS IN EASTERN EUROPE
Authors: SHCHUKIN MARK
Published: April 2014

Summary This article deals with the Celtic penetration of eastern Europe on the basis of archaeological evidence, and particularly the typology of bronze objects, and the light which it throws on an inscription from Olbia. It examines the relationship between cultural groupings and ethnic descriptions, and sets the problem in an historical context.
TORCS IN EARLY HISTORIC SCOTLAND
Authors: CESSFORD CRAIG
Published: April 2014

Summary Torcs are a prominent element in the Gododdin poem from Early Historic Scotland. This is intriguing as the archaeological evidence for torcs is much earlier. Examination of references to torcs in the poem shows that they were important status symbols worn by the entire war band. Archaeological evidence shows that gold torcs were worn in this area during the Iron Age, and in the early Roman period torcs occur on both native and Roman military sites. Some examples on Roman sites seem to be linked to the ala Petriana, an elite cavalry unit. As the poem is concerned with another elite cavalry group whose ancestors interacted with the ala Petriana the poetic prominence of torcs was probably influenced by this. Sculptural and hoard evidence confirms the use of torcs in Early Historic Scotland and reinforces both the idea of Roman influence and the link with cavalry.
Leaks, legislation and freedom of speech: How can the law effectively promote public‐interest whistleblowing?
Authors: FASTERLING Björn , LEWIS David
Published: April 2014

Attention is increasingly being focused on leaking, whistleblowing and associated compliance and incentives questions. The authors outline the differences between leaking and whistleblowing, notably on protection of the disclosers. They review provisions of international conventions on human rights and corruption, and compare approaches to protecting freedom of speech in France, Germany, the United Kingdom and the United States. Their findings highlight the complex, sometimes conflicting issues involved: public, individual, commercial and financial interests; abuse of power; security; confidentiality; the individual as law enforcer; and the employment relationship.
The ILO's Domestic Workers Convention and Recommendation: A window of opportunity for social justice
Authors: OELZ Martin
Published: April 2014

Domestic workers are a predominantly female workforce whose social and labour rights remained largely unattended for decades. Addressing this has become more urgent, as demand for household and personal care services is increasing. Convention No. 189 and Recommendation No. 201 set out global minimum standards for domestic work. The author first describes international labour and human rights law on domestic work prior to 2011. He then examines the instruments' definitions and scope and problems of particular groups; their provisions on working time, pay, work environment and living conditions; social security; and implementation and enforcement.
Changes in nerve‐ and endothelium‐mediated contractile tone of the corpus cavernosum in a mouse model of pre‐mature ageing
Authors: Lafuente‐Sanchis A. , Triguero D. , Garcia‐Pascual A.
Published: April 2014

Erectile dysfunction (ED) is very prevalent in the older population, although the ageing‐related mechanisms involved in the development of ED are poorly understood. We propose that age‐induced differences in nerve‐ and endothelium‐mediated smooth muscle contractility in the corpus cavernosum (CC) could be found between a senescent‐accelerated mouse prone (SAMP8) and senescent‐accelerated mouse resistant (SAMR1) strains. We analysed the changes in muscle tension induced by electrical field stimulation (EFS) or agonist addition ‘in vitro’, assessing nerve density (adrenergic, cholinergic and nitrergic), the expression of endothelial nitric oxide synthase (eNOS), cGMP accumulation and the distribution of interstitial cells (ICs) by immunofluorescence. We observed no change in both the nerve‐dependent adrenergic excitatory contractility at physiological levels of stimulation and in the nitrergic inhibitory response in SAMP8 animals. Unlike cholinergic innervation, the density of adrenergic and nitrergic nerves increased in SAMP8 mice. In contrast, smooth muscle sensitivity to exogenous noradrenaline (NA) was slightly reduced, whereas cGMP accumulation in response to EFS and DEA/NO, and relaxations to DEA/NO and sildenafil, were not modified. No changes in the expression of eNOS and in the distribution of vimentin‐positive ICs were detected in the aged animals. The ACh induced atropine‐sensitive biphasic endothelium‐dependent responses involved relaxation at low concentrations that turned into contractions at the highest doses. CC relaxation was mainly because of the production of NO together with some relaxant prostanoid, which did not change in SAMP8 animals. In contrast, the contractile component was considerably higher in the aged animals and it was completely inhibited by indomethacin. In conclusion, a clear imbalance towards enhanced production of contractile prostanoids from the endothelium may contribute to ED in the elderly. On the basis of these data, we propose the senescence‐accelerated mouse model as a reliable tool to analyse the basic ageing mechanisms of the CC.
Characterization of Barley Leaf Tolerance to Drought Stress by Chlorophyll Fluorescence and Electron Paramagnetic Resonance Studies
Authors: Filek M. , Łabanowska M. , Kościelniak J. , Biesaga‐Kościelniak J. , Kurdziel M. , Szarejko I. , Hartikainen H.
Published: April 2014

