bluuebunny/crossref_metadata_2025 huggingface dataset:
British Public Opinion after a Decade of War: Attitudes to Iraq and Afghanistan
Authors: Gribble Rachael , Wessley Simon , Klein Susan , Alexander David A. , Dandeker Christopher , Fear Nicola T.
Published: September 2014

Using data from the 2011 British Social Attitudes survey (n = 3,311), this article compares British public opinion of the purposes and successes of the Iraq and Afghanistan missions. Public acceptance of military deaths/injuries, the accuracy of public estimates of military fatalities and how these differ according to opinions of the missions are determined. It is found that the British public is doubtful of the missions' achievements and cynical about their purposes. Perceptions of the campaigns were associated with the accuracy of estimations of UK military fatalities, and the acceptability of military deaths/injuries. Implications for social and political theory and British foreign policy are discussed.
Identification of Crystals Forming on Porcine Articular Cartilage: A New Method for the Estimation of the Postmortem Interval
Authors: Rogers Christopher J. , ten Broek Clara M.A. , Hodson Barbara , Whitehead Michael P. , Schmerer Wera M. , Sutton Raul
Published: September 2014

Articular cartilage was examined to determine its decomposition sequence and its potential for assessing the postmortem interval. Scanning electron microscopy of articular cartilage from buried porcine trotters showed the presence of microcrystals on the synovial surface. These orthorhombic pyramidal or “coffin”‐shaped crystals, appeared at 3 weeks (22 days) after interment and disappeared after 6 weeks. The disappearance of these crystals was linked to decompositional changes to the integrity of the synovial joint. The formation and disappearance of these crystals was associated with a pH change at the cartilage surface. Scanning electron microscopy–energy‐dispersive X‐ray (SEM‐EDX) analysis showed that the five main elements contained within these crystals were carbon, nitrogen, oxygen, magnesium, and phosphorous. Such elemental analysis suggested the crystals may be struvite (MgNH4PO46(H2O)). Bacteria cultured from the cartilage synovial surface produced struvite crystals when grown in suitable media and were identified by DNA analysis to be Comamonas sp.
Improved cytotoxic effects of Salmonella‐producing cytosine deaminase in tumour cells
Authors: Mesa‐Pereira Beatriz , Medina Carlos , Camacho Eva María , Flores Amando , Santero Eduardo
Published: September 2014

In order to increase the cytotoxic activity of a Salmonella strain carrying a salicylate‐inducible expression system that controls cytosine deaminase production, we have modified both, the vector and the producer bacterium. First, the translation rates of the expression module containing the Escherichia coli codA gene cloned under the control of the Pm promoter have been improved by using the T7 phage gene 10 ribosome binding site sequence and replacing the original GUG start codon by AUG. Second, to increase the time span in which cytosine deaminase may be produced by the bacteria in the presence of 5‐fluorocytosine, a 5‐fluorouracyl resistant Salmonella strain has been constructed by deleting its upp gene sequence. This new Salmonella strain shows increased cytosine deaminase activity and, after infecting tumour cell cultures, increased cytotoxic and bystander effects under standard induction conditions. In addition, we have generated a purD mutation in the producer strain to control its intracellular proliferation by the presence of adenine and avoid the intrinsic Salmonella cell death induction. This strategy allows the analysis and comparison of the cytotoxic effects of cytosine deaminase produced by different Salmonella strains in tumour cell cultures.
Extraction and purification of high‐value metabolites from microalgae: essential lipids, astaxanthin and phycobiliproteins
Authors: Cuellar‐Bermudez Sara P. , Aguilar‐Hernandez Iris , Cardenas‐Chavez Diana L. , Ornelas‐Soto Nancy , Romero‐Ogawa Miguel A. , Parra‐Saldivar Roberto
Published: September 2014

The marked trend and consumers growing interest in natural and healthy products have forced researches and industry to develop novel products with functional ingredients. Microalgae have been recognized as source of functional ingredients with positive health effects since these microorganisms produce polyunsaturated fatty acids, polysaccharides, natural pigments, essential minerals, vitamins, enzymes and bioactive peptides. For this reason, the manuscript reviews two of the main high‐value metabolites which can be obtained from microalgae: pigments and essential lipids. Therefore, the extraction and purification methods for polyunsaturated fatty acids, astaxanthin, phycoerythrin and phycocyanin are described. Also, the effect that environmental growth conditions have in the production of these metabolites is described. This review summarizes the existing methods to extract and purify such metabolites in order to develop a feasible and sustainable algae industry.
MRI abnormalities in children following sequential chemotherapy, hyperfractionated accelerated radiotherapy and high‐dose thiotepa for high‐risk primitive neuroectodermal tumours of the central nervous system
Authors: Thust Stefanie C , Blanco Esther , Michalski Antony J , Chong WK , Gaze Mark N , Phipps Kim , Mankad Kshitij
Published: September 2014

Introduction

Intensive postsurgical therapies have improved survival in children with primitive neuroectodermal tumour, but there is concern that the combination of chemotherapy and radiotherapy may result in a compound injury to normal brain. The purposes of this analysis were to characterise what types of imaging abnormalities occur, identify risk factors and explore how treatment‐related changes may be distinguished from tumour.