Two kinds of barley genotypes with various water‐stress tolerances, tolerant Cam/B1 and sensitive Maresi, were subjected to 10‐day soil‐drought stress in seedling and flag leaf developmental phases. After this time, both genotypes regardless of the growth stage showed a decrease in quantum yield of PSII photochemistry (ΦPSII) upon stress treatment; however, this effect was stronger in the sensitive plants than in the tolerant ones. The drought stress in the flag leaf stage was associated with an increase in superoxide dismutase (SOD) level in both genotypes, whereas in seedlings, this effect was observed only for Maresi. The activity of other enzymes (catalase and peroxidase) was changed only in small degree. An increase in proline levels and activities of Δ1‐pyrroline‐5‐carboxylate synthetase (P5CS) and ornithine delta‐aminotransferase (OAT) were observed independently of genotype and the phase of plant development, whereas the activity pyruvate dehydrogenase (PDH) decreased in tolerant genotype. Moreover, changes in the concentration of monocarbohydrates (glucose and fructose) and dicarbohydrates (saccharose, raffinose and maltose) were found: in seedlings, the amount of all soluble sugars increased, while in flag leaves decreased. The drought treatment resulted in a drop in starch level in the tolerant genotype, but in the sensitive one, the content of this substance increased in both developmental stages. EPR studies allowed the determination of the amount and character of organic radicals present in leaves. In control conditions, the content of these radical species was higher in the sensitive genotype than in tolerant one and decreased upon water stress, with the exception of flag leaves of the sensitive plant. Simulation procedure revealed four types of signals in the EPR spectra. One of them was attributed to a chlorophyll a cation and decreased upon drought. The second, ascribed to semiquinone radicals, reflected the redox balance disturbed by water deficit. The two remaining signals were connected with carbon‐centred radicals situated in the carbohydrate matrix. Their number was correlated with starch concentration.
Exogenous Abscisic Acid Application During Grain Filling in Winter Wheat Improves Cold Tolerance of Offspring's Seedlings
Authors: Li X. , Cai J. , Liu F. , Dai T. , Cao W. , Jiang D.
Published: April 2014

Low temperature seriously depresses seed germination and seedling growth in winter wheat (Triticum aestivum L.). In this study, wheat plants were sprayed with abscisic acid (ABA) and fluridone (inhibitor of ABA biosynthesis) at 19 days after anthesis (DAA) and repeated at 26 DAA. The seeds of those plants were harvested, and seed germination and offspring's seedling growth under low temperature were evaluated. The results showed that exogenous ABA application decreased seed weight and slightly reduced seed set and seed number per spike. Under low temperature, seeds from ABA‐treated plants showed reduced germination rate, germination index, growth of radicle and coleoptile, amylase activity and depressed starch degradation as compared with seeds from non‐ABA‐treated plants; however, activities of the antioxidant enzymes in both germinating seeds and seedling were enhanced from those exposed to exogenous ABA, resulting in much lowered malondialdehyde (MDA) and H2O2 concentrations and production rate. In addition, the maximum quantum efficiency of photosystem II was also enhanced in ABA‐treated offspring's seedlings. It is concluded that exogenous ABA treatment at later grain‐filling stage could be an effective approach to improve cold tolerance of the offspring during seed germinating and seedlings establishment in winter wheat.
Pyrochlore‐Free Ferroelectric 0.64Pb(Ni1/3Nb2/3)O3–0.36PbTiO3 Ceramics Synthesized by the Combustion Method
Authors: Wang Jianlin , Tang Jian , Lei Zhiwei , Liu Min , Knize Randy J. , Lu Yalin
Published: April 2014