Method

One hundred fifty‐three MRI studies in 14 children treated with sequential chemotherapy, hyperfractionated accelerated radiotherapy and high‐dose thiotepa were retrospectively analysed at a paediatric national referral centre.

Results

We observed 11 episodes of new focal enhancing lesions, 5 of which were transient and judged to be treatment related. In addition, 7/14 (50%) of children demonstrated moderate to severe brain volume loss featuring a leukodystrophy pattern.

Conclusion

Treatment‐related brain MRI abnormalities occurred frequently in this series with a risk of misdiagnosis as tumour. A proportion of patients suffer generalised white matter injury, which has not been appreciated as a side effect of this particular therapy.
Re‐appraisal of the phylogeny and fluorescence in situ hybridization probes for the analysis of the Competibacteraceae in wastewater treatment systems
Authors: McIlroy Simon J. , Nittami Tadashi , Kanai Eri , Fukuda Junji , Saunders Aaron M. , Nielsen Per Halkjær
Published: September 2014

Members of the family Competibacteraceae are common in wastewater treatment plants (WWTPs) designed for enhanced biological phosphorus removal (EBPR) and are putatively deleterious to the process of P removal. Their ability to accumulate large amounts of polyhydroxyalkanoates is also suggested to be of potential commercial interest for bioplastic production. In this study we have updated the 16S rRNA‐based phylogeny of the Competibacter and the Plasticicumulans lineages. The former is delineated by 13 clades including two described genera; ‘Ca. Competibacter’ and ‘Ca. Contendobacter’. The oligonucleotide probes used for detection of the family by fluorescence in situ hybridization (FISH) were re‐evaluated and designed for coverage of these clades. Surveys of full‐scale WWTPs based on 16S rRNA gene amplicon sequencing and FISH analysis indicate that a number of member clades always coexist, with their relative abundances varying substantially between and temporally within plants. The hypothesis that these differences are based on niche partitioning is supported by marked phenotypic differences between clades. An in‐depth understanding of the ecology of the family requires further studies of the metabolism of individual clades in situ. The proposed phylogeny and FISH probes will provide the foundation for such studies.
Angiotensin receptor blockers and risk of dementia: cohort study in UK Clinical Practice Research Datalink
Authors: Goh Kah L. , Bhaskaran Krishnan , Minassian Caroline , Evans Stephen J. W. , Smeeth Liam , Douglas Ian J.
Published: September 2014

Aims

This was a cohort study to evaluate whether individuals exposed to angiotensin receptor blockers have a reduced risk of dementia compared with those exposed to angiotensin‐converting enzyme inhibitors.

Methods

The study included new users of angiotensin receptor blockers or angiotensin‐converting enzyme inhibitors (from 1995 to 2010) from UK primary care practices contributing to the Clinical Research Practice Datalink. The association between exposure to angiotensin receptor blockers and the risk of incident dementia was analysed using a Cox model, adjusting for age, sex, body mass index, diabetes, hypertension, heart failure, statin use, socioeconomic status, alcohol, smoking, number of consultations and calendar year.

Results

A total of 426 089 persons were included in the primary analysis, with 45 541 persons exposed to angiotensin receptor blockers and the remainder to angiotensin‐converting enzyme inhibitors. The total number of new diagnoses of dementia was 6517. There was weak evidence of a decreased risk of dementia with exposure to angiotensin receptor blockers, with follow‐up beginning at 1 year after the start of treatment (adjusted hazard ratio 0.92, 95% confidence interval 0.85–1.00). An analysis restricted to the first 12 months after the index date showed a larger effect on dementia risk (adjusted hazard ratio 0.60, 95% confidence interval 0.50–0.72).

Conclusions

A small reduction in dementia risk was seen with angiotensin receptor blockers in comparison to angiotensin‐converting enzyme inhibitors. However, the strongest association was seen in early follow‐up, suggesting that the inverse association is unlikely to be causal, but instead reflects other important but unmeasured differences between angiotensin receptor blocker and angiotensin‐converting enzyme inhibitor users.
An exploratory double‐blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease
Authors: Süssmuth Sigurd D. , Haider Salman , Landwehrmeyer G. Bernhard , Farmer Ruth , Frost Chris , Tripepi Giovanna , Andersen Claus A. , Di Bacco Marco , Lamanna Claudia , Diodato Enrica , Massai Luisa , Diamanti Daniela , Mori Elisa , Magnoni Letizia , Dreyhaupt Jens , Schiefele Karin , Craufurd David , Saft Carsten , Rudzinska Monika , Ryglewicz Danuta , Orth Michael , Brzozy Sebastian , Baran Anna , Pollio Giuseppe , Andre Ralph , Tabrizi Sarah J. , Darpo Borje , Westerberg Goran ,   the PADDINGTON Consortium
Published: September 2014

Aims

Selisistat, a selective SirT1 inhibitor is being developed as a potentially disease‐modifying therapeutic for Huntington's disease (HD). This was the first study of selisistat in HD patients and was primarily aimed at development of pharmacodynamic biomarkers.