By adopting Nb2O5, HNO3 and coordination agents EDTA as raw materials, pyrochlore‐free 0.64Pb(Ni1/3Nb2/3)O3–0.36PbTiO3(0.64PNN–0.36PT) powders were successfully synthesized via a combustion route. Free of pyrochlore phase was realized by the chelation formation of EDTA‐metal ions which isolate niobium and lead oxides and then prevent the formation of pyrochlore phases, therein generate the desired perovskite phases. Comparing the results with similar samples synthesized by the Columbite method, the new 0.64PNN–0.36PT ceramics here shown much better dielectric and ferroelectric performances: a maximum dielectric constant of 22 856 at 1 kHz and a remnant polarization of 21.6 μC/cm2 at 40 kV/cm.
Samarium‐Doped Oxyfluoride Glass‐Ceramic as a New Fast Erasable Dosimetric Detector Material for Microbeam Radiation Cancer Therapy Applications at the Canadian Synchrotron
Authors: Okada Go , Ueda Jumpei , Tanabe Setsuhisa , Belev George , Wysokinski Tomasz , Chapman Dean , Tonchev Dancho , Kasap Safa
Published: April 2014

There is a special need to develop a dosimetry technique with a large‐dynamic range and high‐spatial resolution to characterize the microstructured X‐ray beams used in microbeam radiation therapy (MRT) for cancer. We report the synthesis and characterization of oxyfluoride glass‐ceramic (SiO2–Al2O3–CaF2–CaO–SmF3) plates, which contain trivalent‐samarium‐doped calcium fluoride (CaF2:Sm3+) nanocrystals, for use as a dosimetric detector material, particularly for MRT applications. Our approach utilizes the extent of Sm3+→Sm2+ valence reduction caused by X‐ray irradiation as a probe of the X‐ray dose delivered; and confocal fluorescent microscopy is used to read out the distribution of valence reduction through the photoluminescence (PL) signal. Our study showed that the Sm3+→Sm2+ valence reduction takes place in CaF2 nanocrystals, but not in the glass matrix. The Sm2+ shows PL emission predominantly due to the fast 4f55d1→7F0 transition, which allows us to read out the detector plate at a high scanning speed. Further, our experiments showed that the detection dose range reaches several thousands of grays, and X‐ray dose distribution is detected at a micrometer scale. In addition, the Sm2+ signal can be erased either by heating the irradiated sample at a suitable high temperature or by exposing it to UV light; and the erased glass‐ceramic plate is reusable. The new Sm‐doped oxyfluoride glass‐ceramic with CaF2 nanocrystals reported in this work shows potential for practical use in high‐dose and high‐resolution dosimetry for MRT.
Quantitative gingival crevicular fluid proteome in health and periodontal disease using stable isotope chemistries and mass spectrometry
Authors: Carneiro Leandro G. , Nouh Hesham , Salih Erdjan
Published: April 2014

Aim

Application of quantitative stable isotope‐labelling chemistries and mass spectrometry (MS) to determine alterations in gingival crevicular fluid (GCF) proteome in periodontal disease.

Material and Methods

Quantitative proteome of GCF from 40 healthy individuals versus 40 patients with periodontal disease was established using 320 GCF samples and stable isotope‐labelling reagents, ICAT and mTRAQ, with MS technology and validated by enzyme‐linked immunosorbent methods.

Results

We have identified 238 distinct proteins of which 180 were quantified in GCF of both healthy and periodontal patients with additional 26 and 32 distinct proteins that were found only in GCF of healthy or periodontal patients. In addition, 42 pathogenic bacterial proteins and 11 yeast proteins were quantified. The data highlighted a series of proteins not quantified previously by large‐scale MS approaches in GCF with relevance to periodontal disease, such as host‐derived Ig alpha‐2 chain C, Kallikrein‐4, S100‐A9, transmembrane proteinase 13, peptidase S1 domain, several collagen types and pathogenic bacterial proteins, e.g. formamidase, leucine aminopeptidase and virulence factor OMP85.

Conclusions

The innovative analytical approaches provided detailed novel changes in both host and microbial derived GCF proteomes of periodontal patients. The study defined 50 host and 16 pathogenic bacterial proteins significantly elevated in periodontal disease most of which were novel with significant potential for application in the clinical arena of periodontal disease.
Survival benefit of radioembolization for inoperable hepatocellular carcinoma using yttrium‐90 microspheres
Authors: Kwok Philip Chong‐Hei , Leung Kwong Chuen , Cheung Moon Tong , Lam Ting Wa , Szeto Lok Tin , Chou Sandas Qi‐Hua , Chia Nam Hung , Tong Cheuk Man , Yuen Pui Kei , Cheung Chun Hung , Law Chun Key
Published: April 2014

Background and Aim

Transarterial radioembolization with yttrium‐90 microspheres is one treatment option for inoperable hepatocellular carcinoma. We compared the survival in a cohort of patients receiving radioembolization or no radioembolization.