Methods

This was a randomized, double‐blind, placebo‐controlled, multicentre exploratory study. Fifty‐five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.

Results

Selisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady‐state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.

Conclusions

Selisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.
A Discrete Time Event-History Approach to Informative Drop-Out in Mixed Latent Markov Models with Covariates
Authors: Bartolucci Francesco , Farcomeni Alessio
Published: September 2014

Mixed latent Markov (MLM) models represent an important tool of analysis of longitudinal data when response variables are affected by time-fixed and time-varying unobserved heterogeneity, in which the latter is accounted for by a hidden Markov chain. In order to avoid bias when using a model of this type in the presence of informative drop-out, we propose an event-history (EH) extension of the latent Markov approach that may be used with multivariate longitudinal data, in which one or more outcomes of a different nature are observed at each time occasion. The EH component of the resulting model is referred to the interval-censored drop-out, and bias in MLM modeling is avoided by correlated random effects, included in the different model components, which follow common latent distributions. In order to perform maximum likelihood estimation of the proposed model by the expectation–maximization algorithm, we extend the usual forward-backward recursions of Baum and Welch. The algorithm has the same complexity as the one adopted in cases of non-informative drop-out. We illustrate the proposed approach through simulations and an application based on data coming from a medical study about primary biliary cirrhosis in which there are two outcomes of interest, one continuous and the other binary.
Reader Reaction to “A Robust Method for Estimating Optimal Treatment Regimes” by Zhang et al. (2012)
Authors: Taylor Jeremy M. G. , Cheng Wenting , Foster Jared C.
Published: September 2014

A recent article (Zhang et al., 2012, Biometrics  168, 1010–1018) compares regression based and inverse probability based methods of estimating an optimal treatment regime and shows for a small number of covariates that inverse probability weighted methods are more robust to model misspecification than regression methods. We demonstrate that using models that fit the data better reduces the concern about non-robustness for the regression methods. We extend the simulation study of Zhang et al. (2012, Biometrics  168, 1010–1018), also considering the situation of a larger number of covariates, and show that incorporating random forests into both regression and inverse probability weighted based methods improves their properties.
Diagnostic accuracy of specific IgE to components in diagnosing peanut allergy: a systematic review
Authors: Klemans R. J. B. , van Os‐Medendorp H. , Blankestijn M. , Bruijnzeel‐Koomen C. A. F. M. , Knol E. F. , Knulst A. C.
Published: September 2014

The diagnostic accuracy of skin prick test (SPT) and specific IgE (sIgE) to peanut extract in diagnosing peanut allergy is suboptimal. Recent studies have evaluated sIgE to peanut components as a possible new diagnostic tool. The aim of our review was to systematically search the literature to assess the diagnostic value of sIgE to peanut components in diagnosing peanut allergy. A literature search was performed in PubMed, Embase and the Cochrane Library. Results were subsequently screened for in‐ and exclusion criteria. The quality of eligible studies was assessed using a standardized quality assessment tool (QUADAS‐2). Data on sensitivity, specificity, and positive and negative likelihood ratios were extracted or calculated for a descriptive analysis. Twenty‐two studies were eligible, of which 21 studies in paediatric populations. Most studies reported on sIgE to peanut extract (15) and sIgE to Ara h 2 (12), followed by SPT (9) and sIgE to Ara h 1 (7). All studies were at risk of bias or caused applicability concerns on at least one item of the quality assessment tool. The best combination of diagnostic accuracy measures of all diagnostic tests was found for sIgE to Ara h 2. This finding was independent of geographical location. Compared to SPT and sIgE to peanut extract, sIgE to Ara h 2 was mainly superior in diagnosing peanut allergy in case of a positive test result. Worst diagnostic accuracy measures were found in general for sIgE to Ara h 8 and sIgE to Ara h 9. sIgE to Ara h 2 showed the best diagnostic accuracy of all diagnostic tests to diagnose peanut allergy. Compared to the currently used SPT and sIgE to peanut extract, sIgE to Ara h 2 was superior in diagnosing peanut allergy and should therefore replace these tests in daily clinical practice, especially in children.
Spatio‐temporal pattern of specific gravity of mangrove diaspore: implications for upstream dispersal
Authors: Kadoya Taku , Inoue Tomomi
Published: September 2014

Mangrove plants, which develop highly productive forests on tropical–subtropical coastlines and river estuaries, rely mainly on river and sea water currents for their diaspore dispersal. Mangrove diaspores are basically dispersed in brackish to sea waters; thus whether they sink or float during the dispersal period could be changed dynamically, both spatially and temporally, depending on the salinity to which they are exposed, as well as on their specific gravity (SG). We found that the SG of diaspores of two mangrove species, Rhizophora stylosa and Bruguiera gymnorrhiza, which are dominant species and form a typical zonation (B. gymnorrhiza in inland areas and R. stylosa in more seaward areas) in the study area, changed spatially and temporally. Bruguiera gymnorrhiza gradually lost its SG in accordance with elapsed time, while R. stylosa lost its SG in the first 6 h and gained gradually according to elapsed time. Hydrodynamic simulation of dispersal patterns, in combination with observed specific gravity changes of both diaspores and river water, demonstrated that the spatio‐temporal pattern of specific gravity change was closely related to the difference in dispersal behaviors between the species. The diaspore of B. gymnorrhiza generally disperses upstream, and covers wider ranges than that of R. stylosa, at least in the early phase of dispersal. These dispersal behaviors agreed well with the distribution pattern of the species across estuaries in the study site. To date, hydrochory has been considered to be a mostly passive process governed by the dynamics of water current and subsequent sediment movement, with fixed diaspore characteristics such as shape and buoyancy. The present study shed new light on an active and dynamic process in hydrochory and found that the buoyancy of diaspores may be controlled by changes in their spatial and temporal SG.
Carbohydrate scarcity increases foraging activities and aggressiveness in the ant Prolasius advenus (Hymenoptera: Formicidae)
Authors: GRANGIER JULIEN , LESTER PHILIP J.
Published: September 2014

1. Behavioural responses to varying macronutrient availability are increasingly studied in highly invasive ant species to better understand their ecological success. However, such work is lacking in relation to native ant species confronted with biological invaders.

2. Here the link between diet and behaviour was examined in Prolasius advenus, a native ant from New Zealand facing intense competition for food with invasive insects, including social wasps. A long‐term laboratory experiment was conducted to assess the impact of protein and carbohydrate restriction on several behavioural parameters.

3. Ants shifted their food‐collecting activity towards the least available macronutrient in both protein‐limited and carbohydrate‐limited colonies. But when lacking carbohydrate, they also strongly increased their efforts to discover resources. After 10 weeks, the proportion of the colony patrolling outside of the nest was eight times higher than at the initiation of the experiment. This high patrolling activity was then maintained for several weeks and resulted in a higher efficiency to explore a novel territory. Moreover, ants fed a carbohydrate‐limited diet engaged in longer aggressive acts towards conspecifics.

4. These behavioural responses to carbohydrate scarcity may, in part, enhance the ability of P. advenus to resist a competing invader under natural conditions. While much of the previous research has linked diet and behavioural dominance in invasive ants, the present study shows that conducting similar investigations in the native species to which they are confronted may shed light on the mechanisms behind biotic resistance and the ability of some native species to coexist with highly abundant invaders.
Historical analysis of mangrove leaf traits throughout the 19th and 20th centuries reveals differential responses to increases in atmospheric CO2
Authors: Reef Ruth , Lovelock Catherine E
Published: September 2014

Aim

To reconstruct the historic response of two dominant mangrove species to increases in atmospheric CO2 over the past two centuries.

Location

Indo‐Pacific.

Methods

We use a novel approach to assess plant responses to rising atmospheric CO2 concentrations by measuring leaf traits of herbarium specimens of two dominant and widespread mangrove species.

Results

Leaf traits were correlated with atmospheric CO2 concentration and latitude, but not with rainfall or the multidecadal multivariate El Niño–Southern Oscillation index. Rhizophora stylosa and Avicennia marina exhibited significant differences in their response to elevated CO2. Increases in atmospheric CO2 concentrations over the past 165 years have led to a corresponding rise in photosynthetic carbon gain by the widespread mangrove A. marina, but not by R. stylosa.

Main conclusions

CO2 fixation is at the heart of plant energy acquisition, global primary productivity and CO2 sequestration. Given that atmospheric CO2 concentrations have been rapidly rising for the past two centuries, surprisingly few datasets have examined the long‐term response of trees to rising CO2. Our results suggest changes to interspecific interactions, nutrient cycling and carbon sequestration in these globally significant forests are expected as CO2 concentrations continue to increase.
Environmental and socio‐economic factors shaping the geography of floristic collections in China
Authors: Yang Wenjing , Ma Keping , Kreft Holger
Published: September 2014

Aim

Effort in collecting biodiversity information often varies strongly in space and may be driven by environmental, cultural and socio‐economic factors. Understanding the constraints on collecting effort is crucial for identifying potential bias in distributional databases and for making future surveys more efficient. Here we test six competing hypotheses on drivers of geographical variation in collecting effort and identify the main factors shaping the geography of floristic collections in China.

Location

China.