Methods

The data of 46 patients referred for radioembolization was retrospectively reviewed. The patient, tumor characteristics, and the survival were compared in the two groups. The independent predictors for survival were studied with multivariate analysis. The side‐effects and the complication of radioembolization‐induced liver disease was recorded.

Results

 Thirty patients received radioembolization; 16 patients did not. The two groups did not differ in the mean age, Child‐Pugh classes, Barcelona Clinic of Liver Cancer (BCLC) stages, tumor types, sum of diameter of the two biggest tumors, and extent of portal vein invasion. Those with BCLC stage C tumor, with portal vein thrombus, or with less than three nodules had significantly longer survival after radioembolization. There was a trend of longer survival in patients with Child‐Pugh A liver function, or with BCLC stage B tumor after radioembolization. The median survival was more than 31.9 months, 14.5 months, and 5.2 months in patients with BCLC stage A, B, and C tumors. The independent predictors for longer survival were Child‐Pugh class, tumor diameter sum, BCLC stage, and receiving radioembolization. Grade 2 irradiation‐induced gastritis occurred in three patients (10%). Radioembolization‐induced liver disease occurred in four patients (13%).

Conclusions

Radioembolization may prolong survival for patients with inoperable hepatocellular carcinoma. Radioembolization‐induced liver disease occurred and should be further studied.
AtHAP5A modulates freezing stress resistance in Arabidopsis through binding to CCAAT motif of AtXTH21
Authors: Shi Haitao , Ye Tiantian , Zhong Bao , Liu Xun , Jin Rui , Chan Zhulong
Published: April 2014

Several eukaryotic Heme‐associated proteins (HAPs) have been reported to bind specifically to DNA fragments containing CCAAT‐box; however, the physiological functions and direct targets of these HAP proteins in plants remain unclear.

In this study, we showed that AtHAP5A as a transcription factor interacted with CCAAT motif in vivo, and AtXTH21, one direct target of AtHAP5A, was involved in freezing stress resistance. The AtHAP5A overexpressing plants were more tolerant, whereas the loss‐of‐function mutant of AtHAP5A was more sensitive to freezing stress than wild‐type plants. Chromatin immunoprecipitation (ChIP) assay demonstrated that AtHAP5A could bind to five fragments that contained CCAAT motifs in the AtXTH21 promoter.

Similarly, the AtXTH21 overexpressing plants exhibited improved freezing resistance, while xth21 knockdown mutants displayed decreased freezing resistance. Notably, the modulated freezing resistance of AtHAP5A overexpressing plants and knockout mutant could be reversed by the xth21 mutant and AtXTH21 overexpressing plants, respectively, indicating that AtHAP5A might act upstream of AtXTH21 in freezing stress. Additionally, modulation of AtHAP5A and AtXTH21 expression had the same effects on abscisic acid (ABA) sensitivity and reactive oxygen species (ROS) metabolism.

Taken together, these results demonstrated that AtHAP5A modulates freezing stress resistance in Arabidopsis through binding to the CCAAT motif of AtXTH21.
The risk/benefit of predicting a post‐antibiotic era: Is the alarm working?
Authors: Fowler Tom , Walker David , Davies Sally C.
Published: April 2014

There have been concerns about antimicrobial resistance since the first widespread use of antibiotics in humans. More recently, this concern has grown and become the focus of clinical, scientific, and political activity. In part, the political interest is a consequence of publicizing a bleak picture of a post‐antibiotic world. There are, however, dangers in using a discourse of fear. In this article, we discuss whether the evidence base is available to justify such claims and, more importantly, put this in the policy context with which it is used. Many governments now use a risk assessment approach to identify security concerns, based on reasonable worst‐case scenarios. There is no doubt that for effective policy‐based action to occur, antimicrobial resistance needs to be seen as a national and international security priority, particularly as the major cost of inaction will mostly be felt in the future. We conclude that presenting the evidence in a manner that is used to encourage prioritization of security policy is not only justified, it is essential to drive action in this area.