Methods

We used the most comprehensive database of Chinese vascular plant distributions including 4,338,516 county‐level occurrences derived from herbarium specimens and literature sources. Explanatory variables were assembled representing six different hypotheses: accessibility, human population density, the ‘botanist effect’, mountains, water availability and conservation priority. Ordinary least‐squares models with eigenvector‐based spatial filters were applied to investigate their effects on spatial patterns of two different facets of collecting effort, i.e. collection density and inventory incompleteness.

Results

All hypotheses except accessibility and human population density received significant support. Elevational range was the strongest predictor with a positive effect on collection density. Inventory incompleteness in turn was best predicted by human population density, but unexpectedly showed a positive effect. In contrast to previous studies, collecting effort was only weakly and negatively related to road density. Counties with herbaria had significantly higher collecting effort, and the presence of herbaria had weakly positive effects on neighbouring counties.

Main conclusions

Our results indicate that China's mountains are most intensively and completely collected, whereas densely populated areas are surprisingly under‐sampled. Because densely populated areas are more seriously threatened by land‐use change, our results show a need to increase biological collections in those areas for conservation assessment and monitoring. More generally, our study suggests that collecting effort and its environmental and socio‐economic constraints have a strong region‐specific component influenced by cultural context and by different botanical traditions.
Trophic effects of polynucleotides and hyaluronic acid in the healing of venous ulcers of the lower limbs: a clinical study
Authors: De Caridi Giovanni , Massara Mafalda , Acri Ignazio , Zavettieri Salvatore , Grande Raffaele , Butrico Lucia , de Franciscis Stefano , Serra Raffaele
Published: September 2014

The aim of this study was to evaluate the results of treatment of venous lower limbs ulcers through the topical application of polynucleotides and hyaluronic acid gel (PNHA): Nucliaskin S™ (Mastelli srl, San Remo, Italy). This study was carried out in 39 consecutive patients who were randomly allocated to two groups: group I (20 patients) received treatment with PNHA (topical gel application two times a week, for a total of 6 weeks); group II (19 patients) received only hyaluronic acid (HA) topical application. All patients received a surgical debridement of the ulcerative lesions before topical treatment with PNHA or HA. Pre‐treatment data indicated the area of ulceration. The number of healed ulcers and the variation in area of ulceration were considered as endpoints. The endpoints were observed after 45 days from the beginning of treatment. Complete wound healing occurred in 60% of limbs of group I and in 22% of those of group II patients. The average area reduction was 67% versus 34% in patients of group I and II, respectively. No side effects were recorded in both groups. Our experience shows that PNHA has an elevated trophic effect and speeds the healing rate of venous lower limb ulcers. This treatment may be a valid option in clinical practice.
Assessment and documentation of non‐healing, chronic wounds in inpatient health care facilities in the Czech Republic: an evaluation study
Authors: Pokorná Andrea , Leaper David
Published: September 2014

The foundation of health care management of patients with non‐healing, chronic wounds needs accurate evaluation followed by the selection of an appropriate therapeutic strategy. Assessment of non‐healing, chronic wounds in clinical practice in the Czech Republic is not standardised. The aim of this study was to analyse the methods being used to assess non‐healing, chronic wounds in inpatient facilities in the Czech Republic. The research was carried out at 77 inpatient medical facilities (8 university/faculty hospitals, 63 hospitals and 6 long‐ term hospitals) across all regions of the Czech Republic. A mixed model was used for the research (participatory observation including creation of field notes and content analysis of documents for documentation and analysis of qualitative and quantitative data). The results of this research have corroborated the suspicion of inconsistencies in procedures used by general nurses for assessment of non‐healing, chronic wounds. However, the situation was found to be more positive with regard to evaluation of basic/fundamental parameters of a wound (e.g. size, depth and location of a wound) compared with the evaluation of more specific parameters (e.g. exudate or signs of infection). This included not only the number of observed variables, but also the action taken. Both were significantly improved when a consultant for wound healing was present (P = 0·047). The same applied to facilities possessing a certificate of quality issued by the Czech Wound Management Association (P = 0·010). In conclusion, an effective strategy for wound management depends on the method and scope of the assessment of non‐healing, chronic wounds in place in clinical practice in observed facilities; improvement may be expected following the general introduction of a ‘non‐healing, chronic wound assessment’ algorithm.
Delayed cutaneous wound closure in HO‐2 deficient mice despite normal HO‐1 expression
Authors: Lundvig Ditte M. S. , Scharstuhl Alwin , Cremers Niels A. J. , Pennings Sebastiaan W. C. , te Paske Jeroen , van Rheden René , van Run‐van Breda Coby , Regan Raymond F. , Russel Frans G. M. , Carels Carine E. , Maltha Jaap C. , Wagener Frank A. D. T. G.
Published: September 2014

Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO‐1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal wound healing in HO‐2 deficient mice is impaired with exorbitant inflammation and absence of HO‐1 expression. This study addresses the role of HO‐2 in cutaneous excisional wound healing using HO‐2 knockout (KO) mice. Here, we show that HO‐2 deficiency also delays cutaneous wound closure compared to WT controls. In addition, we detected reduced collagen deposition and vessel density in the wounds of HO‐2 KO mice compared to WT controls. Surprisingly, wound closure in HO‐2 KO mice was accompanied by an inflammatory response comparable to WT mice. HO‐1 induction in HO‐2 deficient skin was also similar to WT controls and may explain this protection against exaggerated cutaneous inflammation but not the delayed wound closure. Proliferation and myofibroblast differentiation were similar in both two genotypes. Next, we screened for candidate genes to explain the observed delayed wound closure, and detected delayed gene and protein expression profiles of the chemokine (C‐X‐C) ligand‐11 (CXCL‐11) in wounds of HO‐2 KO mice. Abnormal regulation of CXCL‐11 has been linked to delayed wound healing and disturbed angiogenesis. However, whether aberrant CXCL‐11 expression in HO‐2 KO mice is caused by or is causing delayed wound healing needs to be further investigated.
Simple self‐reported behavioral or psychological characteristics as risk factors for future type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 14
Authors: Heianza Yoriko , Arase Yasuji , Kodama Satoru , Tsuji Hiroshi , Fujihara Kazuya , Saito Kazumi , Hara Shigeko , Sone Hirohito
Published: September 2014

Aims/Introduction

Depression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self‐report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.

Materials and Methods

We investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7–13 years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.

Results

Results of Cox regression analysis showed that lack of perseverance (age‐ and sex‐adjusted HR 1.41, 95% confidence interval 1.07–1.84), anger, (HR 1.51, 95% confidence interval 1.07–2.12) or memory loss (HR 1.47, 95% confidence interval 1.14–1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94‐fold (95% confidence interval 1.19–3.15) increased risk of type 2 diabetes than those without those two symptoms.

Conclusions

Responses to a simple self‐report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type 2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals.
Literature review on clinical decision support system reducing medical error
Authors: Jia Peng Li , Zhang Pei Fang , Li Han Dong , Zhang Long Hao , Chen Ying , Zhang Ming Ming
Published: September 2014

Objectives

Quite a number of studies on clinical decision support systems (CDSS) have been published in recent years to assess the characteristics and architecture of CDSS and evaluate the effects of CDSS on clinical work. However, until now there have been no relevant studies to investigate the quantity of these, and their contribution to present day thinking. The aim of this study was to explore the areas of theme, and the study design of research on CDSS in literature published in English and Chinese‐language journals.

Methods

We searched the major database including MEDLINE, EMbase, Cochrane Library and four Chinese databases including Chinese Biomedical Literature Database (CBM), Wanfang Data, Chinese Scientific Journal Database (VIP), and Chinese Journals Full‐text Database (CNKI) and to analyze the publication years, research themes, authors’ affiliations and methodologies of studies. Quality and statistical method were only appraised by classification of study designs.

Results

A total of 616 studies published from 1990 to 2013 were included in our research. In the year of 2011 the number of studies reached its peak with 96 studies accounting for 15.58% of the years’ publication. We grouped the included studies into six major topic areas of which computerized clinical decision support systems dominated the included studies accounting for 51.46% of all studies. Commentary reviews and cross‐sectional studies which took up approximately 46.10% of the included studies, with 30.52% (188 studies) and 15.58% (96 studies) respectively. Most included studies on CDSS were conducted in the following four institutions: universities, hospitals, research institutions and companies.

Conclusions

There is a growing change trend in the number of studies on CDSS research in recent two decades, most of which are non‐comparative studies (46.10%) . Only 21 systematic reviews and 22 randomized controlled trails were published with the percentage of 3.41% and 3.57% of the included studies. More methodologically rigorous designs are needed to improve the research quality on CDSS.
Perceptual clustering for automatic hotspot detection from Ki‐67‐stained neuroendocrine tumour images
Authors: KHAN NIAZI M. KHALID , YEARSLEY MARTHA M. , ZHOU XIAOPING , FRANKEL WENDY L. , GURCAN METIN N.
Published: September 2014

Hotspot detection plays a crucial role in grading of neuroendocrine tumours of the digestive system. Hotspots are often detected manually from Ki‐67‐stained images, a practice which is tedious, irreproducible and error prone. We report a new method to segment Ki‐67‐positive nuclei from Ki‐67‐stained slides of neuroendocrine tumours. The method combines minimal graph cuts along with the multistate difference of Gaussians to detect the individual cells from images of Ki‐67‐stained slides. It, then, automatically defines the composite function, which is used to determine hotspots in neuroendocrine tumour slide images. We combine modified particle swarm optimization with message passing clustering to mimic the thought process of the pathologist during hotspot detection in neuroendocrine tumour slide images. The proposed method was tested on 55 images of size 10 × 5 K and resulted in an accuracy of 94.60%. The developed methodology can also be part of the workflow for other diseases such as breast cancer and glioblastomas.
High resolution SEM imaging of gold nanoparticles in cells and tissues
Authors: GOLDSTEIN A. , SOROKA Y. , FRUŠIĆ‐ZLOTKIN M. , POPOV I. , KOHEN R.
Published: September 2014

The growing demand of gold nanoparticles in medical applications increases the need for simple and efficient characterization methods of the interaction between the nanoparticles and biological systems. Due to its nanometre resolution, modern scanning electron microscopy (SEM) offers straightforward visualization of metallic nanoparticles down to a few nanometre size, almost without any special preparation step. However, visualization of biological materials in SEM requires complicated preparation procedure, which is typically finished by metal coating needed to decrease charging artefacts and quick radiation damage of biomaterials in the course of SEM imaging. The finest conductive metal coating available is usually composed of a few nanometre size clusters, which are almost identical to the metal nanoparticles employed in medical applications. Therefore, SEM monitoring of metal nanoparticles within cells and tissues is incompatible with the conventional preparation methods. In this work, we show that charging artefacts related to non‐conductive biological specimen can be successfully eliminated by placing the uncoated biological sample on a conductive substrate. By growing the cells on glass pre‐coated with a chromium layer, we were able to observe the uptake of 10 nm gold nanoparticles inside uncoated and unstained macrophages and keratinocytes cells. Imaging in back scattered electrons allowed observation of gold nanoparticles located inside the cells, while imaging in secondary electron gave information on gold nanoparticles located on the surface of the cells. By mounting a skin cross‐section on an improved conductive holder, consisting of a silicon substrate coated with copper, we were able to observe penetration of gold nanoparticles of only 5 nm size through the skin barrier in an uncoated skin tissue. The described method offers a convenient modification in preparation procedure for biological samples to be analyzed in SEM. The method provides high conductivity without application of surface coating and requires less time and a reduced use of toxic chemicals.
Ultrafast photon counting applied to resonant scanning STED microscopy
Authors: WU XUNDONG , TORO LIGIA , STEFANI ENRICO , WU YONG
Published: September 2014

To take full advantage of fast resonant scanning in super‐resolution stimulated emission depletion (STED) microscopy, we have developed an ultrafast photon counting system based on a multigiga sample per second analogue‐to‐digital conversion chip that delivers an unprecedented 450 MHz pixel clock (2.2 ns pixel dwell time in each scan). The system achieves a large field of view (∼50 × 50 μm) with fast scanning that reduces photobleaching, and advances the time‐gated continuous wave STED technology to the usage of resonant scanning with hardware‐based time‐gating. The assembled system provides superb signal‐to‐noise ratio and highly linear quantification of light that result in superior image quality. Also, the system design allows great flexibility in processing photon signals to further improve the dynamic range. In conclusion, we have constructed a frontier photon counting image acquisition system with ultrafast readout rate, excellent counting linearity, and with the capacity of realizing resonant‐scanning continuous wave STED microscopy with online time‐gated detection.
Frontal deficits differentiate progressive supranuclear palsy from Parkinson's disease
Authors: Lee Young‐Eun C. , Williams David R. , Anderson Jacqueline F. I.
Published: September 2014

The clinical differentiation of progressive supranuclear palsy from Parkinson's disease can be challenging, due to overlapping clinical features and a lack of diagnostic markers. Abnormalities in cognitive function form part of the clinical spectrums of these diseases and distinctive cognitive profiles may be helpful in differentiating these diseases in the diagnostic period. A comprehensive neuropsychological test battery was administered to 12 patients with clinically diagnosed progressive supranuclear palsy and 12 patients with Parkinson's disease matched for age and disease duration. Effect size (Cohen's d) was calculated for cognitive tests that were significantly different between groups. Patients with progressive supranuclear palsy performed significantly worse than those with Parkinson's disease on measures of processing speed, verbal fluency, planning, verbal abstract reasoning, verbal memory, and made more perseverative responses on a set shifting task. Measures of executive function, manual dexterity and processing speed were most diagnostically useful (Cohen's d > 2.0) in differentiating between progressive supranuclear palsy and Parkinson's disease. These findings suggest that more severe and prominent ‘frontal’ cognitive deficits in patients with progressive parkinsonism would be helpful in predicting progressive supranuclear palsy rather than Parkinson's disease and these findings may contribute to the development of diagnostic criteria.
Pharmacokinetics of danofloxacin andN‐desmethyldanofloxacin in adult horses and their concentration in synovial fluid
Authors: Lopez B. S. , Giguère S. , Berghaus L. J. , Mullins M. A. , Davis J. L.
Published: September 2014

The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metaboliteN‐desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin andN‐desmethyldanofloxacin were measured by UPLC‐MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0mL/h/kg, and an elimination half‐life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax) ofN‐desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.
Physicochemical characterization and pharmacokinetics in broiler chickens of a new recrystallized enrofloxacin hydrochloride dihydrate
Authors: Gutierrez L. , Miranda‐Calderon J. E. , Garcia‐Gutierrez P. , Sumano H.
Published: September 2014

Enrofloxacin, a key antimicrobial agent in commercial avian medicine, has limited bioavailability (60%). This prompted its chemical manipulation to yield a new solvate‐recrystallized enrofloxacin hydrochloride dihydrate entity (enroC). Its chemical structure was characterized by means of mass spectroscopy, Fourier transformed infrared spectroscopy, X‐ray powder diffraction, and thermal analysis. Comparative oral pharmacokinetics (PK) of reference enrofloxacin (enroR) and enroCin broiler chickens after oral administration revealed noticeable improvements in key parameters andPK/PDratios. Maximum serum concentration values were 2.61 ± 0.21 and 5.9 ± 0.42 μg/mL for enroRand enroC, respectively; mean residence time was increased from 5.50 ± 0.26 h to 6.20 ± 0.71 h and the relative bioavailability of enroCwas 336%. Considering Cmax/MICandAUC/MICratios and theMICvalues for a wild‐typeEscherichia coliO78/H12 (0.25 μg/mL), optimal ratios will only be achieved by enroC(Cmax/MIC = 23.6 andAUC/MIC = 197.7 for enroC; vs. Cmax/MIC = 10.4 andAUC/MIC = 78.1 for enroR). Furthermore, enroCmay provide in most cases mutant prevention concentrations (Cmax/MIC ≥ 16). Ready solubility of powder enroCin drinking water at concentrations regularly used (0.01%) to provide an additional advantage of enroCin the field. Further development of enroCis warranted before it can be recommended for clinical use in veterinary medicine.
The rise of Laminaria ochroleuca in the Western English Channel (UK) and comparisons with its competitor and assemblage dominant Laminaria hyperborea
Authors: Smale Dan A. , Wernberg Thomas , Yunnie Anna L. E. , Vance Thomas
Published: September 2014

The distribution of species is shifting in response to recent climate change. Changes in the abundance and distributions of habitat‐forming species can have knock‐on effects on community structure, biodiversity patterns and ecological processes. We empirically examined temporal changes in the abundance of the warm‐water kelp Laminaria ochroleuca at its poleward range edge in the Western English Channel. Resurveys of historical sites indicated that the abundance of L. ochroleuca has increased significantly in recent decades. Moreover, examination of historical records suggested that L. ochroleuca has extended its distribution from sheltered coasts on to moderately wave‐exposed open coasts, where it now co‐exists and competes with the assemblage dominant Laminaria hyperborea. Proliferation of L. ochroleuca at its poleward range edge corresponds with a period of rapid warming in the Western English Channel. Preliminary comparisons between L. ochroleuca and L. hyperborea highlighted some subtle but ecologically significant differences in structure and function. In summer, the average biomass of epiphytic stipe assemblages on L. hyperborea was 86 times greater than on L. ochroleuca whereas, on average, L. ochroleuca had a greater stipe length and its blade supported 18 times as many gastropod grazers (Gibbula cineraria). Differences in summer growth rates were also recorded, with L. ochroleuca being more productive than L. hyperborea throughout July. Comprehensive seasonally replicated comparisons are needed to examine the wider implications of proliferation of L. ochroleuca at its poleward range edge, but our study suggests that local biodiversity patterns and ecological processes (e.g. timing of productivity and trophic pathways) on shallow subtidal reefs may be altered by shifts in the relative abundances of habitat‐forming kelp species.
The short chain fatty acids, butyrate and propionate, have differential effects on the motility of the guinea pig colon
Authors: Hurst Norm R. , Kendig Derek M. , Murthy Karnam S. , Grider John R.
Published: September 2014

Background

Colonic microbiota digest resistant starches producing short chain fatty acids (SCFAs). The main SCFAs produced are acetate, propionate, and butyrate. Both excitatory and inhibitory effects of SCFAs on motility have been reported. We hypothesized that the effect of SCFAs on colonic motility varies with chain length and aimed to determine the effects of SCFAs on propagating and non‐propagating contractions of guinea pig proximal and distal colon.

Methods

In isolated proximal colonic segments, Krebs solution alone or containing 10–100 mM acetate, propionate, or butyrate was injected into the lumen, motility was videorecorded over 10 min, and spatiotemporal maps created. In distal colon, the lumen was perfused with the same solutions of SCFAs at 0.1 mL/min, the movement of artificial fecal pellets videorecorded, and velocity of propulsion calculated.

Key Results

In proximal colon, butyrate increased the frequency of full‐length propagations, decreased short propagations, and had a biphasic effect on non‐propagating contractions. Propionate blocked full and short propagations and had a biphasic effect on non‐propagating contractions. Acetate decreased short and total propagations. In distal colon, butyrate increased and propionate decreased velocity of propulsion.

Conclusions & Inferences

The data suggest that luminal SCFAs have differing effects on proximal and distal colonic motility depending on chain length. Thus, the net effect of SCFAs on colonic motility would depend on the balance of SCFAs produced by microbial digestion of resistant starches.